Romualdo Belardinelli

Exercise and Heart Failure A Statement From the American Heart Association Committee on Exercise, Rehabilitation, and Prevention

Heart failure (HF) may be defined as the inability of the heart to meet the demands of the tissues, which results in symptoms of fatigue or dyspnea on exertion progressing to dyspnea at rest. The inability to perform exercise without discomfort may be one of the first symptoms experienced by patients with HF and is often the principal reason for seeking medical care. Therefore, exercise intolerance is inextricably linked to the diagnosis of HF. It might be expected that a tight relationship would exist between indices of resting ventricular function and exercise capacity. Data indicate, however, that indices of resting ventricular function (such as ejection fraction [EF]) are only weakly correlated to exercise tolerance.1 Exercise intolerance is defined as the reduced ability to perform activities that involve dynamic movement of large skeletal muscles because of symptoms of dyspnea or fatigue. Many investigators have sought mechanisms to explain the source of exercise intolerance. The aims of this position statement are to review (1) factors that affect exercise tolerance, with specific emphasis on chronic HF due to systolic dysfunction; (2) data that support the role of exercise training in chronic systolic HF, including the risks and benefits; (3) data on exercise training in patients with HF due to diastolic dysfunction; and finally (4) the subgroups of patients with HF for which data are lacking, and (5) the subgroups of patients who should not be included in exercise training programs. We anticipate this report will stimulate appropriate use of exercise training in patients with HF when indicated and encourage further studies in those areas in which data are lacking. ### Cardiovascular The capacity for performing aerobic exercise depends on the ability of the heart to augment its output to the exercising muscles and the ability of these muscles to utilize oxygen from the delivered …

Lung Function and Exercise Gas Exchange in Chronic Heart Failure

BACKGROUND The ventilatory response to exercise in patients with chronic heart failure (HF) is greater than normal for a given metabolic rate. The objective of the present study was to determine the mechanism(s) for the high ventilatory output in patients with chronic HF. METHODS AND RESULTS Centers in Germany, Italy, Japan, and the United States participated in this study. Each center contributed studies on patients and normal subjects of similar age and sex. One hundred thirty patients with chronic HF and 52 healthy subjects participated. Spirometric and breath-by-breath gas exchange measurements were made during rest and increasing cycle exercise. Arterial blood was sampled for measurement of pH, PaCO2, PaO2, and lactate during exercise in 85 patients. Resting forced expiratory volume in 1 second (FEV1) and vital capacity (VC) were proportionately reduced at all levels of impairment. Patients with more severe HF had greater tachypnea and a smaller tidal volume (VT) at a given exercise expired volume per unit time (VE). This was associated with an expiratory flow pattern characteristic of lung restriction. VE and VCO2 as a function of VO2 were increased during exercise in HF patients. The increases were greater the lower the peak VO2 per kilogram of body weight. The ratio of VD (physiological dead space) to VT and the difference between arterial and end tidal PCO2 at peak VO2 also increased inversely with peak VO2/kg. In contrast, the difference between alveolar and arterial PO2 and PaCO2 were both normal, on average, at peak VO2 regardless of the level of impairment. The more severe the exercise limitation, the higher the lactate and the lower the HCO3- at a given VO2, although pH was tightly regulated. CONCLUSIONS The increase in VE in chronic HF patients is caused by an increase in VD/VT due to high ventilation/perfusion mismatching, an increase in VCO2 relative to VO2 resulting from HCO3- buffering of lactic acid, and a decrease in PaCO2 due to tight regulation of arterial pH. With regard to the excessive VE in HF patients, the increases in VD/VT and VCO2 relative to VO2 are more important as the patient becomes more exercise limited. Regional hypoperfusion but not hypoventilation typifies lung gas exchange in HF. This and other mechanisms might account for the restrictive changes leading to exercise tachypnea in HF patients.

Exercise training intervention after coronary angioplasty: the ETICA trial ☆

OBJECTIVES The goal of this study was to determine the effects of exercise training (ET) on functional capacity and quality of life (QOL) in patients who received percutaneous transluminal coronary angioplasty (PTCA) or coronary stenting (CS), the effects on the restenosis rate and the outcome. BACKGROUND It is unknown whether ET induces beneficial effects after coronary angioplasty. METHODS We studied 118 consecutive patients with coronary artery disease (mean age 57+/-10 years) who underwent PTCA or CS on one (69%) or two (31%) native epicardial coronary arteries. Patients were randomized into two matched groups. Group T (n = 59) was exercised three times a week for six months at 60% of peak VO2. Group C (n = 59) was the control group. RESULTS Only trained patients had significant improvements in peak VO2 (26%, p < 0.001) and quality of life (26.8%, p = 0.001 vs. C). The angiographic restenosis rate was unaffected by ET (T: 29%; C: 33%, P = NS) and was not significantly different after PTCA or CS. However, residual diameter stenosis was lower in trained patients (-29.7%, p = 0.045). In patients with angiographic restenosis, thallium uptake improved only in group T (19%; p < 0.001). During the follow-up (33+/-7 months) trained patients had a significantly lower event rate than controls (11.9 vs. 32.2%, RR: 0.71, 95% confidence interval [CI]: 0.60 to 0.91, p = 0.008) and a lower rate of hospital readmission (18.6 vs. 46%, RR: 0.69, 95% CI: 0.55 to 0.93, p < 0.001). CONCLUSIONS Moderate ET improves functional capacity and QOL after PTCA or CS. During the follow-up, trained patients had fewer events and a lower hospital readmission rate than controls, despite an unchanged restenosis rate.

Effects of Moderate Exercise Training on Thallium Uptake and Contractile Response to Low-Dose Dobutamine of Dysfunctional Myocardium in Patients With Ischemic Cardiomyopathy

BACKGROUND There is evidence that exercise training can induce myocardial and coronary adaptations in both animals and humans. However, the significance of these potentially important changes remains to be determined in patients with ischemic heart disease and left ventricular (LV) systolic dysfunction. METHODS AND RESULTS To investigate whether exercise training can improve thallium uptake and the contractile response to low-dose dobutamine of dysfunctional myocardium, 46 patients (42 men, 4 women; mean age, 57+/-9 years) with chronic coronary artery disease and impaired LV systolic function (ejection fraction < 40%) were randomly assigned to two groups. The exercise group (n = 26) underwent exercise training at 60% of peak oxygen uptake for 8 weeks. The control group (n = 20) was not exercised. At baseline and after 8 weeks all patients underwent an exercise test with gas exchange analysis and stress echocardiography using low-dose dobutamine (5 to 10 microg/kg per minute) followed by thallium myocardial scintigraphy. Coronary angiography was performed in 23 patients at baseline and after 8 weeks. After 8 weeks, peak oxygen uptake increased significantly only in trained patients (24%). Significant improvements in the contractile response to dobutamine and thallium activity were observed in trained patients (28% and 31%, respectively; trained versus control: P<.001 for both). In a subgroup of trained patients, both improvements were correlated with an increase in the coronary collateral score (P<.005 and P<.001, respectively). CONCLUSIONS Moderate exercise training improves both thallium activity and the contractile response of dysfunctional myocardium to low doses of dobutamine in patients with ischemic cardiomyopathy. The implication of this study is that even a short-term exercise training may improve quality of life by improvement of LV systolic function during mild-to-moderate physical activity in patients with ischemic cardiomyopathy.

Exercise-induced myocardial ischaemia detected by cardiopulmonary exercise testing

BACKGROUND The objective of the study was to identify the parameter(s) of cardiopulmonary exercise testing (CPET) that can detect exercise-induced myocardial ischaemia (EIMI), and to determine its diagnostic accuracy for identifying patients with coronary artery disease (CAD). METHODS AND RESULTS We prospectively studied 202 consecutive patients (173 men, 29 women, mean age 55.7+/-10.8 years) with documented CAD. All patients underwent an incremental exercise stress testing (ECG-St) with breath-by-breath gas exchange analysis, followed by a 2-day stress/rest gated SPECT myocardial scintigraphy (GSMS) as the gold standard for ischaemia detection. ROC analysis selected a two-variable model-O(2)pulse flattening duration, calculated from the onset of myocardial ischaemia to peak exercise, and deltaVO(2)/deltawork rate slope-to predict EIMI by CPET. GSMS identified 140 patients with reversible myocardial defects, with a Summed Difference Score (SDS) of 9.7+/-2.8, and excluded EIMI in 62 (SDS 1.3+/-1.6). ECG-St had low sensitivity (46%) and specificity (66%) to diagnose EIMI as compared with CPET (87% and 74%, respectively). CONCLUSIONS The addition of gas exchange analysis improves the diagnostic accuracy of standard ECG stress testing in identifying EIMI. A two-variable model based on O(2)pulse flattening duration and deltaVO(2)/deltawork rate slope had the highest predictive ability to identify EIMI.

10-Year Exercise Training in Chronic Heart Failure: A Randomized Controlled Trial

OBJECTIVES This study investigated the effect of a very long-term exercise training program is not known in chronic heart failure (CHF) patients. BACKGROUND We previously showed that long-term moderate exercise training (ET) improves functional capacity and quality of life in New York Heart Association class II and III CHF patients. METHODS We studied 123 patients with CHF whose condition was stable over the previous 3 months. After randomization, a trained group (T group, n = 63) underwent a supervised ET at 60% of peak oxygen consumption (Vo(2)), 2 times weekly for 10 years, whereas a nontrained group (NT group, n = 60) did not exercise formally. The ET program was supervised and performed mostly at a coronary club with periodic control sessions twice yearly at the hospitals gym. RESULTS In the T group, peak Vo(2) was more than 60% of age- and gender-predicted maximum Vo(2) each year during the 10-year study (p < 0.05 vs. the NT group). In NT patients, peak Vo(2) decreased progressively with an average of 52 ± 8% of maximum Vo(2) predicted. Ventilation relative to carbon dioxide output (VE/Vco(2)) slope was significantly lower (35 ± 9) in T patients versus NT patients (42 ± 11, p < 0.01). Quality-of-life score was significantly better in the T group versus the NT group (43 ± 12 vs. 58 ± 14, p < 0.05). During the 10-year study, T patients had a significant lower rate of hospital readmission (hazard ratio: 0.64, p < 0.001) and cardiac mortality (hazard ratio: 0.68, p < 0.001) than controls. Multivariate analysis selected peak Vo(2) and resting heart rate as independent predictors of events. CONCLUSIONS Moderate supervised ET performed twice weekly for 10 years maintains functional capacity of more than 60% of maximum Vo(2) and confers a sustained improvement in quality of life compared with NT patients. These sustained improvements are associated with reduction in major cardiovascular events, including hospitalizations for CHF and cardiac mortality.

Diagnostic Criteria and Management of Subacute Ventricular Free Wall Rupture Complicating Acute Myocardial Infarction

In this prospective study we evaluated the value of the main diagnostic criteria for postinfarction subacute rupture of the ventricular free wall. Two-dimensional echocardiograms and recordings of right atrial pressure and waveform were immediately obtained in every patient exhibiting rapid clinical and/or hemodynamic compromise in the acute infarction setting. The same protocol was applied to patients referred from other hospitals for suspected myocardial rupture. In 28 cases a subacute free wall rupture was identified. In most of the patients the diagnosis was based on the demonstration of hemopericardium and cardiac tamponade by echocardiography, cardiac catheterization and, occasionally, by pericardiocentesis. In 2 instances, the identification of intrapericardial echo densities suggesting clots, in the absence of cardiac tamponade, allowed a diagnosis of subacute rupture. Direct, but indistinct visualization of myocardial rupture was obtained in 4 cases. Among the 28 patients with this complication, 4 died while awaiting surgery and 24 underwent surgical repair (mortality rate 33%). Long-term outcome of survivors was favorable. Various myocardial lesions underlie postinfarction subacute free wall rupture. Clinical presentation varied widely. The diagnosis was based, usually but not always, on the association of hemopericardium and signs of cardiac tamponade. An organized approach to management of this complication of acute myocardial infarction was suggested.

Moderate exercise training improves functional capacity, quality of life, and endothelium-dependent vasodilation in chronic heart failure patients with implantable cardioverter defibrillators and cardiac resynchronization therapy

Background The objective of this study was to determine the effects of a moderate exercise training program on functional capacity, quality of life, and hospital readmission rate in chronic heart failure patients with implantable cardioverter defibrillators and cardiac resynchronization therapy. Methods and results We studied 52 men (mean age 55 ± 10 years, ejection fraction 31 ± 7%) in chronic heart failure II (n = 29) and III (n = 23) NYHA functional class with ischemic cardiomyopathy who received implantable cardioverter defibrillators with or without cardiac resynchronization therapy. Patients were randomized into two groups. Group T (n = 30 patients, 15 implantable cardioverter defibrillator, 15 implantable cardioverter defibrillator + cardiac resynchronization therapy) underwent a supervised exercise training program at 60% of peak Vo2 three times a week for 8 weeks. Group C (n = 22 patients, 12 implantable cardioverter defibrillator, 10 implantable cardioverter defibrillator + cardiac resynchronization therapy) avoided physical training. At 8 weeks, only trained patients had improvements in peak Vo2 (P < 0.01 versus C), endothelium-dependent dilatation of the brachial artery (P < 0.001 versus C) and quality of life (P < 0.001 versus C). Among trained patients, those with cardiac resynchronization therapy had greater improvements in peak Vo2 and quality of life. During the follow-up (24 ± 6 months), eight controls had sustained ventricular tachycardia requiring hospital readmission, while no trained patients had adverse events (log rank 8.56; P < 0.001). The improvement in peak Vo2 was correlated with the improvement in endothelium-dependent dilatation (r=0.65). Conclusion Moderate exercise training is safe and has beneficial effects after implantable cardioverter defibrillator implantation, especially when cardiac resynchronization therapy is present. These effects are associated with improvement in quality of life and outcome.

Comparison of impedance cardiography with thermodilution and direct fick methods for noninvasive measurement of stroke volume and cardiac output during incremental exercise in patients with ischemic cardiomyopathy

In the last decade, an inexpensive and simple noninvasive method (i.e., transthoracic electrical bioimpedance cardiography, has been tested in healthy subjects and patients with various heart disease for measuring stroke volume and cardiac output at rest and/or during exercise. However, the results are still controversial, especially when measurements are obtained during exercise and data on reproducibility during exercise are lacking. Twenty-five consecutive patients (20 men and 5 women, mean age 48 +/- 9 years) in sinus rhythm with documented coronary artery disease and a previous myocardial infarct were studied. Patients were divided into 2 groups. Group A had ischemic cardiomyopathy, characterized by left ventricular (LV) enlargement and LV ejection fraction depression (35 +/- 8%). Group B had normal LV dimensions and ejection fraction (62 +/- 9%). After a familiarization study, all patients underwent an exercise test with gas exchange analysis and hemodynamic measurements. Stroke volume and cardiac output were simultaneously obtained at rest and at the end of each work rate stage with 3 methods: impedance, thermodilution, and direct Fick. Group A reached a lower peak oxygen uptake (56%), peak work load (60%), and peak systolic blood pressure (69%) than group B. Cardiac output and stroke volume were significantly greater at submaximal and peak exercise in group B than in group A (p < 0.0001). There were no significant differences in stroke volume and cardiac output in the 3 techniques at any matched work rate. There was no significant difference between measurements obtained by 2 experienced observers or between those obtained on 2 exercise tests performed on 2 different days. These results demonstrate that impedance cardiography is a noninvasive, simple, accurate, and reproducible method of measurement of cardiac output and stroke volume over a wide range of workloads.

Metabolic exercise test data combined with cardiac and kidney indexes, the MECKI score: A multiparametric approach to heart failure prognosis

OBJECTIVES We built and validated a new heart failure (HF) prognostic model which integrates cardiopulmonary exercise test (CPET) parameters with easy-to-obtain clinical, laboratory, and echocardiographic variables. BACKGROUND HF prognostication is a challenging medical judgment, constrained by a magnitude of uncertainty. METHODS Our risk model was derived from a cohort of 2716 systolic HF patients followed in 13 Italian centers. Median follow up was 1041days (range 4-5185). Cox proportional hazard regression analysis with stepwise selection of variables was used, followed by cross-validation procedure. The study end-point was a composite of cardiovascular death and urgent heart transplant. RESULTS Six variables (hemoglobin, Na(+), kidney function by means of MDRD, left ventricle ejection fraction [echocardiography], peak oxygen consumption [% pred] and VE/VCO2 slope) out of the several evaluated resulted independently related to prognosis. A score was built from Metabolic Exercise Cardiac Kidney Indexes, the MECKI score, which identified the risk of study end-point with AUC values of 0.804 (0.754-0.852) at 1year, 0.789 (0.750-0.828) at 2years, 0.762 (0.726-0.799) at 3years and 0.760 (0.724-0.796) at 4years. CONCLUSIONS This is the first large-scale multicenter study where a prognostic score, the MECKI score, has been built for systolic HF patients considering CPET data combined with clinical, laboratory and echocardiographic measurements. In the present population, the MECKI score has been successfully validated, performing very high AUC.