Obesity and the "obesity paradox" in cardiovascular diseases.

Obesity adversely affects most cardiovascular (CV) risk factors and is strongly associated, probably as an independent risk factor, with most CV diseases. However, substantial evidence points to the existence of an "obesity paradox," in that overweight and obese patients with established CV diseases typically have a better prognosis than leaner patients with the same CV disease. Despite this paradox, we believe that the "weight" of evidence still supports efforts at purposeful weight loss in both primary and secondary CV prevention.

Ventricular-vascular uncoupling increases expression of B-type natriuretic peptide in heart transplantation.

BACKGROUND: Allograft adaptation to a foreign circulation is imperfect as noted from persistent limitations to stress. Effective arterial elastance (Ea), a measure of afterload, provides an estimate of aortic impedance. End systolic elastance (Ees) is a load-independent measure of ventricular performance as well as its interaction in the periphery. The ratio (Ea to Ees) characterizes ventricular-vascular coupling; a value close to unity signifies poor mechanical efficiency. The purpose of this investigation was to correlate mechanical efficiency of work with expression of B-type natriuretic peptide BNP, a specific marker of ventricular stress and strain. METHODS: We measured BNP levels in 40 consecutive stable heart transplant recipients free from rejection. In addition, echocardiography was performed to obtain Ea, Ees, and their ratio (Ea to Ees) by the single-beat method. We examined correlates of BNP expression by assessing Ea to Ees, while correcting for mean arterial pressure, body mass index, left ventricular mass index, ejection fraction, and serum creatinine. RESULTS: BNP levels were significantly and positively correlated (r=0.38, P=.05) with an increased Ea to Ees ratio. By multivariable analysis, this relationship persisted independently (t=2.1, P=.04), while the five other measures were insignificant predictors. CONCLUSION: This investigation indicated that the transplanted heart demonstrates poor contractile efficiency and operates at maximal left ventricular work. This is paralleled by a tandem increase in BNP, suggesting that elevation in this stress peptide is at least partly explained by ventriculo-vascular uncoupling in heart transplantation, independent of alterations in blood pressure.

Corticosteroid weaning in the tacrolimus and mycophenolate era in heart transplantation: clinical and neurohormonal benefits.

BACKGROUND: Compared with cyclosporine, tacrolimus-based immunosuppression yields improved metabolic outcomes in heart transplantation. Whether corticosteroid freedom provides incremental metabolic benefits in tacrolimus and mycophenolate mofetil immunoprophylaxis remains uncertain. METHODS: In a prospective trial, 41 heart transplant patients treated with tacrolimus and mycophenolate mofetil underwent steroid weaning immediately after transplantation until weaning was complete. Weaning was interrupted only for treated rejection with or without hemodynamic compromise. Benefits of steroid weaning assessed following the first year included B-type natriuretic peptide (BNP), late infections, lipids, blood pressure, hyperglycemia, and body mass index (BMI). RESULTS: Of this 41 patient cohort (age 53 +/- 9 years, 50% black American, 35% women) followed for a total of 47 +/- 5 months, 25 had corticosteroids discontinued (62%) by an average of 20 +/- 11 months. No differences between the two groups were noted in baseline characteristics. Significant predictors of failure to wean steroids included higher rejection, BNP, and lower dose of mycophenolate mofetil. No significant benefits of steroid weaning were noted on lipids, blood pressure, hyperglycemia, and BMI. However, late infections (after 1 year) requiring hospitalizations were more frequent in the failure to wean group (0.60.4 vs 0 infections/patient/y, P <.001). INFERENCES: Unlike known metabolic benefits of steroid withdrawal with cyclosporine, heart transplant recipients treated with tacrolimus and mycophenolate mofetil demonstrate no incremental metabolic benefits, but instead experience benefits of decreased serious late infections. Furthermore, failure to discontinue corticosteroids in this series is predicted by early allograft rejection, use of lower doses of mycophenolate mofetil, and higher BNP levels suggesting poor cardiac adaptation.

Treatment of heart failure according to William Stokes: the enchanted mercury.

BACKGROUND: It was not until 1919 that the diuretic properties of mercury were observed in patients with syphilis; in the same year the beneficial effects of mercurial diuretics were shown in a patient with severe rheumatic heart disease and anasarca. However, mercury had been used much earlier for the treatment of dropsy without clear guidelines. In this article we describe William Stokes' insights into the treatment of heart failure, focusing on the beneficial diuretic properties of mercury. METHODS: We reviewed the chapter "Treatment of the Weak and Probably Dilated Heart in Connexion With Enlargement of the Liver and Pulmonary Disease" in William Stokes' famous treatise The Diseases of the Heart and the Aorta. CONCLUSIONS: Stokes makes several important clinical observations. First, he provides precise guidelines on when and how to use mercury in these patients. Second, he realizes the importance of mercury for the treatment of decompensated heart failure. Stokes recognizes the cyclical nature of frequent decompensation in congestive heart failure, the relationship of clinical deterioration and reduced urine output, and the importance of reestablishing urinary flow to ameliorate dyspnea. Third, he attempts to define the mechanism of action "... if any of the characteristic action of mercury can be perceived unless we include diuresis." Finally, he gives interesting guidelines on the dosage and side effects of mercury. These observations on the treatment of "congestive" heart failure are an important contribution to the understanding of heart failure pathophysiology and the design of prescription regimens for this disease.

Desperate diseases, desperate measures: tackling malignant hypertension in the 1950s.

BACKGROUND: The conquest of malignant hypertension is one of the most important medical achievements of the second half of the 20th century. As we enter the new millennium, it is critical to examine the efforts that have led to our ability to treat this once incurable disease. METHODS: Review was performed of the literature from 1900 to the 1950s regarding the etiology, clinical evaluation, and treatment of hypertension, focusing on malignant hypertension. RESULTS: Fifty years ago, in a time of sparse treatment options, the occurrence of malignant hypertension was a dreaded event that taxed the aptitude of the clinician. Confronted with an "extreme disease," physicians chose to use "extreme methods of cure" in conformity with the teaching of Hippocrates. In the 1950s malignant hypertension was treated with such drastic measures as rice diet, sympathectomy, and intravenous pyrogens. CONCLUSIONS: In the practice of medicine today, while work is being done to reassert biomolecular mechanisms, we still face patients who have reached the end stages of failure and manifest devastating morbidity. These patients are subjected to "extreme therapies" reminiscent of those that surrounded malignant hypertension in the past. In an era when adequate treatment of hypertension has become a reality for so many patients, it is appropriate to give credit to those who paved the way to such great progress.

Historical perspectives on cardiac transplantation: the past as prologue to challenges for the 21st century.

The development of cardiac transplantation is based on experimental studies that started in the beginning of the last century. The improvement in the surgical technique for cardiac transplantation, associated with other progress in the field of cardiac surgery and a better understanding of the immune responses, allowed cardiac transplantation to become a reality for the treatment of endstage heart disease. Recent development in immunosuppressive agents and advances in cardiac surgery have meant that cardiac transplantation is not a "fantastic speculation for the future," but a reality for the present. Thus, cardiac transplantation is performed around the world with an excellent survival rate and has become a lifesaving treatment for many patients with severe heart disease.

Insights into ventricular repolarization abnormalities in cardiac allograft vasculopathy.

We investigated the relationship of QT dispersion and cardiac allograft vasculopathy in heart transplant recipients. The findings suggest that the development of cardiac allograft vasculopathy is associated with an increase in QT dispersion, suggesting the presence of abnormal repolarization in these patients.

Difficult cases in heart failure: Raison d'Être behind ACE inhibitors and AT1 receptor combinations in chronic heart failure: chemical nuances or clinical significance?

The following case description serves to illustrate the difficulties often faced in clinical practice in implementing what appear to be fairly simple and clear evidence-based guidelines regarding angiotensin-converting enzyme (ACE) inhibitors and no clear guidelines regarding angiotensin receptor blocker (ARB) use or, more importantly, ACE inhibitor and ARB combinations in chronic heart failure. (c)2001 by CHF, Inc.

Valvular heart disease and pregnancy. A high index of suspicion is important to reduce risks.

Pregnant women who have valvular disease represent a major challenge for physicians involved in their care. Careful history taking and physical examination, along with a judicious use of diagnostic tools (mainly echocardiography), can lead to better management and ultimately to excellent outcomes for both mother and baby.

Albert Ochsner, MD: Chicago Surgeon and Mentor to Alton Ochsner.

Albert John Ochsner was a member of a select group of medical practitioners who made their impact on medical practice and surgical techniques. He was a pioneer in microscopy and made numerous contributions to the medical literature, on topics ranging from the organization of hospitals and advances in the treatment of hernias to the conservative treatment of appendicitis. The latter was controversial but saved lives. He was an innovative surgeon and a greathearted human being who influenced the lives of his colleagues. We are pleased to inaugurate Ochsner Profiles with Albert John Ochsner, a leader in the development of surgery in the United States and Europe and a figure of vast importance in the development of Dr. Alton Ochsner's career in medicine.

Study of arterial and autonomic effects of cyclosporine in humans.

Altered sympathetic activity and peripheral vascular function are suspected as a mechanism of the development of arterial hypertension in organ transplantation recipients treated with cyclosporine. We assessed whether cyclosporine might alter peripheral vascular properties or autonomic modulation of the sinus node and the vasculature during rest and standing. We examined 17 orthotopic heart transplantation recipients, 8 solid organ transplantation recipients, 17 patients with essential hypertension, and 42 normotensive control subjects. All except the normotensive control subjects were treated with a long-acting dihydropyridine calcium entry blocker; transplantation recipients also received cyclosporine-based immunosuppression. Radial artery compliance was reduced in patients with essential hypertension and in patients with heart and solid organ transplantation as compared with normotensive control subjects, with this reduction being more marked in heart transplantation recipients. At rest, R-R variance was lowest in heart transplantation recipients, denoting denervation. The spectral profile of both R-R and systolic blood pressure variability as well as the index of baroreflex gain was normal at rest in patients with solid organ transplantation. On standing, both transplantation groups demonstrated reduced responsiveness in markers of autonomic modulation. The decrease in arterial compliance in cyclosporine-induced hypertension seems to imply a degree of ventricular vascular uncoupling more apparent in heart transplantation recipients. These changes are associated with alterations in autonomic modulation that are evidenced by an orthostatic stimulus.

Difficult cases in heart failure: Bridge to beta blockade in severe heart failure: the use of phosphodiesterase inhibitors.

The authors describe the use of milrinone as a bridge to beta blockade in a patient with severe heart failure. This case is clinically important because in patients with severe heart failure phosphodiesterase inhibitors, unlike beta agonists, will retain their positive inotropic and vasodilator effects in the presence of beta blockade and, in addition, these agents will attenuate the negative inotropic side effects of beta blockers. Conversely, a beta blocker associated with a phosphodiesterase inhibitor will protect against myocyte loss and arrhythmias, may prevent sudden death, and will improve long-term symptoms and exercise tolerance. This combination is being investigated in a large, multicenter, double-blind, randomized trial of intravenous milrinone vs. placebo as a therapeutic tool to allow the initiation of carvedilol orally in patients hospitalized with class III/IV heart failure. (c)2000 by CHF, Inc.

Impedance cardiography: a bridge between research and clinical practice in the treatment of heart failure.

This paper proposes that impedance cardiography could narrow the gap between heart failure clinical research and the appropriate and timely application of new knowledge and technology in the care of patients with heart failure. Research variables and measurement strategies, identified in the heart failure scientific literature between 1994-1999, are compared to measures that can be obtained through a cost effective, noninvasive technology--impedance cardiography. Emphasis is placed on case reports that illustrate how "real time" evaluation and trending of key hemodynamic variables through impedance cardiography monitoring has been used to apply state of the science knowledge and technology to improve the inpatient and outpatient management of care for patients with severe heart failure. (c)2000 by CHF, Inc.

Difficult cases in heart failure: beneficial effects of aldosterone blockade in heart failure.

The authors describe the use of spironolactone, an aldosterone receptor blocker, in a patient with heart failure refractory to conventional therapy. The clinical importance of this case is that not only does spironolactone improve symptoms, but its use also improves survival in patients with severe heart failure. Clinicians should be aware that this therapy has to be added to the medical armamentarium for patients with severe heart failure. In addition, it is important to point out that the use of the aldosterone receptor blockers and their beneficial effects in morbidity and mortality in heart failure has helped to understand more clearly the relationship between aldosterone and its importance in the pathophysiology of heart failure. (c)2000 by CHF, Inc.

Bridging patients to cardiac transplantation.

Potential recipients of heart transplants have the most advanced form of congestive heart failure, in which standard therapy fails to maintain clinical stability. In the absence of guidelines derived from evidence obtained in clinical trials, caring for these patients becomes a challenge. A successful approach requires the proper coordination of surgical and nonsurgical strategies, including revascularization and valvular surgery as well as mechanical ventricular support and medical strategies. Intensive medical therapy is the most commonly used approach for prolonged bridging to transplantation. Although carefully individualized regimens are necessary to achieve desired goals, most centers adopt a fairly standardized approach involving vasodilators, diuretics, and inotropic support. Bridging patients with cardiac decompensation to transplantation presents a major therapeutic challenge. Appropriate strategies will maximize patients' chances that the bridge from decompensation to transplantation remains intact. (c)2000 by CHF, Inc.