Rigobert Lapu-Bula

Contribution of exercise-induced mitral regurgitation to exercise stroke volume and exercise capacity in patients with left ventricular systolic dysfunction.

Background—Functional mitral regurgitation (MR) is common in patients with heart failure and left ventricular (LV) dysfunction, and its severity may vary over time, depending primarily on the loading conditions. Because dynamic changes in the severity of functional MR may affect forward stroke volume, we hypothesized that exercise-induced changes in MR severity influence the stroke volume response of patients with LV dysfunction to exercise, and hence their exercise capacity. Methods and Results—Heart failure patients (n=25; mean age 53±12 years) with LV dysfunction underwent dynamic bicycle exercise at steady-state levels of 30%, 60%, and 90% of predetermined peak &OV0312;o2. During each exercise level, right heart pressures, cardiac output, &OV0312;o2, and MR severity were measured simultaneously. During exercise, MR severity, as evaluated by the ratio of MR jet over left atrium area, increased from 15±8% to 33±15%. Peak &OV0312;o2, exercise-induced changes in stroke volume, and those in capillary wedge pressure correlated with the changes in MR (r =−0.55, −0.87, and 0.62, respectively, P <0.01). The changes in MR severity also correlated with those in end-diastolic (r =−0.75, P <0.01) and end-systolic (r =−0.72, P <0.01) sphericity indexes and those in the coaptation distance (r =0.86, P <0.01). Conclusions—Our data indicate that in patients with LV dysfunction, exercise-induced changes in MR severity limit the stroke volume adaptation during exercise and therefore contribute to limitation of exercise capacity.

Relation of exercise capacity to left ventricular systolic function and diastolic filling in idiopathic or ischemic dilated cardiomyopathy

Although exercise intolerance is a cardinal symptom of patients with dilated cardiomyopathy (DC) and heart failure, the factors that limit exercise capacity in these patients remain a matter of debate. To assess the contribution of left ventricular (LV) diastolic filling to the variable exercise capacity of patients with DC, we studied 47 patients (60 +/- 12 years) with DC in stable mild-to-moderate heart failure with a mean LV ejection fraction of 28%. Exercise capacity was measured as total body peak oxygen consumption (VO2) during symptom-limited bicycle (10 W/min) and treadmill (modified Bruce protocol) exercise. LV systolic function and diastolic filling were assessed at rest before each exercise by M-mode, Doppler echocardiography, and radionuclide ventriculography. As expected, treadmill exercise always yielded higher peak VO2 than bicycle exercise (21 +/- 6 vs 18 +/- 5 ml/kg/min, range 12 to 35 and 7 to 30 ml/kg/min, respectively, p <0.001). Both of these VO2 measurements were highly reproducible (R = 0.98). With univariate analysis, close correlations were found between peak VO2 (with either exercise modalities) and Doppler indexes of LV diastolic filling, as well as with the radionuclide LV ejection fraction. Stepwise multiple regression analysis identified 3 nonexercise variables as independent correlates of peak VO2, of which the most powerful was the E/A ratio (multiple r2 = 0.38, p <0.0001), followed by peak A velocity (r2 = 0.54, p <0.0001) and mitral regurgitation grade (r2 = 0.58, p = 0.024). In conclusion, our data indicate that in patients with DC, peak VO2 is better correlated to diastolic filling rather than systolic LV function.

Risk stratification in patients with dilated cardiomyopathy: contribution of Doppler-derived left ventricular filling

Dilated cardiomyopathy (DCM) is a major cause of mortality among patients with heart failure. The aim of the present study was to investigate the independent contribution of Doppler-derived left ventricular (LV) filling to the prediction of survival in patients with DCM, of either ischemic or nonischemic origin, and to derive a simple risk stratification score based on easily available clinical and echocardiographic parameters. We followed 197 consecutive patients (159 men, mean age 60+/-13 years) with an echocardiographic diagnosis of DCM (LV end-diastolic dimension >60 mm, fractional shortening <25%) over an average period of 62+/-13 months. The presumed etiology of DCM was ischemic in 52% of the patients. During follow up, 69 patients died of cardiac causes and 41 required transplantation. At 5 years, overall cardiac event-free survival was 55% and freedom from death or heart transplantation was 43% (compared with 86% for the 5-year age- and sex-adjusted survival rate in our country). Kaplan-Meier survival curves generated for different thresholds of the peak E velocity and the E/A ratio indicated significant worsening of prognosis with increasing values of these parameters in both ischemic and nonischemic patients. Using Cox stepwise regression analyses, age (chi-square to remove 24.4; p <0.001), peak E velocity (chi-square to remove=18.9; p <0.001), LV ejection fraction (chi-square to remove 6.4; p <0.011), and systolic blood pressure (chi-square to remove 4.5; p=0.034) independently predicted cardiac deaths, whereas New York Heart Association (NYHA) functional class (chi-square to remove 48.5; p < 0.001), LV ejection fraction (chi-square to remove 19.1; p <0.001), E/A ratio (chi-square to remove 10.8; p <0.001), and systolic blood pressure (chi-square to remove 5.8; p <0.016) were independently associated with cardiac death or need for transplantation. Based on these parameters, a risk score was elaborated, which allowed appropriate classification of each individual patient into low- (5-year survival rate of 72%), intermediate- (46% survival rate), and high-risk groups (11% survival rate). In conclusion, our data show that among the noninvasive parameters commonly available in patients with either ischemic or nonischemic DCM, age, the NYHA functional class, the LV ejection fraction, the systolic blood pressure, the peak E velocity, and the E/A ratio provide relevant and independent information regarding the risk of cardiac death or the need for heart transplantation.

The 894T allele of the endothelial nitric oxide synthase gene is related to left ventricular mass in African Americans with high-normal blood pressure

BACKGROUND AND OBJECTIVES The 894T allele in exon 7 of the endothelial nitric oxide synthase (eNOS) gene has been inconsistently associated with hypertension in different racial groups. Because high-normal blood pressure (BP) confers an increased risk for the development of hypertension and other cardiovascular disorders, including left ventricular hypertrophy (LVH), we tested the hypothesis that the allelic variation (894T) in the eNOS gene would directly correlate with alterations in LV mass (LVM) in individuals with high-normal BP. METHODS Genotype distribution of G894T was compared between 20 African Americans (10 females/10 males) with high-normal BP (systolic BP of 130-139 and/or diastolic BP of 85-89 mmHg) and 64 counterparts (37 females/27 males) with normal BP (<130/85 mmHg). Echocardiographic LVM was calculated (Devereux formula) and indexed to body surface area to define the presence of LVH (LVMI >134/110 g/m2 for men/women). RESULTS For the entire group, the 894T allelic frequencies (15, 48%) and G894T genotype distributions were consistent with the Hardy-Weinberg equilibrium expectations (estimated disequilibrium coefficient = 0.0118, P=0.40). LVMI was significantly higher in homozygous carriers (TT) of the rare 894T allele (n = 3 females/0 males) than in heterozygous GT (n = 13 females/7 males) and individuals bearing the GG (n=34 females/27 males) variant (124 +/- 70 vs. 82 +/- 24 and 82 +/- 19 g/m2, respectively, P < 0.05). The observed relationship between eNOS 894T allele and LVMI was restricted to individuals with high-normal BP (r = 0.94, P = 0.03) but not in those with normal BP (r = 0.39, P =0.64), by analysis of variance (ANOVA) after adjusting for age, gender, body mass index, smoking and systolic BP. CONCLUSION These findings, not previously described, provide important preliminary evidence to suggest an increased susceptibility to LVH in African Americans who carry the 894T variant of the eNOS gene and have high-normal blood pressure.

Anabolic Doping Agents

This chapter discusses the different types of doping agents that have been used since the pre-Christian era, such as hallucinogenic mushrooms and alcohol, up to those currently used by athletes today. Today, articles 2.1 through 2.8 of the World Anti-Doping Code, define doping as the violation of one or more of these articles through the use of prohibited substances or methods. In the present discussion on anabolic doping agents, the classes of banned substances covered include stimulants, anabolic agents, peptide hormones, and β2-adrenoceptor agonists, as well as masking and antiestrogenic agents. The pharmacokinetics, pharmacodynamics, and toxicology of these substances will be discussed along with some potential historical consequences of the use of certain doping agents by both axis and allied forces during World War II, and the terrible consequences that might be attributed to their use.