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Ischemic Mitral Regurgitation on the Threshold of a Solution From Paradoxes to Unifying Concepts
Abstract
“ More than once in history the discovery of paradox has been the occasion for major reconstruction at the foundations of thought .” — W.V. Quine, The Ways
One thing is certain: Ischemic mitral regurgitation (MR) conveys adverse prognosis, doubling mortality after myocardial infarction (MI), in chronic heart failure, and after surgical or catheter revascularization.1–9 It is common and increases mortality even when mild,3–5 with a graded relationship between severity and reduced survival (Figure 1A).5
Figure 1. A, Decreased survival after MI with increasing MR. Effective regurgitant orifice (ERO) area of 20 mm2 demarcates mild from moderate. Reprinted with permission from Grigioni et al.5 Copyright 2001, American Heart Association, Inc. B, Decreased survival after cardiogenic shock with increasing MR for comparable LV ejection fraction (LVEF). Reprinted with permission from Picard et al.8 Copyright 2003, American Heart Association, Inc.
In many other respects, however, ischemic MR has been a study in controversy and paradox. Its diagnosis is notoriously elusive, both by auscultation and intraoperatively. It may paradoxically decrease as driving pressure increases. Still commonly referred to as “papillary muscle dysfunction,” it cannot generally be produced by direct papillary muscle damage and may actually decrease with papillary muscle ischemia. Although leaflet motion is typically restricted, it may also be excessive, or both. Treatment benefit is hotly debated and will be difficult to resolve so long as existing therapies are incompletely effective in permanently abolishing MR. New therapeutic opportunities are perplexing in their diversity. By exploring such areas of confusion, we aim to clarify fundamental principles and achieve more effective solutions.
Ischemic MR is convenient shorthand for MR caused by changes in ventricular structure and function related ultimately to ischemia; it is predominantly postinfarction MR. Active ischemia can contribute, for example, creating intermittent “flash” pulmonary edema, …
... After myocardial infarction (MI), tethering and fibrosis of mitral leaflets stimulate functional mitral regurgitation (MR), resulting in high morbidity of heart failure (HF) and cardiac mortality [1][2][3][4][5][6][7][8]. As secondary functional MR usually develops as a result of left ventricular (LV) dysfunction [1,6], medications for HF such as beta blockers, angiotensinconverting-enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) are the mainstay of medical therapy for functional MR [9,10]. ...
... As secondary functional MR usually develops as a result of left ventricular (LV) dysfunction [1,6], medications for HF such as beta blockers, angiotensinconverting-enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) are the mainstay of medical therapy for functional MR [9,10]. However, the pharmacological treatment has not been found to be sufficient for reducing ischemic MR or reversing the adverse LV remodeling [5,11,12]. ...
... For patients with secondary functional MR, current medical treatment usually does not sufficiently reduce MR or reverse adverse LV remodeling [5]. Persistence of functional MR leads to high morbidity and mortality in patients managed with medical therapy [29]. ...
Angiotensin receptor neprilysin inhibitor (ARNI) treatment reduces functional mitral regurgitation (MR) to a greater extent than angiotensin receptor blocker (ARB) treatment alone, but the mechanism is unclear. We evaluated the mechanisms of how ARNI has an effect on functional MR. After inducing functional MR by left circumflex coronary artery occlusion, male Sprague Dawley rats (n = 31) were randomly assigned to receive the ARNI LCZ696, the ARB valsartan, or corn oil only (MR control). Excised mitral leaflets and left ventricle (LV) were analyzed, and valvular endothelial cells were evaluated focusing on molecular changes. LCZ696 significantly attenuated LV dilatation after 6 weeks when compared with the control group (LV end-diastolic volume, 461.3 ± 13.8 µL versus 525.1 ± 23.6 µL; p < 0.05), while valsartan did not (471.2 ± 8.9 µL; p > 0.05 to control). Histopathological analysis of mitral leaflets showed that LCZ696 strongly reduced fibrotic thickness compared to the control group (28.2 ± 2.7 µm vs. 48.8 ± 7.5 µm; p < 0.05). Transforming growth factor-β and downstream phosphorylated extracellular-signal regulated kinase were also significantly lower in the LCZ696 group. Consequently, excessive endothelial-to-mesenchymal transition (EndoMT) was mitigated in the LCZ696 group compared to the control group and leaflet area was higher (11%) in the LCZ696 group than in the valsartan group. Finally, the MR extent was significantly lower in the LCZ696 group and functional improvement was observed. In conclusion, neprilysin inhibitor has positive effects on LV reverse remodeling and also attenuates fibrosis in MV leaflets and restores adaptive growth by directly modulating EndoMT.
... In a normal-sized LV, little force is necessary to close this valve, even when there is global LV dysfunction. 31 However, in the presence of increased tethering, an even smaller force is exerted over the leaflets, further impairing normal closure of the mitral valve. This results in greater flow and regurgitant orifice area during early and late systole, but paradoxically decreased in mid-systole (when LV pressure is highest). ...
... This results in greater flow and regurgitant orifice area during early and late systole, but paradoxically decreased in mid-systole (when LV pressure is highest). 31 Moreover, the presence of a left bundle branch block may contribute to worsening MR, since papillary muscle contraction becomes dyssynchronous, resulting in complex LV longitudinal, circumferential, and rotational LV mechanics modifications. 25 Leaflet remodeling is also hypothesized to play a role in the development of MR. ...
The mitral valve apparatus is a complex structure consisting of several coordinating components: the annulus, two leaflets, the chordae tendineae, and the papillary muscles. Due to the intricate interplay between the mitral valve and the left ventricle, a disease of the latter may influence the normal function of the former. As a consequence, valve insufficiency may arise despite the absence of organic valve disease. This is designated as functional or secondary mitral regurgitation, and it arises from a series of distortions to the valve components. This narrative review describes the normal anatomy and the pathophysiology behind the mitral valve changes in ischemic and non-ischemic dilated cardiomyopathies. It also explains the value of a complete multiparametric assessment of this structure. Not only must an assessment include quantitative measures of regurgitation, but also various anatomical parameters from the mitral apparatus and left ventricle, since they carry prognostic value and are predictors of mitral valve repair success and durability.
... The risk of developing recurrent mitral regurgitation was increased with a mitral diastolic annular diameter ≥37 mm, a systolic tenting area >2.5 cm 2 , and a posterior leaflet angle >45 • , indicating significant posterior leaflet restriction [5]. Additionally, severe left ventricular enlargement confers a low likelihood of reverse left ventricular remodeling after repair, as well as poor late-stage outcomes [5,[19][20][21][22][23][24][25]. ...
... This evidence is in agreement with Penicka and colleagues, who revealed, in a series of moderate IMR patients receiving CABG only, that MR resolution after surgery was associated with more vital segments and less LV dyssynchrony at the baseline [26]. Not surprisingly, patients with documented scar tissue, a baseline aneurysm, dyskinesia in the lateral inferiorposterior left ventricle, large ventricles (LVESVI > 60 mL/m 2 and LVEDD > 60 mm) [3][4][5]9], or poor coronary targets in the circumflex and right coronary distributions have a decreased probability that revascularization will provide a notable improvement in left ventricular contractility and left ventricular reverse remodeling [3,9,[25][26][27][28][29]. ...
Objectives:
The current guidelines still do not include specific recommendations on the use of subvalvular repair (SV-r) for treatment of ischemic mitral regurgitation (IMR). Therefore, the objective of our study was to evaluate the clinical impact of mitral regurgitation (MR) recurrence and ventricular remodeling on long-term outcomes after SV-r combined with restrictive annuloplasty (RA-r).
Methods:
We performed a subanalysis of the papillary muscle approximation trial, studying 96 patients with severe IMR and coronary artery disease undergoing restrictive annuloplasty alongside subvalvular repair (SV-r + RA-r group) or restrictive annuloplasty alone (RA-r group). We analyzed treatment failure differences, the influence of residual MR, left ventricular remodeling, and clinical outcomes. The primary endpoint was treatment failure (composite of death; reoperation; or recurrence of moderate, moderate-to-severe, or severe MR) within 5 years of follow-up after the procedure.
Results:
A total of 45 patients showed failure of the treatment within 5 years, of which 16 patients underwent SV-r + RA-r (35.6%) and 29 underwent RA-r (64.4%, p = 0.006). Patients with significant residual MR presented with a higher rate of all-cause mortality at 5 years compared with trivial MR (HR 9.09, 95% CI 2.08-33.33, p = 0.003). MR progression occurred earlier in the RA-r group, as 20 patients in the RA-r group vs. 6 in SV-r + RA-r group had a significant MR 2 years after surgery (p = 0.002).
Conclusions:
RA-r remains a surgical mitral repair technique with an increased risk of failure and mortality at 5 years compared with SV-r. The rates of recurrent MR are higher, and recurrence occurs earlier, with RA-r alone compared to SV-r. The addition of the subvalvular repair increases the durability of the repair, thus extending all of the benefits of preventing MR recurrence.
... The main mechanisms underlying the development of chronic IMR are related to the altered geometry of the mitral valve, which results from left ventricular remodeling following myocardial infarction. Papillary muscle displacement resulting from left ventricular remodeling causes tethering of the mitral valve leaflets and restricted closure resulting in mitral regurgitation (14)(15)(16) . This tethering of the leaflets is effected mainly through secondary (basal) chordae, which attach to the belly of the anterior mitral leaflet resulting in a characteristic bend, often referred to as 'seagull sign' (15) . ...
... Papillary muscle displacement resulting from left ventricular remodeling causes tethering of the mitral valve leaflets and restricted closure resulting in mitral regurgitation (14)(15)(16) . This tethering of the leaflets is effected mainly through secondary (basal) chordae, which attach to the belly of the anterior mitral leaflet resulting in a characteristic bend, often referred to as 'seagull sign' (15) . However this characteristic bend seems to vary between individuals depending on the insertion site of secondary chordae, thus affecting the severity of secondary mitral regurgitation. ...
... Generally, two main types of secondary MR are VFMR and atrial functional MR (AFMR). The VFMR occurs in dilated ventricles as a consequence of the increased distance between the displaced PM and MA, which leads to tethering (with a "seagull sign" of anterior MV leaflet), limited systolic leaflets motion, and a reduced coaptation height [129,130]. Contrarily, in the AFMR, caused by an enlarged LA, LV typically has preserved geometry and function or mildly reduced longitudinal strain [131]. Additionally, there is MA dilation (anteroposterior diameter > 35 mm in parasternal view or systolic annular diameter/diastolic anterior leaflet length ratio > 1.3), a counterclockwise-directed torque of the anterior annulus, a reduction in the posterior MV leaflet area, and relocation of the posterior annulus alongside the LA wall. ...
Observing mitral or tricuspid valve disease in an athlete raises many considerations for the clinician. Initially, the etiology must be clarified, with causes differing depending on whether the athlete is young or a master. Notably, vigorous training in competitive athletes leads to a constellation of structural and functional adaptations involving cardiac chambers and atrioventricular valve systems. In addition, a proper evaluation of the athlete with valve disease is necessary to evaluate the eligibility for competitive sports and identify those requiring more follow-up. Indeed, some valve pathologies are associated with an increased risk of severe arrhythmias and potentially sudden cardiac death. Traditional and advanced imaging modalities help clarify clinical doubts, allowing essential information about the athlete’s physiology and differentiating between primary valve diseases from those secondary to training-related cardiac adaptations. Remarkably, another application of multimodality imaging is evaluating athletes with valve diseases during exercise to reproduce the sport setting and better characterize the etiology and valve defect mechanism. This review aims to analyze the possible causes of atrioventricular valve diseases in athletes, focusing primarily on imaging applications in diagnosis and risk stratification.
... Using an advanced ex vivo simulator and specifically engineered sigmoid-shaped rods, He and colleagues were the first to show that artificial displacement of the PMs by just 10 mm in five different directions (apical, lateral, posterolateral, lateral + apical, and posterolateral + apical displacement) produces tenting of the MV leaflets and regurgitation, with incremental severity for increased PM displacement distances in the bidirectional displacement, and less severity for isolated apical displacement [34]. Importantly, this model reproduced the biphasic early and late systolic peaks of the MR orifice in ischemic hearts [84]. Three-dimensional PM displacement was further investigated in vivo by Bothe et al. and Tibayan et al., each using dedicated radiopaque markers placed on the PM tips and the mitral annulus before induction of a posterolateral MI. ...
The geometrical details and biomechanical relationships of the mitral valve–left ventricular apparatus are very complex and have posed as an area of research interest for decades. These characteristics play a major role in identifying and perfecting the optimal approaches to treat diseases of this system when the restoration of biomechanical and mechano-biological conditions becomes the main target. Over the years, engineering approaches have helped to revolutionize the field in this regard. Furthermore, advanced modelling modalities have contributed greatly to the development of novel devices and less invasive strategies. This article provides an overview and narrative of the evolution of mitral valve therapy with special focus on two diseases frequently encountered by cardiac surgeons and interventional cardiologists: ischemic and degenerative mitral regurgitation.
... Ischemic mitral regurgitation (IMR) is a distinct form of valvular disorder, wherein the left ventricular abnormalities arising as a result of coronary artery disease (CAD) are the primary cause of valve dysfunction. Excluding cases of papillary muscle rupture, IMR is a secondary form of mitral regurgitation (MR) characterized by structurally normal leaflets, though with restricted motion and apical tethering causing displacement of the coaptation zone from the mitral annulus toward the apex of the left ventricle, and leading to incomplete systolic closure of the mitral valve [1]. ...
... Conceivably, this will reduce both tethering and closing forces of the mitral valve, improving leaflet coaptation. Although not directly applicable to clinical practice, this geometrical change may help explain the benefits of preload-reducing medications in acute MR, which are conventionally credited to the reduction of transmitral gradients (Keren et al., 1986;Levine & Schwammenthal, 2005;Yoran et al., 1979). ...
The purpose of this study was to investigate the effects of loading conditions and left ventricular (LV) contractility on mitral annular dynamics. In 10 anesthetized pigs, eight piezoelectric transducers were implanted equidistantly around the mitral annulus. High-fidelity catheters measured left ventricular pressures and the slope of the end-systolic pressure-volume relationship (Ees ) determined LV contractility. Adjustments of pre- and afterload were done by constriction of the inferior caval vein and occlusion of the descending aorta. Mitral annulus area indexed to body surface area (MAAi ), annular circularity index (ACI), and non-planarity angle (NPA) were calculated by computational analysis. MAAi was more dynamic in response to loading interventions than ACI and NPA. However, MAAi maximal cyclical reduction (-Δr) and average deformational velocity (- v ¯ $$ \overline{v} $$ ) did not change accordingly (p = 0.31 and p = 0.22). Reduced Ees was associated to attenuation in MAAi -Δr and MAAi - v ¯ $$ \overline{v} $$ (r2 = 0.744; p = 0.001 and r2 = 0.467; p = 0.029). In conclusion, increased cardiac load and reduced LV contractility may cause deterioration of mitral annular dynamics, likely impairing coaptation and increasing susceptibility to valvular incompetence.
... Ischemic coronary insufficiency (IMR) is coronary insufficiency caused by coronary artery disease in the absence of internal valve lesions, which are common complications of acute myocardial infarction (AMI) (1) that is occurring in 15-64% of patients after the event, which is independent indicator of future cardiovascular mortality (2) . ...
... Left atrial enlargement and atrial fibrillation are the common finding in patients with mitral regurge followed by left ventricular enlargement and then right ventricular enlargement. Patients with mitral stenosis left atrial enlargement is the commonest finding and atrial fibrillation is also common (12) . ...
... It occurs in 20-25% of patients after myocardial infarction and in up to 50% heart failure patients. 2 A distinct class of functional MR in patients with atrial fibrillation (AF), but normal LV size and function has been now recognized and labeled as aFMR. This entity has received little attention and occurs in patients with AF and /or heart failure with preserved ejection fraction (HFpEF) with severe left atrial (LA) dilatation. ...
... In accordance with this theory, current guideline-based clinical practice focuses on volume overload related to chronic severe MR as the main mechanism of LV dilatation in patients with MVP (7,8). LA and LV remodeling in primary MR should be differentiated from remodeling in secondary MR, as this form of MR typically occurs as a result of significant atrial (23) or ventricular (24) dilatation, e.g., in the presence of atrial fibrillation or dilated cardiomyopathy (25). ...
Mitral valve prolapse (MVP) is a common valvular disorder that can be associated with mitral regurgitation (MR), heart failure, ventricular arrhythmias and sudden cardiac death. Given the prognostic impact of these conditions, it is important to evaluate not only mitral valve morphology and regurgitation, but also the presence of left ventricular (LV) function and remodeling. To date, several possible hypotheses have been proposed regarding the underlying mechanisms of LV remodeling in the context of non-syndromic MVP, but the exact pathophysiological explanation remains elusive. Overall, volume overload related to severe MR is considered the main cause of LV dilatation in MVP. However, significant LV remodeling has been observed in patients with MVP and no/mild MR, particularly in patients with bileaflet MVP or Barlow’s disease, generating several new hypotheses. Recently, the concept of “prolapse volume” was introduced, adding a significant volume load to the LV on top of the transvalvular MR volume. Another possible hypothesis is the existence of a concomitant cardiomyopathy, supported by the link between MVP and myocardial fibrosis. The origin of this cardiomyopathy could be either genetic, a second hit (e.g., on top of genetic predisposition) and/or frequent ventricular ectopic beats. This review provides an overview of the different mechanisms and remaining questions regarding LV remodeling in non-syndromic MVP. Since technical specifications of imaging modalities impact the evaluation of MR severity and LV remodeling, and therefore might influence clinical decision making in these patients, this review will also discuss assessment of MVP using different imaging modalities.
... Mechanisms leading to SMR have been extensively described [6][7][8][9][10][11][12]. They are dynamic, complex and involve all components of the mitral valvular and subvalvular apparatus. ...
The approach to the management of mitral valve (MV) disease and heart failure (HF) has dramatically changed over the last decades. It is well recognized that severe mitral regurgitation secondary to ischemic or non-ischemic cardiomyopathy is associated with an excess risk of mortality. Understanding the impact of the surgical treatment modality on mortality outcomes has been difficult due to the broad spectrum of secondary mitral regurgitation (SMR) phenotypes and lack of randomized surgical clinical trials. Over the last 30 years, surgeons have failed to provide compelling evidence to convince the medical community of the need to treat SMR in patients with severe HF. Therefore, the surgical treatment of SMR has never gained uniform acceptance as a significant option among patients suffering from SMR. Recent evidence from randomized trials in a non-surgical eligible patients treated with transcatheter therapies, has provided a new perspective on SMR treatment. Recently published European and American guidelines confirm the key role of percutaneous treatment of SMR and in parallel, these guidelines reinforce the role of mitral valve surgery in patients who require surgical revascularization. Complex mitral valve repair combining subvalvular apparatus repair along with annuloplasty seems to be a promising approach in selected patients in selected centers. Meanwhile, mitral valve replacement has become the preferred surgical strategy in most patients with advanced heart failure and severe LV remodeling or high risk of recurrent mitral regurgitation. In this comprehensive review, we aimed to discuss the role of mitral surgery for SMR in patients with heart failure in the contemporary era and to provide a practical approach for its surgical management.
... CAD is a common reason for HF development [24]. Either AMI or chronic ischemia leads to LV remodeling, ischemic mitral regurgitation and LV dysfunction [25,26]. In acute heart failure syndromes, the high LV diastolic pressure and low systemic blood pressure often result in subendocardial ischemia and lead to worse outcomes [27]. ...
Background
The platelet-to-hemoglobin ratio (PHR) has emerged as a prognostic biomarker in coronary artery disease (CAD) patients after PCI but not clear in CAD complicated with congestive heart failure (CHF). Hence, we aimed to assess the association between PHR and long-term all-cause mortality among CAD patients with CHF.
Methods
Based on the registry at Guangdong Provincial People’s Hospital in China, we analyzed data of 2599 hospitalized patients who underwent coronary angiography (CAG) and were diagnosed with CAD complicated by CHF from January 2007 to December 2018. Low PHR was defined as ˂ 1.69 (group 1) and high PHR as ≥ 1.69 (group 2). Prognosis analysis was performed using Kaplan–Meier method. To assess the association between PHR and long-term all-cause mortality, a Cox-regression model was fitted.
Results
During a median follow-up of 5.2 (3.1–7.8) years, a total of 985 (37.9%) patients died. On the Kaplan–Meier analysis, patients in high PHR group had a worse prognosis than those in low PHR group (log-rank, p = 0.0011). After adjustment for confounders, high PHR was correlated with an increased risk of long-term all-cause mortality in CAD patients complicated with CHF. (adjusted hazard ratio [aHR], 1.31; 95% confidence interval [CI], 1.13–1.52, p < 0.0001).
Conclusion
Elevated PHR is correlated with an increased risk of long-term all-cause mortality in CAD patients with CHF. These results indicate that PHR may be a useful prognostic biomarker for this population. Meanwhile, it is necessary to take effective preventive measures to regulate both hemoglobin levels and platelet counts in this population.
... In secondary mitral regurgitation (previously also referred to as 'functional mitral regurgitation'), the valve leaflets and chordae are structurally normal and mitral regurgitation results from an imbalance between closing and tethering forces on the valve secondary to alterations in LV geometry. 134 It is most commonly seen in dilated or ischaemic cardiomyopathies. Annular dilatation in patients with chronic atrial fibrillation and LA enlargement can also be an underlying mechanism. ...
ESC 2017 valvular heart disease guidelines
... Ischemic mitral regurgitation (IMR) is a common complication of coronary artery disease (CAD) as a result of left ventricular (LV) global or regional remodeling (1,2). The estimated incidence of IMR in patients with CAD is 20-50% (2,3). ...
Background:
The factors that associated with the response of moderate ischemic mitral regurgitation (IMR) to isolated coronary artery bypass grafting (CABG) remain unclear. This study aims to evaluate whether left ventricular (LV) myocardial scar assessed by cardiovascular magnetic resonance (CMR) is associated with the outcome of moderate IMR after isolated CABG.
Methods:
Forty-six patients with coronary artery disease (CAD) and moderate IMR who underwent isolated CABG between January 2014 and February 2019 in Anzhen Hospital Affiliated to Capital Medical University were enrolled in this case-control study. All patients underwent CMR and echocardiography before surgery. Patients were classified into two groups according to the severity of IMR 1 year after CABG: an improved group (no or mild IMR) and an unimproved group (moderate or severe IMR). Univariate and multivariate logistic regression analyses were used to assess the association between individual variables and unimproved IMR at 1-year post-CABG.
Results:
Compared to patients in the improved group, the patients in the unimproved group had a significantly greater amount of LV myocardial scar (18.0%±9.5% vs. 30.8%±11.2%, P<0.001). In the multiple logistic regression model, after adjustment for age, sex, and body mass index, only LV myocardial scar (OR: 0.89, 95% CI: 0.83-0.96, P=0.001) was independently associated with unimproved IMR after isolated CABG. Furthermore, there was no difference in the 3-year overall survival rates between the two groups (92.3% vs. 90.3%, P=0.46). In addition, patients in the unimproved group had a higher New York Heart Association (NYHA) classification (P=0.01) and more major adverse cardiac events such as MI, angina pectoris, and readmission for heart failure (P=0.03).
Conclusions:
A greater amount of preoperative LV myocardial scar was associated with unimproved moderate IMR after isolated CABG. Measuring preoperative LV myocardial scar is helpful to predict post-operative outcome and determine optimal surgery in patients with moderate IMR.
... CAD is a common reason for HF development [25]. Either AMI or chronic ischemia leads to LV remodeling, ischemic mitral regurgitation, and LV dysfunction [26,27]. In acute heart failure syndromes, the high LV diastolic pressure and low systemic blood pressure often result in subendocardial ischemia and lead to worse outcomes [28]. ...
Background
The platelet-to-hemoglobin ratio (PHR) has emerged as a prognostic biomarker in coronary artery disease (CAD) patients after PCI but not clear in CAD complicated with congestive heart failure (CHF). Hence, we aimed to assess the association between PHR and long-term all-cause mortality among CAD patients with CHF.
Methods
Based on the registry at Guangdong Provincial People’s Hospital in China, we analyzed data of 2,599 hospitalized patients who underwent coronary angiography (CAG) and were diagnosed with CAD complicated by CHF from January 2007 to December 2018. Low PHR was defined as˂1.69 (group 1) and high PHR as ≥ 1.69 (group 2). Prognosis analysis was performed using Kaplan-Meier methods. To assess the association between PHR and long-term all-cause mortality, a Cox-regression model was fitted.
Results
During a median follow-up of 5.2 (3.1–7.8) years, a total of 985 (37.9%) patients died. On the Kaplan-Meier analysis, patients in high PHR group had a worse prognosis than low PHR group (log-rank, p = 0.0011). After adjustment for confounders, high PHR was correlated with an increased risk of long-term all-cause mortality in CAD patients complicated with CHF. (adjusted hazard ratio [aHR], 1.21; 95% confidence interval [CI], 1.03–1.41, p = 0.02).
Conclusion
Elevated PHR is correlated with an increased risk of long-term all-cause mortality in CAD patients with CHF. These results indicate that PHR may be a useful prognostic biomarker for this population. Meanwhile, it is necessary to take effective preventive measures to regulate both hemoglobin levels and platelet counts in this population.
... Eventually, annular dilation owing to longstanding LA volume overload may aggravate MR, although the latter is not the main driver for regurgitation in this pathophysiology. 4 In other words, increased annular dimensions may contribute to the imbalance, though concomitant subvalvular tethering typically sets the stage for leaflet malcoaptation in VSMR. ...
Objectives
Atrial secondary mitral regurgitation (ASMR) is a clinically distinct form of Carpentier type I mitral regurgitation (MR), rooted in excessive atrial and mitral annular dilation in the absence of left ventricular dysfunction. Mitral valve annuloplasty (MVA) is expected to provide a more durable solution for ASMR than for ventricular secondary MR (VSMR). Yet data on MR recurrence and outcome after MVA for ASMR are scarce. This study sought to investigate surgical outcomes and repair durability in patients with ASMR, as compared with a contemporary group of patients with VSMR.
Methods
Clinical and echocardiographic data from consecutive patients who underwent MVA to treat ASMR or VSMR in an academic centre were retrospectively analysed. Patient characteristics, operative outcomes, time to recurrence of ≥moderate MR and all-cause mortality were compared between patients with ASMR versus VSMR.
Results
Of the 216 patients analysed, 97 had ASMR opposed to 119 with VSMR and subvalvular leaflet tethering. Patients with ASMR were typically female (68.0% vs 33.6% in VSMR, p<0.001), with a history of atrial fibrillation (76.3% vs 33.6% in VSMR, p<0.001), paralleling a larger left atrial size (p<0.033). At a median follow-up of 3.3 (IQR 1.0–7.3) years, recurrence of ≥moderate MR was significantly lower in ASMR versus VSMR (7% vs 25% at 2 years, overall log-rank p=0.001), also when accounting for all-cause death as competing risk (subdistribution HR 0.50 in ASMR, 95% CI 0.29 to 0.88, p=0.016). Moreover, ASMR was associated with better overall survival compared with VSMR (adjusted HR 0.43 95% CI 0.22 to 0.82, p=0.011), independent from baseline European System for Cardiac Operative Risk Evaluation II surgical risk score.
Conclusion
Prognosis following MVA to treat ASMR is better, compared with VSMR as reflected by lower all-cause mortality and MR recurrence. Early distinction of secondary MR towards underlying ventricular versus atrial disease has important therapeutic implications.
... The prevalence of FMR continues to rise, and 4million people in the USA are expected to be diagnosed with FMR by 2030 (3). Prior studies have shown that significant FMR developed in ~50% of patients after myocardial infarction (MI) (4-7) and up to 50% of patients with heart failure (HF) (8). Moreover, FMR portends poor prognosis, with mortality rates ranging from 15-40% at 1 year (9)(10)(11)(12). ...
Functional mitral regurgitation (FMR) occurs in the absence of organic mitral valve (MV) disease and is a result of LV dysfunction due to ischemic vs. non ischemic etiologies. The prevalence of FMR is increasing, as 2.0-2.5 million people in the USA were diagnosed with FMR in 2000-and this number is expected to double to 4 million by 2030. FMR tends to develop in a significant number of patients after myocardial infarction (MI) and many develop heart failure (HF) subsequently with mortality rates ranging from 15-40% at 1 year. Therefore, there has been much interest and effort to develop optimized methods for quantifying and classifying the severity of FMR, as well as developing effective therapeutic interventions to improve outcomes in patients with significant FMR. Echocardiogram is typically the primary diagnostic method of assessment, however, there have been various technological advances including cardiac CT and cardiac MRI that can better guide quantification and management of this disease. Management of this disease is mostly aimed at optimizing left ventricular (LV) remodeling with surgical and transcatheter management gaining more popularity with recent times. The purpose of this paper is to provide a comprehensive review of the current evaluation methods and interventional strategies for FMR.
... As opposed to degenerative mitral regurgitation, treatment of functional mitral regurgitation (FMR) remains subject to debate [1]. FMR is commonly associated with heart failure and is mainly caused by geometrical or functional abnormalities of structures surrounding the intrinsically normal mitral valve [2]. Currently, FMR therapies-medical or otherwise-are directed at reducing or reversing the remodelling process of the left ventricle [3]. ...
Background
Functional mitral regurgitation (FMR) can be subclassified based on its proportionality relative to left ventricular function and end-diastolic volume. FMR proportionality could help identify responders to transcatheter edge-to-edge mitral valve repair (MitraClip) in terms of residual FMR and/or clinical improvement.
Methods
This single-centre retrospective cohort study evaluated the feasibility of determining FMR proportionality in symptomatic heart failure patients with reduced left ventricular function who were treated with MitraClip for ≥ moderate-to-severe FMR. Baseline proportionate (pFMR) and disproportionate FMR (dFMR) were distinguished. Patient characteristics and MitraClip procedural outcomes were described.
Results
From an overall cohort of 81 eligible FMR patients, 23/81 (28%) had to be excluded due to missing transthoracic echocardiogram parameters, 22/81 were excluded based on FMR severity. The remaining cohort, of 36/81 patients (44%), could be classified into dFMR ( n = 26) or pFMR ( n = 10). Conduction disorders were numerically increased in dFMR. All cases requiring > 2 clips were in the dFMR group and absence of FMR reduction occurred more frequently with dFMR.
Point of view/Conclusion
Important limitations in terms of imaging acquisition affect the translation of the FMR proportionality concept to a real-world data set. We did observe different demographic and FMR response patterns in patients with proportionate and disproportionate FMR that warrant further investigation.
... Therefore, the MA non-planar angle dynamics describe an ascendant-descendent shape in normal group (blue), an ascendant shape in limited MVD group (green) and descendent shape in extensive MVD group (red). Thus, if the purpose is to prevent further MA dilatation -undersized stiff and fl at rings are generally used 43 . If the goal is only remodelling, partially fl exible rings or incomplete bands are preferred [44][45][46] . ...
Myxomatous mitral valve disease (MVD) is a common disorder in which the entire mitral valve apparatus seems to be involved. Mitral valve repair is nowadays the method of choice for the correction of mitral regurgitation but the optimal shape and flexibility of the annuloplasty ring remain controversial. Considering that myxomatous MVD covers a wide spectrum from limited fi bro-elastic deficiency to extensive Barlow disease, we presume that the mitral annulus morphological and functional changes are likely different in different types of myxomatous MVD. We analyze the 3-dimensional geometry and the dynamics of the mitral annulus in 110 patients with significant mitral regurgitation due to different types of myxomatous mitral valve disease and 40 normal subjects using 3D transesophageal echocardiography. The mitral annulus differs in patients with limited MVD, extensive MVD and in normal controls in terms of size, shape, and dynamics. Patients with limited MVD have larger, flatter, dysfunctional and more mobile mitral annulus compared to normal, while patients with extensive MVD have even larger, fl atter and more dysfunctional mitral annulus, with reduced mobility. The non-planar dynamics has different patterns during systole, according to the extension of MV disease. Our data may be important for the appropriate choose of annuloplasty mitral annulus in mitral valve repair, the current trend being to choose the ring according to the underlying pathology.
... D eveloping ischemic mitral regurgitation (IMR) after myocardial infarction (MI) accelerates the progression to symptomatic ischemic cardiomyopathy, independently predicts adverse events, and doubles mortality. 1,2 Mitral regurgitation is the consequence of incomplete mitral valve (MV) leaflet closure that causes blood backflow from the left ventricle (LV) to the left atrium during systole. Regurgitation causes volume overload both in the LV and the left atrium, which initially develop hypertrophy to maintain stroke volume and reduce filling pressure, respectively, but eventually progress to dilation and symptomatic heart failure. ...
Objective
Ischemic mitral regurgitation (IMR) often develops after an ischemic event, which results in distortion of the valvulo-ventricular complex and incomplete mitral valve (MV) leaflet coaptation. After left ventricular ischemic events, only some patients develop IMR. The susceptibility of the MV to remodel may influence whether IMR develops. We hypothesized that impaired signaling response in MV cells may contribute to IMR development by inducing maladaptive tissue remodeling.
Approach and Results
Sheep (n=14) were subjected to ligation of the circumflex coronary artery to induce myocardial infarction. IMR was reported by echocardiography. MV leaflets and MV interstitial cells (MVICs) were collected at baseline (control, n=10), 4 and 8 weeks post-myocardial infarction. RNA sequencing highlighted differences in TGFβ (transforming growth factor beta) signaling between MV with/without IMR. SMAD6/7 and ID2 (inhibitor of DNA binding 2) were the highest increased TGFβ-signaling genes associated with IMR. MVICs from myocardial infarction sheep were less responsive to BMP (bone morphogenic protein) 4 pro-osteogenic stimulation (ID2, OPN [osteopontin], and OC [osteocalcin] mRNA) than control. MVICs from IMR sheep had a diminished COL (collagen) 1A1 mRNA response to TGFβ1 and enhanced prochondrogenic RUNX2 (runt-related transcription factor 2) and SOX9 mRNA response to BMP4 versus non-IMR MVICs. Baseline CD45 expression was detectable only in IMR MVICs. Upon TGFβ1 stimulation, CD45 expression was detected in all groups. Immunostaining confirmed increased presence of CD45+ cells in IMR MV interstitium.
Conclusions
MVs from sheep with IMR had an altered TGFβ/BMP response, associated with increased CD45+ cell presence within the tissue interstitium. Pharmacological strategies aimed to modulate TGFβ/BMP signaling after myocardial infarction may protect from pathological MV remodeling leading to IMR.
... Mitral regurgitation (MR) is the second most frequent indication for valve surgery in Europe [1] with an estimated prevalence of 5% among the adult population [2,3]. The most widely used classification distinguishes between primary and secondary (or functional) MR: the former is caused by a damage to the mitral valve leaflets or chordae tendinae, whereas the latter presents a normal valve apparatus and is the consequence of annular enlargement/dysfunction and leaflet tethering caused in the majority of cases by left ventricular dysfunction [4]. ...
Transcatheter mitral valve repair with MitraClip has emerged as a possible therapeutic option for patients with severe mitral regurgitation (MR) with high risk for surgical valve repair. MitraClip intervention has demonstrated to improve haemodynamics and clinical outcomes in selected patients in observational and randomized studies. Preoperative pulmonary hypertension (PH) is known to affect prognosis in patients undergoing surgical mitral valve intervention. The aim of the present review is to discuss the available literature focused on the haemodynamic and clinical effects of MitraClip in patients with severe MR and PH.
Aim
The RESHAPE‐HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE‐HF2 trial compared to those enrolled in the COAPT and MITRA‐FR trials.
Methods and results
The RESHAPE‐HF2 study is an investigator‐initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate‐to‐severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8–9.0) and median plasma N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) was 2745 (1407–5385) pg/ml. Most patients were prescribed beta‐blockers (96%), diuretics (96%), angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor–neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium–glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end‐diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm ² , respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA‐FR, those enrolled in RESHAPE‐HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT‐proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF.
Conclusion
Patients enrolled in RESHAPE‐HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate‐to‐severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA‐FR trials. The results of RESHAPE‐HF2 will provide crucial insights regarding broader application of the transcatheter edge‐to‐edge repair procedure in clinical practice.
Functional or secondary mitral regurgitation is linked to increased cardiovascular morbidity and mortality. From a mechanical perspective, secondary mitral regurgitation occurs due to an imbalance between the forces that tether the mitral leaflets and those that close them. This results in incomplete coaptation. Most commonly, functional mitral regurgitation, which occurs in both ischaemic and non-ischaemic disease states, is usually caused by dysfunction and changes in the left ventricle. Atrial functional mitral regurgitation (AFMR) is a disease state that has been more recently recognized. It occurs when mitral annular enlargement is associated with left atrial dilatation, preserving left ventricular geometry and function. AFMR is typically seen in patients with chronic atrial fibrillation or heart failure who have a conserved ejection fraction. Published reports and ongoing investigations vary in how they define AFMR. This publication examines the pathophysiology of AFMR and highlights the importance of having a common working standard for the definition of AFMR to ensure consistency in the data reported and to drive forward the much needed research into the outcomes and treatment strategies in this area. Several studies have reported that restrictive annuloplasty and transcatheter edge-to-edge repair can reduce mitral regurgitation and improve symptoms. This narrative review will explore the pathophysiology, echocardiographic diagnosis and treatment of AFMR.
Transcatheter edge-to-edge repair (TEER) is becoming the standard invasive treatment for ventricular functional mitral regurgitation (MR). It is necessary to determine the severity of MR before treatment with MitraClip; however, the severity of secondary MR is usually underestimated compared with that of primary MR and varies temporally. Therefore, to accurately determine the severity of MR, it is important to correctly use the algorithm of the guidelines for valvular heart disease and aggressively perform stress echocardiography. Before performing TEER, the difficulty of the procedure should be evaluated. First, morphological features that make TEER unsuitable, such as cleft of the mitral leaflet, mitral stenosis (MS), or perforation of the mitral leaflet, should be checked. The mitral valve orifice area, transmitral valve pressure gradient, coaptation depth, coaptation length, and posterior leaflet length should be measured to determine the difficulty of the procedure based on the inclusion criteria of Endovascular Valve Edge-to-Edge Repair Study II and the German consensus. After MitraClip implantation, in addition to assessing the severity of MS and residual MR, the pulmonary venous flow pattern and stroke volume should be evaluated to comprehensively assess whether TEER improves the hemodynamics. MitraClip has also been used to treat atrial functional MR, another type of secondary MR. Several reports suggest that MitraClip is effective for atrial functional MR; however, evidence is still being accumulated.
Background
Prosthetic heart valves, rings, and clips commonly used in heart surgery may contain metals, such as nickel and cobalt, that can cause severe hypersensitivity reactions in allergic patients. These reactions can cause paravalvular leakage and valve dysfunction. Similarly, stainless steel sternal wires can cause contact dermatitis. We should select rings, valves, and wires that do not contain any metals known to cause allergies in patients undergoing cardiac surgery.
Case Summary
We report the case of a 79-year-old man with severe functional mitral regurgitation (Type IIIb) and a history of nickel and cobalt allergies. We safely performed mitral valve repair with papillary muscle repositioning with nickel- and cobalt-free rings in this patient. He was discharged from the hospital on the 26th postoperative day without dialysis intervention. Two years after surgery, mitral and tricuspid regurgitation had not worsened.
Discussion
According to the 2020 American Heart Association guidelines, surgery for severe functional mitral valve insufficiency (Type IIIb) is considered class IIb. Meanwhile, transcatheter edge-to-edge repair is class IIa. Long-term regurgitation is difficult to control with valve replacement and annuloplasty alone; recurrence has been observed. Therefore, additional techniques were considered. Papillary muscle repositioning has been reported and shown good results. The method used in the present case made intervening in the subvalvular tissue easy and demonstrated technical feasibility, safety, and effectiveness.
Increased longevity will result in increasing numbers of elderly patients worldwide, among whom heart disease is the most common cause of death. Ageing is the most important risk factor for the development of cardiovascular diseases due to progressive changes in cardiac metabolism, function and structure and for vascular age-related changes. Moreover, cardiovascular comorbidities increase with increasing age, further affecting cardiovascular function and physiology. In the recent years improvement in treatments, also with the development and spread of percutaneous interventions, increased the chance of treatments of even fragile patients. Advanced cardiac imaging plays a crucial role in clinical decisions-making, guidance to treatment and prognostication, providing a comprehensive non-invasive characterization of myocardium and coronary arteries, from morphofunctionality to structural alteration. Currently, no available guidelines provide clear indications on the type and operating modalities of the various imaging techniques available for cardiac imaging in the elderly population. This chapter attempts to summarize the role of advanced cardiac imaging modalities (computed tomography and magnetic resonance) in the setting of most frequent cardiac disease occurring in elderly patients, especially coronary artery disease, valve disease and heart failure.
Purpose
Atrial fibrillation (AF) is common in critically ill patients and can have serious consequences. Postoperative AF (POAF) in critically ill patients following noncardiac surgery has been understudied, contrary to cardiac procedures. Mitral regurgitation (MR) is associated with left ventricular dysfunction, which might contribute to the occurrence of AF in postoperative critically ill patients. This study aimed to investigate the association between MR and POAF in critically ill noncardiac surgery patients and establish a new nomogram for the prediction of POAF in critically ill noncardiac surgery patients.
Patients and Methods
A prospective cohort of 2474 patients who underwent thoracic and general surgery was enrolled in this study. Data on preoperative transthoracic echocardiography (TTE), electrocardiogram (ECG), and several commonly utilized scoring systems (CHA2DS2‐VASc, HATCH, COM-AF, HART, and C2HEST) and baseline clinical data were collected. Independent predictors were selected by univariate and multivariable logistic regression analysis, and a nomogram was constructed for POAF within 7 days after postoperative intensive care unit (ICU) admission. The ability of the MR-nomogram and other scoring systems to predict POAF was compared by receiver operator characteristic (ROC) curve analysis and decision curve analysis (DCA). Additional contributions were evaluated by integrated discrimination improvement (IDI) and net reclassification improvement (NRI) analysis.
Results
A total of 213 (8.6%) patients developed POAF within 7 days after ICU admission. Compared to CHA2DS2‐VASc, HATCH, COM-AF, HART, and C2HEST scoring systems, MR-nomogram showed better predictive ability for POAF with an area under the ROC curve of 0.824 (95% confidence interval: 0.805–0.842, p < 0.001). The improvement of the MR-nomogram in predictive value was supported by NRI and IDI analysis. The net benefit of the MR nomogram was maximal in DCA.
Conclusion
MR is an independent risk factor of POAF in critically ill noncardiac surgery patients. The nomogram predicted POAF better than other scoring systems.
The concept of 'repairing' a degenerated mitral valve in order to restore the native competence means achieving the best physiological result coupled with the least invasive approach: this represents an interesting challenge for cardiac surgeons. The evolution of cardiac surgery through the years has involved techniques and technologies in every field of interest. From 'resect', to 'respect', to 'restore': the micro-invasive approach based on Neochord implant implies a transapical beating heart surgery which is based on the concept of implanting artificial chordae, preserving the physiological dynamics of the mitral annulus and avoiding the disadvantages of cardiopulmonary bypass and cardioplegic arrest of the heart.
Functional or secondary mitral regurgitation (MR) is associated with increased cardiovascular morbidity and mortality. Mechanistically, secondary MR is attributable to an imbalance between mitral leaflet tethering and closure forces, leading to poor coaptation. The pathophysiology of functional MR is most often the result of abnormalities in left ventricular function and remodeling, seen in ischemic or nonischemic conditions. Less commonly and more recently recognized is the scenario in which left ventricular geometry and function are preserved, the culprit being mitral annular enlargement associated with left atrial dilatation, termed atrial functional mitral regurgitation (AFMR). This most commonly occurs in the setting of chronic atrial fibrillation or heart failure with preserved ejection fraction. There is variability in the published reports and in current investigations as to the definition of AFMR. This paper reviews the pathophysiology of AFMR and focus on the need for a collective definition of AFMR to facilitate consistency in reported data and enhance much-needed research into outcomes and treatment strategies in AFMR.
Transcatheter edge-to-edge repair (TEER) is becoming the standard invasive treatment for ventricular functional mitral regurgitation (MR). It is necessary to determine the severity of MR before treatment with MitraClip; however, the severity of secondary MR is usually underestimated compared with that of primary MR and varies temporally. Therefore, to accurately determine the severity of MR, it is important to correctly use the algorithm of the guidelines for valvular heart disease and aggressively perform stress echocardiography. Before performing TEER, the difficulty of the procedure should be evaluated. First, morphological features that make TEER unsuitable, such as cleft of the mitral leaflet, mitral stenosis (MS), or perforation of the mitral leaflet, should be checked. The mitral valve orifice area, transmitral valve pressure gradient, coaptation depth, coaptation length, and posterior leaflet length should be measured to determine the difficulty of the procedure based on the inclusion criteria of Endovascular Valve Edge-to-Edge Repair Study II and the German consensus. After MitraClip implantation, in addition to assessing the severity of MS and residual MR, the pulmonary venous flow pattern and stroke volume should be evaluated to comprehensively assess whether TEER improves the hemodynamics. MitraClip has also been used to treat atrial functional MR, another type of secondary MR. Several reports suggest that MitraClip is effective for atrial functional MR; however, evidence is still being accumulated.
Background
The onset and mechanisms of endothelial‐to‐mesenchymal transition (EndMT) in mitral valve (MV) leaflets following myocardial infarction (MI) are unknown, yet these events are closely linked to stiffening of leaflets and development of ischemic mitral regurgitation. We investigated whether circulating molecules present in plasma within days after MI incite EndMT in MV leaflets.
Methods and Results
We examined the onset of EndMT in MV leaflets from 9 sheep with inferior MI, 8 with sham surgery, and 6 naïve controls. Ovine MVs 8 to 10 days after inferior MI displayed EndMT, shown by increased vascular endothelial cadherin/α‐smooth muscle actin–positive cells. The effect of plasma on EndMT in MV endothelial cells (VECs) was assessed by quantitative polymerase chain reaction, migration assays, and immunofluorescence. In vitro, post‐MI plasma induced EndMT marker expression and enhanced migration of mitral VECs; sham plasma did not. Analysis of sham versus post‐MI plasma revealed a significant drop in the Wnt signaling antagonist sFRP3 (secreted frizzled‐related protein 3) in post‐MI plasma. Addition of recombinant sFRP3 to post‐MI plasma reversed its EndMT‐inducing effect on mitral VECs. RNA‐sequencing analysis of mitral VECs exposed to post‐MI plasma showed upregulated FOXM1 (forkhead box M1). Blocking FOXM1 reduced EndMT transcripts in mitral VECs treated with post‐MI plasma. Finally, FOXM1 induced by post‐MI plasma was downregulated by sFRP3.
Conclusions
Reduced sFRP3 in post‐MI plasma facilitates EndMT in mitral VECs by increasing the transcription factor FOXM1. Restoring sFRP3 levels or inhibiting FOXM1 soon after MI may provide a novel strategy to modulate EndMT in the MV to prevent ischemic mitral regurgitation and heart failure.
Objective Mitral regurgitation (MR) and severe aortic valve stenosis often coexist. Concomitant replacement of both valves is associated with a significantly higher morbidity and mortality. This study sought to investigate the progression of MR after isolated aortic valve replacement.
Methods We analyzed the severity and progression of MR, survival and echocardiographic parameters in 506 patients with severe aortic valve stenosis and moderate to severe functional MR who received isolated aortic valve replacement during a 9-year period.
Results Transcatheter aortic valve implantation (TAVI) was performed in 381 patients and 125 patients received surgical aortic valve replacement (SAVR). The median age of the cohort was 82 years. Median ejection fraction before and after TAVI or SAVR was 35 and 36% respectively (p = 0.64). There was a statistically significant reduction in the MR (p < 0.001) within both groups. Survival in both groups at 5 years was at 25%.
Conclusion Isolated aortic valve replacement in patients with accompanying moderate to severe functional MR may present an adequate treatment option for this high-risk patient collective.
Background
Conventional annuloplasty repair of secondary (functional) ischemic mitral regurgitation (IMR) is associated with a 60% recurrence of ≥ moderate MR at 2 years. We developed a novel repair technique for IMR that addresses the underlying geometric alterations of the mitral valve apparatus and compared outcomes to conventional repair in a swine model.
Methods
Chronic IMR was induced by percutaneous embolization of the circumflex artery. Swine with severe IMR (median 9 weeks after infarction) underwent undersized rigid annuloplasty (n=5) or translocation repair (n=6). Translocation repair consisted of detaching the mitral valve (MV) en bloc at the annulus, creating a 1cm wide frustum-shaped pericardial patch, and suturing the outer circumference of the patch to the annulus and inner circumference to the MV.
Results
Operative survival was 92% (11/12). All animals had none/trace residual central MR and mean inflow gradients were similar (1 (IQR: 1-2) vs. 2 (IQR: 1-2) mmHg) [P=0.75] in the annuloplasty and translocation groups respectively. Median coaptation length marginally improved in conventional swine [3 to 4mm, P=0.05], but dramatically improved in translocation swine [3 to 8mm, P=0.003]. Posterior leaflet (PL) angle increased from 39° to 80° (P=0.05) in annuloplastyswine but decreased from 50° to 31° (P=0.03) in translocation swine. The posterior leaflet was immobile after annuloplasty but had preserved motion after translocation (excursion: 1 vs 24°, P=0.045).
Conclusions
MV translocation effectively treats MR by relieving leaflet tethering. Compared to annuloplasty, MV translocation creates a larger surface of coaptation and preserves leaflet mobility without compromising diastolic function.
Secondary mitral regurgitation has been originally explained by tethering of the structurally normal mitral leaflets or by mitral annular dilation after atrial remodeling. Advances in echocardiography have provided more insights into functional anatomy of the mitral valve leaflets as active participants in this entity.
The aim of the study was to assess the effectiveness of modified mitral valve repair in comparison with traditional methods of correcting ischemic mitral regurgitation.
Materials and methods:
The results of surgical treatment of 80 patients with coronary artery disease complicated by ischemic mitral regurgitation were analyzed. The mean age of the patients was 58.95±8.36 years; the ratio of men and women was 67:13. Heart failure of FC II (according to the NYHA classification) was detected in 6 patients (7.50%), FC III - in 69 (86.25%) patients, FC IV - in 5 (6.25%) patients.Echocardiographic examination was used to determine the significance and genesis of mitral regurgitation in the preoperative period. 57 patients (71.25%) were detected with grade II mitral regurgitation, 23 (28.75%) had grade III.Annuloplasty was chosen as the operation for the correction of the valve apparatus. The patients of group 1 (n=23) underwent reconstructive surgery on the mitral valve using an autopericardial strip according to the technique, which we have developed, in combination with coronary artery bypass grafting (CABG), the patients of group 2 (n=26) underwent plastic surgery using a support ring in combination with CABG, patients of group 3 (n=31) had myocardial revascularization without correction of the valve apparatus.
Results:
The patients of group 2 underwent restrictive mitral annuloplasty performed with rigid support rings, group 1 - with an autopericardial strip as a soft support ring, the patients of group 3 underwent CABG alone.One patient from group 2 died in the early postoperative period due to acute perioperative myocardial infarction.The most common complications were pleurisy, acute cardiovascular failure, acute respiratory failure, and cardiac arrhythmias. The smallest number of complications was noted in the group 3, where patients underwent CABG alone. After surgery, all the patients showed a decrease in mitral regurgitation, which was most pronounced in the groups with annuloplasty.When analyzing the immediate results of the operations, it was revealed that the patients of groups 1 and 2, who underwent combined interventions, had a higher percentage of complications, and the length of their stay in the ICU increased. However, these groups showed a significant improvement in mitral valve functioning. Plasty of the mitral valve with an autopericardial strip according to the technique, which we have developed, demonstrated a good hemodynamic effect, the absence of significant regurgitation in the postoperative period.
Background
Atrial fibrillation (AF), mitral regurgitation (MR), and left ventricular (LV) ejection fraction have a complex interplay. We evaluated the role of AF in patients with heart failure and moderate-to-severe or severe secondary MR enrolled in the randomized COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) and its impact on mechanisms and outcomes with the MitraClip.
Methods
Patients in the COAPT trial were stratified by the presence (n=327) or absence (n=287) of a history of AF and by assignment to treatment group. Clinical, echocardiographic, and outcome measures were assessed. The primary outcome was the composite rate of death or heart failure hospitalization at 24 months.
Results
Patients with history of AF were older and more often male. They had a higher LV ejection fraction, larger left atrial volumes and mitral valve orifice areas, smaller LV volumes, and similar MR severity. Patients with AF compared with those without a history of AF had a higher unadjusted (hazard ratio [HR], 1.32 [95% CI, 1.06–1.64], P =0.01) and adjusted (HR, 1.30 [1.03–1.64], P =0.03) 2-year rate of the primary outcome. Treatment with the MitraClip compared with guideline-directed medical therapy alone reduced death or heart failure hospitalization in both those with (HR, 0.61 [0.46–0.82]) and without (HR, 0.46 [0.33–0.66]) a history of AF ( P int =0.18). Treatment with the MitraClip was associated with a lower risk of stroke in patients with a history of AF (HR, 0.18 [0.04–0.86]) but not in those without a history of AF (HR, 1.64 [0.58–4.62]; P int =0.02).
Conclusions
In the COAPT trial, patients with a history of AF had larger left atrial and mitral valve orifice areas with higher LV ejection fraction and smaller LV volumes, suggesting an atrial mechanism contribution to functional MR. Despite the worse prognosis of heart failure patients with a history of AF, MR reduction with the MitraClip still afforded substantial clinical benefits. Treatment with MitraClip was associated with a lower risk of stroke in patients with a history of AF.
REGISTRATION
URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01626079.
The effects of ring annuloplasty on mitral leaflet motion are incompletely known. The three-dimensional dynamics of the mitral valve in vivo were examined to determine how two types of annuloplasty rings affect leaflet motion during valve closure.
Miniature radiopaque markers on the mitral leaflets, annulus, and left ventricle were implanted in three groups of sheep. One group served as control (n = 7); other sheep were randomly assigned to receive either a flexible Duran (n = 6) or a semirigid Carpentier-Edwards Physio ring (n = 6). After recovery, three-dimensional marker coordinates were computed from simultaneous (60 Hz) biplane videofluoroscopic marker images.
Both types of rings immobilized the middle scallop of the posterior leaflet without affecting anterior leaflet motion. The excursion of the anterior leaflet edge from maximally open to fully closed was not different between the groups (control, 13+/-2 mm; Duran 13+/-1 mm; Physio ring, 14+/-1 mm; p > 0.05), but posterior leaflet edge excursion was restricted (control, 7.4+/-0.4 mm; 2.3+/-0.3 mm [p < 0.001]; Physio, 2.7+/-0.2 mm [p < 0.001]) by both rings.
Mitral annuloplasty with either ring type markedly reduced the mobility of the central posterior leaflet in normal ovine hearts such that valve closure became essentially a single (anterior) leaflet process with the frozen posterior leaflet serving only as a buttress for closing.
Papillary muscle dysfunction (PMD) has been implicated in the pathogenesis of ischemic mitral regurgitation (MR). We hypothesized that ischemic MR is not caused by PMD and/or dysfunction of the myocardial regions from where the papillary muscles arise but is related to reduction in global left ventricular (LV) function. To test this hypothesis, three groups of dogs were studied.
In group 1 dogs (n = 8), varying degrees of regional and global LV dysfunction were produced. In group 2 dogs (n = 7), the circulation to the papillary muscles was isolated from that of the rest of the LV. Dysfunction of one or both papillary muscles was produced without producing global LV dysfunction. Global LV dysfunction was also produced while keeping papillary muscle function intact. The degree of MR (assessed using contrast echocardiography) was correlated in both groups of dogs with thickening of the papillary muscles and regional and global LV function. In the group 3 dogs (n = 6), the spatial distribution of blood flow within each papillary muscle was determined during ischemia by using radiolabeled microspheres. Thickening of the papillary muscles was assessed at three different levels along their lengths and was correlated with average blood flow at these levels. In group 1 dogs, MR was noted only when global LV function was affected and its severity correlated inversely with global LV function (r = -0.84 with peak positive LV dP/dt and r = -0.95 with global LV thickening, respectively). In comparison, there was poor correlation between MR and anterior and posterior papillary muscle thickening (r = -0.38 and r = -0.49, respectively). In group 2 dogs, MR did not occur in the presence of either PMD or akinesia of the immediately adjacent LV myocardium. MR occurred only when global LV dysfunction was produced (with the papillary muscle function intact), and its severity correlated inversely with global LV function (r = -0.92 with LV dP/dt and r = -0.86 with global LV thickening, respectively). There was poor correlation between the degree of MR and thickening of the anterior and posterior papillary muscles (r = -0.24 and r = -0.38, respectively). In both groups of dogs, MR was associated with incomplete mitral leaflet closure (IMLC), and the severity of MR correlated linearly with the degree of IMLC (r = 0.98). MR was never associated with mitral valve prolapse. In the group 3 dogs, despite more inhomogeneous flow during ischemia to the anterior compared with the posterior papillary muscle, mean thickening of these muscles was similar (3 +/- 10% and 3 +/- 4%, respectively). Furthermore, there was minimal variability in thickening between different parts of the muscles (3 +/- 2% and 5 +/- 3%, respectively).
It is concluded that PMD and/or dysfunction of the immediately adjacent LV myocardium does not result in MR. MR occurs during ischemia only when global LV function is affected, even when thickening of the papillary muscles and the immediately adjacent LV remains intact. MR in this situation is related to IMLC; the greater the degree of IMLC, the greater the MR. These findings suggest that the mechanism of ischemic MR is not related to PMD. There may also be important therapeutic implications of these findings.
Background The optimal management of moderate (3+ on a scale of 0 to 4+) ischemic mitral regurgitation (MR) remains controversial. Some advocate CABG alone, whereas others favor concomitant mitral annuloplasty. To clarify the optimal management of these patients, we evaluated the early impact of isolated CABG on moderate ischemic MR.
Methods and Results Between January 1992 and August 1999, 136 patients (54% male, mean age 70.5 years, mean New York Heart Association class 2.7, mean ejection fraction 38.1%) with a preoperative diagnosis of moderate ischemic MR, without leaflet prolapse or pathology, underwent isolated CABG. Thirty-eight (28%) of 136 patients had intraoperative transesophageal echocardiography (TEE) before CABG, and 68 (50%) had postoperative transthoracic echocardiography (TTE) within 6 weeks of surgery. The subgroups of patients undergoing intraoperative TEE and postoperative TTE had preoperative characteristics similar to the overall group. The 30-day operative mortality was 2.9% ( \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{4}{136}\) \end{document} ). Intraoperative TEE downgraded the severity of MR to mild or less (0 to 2+) in 89% ( \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{34}{38}\) \end{document} ). On postoperative TTE, 40% ( \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{27}{68}\) \end{document} ) continued to have at least moderate MR (3 to 4+), 51% ( \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{35}{68}\) \end{document} ) improved somewhat to mild (2+) MR, and only 9% ( \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{6}{68}\) \end{document} ) had resolution of their MR (0 to 1+). The mean preoperative, intraoperative, and postoperative MR grades were 3.0±0.0, 1.4±1.0, and 2.3±0.8, respectively ( P <0.001).
Conclusions CABG alone for moderate ischemic MR leaves many patients with significant residual MR and may not be the optimal therapy for most patients. Intraoperative TEE may significantly underestimate the severity of ischemic MR. A preoperative diagnosis of moderate MR may warrant concomitant mitral annuloplasty.
Background Edge-to-edge approximation of the mitral valve leaflets (Alfieri procedure) is a novel surgical treatment for patients with ischemic mitral regurgitation (IMR). Long-term durability may be limited if abnormal mitral leaflet stresses result from this procedure. The aim of the current study was to measure Alfieri stitch tension (F A ) and to explore its geometric determinants in an ovine model of acute IMR as a reflection of the mitral leaflet stresses imposed by the procedure.
Methods and Results Eight sheep were studied immediately after surgical placement of (1) a force transducer interposed between sutures approximating the central leaflet edges and (2) radiopaque markers around the mitral annulus and leaflet edges. Computer-aided analysis of videofluorograms was used to obtained 3D marker coordinates. Simultaneous measurements of F A , septal-lateral annular dimension (L S-L ), leaflet edge separation (L SEP ), anterior (L AL ) and posterior (L PL ) leaflet length, and hemodynamic variables were obtained at baseline (CTL) and during acute IMR (circumflex artery occlusion). F A was significantly elevated throughout the cardiac cycle during IMR compared with CTL, with maximum F A in diastole (0.26±0.05 versus 0.46±0.08 N, CTL versus IMR; P <0.05). Multivariable analysis revealed L S-L as the single independent predictor of maximum F A ( P <0.001). Positive linear correlations were shown between values of F A and L AL and L PL (dependent variables).
Conclusions These experimental data demonstrate higher F A during IMR and cyclic changes in F A closely paralleling changes in L S-L , eg, being greatest in diastole when the annulus is largest. Increased F A during IMR is probably indicative of successful therapeutic intent, but higher diastolic leaflet stresses resulting from persistent or progressive mitral annular dilatation may adversely affect repair durability. This indirectly implies that concomitant mitral ring annuloplasty should be added to the Alfieri repair.
An endoscope was used to study the anatomy and morphology of the native mitral valve inside an isolated pig heart working under physiological conditions. Annulus motion, valve leaflet function, and the anatomy of the chords and branching pattern are described. Anatomical and functional details relevant to mitral valve reconstruction and valve replacement are outlined. Because of the similarity with the human heart, we have assumed that the observations made in the pig heart also apply to humans.
The unimpeded, forward flow of blood across the mitral orifice is contingent upon a coordinated interaction between the mitral annulus, the mitral valve leaflets, the chordae tendineae, and the papillary muscles. An understanding of the functional anatomy and physiology of each of these components of the "mitral complex" is clinically important for derangement of any part may produce obstruction to blood flow or allow mitral regurgitation. The differential diagnosis then of mitral stenosis and mitral regurgitation can be functionally analyzed in terms of diseases of the mitral annulus, diseases of the mitral valve leaflets, diseases of the chordae tendineae, and diseases of the papillary muscles. By this consideration of selective involvement of the mitral complex, certain physical signs, such as the late systolic murmur that may occur in papillary muscle dysfunction, the "murmur on top of the head" heard with a ruptured chordae tendineae to the anteromedial mitral leaflet, the chordal snap of a redundant chordae tendineae, or the atrial gallop of an acutely ruptured chordae tendineae, can be sought for in an attempt to differentiate clinically the possible etiology of the disease and its anatomic area of involvement. This correlation of physical signs with the functional anatomy helps to provide an additional scientific basis to the physical examination.
Background— This study was conducted to elucidate the geometric differences of the mitral apparatus in patients with significant mitral regurgitation caused by ischemic cardiomyopathy (ICM-MR) and by idiopathic dilated cardiomyopathy (DCM-MR) by use of real-time 3D echocardiography (RT3DE).
Methods and Results— Twenty-six patients with ICM-MR caused by posterior infarction, 18 patients with DCM-MR, and 8 control subjects were studied. With the 3D software, commissure-commissure plane and 3 perpendicular anteroposterior (AP) planes were generated for imaging the medial, central, and lateral sides of the mitral valve (MV) during mid systole. In 3 AP planes, the angles between the annular plane and each leaflet (anterior, Aα; posterior, Pα) were measured. In ICM-MR, Aα measured in the medial and central planes was significantly larger than that in the lateral plane (39±5°, 34±6°, and 27±5°, respectively; P<0.01), whereas Pα showed no significant difference in any of the 3 AP planes (61±7°, 57±7°, and 56±7°, P>0.05). In DCM-MR, both Aα (38±8°, 37±9°, and 36±7°, P>0.05) and Pα (59±6°, 58±5°, and 57±6°, P>0.05) revealed no significant differences in the 3 planes.
Conclusions— The pattern of MV deformation from the medial to the lateral side was asymmetrical in ICM-MR, whereas it was symmetrical in DCM-MR. RT3DE is a helpful tool for differentiating the geometry of the mitral apparatus between these 2 different types of functional mitral regurgitation.
Background— In ischemic mitral regurgitation (MR), mitral leaflet closure is restricted by ventricular remodeling with displacement of the papillary muscles (PMs). Therapy is uncertain because ring annuloplasty does not alleviate PM displacement. We tested the hypothesis that echo-guided PM repositioning using an external device can reduce MR without compromising left ventricular (LV) function.
Methods and Results— We studied 10 sheep with ischemic MR produced by circumflex ligation with inferior infarction, 6 acutely and 4 eight weeks after myocardial infarction (MI). A Dacron patch containing an inflatable balloon was placed over the PMs and adjusted under echo guidance to reverse LV remodeling and reposition the infarcted PM. 3D echo assessed mitral valve geometric changes. In 7 sheep, sonomicrometry and Millar catheters assessed changes in end-systolic and end-diastolic pressure-volume relationships, and microspheres were injected to assess coronary flow. Moderate MR after MI resolved with patch application alone (n=3) or echo-guided balloon inflation, which repositioned the infarcted PM, decreasing the PM tethering distance from 31.1±2.5 mm after MI to 26.8±1.8 with patch ( P <0.01; baseline=25.5±1.5). LV contractility was unchanged (end-systolic slope=3.4±1.6 mm Hg/mL with patch versus 2.8±1.6 after MI). Although there was a nonsignificant trend for a mild increase in stiffness constant (0.07±0.05 mL−1 versus 0.05±0.03 after MI, P =0.06), LV end-diastolic pressure was unchanged as MR resolved. Coronary flow to noninfarcted regions was not reduced.
Conclusions— An external device that repositions the PMs can reduce ischemic MR without compromising LV function. This relatively simple technique can be applied under echo guidance in the beating heart.
Received June 3, 2002; revision received August 28, 2002; accepted September 2, 2002.
The sudden development of a harsh apical systolic murmur in a patient with a recent myocardial infarct is usually considered to indicate rupture of a papillary muscle or perforation of the interventricular septum.1,2 the differential diagnosis of a loud precordial systolic murmur of sudden onset may be difficult and to describe a syndrome whereby such a murmur may occur secondary to mechanical dysfunction of a papillary muscle.
Illustrative Patients
Patient 1.
—An 85-year-old white male, previously in good health, was admitted to hospital with severe crushing substernal pain which he had had for several hours. His blood pressure was 135/75 mm Hg, and his pulse rate was 88 per minute and regular. The lungs were clear on auscultation. The heart was not enlarged, and there were no murmurs or gallop sounds. The electrocardiogram on admission showed an acute anteroseptal myocardial infarct. The serum glutamic oxaloacetic transaminase (SGOT) was 165
Background— Functional mitral regurgitation (MR) is common in patients with heart failure and left ventricular (LV) dysfunction, and its severity may vary over time, depending primarily on the loading conditions. Because dynamic changes in the severity of functional MR may affect forward stroke volume, we hypothesized that exercise-induced changes in MR severity influence the stroke volume response of patients with LV dysfunction to exercise, and hence their exercise capacity.
Methods and Results— Heart failure patients (n=25; mean age 53±12 years) with LV dysfunction underwent dynamic bicycle exercise at steady-state levels of 30%, 60%, and 90% of predetermined peak V̇ o 2 . During each exercise level, right heart pressures, cardiac output, V̇ o 2 , and MR severity were measured simultaneously. During exercise, MR severity, as evaluated by the ratio of MR jet over left atrium area, increased from 15±8% to 33±15%. Peak V̇ o 2 , exercise-induced changes in stroke volume, and those in capillary wedge pressure correlated with the changes in MR ( r =−0.55, −0.87, and 0.62, respectively, P <0.01). The changes in MR severity also correlated with those in end-diastolic ( r =−0.75, P <0.01) and end-systolic ( r =−0.72, P <0.01) sphericity indexes and those in the coaptation distance ( r =0.86, P <0.01).
Conclusions— Our data indicate that in patients with LV dysfunction, exercise-induced changes in MR severity limit the stroke volume adaptation during exercise and therefore contribute to limitation of exercise capacity.
Objectives. We used color Doppler flow mapping to determine whether vena contracta width (VCW) is a load-independent measure of the severity of mitral regurgitation.
Background. VCW has been proposed to be a relatively load-independent measure of mitral regurgitation severity in flow models using a fixed orifice. However, in patients with mitral regurgitation, VCW may not be load independent because of a dynamic regurgitant orifice.
Methods. VCW, effective regurgitant orifice area and regurgitant volume were measured by quantitative Doppler mapping in 31 patients with chronic mitral regurgitation at baseline and during nitroprusside infusion. Patients with rheumatic heart disease, annular calcification or endocarditis were considered to have a fixed regurgitant orifice, whereas patients with mitral valve prolapse, dilated cardiomyopathy or ischemia were considered to have a dynamic regurgitant orifice.
Results. Systolic blood pressure (148 ± 27 to 115 ± 25 mm Hg) and end-systolic wall stress (121 ± 50 to 89 ± 36) decreased with nitroprusside (p < 0.05). Although nitroprusside did not significantly change mean values for VCW (0.5 ± 0.2 to 0.5 ± 0.2 cm), regurgitant volume (69 ± 47 to 69 ± 56 ml) or effective regurgitant orifice area (0.5 ± 0.4 to 0.5 ± 0.6 cm2), individual patients exhibited marked directional variability. Specifically, VCW decreased in 16 patients (improved mitral regurgitation), remained unchanged in 7 patients and increased in 8 patients (worsened mitral regurgitation) with nitroprusside. Also, the VCW response to nitroprusside was concordant with changes in effective regurgitant orifice area and regurgitant volume, and was not different between dynamic and fixed orifice groups.
Conclusions. Contrary to the results from in vitro studies, VCW is not load independent in patients with mitral regurgitation caused by dynamic changes in the regurgitant orifice. The origin of mitral regurgitation does not predict accurately whether the regurgitant orifice is fixed or dynamic. Finally, short-term vasodilation with nitroprusside may significantly worsen the severity of mitral regurgitation in some patients.
OBJECTIVES We used the Doppler proximal flow convergence technique as a physiologic tool to explore the effects of the time courses of mitral annular area and transmitral pressure on dynamic changes in regurgitant orifice area. BACKGROUND In functional mitral regurgitation (MR), regurgitant flow rate and orifice area display a unique pattern, with peaks in early and late systole and a midsystolic decrease. Phasic changes in both mitral annular area and the transmitral pressure acting to close the leaflets, which equals left ventricular-left atrial pressure, have been proposed to explain this dynamic pattern.
Objectives
We sought to test whether isolated mitral annular (MA) dilation can cause important functional mitral regurgitation (MR).
Introduction:
Mitral valve regurgitation (MR) occurring as a result of myocardial ischemia and global left ventricular (LV) dysfunction predicts poor outcome. This study assessed the feasibility of mitral valve (MV) surgery concomitant with coronary artery bypass grafting (CABG) in patients with mild-to-moderate and moderate ischemic MR and impaired LV function.
Materials and method:
From January 1996 to July 2000, 49 patients (group 1) and 50 patients (group 2) with grade II and grade III ischemic MR and LV ejection fraction (EF) between 17% and 30% underwent combined MV surgery and CABG (group 1) or isolated CABG (group 2). LVEF (%), LV end-diastolic diameter (EDD) (mm), LV end-diastolic pressure (EDP) (mmHg), and LV end-systolic diameter (ESD) (mm) were 27.5 +/- 5, 67.7 +/- 7,27.7 +/- 4, and 51.4 +/- 7, respectively in group 1 versus 27.8 +/- 4, 67.5 +/- 6, 27.5 +/- 5, and 51.2 +/- 6, respectively in group 2. Groups 1 and 2 were divided into Groups 1A and 2A with mild-to-moderate MR (22 [45%] and 28 [56%] patients, respectively) and groups 1B and 2B with moderate MR (27 [55%] and 22 [46%], respectively). In group 1, MV repair was performed in 43 (88%) patients and MV replacement in 6 (12%) patients.
Results:
Preoperative data analysis did not reveal any difference between groups. Five (10%) patients in group 1 died versus 6 (12%) in group 2 (p = ns). Within 6 months after surgery, LV function and its geometry improved significantly in group 1 versus group 2 (LVEF, p < 0.001; LVEDD, p = 0.002; LVESD, p = 0.003; and LVEDP (p < 0.001) improved significantly in group 1 instead of a mild improvement in Group 2). The regurgitation fraction decreased significantly in group 1 patients after surgery (p < 0.001). There was an inverse strong correlation between postoperative forward cardiac output and regurgitation fraction (p < 0.001). LVEF and LVESD improved significantly in group 1 versus group 2 patients (p = 0.04 and p = 0.02, respectively). The cardiac index increased significantly in group 1 and 2 (p < 0.001 and p = 0.03, respectively). LV function and geometry improved significantly postoperatively in group 1B versus group 2B (LVEDD, p = 0.027; LVESD, p = 0.014; LVEDP, p = 0.034; and LVEF, p = 0.02), instead of a mild improvement in group 1A versus group 2A (LVESD, p = 0.015; LVEF, p = 0.046; and LVEDD and LVEDP, p = 0.05). At follow-up, 4 (67%) of 6 patients undergoing MV replacement died versus 5 (11.5%) of 43 patients undergoing MV repair in group 1 (p = 0.007). The overall survival at 3 years in Group 2 was significantly lower than group 1 (p < 0.009).
Conclusion:
MV repair and replacement-preserving subvalvular apparatus in patients with impaired LV function offered acceptable outcomes in terms of morbidity and survival. Surgical correction of mild-to-moderate and moderate MR in patients with impaired LV function should be taken into consideration since it yields better survival and improved LV function.
Mitral regurgitation (MR) may start during the acute phase of myocardial infarction and it may increase, decrease, or remain unchanged as the necrotic muscle is replaced by fibrous tissue and remodeling of the ventricle takes place. Acute infarction can cause MR because of rupture of papillary muscle (PM) head or dysfunction of the PM and underlying ventricular wall. When MR is due to rupture of a single PM head and the surrounding muscle is not extensively Infarcted, it is possible to suture the PM head in place with pledget sutures or to use other techniques of repair of flail leaflets such as chordal transfer or chordal replacement. When MR Is due to extensive necrosis of the PM and the ventricular wall, it is safer to replace the mitral valve with preservation of the chordae tendineae. Correction of MR by means of valve repair in patients with healed myocardial infarction is frequently possible when the cause of MR is determined by Doppler echocardiography. The most common cause of MR Is incomplete closure of the mitral valve due to apical displacement of the PM. Prolapse of the leaflets is rare in patients with healed myocardial infarction. Mitral annuloplasty decreases or abollshes MR in most cases when lack of coaptation of the leaflets is the problem. Transient Ischemia can also cause MR. Successful myocardial revas-cularization either by angioplasty or coronary artery bypass often cures episodic ischemic MR. (J Card Surg 1994;9[Suppl]:274–277)
A strong association has been recognized between partial or complete mitral leaflet flail and highly eccentric mitral regurgitation jets. In light of anecdotal observation of eccentric mitral regurgitation apparently due to geometric and functional changes accompanying inferior wall myocardial infarction, the present study was performed to systematically study the eccentricity of mitral regurgitation jets complicating nonacute inferior wall myocardial infarction. Forty-eight consecutive patients with evidence of prior isolated inferior wall myocardial infarction and at least moderate mitral regurgitation but without other valvular, annular, chordal, or ventricular pathology potentially contributory to mitral regurgitation were studied. Mitral regurgitation jets were characterized with respect to eccentricity and anterior versus posterior direction. Regurgitant jet and mitral leaflet position were quantified relative to the mitral annulus. Five of 48 patients (10.4%) had eccentric jets, of which four were directed posterior and one anterior. Although not reaching statistical significance, patients with eccentric jets tended to have somewhat smaller left atrial size (41.2 ± 7.8 vs 47.2 ± 9.3 mm, P= 0.17) and left ventricular size (51.5 ± 3.4 vs 55.1 ± 7.8 mm, P= 0.13), and higher left ventricular ejection fraction (0.52 ± 0.11 vs 0.46 ± 0.09, P= 0.25) compared with patients with noneccentric jets. Leaflet position relative to the mitral annulus was significantly different among patients with eccentric compared with noneccentric posterior jets (54 ± 10° vs 33 ± 11°, P= 0.02), implying greater leaflet restriction toward the left ventricular apex. In conclusion, approximately one in 10 patients with isolated inferior wall myocardial infarction and at least moderate mitral regurgitation was found to have marked eccentricity of the regurgitant jet. Leaflet position was more apically displaced among patients with eccentric jets, suggesting greater leaflet restriction in systole. The finding of a highly eccentric posterior mitral regurgitation jet can be due to inferior wall myocardial infarction with posterior leaflet restriction as well as partial or complete anterior mitral leaflet flail.
Background:
Chordal transposition is used in mitral valve repair, yet the effects of second-order chord transection on valve function have not been extensively studied. We evaluated leaflet coaptation, three-dimensional anterior mitral valve leaflet shape, and valve competence after cutting anterior second-order chordae.
Methods:
In 8 sheep radiopaque markers were affixed to the left ventricle, mitral annulus, and leaflets. Animals were studied immediately with biplane videofluoroscopy and echocardiography before (Control) and after (Cut2) severing two anterior second-order "strut" chordae. Leaflet coaptation was assessed as separation between leaflet edge markers in the midleaflet and near each commissure (anterior commissure, posterior commissure). Anterior leaflet geometry was determined 100 milliseconds after end-diastole from three-dimensional coordinates of 13 markers.
Results:
Anterior leaflet geometry changed only slightly after chordal transection without inducing mitral regurgitation. Leaflet coaptation times were 79+/-17 and 87+/-22 milliseconds at the anterior commissure; 72+/-21, 72+/-19 milliseconds at midleaflet, and 71+/-12 and 75+/-8 milliseconds at the posterior commissure (p = NS) for Control and Cut2, respectively.
Conclusions:
Cutting anterior second-order chordae did not cause delayed leaflet coaptation, alter leaflet shape, or create mitral regurgitation. These data indicate that transposition of second-order anterior chordae ("strut" chordae) is not deleterious to anterior leaflet motion per se.
Background:
Ischemic mitral regurgitation or ventricular wall motion abnormalities will alter the stress distribution in the mitral valve. We hypothesize that in response, the regional collagen concentration will be altered and will significantly impact the stress distribution in the mitral valve.
Methods:
Two sheep served as normal (sham) controls. Two other sheep had coronary ligation resulting in abnormal ventricular wall motion. Four sheep underwent ligation to infarct the posteromedial papillary muscle, resulting in ischemic regurgitation. After 4 or 8 weeks, the mitral valves were excised, and the anterior leaflet sections were subjected to an assay for collagen concentration. Next, in a finite element model, to simulate changes in collagen concentration, the tissue stiffness was increased by 20%, and then decreased by 20%. In another model, the thickness of the tissue was increased by 20%, and then combined with decreased tissue stiffness. Physiologic loading pressures were applied, and leaflet stress, chordal stress, and coaptation results were analyzed.
Results:
The average collagen concentration in the normal sheep leaflets was 59.2% (dry weight), 50.6% in the ischemic controls, and 45.8% in the papillary muscle infarct group. Collagen concentration was greatest at the midline and decreased toward the commissures. Increased tissue stiffness resulted in increased leaflet and chordal stresses, as well as reduced coaptation. Decreased stiffness resulted in the opposite. Increased tissue thickness reduced leaflet and chordal stresses, but also reduced coaptation. The combination of increased tissue thickness and decreased stiffness demonstrated the greatest reduction in leaflet and chordal stress, while maintaining normal leaflet coaptation.
Conclusions:
The observed changes may demonstrate an early effort to compensate for increased leaflet stress. Microstructural alterations may demonstrate an early effort to compensate for altered physiologic loading to reduce stress and maintain coaptation. It is crucial in repairing or partially replacing thickened tissue that normal geometry and physiology be restored.
Objectives:
This study was designed to test the hypothesis that reperfusion therapy with thrombolysis will prevent the development of significant mitral regurgitation in patients with inferior myocardial infarction.
Background:
The value of thrombolytic therapy in patients with inferior or posterior wall myocardial infarction has been controversial. We hypothesized that successful reperfusion therapy with intravenous thrombolysis may reduce the incidence and severity of postinfarction mitral regurgitation in this patient group.
Methods:
We prospectively studied 104 patients with a first inferior myocardial infarction. Thrombolytic therapy was administered to 55 patients (treatment group) 3.2 +/- 2.1 h after the onset of symptoms. The other 49 patients formed the control group. Doppler echocardiographic color flow imaging was performed in all patients within 24 h, at 7 to 10 days and at 28 to 30 days after myocardial infarction. Significant mitral regurgitation was defined as moderate or severe (grade 2 or 3).
Results:
No significant differences in baseline clinical characteristics were observed between the treatment and control groups. The overall incidence rates of significant mitral regurgitation at 24 h, 7 to 10 days and at 28 to 30 days were 10 (10%) of 104 patients, 18 (17%) of 104 patients and 11 (11%) of 100 patients, respectively. Multivariate analysis reveals the following independent predictors of the occurrence of significant mitral regurgitation: female gender (at 7 to 10 days, odds ratio 5.3, 90% confidence interval [CI] 1.8 to 15.5; at 28 to 30 days, odds ratio 3.7, 90% CI 1.1 to 12.7), heart failure (at 7 to 10 days, odds ratio 7.7, 90% CI 2.2 to 26.9) and transient complete atrioventricular block (at 24 h of myocardial infarction, odds ratio 5.8, 90% CI 1.2 to 27). Compared with the control group, the treatment group exhibited marked reduction in the incidence of significant mitral regurgitation at 24 h (16% vs. 4%; odds ratio 0.1, 90% CI 0.0 to 0.7); at 7 to 10 days (24% vs. 11%; odds ratio 0.3, 90% CI 0.1 to 0.9) and at 28 to 30 days (15% vs. 7%; odds ratio 0.4, 90% CI 0.1 to 1.6). Severe (grade 3) mitral regurgitation developed in five patients in the control group but in no patient in the treatment group.
Conclusions:
Thrombolytic therapy in the patients with a first inferior myocardial infarction was associated with a reduced incidence of significant mitral regurgitation. These results support the use of such therapy in patients with inferior myocardial infarction.
Previously described Doppler color How mapping methods for estimating the severity of valvular regurgitation have focused on the distal jet. In this study, a newer Doppler color flow technique, focusing on the flow proximal to an orifice, was used. This method identifies a proximal isovelocity surface area (PISA) by displaying an aliasing interface. Volume flow rate (cm3/s) can be calculated as PISA (cm2) × aliasing velocity (cm/s). For planar circular orifices, a hemi-elliptic model accurately approximated the shape of PISA.
Objectives:
The aim of this study was to examine the temporal association between the onset of functional mitral regurgitation and the development of changes in left ventricular shape, chamber enlargement, mitral anulus dilation and regional wall motion abnormalities during the course of evolving heart failure.
Background:
Despite extensive characterization, the exact etiology of functional mitral regurgitation in patients with chronic heart failure remains unknown.
Methods:
Heart failure was produced in seven dogs by multiple sequential intracoronary microembolizations. Serial changes in left ventricular chamber volume and shape were evaluated from ventriculograms. Changes in mitral anulus diameter and ventricular regional wall motion abnormalities were evaluated echocardiographically. The presence and severity of mitral regurgitation were determined with Doppler color flow mapping. Measurements were obtained at baseline and then biweekly until mitral regurgitation was first observed.
Results:
No dog had mitral regurgitation at baseline but all developed mild to moderate regurgitation 12 +/- 1 weeks after the first embolization. The onset of mitral regurgitation was not associated with an increase in left ventricular end-diastolic volume relative to baseline (58 +/- 3 vs. 62 +/- 3 ml), mitral anulus diameter (2.4 +/- 0.1 vs. 2.4 +/- 0.1 cm) or wall motion abnormalities of left ventricular wall segments overlying the papillary muscles. In contrast, the onset of mitral regurgitation was accompanied by significant changes in global left ventricular shape evidenced by increased end-systolic chamber sphericity index (0.22 +/- 0.02 vs. 0.30 +/- 0.01) (p < 0.01) and decreased end-systolic major axis/minor axis ratio (1.71 +/- 0.05 vs. 1.43 +/- 0.04) (p < 0.001).
Conclusions:
These data indicate that transformation of left ventricular shape (increased chamber sphericity) is the most likely substrate for the development of functional mitral regurgitation.
Objectives:
This study was designed to investigate the association between wall motion abnormalities and the occurrence of ischemic mitral regurgitation in patients with a first inferior or posterior myocardial infarction and to reassess the role of thrombolytic treatment in these patients.
Background:
We previously demonstrated that thrombolytic therapy reduces the incidence of significant mitral regurgitation in patients with a first inferior myocardial infarction, but the mechanisms responsible for this decrease were not clear.
Methods:
Wall motion score on two-dimensional echocardiography (16 segments) and mitral regurgitation grade (0 to 3) on Doppler color flow imaging were assessed in 95 patients (in 47 after thrombolysis) at 24 h, 7 to 10 days and 1 month after myocardial infarction. Significant mitral regurgitation was defined as moderate or severe (grade 2 or 3).
Results:
Multivariate analysis revealed that the presence of an advanced wall motion abnormality of the posterobasal segment of the left ventricle was the most significant independent variable associated with significant mitral regurgitation: odds ratio (OR) 15.0, 90% confidence interval (CI) 1.4 to 165.6 at 24 h; OR 2.8, CI 0.9 to 9.3 at 7 to 10 days; OR 4.2, CI 1.2 to 11.4 at 1 month. Thrombolysis reduced the prevalence of advanced wall motion abnormalities in the posterobasal segment at 24 h (55% vs. 75%, OR 0.5, CI 0.2 to 0.99), 7 to 10 days (44% vs. 73%, OR 0.3, CI 0.1 to 0.7) and 1 month (36% vs. 56%, OR 0.4, CI 0.2 to 0.9).
Conclusions:
There is a strong association between advanced wall motion abnormalities in the posterobasal segment and significant mitral regurgitation. In this study group, thrombolysis reduced the prevalence of advanced wall motion abnormalities in the posterobasal segment and thereby reduced the incidence of significant mitral regurgitation.
Cross-sectional echocardiography identified two abnormal patterns of mitral valve closure in 14 patients with mitral regurgitation due to papillary muscle dysfunction: (1) in three patients with an akinetic inferior-posterior wall but normal cavity size, papillary muscle fibrosis was associated with late systolic mitral valve prolapse, and (2) in nine patients with ventricular dilatation or ventricular aneurysm, the point of mitral valve coaptation was displaced towards the apex of the left ventricle. In two of these patients both abnormalities were observed. In contrast, abnormal patterns were identified in only four of a group of 40 patients without angiographic evidence of mitral regurgitation (10, normal; 27, coronary artery disease; three, congestive cardiomyopathy). Thus, cross-sectional echocardiography can be useful to identify mitral regurgitation secondary to papillary muscle dysfunction.
To investigate mitral regurgitation occurring early in the course of acute myocardial infarction with respect to its incidence, the impact of infarct size and location, the accuracy of clinical detection, the contribution of global and regional left ventricular performance, and its influence on prognosis.
Prospective observational study derived from patients entering Phase I of the Thrombolysis in Myocardial Infarction (TIMI) trial.
Multicenter trial involving 13 university-affiliated medical centers.
A total of 206 patients studied within 7 hours of symptom onset during their first myocardial infarction.
Contrast left ventriculography was used to document mitral regurgitation.
Mitral regurgitation was present in 27 patients (13%). Although the presence of regurgitation correlated with the site of infarction (20 of 27 had anterior infarctions) and the number of akinetic chords, it was not statistically related to the peak creatine kinase value or to left ventricular chamber size or filling pressure. A murmur of mitral regurgitation was heard in only 2 patients (1 incorrectly). The presence of early mitral regurgitation predicted cardiovascular mortality at 1 year by univariate (relative risk, 12.2; 95% Cl, 3.5 to 42; P less than 0.0001) and multivariate (relative risk, 7.5; Cl, 2.0 to 28.6; P = 0.0008) analyses.
Mitral regurgitation in early myocardial infarction is generally clinically "silent," is more common in anterior infarction, is associated with regional dysfunction but not early ventricular dilation or peak enzyme release, and is an important predictor of cardiovascular mortality.
The temporal relationship between left ventricular (LV) shape changes and the development of LV dysfunction, dilation, and sympathoadrenergic hyperactivity was examined in 10 dogs with chronic heart failure produced by multiple sequential intracoronary microembolizations. LV shape was quantitated from serial ventriculograms based on the ratio of the major to minor axis at end systole and end diastole. Measurements were made at baseline (before embolizations) and were repeated at 2, 8, and 16 wk after the last embolization. A significant increase of LV sphericity was present at 2 wk, with only minimal changes occurring thereafter. Despite the tendency for LV shape changes to plateau between 2 and 16 wk, LV ejection fraction continued to decline (31 +/- 1 vs. 20 +/- 2%; P less than 0.001), and LV end-diastolic volume continued to increase (86 +/- 6 vs. 103 +/- 9 ml; P less than 0.01) as did plasma norepinephrine concentration (456 +/- 30 vs. 868 +/- 172 pg/ml; P less than 0.02). These data indicate that in the course of evolving heart failure, LV shape abnormalities precede the development of profound LV dysfunction, dilation, and overt activation of the sympathetic nervous system.
Intraoperative transesophageal Doppler color flow imaging (TDCF) affords the opportunity to assess mitral valve competency immediately before and after cardiopulmonary bypass (CPB). The purpose of this study was to assess the utility of TDCF to assist in the selection and operative treatment of ischemic mitral regurgitation (MR).
Two hundred forty-six patients undergoing surgery for ischemic heart disease were prospectively studied. All had preoperative cardiac catheterization. Catheterization and pre-CPB TDCF were discordant in their estimation of MR in 112 patients (46%). Compared with patients in whom both techniques agreed in estimation of MR, patients with discordance in MR were more likely to have had unstable clinical syndromes at the time of catheterization (79% versus 40%, p less than 0.05) or to have received thrombolytics (16% versus 8%, p less than 0.05). Pre-CPB TDCF resulted in a change in the operative plan with respect to the mitral valve in 27 patients (11%). Because less MR was found by TDCF than catheterization, 22 patients had only coronary bypass grafting when combined coronary bypass and mitral valve surgery had been planned. Because more MR was found by TDCF than catheterization, five patients had combined coronary bypass and mitral valve surgery when coronary bypass alone had been planned. Unsatisfactory results noted by TDCF following mitral valve surgery in five patients resulted in immediate corrective surgery. Cox regression analysis identified residual MR at the completion of surgery to be an important predictor of survival (chi 2 = 21.4) after surgery--more important than patient age (chi 2 = 8.3) or left ventricular ejection fraction (chi 2 = 5.3).
These results indicate that TDCF is useful in guiding patient selection and operative treatment of ischemic MR and that in such patients, intraoperative TDCF should be performed routinely.
To define the prevalence and role of left ventricular (LV) systolic dysfunction, LV diastolic dysfunction and mitral regurgitation (MR) in patients with acute pulmonary edema, 40 patients with coronary artery disease and acute pulmonary edema were prospectively evaluated within 36 hours of presentation. LV ejection fraction and 3 parameters of LV diastolic function were measured with radionuclide ventriculography, whereas MR was assessed with Doppler echocardiography. LV ejection fraction was normal in 11 (27%) and depressed in 29 (73%) patients. Moderate or severe MR without LV diastolic dysfunction was common and equally prevalent in patients with and without LV systolic dysfunction (33 vs 38%; difference not significant). Diastolic dysfunction without MR was less frequent but equally prevalent in patients with and without systolic dysfunction (17 vs 27%; difference not significant). Two (18%) of 11 patients without and 12 (33%) of 36 patients with LV systolic dysfunction had both MR and LV diastolic dysfunction. Furthermore, MR was clinically silent and unsuspected in two-thirds of all patients with MR, regardless of a normal or depressed systolic function. These data show that there is a high prevalence of unrecognized moderate to severe MR in patients with acute pulmonary edema, regardless of the presence or absence of LV systolic dysfunction. Furthermore, the prevalence of LV diastolic dysfunction without MR is relatively low even in patients with normal LV systolic function and pulmonary edema. Thus, unrecognized MR may be an important contributor to the syndrome of acute pulmonary edema in patients with normal or depressed LV systolic function.
Afterload reduction therapy can acutely improve hemodynamic function in patients with advanced heart failure; however, it is unknown if initial reductions in mitral and tricuspid regurgitation and atrial volumes can be sustained with oral therapy. Atrial volumes and atrioventricular valve regurgitation were measured using 2-dimensional and Doppler echocardiography with color-flow imaging in 14 patients with dilated heart failure (ejection fraction 17 +/- 4%) before and after 3 +/- 1 days of intensive vasodilator and diuretic therapy tailored to hemodynamic goals. Echocardiography was repeated again after 6 +/- 2 months on oral vasodilators and a flexible diuretic regimen. Acute therapy reduced systemic vascular resistance from 1,760 +/- 460 to 1,010 +/- 310 dynes.s.cm-5, pulmonary artery wedge pressure from 30 +/- 5 to 17 +/- 4 mm Hg, and right atrial pressure from 13 +/- 5 to 7 +/- 3 mm Hg, and led to a 61% increase in stroke volume (from 36 +/- 10 to 58 +/- 14 ml) (p less than 0.01). Mitral and tricuspid regurgitation, determined by color-flow fraction, initially decreased from 0.34 +/- 0.17 to 0.20 +/- 0.20 and from 0.33 +/- 0.15 to 0.13 +/- 0.13, respectively (p less than 0.001). This reduction was sustained at 6 months. Significant decreases occurred with acute therapy, with further reductions at 6 months in both mean left atrial volume (from 100 +/- 25 to 80 +/- 19 to 65 +/- 15 cm3) and right atrial volume (from 85 +/- 23 to 64 +/- 23 to 52 +/- 14 cm3) (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
The authors determined the stress/strain characteristics of basal and marginal mitral valve chordae tendineae. The chordae exhibit a nonlinear stress/strain behavior typical of biologic materials, with a discrete transition in the tensile elastic modulus. The post-transition moduli for both basal and marginal chordae are greater than the pretransition values by a factor of approximately 10. In addition, the stress carried by the marginal chordae is higher than that supported by the basal ones at all recorded strains, indicating the marginal chordae are stiffer than the basal chordae. The authors determined the number and distribution of chordal insertions, and found a marginal to basal insertion ratio of almost 2 to 1. The implication is that it may be possible surgically to remove basal chordae without seriously compromising mitral valve function.
To define the frequency, natural history and clinical correlates of the murmur of mitral regurgitation (MR) detected after myocardial infarction, clinical data from 849 patients with documented acute myocardial infarction were analyzed. A murmur suggestive of MR was present on admission in 76 patients (9%). Patients with MR on admission were older and more apt to be female and nonwhite. They also had a significantly greater frequency of prior infarction and signs and symptoms of congestive heart failure. There was no difference in the location (anterior or inferior) of infarction. Patients with MR on admission had a 36% mortality compared to 16% for those who developed MR later in the hospitalization and 15% for those without MR by auscultation (p less than 0.001). Correction for differences in baseline variables indicated that the presence of MR on admission did not contribute independently to mortality. Thus, the murmur of MR derives its prognostic significance from integration of multiple clinical, radiographic and electrocardiographic characteristics.
Cardiac performance and mitral regurgitation were measured by Doppler echocardiography and right heart catheterization in 12 patients with severe congestive heart failure who performed isometric exercise during control and intravenous administration of dobutamine and nitroglycerin. During control isometric exercise, mitral regurgitant volume increased from 18 +/- 13 to 31 +/- 17 ml (p less than 0.01), while forward stroke volume, by both thermodilution and Doppler echocardiography, substantially decreased. At rest, dobutamine decreased mitral regurgitant volume from 18 +/- 13 to 11 +/- 10 ml (p less than 0.05), while forward stroke volume increased from 46 +/- 13 to 55 +/- 15 ml (p less than 0.05). During isometric exercise, dobutamine tended to decrease mitral regurgitant volume (24 +/- 12 vs. 31 +/- 17 ml; NS) when compared with control exercise. At rest, nitroglycerin decreased mitral regurgitant volume from 18 +/- 13 to 11 +/- 11 ml (p less than 0.05), while forward stroke volume, by both thermodilution and Doppler echocardiography, substantially increased. Similarly, during isometric exercise, nitroglycerin decreased mitral regurgitant volume from 31 +/- 17 to 20 +/- 14 ml (p less than 0.05), while significantly increasing forward stroke volume. At control rest, the median mitral regurgitant fraction was 24% for the 12 patients. Neither dobutamine nor nitroglycerin changed significantly forward stroke and mitral regurgitant volumes at rest and during isometric exercise in the six patients with resting mitral regurgitant fraction below the median. In contrast, dobutamine and nitroglycerin significantly decreased mitral regurgitant volume and increased forward stroke volume both at rest and during isometric exercise in the six patients with mitral regurgitant fraction greater than the median.(ABSTRACT TRUNCATED AT 250 WORDS)
Left ventricular function in volume overload hypertrophy is controversial. In humans, chronic severe volume overload eventually results in left ventricular dysfunction; paradoxically, experimental volume overload hypertrophy has nearly always been associated with normal left ventricular function. However, in most cases, experimental volume overload hypertrophy has either been mild or only present for a short duration. To help resolve the issue of contractile function in volume overload hypertrophy, we examined ventricular function in a recently described model of severe chronic experimental mitral regurgitation. Left ventricular function was measured before and 3 mo after the creation of severe mitral regurgitation (averaged regurgitant fraction 0.64 +/- 0.04). At 3 mo end-diastolic volume had increased from 78 +/- 5 to 114 +/- 7 ml (P less than 0.01). Significant left ventricular hypertrophy had occurred with an increase in the left ventricular weight-to-body weight ratio from 3.84 +/- 0.2 to 5.22 +/- 0.2 (P less than 0.01). All indicators of left ventricular function (ejection fraction, the end ejection stress-volume relationship, this relationship corrected for eccentric hypertrophy, and mean velocity of circumferential fiber shortening at a common stress) were reduced at 3 mo. Our study produced 64% volume overload which was maintained for 3 mo at which time there was a 36% increase in left ventricular mass. This amount of volume overload of this duration produced significant left ventricular dysfunction.
Mitral valve prolapse has been diagnosed by two-dimensional echocardiographic criteria with surprising frequency in the general population, even when preselected normal subjects are examined. In most of these individuals, however, prolapse appears in the apical four-chamber view and is absent in roughly orthogonal long-axis views. Previous studies of in vitro models with nonplanar rings have shown that systolic mitral annular nonplanarity can potentially produce this discrepancy. However, to prove directly that apparent leaflet displacement in a two-dimensional view does not constitute true displacement above the three-dimensional annulus requires reconstruction of the entire mitral valve, including leaflets and annulus. Such reconstruction would also be necessary to explore the complex geometry of the valve and to derive volumetric measures of superior leaflet displacement. A technique was therefore developed and validated in vitro for three-dimensional reconstruction of the entire mitral valve. In this technique, simultaneous real-time acquisition of images and their spatial locations permits reconstruction of a localized structure by minimizing the effects of patient motion and respiration. By applying this method to 15 normal subjects, a coherent mitral valve surface could be reconstructed from intersecting scans. The results confirm mitral annular nonplanarity in systole, with a maximum deviation of 1.4 +/- 0.3 cm from planarity. They directly show that leaflets can appear to ascend above the mitral annulus in the apical four-chamber view, as they did in at least one view in all subjects, without actual leaflet displacement above the entire mitral valve in three dimensions, thereby challenging the diagnosis of prolapse by isolated four-chamber view displacement in otherwise normal individuals. This technique allows us to address a uniquely three-dimensional problem with high resolution and provide new information previously unavailable from the two-dimensional images. This new appreciation should enhance our ability to ask appropriate clinical questions relating mitral valve shape and leaflet displacement to clinical and pathologic consequences.
We conducted a double-blind, placebo-controlled trial to determine whether ventricular dilatation continues during the late convalescent phase after myocardial infarction and whether therapy with captopril alters this process. Fifty-nine patients with a first anterior myocardial infarction and a radionuclide ejection fraction of 45 percent or less underwent cardiac catheterization 11 to 31 days after infarction, when they were not in overt congestive heart failure. They were randomly assigned to placebo or captopril and were followed for one year. A repeat catheterization was performed to evaluate interval changes in hemodynamic function and left ventricular volume. Thirty-eight male patients were evaluated with maximal-exercise treadmill tests every three months. No differences were detected at base line in clinical, hemodynamic, or quantitative ventriculographic variables. During one year of follow-up, the end-diastolic volume of the left ventricle increased by a mean [+/- SEM] of 21 +/- 8 ml (P less than 0.02) in the placebo group, but by only 10 +/- 6 ml (P not significant) in the captopril group. The left ventricular filling pressure remained elevated with placebo but decreased (P less than 0.01) with captopril. In a subset of 36 patients who were at high risk for ventricular enlargement because they had persistent occlusion of the left anterior descending coronary artery, captopril prevented further ventricular dilatation (P less than 0.05). Patients given captopril also had increased exercise capacity (P less than 0.05). This preliminary study indicates that after anterior myocardial infarction, ventricular enlargement is progressive and that captopril may attenuate this process, reduce filling pressures, and improve exercise tolerance.
Seven patients with decompensated chronic heart failure and functional mitral regurgitation were studied before and during administration of nitroglycerin at a mean dose of 42 micrograms/min (range 20 to 90 micrograms/min). Forward aortic flow obtained by pulsed Doppler increased significantly from 35 +/- 8 to 45 +/- 9 ml/beat (p less than 0.001) and correlated well with the cardiac output measured by thermodilution technique (r = 0.8). Whereas regurgitant mitral volume calculated from the difference between echocardiographic total stroke volume and forward aortic flow decreased significantly from 19 +/- 9 to 3 +/- 3 ml/beat (p less than 0.001), peak velocity of mitral regurgitant flow increased from 4.1 +/- 0.9 to 4.4 +/- 1.0 m/sec (p less than 0.05). The decrease in effective mitral regurgitation area derived from a modified Gorlin formula average 80%. Accordingly, in patients with decompensated chronic heart failure and functional mitral regurgitation, nitroglycerin decreases mitral regurgitant area substantially, and thus almost abolishes mitral regurgitation despite an increase in systolic pressure gradient between left ventricle and atrium. Moreover, the increase in forward flow can be entirely accounted for by the reduction in mitral regurgitant flow.
Mechanical characteristics of the left ventricle in chronic aortic regurgitation (AR) differ from those in chronic mitral regurgitation (MR). The differences are thought to be responsible, in part, for the changes in left ventricular (LV) function observed after surgical correction of AR or MR. To test this hypothesis, LV stress-dimension-shortening relations were determined before and after valve replacement in patients with compensated and decompensated chronic AR and MR. Echocardiographic data from 32 patients with AR and 20 patients with MR were used; preoperatively, all 52 patients had LV enlargement. Based on postoperative data, 2 subgroups were defined for each lesion: Patients in group A achieved a normal end-diastolic dimension (less than 3.3 cm/m2) and patients in group B had persistent LV enlargement. Preoperatively, the patients in group A with AR had increased peak systolic stress, but end-systolic stress and fractional shortening were normal; the patients in group B with AR had increased peak systolic stress, increased end-systolic stress and depressed shortening. One year after aortic valve replacement the patients in group A had normal systolic wall stresses and normal shortening, whereas those in group B had persistently abnormal wall stresses and a decrease in shortening. Preoperatively, patients in group A with MR had only modest elevations of peak stress, while end-systolic stress and fractional shortening were normal; in patients in group B with MR the peak stress was similar to that seen in group A, but end-systolic stress was increased and shortening was depressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Simultaneous left ventricular micromanometry and biplane cineangiography were performed in nine control subjects (group 1), 14 patients with chronic mitral regurgitation and an ejection fraction of 57% or greater (group 2), and 13 patients with mitral regurgitation and an ejection fraction of less than 57% (group 3). End-diastolic volume index was increased in both groups with mitral regurgitation (p less than .001) compared with the control group. Left ventricular end-diastolic wall thickness did not differ among the three groups, but the left ventricular muscle mass index was greater in both groups with mitral regurgitation than in controls (p less than .001). End-diastolic pressure was elevated in both groups 2 and 3 compared with group 1 (p less than .05), but peak systolic, mean systolic, and incisural pressure were not different among the three groups. End-diastolic stress was larger in groups 2 and 3 than in group 1 (p less than .05). Muscle fiber stretch was greater in group 2 than in the control group (p less than .05) but was not different between the controls and group 3. End-systolic stress, determined as the circumferential stress at aortic valve closure, at the maximal pressure/volume ratio, or using a nonsimultaneous method, was larger in group 3 than in groups 1 and 2. Mean systolic stress was evaluated from aortic valve opening to aortic valve closure in all patients; mean stress from end-diastole to aortic valve closure and from end-diastole to minimum volume was assessed in mitral regurgitation alone.(ABSTRACT TRUNCATED AT 250 WORDS)
The mechanism by which afterload reduction increases left ventricular stroke volume while decreasing left ventricular filling pressure has not previously been established. In 15 patients with severe congestive heart failure due to ischemic or idiopathic dilated cardiomyopathy, absolute ventricular volume, ejection fraction and total stroke volume from radionuclide ventriculography were compared with thermodilution stroke volume before and after intensive afterload reduction with vasodilators and diuretics titrated to hemodynamic goals. After 48 to 72 hours, pulmonary artery wedge pressure decreased from 32 +/- 8 to 16 +/- 4 mm Hg and systemic vascular resistance from 1,960 +/- 700 to 1,200 +/- 400 dynes s cm-5. End-diastolic volume decreased from 390 +/- 138 to 301 +/- 126 ml (p less than 0.01) and end-systolic volume from 316 +/- 127 to 241 +/- 111 (p less than 0.01). Ejection fraction did not change and total stroke volume decreased from 74 +/- 22 to 59 +/- 20 ml (p less than 0.01). Simultaneous forward stroke volume by thermodilution increased from 37 +/- 14 to 52 +/- 14 ml (p less than 0.01), and forward fraction increased from 0.55 +/- 0.40 to 0.96 +/- 0.42. Intensive reduction of ventricular filling pressure and systemic vascular resistance decreased total ventricular stroke volume by 20% but increased forward stroke volume by 40%. The major effect of intensive afterload reduction for severe congestive heart failure may be the reduction of ventricular volume and mitral regurgitation.
The function of the papillary muscles to restrain the mitral valves is obvious. However, the dynamic nature of this function is not always appreciated. Failure of one or both papillary muscles to shorten during the ejection phase of ventricular systole, fibrosis, and atrophy of a papillary muscle or centrifugal migration of the papillary muscles due to left ventricular dilatation result in mitral incompetence. Depending upon the etiology of the papillary muscle dysfunction, apical systolic murmurs of varying characteristics may be heard. In general, a noncontracting papillary muscle in a normal-sized heart is associated with a murmur which is late in onset and crescendo-decrescendo in quality, whereas in the dilated heart the murmur is early, beginning with the first heart sound, and may be decrescendo, plateau, or crescendo-decrescendo in quality. Obviously, the murmurs of papillary muscle dysfunction may vary considerably depending upon the nature of the dysfunction and time course of activation of the muscle and other portions of the ventricular musculature. Associated electrocardiographic abnormalities may also occur.
The unimpeded, forward flow of blood across the mitral orifice is contingent upon a coordinated interaction between the mitral annulus, the mitral valve leaflets, the chordae tendineae, and the papillary muscles. An understanding of the functional anatomy and physiology of each of these components of the "mitral complex" is clinically important for derangement of any part may produce obstruction to blood flow or allow mitral regurgitation. The differential diagnosis then of mitral stenosis and mitral regurgitation can be functionally analyzed in terms of diseases of the mitral annulus, diseases of the mitral valve leaflets, diseases of the chordae tendineae, and diseases of the papillary muscles. By this consideration of selective involvement of the mitral complex, certain physical signs, such as the late systolic murmur that may occur in papillary muscle dysfunction, the "murmur on top of the head" heard with a ruptured chordae tendineae to the anteromedial mitral leaflet, the chordal snap of a redundant chordae tendineae, or the atrial gallop of an acutely ruptured chordae tendineae, can be sought for in an attempt to differentiate clinically the possible etiology of the disease and its anatomic area of involvement. This correlation of physical signs with the functional anatomy helps to provide an additional scientific basis to the physical examination.
This review deals with the functional anatomy of the six components of the mitral apparatus, namely, the left atrial wall, annulus, leaflets, chordae tendineae, papillary muscles, and left ventricular wall. Each component is considered individually, in the context of the apparatus as a whole, in relation to the mode of closure of the normal mitral valve, and in the light of many acquired and congenital disorders that disturb the harmony of the finely coordinated mitral mechanism and render it incompetent.
The left atrium is related to mitral valve competence in terms of contraction and relaxation and in terms of dilatation of its posterior wall. The annulus not only serves as a fulcrum for the leaflets but exhibits sphincteric contraction in systole that decreases the size of the orifice. The two leaflets differ in shape but are nearly identical in area, and together are about two and one half times the area of the orifice that they are required to close. Leaflet abnormalities causing acquired or congenital mitral regurgitation result from deficient leaflet tissue, excessive leaflet tissue, or restricted leaflet mobility. Chordae tendineae are considered according to their leaflet attachments, ventricular attachments, thicknesses, lengths, and arborization patterns. Mitral regurgitation due to chordal abnormalities results from chordae that are abnormally long, abnormally short, ectopically inserted, or ruptured. In this context, systolic clicks and late systolic murmurs are discussed, and severe acute mitral regurgitation is contrasted with severe chronic mitral regurgitation. The papillary muscles and the left ventricular wall represent the two muscular components of the mitral apparatus. An appraisal of papillary muscle dysfunction includes dysfunction with loss in continuity (rupture) and dysfunction without loss in continuity (fibrosis, ischemia, replacement). Finally, the role of altered left ventricular shape is discussed in the context of mitral regurgitation, and the effect of dilatation is ascribed chiefly to alterations in the position of papillary muscles and their directional axes of tension.
Papillary muscle infarction was produced in 16 mongrel dogs by placing sutures around the base of one of the papillary muscles. In addition, patchy infarction of the adjacent left ventricular wall was produced by placing an Ameroid constrictor around the appropriate coronary artery. Mitral insufficiency developed in 14 of these animals; it was severe in four and mild to moderate in ten. Mitral insufficiency was not produced by isolated infarction of a papillary muscle or by isolated infarction of the left ventricular wall.
It is concluded that papillary muscle infarction alone does not lead to mitral regurgitation, but that papillary; muscle dysfunction acts in concert with left ventricular wall dyskinesia or dilatation to produce mitral valve incompetency.
Diastolic time intervals (DTIs) were calculated from simultaneous recordings of a phonocardiogram, apexcardiogram, and echocardiogram in 84 patients with hypertrophic cardiomyopathy and 35 patients with hypertrophy secondary to chronic pressure and volume loading and were compared with those in 31 normal subjects. The isovolumetric relaxation period (IRP) was measured as the interval from the aortic closure sound (A2, phonocardiography) to the opening of the mitral valve (MO, echocardiography) and the interval from A2 to the 0 point of the apexcardiogram was used as an index of total relaxation. Their difference, the MO-0 interval, was also calculated. In 12 patients with volume loading secondary to mitral regurgitation there was no significant difference in any of the DTIs compared with those of normal subjects. There was a wide range of IRPs (from 10 to 90 msec), and hemodynamic correlation in a representative patient with a short A2-MO interval revealed that this was due to premature MO secondary to a high V wave in the wedge pressure. In 12 patients with volume loading secondary to chronic aortic regurgitation there was an increase in the IRP (83 ± 26 vs 62 ± 11 msec; p < .001) and a decrease in the MO-0 interval (48 ± 27 vs 67 ± 15 msec; p < .01), with no significant difference in their sum (the A2-0 interval). Hemodynamic data in one patient demonstrated that prolonged IRP was secondary to the large pressure drop from the A2 to the MO. In 11 patients with chronic pressure overload secondary to valvular aortic stenosis and in the 84 patients with hypertrophic cardiomyopathy there was no significant difference in the IRP as compared with that in normal subjects; in patients with these conditions the MO-0 interval was significantly increased, as was the A2-0 interval in the patients with hypertrophic cardiomyopathy. In four of the patients with aortic stenosis and in 15 patients with hypertrophic cardiomyopathy, the IRP was more than 2 SDs below the mean value in normal subjects. Hemodynamic correlation at cardiac catheterization in patients with both conditions demonstrated that a delayed A2 was primarily responsible for the abbreviated A2-MO interval and that this was secondary to a large left ventriculoaortic pressure gradient and/or the 'hangout' phenomenon. In this situation A2 is an inappropriate marker of the onset of rapid left ventricular pressure decline and the A2-MO interval is not a valid reflection of diastolic relaxation. We conclude that the duration of DTIs is multifactorially determined and that none of these noninvasively measured intervals is a consistently valid gauge of left ventricular relaxation. In left ventricular hypertrophy, in which alterations in preload, afterload, and the timing of A2 are common, as are primary changes in the rate of left ventricular pressure decline, the duration of these intervals will represent the net effect of all of their determinants.