PURPOSE: In contrast to renal and hepatic failure, congestive heart failure (CHF) has not been associated with a defined metabolic bone disorder. However, low bone mass has been reported in patients with CHF who receive a cardiac transplant. Both the pathophysiology and therapy of CHF may influence bone and mineral homeostasis and evidence that calciotropic hormones may affect cardiovascular function is accumulating. Therefore, we evaluated patients with severe CHF to determine the prevalence of osteoporosis and to characterize relationships between mineral homeostasis, bone turnover, bone mass, and severity of CHF. PATIENTS AND METHODS: One hundred one patients (79 men and 22 women, aged 25 to 70 years) with severe CHF (New York Heart Association functional class III or IV) referred for consideration for cardiac transplantation were evaluated with measurements of serum 25-hydroxyvitamin D (25-OHD), 1,25 dihydroxyvitamin D [1,25(OH)2D], intact parathyroid hormone (PTH), markers of bone turnover (serum osteocalcin, urinary hydroxyproline, and pyridinium crosslinks); bone mineral density (BMD) by dual energy x-ray absorptiometry was measured in 91 patients. Left ventricular ejection fraction (LVEF) and resting cardiac output (CO) were determined in 88 and maximal treadmill exercise testing and peak oxygen consumption were performed in 45 patients. RESULTS: Osteoporosis (T score < or = -2.5) was present in 7% at the lumbar spine, 6% at the total hip, and 19% at the femoral neck. Osteopenia (T scores between -1.0 and -2.5) was present in 43% at the lumbar spine, 47% at the total hip, and 42% at the femoral neck. Women were more severely affected (P = 0.007). Frankly low serum 25-OHD (< or = 9 pg/mL) and 1,25(OH)2D (< or = 15 pg/mL) levels were found in 17% and 26% of the patients, respectively, and elevated serum PTH (> or = 65 pg/mL) in 30%. Both low serum 1,25(OH)2D and increased serum PTH were associated with prerenal azotemia. Low serum vitamin D metabolites were associated with biochemical evidence of increased bone turnover, but BMD did not differ by vitamin D or PTH status. Patients with more severe CHF had significantly lower vitamin D metabolites and higher bone turnover, whereas elevated PTH was associated with better LVEF (21 +/- 1 versus 18 +/- 1%; P = 0.05) and correlated positively with resting CO (R = 0.220; P = 0.04). CONCLUSIONS: Osteopenia or osteoporosis were observed in approximately half of these patients with severe CHF. Abnormal calciotropic hormone concentrations, also common, were associated with evidence of increased bone resorption but were not related to BMD in this cross-sectional study. Abnormal concentrations of calciotropic hormones were related to the severity of cardiovascular compromise. Because both low BMD and low serum concentrations of 25-OHD in patients with CHF are associated with higher rates of bone loss and fracture after cardiac transplantation, patients should be evaluated for and receive appropriate therapy for these disorders.

Absorptiometry, Photon↗

PubMed1997

Mitral valve replacement and tricuspid valve repair after cardiac transplantation.

Efforts aimed at limiting the pool of cardiac retransplantation candidates have focused increasingly on attempts to preserve cardiac allograft function. The present report reviews the course of a patient who underwent mitral valve replacement and tricuspid annuloplasty for bivalvular incompetence after cardiac transplantation and examines the limited reported world experience with valve replacement after transplantation. The limited yet successful experiences with these and other operations in cardiac allograft recipients suggest that worsening donor organ shortages will likely lead to increased clinical experience with conventional operations in the transplanted heart.

Cardiomyopathy, Dilated↗

PubMed1997

Bone loss and turnover after cardiac transplantation.

Cardiac transplantation is associated with increased prevalence and incidence of fracture, and rapid bone loss has been reported during the first posttransplant year. To define further the pattern and etiology of bone loss after cardiac transplantation, we enrolled 70 patients (52 men and 18 women) in a prospective 3-yr study. Bone densitometry (BMD) and biochemical indexes of mineral metabolism were performed before and at defined times after transplantation. Despite supplementation with elemental calcium (1000 mg/day) and vitamin D (400 IU/day), the mean rate of bone loss during the first year was 7.3 +/- 0.9% (+/- SEM) at the lumbar spine and 10.5 +/- 1.1% at the femoral neck. The rate of bone loss slowed (P < 0.001 compared to year 1) at both sites (0.9 +/- 0.9% and 0.1 +/- 1.0%, respectively) during the second year. During the third year, lumbar spine BMD increased at a rate of 2.4 +/- 0.8%/yr (P < 0.02 compared to year 2), but femoral neck BMD did not change. At the radius, the rate of decline in BMD was negligible during the first year (0.9 +/- 0.5%), but was significant during the second (2.1 +/- 0.6%; P < 0.01) and third (2.9 +/- 0.8%; P < 0.03) years. Evaluation of the pattern of bone loss during the first year demonstrated that mean lumbar spine BMD decreased rapidly during the first 6 months, after which there was no further decline. In contrast, femoral neck BMD continued to fall at an annualized rate of 8.2 +/- 1.3% during the second half of the year. The pattern and rates of bone loss were similar in men and women. Biochemistries revealed decreases in serum testosterone and osteocalcin and increases in all bone resorption markers 1 and 3 months after transplantation, with a return to baseline by 6 months. Higher rates of bone loss were associated with greater exposure to prednisone, lower serum concentrations of vitamin D metabolites, greater suppression of osteocalcin, higher levels of bone resorption markers, and, in men, lower serum testosterone concentrations. We conclude that rapid bone loss is primarily confined to the initial year after transplantation. During the first 6 months, bone loss is accompanied by alterations in markers of bone turnover consistent with biochemical uncoupling of bone formation and resorption. Greater exposure to glucocorticoids, lower serum concentrations of vitamin D metabolites and testosterone, and higher bone turnover were associated with more rapid bone loss.

Adult↗

PubMed1996

Coupling of hemodynamic measurements with oxygen consumption during exercise does not improve risk stratification in patients with heart failure.

BACKGROUND: Measurement of peak Vo2 has become an accepted method to select patients for cardiac transplantation. Some investigators have suggested that the addition of exercise hemodynamic measurements can further enhance risk stratification because these measurements may identify patients with a noncardiac limitation to exercise. METHODS AND RESULTS: Accordingly, we performed maximal bicycle exercise with respiratory gas analysis and hemodynamic measurements in 65 patients (47 men, 18 women) 53 +/- 10 years old (mean +/- SD) who underwent a transplant evaluation at Columbia Presbyterian Medical Center. Skeletal muscle oxygenation of the vastus lateralis during exercise was assessed with near-infrared spectroscopy. Exercise hemodynamic, ventilatory, and muscle oxygenation measurements were obtained in all patients. For each subject, a linear correlation was derived between Vo2 and pulmonary artery saturation (PA Sao2). The slope of this relationship and a theoretical Vo2max at a PA Sao2 of 0% (Vo2 intercept) was derived. Baseline measurements were left ventricular ejection fraction, 22 +/- 9%; pulmonary capillary wedge pressure (PCWP), 16 +/- 10 mm Hg; cardiac index (CI), 2.1 +/- 0.5 L. min-1. m-2; and PA Sao2, 53 +/- 8%. The cardiac output response to exercise was categorized as normal or abnormal by comparison to the linear equation of peak Vo2 versus peak cardiac output as described by Higginbotham. Exercise measurements were peak Vo2, 12.1 +/- 3.0 mL.kg-1.min-1; Vo2 intercept, 19.1 +/- 5.5 mL. kg-1.min-1; PCWP, 31 +/- 11 mm Hg; CI, 3.8 +/- 1.3 L.min-1.m-2; and PA Sao2, 27 +/- 9%. Only 6% of patients exhibited a normal cardiac output response to exercise. Multivariate analysis was performed with peak Vo2, Vo2 intercept, skeletal muscle oxygenation at end exercise, and peak exercise hemodynamic variables. Only left ventricular stroke work and left ventricular stroke work index were shown to be predictive of survival. CONCLUSIONS: Addition of exercise hemodynamic measurements to noninvasive metabolic stress testing minimally improves risk prognostication in patients with severe heart failure.

Adult↗