Risk Factor For Cardiac Mortality Research Articles

Atrial fibrillation—rate or rhythm control?

Atrial fibrillation is an independent risk factor for cardiac mortality. The main causes of hemodynamic impairment are the loss of atrial contribution and the development of tachycardiomyopathy. Therefore, the therapeutic aim should be rhythm control or rate control. The results of large trials, e.g., AFFIRM study, suggested that rate control is as good as rhythm control. Considering the limitations of these studies and the development of new antiarrhythmic drugs and interventional techniques, a re-evaluation of either rhythm or rate control as the therapeutic aim is necessary. New techniques and drugs offer the opportunity to restore sinus rhythm, so that in the future rhythm control will be preferable.

Heart rate, autonomic markers, and cardiac mortality

Heart rate is a precisely regulated variable, which plays a critical role in health and disease. Numerous epidemiologic studies and large post-myocardial infarction trials have provided evidence that elevated resting heart rate is an independent risk factor for cardiac mortality. This body of knowledge has prompted the development and evaluation of negative chronotropic agents, prototypically the I(f) inhibitor Ivabradine. The present review addresses several fundamental questions: (1) How is heart rate regulated at the integrative, cellular, and molecular levels? (2) How are autonomic tone and reflexes measured clinically, and what is the prognostic utility of these parameters? (3) What mechanisms are responsible for the cardiovascular pathology associated with elevated heart rates? (4) Does reducing heart rate independent of effects on other factors protect against cardiovascular events?

New insights into cardiac resynchronization therapy.

Ventricular dyssynchrony plays a central role in the expression and progression of heart failure (HF). An independent risk factor for cardiac mortality, ventricular dyssynchrony is characterized by delay in left ventricular (LV) lateral wall contraction. This leads to decreased pumping efficiency, with resulting fluid retention and impaired exercise tolerance. Cardiac resynchronization therapy (CRT) attempts to improve cardiac efficiency by restoring the normal mechanical relationship between right and left ventricular contraction. Cardiac output increases with resynchronization, while ventricular filling pressure decreases without increasing cardiac oxygen consumption. Cardiac resynchronization therapy can also reverse LV dysfunction and reduce mitral regurgitation in patients with HF. Since 1999, the efficacy of implantable CRT devices has been evaluated in clinical trials enrolling more than 4,000 patients with heart disease. In the CARE-HF trial, CRT reduced the risk of death by 36% relative to standard pharmacologic therapy. Combining CRT with a defibrillator might produce an added benefit. In the COMPANION trial, all-cause mortality in patients randomized to a CRT-defibrillator combination was less than in patients receiving CRT therapy alone. Cardiac resynchronization therapy has also been found to decrease morbidity and improve functional status and quality of life. At the present time, the indications for CRT are limited and include symptomatic HF despite optimal medical therapy, prolonged QRS interval, and LVEF < or = 35%. However, indications for CRT are still evolving and may be expanded as further studies identify those most likely to benefit.

Impact of left bundle branch block and activation pattern on the heart

Left bundle branch block (LBBB) is known to impair the mechanical function of the left ventricle. For a better understanding of the impact of LBBB on the structure and function of the heart and how this influences the management and outcome in patients with heart failure, we reviewed the most pertinent articles published from 1950 to 2007. Epidemiological studies identified LBBB as an independent risk factor for cardiac mortality. It is not only the morphology or duration of QRS but also the underlying myocardial pathology, ejection fraction or New York Heart Association class that may determine the clinical implications of LBBB. Data indicate that LBBB inversely affects the perfusion, systolic, diastolic performance and hemodynamics of the heart. However, there is no solid evidence answering the question of whether LBBB is a predictor, cause or consequence of myocardial dysfunction. Further studies are warranted for better understanding of these relationships, as this will allow better selection of patients and optimal time for resynchronization therapy in patients with LBBB.

Systolic Dysfunction Portends Increased Mortality among Those Waiting for Renal Transplant

Individuals waiting for a renal transplant experience excessive cardiovascular mortality, which is not fully explained by the prevalence of ischemic heart disease in this population. Overt heart failure is known to increase the mortality of patients with ESRD, but the impact of lesser degrees of ventricular systolic dysfunction is unknown. For examination of the association between left ventricular ejection fraction(LVEF) and mortality of renal transplant candidates, the records of 2718 patients evaluated for transplantation at one institution were reviewed. During 6355 patient-years (median 27 mo) of follow-up, 681 deaths occurred. Patients with systolic dysfunction (LVEF <or= 0.40) had significantly lower survival than those with higher systolic function (median 49 +/- 3.1 versus 72 +/- 4.0 mo; P 0.001) but had similar survival to patients with ischemia (48 +/- 2.5 mo). Multivariate modeling showed that those with systolic dysfunction were nearly twice as likely to die as those with normal systolic function, adjusted for risk factors including diabetes, left ventricular hypertrophy, and ischemia (adjusted hazard ratio 1.7; 95%confidence interval 1.43 to 2.07). In addition, a graded, reverse association between LVEF and mortality was identified. In conclusion, systolic dysfunction is strongly associated with mortality, in a graded manner, in renal transplant candidates.

The role of vitamin D in left ventricular hypertrophy and cardiac function

The role of vitamin D in left ventricular hypertrophy and cardiac function. Cardiovascular disease is the leading cause of death among patients with end-stage renal disease (ESRD). Traditional cardiac risk factors, as well as other factors specific to the ESRD population such as hyperphosphatemia, elevated calcium and phosphate product, abnormal lipid metabolism, hyperhomocysteinemia, and chronic inflammation play a role in the excessive risk of cardiovascular death in this population. Left ventricular disorders are proven risk factors for cardiac mortality in hemodialysis patients. These disorders are present in incident ESRD patients at rates far above the general population. There is an accumulating body of evidence that suggests that vitamin D plays a role in cardiovascular disease. Abnormal vitamin metabolism, through deficiency of the active form of 1,25-dihydroxyvitamin D(3), and acquired vitamin D resistance through the uremic state, have been shown to be important in ESRD. Vitamin D deficiency has long been known to affect cardiac contractility, vascular tone, cardiac collagen content, and cardiac tissue maturation. Recent studies using vitamin D receptor deficient mice as a model demonstrate a crucial role of vitamin D in regulation of the renin-angiotensin system. Additionally, there is emerging evidence linking treatment with vitamin D to improved survival on hemodialysis and improvement in cardiac function. The emergence of this data is focusing attention on the previously underappreciated nonmineral homeostatic effects of vitamin D that very likely play an important role in the pathogenesis of cardiac disease in ESRD.

Autonomic dysfunction in uremia assessed by heart rate variability.

Decreased heart rate variability is an independent risk factor for cardiac mortality in hemodialysis patients. Our aim was to determine whether it is already present in uremic children and young adults on hemodialysis and following renal transplantation. Twenty-two hemodialysis patients [age 17.2 years (median, quartiles 13.0-22.6)], 22 transplant patients [18.4 years (14.4-21.2)], and 29 healthy controls [16.4 years (15.7-21.1)] were examined. Heart rate and its high (HF) and low (LF) frequency variability were measured in the supine position for 10 min. High and low frequency variability was significantly reduced, whereas heart rate and LF/HF ratio was significantly elevated in both patient groups compared with controls. There was a clear-cut difference between the dialyzed and the transplanted groups based on the HF variability, with the lowest values in the dialysis group ( P<0.01). LF and LF/HF data did not allow us to distinguish between the patient groups. In conclusion, heart rate variability in the HF range is a sensitive tool for detecting cardiovascular autonomic dysfunction that is already present in children and adolescents with impaired kidney function.

Effects of depression on QT interval variability after myocardial infarction.

Clinical depression is a risk factor for cardiac mortality in patients with coronary heart disease. High QT interval variability is a risk factor for arrhythmic events, including sudden cardiac death. The purpose of this study was to determine whether depression is associated with increased QT variability in patients recovering from myocardial infarction. Twenty patients with major depression recovering from a recent myocardial infarction were matched with 20 nondepressed post-myocardial infarction patients on age and sex, and all underwent 24-hour Holter monitoring. There were no differences between groups on average heart rate, heart rate variability, or other electrocardiographic measures. However, the QT interval showed significantly greater variability in the depressed than in the nondepressed group, especially at midnight and at 6:00 AM. Depressed post-myocardial infarction patients may be at greater risk for sudden cardiac death as a result of abnormalities in ventricular repolarization. More work is needed to determine the clinical and prognostic significance of QT variability in these patients.

Depression as a risk factor for cardiac mortality and morbidity: A review of potential mechanisms

Depression increases the risk of cardiac mortality and morbidity in patients with coronary heart disease (CHD), but the mechanisms that underlie this association remain unclear. This review considers the evidence for several behavioral and physiological mechanisms that might explain how depression increases the risk for incident coronary disease and for subsequent cardiac morbidity and mortality. The candidate mechanisms include: (1) antidepressant cardiotoxicity; (2) association of depression with cardiac risk factors such as cigarette smoking, hypertension, diabetes, and reduced functional capacity; (3) association of depression with greater coronary disease severity; (4) nonadherence to cardiac prevention and treatment regimens; (5) lower heart rate variability (HRV) reflecting altered cardiac autonomic tone; (6) increased platelet aggregation; and (7) inflammatory processes. Despite recent advances in our understanding of these potential mechanisms, further research is needed to determine how depression increases risk for cardiac morbidity and mortality.

Prognostic value of serum gamma-glutamyl transferase activity after myocardial infarction.

Serum gamma-glutamyl transferase activity (gamma-GT) is able to catalyse low-density lipoprotein oxidation and has been detected in coronary atherosclerotic plaques. gamma-GT has been documented as an independent risk factor for cardiac mortality in middle-aged men. The purpose of this study is to determine the prognostic value of gamma-GT in patients with coronary artery disease. In a prospective study, gamma-GT and other cardiac risk factors were evaluated in 469 consecutive subjects with angiographically documented coronary artery disease, using mortality and mortality plus non-fatal myocardial infarction as end-points. gamma-GT showed an independent prognostic value beyond known established risk factors in the subgroup of 262 patients with previous myocardial infarction. At a 6-year follow-up, cardiac mortality was 25.2% in patients with gamma-GT >40 U x l(-1)vs 13.9% in those with gamma-GT <40 U x l(-1)(P=0.038). When both cardiac mortality and non-fatal myocardial infarction were considered as end-points, these events were recorded in 32.7% of patients with gamma-GT >40 U x l(-1)and in 20.4% of those with levels <40 U x l(-1)(P=0.031). Excess mortality and non-fatal infarction in patients with high gamma-GT levels were concentrated in the first 2 years of follow-up (P=0.014). The association of gamma-GT values >40 U x l(-1), previous myocardial infarction, and multiple vessel disease identified a subgroup of 168 patients with the highest risk of cardiac events at 6 years (P=0.024). The relationship between gamma-GT levels and cardiac events remained significant after adjustment for cardiac risk factors, and possible confounders, including alcohol consumption. gamma-GT did not show significant prognostic value in the 207 patients without previous myocardial infarction. gamma-GT is an independent cardiac risk factor in ischaemic patients with established coronary atherosclerosis and previous myocardial infarction.

Dilated Cardiomyopathy in Dialysis Patients—Beneficial Effects of Carvedilol: A Double‐Blind, Placebo‐Controlled Trial

Objectives. The aim of this study was to investigate, in dialysis patients with symptomatic heart failure, New York Heart Association (NYHA) functional class II or III, whether the addition of carvedilol to conventional therapy is associated with beneficial effects on cardiac architecture, function, and clinical status. Background. Congestive heart failure (CHF) in chronic hemodialyzed patients, particularly when associated with dilated cardiomyopathy, represents an ominous complication and is an independent risk factor for cardiac mortality. Methods. We enrolled 114 dialysis patients with dilated cardiomyopathy. All patients were treated with carvedilol for 12 months in a double-blind, placebo-controlled, randomized trial. The patients underwent M-mode and two-dimensional echocardiography at baseline and 1, 6, and 12 months after the randomization. Each patient's clinical status was assessed using an NYHA functional classification that was determined after 6 and 12 months of treatment. Results. Carvedilol treatment improved left ventricular (LV) function. In the active-treatment group, the increase in LV ejection fraction (from 26.3% to 34.8%; p<0.05 vs. basal and placebo group) and the reduction of both LV end-diastolic volume (from 100 ml/m2 to 94 ml/m2; p<0.05 vs. basal and placebo group) and end-systolic volume (from 74 ml/m2 to 62 ml/m2; p<0.05 vs. basal and placebo group) reached statistical significance after 6 months of therapy, compared with baseline and corresponding placebo values, and they remained constant at 1 year of treatment (p<0.05 vs. basal and placebo group). The clinical status of patients, assessed by NYHA functional classification, improved during the treatment period. Moreover, at the end of the trial, there were no patients in NYHA functional class IV in the carvedilol group, compared with 5.9% of the patients in the placebo arm. Conclusions. One year of therapy with carvedilol in dialysis patients with CHF and dilated cardiomyopathy reduces LV volumes and improves LV function and clinical status.—Cice G, Ferrara L, Di Benedetto A, et al. Dilated cardiomyopathy in dialysis patients—beneficial effects of carvedilol: A double-blind, placebo-controlled trial. J Am Coll Cardiol. 2001;37:407–411. Comment. The authors of this trial sought to determine the effects of β blockade with carvedilol in patients suffering from dilated cardiomyopathy and end-stage renal disease. It is now well established that patients with symptomatic heart failure can gain significant benefit from therapy with β blockers. With this in mind, the authors conducted a double-blind, placebo-controlled trial to assess whether carvedilol therapy has beneficial effects on cardiac remodeling as well as both functional and clinical status. The trial involved 114 dialysis patients who had dilated cardiomyopathic ventricles. The protocol included 12 months of treatment with this α- and β-blocking agent. All patients underwent imaging at the time of randomization and then again at 1-, 6-, and 12-month intervals after starting therapy. Clinical and functional classifications were determined at the 6- and 12-month examinations. The authors found a significant increase in the LV ejection fraction in the treated group. Also, both end-diastolic and end-systolic volumes were significantly reduced. The improvements were consistent and were persistent at the end of 1 full year of treatment. Furthermore, it was noted that patients' clinical status improved during the treatment period, and that the treated group had no significant functional decline. On the basis of their data, the authors concluded that in this very high-risk group of patients, treatment with carvedilol can improve both objective and subjective parameters. Given that heart failure carries a very poor prognosis in dialysis patients, these data should encourage clinicians who care for this unfortunate subpopulation to be aggressive in their pharmacologic interventions. This paper presents very important clinical data that should be considered for integration into standard clinical practice.

Changes in left ventricular mass in children and adolescents during chronic dialysis.

Left ventricular hypertrophy (LVH) is an independent risk factor for cardiac mortality in adults with end-stage renal disease (ESRD). It is prevalent in pediatric patients on chronic dialysis. The objectives of this study were to evaluate left ventricular mass (LVM) in children and adolescents at the initiation of dialysis and to assess its changes during chronic dialysis therapy. In this longitudinal analysis, 29 patients aged 4-18 years had an echocardiographic evaluation within 90 days of starting dialysis therapy and a follow-up study at least 6 months later. LVH was defined as LVM index (g/m2.7) > 95th percentile for normal children and adolescents. On the initial echocardiogram 20 of 29 (69%) patients had LVH and 24 patients (83%) had abnormal LV geometry (38% eccentric LVH, 31% concentric LVH, and 14% concentric remodelling). Patients with LVH were more likely to be on antihypertensive medications (16/20) than patients without LVH (3/9) (P = 0.005). Repeat echocardiogram, performed after 10 +/- 3 months on chronic dialysis, showed no significant difference in the mean LVM index (49.6 +/- 17.5 g/m2.7 and 49.7 +/- 16.1 g/m2.7, respectively) or in the prevalence of LVH or LV geometric pattern. However, 14 of 29 patients had a progressive increase in LVM index and 15 patients had regression. Multiple regression analysis showed that baseline LVM index (P = 0.005) and interval change in indexed systolic blood pressure (P = 0.027) were independent predictors for LVM index changes. In summary, LVH and abnormal LV geometry are already prevalent in children and adolescents with renal failure at the time of initiation of dialysis therapy, indicating that LVH develops during the pre-ESRD course. Early intervention to control blood pressure may be an important factor to improve and prevent progression of LVH in pediatric patients with ESRD.

QT intervals and heart rate variability in hypertensive patients.

Low heart rate variability and increased QT dispersion are risk factors for cardiac mortality in various patient populations. We studied dispersion of QT interval, i.e. an index of inhomogeneity of repolarization, and heart rate variability (HRV) i.e., a measure of cardiac autonomic modulation in 76 essential hypertension cases (45 women, 53.0 +/- 11.1 years, body mass index: 25.1 +/- 1.4 kg/m2) and 70 healthy cases (42 women, 54.0 +/- 10.2 years, body mass index: 25.5 +/- 1.6 kg/m2, p > 0.05). QT-corrected QT intervals and their dispersions were significantly higher in the hypertensive group (p < 0.0001), all showing a direct relation with the level of systolic and diastolic blood pressures, ventricular mass index and high Lown grade ventricular rhythm problems. Time domain measures like standard deviation of RR intervals, standard deviation of the means of all corrected RR intervals calculated at 5 min intervals (p < 0.0001), proportion of adjacent RR intervals differing by > 50 msec (p = 0.005), HRV triangular index (p = 0.007), the square root of the mean squared differences of successive RR intervals (p = 0.011), and the high frequency (HF, 0.16-0.40 Hz, p < 0.0001) part of the frequency domain measure of HRV were all decreased, whereas the low frequency (LF, 0.04-0.15 Hz, p = 0.013) part of the frequency domain measures and LF / HF ratio (p < 0.0001) were increased in hypertensive cases. Time domain and the HF part of frequency domain measures of heart rate variability showed an inverse relation with the increased levels of both systolic and diastolic blood pressures and Lown grading system of ventricular rhythm problems, whereas LF and LF / HF showed direct relations with high levels of systolic and diastolic blood pressures and high Lown grade ventricular rhythm problems. The measures of heart rate variability apart from LF and LF / HF were inversely related with the QT intervals and dispersions, whereas LF / HF was directly related with them. Therefore, we conclude that the levels of both systolic and diastolic blood pressures are related to the generation of ventricular rhythm problems either via increasing left ventricular mass which results in an increase in QT parameter measurements, or by altering heart rate variability measures indicating a disturbance in cardiac autonomic balance in essential hypertension.

Cardiovascular risk factors and psychiatric illness

Psychiatric illness and cardiovascular disease occur together more frequently than expected then by chance alone. Several of the established risk factors for coronary artery disease account for this increased risk of comorbidity. Psychiatric illness appears to increase the risk for hypertension. Smoking rates are higher in patients with psychiatric illness than for populations without psychiatric illness. Elevated serum cholesterol levels often occur in panic and other anxiety disorders. In contrast, there is accumulating evidence that low cholesterol levels are linked to violent death, including suicide. Myocardial infarction represents a major life stressor that can precipitate an episode of major depression. Prolonged depression following myocardial infarction can become an independent risk factor for cardiac mortality. These associations increase the need for psychiatrists to be aware of the risk factors for coronary heart disease and to assist with the assessment and management of these risk factors in patients with mental illness.

Elevated platelet factor 4 and β-thromboglobulin plasma levels in depressed patients with ischemic heart disease

Clinical depression has recently been recognized as an independent risk factor for cardiac mortality in patients after myocardial infarction. The underlying mechanisms of this increased mortality remain unclear. This study investigated the hypothesis that patients suffering from ischemic heart disease (IHD) and depression concurrently may have abnormal platelet activation resulting in an increased risk of thrombosis. Platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were measured in young healthy control subjects, in nondepressed patients with IHD, and in depressed patients with IHD. Mean PF4 and beta-TG plasma levels in the IHD group with depression were found to be significantly higher than those of the control and IHD groups. This increase was not related to age, gender, racial difference, aspirin use, or severity of cardiac disease. This finding suggests that in depressed patients with IHD there is greater platelet activation, and may indicate an increased risk of thrombotic complications.

Diagnostic procedures for myocardial ischaemia.

It is important to detect the problem of ischaemic heart disease at a manageable stage at which treatments could have beneficial effects. A positive exercise test in patients with known ischaemic heart disease is a risk factor for cardiac mortality and there is a need to devise treatment strategies that take into account different approaches to higher- and lower-risk patients with ischaemic heart disease. In patients with stable angina pectoris, ST-segment depression on continuous ambulatory ECG monitoring is a reliable method of assessing ischaemic events in patients going about their normal daily activities. However, at the present time both of these assessment methods should only be considered for screening individuals already suspected of being at high risk of cardiovascular morbidity and mortality.

Heart rate variability in systemic hypertension

Low heart rate (HR) variability is a risk factor for cardiac mortality in various patient populations, but it has not been well established whether patients with long-standing hypertension have abnormalities in the autonomic modulation of HR. Time and frequency domain measures of HR variability were compared in randomly selected, age-matched populations of 188 normotensive and 168 hypertensive males (mean age 50 ± 6 years for both). The standard deviation of the RR intervals was lower in the hypertensive subjects than in the normotensive ones (52 ± 19 vs 59 ± 20 mss; p < 0.01), and the very low and low-frequency spectral components of HR variability analyzed as absolute units were reduced in the hypertensive patients relative to the normotensive controls (p < 0.001 for both). Hypertensive subjects also had blunted changes of the normalized low- and high-frequency components in response to an upright (sitting) posture (NS) as compared with normotensive subjects (p < 0.001 for both). Multiple regression analysis showed the standard deviation of the RR intervals to be predicted most strongly by systolic blood pressure, both in the patients with hypertension (β − 0.20, p = 0.01) and in the normotensive subjects (β − 0.28, p = 0.0002). After adjustment for the baseline differences in blood pressure and body mass index, none of the absolute measures of the HR variability or the responses of the normalized units of HR variability to a change in the body posture differed between the hypertensive subjects and normotensive controls. These data show that long-standing hypertension results in reduced overall HR variability and blunted autonomic responses to a change in body posture. Altered autonomic modulation of HR in hypertension is mainly due to elevated blood pressure and obesity in males with long-standing hypertension as compared with normotensive subjects.

The Coronary Circulation in Cardiac Hypertrophy

Left ventricular hypertrophy is a common and important risk factor for cardiac mortality and morbidity. Cardiac hypertrophy adversely affects coronary perfusion because hypertension, its most frequent cause, is a major risk factor for coronary disease, and because cardiac hypertrophy may be associated with myocardial ischemia even in the absence of atheromatous coronary disease due to disturbances in coronary physiology. Several studies have demonstrated impairment of coronary reserve in human and experimental cardiac hypertrophy. Normal autoregulation of coronary flow may be disturbed in cardiac hypertrophy for many reasons, including (a) increased perfusion pressure in hypertension, (b) increased diastolic and systolic left ventricular pressures, in addition to disturbed coronary physiology. Studies undertake in the presence of maximal coronary vasodilatation indicate an increased minimal coronary vascular resistance in hypertrophied hearts. Because such measurements were determined in the presence of maximal coronary vasodilation, they are likely to indicate a reduced arteriolar lumenal cross-sectional area per unit mass of tissue. Studies of cardiac and coronary morphology support an imbalance in myocardial and coronary growth in cardiac hypertrophy, but further evidence is needed to confirm this. Myocardial contraction impairs coronary flow, and available evidence suggests that this systolic impairment may be greater in hypertrophied myocardium, and that this may be an additional factor in limiting coronary flow in hypertrophy. A further important feature of impaired coronary reserve in cardiac hypertrophy is its distribution. Studies using radiolabeled microspheres indicate that coronary reserve is reduced in endocardial regions to a much greater extent than epicardial regions. Previously, treatment of conditions such as hypertension, which are commonly associated with hypertrophy, have concentrated on correction of the main defect. It is important to bear in mind, however, that such treatments may have direct and indirect effects on the coronary circulation, which may have an important bearing on preserving myocardial function. An important aspect of future research will be to determine the effects of treatment on coronary perfusion.

Cardiac and Cerebrovascular Disease in Chronic Uremia

Cardiovascular disease causes death in more than 40% of dialysis patients and the burden of its morbidity is high. The relationships between traditional risk factors for cardiac mortality, as identified by the Framingham study, and potential uremia-related risk factors are unclear. The characteristic echocardiographic pattern in dialysis patients is a dilated left ventricle with normal systolic function and left ventricular hypertrophy. Dilated cardiomyopathy, severe left ventricular hypertrophy, and coronary artery disease occur frequently and predispose to congestive heart failure, arrhythmias, and ischemic heart disease. The risk factors that predispose to each disease and the natural history of each disorder have not been studied with sufficient precision. Few quality studies have been undertaken to identify the interventions that effectively ameliorate the impact of cardiac disease in dialysis patients. In some subsets of patients, erythropoietin or renal transplantation will be useful in inducing regression of some cardiac diseases. However, the impact of various antihypertensive agents, lipid-lowering agents, or normalization of hematocrit is unknown.