Lip Bun Tan

Felodipine in patients with chronic heart failure: discrepant haemodynamic and clinical effects.

Previous open studies have suggested that felodipine, a selective calcium antagonist and vasodilator, may be useful in the treatment of heart failure. A double blind placebo controlled crossover trial was therefore conducted to investigate the clinical and haemodynamic effects of felodipine in 15 patients with chronic ischaemic heart failure in New York Heart Association symptom class III. Felodipine significantly increased resting and exercise (25W bicycle ergometry) cardiac output without producing concomitant changes in resting or exercise heart rate or right and left ventricular filling pressures. Felodipine did not significantly improve symptom scores or exercise capacity in the group as a whole. It also resulted in significant fluid retention as shown by a rise in ankle circumference, body weight, and a fall in haematocrit. Further research is required to elucidate the mechanism that is responsible for the discrepancy between the haemodynamic and clinical effects of felodipine in patients with moderately severe heart failure.

Maximizing Patient Benefit From Cardiac Resynchronization Therapy With the Addition of Structured Exercise Training : A Randomized Controlled Study

OBJECTIVES We evaluated the benefits of additional exercise training after cardiac resynchronization therapy (CRT). BACKGROUND Cardiac resynchronization therapy results in improved morbidity and mortality in appropriate patients. We hypothesized that a structured exercise training program in addition to CRT would maximize the improvements in exercise capacity, symptoms, and quality of life (QOL). METHODS Fifty patients referred for CRT were recruited. Patients were assessed before and 3 and 6 months after CRT. Functional class and QOL scores were recorded, and exercise tests were performed with hemodynamic measurements. Peak lower limb skeletal muscle torque was measured during extension, and echocardiography was undertaken at each visit. At 3 months, patients were randomized with a simple sealed envelope method to exercise training (n = 25) or control group (n = 25). The exercise group underwent an exercise program consisting of 3 visits/week for 3 months. Paired sample t tests were used to look for in-group differences and independent sample t tests for between-group differences. RESULTS Three months after CRT there were significant improvements in all functional, exercise hemodynamic, and echocardiographic measures. After randomization the exercise group showed further significant improvements in functional, exercise hemodynamic, and QOL measures compared with the control group. There were also significant in-group improvements in peak skeletal muscle function and ejection fraction that did not reach statistical significance on intergroup analysis. CONCLUSIONS Exercise training leads to further improvements in exercise capacity, hemodynamic measures, and QOL in addition to the improvements seen after CRT. Therefore, exercise training allows maximal benefit to be attained after CRT.

Cardioreparation and the concept of modulating cardiovascular structure and function.

Hypertension and atherosclerotic cardiovascular disease represent major global health problems. Practising physicians are challenged daily by patients suffering adverse cardiovascular events, such as myocardial infarction, stroke, heart failure and sudden cardiac death. Major risk factors have been identified of which the most important is left ventricular hypertrophy. In recent years, growth factors, regulatory peptides and effector hormones of the renin-angiotensin-aldosterone system have been identified as important modulators of cell growth and behaviour. It therefore follows that a major emphasis has been placed on the importance of abnormalities in organ structure as the primary basis for impaired function of the heart and vasculature, including large and medium sized arteries and resistance vessels, or arterioles. The concept of reparation recognizes the importance of abnormalities in tissue structure to the functional basis of disease. It suggests that the structurally remodelled heart and vasculature can be restored to, or toward, normal structure and function by suitable therapy. Experimental and clinical trials which address this premise are reviewed herein.

Does beta adrenergic blockade influence the prognostic implications of post-myocardial infarction exercise testing?

The influence of beta blockade on the ability of ST depression, during pre-discharge exercise testing, to predict coronary anatomy and subsequent complications was studied in 300 consecutive post-infarct patients, 125 of whom underwent cardiac catheterisation. At the time of exercise 62 patients were taking a beta blocker. The exercise test had a higher sensitivity in predicting multivessel disease in patients who were not taking beta blockers than in patients who were (95% v 76%). beta Blockade did not, however, influence the ability of the test to identify patients at risk of subsequent cardiac events (sensitivity 84% and 85% respectively). These results suggest that it is not necessary to stop treatment with beta blockers before predischarge exercise testing of patients who have had an acute myocardial infarction.

Prognostic stratification of patients after myocardial infarction.

An attempt was made to stratify risk of subsequent cardiac events in post-infarct patients according to a combination of the results of clinical assessment, routine diagnostic investigations, and pre-discharge exercise testing in 350 consecutive patients who were followed up for one year. Patients were classified prospectively on the basis of the extent of myocardial damage as assessed by peak enzyme release, reciprocal change on the electrocardiogram at the time of myocardial infarction, Norris prognostic index, ability to perform a pre-discharge exercise test (and test result), and ability to tolerate beta adrenergic blockade on discharge. Of the 50 patients with contraindications to pre-discharge exercise testing, 26% died or had reinfarctions compared with 9% of the 300 exercised patients; the 24 non-exercised patients with evidence of extensive myocardial damage or reciprocal changes on the electrocardiogram were particularly at risk. Similarly, among the 300 exercised patients, extensive myocardial damage, reciprocal change on the electrocardiogram, and ST depression on exercise testing were the major risk markers in that each identified at least 75% of the patients who had subsequent cardiac events. The 63 exercised patients who had all three of these major risk markers constituted a high risk group: 18 (29%) died or had reinfarction. Of the remaining 237 patients, only 9 (4%) had cardiac events. The 35 high risk patients with exercise induced angina pectoris or clinical contraindications to beta blockade were particularly at risk; 15 (43%) died or had reinfarction. This approach to risk stratification identified a small cohort of high risk patients in a large population of myocardial infarction survivors; it also identified a large group with a very low risk of subsequent cardiac events.

36 Direct Measurement of Cardiac Compensation in Valvular Heart Disease

Purpose The natural history of valvular heart disease (VHD) suggests that the heart initially adapts to compensate for valve lesions and thereby maintain physiological function. When these compensatory mechanisms become exhausted, cardiac decompensation commences. We tested the hypothesis that all VHD patients with normal exercise capacity are in the compensatory phase with no symptoms and normal cardiac reserve. Methods Unselected consecutive male patients with VHD performed cardiopulmonary exercise (CPX) testing with non-invasive central haemodynamic measurements during symptom-limited treadmill exercise. Exercise capacity was represented by peak oxygen consumption (VO2max) and cardiac pumping capability by peak exercise cardiac power output (CPOmax). Data are given as mean±SD. Results Of the entire VHD patient cohort (n = 215), 81.4% (n = 175) had VO2max which were within or above the reference range of healthy male sedentary controls (n = 101). This is shown in Figure 1A where individual patient VO2max is expressed as a percentage of the average VO2max of age- and sex-matched controls. These 175 patients with normal VO2max had a mean age of 63.1 ± 14.0 years, and consisted of 98 (56%) who were asymptomatic (NYHA class I) and 77 (44%) who were discordantly symptomatic in NYHA II+ (.001). As shown in Figure 1B, 117 patients (66.9%) had CPOmax within the normal range, of whom 80 (45.7%) were asymptomatic, but 37 (21.1%) were in NYHA II+ despite having normal VO2max and CPOmax (.001). Conversely, 58 (33.1%) had CPOmax below the normal range, and yet 18 (10.3%) of these were discordantly still in NYHA I (P < 0.001). These patients were classified asymptomatic by their responsible clinicians but our results revealed they had early, objective evidence of cardiac decompensation. Abstract 36 Figure 1 (a) Peak O2 consumption (VO2max) and (b) peak cardiac power output (CPOmax) expressed as a percentage of the average VO2max of age- and sex-matched controls Conclusions This investigation demonstrates that it is now possible to directly and objectively measure whether patients are in the compensated or decompensated phases of VHD. There were discrepancies between subjective symptomatic statuses and objectively measured cardiac and physical functional statuses. The possibility to determine whether patients are in the compensatory phase or not, might help in the management of difficult VHD cases. Abstract 36 Figure 2 Valve disease patients with normal exercise capacity (VO 2max ) and their compositions with respect to NHYA classification and low or normal peak cardiac power output (CPOmax)