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Treadmill exercise in assessment of the functional capacity of patients with cardiac disease
Abstract
The effort tolerance of 43 patients with cardiac disease was evaluated with use of an intermittent multistage treadmill exercise test. The results were compared with independently made clinical estimates of functional classification using the criteria of the New York Heart Association.The 43 adult patients were classified into 4 groups on the basis of peak oxygen consumption (V̇O2) achieved during treadmill exercise; 11 patients (26 percent) achieved a plateau in V̇O2, and 32 (74 percent) had a symptom-limited capacity. Subjects in Group 1 had a VO2 of 23 ml/kg per min or greater; Group 2, 16 to 22 ml/kg per min; Group 3, 10 to 16 ml/kg per min; and Group 4, 10 ml/kg per min or less. Although the correlation between treadmill exercise and the physician's assessment of functional classification was significant (r = 0.84, P < 0.01), the agreement was inversely related to the seriousness of impairment. There was total agreement between the 2 methods for patients with functional class I status, but disagreement in 6 of 16 (38 percent) patients considered to have functional class II status, 4 of 15 (27 percent) with functional class III, and 1 of 2 (50 percent) with functional class IV status. When a discrepancy occurred between measured performance capacity and the clinically rated functional class, a review of the hemodynamic data recorded during cardiac catheterization usually indicated that graded exercise more accurately reflected the degree of cardiac impairment.These results indicate that patients with cardiac disease begin to experience limiting symptoms when peak oxygen consumption is less than 22 ml/kg per min and usually consider themselves severely limited when peak oxygen consumption is 16 ml/kg per min or less. The determination of a patient's performance capacity affords an objective measurement of the degree of cardiac impairment and may be useful in the planning of patient management.
... Modified and less intense protocols have been created and validated for the apparently healthy population, such as the modified Bruce, Balke-Ware, and the United States Air Force Space and AeroMedicine (USAFSAM) protocols [24][25][26]. However, none of these protocols have been validated for cancer survivors. ...
... Additionally, the median age of cancer diagnosis is 65 years of age, and other validated protocols have been deemed unsuitable for the gerontological population due to general exhaustion [46]. Because CS experience unique detrimental side effects, a protocol should be designed with cancer specific side-effects in mind, just as the modified Naughton protocol was tailored for individuals diagnosed with congestive heart failure [25]. ...
Utilizing protocols to obtain peak oxygen consumption (VO2peak) that were designed for the apparently health population may be inappropriate for cancer survivors (CS). The University of Northern Colorado Cancer
Rehabilitation Institute (UNCCRI) has developed a treadmill protocol designed for CS to address this issue. Objective: To assess the construct validity of VO2 peak prediction equations for the UNCCRI multistage treadmill protocol against obtained VO2peak values in a population of CS.
Methods: Forty-five CS completed the UNCCRI VO2peak treadmill protocol utilizing gas analysis (GAS) to obtain a true VO2peak value. A VO2peak value was also estimated from the gas analysis test (EstGAS) using American College of Sports Medicine’s (ACSM) prediction equations. Additionally, a separate UNCCRI treadmill protocol not
using gas analysis (NoGAS) was conducted using ACSM VO2 prediction equations to determine VO2peak. An ANOVA was used to compare GAS, EstGAS, and NoGAS to assess the validity of the prediction equations versus the VO2peak obtained from gas analysis. A paired t-test was utilized to compare treadmill times between GAS and NoGAS to assess differences attributed to the use of gas analysis. A Pearson correlation was used to analyze the relationship between GAS and EstGAS VO2 peak values. Results: VO2 peak (mL•kg-1•min-1) did not significantly differ between GAS (26.8+7.0), EstGAS (26.2+6.5), and NoGAS (27.1+6.5) (P=0.2). Total treadmill time (min) differed significantly between GAS (12.1+2.8) and NoGAS (12.6+3.0; P<0.05). A significant, strong positive correlation was observed in VO2peak values between GAS and
EstGAS (r=0.9; P<0.001). Conclusion: The UNCCRI treadmill protocol accurately predicts VO2peak when using gas analysis and when
used with ACSM’s prediction equations demonstrating its construct validity. The UNCCRI treadmill protocol offers a safe and alternative measure of VO2peak for the cancer population.
... Table 2 provides participant characteristics. On average, participants were considered overweight, were normotensive, appeared to have well-managed lipids, and had a moderate-tohigh functional capacity [25,26]. ...
... The low or lack of correlations with the other variables may be partially explained by the minimal variability among the various markers within this study population. On average, participants were considered overweight and exceeded waist circumference guidelines [32], but were normotensive, appeared to have their lipids well-managed (within Canadian guideline target lipid values [33,34]), and had a relatively high functional capacity [26]. It is also possible that participants were engaging in a greater amount of MVPA due to a reactive response from wearing the monitors, and the MVPA results reported herein are not typical. ...
Background:
Accurate assessment of physical activity among coronary artery disease patients is important for assessing adherence to interventions. The study compared moderate-to-vigorous physical intensity activity and relationships with cardiometabolic health/fitness indicators using accelerometer cut-points developed for coronary artery disease patients versus those developed in younger and middle-aged adults.
Methods:
A total of 231 adults with coronary artery disease wore an Actigraph GT3X accelerometer for ≥4 days (≥10 hours/day). Moderate-to-vigorous intensity physical activity between cut-points was compared using Bland-Altman analyses. Partial spearman correlations assessed relationships between moderate-to-vigorous intensity physical activity from each cut-point with markers of cardiometabolic health and fitness while controlling for age and sex.
Results:
Average time spent in bouts of moderate-to-vigorous intensity physical activity using coronary artery disease cut-points was significantly higher than the young (mean difference: 13.0±12.8 minutes/day) or middle-aged (17.0±15.2 minutes/day) cut-points. Young and middle-aged cut-points were more strongly correlated with body mass index, waist circumference and systolic blood pressure, while coronary artery disease cut-points had stronger relationships with triglycerides, high-density and low-density lipoproteins. All were similarly correlated with measures of fitness.
Conclusion:
Researchers need to exert caution when deciding on which cut-points to apply to their population. Further work is needed to validate which cut-points provide a true reflection of moderate-to-vigorous intensity physical activity and to examine relationships among patients with varying fitness.
... The functional classification of the New York Heart Association is often misleading (37,38) . A significant negative relationship exists between exercise capacity and the severity of the valvular lesion as measured by cardiac catheterization and left ventriculography (37,(39)(40)(41). ...
... The functional classification of the New York Heart Association is often misleading (37,38) . A significant negative relationship exists between exercise capacity and the severity of the valvular lesion as measured by cardiac catheterization and left ventriculography (37,(39)(40)(41). Data obtained at rest from such tests or the medical history, however, often do not predict accurately the individual patient's response to exercise. ...
... Patients developing HVD during the follow-up period (while having normal echocardiography upon APS diagnosis), were classified as pAPS-HVD. Symptoms associated with heart failure were assessed according to New York Heart Association (21). ...
Objectives
Antiphospholipid syndrome (APS)-associated heart valve disease (HVD) is well described. Nonetheless, limited data exist on clinical parameters associated with the course of primary APS (pAPS) patients with HVD. The goal of this study was to assess clinical features and related outcomes in patients with APS associated HVD.
Methods
In this multicentre retrospective study, we identified 33 pAPS patients with HVD (pAPS-HVD group) and compared their clinical course with 128 pAPS patients with normal heart valves on echocardiography (pAPS-control group).
Results
pAPS-HVD patients had more cerebrovascular events 56.3% vs 25% (p= 0.005) and livedo reticularis 24.2% vs 7.8% (p= 0.013) than pAPS-controls. Furthermore, catastrophic-APS (CAPS) (12.1% vs 2.4%, p= 0.034), recurrent thrombosis (33.3% vs 4.7%, p< 0.001), and need for advanced therapy (i.e. IVIG, plasmapheresis or rituximab) were more frequent in pAPS-HVD patients. Anti-B2GPI-IgG. [84.8% vs 63.2% (p= 0.034)], anti-cardiolipin IgG [90.9% vs. 64.8% (p= 0.005)] and triple positive aPL [75.8% vs 56.5% (p= 0.047)] were commoner in pAPS-HVD patients vs pAPS-controls. Ten of the 33 patients with pAPS-HVD underwent valve surgery which was associated with male gender, smoking, arterial limb ischaemia and livedo reticularis.
Conclusion
pAPS-HVD patients had a more severe APS clinical course including CAPS and thrombotic events as well as with specific serology namely IgG isotype aPL antibodies and triple positivity. Our data suggest that pAPS-HVD represents a high-risk subgroup of APS patients.
... The RMR, also termed resting energy expenditure, is defined as the energy needed to maintain essential body functions in an awake, restful, postabsorptive and thermoneutral state, and is usually measured by indirect calorimetry [9]. When the RMR cannot be directly assessed, an RMR value of 3.5 mL O 2 kg −1 min −1 is commonly assumed, originally derived from a single 70-kg, 40-year-old man [8,[10][11][12], and is generally regarded as 1 standard MET. However, studies conducted by Kozey et al. [13], Byrne et al. [11] or Ainsworth et al. [14] have shown this reference value may be overestimated for several population subgroups including older adults. ...
Background
It is important for sport scientists and health professionals to have estimative methods for energy demand during different physical activities. The metabolic equivalent of task (MET) provides a feasible approach for classifying activity intensity as a multiple of the resting metabolic rate (RMR). RMR is generally assumed to be 3.5 mL of oxygen per kilogram of body mass per minute (mL O2 kg−1 min−1), a value that has been criticized and considered to be overestimated in the older adult population. However, there has been no comprehensive effort to review available RMR estimations, equivalent to 1 MET, obtained in the older adult population.Objective
The aim of this review was to examine the existing evidence reporting measured RMR values in the older adult population and to provide descriptive estimates of 1 MET.MethodsA systematic review was conducted by searching PubMed, Web of Science, Scopus, CINAHL, SPORTDiscus, and Cochrane Library, from database inception to July 2021. To this end, original research studies assessing RMR in adults ≥ 60 years old using indirect calorimetry and reporting results in mL O2 kg−1 min−1 were sought.ResultsTwenty-three eligible studies were identified, including a total of 1091 participants (426 men). All but two studies reported RMR values lower than the conventional 3.5 mL O2 kg−1 min−1. The overall weighted average 1 MET value obtained from all included studies was 2.7 ± 0.6 mL O2 kg−1 min−1; however, when considering best practice studies, this value was 11% lower (2.4 ± 0.3 mL O2 kg−1 min−1).Conclusion
Based on the results of this systematic review, we would advise against the application of the standard value of 1 MET (3.5 mL O2 kg−1 min−1) in people ≥ 60 years of age and encourage the direct assessment of RMR using indirect calorimetry while adhering to evidence-based best practice recommendations. When this is not possible, assuming an overall value of 2.7 mL O2 kg−1 min−1 might be reasonable. Systematic review registration: International Prospective Register of Systematic Reviews on 30 September 2020, with registration number CRD42020206440.
... Although 42 patients (40.3%) presented some of these high-risk criteria, no relationship with mortality was found. In this sense, we should consider the significant progress in critically ill pediatric patients' management, which becomes a topic of interest to be considered in future research [14][15][16][18][19][20][21][22][23][24][25] . ...
Background:
This study describes 35 years of experience in a tertiary care level hospital that treats cardiac patients with univentricular heart physiology who underwent Glenn surgery.
Methods:
The study consisted of a retrospective analysis of patients who underwent Glenn surgery, including variables related to pre-operative, intra-operative, and post-operative morbidity and mortality.
Results:
From 1980 to 2015, 204 Glenn surgeries were performed. The most common heart disease was tricuspid atresia IB (19.2%). In 48.1% of the cases, the procedure was performed with antegrade flow. A bilateral Glenn procedure was performed in 12.5% of the cases and 10.3% were carried out without using a cardiopulmonary bypass pump. Reported complications included infections, bleeding, arrhythmias, chylothorax, neurological alterations, and pleural effusion. The mortality rate was 2.9%.
Conclusions:
Glenn surgery is a palliative surgery with good results. It significantly improves patient quality of life over a long period until a total cavopulmonary shunt is performed. The complications observed are few, and the mortality rate is low. Therefore, it is a safe surgery that should be used for univentricular congenital heart disease.
... All patients underwent a symptom-limited CPET on a standard treadmill according to the Naughton protocol [11]. During the test, patients inspired room air through a low-resistance mask, and expired oxygen and carbon dioxide partial pressures were measured with a gas analyzer (MedGraphics, St Paul, MN, USA). ...
PurposeChronotropic incompetence (CI) in patients with heart failure is common and associated with impaired exercise intolerance and adverse outcomes. This study sought to determine the effects of closed loop stimulation (CLS) rate-adaptive pacing on functional capacity in patients with heart failure with reduced ejection fraction (HFrEF) and CI implanted with cardiac resynchronization therapy (CRT) devices.MethodsA randomized, blinded, cross-over designed trial enrolled patients with HFrEF and CI implanted with a Biotronik CRT-D to complete a quality of life questionnaire, 6-min walk distance (6MWD), and cardiopulmonary exercise testing after two programmed periods: 1-week period of CLS and 1-week period of standard accelerometer (DDDR).ResultsNine patients (6 males, mean age 71.4 years, 7 with New York Heart Association Class III, mean ejection fraction 39 ± 8%) were enrolled. Quality of life trended higher in CLS as compared to DDDR (550.8 ± 123.9 vs 489.3 ± 164.9, p = 0.06). There were no differences between CLS and DDDR in 6MWD (293.1 ± 90.2 m vs 315.1 ± 95.5 m, p = 0.52), peak heart rate (HR) 110.7 ± 14.7 bpm vs 109.7 bpm ± 14.1, p = 0.67), or peak VO2 (12.3 ± 4.9 ml/kg/min vs 12.9 ± 5.9, p = 0.47). As tests were submaximal as indicated by low respiratory exchange ratios (0.98 ± 0.11 vs 1.0 ± 0.8, p = 0.35), VE/VCO2 slope also showed no difference between CLS and DDDR (35.8 ± 5.6 vs 35.4 ± 5.7, p = 0.65). Five patients (56%) preferred CLS programming (p = 1.0).Conclusions
In patients with HFrEF and CI implanted with a CRT-D, peak HR, peak VO2, and 6MWD were equivalent, while there was a trend toward improved quality of life in CLS as compared to DDDR.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT02693262.
... Trotzdem sei darauf hingewiesen, dass diese Art der Erhebung -mittels Patientenbefragungen -nur einen subjektiven Eindruck widerspiegeln kann. Gerade weil die von der New York Heart Association erstellten Stadieneinteilungen nur eine grobe Orientierung für den Untersucher darstellen, kann nicht ausgeschlossen werden, dass verschiedene Untersucher auch bei dem gleichen Patienten zu einer unterschiedlichen Einteilung kommen ( GOLDMAN et al., 1981;PATTERSON et al., 1972;RAPHAEL et al., 2007). können daher mit der durchgeführten Untersuchung nicht immer zuverlässig erkannt werden. ...
... • Regulação da altura do assento para o indivíduo . 7 • Iniciar com um período de ativação de 3 min no cicloergómetro a 50 RPM, com uma carga de 50 W (≈ 300 kpm.min -1 ). ...
Ao longo deste livro, serão apresentados protocolos de avaliação da capacidade aeróbia, quer através de Testes Submaximais para Estimação do Consumo Máximo de Oxigénio, quer através de Testes Maximais para Determinação do Consumo Máximo de Oxigénio. Serão igualmente apresentados protocolos de avaliação da capacidade anaeróbia através dos Testes Supramaximais para Determinação da Capacidade Anaeróbia.
Após a descrição dos protocolos, são propostas tarefas práticas que permitem aplicar os conhecimentos teórico-científicos subjacentes aos testes referidos, bem como adquirir competências na avaliação do VO2máx e da aptidão anaeróbia em humanos.
... Exercise treadmill testing (ETT) approximates the total metabolic equivalents utilized by a patient during testing. 31 It is a relatively new biomarker in PAH, but appears equivalent to 6MWD in predicting survival in sick and moderately sick populations and offers an alternative to 6MWD in less sick populations. [32][33][34] Reduced exercise capacity on ETT indicates a worse hemodynamic profile, and importantly, predicts mortality in patients with PAH. ...
Pulmonary arterial hypertension (PAH) is a chronic and rapidly progressive disease that is characterized by extensive narrowing of the pulmonary vasculature, leading to increases in pulmonary vascular resistance, subsequent right ventricular dysfunction, and eventual death. There are currently multiple approved drugs—developed as single or combination therapies in the last few years—that have improved outcome and functionality in PAH. However, despite improvement in short-term survival with these new effective therapies, PAH remains an incurable disease with a median survival of 7 years (Figure 1).1 This chronic disease state may be characterized by morbid events such as hospitalizations that herald rapid disease progression and account for a significant disease burden (Figure 2).23 Physician ability to predict PAH disease progression is critical for determining optimal care of patients. Accurate risk assessment allows clinicians to determine the patient's prognosis, identify treatment goals, and monitor disease progression and the patient's response to treatment. Risk assessment for PAH patients should include a range of clinical, hemodynamic, and exercise parameters, performed in a serial fashion over the treatment course. Patient risk stratification can also help physicians better allocate treatment resources in settings where they are scarce. If widely adopted, risk prediction can enhance the consistency of treatment approaches across PAH practitioners and improve the timeliness of referral for lung transplantation. Hence, along with advancing PAH treatment options, comprehensive risk prediction is essential to make individualized treatment decisions in the current treatment era.
Several tools are currently available for assessing risk in PAH (Figure 3). These include the 2015 European Society of Cardiology/European Respiratory Society pulmonary hypertension guidelines' risk variables,4 the French registry equation,5 the National Institutes of Health risk equation,6 or a risk score such as the one derived from the Registry to Evaluate Early And Long-term PAH Disease Management.1 These registries and evaluations of clinical trial sets have provided important insights into the importance of both modifiable (eg, 6-minute walk distance, functional class, brain natriuretic peptide, and nonmodifiable (eg, age, gender, PAH etiology) risk factors that predict survival. The following review explores commonly cited risk factors, both modifiable and nonmodifiable, and their implications for patient outcomes.
... All patients underwent a maximum symptom-limited (fatigue and/or dyspnea) treadmill exercise test according to a modified Noughton protocol 24 . It consisted of 6 levels lasting for 3 minutes, with constant seed of 3 km/h, and start 0 elevation increasing for 3,5% for each interval. ...
Background/Aim. Echocardiography represents the most commonly performed noninvasive cardiac imaging tests for the patients with heart failure (HF). The aim of this study was to assess the relationship between the exercise capacity parameters [peak oxygen consumption (VO2) and the minute ventilation-carbon dioxide production relationship (VE/VCO2)] and the three-dimensional speckle-tracking echocardiography (3D-STE) imaging of left ventricular (LV) function in the HF patients with the reduced LV ejection fraction (LVEF). Methods. This cross-sectional study included 80 patients with diagnosed ischemic LV systolic dysfunction (LVEF < 45%) divided into subgroups based on the proposed values of analyzed cardiopulmonary exercise testing (CPET) variables: VO2 peak ≤ 15 mL/kg/min, VO2 peak > 15 mL/kg/min, VE/VCO2 slope < 36 and VE/VCO2 slope ≥ 36. All patients underwent a physical examination, laboratory testing, two-dimensional (2D) and 3DE, and CPET. Results. LVEF, global longitudinal, circumferential, radial and area strains were significantly lower in the subgroups of subjects with a peak VO2 less, or equal to 15 mL O2/kg per min and with a VE/VCO2 slope greater, or equal to 36 compared to the subgroups of subjects with a peak VO2 greater than 15 mL O2/kg per min and with a VE/VCO2 slope less than 36. There was a significantly positive correlation between the peak VO2 values and parameters of 3DE, and a significantly negative correlation between the VE/VCO2 slope values and parameters of 3DE. Conclusion. The results of this study provide further evidence that the LV function can be noninvasively and objectively measured by 3D-STE. A significant correlation between examined parameters suggests that LVEF and strain derived by 3DE are associated with exercise capacity in the patients with HF.
... At baseline all participants were tested on a treadmill using a modified Naughton protocol [21,22] to determine the individual aerobic capacity and walking ability. Peak oxygen consumption (VO 2 ) was measured by spirometry. ...
Purpose
To determine if long-term endurance exercise improves quality of life (QOL) in patients with multiple sclerosis (MS).
Methods
89 patients with relapsing–remitting MS and an EDSS of <3.5 participated in a prospective non-randomized controlled exploratory trial. The exercise program comprised a walking exercise three times weekly for 30 min (“interval training” twice weekly, “endurance training” once weekly) for 12 months. Participants were tested every 3 months on a treadmill according to a modified Naughton protocol. Fatigue was assessed by the Fatigue Severity Scale (FSS) and QOL by a German version of the Short Form Health Survey (SF-36). Data were analyzed using analysis of variance (ANOVA) with repeated measurements.
Results
20 patients without and 24 with fatigue completed the program. QOL was reduced in several subscales of the SF-36 in MS patients with fatigue at baseline: physical functioning (p < 0.001), physical role functioning (p < 0.002), bodily pain (p ≤ 0.04), vitality (p ≤ 0.001), social role functioning (p ≤ 0.004), emotional role functioning (p ≤ 0.03), mental health (p ≤ 0.006). Exercise training resulted in a significant improvement of the subscale general health perceptions (p ≤ 0.01).
Conclusions
Fatigue contributes significantly to QOL in MS patients. A significant improvement in the subscale general health perceptions was demonstrated by a 12-month endurance walking program in MS patients with fatigue.
... The symptom-limited maximal treadmill exercise test adopted the modified Naughton-Balke method [18]. Briefly, the total time of treadmill exercise testing was 14 min with two minutes at base speed with slope 0 (no inclination), two minutes at slope 1 level and speed 2, and two minutes at each of next five slopes with no change in speed. ...
Background
While exercise-based cardiac rehabilitation has a beneficial effect on heart failure hospitalization and mortality, it is limited by the presence of chronotropic incompetence (CI) in some patients. This study explored the feasibility of using wearable devices to assess impaired chronotropic response in heart failure patients.
Methods
Forty patients with heart failure (left ventricular ejection fraction, LVEF: 44.6 ± 5.8; age: 54.4 ± 11.7) received ECG Holter and accelerometer to monitor heart rate (HR) and physical activities during symptom-limited treadmill exercise testing, 6-min hall walk (6MHW), and 24-h daily living. CI was defined as maximal HR during peak exercise testing failing to reach 70% of age-predicted maximal HR (APMHR, 220 – age). The correlation between HR and physical activities in Holter-accelerometer recording was analyzed.
Results
Of 40 enrolled patients, 26 were able to perform treadmill exercise testing. Based on exercise test reports, 13 (50%) of 26 patients did not achieve at least 70% of APMHR (CI patients). CI patients achieved a lower % APMHR (62.0 ± 6.3%) than non-CI patients who achieved 72.0 ± 1.2% of APMHR (P < 0.0001). When Holter-accelerometer recording was used to assess chronotropic response, the percent APMHR achieved during 6MHW and physical activities was significantly lower in CI patients than in non-CI patients. CI patients had a significantly shorter 6MHW distance and less physical activity intensity than non-CI patients.
Conclusion
The study found impaired chronotropic response in 50% of heart failure patients who took treadmill exercise testing. The wearable Holter-accelerometer recording could help to identify impaired chronotropic response to physical activities in heart failure patients.
Trial registration
ClinicalTrials.gov ID NCT02358603. Registered 16 May 2014.
... Clinical NYHA-class evaluation is subjective, has substantial interobserver variability and a poor correlation with functional class calculated from exercise time. 21,22 Accordingly we found substantial variation in the METs achieved during exercise among patients who are evaluated to be in the same NYHA class see figure 1. Therefore, exercise testing of obstructive HCM patients is reasonable especially in cases where an accurate assessment of function class is important, such as before invasive septal reduction therapy. ...
Methods:
We evaluated clinical characteristics, hemodynamics, and imaging variables in 499 consecutive patients with HCM who performed 959 exercise tests. Patients were divided based on peak left ventricular outflow tract gradients using a 30-mm Hg threshold into the following: obstructive (n=152), labile-obstructive (n=178), and nonobstructive (n=169) groups.
Results:
There were no deaths during exercise testing. We noted 20 complications (2.1% of tests) including 3 serious ventricular arrhythmias (0.3% of tests). There was no difference in complication rate between groups. Patients with obstructive HCM had a higher frequency of abnormal blood pressure response (obstructive: 53% vs labile: obstructive: 41% and nonobstructive: 37%; P=.008). Obstructive patients also displayed a lower work capacity (obstructive: 8.4±3.4 vs labile obstructive: 10.9±4.2 and nonobstructive: 10.2±4.0, metabolic equivalent; P<.001). Exercise testing provided incremental information regarding sudden cardiac death risk in 19% of patients with high-gradient HCM, and we found a poor correlation between patient-reported functional class and work capacity.
Conclusion:
Our results suggest that exercise testing in HCM is safe, and serious adverse events are rare. Although numbers are limited, exercise testing in high-gradient HCM appears to confer no significant additional safety hazard in our selected cohort and could potentially provide valuable information.
... Très largement utilisée, aussi bien en pratique clinique que dans le cadre d'essais randomisés, elle laisse une part importante au jugement du médecin sur le caractère courant ou non d'une activité. Certains auteurs ont mis en évidence sa reproductibilité limitée 16,17 , mais sa validité a été également mise en cause 18,19 . Goldman a montré le caractère subjectif des perceptions exprimées, les patients les plus handicapés tendant à s'ajuster progressivement à la détérioration de leur état de santé en réduisant leur activité. ...
... Initially, all patients underwent resting standard 12lead electrocardiography and exercise testing with continuous electrocardiographic monitoring (Max 1; Marquette Electronics; Milwaukee, WI, USA), with blood pressure monitoring through the auscultation method, and with monitoring of ventilation and gas exchange during the exercise test. The test was performed on a programmable treadmill (Series 2000; Marquette Electronics; Milwaukee, WI, USA) according to the modified Naugthon protocol 17 . After 2 minutes standing without exercising, all patients were encouraged to exercise until the symptoms (fatigue or dyspnea) prevented them from continuing the test. ...
... Exercise tests were performed with a modified Naughton protocol. 12 The same cardiac technologist performed all tests. ...
Background— Inflammatory immune activation commonly occurs in heart failure and may perpetuate this syndrome. We sought to determine whether the immunomodulating agent pentoxifylline enhances left ventricular function in patients with ischemic cardiomyopathy. We also investigated the effect of therapy on levels of brain natriuretic peptide (NT-pro BNP), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and the marker of apoptosis, Fas/Apo-1.
Methods and Results— In a single-center, prospective, randomized, double-blind, placebo-controlled study, 38 patients with ischemic cardiomyopathy received pentoxifylline 400 mg TID or placebo in addition to standard therapy. Clinical assessment, radionuclide ventriculography, echocardiography, and blood analyses were performed at baseline and after 6 months. There were no differences in baseline characteristics between the groups. Five patients died (4 in the placebo group). Pentoxifylline treatment resulted in an improvement in functional class ( P <0.005) and an increase in systolic blood pressure ( P <0.05) and left ventricular radionuclide ejection fraction ( P <0.05) compared with the placebo-treated group. There were reductions in plasma concentrations of CRP, NT-pro BNP, TNF-α, and Fas/Apo-1 in the pentoxifylline compared with the placebo-treated group.
Conclusions— In patients with heart failure due to ischemic left ventricular dysfunction, the addition of pentoxifylline to standard therapy results in improvements in clinical status and radionuclide ejection fraction, which are accompanied by reductions in plasma markers of inflammation, prognosis, and apoptosis.
Introduction
The 6-minute walk test (6MWT) has been used for over 30 years to assess exercise capacity in patients with respiratory disease, and more recently, in those with heart failure. However, despite being a simple and reproducible test of real-world exercise capacity, its use in patients with ischemic heart disease (IHD) is less well accepted. We sought to review systematically the evidence surrounding the 6MWT in IHD.
Methods
We searched the Medline, PubMed, Embase, and Scopus databases for the following key terms: “six minute walk test/6 minute walk test/6MWT” and “angina/coronary artery disease/coronary disease/IHD/ischemic heart disease.” We followed Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines to select publications for full-text review and analyzed the collated data.
Results
A total of 1228 unique papers were found, of which 71 were chosen for full-text review and 37 for detailed analysis. Most (23) concerned the effect on 6MWT distance (6MWTd) of cardiac rehabilitation, with measurements commenced after an intervention (acute myocardial infarction, n = 4; open heart surgery (OHS), n = 5; percutaneous coronary intervention (PCI), n = 3; or other, n = 11). The effect on 6MWTd of OHS was investigated in 6 studies and of PCI in one study. The 6MWT is a useful measurement of physical capacity; data are limited on its ability to assess benefit following PCI.
Conclusions
The 6MWT has been studied inconsistently in IHD. The majority of data are on patients before and after CR. Data are limited concerning the effect on 6MWTd of OHS or PCI. The available data support the 6MWT as a measure of change in performance status following coronary intervention. More work is required to confirm this hypothesis.
Purpose:
Suboptimal adherence is a major limitation to achieving the benefits of exercise interventions, and our ability to predict and improve adherence is limited. The purpose of this analysis was to identify baseline clinical and demographic characteristics predicting exercise training adherence in the HF-ACTION study cohort.
Methods:
Adherence to exercise training, defined by the total duration of exercise performed (min/wk), was evaluated in 1159 participants randomized to the HF-ACTION exercise intervention. More than 50 clinical, demographic, and exercise testing variables were considered in developing a model of the min/wk end point for 1-3 mo (supervised training) and 10-12 mo (home-based training).
Results:
In the multivariable model for 1-3 mo, younger age, lower income, more severe mitral regurgitation, shorter 6-min walk test distance, lower exercise capacity, and Black or African American race were associated with poorer exercise intervention adherence. No variable accounted for >2% of the variance and the adjusted R2 for the final model was 0.14. Prediction of adherence was similarly limited for 10-12 mo.
Conclusions:
Clinical and demographic variables available at the initiation of exercise training provide very limited information for identifying patients with heart failure who are at risk for poor adherence to exercise interventions.
En 22 pacientes con valvulopatía mitral, a 11 se les implantó una prótesis de Bjork y a los otros 11 una prótesis de Starr-Edwards modelo 6.320. A todos se les realizó en el preoperatorio y a los 3 meses de la intervención, una prueba de esfuerzo en bicicleta ergométrica. A 12 pacientes (6 con Bjork y 6 con Starr-Edwards) se les repitió el estudio a los 3 años de la intervención. La prueba se realizó con aumento progresivo de cargas de 30 en 30 watios, previa estabilización del consumo de O2 y de la frecuencia cardíaca. Se determinó directamente cada minuto, el consumo de O2, el consumo de CO2 y volumen respiratorio y número de mets. Las diferencias obtenidas entre las 2 prótesis a los 3 meses, se deben a que el grupo con válvula de Starr-Edwards había sido rehabilitado, ya que a los 3 mios las diferencias no fueron estadísticamente significativas, cuando ya habían abandonado la rehabilitación. Comparando el número de mets alcanzados en las diferentes clases clínicas de la clasificación de la New York Heart Association, se observa que no existen diferencias estadísticamente significativas. Aunque el grupo de pacientes estudiado no es suficiente para dar conclusiones definitivas, se puede indicar que la prueba de esfuerzo es un método seguro y reproducible para valorar la capacidad funcional del cardiópata valvular, dando información más objetiva que las clasificaciones clínicas actuales que se basan en datos subjetivos. Por otra parte, el tipo de prótesis utilizada no es determinante para el pronóstico funcional a largo plazo y es posible que el paciente intervenido se beneficie de algún tipo de rehabilitación.
Undergraduate programs related to allied health are often pursued by students to prepare for entrance into professional programs, but many students also ask about what types of employment options they may have upon completion of the bachelor's degree. This experiential learning course in cardiovascular and sleep technology was designed to provide opportunities for students to gain hands-on clinical skills that could help them to enter professional programs or to find employment in an allied health field such as cardiopulmonary rehabilitation, cardiovascular technology, or sleep technology. The prerequisites for this course were the completion of two semesters of anatomy and physiology. This course was based on experiential learning and was structured into three modules: clinical exercise physiology, autonomic physiology, and sleep physiology. As part of the course students completed a 4-page scientific report for one designated topic within each of the modules. The two exams in the course were essay-based. The design of this course required students to review key topics from anatomy and physiology, to comprehend peer-reviewed manuscripts, to gain hands-on experiences with sophisticated physiological equipment, to work as individuals and in groups, and to become better oral and written communicators. The sleep physiology module included an introduction to electroencephalography (EEG) and student led nap study which may be an effective way to introduce students to sleep medicine. We are hopeful that the summary of this course will be useful to physiology educators as they work to provide the most meaningful experiences to their undergraduates in the health sciences.
Introduction
Echocardiography represents the most commonly performed noninvasive cardiac imaging test for patients with heart failure (HF). The aim of this study was to assess the relationship between exercise capacity parameters (peak oxygen consumption (VO2) and the minute ventilation-carbon dioxide production relationship (VE/VCO2)), two-dimensional speckle-tracking echocardiography (2D-STE) and three-dimensional echocardiography (3DE) imaging of right ventricular (RV) function in HF patients with reduced ejection fraction (EF).
Material and methods
This cross-sectional study included 54 patients with diagnosed ischemic LV systolic dysfunction (HF with reduced EF <40%) divided in subgroups based on the proposed values of the analyzed cardiopulmonary exercise testing (CPET) variables: VO2 peak ≤ 15 ml/kg/min, VO2 peak > 15 ml/kg/min, VE/VCO2 slope < 36 and VE/VCO2 slope ≥ 36. All patients underwent a physical examination, laboratory testing, conventional echocardiography, 2D-STE, 3DE, and CPET.
Results
RV fractional area change (FAC), 2D RV global longitudinal strain (GLS), 3D RV EF were significantly decreased, and RV basal diameter (BD), systolic pulmonary artery pressure (SPAP), tricuspid annular plane systolic excursion (TAPSE), ratio between tricuspid flow and tissue Doppler derived e’ of the lateral tricuspid annulus (TV E/e’) were significantly increased in the subgroups of subjects with a worse VO2 peak and VE/VCO2 slope values. There was a significant positive correlation between the peak VO2 values and TAPSE, 2D RV GLS, 3D RV SV, and 3D RV EF as well as a significantly inverse correlation with VE/VCO2 slope.
Conclusions
The observed significant correlation between the examined parameters suggests that 2D RV GLS and 3D RV EF, SV are associated with exercise capacity in patients with reduced HF.
In order to evaluate physical capacity it is neccesary to choose an appropriate method depending on the condition of the subject being tested and on the purpose of testing. A review has been carried out in order to present some of the protocols for evaluating exercise capacity which are in practical use. Twenty different test protocols for evaluating exercise capacity; 12 cycle protocols, six treadmill protocols and two protocols including both cycle and treadmill, are described in detail, as well as some of the physiological background of the tests. When testing subjects with reduced physical capacity, a protocol starting with a low work load and small increments is preferred. The test results can be reported as achieved oxygen uptake (V˙O2), metabolic equivalents (METs)or achieved work load (W). When testing healthy subjects and athletes, submaximal tests which estimate maximal oxygen uptake (V˙O2max) may be used. If high accuracy is required direct measurements of V˙O2 or V˙O2max are most reliable, regardless of which protocol is used.
While obesity mainly results from an imbalance between energy intake and expenditure, physical activity has to be part of prevention and treatment strategies, especially among children and adolescents. Increasing physical activity level mainly depends on the ability to perform exercise, necessitating an objective and accurate evaluation of physical fitness, both aerobic and anaerobic. While this chapter describes how overall fitness is altered by pediatric obesity, it also provides clinicians and practitioners with accurate direct and indirect methods of evaluation. Physical activity must be seen as more than a means to increase energy expenditure; it also favors particular compensatory responses in terms of both expenditure and intake that seem today necessary to consider in order to improve the efficacy of our interventions, as described in the last part of this chapter.
Before the admission into a cardiac rehabilitation program (CRP), every patient is submitted to a clinical assessment which must include a medical consultation, an evaluation of LV function (usually by echocardiography), a maximal exercise test (ET) limited by symptoms, and blood tests to evaluate the CVD risk factor profile. In special cases, after the clinical assessment, the patients need further diagnostic tests like a 24 h Holter monitoring, an imaging technique to study perfusion or coronary anatomy or bypass grafting [1–5].
Heart failure patients have a high incidence of chronotropic incompetence (CI) that receives less clinical attention. This study assessed a method using wearable devices to identify CI in heart failure patients.
Twenty-six heart failure patients (LVEF: 43.9 ± 5.7% with LVEF ≥40% in 19 patients; age: 52.8 ± 12.4 years, female patients = 6) were enrolled. Each patient underwent symptom-limited treadmill maximal exercise testing during which the simultaneous recording of ECG Holter and physical activity using Actigraph was conducted. The APMHR ratio, the maximal heart rate during peak exercise over the age-predicted maximal heart rate (APMHR, 220-age), was determined. CI was diagnosed in patients who failed to reach at least 0.70 APMHR ratio. Holter-Actigraph recording was also applied during a 6 min hall walk (6MHW) and for 24 h to validate the method to assess impaired chronotropic response.
Based on the reports of exercise testing in 26 patients, 13 patients (50%) failed to reach at least 0.70 APMHR ratio while the remaining 13 patients achieved ≥0.70 APMHR ratio. The APMHR ratio measured by Holter-Actigraph recording was significantly correlated with the APMHR ratio based on exercise test reports (R = 0.99, P < 0.001). The cut-off values of APMHR ratio (0.65) measured during 6MHW, APMHR ratio (0.69) measured during daily activities, and maximum Δ heart rate (37.8 bpm) measured during daily activities significantly predicted the results of exercise test reports with an area under the ROC curve of 0.7337, 0.7544 and 0.7870, respectively (all P values < 0.05).
This pilot study found that the wearable device can potentially help in the identification of chronotropic incompetence in heart failure patients.
Die Gründe für eine invasive Diagnostik bei Patienten mit Herzinsuffizienz können am Beispiel eines 48jährigen Patienten dargestellt werden. Dieser Patient wurde mit Zeichen einer akuten Herzinsuffizienz mit grenzwertigen Erhöhungen kardialer Enzyme (CK, LDH) und Kammerendteilabweichungen im EKG aufgenommen. Die Ventrikulographie (Abb. la) zeigte eine erheblich eingeschränkte linksventrikuläre Funktion. Bei der Koronarangiographie (Abb. lb) konnte eine hochgradige Hauptstammstenose und ein Verschluß der rechten Herzkranarterie nachgewiesen werden. Die globale Funktionseinschränkung des linken Ventrikels, die grenzwertigen Enzymerhöhungen und Ischämiezeichen im EKG mußten demnach als ausgeprägte globale Ischämie des Herzens bei schwerer koronarer Herzkrankheit interpretiert werden. Dieser Patient wurde deshalb umgehend in der thoraxchirurgischen Abteilung vorgestellt.
Dilative cardiomyopathy (DCM) is characterized by diminished contractility, enlarged volumes at endsystole and enddiastole, and reduced ejection fraction of the left ventricle.
Over the past five years multi-stage exercise stress testing has become an integral part of cardiologic evaluation in most major medical centers in this country. Such testing provides a noninvasive technique for:
1.
Detection or confirmation of overt or latent coronary heart disease.
2.
Evaluation of cardiovascular functional capacity, particularly as a means of clearing individuals for strenuous work or exercise programs.
3.
Detection or confirmation of arrhythmias.
4.
Increase of individual motivation for entering and adhering to exercise programs.
Exercise has long been recognized as a cornerstone in the management of patients with noninsulin dependent diabetes (NIDDM). Over 70 years ago, Allen and others reported that acute bouts of exercise lowered the blood glucose concentration of persons with diabetes and improved glucose tolerance temporarily (1). Since that time, numerous studies have confirmed beneficial effects of exercise for the person with NIDDM. The potential benefits of exercise or even an increased level of habitual physical activity for persons with NIDDM are multiple, ranging from the prevention of diabetes to the treatment and management of diabetes. In addition, these benefits occur both in terms of both metabolic and cardiovascular parameters.
Over the past few years, the potential therapeutic usefulness of a new class of phosphodiesterase (PDE) inhibitors (Table 1) has been investigated in patients with chronic cardiac failure. From the data currently available, one can only conclude that despite acute hemodynamic efficacy characterized by enhanced cardiac output with reduced filling pressure, the benefits of this new class of agents are highly controversial. Some investigators have concluded that these agents may not be effective treatment for patients with severe chronic heart failure, and have noted that short-term gains may occur with long-term detrimental effects on the myocardium (1–4). Other investigators have observed long-term clinical benefits with chronic administration of these agents, but have also pointed out that the clinical improvement produced by the new PDE inhibitors may be viewed as only palliative, since the underlying disease showed evidence of continued progression (5–8).
Like many ancient terms in medicine, angina pectoris is not a diagnosis but a symptom. The term implies the occurrence of myocardial ischaemia, the usual mechanism of which is an increase in myocardial oxygen demand that cannot be met by an appropriate increase in coronary blood flow because of the physical obstruction imposed by atheromatous coronary heart disease. Thus, as noted by Heberden in 1772, angina is precipitated mainly by effort and disappears with rest1. Several noncardiac mechanisms, including anaemia or polycythaemia, can also cause angina; as can a number of other cardiac or vascular mechanisms independently of or in association with atheroma — including coronary vasoconstriction, ventricular hypertrophy with or without associated valve disease and platelet aggregation or thrombosis.
It has been suggested that the vasodilator neuropeptides may be involved in both the control of blood pressure and the antihypertensive effect of the angiotensin-converting enzyme inhibitor captopril (Ajayi et al. 1985). The angiotensin-converting enzyme has many similarities to a membrane-bound enzyme which inactivates metenkephalin (Beruck and Marks 1979), and captopril has been said to increase enkephalin levels in patients with migraine (Baldi et al. 1983). In experimental models angiotensin-converting enzyme inhibition has also been shown to block the increase in plasma beta-endorphins produced by angiotensin I (Beuers et al. 1982). In normal volunteers angiotensin-converting enzyme inhibition with enalapril did not alter metenkephalins (VandenBurg et al. 1985), and in hypertensive patients beta-endorphins were not affected (VandenBurg et al. 1984).
Patients after myocardial infarction have different lactate kinetics compared to healthy subjects (4, 5). The aim of this study was to examine the relationship between left ventricular function and the lactate kinetics during and after exercise in a large number of patients.
Für die Erkennung und Beurteilung von Krankheiten des Herzens und des Kreislaufs ist die Erfassung der Vorgeschichte, des Beschwerdebildes und die körperliche Untersuchung des Kranken mit den einfachen Methoden der bettseitigen Untersuchung unerläßlich und von ergiebiger Aussagekraft. Aber erst die Verknüpfung der hierdurch gewonnenen Einzelbefunde erlaubt brauchbare diagnostische Überlegungen. Dagegen verrät der Versuch, aus einem einzigen Symptom bzw. Befund eine umfassende Diagose zu formulieren, den klinisch Unerfahrenen. Unrationell und unverantwortlich ist es, ungezielt, d. h. ohne gründliche Untersuchung mit nichtinvasiven Methoden, die speziellen, oft risikobelasteten Untersuchungstechniken einzusetzen.
Introduction: Gait impairment is a significant problem in patients with multiple sclerosis (MS), leading to decreased activity and functional limitations. The current pilot study without control group investigated the impact of 12-week endurance training on walking parameters including cadence, stride length and step time. Objective: Te aim of the present study was to analyze the effect of an endurance training program on walking parameters in patients with gait disturbances due to multiple sclerosis. Methods: Twelve untrained female patients with relapsing-remitting MS participated in this study (age 33.5±7.0 years). The mean disability according to the EDSS was less than 3.5. Individuals were assessed at baseline and at the end of the exercise program by means of a video analysis during treadmill walking. Two levels of work load were analyzed (1. 3.2 km/h, gradient: 3.5%; 2. 4.8 km/h, gradient: 7.5%). The intervention consisted of three aerobic training sessions per week for a period of 12 weeks. Results: There was a significant change in the three walking parameters. The cadence was significantly reduced (1. p≤0.0001; 2. p≤0.016), the stride length significantly increased (1. p≤0.001; 2. p≤0.046) and the step time significantly increased (1. p≤0.001; 2. p≤0.026). Discussion: We conclude that the exercise program had a significant effect on walking performance. Therefore, moderate exercise is recommendable for MS patients.
Background:
Sedentary time is an independent risk factor for cardiometabolic disease and mortality. It is unknown how much time individuals with coronary artery disease spend being sedentary or how their sedentary time relates to markers of health. The objectives of this study were to: (a) quantify sedentary time in a post-cardiac rehabilitation (CR) population, and (b) assess association with cardiometabolic risk, independent of moderate-to-vigorous physical activity.
Design:
Cross-sectional.
Methods:
As part of a larger trial, 263 recent CR graduates (∼10 days post-CR, mean age 63.6 ± 9.3 years, 75% male) wore an ActiGraph GT3X accelerometer during waking hours (≥4 days, ≥10 hours/day) to quantify sedentary time (≤150 counts per minute). Spearman correlations were computed to assess relationships between sedentary time (adjusted for wear time) with markers of cardiometabolic health and fitness. Significant markers were examined using multiple linear regressions.
Results:
Participants spent an average of almost 8 hours/day sedentary (∼14 bouts/day). Sedentary time was negatively correlated with high-density lipoprotein and [Formula: see text]O2peak and positively correlated with triglycerides, body mass index and waist circumference. After adjusting for age, sex, medications and moderate-to-vigorous physical activity, hours/day of sedentary time remained significantly associated with log[Formula: see text]O2peak (β = -0.02, p = 0.003) and body mass index (β = 0.47, p = 0.03).
Conclusions:
Findings suggest that even among a group of post-CR individuals who are already probably more active than patients who have not undergone CR, sedentary time remains high and is associated with poorer cardiorespiratory fitness, suggesting a possible new area of focus among CR programs.
Unlabelled:
Pulmonary arterial hypertension (PAH) causes right ventricular ischemia, dysfunction, and failure. PAH patients may benefit from antianginal agents based on a shared pathophysiology with left ventricular ischemia. A single-center, randomized, placebo-controlled trial (1∶1) to assess the acute vasoreactivity and safety of ranolazine in PAH was conducted. Plasma samples for pharmacokinetic (PK) studies were drawn during hemodynamic measurements at 0, 60, 90, 120, 240, and 360 minutes from a Swan-Ganz catheter. All patients received 500-mg doses, uptitrated to 1,000 mg at week 4, monthly evaluations, and a complete objective assessment after 12 weeks, followed by an open-label extension. Thirteen patients were randomized and 12 enrolled (6 ranolazine, 6 placebo). All patients completed the acute phase; 10 completed the 12-week study. There were no acute changes in invasive hemodynamics. At 12 weeks ranolazine was well tolerated. Only 1 of the 5 patients on ranolazine had a serum concentration considered to be in the therapeutic range. Two serious adverse events required early withdrawal (both in the ranolazine group); gastrointestinal complaints were the most common adverse event. Efficacy measures did not demonstrate any differences between treatment groups. During the open-label trial, 2 additional patients reached a therapeutic concentration. Ranolazine in PAH appears safe, without acute hemodynamic effects after a 500-mg dose. Ranolazine administrated to PAH patients receiving background PAH therapies did not consistently reach therapeutic levels. Future studies should first perform PK analysis in PAH patients receiving PAH therapies and explore the safety and tolerability of the higher doses perhaps necessary to achieve therapeutic levels in PAH patients. (
Trial registration:
Clinicaltrials.gov identifier NCT01757808.).
This work was supported by the Squibb Institute for Medical Research, Princeton, New Jersey and in part by the U.S. Public Health Service (Grant HL 14148) and the Medical Research Service, Veterans Administration, Washington, D.C.
Synopsis
Milrinone is a bipyridine derivative of amrinone, with approximately 10 to 75 times greater positive inotropic potency, and separate direct vasodilatory properties. As with amrinone, the relative importance of these properties to treatment of congestive heart failure still remain controversial. The mode of action of milrinone appears to be due in part to selective inhibition of a specific cardiac phosphodiesterase with a subsequent increase in intracellular cyclic adenosine monophosphate and alteration in intracellular and extracellular calcium transport. Clinical experience has involved both short and long term treatment of a limited number of patients with moderate to severe congestive heart failure refractory to conventional therapy. Milrinone has usually been administered as intravenous bolus doses (12.5 to 75 μg/kg) and/or continuous intravenous infusion (0.5 μg/kg/ min), or orally (30 to 40 mg/day in divided doses). Milrinone rapidly improves cardiac performance by enhancing myocardial contractility, and by decreasing systemic vascular resistance (afterload), left ventricular filling pressure (preload), and pulmonary arterial pressure. Exercise performance improvement occurs with enhancement of left ventricular performance but without a significant increase in myocardial oxygen consumption or significant decrease in mean arterial pressure. Milrinone has been compared with dobutamine, nitroprusside and captopril in preliminary short term studies in patients with severe congestive heart failure. Milrinone significantly increased stroke work index and decreased left ventricular filling pressure compared to nitroprusside. When compared with dobutamine, both drugs improved cardiac index (to a similar degree), but milrinone significantly reduced right atrial pressure, pulmonary capillary wedge pressure and left ventricular end-diastolic pressure. One small study suggests that short term effects of intravenous milrinone may be superior to those of oral captopril, and it appears that the addition of captopril to milrinone therapy may produce a synergistic haemodynamic effect.
Preliminary long term studies suggest that tolerance to the haemodynamic effects of milrinone does not occur, and that the drug is well tolerated and without the thrombocytopenic effects, fever and gastrointestinal complications observed with amrinone. However, it has not been demonstrated that milrinone improves the prognosis of the disease or the overall mortality and its propensity to produce arrhythmias has not been fully agreed upon. Until these questions have been adequately addressed, milrinone will probably remain a drug used only in patients with severe congestive heart failure refractory to more established treatments.
Pharmacodynamic Studies
Milrinone produces concentration-dependent inotropic effects in isolated atrial and papillary muscles from a number of animal species, with an attenuation of inotropic effects occurring at high concentrations. In dog Purkinje fibres, milrinone significantly prolonged action potential duration.
Single intravenous bolus doses, continuous infusions or oral doses in anaesthetised or conscious healthy dogs produced significant dose-related increases in contractile force and heart rate with minimal effects on systolic and diastolic blood flow at lower doses. At higher doses (up to 1.0 mg/kg), milrinone decreased both systolic and diastolic blood pressure, and produced dose-related increases in left ventricular filling pressure. Pretreatment with reserpine, indomethacin, α - and β-adrenergic blockers, histamine antagonists, ganglionic or cholinergic blocking agents does not affect the inotropic responses to milrinone. Intravenous administration of milrinone to anaesthetised dogs with experimentally induced heart failure improved cardiac output and increased contractile force.
Milrinone significantly increased renal artery blood flow with significant decreases in renal vascular resistance in anaesthetised dogs. Similarly, a substantial increase in human renal blood flow has been demonstrated following single oral doses. However, the effect of multiple doses of milrinone on renal blood flow was less consistent. In one study, 1 month’s oral therapy produced marked improvement in forearm vascular resistance with no significant change in renal blood flow, renal vascular resistance or glomerular filtration rate, whereas other short term studies have demonstrated significant increases in renal artery blood flow with corresponding decreases in renal vascular resistance.
Milrinone appears to have significant direct vasodilatory (particularly of the systemic beds) and smooth muscle relaxant activity as evidenced by in vitro and in vivo studies in both animal models and humans. Milrinone reduces both right atrial pressure and systemic arterial pressure despite an increase in cardiac output. However, nitroprusside is more effective as a vasodilator than milrinone. The observed effects of milrinone on blood pressure in congestive heart failure patients are variable with both increases and decreases in peak arterial pressure being seen.
Milrinone markedly improves conduction and action potential in depressed animal heart preparations, although enhancement of atrioventricular conduction is the only significant electrophysiological change observed in congestive heart failure patients.
Milrinone’s mechanism of action remains controversial but appears to involve the inhibition of the cardiac phosphodiesterase fraction which is specific for cyclic adenosine monophosphate and suggests that the drug’s effect may be dependent on intracellular and extracellular calcium transport.
Pharmacokinetic Studies
The pharmacokinetics of milrinone have been studied following single and repeated oral doses, single intravenous bolus doses and after continuous intravenous infusion. Initial studies suggest that the pharmacokinetic profile of milrinone does not change with repeated doses. Peak plasma concentrations of 133 to 454 μg/L (intravenous bolus doses of 12.5 to 75 μg/kg), 81 to 277 μg/L (intravenous infusion of 0.2 to 0.7 μg/kg/min) and 63 to 294 μg/L (oral doses of 2.5 to 10mg) have been recorded in patients with congestive heart failure.
Volume of distribution was 0.32 L/kg after intravenous bolus administration of milrinone in healthy subjects, and 0.3 to 0.42 L/kg (intravenous bolus), 0.47 L/kg (intravenous infusions) and 0.53 to 0.56 L/kg (oral) in congestive heart failure patients. Bio-availability is approximately 85 to 92% after oral administration.
In animal species, the major metabolic pathways for milrinone metabolism appear to be oxidative and conjugative, with glucuronidation being the major pathway of bio-transformation, although the parent drug is the major excretion product. Elimination half-life of milrinone is approximately 48 to 56 minutes in healthy subjects following intravenous or oral administration of 10 to 125 μg/kg and 1.0 to 12.5mg, respectively, but is extended to 3.2 hours in patients with severe chronic renal failure. In patients with congestive heart failure, elimination half-lives of 1.2 to 2.7 hours are seen. Plasma clearance following oral and intravenous administration of milrinone is about 18 to 24 L/h in healthy subjects, about 7.8 to 12 L/h in congestive heart failure patients and about 1.8 L/h in patients with chronic renal failure.
Therapeutic Trials
Milrinone has been used only in the treatment of moderate to severe congestive heart failure (New York Heart Association functional Class HI and IV) refractory to conventional therapy. Patients treated with milrinone usually continued receiving cardiac glycosides and diuretic therapy whereas vasodilator drugs were usually discontinued. Single-dose and short term administration using oral and intravenous doses demonstrated significant improvement in left ventricular filling pressure (10 to 34%), cardiac index (10 to 76%) and left ventricular stroke work index (21 to 57%), and significant decreases in left ventricular end-diastolic pressure (31 to 45%), pulmonary capillary wedge pressure (4 to 52%), pulmonary arterial pressure (10 to 29%), right atrial pressure (13 to 60%), systemic vascular resistance (14 to 42%) and peripheral vascular resistance (17 to 53%). Left ventricular ejection was consistently improved by milrinone therapy. Following intravenous administration, peak haemodynamic responses occurred after 5 to 10 minutes and lasted about 1 hour, whereas following oral administration of milrinone, peak haemodynamic effects occurred at 1.2 to 2.1 hours and persisted for up to 6 hours. Many studies found dose-dependent haemodynamic responses to both oral and intravenous administration of milrinone although some inconsistencies in this trend have been observed. Repeated oral administration, and continuous intravenous infusion or intravenous bolus administration have demonstrated no evidence of tolerance to the haemodynamic effects of milrinone.
Long term therapy in relatively small numbers of congestive heart failure patients has shown oral milrinone to be well tolerated with few side effects. Substantial improvement in cardiac haemodynamics and reduction in fatigue were usually seen within the first 1 to 2 weeks of therapy and most studies reported sustained haemodynamic benefits during long term therapy. However, improvements in long term survival following milrinone therapy have yet to be demonstrated and as there are no placebo-controlled studies it is not possible to discount a training effect. Haemodynamic deterioration has been observed following withdrawal of long term milrinone therapy, but which haemodynamic parameters are modified and to what extent the underlying disease has progressed or been retarded has yet to be clarified.
Significant improvement in exercise capacity along with increases in cardiac index, cardiac output, stroke volume index, improvement in left ventricular function and maximal oxygen uptake have been seen following single and repeated doses of intravenous and oral milrinone in patients with congestive heart failure. In one study these improvements were sustained for at least 3 months, and were more significant than those produced by digoxin.
Milrinone has been evaluated in several single-dose or short term comparative studies with other inotropic and vasodilator agents including dobutamine, nitroprusside and captopril. When dobutamine infusion (0.5 to 1.0 μg/kg/min) was compared with intravenous milrinone (50 to 75 μg/kg), both drugs produced similar sustained improvement in cardiac index; however, milrinone significantly decreased pulmonary capillary wedge pressure, right atrial pressure, left ventricular end-diastolic pressure and mean systemic arterial pressure more than dobutamine, whereas dobutamine increased heart rate to a greater extent than did milrinone, thereby increasing myocardial oxygen demand which was not evident with milrinone. Milrinone (12.5 to 75 μg/kg) increased cardiac output to a much greater extent than did nitroprusside infusions (10 to 300 μg/min), with left ventricular end-diastolic pressure being significantly lower with milrinone. In addition, stroke volume and stroke work index were higher with milrinone and milrinone exhibited a significant dose-related increase in peak rate of change of left ventricular filling pressure. Heart rate was also more significantly increased with milrinone. In studies comparing captopril with milrinone it was observed that milrinone increases cardiac index to a greater extent than does captopril. Improvements in renal blood flow were seen with both drugs. Captopril significantly decreased systemic arterial pressure which was not observed with milrinone, whereas milrinone produced greater improvement in ventricular performance. Neither drug had any significant effect on heart rate. There is some evidence to suggest the potential for synergistic clinical effects with milrinone and captopril. In preliminary long term comparative studies milrinone showed evidence of producing more sustained and significant improvements in haemodynamic measurements than digoxin in both resting and exercised patients, although, again, improvements in long term mortality rates were not demonstrated.
Side Effects
Thus far, the side effects that have been reported with milrinone are few in number, but may not represent a true and complete profile that only long term use in a large number of patients may reveal. Preliminary data from studies so far conducted have shown that milrinone use has been associated with a low frequency of headache, mild diarrhoea, hyperthyroidism, increased frequency of anginal pain, and fluid retention. Thrombocytopenia does not appear to be a major adverse effect with milrinone, as it was with amrinone, although it does occur in a small proportion of patients. The most worrisome possibility is that of increased incidence of cardiac arrhythmias with milrinone, and this requires further investigation.
Dosage and Administration
Most studies using intravenous doses suggest that bolus doses of 25 μg/kg or infusion doses of up to 0.7 μg/kg/min produce the optimal therapeutic response (improved haemodynamic indices and acceptable tolerance). Higher doses may not necessarily improve the haemodynamic response to milrinone but may increase unwanted effects. With oral dosages, maximal improvements occur with 10mg doses at 6-hourly dosing intervals.
One of the major goals of bronchodilator therapy in patients with COPD is to decrease airflow limitation in the airways and, as a consequence, improve dyspnea and exercise tolerance. The focus of this systematic review is to assess the effects of treatment with -agonists, anticholinergics, and theophyllines on dyspnea, and steady-state and incremental exercise capacity. Thirty-three, double-blind, randomized, placebo-controlled studies written in English were selected. This review shows that approximately half of the studies showed a significant effect of bronchodilator therapy on exercise capacity. Anticholinergic agents have significant beneficial effects in the majority of studies, especially when measured by steady-state exercise protocols. There is a trend toward a better effect of high-dose compared to low-dose anticholinergics. Short-acting 2-mimetics have favorable effects on exercise capacity in more than two thirds of the studies; surprisingly, the situation is less clear for long-acting 2-agents. The majority of the results of the published reports on theophyllines and their effects on exercise are negative. Direct comparisons of different classes of bronchodilators have not been made in a sufficient number of studies for a rational preference. The addition of a second bronchodilator has no proven advantage for improving exercise test results, but this has not been studied extensively and not in sufficiently large studies. The majority of studies reporting a measure of dyspnea found improvements, even in the absence of improvement in exercise capacity. (CHEST 2002; 121:597– 608)
In this article literature concerning the major drugs used in the treatment of heart failure is reviewed. Because of major discrepancies in results from short term and uncontrolled studies versus long term randomised control trials, only the latter group of studies are addressed in detail. Of 3 randomised control trials of digoxin, 1 has been positive, and 2 negative. Digoxin is probably of benefit to a minority of heart failure patients. Four randomised control trials of oral nitrates have shown a reduction in left ventricular filling pressure, and trends favouring active treatment for the indices of exercise capacity and functional status. Of 2 randomised control trials of hydralazine one is totally negative, the other difficult to interpret because of major loss of patients to followup. Of 5 trials of quinazolone derivatives (prazosin and trimazosin), 2 have been positive, 2 showed non-statistically significant trends favouring active treatment, and 1 was completely negative. These results are consistent with a modest benefit of prazosin and trimazosin in some heart failure patients. Five trials of angiotensin-converting enzyme inhibitors (captopril and enalapril) have shown dramatic and consistent benefit in exercise capacity and functional status.
These results support a clinical policy of initial treatment with diuretics and addition of either captopril or enalapril for patients who remain symptomatic on optimal diuretic therapy. A trial of digoxin is warranted in patients whose functional capacity remains reduced on this regimen.
Treadmill exercise tests were performed on 32 active duty military personnel 9 to 11 months after acute myocardial infarction to enable more objective selection of candidates for return to military service. Treadmill exercise tests were terminated at heart rates averaging 92 percent maximal predicted rate for age, or when chest discomfort with ischemic ECG changes occurred. The incidence of lipid abnormalities, hypertension, and other coronary risk factors did not differ among the groups.
However, treadmill exercise tests appeared to identify a high risk group. Treadmill exercise testing in young postmyocardial infarction patients suggests that those with ischemic responses are at high risk of subsequent cardiac complications. Early surgery in this group may be warranted. The more frequently encountered negative response appears to be associated with a benign clinical course and better immediate prognosis.
A população de idosos vem crescendo de forma importante no mundo e o que parecia ser um problema dos países desenvolvidos vem se reproduzindo nos países mais pobres. A atividade física aparece como uma forma de permitir que os indivíduos mais velhos tenham mais saúde e se tornem mais independentes. Para que isso possa ocorrer, o programa de exercícios deve ser feito com segurança, habitualmente precedido de um teste ergométrico com protocolo individualizado, com programas de atividades apresentando períodos de aquecimento e relaxamento mais longos e graduais. Os benefícios são evidentes tanto na aptidão física quanto na esfera psicológica, levando essa população a maior integração na sociedade.
To better understand the mechanisms responsible for exercise intolerance in heart failure with reduced ejection fraction (HFrEF), the present study sought to evaluate the hemodynamic responses to small muscle mass exercise in this cohort. In 25 HFrEF patients (64 ± 2 yrs) and 17 healthy, age-matched control subjects (64 ± 2 yrs), mean arterial pressure (MAP), cardiac output (CO), and limb blood flow were examined during graded static-intermittent handgrip (HG) and dynamic single leg knee-extensor (KE) exercise. During HG exercise, MAP increased similarly between groups. CO increased significantly (+1.3 ± 0.3 L/min) in the control group, but remained unchanged across workloads in HFrEF patients. At 15% maximum voluntary contraction (MVC), forearm blood flow was similar between groups, while HFrEF patients exhibited an attenuated increase at the two highest intensities compared to controls, with the greatest difference at the highest workload (352 ± 22 vs. 492 ± 48 ml/min, HFrEF vs. control, 45% MVC). During KE exercise, MAP and CO increased similarly across work rates between groups. However, HFrEF patients exhibited a diminished leg hyperemic response across all work rates, with the most substantial decrement at the highest intensity (1842 ± 64 vs. 2675 ± 81 ml/min, HFrEF vs. control, 15 W). Together, these findings indicate a marked attenuation in exercising limb perfusion attributable to impairments in peripheral vasodilatory capacity during both arm and leg exercise in patients with HFrEF, which likely plays a role in exacerbating exercise intolerance in this patient population.
Evaluation of cardiac reserve under myocardial infarction in patients is important for prognosis. However, this evaluation is difficult to be done due to high risk for mortality in patients with severe myocardial infarction. The present study was undertaken using non-human primate model as a substitute for humans to investigate the relationship between cardiac reserve and myocardial infarct size. Rhesus monkeys of 2-3 years old (n = 27) were subjected to left anterior descending artery ligation to introduce acute myocardial infarction. By altering the ligation position along the artery, varying sizes of myocardial infarction were generated, from 20 to 58 % of the total myocardium mass. These subjects were divided into 4 groups based on the infarct size: below 25 %, between 25 and 35 %, between 35 and 45 %, and above 45 % of the total mass. Changes in cardiac contractility were determined by echocardiography along with the development of myocardial infarction, and by invasive hemodynamic measurement at the end of the experiment. Correlation analysis revealed that hearts with infarct sizes <25 % of the total mass fully responded to the increase in the load generated by heart rate escalation. Hearts with infarct sizes between 25 and 45 % responded the load increase with gradient decline in the maximum contractility. Hearts with infarct sizes more than 45 % failed to respond to the increase in the load. Therefore, we consider myocardial infarct size <25 % of the total mass as compensable injury, between 25 and 45 % as depleting injury, and more than 45 % as exhausted injury with regard to cardiac reserve. This would serve as a surrogate model for patients with myocardial infarction.
Little is known about the sustainability of exercise effects in patients with relapsing-remitting Multiple Sclerosis (RRMS). We present the results of a prospective, observer-blinded, single-center case control study using a "pre-post" design including 89 ambulatory patients with RRMS and an EDSS score of ≤3.5 who participated in an individualized 12month aerobic endurance exercise program. Peak oxygen consumption (VO2 peak) increased and fatigue levels decreased significantly over time (p=0.03, p<0.02). Subgroup analysis of patients with fatigue (FSS>4) revealed that the increase of VO2 peak remained significant after 12months whereas patients without fatigue did not improve any further after six months. A significant decrease of the FSS score was only observed after nine months (p<0.03) In conclusion, aerobic exercise leads to a sustainable improvement of VO2 peak over an extended exercise period of 12months. There is a weak, but significant effect on fatigue levels which becomes detectable only after nine months. Since subgroup analysis revealed that MS patients behaved differently according to their baseline fatigue levels, adjustment to the individual fatigue levels is recommended for future exercise interventions in RRMS patients.
Background A study was conducted to determine the efficacy and safety of ibutilide fumarate versus placebo in the acute termination of atrial flutter and fibrillation. Methods and Results Two hundred sixty-two patients aged 28 to 88 years with atrial flutter or fibrillation duration of 3 hours to 90 days were randomly assigned in a 5:1 ratio (ibutilide:placebo) to receive two 10-minute infusions, 10 minutes apart, of ibutilide (1 mg) or placebo. Patients were hospitalized and monitored by telemetry for 24 hours, with follow-up 72 hours later. Seventy-three (34.9%) of 209 evaluable ibutilide recipients had termination of atrial flutter or fibrillation within 1.5 hours compared with 0 (0%) of 41 placebo recipients. Those with atrial flutter had a higher success rate. At hour 24, 86.3% remained in normal or alternative sinus rhythm. Of the patients who received ibutilide, 2.3% experienced drug-related sustained polymorphic or monomorphic ventricular tachycardia and recovered after intervention. Additionally, 7.3% experienced nonsustained polymorphic or monomorphic ventricular tachycardia. Other frequent medical events in ibutilide recipients were generally also noted in the placebo group. Conclusions Ibutilide is effective and safe for acute termination of atrial fibrillation or atrial flutter. (Am Heart J 1998;136:632-42.)
THE possibility that the invasiveness of malignant tissues may result from collagenolytic action of tumour cells was early considered1-3. This idea, however, was not supported by subsequent efforts to isolate a specific enzyme from neoplastic tissues or by attempts to obtain lysis of collagen enclosed in perfusion chambers embedded in tumour bearing animals4.
A group of presumably healthy, sedentary men participated in a physical fitness program for seven months. Their maximum oxygen intake was determined during either a standard treadmill test or an "all-out run" or both. Eighteen men tested on the treadmill before and after the test had an increase in their peak oxygen uptake from 31.3 to 36.8 ml/kg/min (P <0.001). Ten of the subjects who were tested by both methods before and after seven months of training had statistically significant increases in their peak oxygen intakes. Their peak performance was consistently higher with the "all-out run" than it was on the treadmill. Eight men failed to increase their peak energy expenditure following training; four of these subjects were tested twice with the treadmill test and their peak performances remained the same before and after the program.
Diseases of the Heart and Blood Vessels: Nomenclature and Criteria for Diagnosis
- The Criteria Committee of the New York Heart Association
Use of exercise testing for diagnostic and functional evaluation of patients with arteriosclerotic heart disease
- Blomquist