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N-Terminal Pro-Brain Natriuretic Protein Levels in Takotsubo Cardiomyopathy
Abstract
Takotsubo cardiomyopathy (TTC) is characterized by reversible left ventricular (LV) systolic dysfunction independent of fixed coronary disease or coronary spastic pathogenesis. A number of investigators have documented marked elevation of natriuretic peptide levels at presentation in such patients. We sought to determine the pattern, extent, and determinants of the release of N-terminal pro-B type natriuretic peptide/B type natriuretic peptide (NT-proBNP/BNP) in patients with TTC. We evaluated NT-proBNP/BNP release acutely and during the first 3 months in 56 patients with TTC (96% women, mean age 69 ± 11 years). The peak plasma NT-proBNP levels were compared to the pulmonary capillary wedge pressure and measures of regional and global LV systolic dysfunction (systolic wall stress, wall motion score index, and LV ejection fraction) as potential determinants of NT-proBNP/BNP release. In patients with TTC, the plasma concentrations of NT-proBNP (median 4,382 pg/ml, interquartile range 2,440 to 9,019) and BNP (median 617 pg/ml, interquartile range 426 to 1,026) were substantially elevated and increased significantly during the first 24 hours after the onset of symptoms (p = 0.001), with slow and incomplete resolution during the 3 months thereafter. The peak NT-proBNP levels exhibited no significant correlation with either pulmonary capillary wedge pressure or systolic wall stress. However, the peak NT-proBNP level correlated significantly with the simultaneous plasma normetanephrine concentrations (r = 0.53, p = 0.001) and the extent of impairment of LV systolic function, as measured by the wall motion score index (r = 0.37, p = 0.008) and LV ejection fraction (r = -0.39, p = 0.008). In conclusion, TTC is associated with marked and persistent elevation of NT-proBNP/BNP levels, which correlated with both the extent of catecholamine increase and the severity of LV systolic dysfunction.
... Thus, it becomes very important to have clinical clarity in the diagnosis of Broken Heart Syndrome and to have a high index of suspicion. This is largely helped by diagnostic criteria such as the Mayo Clinic Criteria [92,93], Gothenburg Criteria [94], and ESC Heart Failure Association Criteria [8] (Figure 3). ...
... Table 1 provides a comparison between most common differential diagnosis for TS. diagnostic criteria such as the Mayo Clinic Criteria [92,93], Gothenburg Criteria [94], and ESC Heart Failure Association Criteria [8] (Figure 3). ...
... Table 1 provides a comparison between most common differential diagnosis for TS. [93,94], Gothenburg Criteria [95], and ESC Heart Failure Association Criteria [8]. a Acute, reversible dysfunction of a single coronary territory. b Left bundle branch block may be permanent after Takotsubo Syndrome, but other cardiomyopathies should be excluded. ...
Abstract: Broken Heart Syndrome, also known as Takotsubo Syndrome (TS), is sudden and transient dysfunction of the left and/or right ventricle which often mimics Acute Coronary Syndrome (ACS). Japan was the first country to describe this syndrome in the 1990s, and since then it has received a lot of attention from researchers all around the world. Although TS was once thought to be a harmless condition, recent evidence suggests that it may be linked to serious complications and mortality on par with Acute Coronary Syndrome (ACS). The understanding of TS has evolved over the past few years. However, its exact etiology is still poorly understood. It can be classified into two main types: Primary and Secondary TS. Primary TS occurs when the symptoms of myocardial damage, which is typically preceded by emotional stress, are the reason for hospitalization. Secondary TS is seen in patients hospitalized for some other medical, surgical, obstetric, anesthetic, or psychiatric conditions, and the dysfunction develops as a secondary complication due to the activation of the sympathetic nervous system and the release of catecholamines. The etiopathogenesis is now proposed to include adrenergic hormones/stress, decreased estrogen levels, altered microcirculation, endothelial dysfunction, altered inflammatory response via cardiac macrophages, and disturbances in the brain-heart axis. The role of genetics in disease progression is becoming the focus of several upcoming studies. This review focuses on potential pathophysiological mechanisms for reversible myocardial dysfunction observed in TS, and comprehensively describes its epidemiology, clinical presentation, novel diagnostic biomarkers, and evolving principles of management. We advocate for more research into molecular mechanisms and promote the application of current evidence for precise individualized treatment.
... The mild troponin increase is disproportionated to the remarkable ECG changes, LV systolic dysfunction, and important wall motion abnormalities [2]. Natriuretic peptides, B-type natriuretic peptide (BNP), and N-terminal pro-BNP (NT-proBNP) are 3-to fourfold higher in patients with TC than in those with AMI [11]. NT-proBNP is higher in patients with apical TC compared to the other subtypes due to a more important degree of acute LV dilation and myocardial stretch [2]. ...
... NT-proBNP is higher in patients with apical TC compared to the other subtypes due to a more important degree of acute LV dilation and myocardial stretch [2]. The elevation of cardiac biomarkers is secondary to LV systolic dysfunction, myocardial stretch, and increased plasma catecholamine levels [11]. ...
Background
Takotsubo cardiomyopathy (TC) is an emergency cardiovascular disease, with clinical and paraclinical manifestations similar to acute myocardial infarction (AMI), but it is characterized by reversible systolic dysfunction of the left ventricle (LV) in the absence (most of the time) of obstructive coronary artery disease (CAD).
Management of patients with TC
TC seems to be more frequent in post-menopausal women and it is triggered by emotional or physical stress. The diagnosis of TC is based on the Mayo Clinic criteria. Initially, patients with TC should be treated as those with AMI and carefully monitored in intensive care unit. Urgent clinical and paraclinical distinction between TC and AMI is mandatory in all patients, because of the different therapeutical management between the two diseases. Chest pain and dyspnea are the most common symptoms in TC. Paraclinical diagnosis is based on cardiac biomarkers, electrocardiogram (ST-segment elevation/T wave inversion in precordial leads without reciprocal ST-segment depression in inferior leads and absence of Q waves), echocardiography (LV systolic dysfunction, regional wall motion abnormalities extended in more than one coronary territory), cardiac magnetic resonance and in most of the cases the positive diagnosis is established by performing CA to exclude obstructive CAD. The prognosis of patients with TC is considered benign in most cases, with a complete LV function recovery, but severe complications may occur, such as cardiogenic shock, LV free wall rupture, life-threatening arrhythmia, and cardiac arrest. Postoperative TC may develop after any type of surgical intervention due to acute stress and it should be differentiated from postoperative AMI. The management of patients with TC is medical and it is based on supportive care and the treatment of heart failure, while patients with AMI require myocardial revascularization.
Conclusions
TC leads to transient LV dysfunction that mimics AMI from which it should be differentiated for a good therapeutic approach. Patients with TC should be carefully monitored during hospitalization because they have a high recovery potential if optimally treated.
... It is believed to be secondary to the increase abundance of catecholamines rather than to necrosis of myocardial cells; the damage may be related to edema rather than to cellular death [77]. Higher levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are found in TTS compared to ACS; which peak in 24-48 h [78] and resolves within months [79]. Levels of NT-proBNP/troponin seems to have a tremendous discriminating power between TTS and ACS, as well as High-Sensitivity Troponin I (hs-TnI) and creatine kinasemyoglobin binding (CK-MB) rate. ...
... Individuals predisposed to a higher increase in norepinephrine and epinephrine also have higher levels of resting catecholamines and suffer more frequently from panic disorders [117]. Acute emotional stressors have been shown to induce the activation of different anatomic structures in the central and autonomic nervous systems [78]. The perception of a traumatic event by the cortex triggers the subcortical cerebral circuit through the networks that control the emotions and the functions of the visceral systems, whose activation triggers the release of norepinephrine. ...
An acute, transient episode of left ventricular dysfunction characterizes Takotsubo syndrome. It represents about 2% of all cases of acute coronary syndrome (ACS), and occurs predominantly in postmenopausal women, generally following a significant physical or emotional stressor. It can be diagnosed based on clinical symptoms and the absence of coronary artery disease on angiography. Ventriculography remains the gold standard for the diagnosis. Despite its transitory characteristic Takotsubo syndrome should not be considered a benign condition since complications occur in almost half of the patients, and the mortality rate reaches 4–5%. Lately, it has been revealed that Takotsubo syndrome can also lead to permanent myocardial damage due to the massive release of catecholamines that leads to myocardial dysfunction. Different mechanisms have been advanced to explain this fascinating syndrome, such as plaque rupture and thrombosis, coronary spasm, microcirculatory dysfunction, catecholamine toxicity, and activation of myocardial survival pathways. Here are still several issues with Takotsubo syndrome that need to be investigated: the complex relationship between the heart and the brain, the risk of permanent myocardial damage, and the impairment of cardiomyocyte. Our review aims to elucidate the pathophysiology and the mechanisms underlying this complex disease to manage the diagnostic and therapeutic algorithms to create a functional synergy between physicians and patients.
... Additionally, it has been discovered that B-type natriuretic peptide (BNP) and Nterminal pro-BNP (NT-proBNP) are commonly elevated up to 3-4 times greater compared to individuals with ACS. 29 According to one study, significantly increased levels of these biomarkers were linked to decreased ejection fraction (EF) and raised plasma catecholamine levels rather than pulmonary congestion or pulmonary capillary wedge pressure, indicating the pathophysiology of TC and its severity. 29 Apical ballooning of the LV during echocardiography is the pathognomonic finding of TC. ...
... Additionally, it has been discovered that B-type natriuretic peptide (BNP) and Nterminal pro-BNP (NT-proBNP) are commonly elevated up to 3-4 times greater compared to individuals with ACS. 29 According to one study, significantly increased levels of these biomarkers were linked to decreased ejection fraction (EF) and raised plasma catecholamine levels rather than pulmonary congestion or pulmonary capillary wedge pressure, indicating the pathophysiology of TC and its severity. 29 Apical ballooning of the LV during echocardiography is the pathognomonic finding of TC. It was noted that 75% of patients had this particular morphology. ...
p class="abstract">Takotsubo cardiomyopathy (TCM) is a type of neuro cardiological disorder that evince as acute but reversible heart failure. On the whole, it occurs by stress-related cardiomyopathy which illustrates the heart-brain connection. It was first discovered in 1990, by a Japanese cardiovascular specialist. That's the beginning of this heart disease in gaining worldwide acceptance as an independent disease entity. TCM is entirely different from acute myocardial infarction as usually occurs in postmenopausal elderly women due to emotional or physical stress. It is characterized by transient hypokinesis of the left ventricular apex. However, there are complications too that need to be addressed. Some reports of serious TCM include hypotension, thrombosis involving LV apex, heart failure, and ventricular rupture. It is also suggested that coronary spasms, myocarditis, and coronary microvascular dysfunction might contribute to the pathogenesis of TCM. But in total, its pathophysiology is unclear. In this review article, we review the pathogenesis and etiology of this rare complex disorder along with its clinical features, findings, challenges in diagnosis, and a comprehensive discussion on the same.</p
... The association of persistent symptoms with echocardiographic and laboratory abnormalities could suggest that symptoms are due to persistent myocardial dysfunction and not to psychosomatic factors. Consistent with this hypothesis, elevated natriuretic peptide values [75], persisting cardiac limitation on CPET and reduction in longitudinal strain on the echocardiogram were observed in symptomatic patients with previous TTS even after more than one year from the acute event [65]. Moreover, dyspnea was reported to be an independent predictor of long-term mortality [25]. ...
... On the contrary, a considerable elevation of natriuretic peptides (B-type natriuretic peptide, BNP, and N-terminal pro BNP, NT-proBNP) is frequently found, with the highest level reached 24-48 h after symptom onset, mainly related to myocardial stretch. It has been described that a gradual normalization of natriuretic peptides levels occurs within a few months after the acute phase [78], however elevated values were observed in symptomatic patients after 3 months from the acute event [75]. Higher in-hospital levels of BNP [79] and troponin [6] are associated with acute complications. ...
Takotsubo syndrome (TTS) is an intriguing clinical entity, characterized by
usually transient and reversible abnormalities of the left ventricular systolic
function, mimicking the myocardial infarction with non-obstructive coronary
arteries. TTS was initially regarded as a benign condition, however recent
studies have unveiled adverse outcomes in the short- and long-term, with rates of
morbidity and mortality comparable to those experienced after an acute myocardial
infarction. Given the usual transient nature of TTS, this is an unexpected
finding. Moreover, long-term mortality seems to be mainly driven by
non-cardiovascular causes. The uncertain long-term prognosis of TTS warrants a
comprehensive outpatient follow-up after the acute event, although there are
currently no robust data indicating its modality and timing. The aim of the
present review is to summarize recent available evidence regarding long-term
prognosis in TTS. Moreover methods, timing and findings of the long-term
management of TTS will be discussed.
... It is reasonable to assume that activation of the HPA axis during acute illness may mediate TTS by inducing catecholamines secretion. One of the key biomarkers in TTS is N-terminal pro-brain-type natriuretic peptide (NT-proBNP) which is released following increased ventricular wall stress as part of the neurohormonal activation in the setting of heart failure (67). Similar to other forms of heart failure, NT-proBNP levels in TTS have been shown to correlate with the severity of left ventricle (LV) dysfunction (67). ...
... One of the key biomarkers in TTS is N-terminal pro-brain-type natriuretic peptide (NT-proBNP) which is released following increased ventricular wall stress as part of the neurohormonal activation in the setting of heart failure (67). Similar to other forms of heart failure, NT-proBNP levels in TTS have been shown to correlate with the severity of left ventricle (LV) dysfunction (67). Compared to patients with ST segment elevation myocardial infarction (STEMI), TTS is associated with higher brain natriuretic peptide (BNP) and lower troponin levels at admission, at peak, and at discharge (68). ...
The current coronavirus disease 2019 (COVID-19) presents an ongoing medical challenge with multiple organs involvement, including the cardiovascular system. Takotsubo syndrome (TTS) has been described in the context of COVID-19 in two different scenarios: as a direct complication of the infection, and as an indirect outcome secondary to psychological burden of quarantine and social isolation (i.e., stress induced cardiomyopathy). Confirming the diagnosis of TTS in COVID-19 may be challenging due to the limited use of coronary angiography consistent with the recommended guidelines aimed to minimize contact with infected individuals. The use of natriuretic peptide as a diagnostic and prognostic marker in this context may not be reliable since this peptide is already elevated in severe cases of COVID-19 regardless of TTS diagnosis. A relatively high incidence of complications has been reported in these cases, probably related to the severity of the underlying infectious disease. Although quarantine-induced stress cardiomyopathy is a reasonable outcome of the powerful stress during the current pandemic, conflicting results have been reported, and further studies are encouraged to determine the true incidence.
... A likely explanation is the acute left ventricular ballooning and raised filling pressures in a left ventricular cavity which has suddenly lost its contractile function. BNP is also an acute phase reactant and it is also possible that this elevation reflects its antiinflammatory contribution to the syndrome [8]. BNP tests are widely available, also as point of care assays [9,10]. ...
... Scally et al showed that levels of TnI, BNP, IL-6 and IL-8 remain modestly elevated at follow-up in patients with Takotsubo syndrome [2]. BNP was also noticed to be elevated at follow-up by Nguyen et al. [8]. This suggests that the abnormalities in patients with Takotsubo syndrome persist for many months after the acute diagnosis. ...
Background
The diagnosis of Takotsubo syndrome is made based on clinical presentation, ECG, biomarker, imaging and coronary angiography. There is a lack of diagnostic biomarkers that can discriminate patients with Takotsubo syndrome from those with acute myocardial infarction (AMI) and provide clinical monitoring and prognostic information in the long-term.
Methods
A literature search of published Takotsubo syndrome biomarkers from PubMed was performed. All studies that included numerical biomarker data on Takotsubo syndrome was included. Exclusion criteria was any study without an AMI cohort for comparison in the acute phase biomarkers or due to the absence of numerical values. The results were tabulated in table form with results expressed as either mean ± SD or median (interquartile range).
Results
The literature search produced 14 relevant studies that met search criteria. The results showed; high sensitivity Troponin I (3.21 ± 4.4 vs 34.4 ± 37 ng/ml), BNP [972 (578.5–1671.0) pg/L vs 358 (50.5–688.0) pg/L in NSTEMI and vs 381 (106.0–934.0) pg/L in STEMI] and BNP/Troponin I ratio [642 (331.8–1226.5) vs 184.5 (50.5–372.3) pg/ug in NSTEMI and 7.5 (2.0–29.6) pg/ug in STEMI] patients.
Discussion
This study is limited by many studies being retrospective cohort studies. This data shows that acutely troponin is raised in Takotsubo syndrome but not enough to be discriminating from AMI. BNP level is significantly raised in Takotsubo syndrome compared to AMI.
Conclusion
Current specificity of acute and chronic biomarkers for Takotsubo syndrome is lacking and further work is needed to address the gap in knowledge.
... Interestingly, patients with different contraction pattern did not differ in the extent of chronic symptoms. TTS was lately revealed to be more a chronic than an acute disease [16][17][18]. In animal models, histological abnormalities persist despite echocardiographic normalization of the LVEF [19]. ...
... In animal models, histological abnormalities persist despite echocardiographic normalization of the LVEF [19]. In fact, even though wall motion abnormalities may resolve, inflammation and myocardial dysfunction seem to be persisting in patients with TTS [17,18]. The high rate of persisting symptoms in our cohort supports the notion of a chronic disease and is in agreement with data from a smaller cohort [20]. ...
Background
Takotsubo Syndrome (TTS) is diagnosed in 1–2% of all patients presenting with acute coronary syndrome. Next to the typical apical manifestation, other locations of left ventricular contraction abnormality are possible, but their relationship to patient characteristics, clinical correlates as well as long-term outcome are poorly understood.
Methods & results
We retrospectively analyzed 126 patients presenting TTS. Cases were categorized according to left ventricular contraction abnormality patterns: typical apical pattern (71%, n = 89) vs. atypical patterns (29%, n = 37). Cases with typical TTS showed significantly higher levels of troponin I (3.12 ng/ml vs. 1.32 ng/ml, p = 0.013) and creatin kinase (CK) on admission (461 (±1207)U/l vs. 173 (±177) U/l, p = 0.03) as well as peak CK (973 (±2860)U/l vs. 301 (±328) U/l, p = 0.03) and more often ischemia related ECG changes (p = 0.02). Follow-up data was available for 85% of the patients. Median FU time was 4.4 years (IQR 1.4–7.7 years). All-cause mortality during follow-up was 39%, with no significant difference between patients with typical or atypical TTS (43% vs. 29%, p = 0.17). In multivariate logistic regression analysis, only anemia was predictive for long-term mortality (OR 3.93, 95%CI 1.02–2.08, p = 0.015). The majority of surviving patients (69%) reported good quality of life, even though only 56% reported being symptom-free.
Conclusion
Patients with TTS have poor long-term prognosis with an overall mortality of 39.1% within 4 years and nearly half of all patients report persisting symptoms. Even though the apical contraction pattern is associated with higher elevation of serum markers for myocardial damage, it was not associated with higher long-term mortality.
... 5 The rise in NT-proBNP level associated with TTS is comparable to that seen with decompensated HF. 28 Moreover, peak NT-proBNP levels in TTS are correlated with the severity of LV systolic dysfunction as well as the degree of sympathetic overactivation and long-term prognosis. 29 ...
... 5,11,21 N-Terminal prohormone of brain natriuretic peptide may serve as a particularly useful biomarker for prognostication, as the degree of elevation is directly correlated with the level of sympathetic overactivation and systolic LV dysfunction. 29 In-hospital TTS also carries with it reduced survival as compared with out-of-hospital TTS, probably owing to serious antecedent comorbidities. 52 Recovery from TTS can be slow, with persistent abnormalities on echocardiography and cardiac MRI, prolonged NT-proBNP elevation, impaired quality of life, and even long-term myocardial fibrosis in up to 10% of patients with TTS. ...
Takotsubo syndrome (TTS), also known as stress cardiomyopathy and broken heart syndrome, is a neurocardiac condition that is among the most dramatic manifestations of psychosomatic disorders. This paper is based on a systematic review of TTS and stress cardiomyopathy using a PubMed literature search. Typically, an episode of severe emotional or physical stress precipitates regions of left ventricular hypokinesis or akinesis, which are not aligned with a coronary artery distribution and are out of proportion to the modest troponin leak. A classic patient with TTS is described; one who had chest pain and dyspnea while watching an anxiety-provoking evening news program on the coronavirus disease 2019 (COVID-19) pandemic. An increase in the incidence of TTS appears to be a consequence of the COVID-19 pandemic, with the TTS incidence rising 4.5-fold during the COVID-19 pandemic even in individuals without severe acute respiratory syndrome coronavirus 2 infection. Takotsubo syndrome is often mistaken for acute coronary syndrome because they both typically present with chest pain, electrocardiographic changes suggesting myocardial injury/ischemia, and troponin elevations. Recent studies report that the prognosis for TTS is similar to that for acute myocardial infarction. This review is an update on the mechanisms underlying TTS, its diagnosis, and its optimal management.
... T2-weighted signal intensity on CMR imaging suggesting myocardial edema and inflammation in TTS also persists even after the improvement of wall motion abnormalities [21]. Recent studies have reported the persistence of symptoms and elevated brain-type natriuretic peptide release well beyond this period, even after the improvement of LV dysfunction in TTS [22,23], suggesting an association with these residual cardiac dysfunctions. These findings highlight that in addition to the improvement of cardiac wall motion abnormality and LVEF, evaluating other aspects of cardiac function is also crucial for understanding the patient's condition after TTS. ...
Background: Although takotsubo syndrome (TTS) is characterized by transient systolic dysfunction of the left ventricle (LV), the time course and mechanism of LV function recovery remain elusive. The aim of this study is to evaluate cardiac functional recovery in TTS via serial cardiac magnetic resonance feature tracking (CMR-FT). Methods: In this Japanese multicenter registry, patients with newly diagnosed TTS were prospectively enrolled. In patients who underwent serial cardiovascular magnetic resonance (CMR) imaging at 1 month and 1 year after the onset, CMR-FT was performed to determine the global circumferential strain (GCS), global radial strain (GRS) and global longitudinal strain (GLS). We compared LV ejection fraction, GCS, GRS and GLS at 1 month and 1 year after the onset of TTS. Results: Eighteen patients underwent CMR imaging in one month and one year after the onset in the present study. LV ejection fraction had already normalized at 1 month after the onset, with no significant difference between 1 month and 1 year (55.8 ± 9.2% vs. 58.9 ± 7.3%, p = 0.09). CMR-FT demonstrated significant improvement in GCS from 1 month to 1 year (−16.7 ± 3.4% vs. −18.5 ± 3.2%, p < 0.01), while there was no significant difference in GRS and GLS between 1 month and year (GRS: 59.6 ± 24.2% vs. 59.4 ± 17.3%, p = 0.95, GLS: −12.8 ± 5.9% vs. −13.8 ± 4.9%, p = 0.42). Conclusions: Serial CMR-FT analysis revealed delayed improvement of GCS compared to GRS and GLS despite of rapid recovery of LV ejection fraction. CMR-FT can detect subtle impairment of LV systolic function during the recovery process in patients with TTS.
... Consequently, relying solely on troponin levels may not be sufficient for distinguishing the two conditions. During the acute phase of takotsubo cardiomyopathy (TTC), significantly elevated levels of serum brain natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) can be detected [29][30][31][32]. In the majority of cases, cardiac biomarkers, such as troponin (Tn), creatine kinase (CK), and CK-MB, are slightly elevated [33][34][35]. ...
Background: cardiovascular diseases, including acute myocardial infarction (AMI) and takotsubo cardiomyopathy (TTC), are significant causes of morbidity and mortality worldwide. Timely differentiation of these conditions is essential for effective patient management and improved outcomes. Methods: We conducted a review focusing on studies that applied artificial intelligence (AI) techniques to differentiate between acute myocardial infarction (AMI) and takotsubo cardiomyopathy (TTC). Inclusion criteria comprised studies utilizing various AI modalities, such as deep learning, ensemble methods, or other machine learning techniques, for discrimination between AMI and TTC. Additionally, studies employing imaging techniques, including echocardiography, cardiac magnetic resonance imaging, and coronary angiography, for cardiac disease diagnosis were considered. Publications included were limited to those available in peer-reviewed journals. Exclusion criteria were applied to studies not relevant to the discrimination between AMI and TTC, lacking detailed methodology or results pertinent to the AI application in cardiac disease diagnosis, not utilizing AI modalities or relying solely on invasive techniques for differentiation between AMI and TTC, and non-English publications. Results: The strengths and limitations of AI-based approaches are critically evaluated, including factors affecting performance, such as reliability and generalizability. The review delves into challenges associated with model interpretability, ethical implications, patient perspectives, and inconsistent image quality due to manual dependency, highlighting the need for further research. Conclusions: This review article highlights the promising advantages of AI technologies in distinguishing AMI from TTC, enabling early diagnosis and personalized treatments. However, extensive validation and real-world implementation are necessary before integrating AI tools into routine clinical practice. It is vital to emphasize that while AI can efficiently assist, it cannot entirely replace physicians. Collaborative efforts among clinicians, researchers, and AI experts are essential to unlock the potential of these transformative technologies fully.
... NT pro-BNP which is also markedly elevated in the TCM cases is of special significance since the level of rise is 3-fourfold more than in the MI cases [7,22,33]. The increased NT pro-BNP is correlated with excessive catecholamine release and LV systolic dysfunction [34]. ...
Background
Owing to the limited research on Takotsubo Cardiomyopathy (TCM) in Asia, we aim to evaluate in detail the clinical profiles, lab parameters, investigations, and major adverse cardiovascular events (MACE) seen in patients with TCM in the Indian subcontinent. Additionally, we have compared the electrocardiographic findings of patients with TCM to those of patients with myocardial infarction (MI).
Results
The average age of the patients affected was found to be 60 ± 11 years. Women (87.5%) and patients with hypertension (40%) were found to be at an increased risk of developing the syndrome. The most common presenting symptom was dyspnea (48%) following a trigger most commonly emotional (45%). ST elevation and significant T wave inversions were observed in 40% of patients with TCM. Echocardiography revealed a low left ventricular ejection fraction of 43 ± 9%. Coronary angiography was normal in 60%, the rest had mild/subcritical stenoses. The 6-month MACE was 20% and the mortality rate was 7.5%. Follow-up echocardiography of patients with TCM showed improvement in EF in 75% patients.
Conclusions
TCM was majorly seen in postmenopausal women following an emotional trigger, but a variety of other triggers were noted. T-wave inversions in TCM follow a diffuse pattern in contrast to specific leads seen in MI. Normal or subcritical stenosis in coronaries at presentation, along with a low EF which improves on follow up provide greater evidence for the diagnosis of TCM.
... The troponin level in TTS is usually less than 1ng/ml and there is no signi cant stenosis on coronary angiography 32 . In contrast, the levels of BNP or Nterminal pro-BNP (NT-proBNP) are often 3-4 fold higher than in acute coronary syndrome 33 . Furthermore, in TTS, the level of NT-proBNP or BNP correlated with the degree of catecholamine elevation and the severity of left ventricular systolic dysfunction 33 . ...
Background
Medullary thyroid carcinoma (MTC) and pheochromocytoma are rare neuroendocrine tumors, which are diagnosed simultaneously in approximately 35% of patients. Heart failure and Takotsubo Syndrome (TTS) are rare and life-threatening cardiovascular complications of pheochromocytoma.
Case presentation
A 42-year-old woman was admitted to the hospital for surgery because of a thyroid nodule detected on physical examination. After surgery, she presented with acute heart failure in the general ward. The clinical manifestations combined with electrocardiogram, echocardiography, coronary angiography, and myocardial enzyme examination were consistent with the diagnosis of TTS. Postoperative abdominal enhanced CT and catecholamine levels at the time of heart failure supported that acute heart failure and TTS are due to enhanced adrenal pheochromocytoma activity.
Conclusions
MTC may be complicated with pheochromocytoma. Preoperative examination should be completed. It is recommended to perform pheochromocytoma surgery before MTC resection. In addition, acute heart failure and TTS are rare and serious complications of pheochromocytoma. Further studies are needed on the treatment and pathogenesis of TTS.
... 7 With regard to laboratory markers, troponin has been shown to predict EF 6 as well as in-hospital complications with an odds ratio (OR) of 1.68 if the initial troponin is above 10x the upper limit of normal (P = 0.007). 1 Moreover, NT-proBNP elevation has been observed to be more pronounced in TTS compared with troponin and correlated to peak c-reactive protein (CRP) concentrations and systolic LV dysfunction. 1,8 Mechanistically, TTS has been suggested to be caused by catecholamine storm due to sympathetic overdrive with subsequent paradoxical AHF 9 as well as systemic and myocardial inflammation. 10 Catecholamines cause a rise in plasma glucose due to elevated glycogenolysis and gluconeogenesis. ...
Aims
Takotsubo syndrome (TTS) is an acute heart failure (AHF) syndrome mimicking the symptoms of acute myocardial infarction. Impaired outcome has been shown, making risk stratification and novel therapeutic concepts a necessity. We hypothesized insulin resistance with elevated plasma glucose and potentially myocardial glucose deprivation to contribute to the pathogenesis of TTS and investigated the therapeutic benefit of insulin in vivo.
Methods and results
First, we retrospectively analysed patient data of n = 265 TTS cases (85.7% female, mean age 71.1 ± 14.1 years) with documented initial plasma glucose from the Department of Cardiology of the University Hospital Heidelberg in Germany (May 2011 to May 2021). Median split of the study population according to glucose levels (≤123 mg/dL vs. >123 mg/dL) yielded significantly elevated mean heart rate (80.75 ± 18.96 vs. 90.01 ± 22.19 b.p.m., P < 0.001), left ventricular end‐diastolic pressure (LVEDP, 18.51 ± 8.35 vs. 23.09 ± 7.97 mmHg, P < 0.001), C‐reactive protein (26.14 ± 43.30 vs. 46.4 ± 68.6 mg/L, P = 0.006), leukocyte count (10.12 ± 4.29 vs. 15.05 ± 9.83/nL, P < 0.001), peak high‐sensitive Troponin T (hs‐TnT, 515.44 ± 672.15 vs. 711.40 ± 736.37 pg/mL, P = 0.005), reduced left ventricular ejection fraction (EF, 34.92 ± 8.94 vs. 31.35 ± 8.06%, P < 0.001), and elevated intrahospital mortality (2.3% vs. 12.1%, P = 0.002) in the high‐glucose group (Student's t‐test, Mann–Whitney U test, or chi‐squared test). Linear regression indicated a significant association of glucose with HR (P < 0.001), LVEDP (P = 0.014), hs‐TnT kinetics from admission to the next day (P < 0.001), hs‐TnT the day after admission (P < 0.001), as well as peak hsTnT (P < 0.001). Logistic regression revealed significant association of glucose with a composite intrahospital outcome including catecholamine use, respiratory support, and resuscitation [OR 1.010 (1.004–1.015), P = 0.001]. To further investigate the potential role of glucose in TTS pathophysiology experimentally, we utilized an in vivo murine model of epinephrine (EPI)‐driven reversible AHF. For this, male mice underwent therapeutic injection of insulin (INS, 1 IU/kg) or/and glucose (GLU, 0.5 g/kg) after EPI (2.5 mg/kg), both of which markedly improved mean EF (EPI 34.3% vs. EPI + INS + GLU 43.7%, P = 0.025) and significantly blunted mean hs‐TnT (EPI 14 393 pg/mL vs. EPI + INS 6864 pg/mL at 24 h, P = 0.039). Particularly, insulin additionally ameliorated myocardial pro‐inflammatory gene expression, suggesting an anti‐inflammatory effect of acute insulin therapy.
Conclusions
Elevated initial plasma glucose was associated with adverse outcome‐relevant parameters in TTS and may present a surrogate parameter of heightened catecholaminergic drive. In mice, insulin‐ and glucose injection both improved EPI‐induced AHF and myocardial damage, indicating insulin resistance rather than detrimental effects of hyperglycaemia itself as the underlying cause. Future studies will investigate the role of HbA1c as a risk stratifier and of insulin‐based therapy in TTS.
... They peak within 48 hours, and it may take months to normalize. [101][102][103] Echocardiogram (Table 5) Transthoracic echocardiography (ECHO) is essential in the acute phase of CT to establish the initial diagnostic suspicion. The characteristic pattern of segmental alteration is the presence of apical and mesoventricular akinesia or dyskinesia of the anteroseptal segments with hyperdynamia of the basal segments. ...
... The hs-TnT/CKMB ratio is a readily available parameter that could be used in conjunction with clinical risk scores, other biomarkers, and ECG findings to discriminate between TS and MI [42]. TS is associated with marked and persistent elevation of NT-proBNP/BNP levels, which correlates with the extent of catecholamine increase and the severity of LV systolic dysfunction [43]. Recently published studies focused on the potential utility of the release and circulation of specific microRNAs (miRNAs) associated with TTS onset [44]. ...
Takotsubo syndrome, also known as stress-induced cardiomyopathy or "broken heart syndrome," is a transient cardiac condition characterized by sudden and reversible left ventricular dysfunction. It predominantly affects postmenopausal women, although it can occur in men and individuals of all ages. Various risk factors have been associated, including emotional or physical stressors. The clinical presentation of Takotsubo often resembles acute myocardial infarction, with symptoms such as chest pain or discomfort, shortness of breath, palpitations, and fatigue. The absence of significant coronary artery disease on angiography and the characteristic apical ballooning or other regional wall motion abnormalities seen on echocardiography help differentiate it from myocardial infarction. The diagnosis of Takotsubo relies on clinical findings, electrocardiographic changes, elevated cardiac biomarkers, and characteristic findings in imaging studies. The management of Takotsubo syndrome involves supportive care, including addressing the underlying triggers or stressors, symptomatic treatment, and close monitoring of cardiac function and hemodynamics. In most cases, the left ventricular dysfunction resolves spontaneously within days to weeks, and the prognosis is generally favorable, with a low risk of recurrence or long-term complications. However, cardiogenic shock or fatal arrhythmias may also occur as a complication of this condition. An overview of this common cardiomyopathy is provided in this article, highlighting its differences from acute myocardial infarction.
... Concerning serum biomarkers, cardiac troponin T or I, measured by the conventional assays (not high sensitivity), are elevated in > 90% of patients [15] and peak troponin levels are generally < 10 ng/ml [1], substantially lower than in classical ACS. Serum cardiac natriuretic peptides (BNP and NT-pro-BNP) are almost always elevated, with higher levels correlating with the degree of ventricular wall motion abnormalities [16] and usually greater than in ACS [1]. ...
Given the aging of general population, very elderly females with Takotsubo syndrome (TTS) are not rarely encountered in clinical practice. Although coronary angiography with left ventriculography is the gold standard diagnostic tool to exclude or confirm TTS, currently, this invasive procedure is less frequently performed in older patients with several comorbidities, such as renal failure, anemia, infections, neurological disorders, malignancy, and severe frailty. In these patients, a "presumed" TTS is diagnosed on the basis of clinical presentation, electrocardiogram, cardiac biomarkers, and echocardiographic findings without coronary angiography. While, in younger patients, TTS is generally a benign condition, in very elderly females, it is associated with higher in-hospital mortality and poor prognosis. Herein, we present four cases of ultra-octogenarian females diagnosed with "presumed TTS", who did not undergo coronary angiography due to severe frailty and multiple comorbidities and who exhibited poor outcome. This could arise the question if an early more aggressive approach could have changed final results. Probably, the solution could only be a personalized decision deriving from a profound and detailed discussion of each case through a multidisciplinary team approach.
... Typical electrocardiographic findings are ST-segment elevation and T-wave inversion, mainly affecting precordial (V1 to V6) and lateral (DI and aVL) leads 11 . Elevation of cardiac biomarkers such as troponins and natriuretic peptides (BNP and NT-proBNP) have prognostic utility 12 . Although non-invasive imaging modalities (Doppler echocardiogram) are useful in the diagnosis of patients with TTS, final differential diagnosis of an ACS requires invasive coronary angiography, especially in the context of ST-segment elevation. ...
... Cardiac catheterization usually demonstrates unremarkable coronary arteries [1]. Troponin, brain natriuretic peptide (BNP), and N-terminal pro-BNP will be increased [1,11]. ...
Takotsubo cardiomyopathy (TCM) is a rare stress-induced condition that appears rarely in suspected acute myocardial infarction cases. It causes unexplained left ventricular failure, but most cases are reversible with supportive treatment. In this report, we present the case of a 70-year-old female who developed acute hypotension after a laparoscopic Toupet fundoplication on postoperative day one, requiring care in the surgical intensive care unit. Following consultation with the cardiology service and further imaging and tests, she was diagnosed with TCM. This report outlines the potential mechanisms and management of TCM in the intensive care unit, emphasizing the importance of prompt diagnosis and treatment.
... Los hallazgos electrocardiográficos típicos son la elevación del segmento ST y la inversión de la onda T, afectando principalmente a derivaciones precordiales (V1 a V6) y laterales (DI y aVL) 11 . La elevación de biomarcadores cardiacos como troponinas y péptidos natriuréticos (BNP y NT-proBNP) tienen utilidad pronóstica 12 . Aunque las modalidades de imagen no invasivas (ecocardiograma Doppler) son útiles en el diagnóstico de pacientes con STT, el diagnóstico diferencial final de un SICA requiere coronariografía invasiva, sobre todo en el contexto de elevación del segmento ST. ...
Introduction:
takotsubo syndrome (TTS) is a recently recognized entity that resembles an acute coronary syndrome. Its epidemiology has been studied in various populations around the world. The most frequent trigger is an emotional stressful event.
Objective:
To describe the clinical characteristics of a series of cases with TTS.
Material and methods:
A descriptive and retrospective study was carried out. The variables of age, gender, clinical characteristics, cardiovascular risk factors, triggering factors, biomarkers, electrocardiographic, echocardiographic, and angiographic findings in the clinical records of a group of cases of patients with TTS were evaluated.
Results:
19 cases of TTS were included. There were 16 women and 3 men, the average age was 62 ± 14 years; the main cardiovascular risk factor was sedentary lifestyle in 13 cases. The emotional trigger was present in most cases. The most frequent symptom was chest pain, eight cases presented data of shoCKP and heart failure. The most common variant by echocardiography was apical ballooning in 79%, as well as by ventriculography. The most common complication was cardiogenic shoCKP.
Conclusions:
The clinical characteristics of our population are like those previously described in the literature. TTS is a transient and reversible cardiomyopathy with a good prognosis.
... Elevated NT-proBNP levels within 24 to 48 hours from the onset of an acute brain event estimate the magnitude of LV dysfunction in both TTS and NSM. LV systolic dysfunction accompanies myocardial stunning and is found in 8 to 12% of patients with stroke and TTS (25). Elevated NT-proBNP levels return to normal within five to seven days in NSM but can persist for weeks or months in TTS with apical ballooning (26). ...
Stress cardiomyopathy (SCM), also called Takotsubo syndrome (TTS), is a topic of current interest that extends beyond cardiology. The neurological framework currently includes neurogenic stunned myocardium (NSM), an abnormal condition that shares many common features with TTS. Unlike TTS, the main triggers for NSM are mostly neurological events (e.g., acute stroke, subarachnoid haemorrhage [SAH], brain trauma, etc) inducing adrenergic hyperstimulation and ultimately myocardial stunning. Clinical examination, echocardiogram, electrocardiography, and cardiac markers share many similarities and differences between TTS and NSM. The common feature of the two conditions is their shared pathophysiological mechanisms, which ultimately lead to hypercatecholaminaemia and myocardial stunning. Takotsubo syndrome and NSM can be seen as two phenotypes of SCM. Treatment of SCM is based on pathophysiological data and differs according to the risk level: low or high. The course of the disease is not always favourable; for TTS, the immediate prognosis is like that of acute myocardial infarction (MI).
... [1] [10] Objawem patognomicznym dla tego schorzenia obecnym u ok.75% chorych jest stwierdzane w badaniu echokardiograficznym balotowanie koniuszka, czyli akineza lub dyskineza koniuszka i środkowej części lewej komory z jednoczesnym hiperkinetycznym skurczem segmentów podstawnych tej komory. W literaturze opisywano także inne warianty echokardiograficzne choroby Takotsubo takie jak: wariant środkowo-komorowy, w którym akineza obejmuje środkową część lewej komory przy zachowanej kurczliwości koniuszka i segmentów podstawnych oraz wariant podstawny -akineza segmentów środkowych i podstawnych lewej komory z prawidłową kurczliwością koniuszka serca. ...
Takotsubo syndrome (TTS) also known as broken heart syndrome is acute cardiac disease, which is characterized by reversible ventricular motion abnormalities, in the absence of justifying coronary artery disease. The clinical entity was first described in Japan in 1991. The word “Takotsubo” is a container used by the Japanese to catch octopus, which has a narrow neck and a relatively wide base, which resembles the heart's shape in TTS. The cardiomiopathy predominantly affects postmenopausal women and is often preceded by emotional (death of close family member, domestic abuse) or physical (external injury, severe pain) stress. The exact pathophysiological mechanism has not yet been fully clarified. Inordinate amount of catecholamines released into bloodstream after stress attack plays a crucial role in the pathogenesis of TTS. Symptoms of Takotsubo cardiomyopathy such as chest pain and dyspnea are similar to acute myocardial infarction due to it TTS requires careful diagnosis. The main tools for making diagnosis are echocardiography, coronary angiography, ECG, cardiac biomarkers and cardiac magnetic resonance. The syndrome is usually reversible, nevertheless number of patients may develop complications such as cardiogenic shock, arrhythmias, heart failure. Treatment is mostly supportive including Angiotensin-converting enzyme (ACEi) inhibitors and angiotensin receptor blockers (ARBs), which may reduce the likelihood of recurrent episodes. Generally patients with TSS have favourable prognosis, although some deaths are reported. This article is a review of current medical knowledge about Takotsubo syndrome based on available publications in Pubmed and Google Scholar databases.
... The release of NT-proBNP is associated with the degree of LV wall stress while hs-cTnT is a marker of myocardial injury. Thus, a worse myocardial contractility during the acute phase of TTS would favor a higher release of both cardiac biomarkers [33][34][35]. On the other hand, although we did not find a significant correlation between NH-IMRangio and GLS values, we observed a trend towards worse GLS values in those patients with less impaired MR, suggesting that ventricular dysfunction in TTS patients may not be only due to myocardial damage. ...
Background:
Global longitudinal strain (GLS) allows an accurate assessment of left ventricular function with prognostic value. We aimed to evaluate whether the assessment of GLS in the acute phase of Takotsubo syndrome (TTS) provides incremental prognostic value to the degree of impaired microvascular resistance (MR) in TTS patients at 1-year follow-up.
Methods:
We recruited patients admitted for TTS who underwent cardiac angiography and echocardiography from January 2017 to June 2020. Left anterior descending coronary artery non-hyperaemic angiography-derived index of microcirculatory resistance (LAD NH-IMRangio) was calculated. NT-proBNP, high-sensitive cardiac troponin T (hs-cTnT), left ventricular ejection fraction (LVEF) and GLS were measured at admission. Major adverse cardiac events (MACE) were defined as the composite of cardiovascular death, repeat hospitalizations for heart failure (HF) and acute myocardial infarctions.
Results:
67 patients had both GLS and NH-IMRangio available and were included in the study. Median age was 75.2 years and 88% were women. Rate of MACE at 1-year was 13.4%. Kaplan-Meier curves showed higher rates of MACE at 1-year in patients with both higher LAD NH-IMRangio and GLS values compared with those with higher LAD NH-IMRangio and lower GLS values (33.3% vs. 11.1%; p = 0.049). NT-proBNP levels at admission and the recovery of LVEF were correlated with GLS values while MR and hs-cTnT were not.
Conclusion:
GLS provides incremental prognostic value to the degree of impaired MR in TTS patients. The combination of a poorer GLS with a higher degree of impaired MR was associated with a higher rate of MACE in these patients.
... The 12-lead ECG at hospital admission is central in the evaluation of all patients with chest pain, shortness of breath, and dizziness. The most typical changes of the ECG in the SC display ischemic ST-segment and T wave changes [31], usually with T-wave in-the start of symptoms and stays elevated for several days (10 days) and marginally at three months [37,38]. ...
Stress Cardiomyopathy (SC) – also known as Tako-tsubo cardiomyopathy, transient apical ballooning, and broken heart syndrome – is a disease that emerged as an essential form of acute reversible myocardial injury, produced after emotional or physical stress, and described by acute onset of chest pain and related with lectrocardiographic (ECG) changes such as ST-segment elevation, ST-segment depression, or deep T wave inversion, with cardiac biomarker (myocardial CK and troponin T or I) often marginally elevated, and transient regional Left Ventricular (LV) systolic dysfunction, which simulate an Acute Coronary Syndrome (ACS), but in the lack of obstructive coronary artery disease or plaque rupture [1-4].
Since its first description by Saton et al. and Dote et al. in 1990 [4,5], SC has increased recognition between researchers and physicians worldwide; however, it remains an underappreciated and often misdiagnosed disorder [6].
This review aims to describe SC and provide the necessary tools for diagnosis and treatment, and potential complications involved in the disease.
... 15 after the onset of symptoms and can remain elevated for 3 months, providing a useful indicator of severity of LV dysfunction through correlation with LVEF. 18 However, we did not measure these levels. Cardiac troponin levels measured by conventional assays also remain elevated in > 90% of cases but generally < 10 mg/mL, which was observed in our case as well. ...
We discuss a case of a 42-year-old female who was admitted for chronic intractable lower back pain requiring elective spinal surgery. Postoperatively, she experienced chest pressure and abdominal pain with a notable elevation in cardiac markers. A cardiac catheterization and left ventriculogram revealed normal coronary arteries and basal anterolateral hypokinesis, with the normal movement of the distal segment of the anterior wall. A rare variant of stress cardiomyopathy was diagnosed.
... During the acute phase, the findings may include ST-segment elevation (usually in the anterior precordial leads), ST depression, new left bundle branch block (LBBB), T-wave inversion, Q wave abnormalities, and/or QTc prolongation and even complete AV block with ventricular asystole [31,32]. Cardiac biomarkers maybe show elevated levels of serum cardiac troponin and brain natriuretic peptide (BNP) [5,33], while the creatine kinase remains normal or is mildly elevated [5,34]. During the acute phase, the echocardiography shows characteristic features consisting of regional wall motion abnormalities of the LV (or occasionally RV myocardium) that extend beyond a single epicardial coronary artery perfusion territory with a significant reduction in left ventricular ejection fraction (EF) [5,35]. ...
... During the acute phase, the findings may include ST-segment elevation (usually in the anterior precordial leads), ST depression, new left bundle branch block (LBBB), T-wave inversion, Q wave abnormalities, and/or QTc prolongation and even complete AV block with ventricular asystole [31,32]. Cardiac biomarkers maybe show elevated levels of serum cardiac troponin and brain natriuretic peptide (BNP) [5,33], while the creatine kinase remains normal or is mildly elevated [5,34]. During the acute phase, the echocardiography shows characteristic features consisting of regional wall motion abnormalities of the LV (or occasionally RV myocardium) that extend beyond a single epicardial coronary artery perfusion territory with a significant reduction in left ventricular ejection fraction (EF) [5,35]. ...
Introduction
Takotsubo cardiomyopathy is a transient type of acute heart failure with distinct wall motion abnormalities and unclear pathophysiology. This review focuses on the proposed pathophysiological mechanisms that could be involved in the occurrence takotsubo cardiomyopathy.
Main body
Acute stress and subsequent excessive activation of the sympathetic nervous system are major factors in the pathophysiology of takotsubo cardiomyopathy. The high levels of catecholamine work in a triggering manner, generate reactive oxygen species, release inflammatory cytokines, and induce endothelial injury. The incidence of Takotsubo cardiomyopathy has increased following COVID-19 infection and vaccination, which suggests that neurohormonal and psychological factors (i.e., fear and anxiety of infection or vaccination) may have an additional role in the pathophysiology. In addition, inflammatory state, cytokine storm, augmented sympathetic activity, and endothelial dysfunction during the acute phase of COVID-19 infection may participate in Takotsubo cardiomyopathy. Chronic stress is also linked to this complex mechanism by accelerating cripple of endocrinal hypothalamic-pituitary-adrenal axis activity, which influences the cortisol effect on releasing catecholamine, which is directly related to the pathogenesis of takotsubo cardiomyopathy.
Conclusion
The excessive activation of the sympathetic nervous system and subsequent high levels of catecholamines could initiate the process. The catecholamines, in turn, generate reactive oxygen species and release inflammatory cytokines (i.e., IL-1, IL-2, IL-6, IL-7, IL-8, CXCL1, TNF-α, and IFN-γ), which causes endothelial injury.
... They also reported a higher blood level of BNP, a brain natriuretic peptide normally produced in the heart and released in the event of heart stress, compared to control subjects [36]. Several investigators documented a higher level of BNP in TC, noting a marked and persistent plasma levels elevation of NT-proBNP/BNP ratio that correlated with both the extent of catecholamine increase and the severity of LV systolic dysfunction [37]. Wittstein and colleagues showed that patients with stress cardiomyopathy had supraphysiological levels of plasma catecholamines and stress-related neuropeptides whose peak values remain high, even when compared to patients with myocardial infarction [6]. ...
Takotsubo cardiomyopathy (TC) is a reversible cardiomyopathy mimicking an acute coronary syndrome, usually observed in response to acute stress situations. The association between acute ischemic stroke and TC is already known, since it has been previously reported that ischemic stroke can be both a consequence and a potential cause of TC. However, the precise pathophysiological mechanism linking the two conditions is still poorly understood. The aim of our review is to expand insights regarding the genetic susceptibility and available specific biomarkers of TC and to investigate the clinical profile and outcomes of patients with TC and stroke. Since evidence and trials on TC and stroke are currently lacking, this paper aims to fill a substantial gap in the literature about the relationship between these pathologies.
... Other researchers consider that TTS can trigger AMI in turn. [19] The third viewpoint is that the two diseases cannot be completely delinked, because they may be two different names for the same phenomenon. [14,16] The clinical process of the current patient is more consistent with that asserted in the third viewpoint. ...
... The release of NT-proBNP is associated with the degree of LV wall stress while hs-cTnT is a marker of myocardial injury. Thus, a worse myocardial contractility during the acute phase of TTS would favor a higher release of both cardiac biomarkers (33)(34)(35). On the other hand, although we did not nd a signi cant correlation between NH-IMRangio and GLS values, we observed a trend towards worse GLS values in those patients with less impaired MR, suggesting that ventricular dysfunction in TTS patients may not be only due to myocardial damage. ...
Background: Global longitudinal strain (GLS) allows an accurate assessment of left ventricular function with prognostic value. We aimed to evaluate whether the assessment of GLS in the acute phase of Takotsubo syndrome (TTS) provides incremental prognostic value to the degree of impaired microvascular resistance (MR) in TTS patients at 1-year follow-up.
Methods: We recruited 78 consecutive patients admitted for TTS who underwent cardiac angiography and echocardiography from January 2017 to June 2021. Left anterior descending coronary artery non-hyperaemic angiography-derived index of microcirculatory resistance (LAD NH-IMRangio) was calculated. NT-proBNP, high-sensitive cardiac troponin T (hs-cTnT), left ventricular ejection fraction (LVEF) and GLS were measured at admission. Major adverse cardiac events (MACE) were defined as the composite of cardiovascular death, heart failure (HF) events, symptomatic arrythmias and acute myocardial infarctions.
Results: 67 patients had both GLS and NH-IMRangio available. Median age was 75.2 years and 88 % were women. Rate of MACE at 1-year was 23.9% mainly due to mild HF events. Kaplan-Meier curves showed higher rates of MACE at 1-year in patients with both higher LAD NH-IMRangio and GLS values compared with those with higher LAD NH-IMRangio and lower GLS values (60.0% vs 22.2%; p=0.0373). NT-proBNP levels at admission and the recovery of LVEF were correlated with GLS values while MR and hs-cTnT were not.
Conclusions: GLS provides incremental prognostic value to the degree of impaired MR in TTS patients. The combination of a poorer GLS with a higher degree of impaired MR was associated with a higher rate of MACE in these patients.
... The main cardiac biomarkers reported to be modified in Takotsubo syndrome are NT-proBNP and BNP (19). There is a significant and persistent elevation of NT-proBNP and BNP levels during the acute phase of the disease, which correlates with both the elevation of catecholamines and the severity of left ventricular systolic dysfunction (20). BNP levels ≥238 ng/L and the absence of calcium channel blocker use are independent risk factors for delayed recovery, whereas a leptosomic build (BMI < 20 kg/m 2 ) is an independent predictor of rapid recovery (21). ...
Background
Takotsubo syndrome is an acute cardiac condition involving sudden, transient apical ballooning of the left ventricle of the heart that may be triggered by emotional stress and some non-cardiac conditions. Its diagnosis is based on clinical presentation, electrocardiogram, cardiac imaging and biomarkers.
Case Summary
Here, we present a novel and original case report of a patient presenting very soon in the post-partum period with an unusual form of Takotsubo syndrome without clinical symptoms of cardiac disease and accompanied by HELLP syndrome. The overall dynamics of the changes in troponin I, troponin T and NT-proBNP levels after delivery were generally similar, but the amount of troponin I was much greater than that of troponin T and troponin I was already elevated before delivery. NT-proBNP levels peaked around the same time as the troponins and the peak concentration was within the same range as that of troponin I.
Discussion
Our findings indicate that assaying circulating cardiac biomarkers, especially troponin I and NT-proBNP, may be a useful complement to non-invasive cardiac imaging including transthoracic echocardiography and cardiovascular magnetic resonance imaging, in the diagnosis of Takotsubo syndrome. They illustrate the importance of cardiac biomarkers in assisting diagnosis of this disease.
... Matsuo et al. observed impaired metabolism in the apical region by (123)I-beta-methy-iodophenyl pentadecanoic acid ((123)I-BMIPP) imaging, which may result from a myocardial metabolism disorder caused by a surge of catecholamines or microvasospasm [158]. Furthermore, N-terminal pro-B-type natriuretic peptide/B-type natriuretic peptide (NT-pro-BNP/BNP) increased significantly during the first 24 hours after the onset of TTS, which is related to the level of increased catecholamines and the severity of LV contractile dysfunction [159]. ...
Takotsubo syndrome (TTS) is identified as an acute severe ventricular systolic dysfunction, which is usually characterized by reversible and transient akinesia of walls of the ventricle in the absence of a significant obstructive coronary artery disease (CAD). Patients present with chest pain, ST-segment elevation or ischemia signs on ECG and increased troponin, similar to myocardial infarction. Currently, the known mechanisms associated with the development of TTS include elevated levels of circulating plasma catecholamines and their metabolites, coronary microvascular dysfunction, sympathetic hyperexcitability, inflammation, estrogen deficiency, spasm of the epicardial coronary vessels, genetic predisposition and thyroidal dysfunction. However, the real etiologic link remains unclear and seems to be multifactorial. Currently, the elusive pathogenesis of TTS and the lack of optimal treatment leads to the necessity of the application of experimental models or platforms for studying TTS. Excessive catecholamines can cause weakened ventricular wall motion at the apex and increased basal motion due to the apicobasal adrenoceptor gradient. The use of beta-blockers does not seem to impact the outcome of TTS patients, suggesting that signaling other than the beta-adrenoceptor-associated pathway is also involved and that the pathogenesis may be more complex than it was expected. Herein, we review the pathophysiological mechanisms related to TTS; preclinical TTS models and platforms such as animal models, human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) models and their usefulness for TTS studies, including exploring and improving the understanding of the pathomechanism of the disease. This might be helpful to provide novel insights on the exact pathophysiological mechanisms and may offer more information for experimental and clinical research on TTS.
... Almost 50% of patients with HFpEF and borderline HFpEF had an NT-proBNP concentration <5000 pg/mL and 60% of patients with HFrEF had an NT-proBNP concentration >5000 pg/mL. The pathophysiological interpretation of these values is related to the primary stimulus of NT-proBNP release: left ventricular wall stress, which is explained by the interrelated components of LaPlace's Law (transmural pressure gradient, ventricular internal dimensions, wall thickness) 17 . Therefore, patients with HFpEF are more likely to have lower NT-proBNP levels. ...
Objective. The prognostic value of N-terminal procerebral natriuretic peptide (NT-proBNP) in patients with heart failure (HF) is well established. In contrast, its role as an early predictor of mortality in patients hospitalized for heart failure with preserved ejection fraction (HF-EF) and heart failure with reduced ejection fraction (HF-EF) is less well documented. Therefore, the objective of this study is to evaluate the usefulness and prognostic value of plasma NT-proBNP in these patients.
Method. This retrospective observational study included 620 patients admitted for acute heart failure, classified into 3 groups according to their left ventricular ejection fraction (LVEF): HF-EF (LVEF ≥ 50%), HF-mEF (heart failure with ejection fraction mean) (LVEF 35-49%) and HF-rEF (LVEF 15001pg / ml (30.6%). The mortality rate increased significantly in patients with NT-proBNP concentrations > 15001 pg / ml (40%) and decreased with NT-proBNP levels
... It is known that the release of NT-proBNP in acute coronary syndromes is produced by the stress of the LV wall when its filling pressures are raised. However, in TTS patients, NT-proBNP release has been correlated with the plasma catecholamines concentration and with LVEF [35]. We found that patients with higher NH-IMRangio presented higher NT-proBNP values and with lower LVEF, while patients with more extensive CMD (greater number of arteries affected) had higher NT-proBNP values without differences in LVEF. ...
Background:
Coronary microvascular dysfunction (CMD) has been proposed as a key mechanism in Takotsubo syndrome (TTS). The non-hyperaemic angiography-derived index of microcirculatory resistance (NH-IMRangio) has been validated as a pressure-wire-free tool for the assessment of coronary microvasculature. We aimed to study the presence of CMD in TTS patients and its association with levels of cardiac biomarkers and systolic dysfunction patterns.
Methods:
We recruited 181 consecutive patients admitted for TTS who underwent cardiac angiography at a tertiary center from January 2014 to January 2021. CMD was defined as an NH-IMRangio ≥ 25. Plasma levels of NT-proBNP, high-sensitive cardiac troponin T (hs-cTnT) and the left ventricular ejection fraction (LVEF) by echocardiography were measured at admission.
Results:
Mean age was 75.3 years, 83% were women and median LVEF was 45%. All patients presented CMD (NH-IMRangio ≥ 25) in at least one epicardial coronary artery. The left anterior descending artery (LAD) showed higher median NH-IMRangio values than left circumflex (LCx) and right coronary arteries (RCA) (44.6 vs. 31.3 vs. 36.1, respectively; p < 0.001). NH-IMRangio values differed among ventricular contractility patterns in the LAD and RCA (p = 0.0152 and 0.0189, respectively) with the highest values in the mid-ventricular + apical and mid-ventricular + basal patterns. NT-proBNP levels, but not high-sensitive cardiac troponin T (hs-cTnT), were correlated with both the degree and the extent of CMD in patients with TTS. Lower LVEF was also associated with higher NH-IMRangio values.
Conclusions:
CMD is highly prevalent in patients admitted for TTS and is associated with both a higher degree of systolic dysfunction and higher BNP levels, but not troponin.
... Initial surges of catecholamines appear to correlate with NT-proBNP levels and the extent of LV systolic function. 43,44 Since epinephrine and norepinephrine work on the beta receptors in the ventricular myocardium, it would appear beta blockers would be the ideal treatment of this syndrome in acute TTS. 13 However, patients receiving beta blockers in earlier studies have not demonstrated a significant difference in 30-day mortality cardiovascular complications, or TTS recurrence. 17,18 Inflammation also likely plays a significant role in the pathogenesis of TTS. ...
Context:
Approximately 1-2% of patients with suspected acute coronary syndrome also develop Takotsubo syndrome (TTS). This syndrome is characterized by transient systolic dysfunction of the apical and/or mid segments of the left ventricle that mimics myocardial infarction in the absence of obstructive coronary artery disease. Up to 21.8% of TTS patients develop serious complications, including death. Currently, there is no consensus on management of these patients and their complications. Thus, identifying TTS patients at higher risk for complications becomes valuable in managing their hospital course. The aim of this study was to examine the predictive significance of laboratory, echocardiographic, and clinical parameters on in-hospital mortality in a sample subgroup of TTS patients. Secondary analyses were performed on patients with reduced (i.e., <35%) ejection fractions.
Methods:
This retrospective study at a community hospital identified patients from October 1, 2009 to August 31, 2015 who presented with ACS and underwent cardiac catheterization. Patients were diagnosed with TTS by features of cardiomyopathy on cardiac catheterization or echocardiogram.
Results:
The authors analyzed data from a total of 177 eligible patients identified with TTS. The in-hospital mortality rate was 5.65%. Compared to the non-mortality subgroup, patients who suffered in-hospital mortality had significantly lower diastolic blood pressure on admission (p < 0.050), lower hemoglobin levels (p < 0.001), lower sodium (p = 0.020), higher blood urea nitrogen (p = 0.009), lower glomerular filtration rate (p = 0.016), and lower albumin levels (p < 0.001). Cox regression analyses demonstrated admission hemoglobin was significant, yielding a mortality hazard ratio of 0.760 (95% CI of 0.594-0.972, p = 0.029).
Conclusions:
Patients who present with TTS and hypotension, anemia, low albumin levels, elevated lactic acid and renal dysfunction were associated with higher rates of in-hospital mortality in this study's sample population. Further, admission hemoglobin had the strongest association with death. Every unit decrease in hemoglobin increased mortality risk by 24%.
... Further underlining the value of cardiac biomarkers in the early diagnosis of TTS, Dagrenat et al. recently developed a score enabling sufficient distinction between TTS and STEMI by assessing age, gender, history of psychiatric disorders, LVEF, and BNP/troponin I ratio at admission (sensitivity of 92% and specificity of 77%) [63]. Notably, NT-proBNP levels correlate with both the extent of catecholamine increase and the severity of LV systolic dysfunction [64], and NT-proBNP levels are higher in patients with typical TTS than in patients with atypical TTS [3]. ...
First recognized in 1990, takotsubo syndrome (TTS) constitutes an acute cardiac condition that mimics acute myocardial infarction commonly in the absence of obstructive coronary artery disease; it is characterized by temporary left ventricular dysfunction, regularly in a circumferential apical, midventricular, or basal distribution. Considering its acute clinical presentation, coronary angiography with left ventriculography constitutes the gold standard diagnostic tool to exclude or confirm TTS. Frequently, TTS is related to severe emotional or physical stress and a subsequent increased adrenergic stimulation affecting cardiac function. Beyond clinical presentation, epidemiology, and novel diagnostic biomarkers, this review draws attention to potential pathophysiological mechanisms for the observed reversible myocardial dysfunction such as sympathetic overdrive-mediated multi-vessel epicardial spasms, microvascular dysfunction, the direct toxicity of catecholamines, lipotoxicity, and inflammation. Considering the long-term prognosis, further experimental and clinical research is indispensable to elucidate further pathophysiological mechanisms underlying TTS before randomized control trials with evidence-based therapeutic management can be performed.
... The clinical and laboratory manifestations of TCM are similar to those of acute coronary syndrome. Almost all patients with TCM show evidence of myocardial necrosis [14][15][16][17] . Most patients have elevated cardiac troponin levels as a predictor for inhospital prognosis, which may be due to the increase of troponin in membrane leakage caused by acute myocardial necrosis, and troponin is elevated in proportion to the hypodynamic region [18][19][20] . ...
Background:
Takotsubo cardiomyopathy (TCM) is characterized by reversible left ventricular dysfunction triggered by emotional or physical stress. Only 1%-2% of patients with acute coronary syndrome are diagnosed with TCM. Although obstructive coronary artery disease is frequently considered to be the cause of chest pain, TCM should be considered in some clinical settings. In this case, clinicians did not make a timely and accurate diagnosis for TCM due to a lack of knowledge until the third hospitalization with a left ventriculogram.
Case summary:
A 55-year-old postmenopausal woman had intermittent chest pain following emotionally stressful events three times in the past 3 years. Cardiac troponin levels increased after each instance of symptom onset. A transthoracic echocardiogram showed reversible left ventricular dysfunction. The patient underwent three coronary angiograms without evidence of coronary artery disease. A left ventriculogram was first performed at the third hospitalization and revealed apical akinesia with ballooning of the apical region and consistent hypercontractile basal segments. The diagnosis of TCM was confirmed. The patient was treated with an angiotensin-converting-enzyme inhibitor (perindopril) and a β-blocker (metoprolol). No complications occurred during the patient's hospitalization. The patient was told to avoid stressful events. During the 9-mo follow-up visit, the patient was asymptomatic with an ejection fraction of 55%.
Conclusion:
Clinicians should be conscious of the possibility of TCM, especially in postmenopausal women presenting with clinical manifestations similar to acute coronary syndrome without coronary occlusion.
Introducción:
El término MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries) ha cobrado relevancia como diagnóstico de trabajo en el contexto de pacientes con sospecha de isquemia miocárdica y estudio coronario sin lesiones obstructivas.
Objetivos:
Describir las distintas etiologías y variables clínicas de pacientes con MINOCA hospitalizados en la unidad coronaria de nuestro centro (Hospital de la P Universalidad de Chile)
Métodos:
Estudio observacional retrospectivo en el que se realizó un análisis descriptivo de las variables estudiadas. Además, se analizó el uso de los métodos de imágenes complementarios y otras variables pronósticas. El seguimiento se realizó dentro del primer año posterior al evento.
Resultados:
El diagnóstico etiológico más frecuente de los pacientes con MINOCA fue el de miocardiopatía por estrés (MCE). Se incluyeron 55 pacientes, 55% de ellos mujeres. La edad promedio fue 57 años y la frecuencia de factores de riesgo cardiovascular clásicos (FRCV) fue baja. En los pacientes con MCE se observó menores niveles de troponina ultrasensible; mayores niveles de NT-proBNP y mayor mortalidad en comparación a otras etiologías.
Conclusiones:
El perfil de pacientes con MINOCA hospitalizados en nuestro centro correspondió predominantemente a mujeres postmenopáusicas con baja frecuencia de FRCV. La mortalidad de los pacientes con MINOCA se concentró en el grupo con MCE.
Backgrounds
Takotsubo syndrome (TTS) is an intriguing clinical entity characterized by transient myocardial dysfunction. The precise pathophysiological mechanism of TTS is still unknown, but recent evidence suggests a central role of systemic inflammation associated with adrenergic discharge. Although initially considered benign, TTS has shown several potential short-term and long-term complications and adverse outcomes. To improve understanding and management, advanced cardiovascular magnetic resonance (CMR) techniques, such as feature tracking (FT) and parametric mapping, have gained attention.
Purpose of Review
The purpose of this review is to summarize the current literature on the clinical applications of CMR-FT and mapping in TTS. Additionally, the most significant and recent findings will be discussed.
Recent Findings
FT-CMR enables the parametric quantification of myocardial deformation, allowing a comprehensive evaluation of left ventricular, right ventricular, and atrial function. It provides an accurate definition of areas of myocardial dysfunction and potentially serves as a superior prognostic tool compared to ejection fraction. Tissue mapping techniques enable precise and comprehensive tissue characterization by quantifying areas of oedema, and myocardial fibrosis.
Summary
FT-CMR and mapping techniques serve as valuable prognostic tools both in the acute and chronic phases of TTS. They can detect subtle alterations and pan-cardiac involvement, while also providing important insights into the complex underlying mechanisms of the syndrome.
This comprehensive review delves into the multifaceted aspects of Takotsubo Cardiomyopathy (TCM), commonly known as Broken Heart Syndrome, exploring its intricate connection with psychological stress. Beginning with an introduction and historical context, the discussion progresses to elucidate the significance of understanding the link between psychological stress and TCM, emphasizing its impact on symptomatology, quality of life, treatment approaches, and psychological well-being. Further, the review unravels the underlying mechanisms and complex pathophysiology of TCM, categorizing its triggers and stressors while exploring the intricate relationship between psychological stress and TCM onset. Additionally, it discusses the implications of war-related stressors on TCM development, underscoring the need for effective stress management strategies tailored to individuals with TCM. Overall, this review offers a comprehensive exploration of TCM, shedding light on its nuanced relationship with psychological stress and advocating for tailored treatment approaches to address the unique needs of affected individuals.
Objective. This study evaluates the severity of chronic heart failure (CHF), ejection fraction (EF), and global contractility of the left ventricle (LV) using Speckletracking (STE) in patients with takotsubo syndrome (TS) in the early and late disease stages of the disease and compares these data with an assessment of the quality of life (QoL) of patients.
Material and methods. The study included 60 patients with TS, with a mean age of 65.513.4 years. The severity of CHF symptoms was assessed using the SHOKS scale (assessment of the clinical condition in CHF). The Minnesota Questionnaire and the HeartQol questionnaire were used to study QoL. Echocardiography data (ECHOCG) were recorded during the acute period and at discharge from the hospital. In the late disease period, ECHOCG was performed using the STE method. After 1 year, endothelial function was studied using the EndoPAT 2000 device to determine the reactive hyperemia index.
Results. According to the SHOKS scale, the severity of CHF symptoms corresponded to 12 functional class (FC) in all patients with TS in the long-term disease; however, before the development of TS, only 15 people had signs of CHF at the level of 12 FC. According to ECHOCG, LVEF in patients with TS was 44.59.7% at admission, 60.27.6% at discharge, 61.69.2% after a year, and 60.09.0% after 2 years. The average values of global longitudinal and global circular deformation of the left ventricle in patients with TS were 14.03.1 and 15.04.1%, respectively, after 1 year from disease onset and 12.31.9 and 13.11.9%, respectively, after 2 years. When comparing the data of the Minnesota Questionnaire and HeartQol questionnaires, QoL in the long-term of ST was significantly lower than the initial one before disease development. Mean reactive hyperemia index values after 1 year were 1.740.19.
Conclusion. Despite the complete restoration of LVEF in patients with TS, clinical manifestations of CHF persist. Using the STE technique during the long term, 90% of patients had abnormalities in the global tissue deformity of the left ventricle. These changes may explain the CHF clinical manifestations and QoL decrease in patients with TS during long-term disease.
Background:
Takotsubo syndrome (TTS) is characterized by transient contractile dysfunction with its mechanism undefined. We showed that activation of cardiac Hippo pathway mediates mitochondrial dysfunction, and that stimulation of β-adrenoceptors (βAR) activates Hippo pathway. Here we investigated the role of βAR-Hippo signaling in mediating mitochondrial dysfunction in isoproterenol-induced TTS-like mouse model.
Methods:
Elderly post-menopausal female mice were administered with isoproterenol (1.25 mg/kg/h for 23 hours). Cardiac function was determined by serially echocardiography. At day-1 and day-7 post-isoproterenol exposure, mitochondrial ultrastructure and function were examined by electron microscopy and various assays. Alterations in cardiac Hippo pathway and effects of genetic inactivation of Hippo kinase (Mst1) on mitochondrial damage and dysfunction in the acute phase of TTS were investigated.
Results:
Isoproterenol exposure induced transient increase in biomarkers of cardiac damage, and ventricular contractile dysfunction and dilation. At day-1 post-isoproterenol, we observed extensive abnormalities in mitochondrial ultrastructure, downregulation of mitochondrial marker proteins, and mitochondrial dysfunction evidenced by lower ATP content, increased lipid droplets, higher contents of lactate and augmented ROS. All changes were reversed by day-7. βAR stimulation led to activation of cardiac Hippo pathway with enhanced expression of Hippo kinase Mst1 and inhibitory YAP phosphorylation, as well as reduced nuclear YAP-TEAD1 interaction. In mice with cardiac expression of inactive mutant Mst1 gene, acute mitochondrial damage and dysfunction were mitigated.
Conclusion:
Stimulation of cardiac βAR activates Hippo pathway that mediates mitochondrial dysfunction with energy insufficiency and enhanced ROS, promoting acute but transient ventricular dysfunction.
Takotsubo syndrome (TTS) is a condition that has gained increasing interest in the past two decades. This chapter describes information support needs for people with takotsubo syndrome during hospitalisation and after hospital discharge. The pathophysiological mechanisms of TTS are incompletely understood, but increased levels of catecholamines have a central role in its development. TTS may occur in males and females of all age groups, including children and neonates. Several pathophysiological mechanisms for the myocardial stunning that typifies TTS have been proposed. Typically, there is a history of an acute physical or emotional stressor within the preceding hours/few days that triggers TTS. The clinical presentation for TTS is much the same as that for acute coronary syndrome. Transthoracic echocardiography is useful in identifying wall motion abnormalities that typify TTS and monitoring functional recovery. The chapter discusses the current management of TTS and the rationale for various treatments.
Résumé
La cardiomyopathie de Tako-tsubo est définie par une réversibilité totale des troubles de cinétique du ventricule gauche (VG), ainsi qu'une normalisation de la fraction d’éjection du VG après la phase aigüe. Toutefois, des études récentes ont montré que certains patients présentaient des anomalies fonctionnelles, métaboliques, et morphologiques à distance de la phase aigüe remettant en question le caractère totalement réversible de la maladie. Dans cette revue nous évoquons à travers les différents outils utilisés dans ces études cette remise en question (échocardiographie, épreuve d'effort, IRM, médecine nucléaire, biologie, entre autres).
Purpose
To investigate the association between two cardiac biomarkers, NT-proBNP and TnI, with intracranial pressure (ICP)−/cerebral perfusion pressure (CPP)-insults, cerebral pressure autoregulation, delayed ischemic neurological deficits (DIND), and clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH).
Methods
In this retrospective study, 196 aSAH patients treated at the neurointensive care unit, Uppsala University Hospital, Sweden, 2011–2018, with ICP-monitoring and serial NT-proBNP and TnI measurements were included. The first 10 days were divided into early phase (day 1–3) and vasospasm phase (day 4–10).
Results
NT-proBNP and TnI were elevated above the reference interval at least once the first 10 days in 175 (89%) and 116 (59%) patients, respectively. In the vasospasm phase, higher NT-proBNP and TnI were associated with increased percentage of CPP below 60 mmHg. Higher TnI also correlated with more ICP-insults above 20 mmHg. NT-proBNP and TnI did not predict worse pressure autoregulation and DIND. Higher NT-proBNP and TnI were associated with mortality and unfavorable outcome in univariate, but not multivariate, analyses.
Conclusion
Elevated NT-proBNP and TnI correlated with an increased burden of secondary ICP-/CPP-insults, but not with worse pressure autoregulation, DIND, and without independent association with clinical outcome.
Takotsubo syndrome (TS), also known as apical ballooning syndrome is a transient stress‐related cardiomyopathy characterised by acute but reversible left ventricular dysfunction. The condition tends to occur in postmenopausal women after a stressful event. At presentation TS typically mimics acute myocardial infarction (MI) and the incidence of TS has been increasing worldwide. This is likely a consequence of an improved awareness of the existence of this syndrome and easier access to early echocardiography and coronary angiography. However, its aetiology remains poorly understood and it is probably still underdiagnosed. Similar to other countries. TS is being increasingly recognised in New Zealand. In this review, we discuss the demographics, clinical features and outcomes of patients with TS in New Zealand. Doing so informs us not only of the pattern of disease in New Zealand but it also provides insights into the condition itself. This article is protected by copyright. All rights reserved.
Takotsubo syndrome is an acute reversible heart failure syndrome, most frequently seen in postmenopausal women and precipitated generally by significant emotional stress or physical illness. A sudden sympathetic activation seems to play a key role in the pathophysiology, but growing evidence is emerging about the role of inflammation in the subacute and chronic phases. An incidence of life-threatening complications occurring in the acute phase and at long-term follow-up has been demonstrated, comparable with the acute coronary syndrome. Multimodality imaging could be useful to stratify in-hospital and long-term prognosis. The efficacy of specific medical treatments in long-term follow-up should be investigated.
Dynamic intraventricular obstruction has been observed in patients with left ventricular ballooning syndrome (LVBS) and has been hypothesized as a possible mechanism of the syndrome. The aim of this study was to assess the prevalence and significance of dynamic intraventricular obstruction in patients with LVBS.
Dobutamine stress echocardiography was carried out in 22 patients with LVBS (82% apical), all women, aged 68 +/- 9 years. At baseline 1 patient had a > 30 mmHg LV gradient; during stress a LV gradient > 30 mm Hg developed in 6/21 patients (28%) and was caused by systolic anterior motion of the mitral valve in the 3 patients with severe gradient (mean 116 +/- 29 mmHg), who developed mitral regurgitation and impaired apical wall motion and by obstruction at mid-ventricular level in the other 3 with a moderate gradient (mean 46 +/- 16 mmHg). Compared with patients without obstruction those with obstruction had a greater mean septal thickness (11.6 +/- .6 vs 9.8. +/- 3, p < .01), a higher prevalence of septal hypertrophy (71% vs 7%, p < .005) and a higher peak wall motion score index (1.62 +/- .4 vs 1.08 +/- .4, p < .01).
Spontaneous or dobutamine-induced dynamic LV obstruction is documented in 32% of patients with LVBS, is correlated with the presence of septal hypertrophy and may play a role in the development of LVBS in this subset of patients. In those without septal hypertrophy a dynamic obstruction is rarely induced with dobutamine and is unlikely to be a major pathogenetic factor of the syndrome.
To investigate whether and how cold pressor test (CPT) could affect myocardial perfusion and left ventricular (LV) function in patients with previous LV ballooning syndrome (LVBS).
Cold pressor test (3 min hand immersion in ice-water) was performed in 17 women with previous LVBS and in 7 age- and risk factor-matched women with chest pain and normal coronary arteries. At baseline and peak CPT, global and regional LV function, and myocardial perfusion were quantitatively assessed by real-time three-dimensional echocardiography (RT3DE) and myocardial contrast (SonoVue, Bracco) 2D echocardiography (MCE), respectively (Philips iE33 machine, X3-1 and S5-1 probes). Data were analysed off-line (QLab 6.0 software). Peripheral venous catecholamines were assayed by high performance liquid chromatography with electrochemical detection. Cold pressor test induced similar haemodynamic changes and catecholamine increase in controls and LVBS patients. Left ventricular ejection fraction decreased and transient new mid-ventricular and apical motion abnormalities developed in LVBS patients only (quantitative RT3D analysis), without corresponding perfusion defects (MCE). At peak CPT, coronary blood flow and velocity increased (quantitative MCE analysis) in control subjects only.
Cold pressor test induced LV wall motion abnormalities unmatched to regional coronary flow reduction in LVBS patients only. The reduced coronary reserve in response to CPT suggests microvascular dysfunction in LVBS patients.
To gain more insight into the involvement of inflammatory response and neurohumoral activation in Takotsubo cardiomyopathy (TTC), we investigated C-reactive protein (CRP), leukocytes, plasma catecholamines levels, iodine 123 meta-iodobenzylguanidine (123I-mIBG) myocardial uptake, myocardial perfusion (thallium 201 [201Tl] or technetium [Tc] 99m-tetrofosmin myocardial single photon emission computed tomography [SPECT]), and metabolism (fluorine 18-fluorodeoxyglucose positron emission tomography).
Inflammatory status and brain natriuretic peptide (BNP) levels in 17 patients with TTC were compared with 14 age-matched patients. In TTC, elevated levels of CRP were evidenced on admission, reaching a peak in the following days (P < .01). CRP levels were correlated to baseline left ventricular ejection fraction (LVEF) and BNP levels (P < .05). Leukocytes were correlated to BNP and noradrenaline levels. Myocardial 123I-mIBG SPECT showed a reduced activity in the midventricle and apex corresponding to 35% +/- 23% of the total myocardial mass, partially reversible at follow-up. An identical pattern was retrieved when assessing myocardial glucose metabolism. At rest, no relevant abnormalities of myocardial perfusion could be evidenced at the subacute phase.
Inflammatory status in TTC was related to LVEF impairment and to the extent of neurohormonal activation. The hypothesis of a catecholamine-induced myocardial "stunning" is emphasized by the evidence of a reduced 123I-mIBG myocardial activity, impairment of myocardial glucose metabolism, and wall motion kinetic after the same temporospatial distribution.
Quantification of plasma free metanephrines is usually accomplished by HPLC with electrochemical detection, but sample preparation is labor-intensive and time-consuming, run times are long, and interfering substances sometimes obscure the relevant peaks. The aim of this study was to develop a sensitive and specific LC-MS/MS method for plasma free metanephrines.
After solid-phase extraction, chromatographic separation of normetanephrine (NMN) and metanephrine (MN) was accomplished by use of a cyano analytical column. NMN, MN, d(3)-NMN, and d(3)-MN positive ions were detected in the multiple-reaction monitoring mode using the specific transitions m/z 166-->134, 180-->148, 169-->137, and 183-->151, respectively, with an atmospheric pressure chemical ionization source.
Multiple calibration curves exhibited consistent linearity and reproducibility. Interassay imprecision values (CV; n = 20) for NMN at 0.64, 1.9, and 2.7 nmol/L were 6.6%, 7.8%, and 13%, respectively. Interassay CV for MN at 0.60, 1.2, and 2.1 nmol/L (n = 20) were 9.2%, 6.8%, and 9.8%, respectively. The mean recoveries of NMN and MN relative to the internal standard were 100% and 96%, respectively. The assays were linear between 0.20 and 10.0 nmol/L. Deming regression of HPLC and LC-MS/MS results yielded slopes of 0.93 (95% confidence interval, 0.89-0.98) and 0.89 (0.85-0.93) and y-intercepts of -0.16 and 0.03 nmol/L for NMN (n = 132) and MN (n = 92), respectively.
This novel LC-MS/MS approach provides a precise, rapid, and specific alternative method to HPLC for the quantification of the low nanomolar concentrations of free metanephrines in plasma.
Reversible left ventricular dysfunction precipitated by emotional stress has been reported, but the mechanism remains unknown.
We evaluated 19 patients who presented with left ventricular dysfunction after sudden emotional stress. All patients underwent coronary angiography and serial echocardiography; five underwent endomyocardial biopsy. Plasma catecholamine levels in 13 patients with stress-related myocardial dysfunction were compared with those in 7 patients with Killip class III myocardial infarction.
The median age of patients with stress-induced cardiomyopathy was 63 years, and 95 percent were women. Clinical presentations included chest pain, pulmonary edema, and cardiogenic shock. Diffuse T-wave inversion and a prolonged QT interval occurred in most patients. Seventeen patients had mildly elevated serum troponin I levels, but only 1 of 19 had angiographic evidence of clinically significant coronary disease. Severe left ventricular dysfunction was present on admission (median ejection fraction, 0.20; interquartile range, 0.15 to 0.30) and rapidly resolved in all patients (ejection fraction at two to four weeks, 0.60; interquartile range, 0.55 to 0.65; P<0.001). Endomyocardial biopsy showed mononuclear infiltrates and contraction-band necrosis. Plasma catecholamine levels at presentation were markedly higher among patients with stress-induced cardiomyopathy than among those with Killip class III myocardial infarction (median epinephrine level, 1264 pg per milliliter [interquartile range, 916 to 1374] vs. 376 pg per milliliter [interquartile range, 275 to 476]; norepinephrine level, 2284 pg per milliliter [interquartile range, 1709 to 2910] vs. 1100 pg per milliliter [interquartile range, 914 to 1320]; and dopamine level, 111 pg per milliliter [interquartile range, 106 to 146] vs. 61 pg per milliliter [interquartile range, 46 to 77]; P<0.005 for all comparisons).
Emotional stress can precipitate severe, reversible left ventricular dysfunction in patients without coronary disease. Exaggerated sympathetic stimulation is probably central to the cause of this syndrome.
The aim of our study is to assess the incidence and clinical significance of right ventricular (RV) involvement in Takotsubo cardiomyopathy (TTC).
Between February 2002 and December 2005, 47 patients with TTC underwent cardiovascular magnetic resonance (CMR) at our institutions. 13 patients with delayed initial CMR were excluded. In the remaining 34 patients (32 women), RV wall motion abnormalities (WMAs) were present in nine (26%). Left ventricular ejection fraction (LVEF) was significantly lower in patients with RV involvement (40 +/- 6 vs. 48 +/- 10%, P = 0.04). The most frequently affected RV segments were the apico-lateral (89%), the antero-lateral (67%), and the inferior segment (67%). All RV WMA improved or disappeared in eight of nine patients who underwent a follow-up CMR study. Pleural effusion was more common in patients with RV involvement (67 vs. 8%, P < 0.001) and was predictive of RV dysfunction (sensitivity 67% and specificity 92%). Significant or bilateral pleural effusions were seen exclusively in patients with RV involvement.
RV involvement is common in TTC and seems to be associated with a more severe impairment in LV systolic function. It may be suspected by the presence of pleural effusion.
The goal of this study was to assess the regional variations of end-systolic wall stress in patients with reperfused Q wave acute myocardial infarction (AMI), with the use of a three-dimensional (3-D) approach. Fifteen normal volunteers and fifty patients with reperfused AMI underwent cardiac MRI that used a short-axis fast-gradient-echo sequence. The end-systolic wall stress was calculated with the use of the Grossman formula with the radius and the wall thickness defined with a 3-D approach using the tridimensional curvature. The mean wall stress was significantly increased at each level of the short-axis plane only in patients with anterior AMI. When calculated at a regional level in patients with anterior AMI, wall stress significantly increased in anterior sector as well as normal sector. In patients with inferior AMI, wall stress significantly increased only in inferior and lateral sectors. In conclusion, the quantification of regional wall stress by cardiac MRI is better with the 3D approach than other methods for precise evaluation in patients with AMI. Despite early reperfusion, the wall stress remained high in patients with anterior AMI.
We investigated B-type natriuretic peptide (BNP) levels in 10 consecutive patients (all women, mean age 60.4+/-7.8 years) with apical ballooning syndrome. Mean baseline plasma BNP level was 272.6+/-170.4 pg/ml and exceeded the normal range in 8 (80%) patients. When normal levels were adjusted for age and gender, all 10 patients had elevated BNP. Two patients with the highest BNP levels (630 and 423 pg/ml) presented with significant hemodynamic compromise. BNP levels correlated negatively with left ventricular ejection fraction. Increase in BNP levels in apical ballooning syndrome may support the neurohormonal etiology in these patients and requires further studies.
Tako-Tsubo cardiomyopathy (TTC) is a reversible cardiomyopathy with a clinical presentation indistinguishable from myocardial infarction. TTC is estimated to represent 1%-2% of patients presenting with acute myocardial infarction. It most commonly occurs in postmenopausal women and is frequently precipitated by a stressful event. Chest pain and dyspnea are the typical presenting symptoms. Transient ST-segment elevation on ECG and a small rise in cardiac biomarkers are common. Characteristic wall motion abnormalities extend beyond the territory of a single epicardial coronary artery in the absence of obstructive coronary lesions. Supportive treatment leads to spontaneous rapid recovery in nearly all patients. The prognosis is excellent, and recurrence occurs in < 10% of patients. In this article, we review the clinical features of TTC that form the basis of the Mayo Clinic diagnostic criteria, as well as the long-term prognosis for this type of cardiomyopathy.
To evaluate the stress neurohumoral and cardiac biomarker profile of patients with apical ballooning syndrome (ABS).
Plasma-free metanephrines, B-type natriuretic peptide (BNP), high sensitivity C-reactive protein (hsCRP) and troponin T, as well as 24-hour urine catecholamines, metanephrines and free cortisol were measured in 19 ABS and 10 ST-elevation myocardial infarction (STEMI) patients.
An antecedent stressful event was identified in 15 ABS patients. There were no differences in plasma normetanephrine (median 0.64 (IQ range 0.43-0.97) nmol/l vs 0.53 (0.32-0.77) nmol/l, p = 0.44), metanephrine (0.10 (0.10-0.22) nmol/l vs 0.16 (0.10-0.38) nmol/l, p = 0.29), or cortisol levels (16.0 (7.3-44.0) microg/dl vs 13.0 (10.5-23.5) microg/dl, p = 0.95) between ABS and STEMI patients. The 24-hour urine metanephrines, catecholamines and cortisol levels were normal in the majority of ABS patients. Troponin T levels were lower (0.62 (0.18-0.84) ng/ml vs 3.80 (2.04-6.57) ng/ml, p<0.001), but BNP levels were higher in ABS compared with STEMI (944 (650-2022) pg/ml vs 206 (140-669) pg/ml, p = 0.009). HsCRP was similarly elevated in the two groups (11.0 (5.1-110.8) mg/l and 24.3 (8.1-88.6) mg/l, p = 0.78).
Catecholamine and cortisol levels were not elevated in our cohort of ABS, suggesting that routine measurement of these stress hormones is unlikely to be of diagnostic value in practice. In contrast to STEMI, ABS is characterised by a greater elevation in BNP and less myonecrosis.
The present study was designed to delineate and compare the clinical characteristics of patients with apical and non-apical takotsubo syndrome in a high-volume U.S. hospital.
A comparison between apical and non-apical variants of the "broken heart," or takotsubo syndrome, has not been performed in the United States.
From 2004 through 2007, patients with takotsubo syndrome were identified according to the following criteria: acute chest pain with electrocardiographic changes or elevation of cardiac enzymes, absence of significant coronary narrowing, left ventricular (LV) segmental akinesia ("ballooning"), with or without antecedent stressful events. Based upon the location of LV ballooning, the patients were divided into two subgroups: apical and non-apical.
Of 38 patients (age 64 +/- 12 years) fulfilling the inclusion criteria, 84% were women, 79% had documented stressors, 76% had apical and 24% non-apical LV ballooning. When compared to non-apical subjects, apical patients presented predominantly with ST-elevation, had a higher incidence of hypertension, had significantly higher levels of Troponin T (8.5 +/- 6.7 ng/ml vs. 3.4 +/- 2.1 ng/ml, respectively; p = 0.032), and lower ejection fraction (31 +/- 9% vs. 43 +/- 5%, respectively; p < 0.001). Severe complications occurred only in apical subjects: pulmonary edema (10.3%), ventricular tachycardia (6.9%), cardiogenic shock (6.9%), LV apical thrombus (3.4%), transient LV outflow tract obstruction (3.4%), and death (3.4%).
Apical and non-apical ballooning subgroups may represent different manifestations of a single syndrome. When compared with non-apical ballooning, the apical ballooning group may represent a more severe subset characterized by more heart failure and an increased rate of cardiac complications.
Apical ballooning syndrome (ABS) is a unique transient cardiomyopathy that mimics an acute myocardial infarction. The relative frequency of ST-segment elevation on the 12-lead electrocardiogram (ECG) and its prognostic significance is unknown. The aims of this study were to evaluate the frequency and the clinical correlates of ST- and T-wave abnormalities on the admission ECG in patients with ABS.
Patients were retrospectively identified from the cardiac catheterization database--those who underwent coronary and left ventricular angiography and fulfilled the Mayo criteria for ABS during the period January 1988 to November 2006. They were divided into 3 groups according to the presence of (1) ST-segment elevation (>1 mm in 2 contiguous lead) or new left bundle branch block, (2) T-wave inversion (>3 mm in 3 contiguous leads) but no ST shift, and (3) nonspecific ST-T abnormalities or normal ECG at the time of admission. Clinical and echocardiographic findings were compared between groups.
Among the 105 patients, 36 (34.2%), 32 (30.4%), and 37 (35.2%) patients were in the three respective groups. There were no differences in the clinical characteristics, ejection fraction, and outcomes between the 3 groups. Over a median follow-up of 2.5 years, there was no difference in the 5-year recurrence rate of ABS between the 3 groups (13%, 5%, 17% patients, respectively, P = .25). The 5-year mortality was similar in the 3 groups (24%, 7.3%, 10.8%, P = .58).
ST-segment elevation is absent in two thirds of patients with ABS. Thus, the cardiomyopathy may mimic either ST-elevation or non-ST-elevation myocardial infarction. The ECG abnormalities at presentation do not correlate with the magnitude of ventricular dysfunction or outcomes.
The genetic expression and secretion of the cardiac polypeptide hormones atrial natriuretic factor (ANF or ANP) and brain natriuretic peptide (BNP) have been studied mainly in the context of cardiac diseases associated with neuroendocrine and hemodynamic changes arising from cardiac dysfunction such as in chronic congestive heart failure. In this type of pathology, both ANF and BNP plasma levels change in an approximate coordinated fashion so that the use of these hormones as biomarkers of cardiac disease is, in principle, indistinctive. However, we reported that during an acute cardiac allograft rejection episode, BNP plasma levels can significantly increase in the absence of a similar increase in ANF plasma levels. We tested the hypothesis that these changes were related to cytokines and found that some pro-inflammatory cytokines, including TNFα and IL-1β, selectively promote BNP synthesis and secretion in cultures of neonatal rat ventricular cardiocytes. This effect was found related to increased BNP promoter activity and sensitive to p38 mitogen-activated protein kinase inhibition.
In order to determine in vivo if the selective up-regulation of BNP would be observed in inflammatory processes other than acute cardiac allograft rejection, we carried out investigation using the experimental autoimmune myocarditis rat model, which histologically resembles human giant cell myocarditis. It was found that this model is also accompanied by a specific increase in BNP-circulating levels although the cytokines involved seem to differ from those characterized earlier through in vitro studies.
Recent studies in humans have found that in sepsis, plasma BNP levels increase in the absence of hemodynamic changes.
In conclusion, BNP appears to be regulated uniquely in the setting of an inflammatory process. This sets it apart from ANF in terms of potential roles in the pathogenesis of disease and in its use as a biomarker of cardiac disease.
It is generally recognized that chronic left ventricular (LV) pressure overload results primarily in wall thickening and concentric hypertrophy, while chronic LV volume overload is characterized by chamber enlargement and an eccentric pattern of hypertrophy. To assess the potential role of the hemodynamic factors which might account for these different patterns of hypertrophy, we measured LV wall stresses throughout the cardiac cycle in 30 patients studied at the time of cardiac catheterization. The study group consisted of 6 subjects with LV pressure overload, 18 with LV volume overload, and 6 with no evidence of heart disease (control). LV pressure, meridional wall stress (sigman), wall thickness (h), and radius (R) were measured in each patient throughout the cardiac cycle. For patients with pressure overload, LV peak systolic and end diastolic pressures were significantly increased (220 plus or minus 6/23 plus or minus 3 mm Hg) compared to control (117 plus or minus 7/10 plus or minus 1 mm Hg, P less than 0.01 for each). However, peak systolic and end diastolic (sigman) were normal (161 plus or minus 24/23 plus or minus 3 times 10-3 dyn/cm-2) compared to control (151 plus or minus 14/17 plus or minus 2 times 10-3 dyn/cm-2, NS), reflecting the fact that the pressure overload was exactly counterbalanced by increased wall thickness (1.5 plus or minus 0.1 cm for pressure overload vs. 0.8 plus or minus 0.1 cm for control, P less than 0.01). For patients with volume overload, peak systolic (sigman) was not significantly different from control, but end diastolic (sigmam) was consistently higher than normal (41 plus or minus 3 times 10-3 dyn/cm-2 for volume overload, 17 plus or minus 2 times 10-3 dyn/cm-2 for control, P less than 0.01). LV pressure overload was associated with concentric hypertrophy, and an increased value for the ratio of wall thickness to radius (h/R ratio). In contrast, LV volume overload was associated with eccentric hypertrophy, and a normal h/R ratio. These data suggest the hypothesis that hypertrophy develops to normalize systolic but not diastolic wall stress. We propose that increased systolic tension development by myocardial fibers results in fiber thickening just sufficient to return the systolic stress (force per unit cross-sectional area) to normal. In contrast, increased resting or diastolic tension appears to result in gradual fiber elongation or lengthening which improves efficiency of the ventricular chamber but cannot normalize the diastolic wall stress.
We have presented recommendations for the optimum acquisition of quantitative two-dimensional data in the current echocardiographic environment. It is likely that advances in imaging may enhance or supplement these approaches. For example, three-dimensional reconstruction methods may greatly augment the accuracy of volume determination if they become more efficient. The development of three-dimensional methods will depend in turn on vastly improved transthoracic resolution similar to that now obtainable by transesophageal echocardiography. Better resolution will also make the use of more direct methods of measuring myocardial mass practical. For example, if the epicardium were well resolved in the long-axis apical views, the myocardial shell volume could be measured directly by the biplane method of discs rather than extrapolating myocardial thickness from a single short-axis view. At present, it is our opinion that current technology justifies the clinical use of the quantitative two-dimensional methods described in this article. When technically feasible, and if resources permit, we recommend the routine reporting of left ventricular ejection fraction, diastolic volume, mass, and wall motion score.
We previously demonstrated that brain natriuretic peptide (BNP) is a cardiac hormone mainly produced in the ventricle, while the major production site of atrial natriuretic peptide (ANP) is the atrium. To assess the pathophysiological role of BNP in ventricular overload, we have examined the gene expression of BNP, In comparison with that of ANP, in a model of cardiac hypertrophy using cultured neonatal rat ventricular cardiocytes. During cardiocyte hypertrophy evoked by endothelin-1, Phenylephrine, or PMA, the steady state level of BNP mRNA increased as rapidly as the "immediate-early" induction of the c-fos gene expression, and reached a maximal level within 1 h. Actinomycin D, a transcriptional inhibitor, completely diminished the response, while the translational blocked with cycloheximide did not inhibit it. In contrast, ANP mRNA began to increase 3 h after the stimulation, and accumulated during cardiocyte hypertrophy. The BNP secretion from ventricular cardiocytes was also stimulated, more rapidly than the ANP secretion. Furthermore, the turnover of BNP mRNA was significantly faster than that of ANP mRNA, being consistent with the existence of AUUUA motif in the 3'-untranslated region of BNP mRNA. These results demonstrate that the gene expression of BNP is distinctly regulated from that of ANP at transcriptional and posttranscriptional levels, and indicate that the characteristics of the BNP gene expression are suitable for its possible role as an " emergency" cardiac hormone against ventricular overload.
Cardiac natriuretic peptides, especially amino terminal pro-Brain Natriuretic Peptide (NT-proBNP), are emerging as powerful circulating markers of cardiac function. However, the in vivo secretion and elimination (t1/2) of these peptides during acute volume overload have not been studied. We present the first report of the secretion and elimination of cardiac natriuretic peptides, based on deconvolution analysis of endogenous ovine plasma levels measured by specific radioimmunoassay. Four normal, conscious sheep underwent rapid right ventricular pacing (225 bpm) for 1 hour to stimulate acute cardiac natriuretic peptide release. Plasma samples and right atrial pressure measurements were taken at regular intervals 30 minutes before, during, and 4 hours after pacing. Baseline right atrial pressure significantly increased (P:=0.02) during the 1 hour of pacing in association with a prompt increase in plasma BNP (P:=0.03), atrial natriuretic peptide (P:=0.01), and NT-proBNP (P:=0.02). Deconvolution analysis showed that the t1/2 of NT-proBNP (69.6+/-10.8 minutes) was 15-fold longer than BNP (4.8+/-1. 0 minutes). Despite sustained increases in atrial pressure, cardiac secretion of natriuretic peptides (particularly atrial natriuretic peptide) fell during the pacing period, suggesting a finite source of peptide for secretion. Size-exclusion high-performance liquid chromatography revealed NT-proBNP to be a single immunoreactive peak, whereas BNP comprised at least 2 immunoreactive forms. These findings, especially the prompt secretion of BNP and the prolonged t1/2 of NT-proBNP, clarify the metabolism of BNP forms and help to explain the diagnostic value of NT-proBNP measurement as a sensitive marker of ventricular function.
The cause of chest pain in patients with normal coronary arteriograms (CAG) remains poorly understood.
Left ventricular endomyocardial biopsies from 11 anginal patients with normal CAG and normal left ventriculograms and from seven anginal patients with coronary stenosis were studied by light and electron microscopy. Biopsies from seven non-anginal patients (non-ischemic electrocardiogram abnormalities but no evident heart or systemic diseases) served as controls. In anginal patients with normal CAG, both cardiocytic diameter (17.2 +/- 5.5 microm) and interstitial space percentage area (37.6 +/- 14.9%) were significantly larger than those (13.7 +/- 0.9 microm, 14.9 +/- 2.9%) in control participants. Some cardiocytic nuclei (1.9% of 2000 randomly selected nuclei) exhibited DNA degradation by in-situ nick-end labeling. Electron microscopy revealed cardiocytic nuclei with distinct apoptotic ultrastructures (2.8% of 200 nuclei), phagocytic degradation of cardiocytic cytoplasm, and capillary endothelial swelling (7.1% of 200 capillary transverse sections). No significant infiltration of inflammatory cells was seen. In anginal patients with coronary narrowing (cardiocytic diameter, 16.8 +/- 1.1 microm; interstitial space, 20.1 +/- 5.8%; DNA degraded nuclei, 1.3%), there were however no apoptotic cardiocytic nuclei or cytoplasm and less capillary endothelial swelling (1.6%) in ultrastructure.
In biopsies from anginal patients with normal CAG, the presence of cardiocytic hypertrophy and replacement fibrosis are both abnormal. Cardiocytic apoptosis and capillary endothelial swelling, found by others as characteristic of experimental myocardial reperfusion injury, are evident. This supports the possibility of myocardial transient ischemia and reperfusion injury in patients with angina and normal CAG.
Cardiologists have recently recognized a reversible form of heart failure of unknown origin characterized by a takotsubo-shaped hypokinesis of the left ventricle on left ventriculography.
To clarify the clinical features of this cardiomyopathy.
Observational study.
Seven patients with reversible ventricular dysfunction were followed for 4.5 years. Clinical course, routine examinations, and cardiac catheterizations in each patient were documented.
The cardiomyopathy developed in six elderly female and one male patients (mean age 75.3 years), all of whom had been exposed to stress. Cardiac enzymes did not significantly increase, but serum norepinephrine increased remarkably (1.19 ng/ml). Coronary angiography revealed normal coronary arteries. However, left ventriculography showed akinesis in the apical segments, together with hyperkinesis in the basal segments (a takotsubo shape). The abnormal kinesis normalized within 17.4 hospital days without any treatment in five patients, and with haemodynamic support for 3 days in the other two. Endocardial biopsies did not suggest any specific pathology. The cardiac events did not recur over a 1-4 year follow-up.
Coronary vasospasm, myocarditis and other substantial diseases previously described were ruled out as the cause of takotsubo cardiomyopathy in our subjects. Prognosis was good without any form of treatment, provided that the patients survived the severe heart failure state. Catecholaminergic or adrenoceptor-hyperactive cardiomyopathy may be the cause of this cardiomyopathy.
The aim of the present study was to investigate the putative role of endothelin (ET) in mediating ischemia/hypoxia-induced ANP release utilizing exogenous ET-1 or ET receptor antagonists (BQ-123 or Bosentan). Isolated rat hearts with non-distended atria were perfused using a Langendorff apparatus and heart rate maintained constant via atrial pacing. Global ischemia was induced either by direct reduction in perfusion or by infusion of exogenous ET-1 (5 x 10(-10) M) for 30 minutes. Perfusion with the ET receptor antagonists, BQ-123 (10(-6) M) or Bosentan (10(-5) M) was initiated 10 minutes before onset of ischemia. Moderate or severe ischemia was induced by reduction (52-61% and 70-82%, respectively) in perfusate flow. Thirty minutes of ischemia/hypoxia (5% O2) was followed by 30 minutes of reperfusion/re-oxygenation. Both moderate and severe ischemia increased ANP release. BQ-123 and Bosentan did not affect basal or ischemia-induced ANP release. Exogenous ET-1 perfusion induced a late increase in ANP release (P < 0.01) that did not exceed the increase in ANP release associated with equivalent direct flow reduction. Hypoxia induced an 8-fold increase in ANP release rate. The ANP release rate returned toward basal levels after re-oxygenation. Bosentan, but not BQ-123, significantly attenuated (P < 0.01) hypoxia-induced ANP release. In conclusion, in this system, ANP release is stimulated by moderate (or severe) ischemia and severe hypoxia independent of change in atrial distension; endogenous ET does not mediate basal and ischemia-induced ANP release; and hypoxia-induced ANP release is partially modulated via interaction with endogenous ET.
Takotsubo cardiomyopathy is a reversible left ventricular dysfunction with symptoms resembling acute myocardial infarction, but without coronary lesions. Patients have wall motion abnormalities (apical akinesis and basal hyperkinesis), and characteristic left ventricular morphology.
To investigate plasma brain natriuretic peptide (BNP) concentrations in takotsubo cardiomyopathy.
Ten consecutive patients with takotsubo cardiomyopathy underwent cardiac catheterization on their first hospital day, and blood was collected to measure BNP. To evaluate acute basal hyperkinesis, the difference in diameter between systole and diastole was measured at 10 mm below the aortic valve (the deltaBase value).
Coronary angiography revealed no significant stenosis in any patient. Initial ejection fraction was 42.2 +/- 7.3%, cardiac index was 1.90 +/- 0.39 l/min/m(2), and plasma BNP was 522.5 +/- 632.9 pg/ml. Ventricular contraction and the ejection fraction were normalized on echocardiography after 17.9 +/- 6.3 days. BNP was significantly correlated with deltaBase, but not with other cardiac parameters.
Initial deltaBase value seems to be a good indicator of the severity of basal hyperkinesis in patients with takotsubo cardiomyopathy. In contrast to other diagnoses, a high BNP concentration is not associated with a poor prognosis in this condition.
To the Editor: Reports on “the transient left ventricular apical ballooning syndrome” (TLVABS) have described the peculiar, yet characteristic transient regional systolic dysfunction involving the left ventricle (LV) ([1][1]). None of these studies have reported right ventricular (RV)
B-type natriuretic peptide (BNP) is chronically elevated in heart transplantation and reflects diastolic dysfunction, cardiac allograft vasculopathy, and poor late outcome. This investigation studied peripheral gene expression signatures of elevated BNP concentrations in clinically quiescent heart transplant recipients in an effort to elucidate molecular correlates beyond hemodynamic perturbations.
We performed gene microarray analysis in peripheral blood mononuclear cells of 28 heart transplant recipients with clinical quiescence (absence of dyspnea or fatigue; normal left ventricular ejection fraction [EF >55%]; ISHLT biopsy score 0 or 1A; and normal hemodynamics [RAP <7 mm Hg, PCWP < or = 15 mm Hg, and CI > or = 2.5 L/min per m2]). BNP levels were performed using the Triage B-type Natriuretic Peptide test (Biosite Diagnostics Inc, San Diego, Calif) and median BNP concentration was 165 pg/mL. Seventy-eight probes (of 7370) mapped to 54 unique genes were significantly correlated with BNP concentrations (P<0.001). Of these, the strongest correlated genes (P<0.0001) were in the domains of gelsolin (actin cytoskeleton), matrix metallopeptidases (collagen degradation), platelet function, and immune activity (human leukocyte antigen system, heat shock protein, mast cell, and B-cell lineage).
In the clinically quiescent heart transplant recipient, an elevated BNP concentration is associated with molecular patterns that point to ongoing active cardiac structural remodeling, vascular injury, inflammation, and alloimmune processes. Thus, these findings allude to the notion that BNP elevation is not merely a hemodynamic marker but should be considered reflective of integrated processes that determine the balance between active cardiac allograft injury and repair.
Tako-Tsubo cardiomyopathy (TTC) which is usually precipitated by profound emotional stress has been widely reported in the past. Recently, several co-morbidities have been found to be associated with this new cardiac entity. In this case we report from a female patient suffering from both, physical and emotional stress. After a persistent episode of severe abdominal pain due to acute cholecystitis and recurrent events of emotional stress, characteristic features of TTC could be documented. Histopathological analysis documented characteristic structural alterations including contraction band necrosis. Thus, this case confirms the hypothesis of an overstimulated sympthatoadrenergic system in TTC resulting from both, severe physical and emotional stress.
Aims Our study aims to investigate the pathophysiologic mechanism underlying tako-tsubo cardiomyopathy using F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET).
Methods and results Fifteen patients with tako-tsubo cardiomyopathy were enrolled in this study. Plasma catecholamines, cardiac troponin T (cTnT), and D-dimer were serially evaluated in all patients. Thallium-201 (201Tl) single-photon emission computed tomography (SPECT) and F-18 FDG PET were performed in 10 and eight patients, respectively. Emotional or physical stress occurred in 12 (80.0%) patients. ST-T segment abnormalities existed in all patients. Thirteen patients exhibited mildly elevated cTnT, although coronary angiography did not reveal significant stenosis in any patient. Endomyocardial biopsy specimens (n = 9) demonstrated contraction-band necrosis (n = 4) and mononuclear cell infiltration (n = 3). The levels of norepinephrine and epinephrine peaked on admission (744 ± 452 and 140 ± 166 pg/mL, respectively). There was severely reduced uptake at the apex on F-18 FDG PET image, despite slightly reduced uptake of 201Tl. Elevation of D-dimer was observed in nine patients.
Conclusion The extent of metabolic defect involving apical akinetic area was more severe than perfusion abnormality. Our data suggest that sudden emotional or physical stress may cause a catecholamine-induced metabolic disorder in the myocardium, which is probably central to this syndrome.
Subcommittee on Quantitation of Two-Dimensional Echocardiograms
cle by two-dimensional echocardiography. American Society of
Echocardiography Committee on Standards, Subcommittee on
Quantitation of Two-Dimensional Echocardiograms. J Am Soc
Echocardiogr 1989;2:358 -367.