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D Mancini

Publications and source records attributed to D Mancini.

At least 37 records · Page 2Linked to original sources
PubMed1999

Nuclear magnetic resonance spectroscopy: its role in providing valuable insight into diverse clinical problems.

Skeletal muscle plays an important role in respiratory and cardiovascular physiology. The ability to measure metabolic changes in skeletal muscle has been enhanced with the advent of magnetic resonance spectroscopy (MRS). MRS measurements have been used to understand the metabolic control of respiration and to evaluate metabolic changes in the muscle in patients with respiratory and cardiac diseases. The key to the respiratory control measurements is the ability to measure intracellular pH with MRS. Muscle oxidative metabolism has been measured in two ways: during steady-state exercise and using recovery kinetics. The similarities in the metabolic findings for pulmonary and coronary disease suggest the potential for some interesting common pathways.

Adenosine Diphosphate↗
PubMed1998

Comparison of exercise performance in patients with chronic severe heart failure versus left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVADs) are frequently used as a bridge to cardiac transplantation and may be useful as long-term therapy. The purpose of this study was to compare the exercise performance of LVAD patients with that of ambulatory heart failure patients. METHODS AND RESULTS: Exercise testing with hemodynamic and respiratory gas measurements was performed in 65 congestive heart failure (CHF) patients (age 53+/-10 years) and 20 LVAD patients (age 49+/-8 years). Peak Vo2 was significantly higher in the LVAD than the CHF patients (CHF, 12+/-3; LVAD, 15. 9+/-3.8 mL . kg-1 . min-1; P<0.001), as was the Vo2 at the anaerobic threshold (CHF, 8.1+/-2.1; LVAD, 12.2+/-2.9 mL . kg-1 . min-1; P<0.001). At rest, mean arterial blood pressure (CHF, 87+/-11; LVAD, 94+/-9 mm Hg) and cardiac output (CHF, 4+/-1; LVAD, 4. 9+/-0.9 L/min) were increased, whereas mean pulmonary artery pressure (CHF, 28+/-11; LVAD, 18+/-4 mm Hg) and pulmonary artery wedge pressure (CHF, 16+/-10; LVAD 5+/-3 mm Hg) were reduced (all P<0.01). At peak exercise, heart rate (CHF,125+/-24; LVAD, 148+/-24 bpm), blood pressure (CHF, 87+/-14; LVAD,96+/-12 mm Hg), and cardiac output (CHF, 7.6+/-2.2; LVAD, 11.2+/-2.6 L/min) were higher (all P<0. 01), whereas mean pulmonary artery pressure (CHF, 48+/-12; LVAD, 30+/-5 mm Hg) and mean pulmonary capillary wedge pressure (CHF, 31+/-11; LVAD, 14+/-6 mm Hg) were lower in the LVAD group (both P<0. 001). In the LVAD patients, Fick cardiac output was higher than LVAD flow sensor value measurements (Fick, 11.6+/-2.5; LVAD, 8.1+/-1.2 L/min; P<0.001). CONCLUSIONS: Hemodynamic measurements at rest and during exercise are significantly improved in patients with devices compared with those in ambulatory heart failure patients awaiting cardiac transplantation. Similarly, the exercise capacity of device patients is better than that of transplant candidates and in the majority of patients is similar to that of patients with mild CHF.

Adult↗
PubMed1998

A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients. Mycophenolate Mofetil Investigators.

BACKGROUND: After heart transplantation, 1-year and 5-year survival rates are 79% and 63%, respectively, with rejection, infection, and allograft coronary artery disease accounting for the majority of deaths. Mycophenolate mofetil (MMF), an inhibitor of the de novo pathway for purine biosynthesis, decreases rejection in animals and in human renal transplantation. METHODS: In a double-blind, active-controlled trial, 28 centers randomized 650 patients undergoing their first heart transplant to receive MMF (3000 mg/day) or azathioprine (1.5-3 mg/kg/day), in addition to cyclosporine and corticosteroids. Rejection and survival data were obtained for 6 and 12 months, respectively. Because 11% of the patients withdrew before receiving study drug, data were analyzed on all randomized patients (enrolled patients) and on patients who received study medications (treated patients). RESULTS: Survival and rejection were similar in enrolled patients (MMF, n=327; azathioprine, n=323). In treated patients (MMF, n=289; azathioprine, n=289), the MMF group compared with the azathioprine group was associated with significant reduction in mortality at 1 year (18 [6.2%] versus 33 deaths [11.4%]; P=0.031) and a significant reduction in the requirement for rejection treatment (65.7% versus 73.7%; P=0.026). There was a trend for fewer MMF patients to have > or = grade 3A rejection (45.0% versus 52.9%; P=0.055) or require the murine monoclonal anti-CD3 antibody or antithymocyte globulin (15.2% versus 21.1%; P=0.061). Opportunistic infections, mostly herpes simplex, were more common in the MMF group (53.3% versus 43.6%; P=0.025). CONCLUSIONS: Substitution of MMF for azathioprine may reduce mortality and rejection in the first year after cardiac transplantation.

Aged↗
PubMed1998

An immunological algorithm to predict risk of high-grade rejection in cardiac transplant recipients.

BACKGROUND: Transplant-related coronary-artery disease (TCAD) develops frequently in cardiac-allograft recipients, and limits long-term survival. We examined the relation between this disorder and cumulative frequency of high-grade rejection, and investigated whether concomitant use of three immunological factors at the time of a low-grade endomyocardial biopsy can predict progression to high-grade rejection. METHODS: We investigated the relation between the cumulative annual frequency of high-grade rejection and TCAD in 198 recipients of cardiac transplantation between 1992 and 1996 by means of Kaplan-Meier actuarial life-tables. Endomyocardial biopsy, lymphocyte-growth assays, and anti-HLA antibody measurements were compiled over 12 months in 102 patients during their first post-transplant year. We calculated predictive values for high-grade rejection within 90 days by chi2, Kaplan Meier survival curves, and by multivariable logistic regression analyses. FINDINGS: We found a direct correlation between cumulative annual frequency of rejection and TCAD onset with highest risk in those with more than 0.75 rejections per year (p=0.0002). After a low-grade endomyocardial biopsy (0 or 1A), one or more donor-recipient HLA-DR matches protected against high-grade rejections (p<0.001). Among individuals with one or two DR matches, the negative predictive value for progression from a low-grade biopsy to a high-grade rejection was 87% in the presence of a negative lymphocyte-growth assay. Among individuals with no DR matches, the presence of either a positive lymphocyte-growth assay or IgG anti-major-histocompatibility complex (MHC) class II antibodies was independently associated with high probability of progression to rejection (64% and 66%, respectively, p<0.0005). When both assays were positive, concomitantly with a low-grade endomyocardial biopsy, the positive predictive value for progression to a high-grade rejection was 86% (p<0.0001). For endomyocardial-biopsy grades 1B or 2, a positive lymphocyte-growth assay alone was associated with high-grade rejection in 100% of cases. INTERPRETATION: Use of an algorithm combining three immunological factors at the time of a low-grade endomyocardial biopsy enables prospective stratification of cardiac transplant recipients into risk categories for progression to high-grade rejection. Low-risk individuals require fewer biopsies, moderate-risk individuals require an ongoing schedule of surveillance biopsies, and high-risk individuals require rational organisation of interventional strategies aimed at preventing rejection. Additional predictive factors are needed to identify moderate-risk individuals who will progress to rejection. Ultimately, successful intervention may have an impact on the subsequent complication of TCAD.

Adult↗
PubMed1998

Improvement of myocardial mitochondrial function after hemodynamic support with left ventricular assist devices in patients with heart failure.

OBJECTIVES: Mitochondrial abnormalities have been described in cardiac tissue of patients with heart failure. These changes may result from chronic hypoxia. Our goal was to determine whether mitochondrial functional capacity can be improved in patients with heart failure by means of long-term left ventricular assist device therapy, which improves myocardial oxygen supply by decreasing myocardial work. METHODS: Mitochondria were isolated from myocardial tissue obtained from 13 patients with heart failure without a left ventricular assist device (HF group) and seven patients with heart failure treated with a left ventricular assist device (LVAD-HF group). Mitochondrial respiratory rates (State 2, State 3, and State 4) were measured by means of polarographic techniques with reduced nicotinamide adenine dinucleotide-dependent (pyruvate/malate, alpha-ketoglutarate, glutamate) and -independent (succinate) substrates. The respiratory control index of Chance (State 3/State 4) and Lardy (State 3/State 2) and phosphorus to oxygen ratios were determined. RESULTS: The respiratory control index of Chance was higher in LVAD-HF than in HF when using NADH-dependent substrates pyruvate/malate and alpha-ketoglutarate (pyruvate/malate HF: 4.9 +/- 1.0; LVAD-HF: 6.5 +/- 1.5; alpha-ketoglutarate HF: 8.5 +/- 2.4; LVAD-HF: 11.8 +/- 2.9; both p = 0.04). Similarly, the respiratory control index of Lardy was greater in the LVAD-HF than the HF group when alpha-ketoglutarate and glutamate were used as substrates (alpha-ketoglutarate HF: 7.8 +/- 1.7; LVAD-HF: 9.9 +/- 1.5; glutamate HF: 7.6 +/- 2.2; LVAD-HF: 10.7 +/- 2.1; both p = 0.04). The phosphorus to oxygen ratio was comparable for both groups using all substrates. No change in mitochondrial respiration was observed after left ventricular assist device therapy with the NADH-independent substrate, succinate. CONCLUSION: Cardiomyocyte mitochondrial function is improved by long-term therapy with a left ventricular assist device. This improvement suggests that cardiomyocyte metabolic dysfunction in heart failure may be reversed with left ventricular assist device support.

Adult↗
PubMed1998

Prevention of bone loss after heart transplantation with antiresorptive therapy: a pilot study.

BACKGROUND: Heart transplantation, with its attendant glucocorticoid and cyclosporine therapy, has deleterious effects on the skeleton. We have previously reported rapid bone loss and high fracture rates (36% of patients) during the first year after heart transplantation. The bone loss was accompanied by declines in serum 1,25-dihydroxyvitamin D and osteocalcin levels and increased urinary excretion of markers of bone resorption (hydroxyproline, pyridinoline, and deoxypyridinoline). We therefore investigated whether bone loss could be prevented by bisphosphonates, agents that inhibit bone resorption. METHODS: Serial measurements of bone mineral density (BMD) and biochemical indexes of mineral metabolism were compared in 18 group A patients who received a single intravenous infusion of pamidronate (60 mg) within 2 weeks of heart transplantation, followed by 4 cycles of oral etidronate (400 mg daily for 14 days every 3 months) and oral calcitriol 0.25 microg daily, to those of 52 patients who previously underwent transplantation (group B) who did not receive antiresorptive therapy. Both groups received elemental calcium 1000 mg and vitamin D 400 IU daily. RESULTS: At 12 months after transplantation, there was virtually no lumbar spine bone loss in group A patients, whereas lumbar spine BMD had declined significantly in group B patients (0.2% +/- 0.9% vs 6.8% +/- 1.0%, respectively; P < .0001). Similarly, femoral neck BMD fell by 10.6% +/- 1.1% in group B patients and by only 2.7% +/- 1.4% in group A patients (P < .0001). Three incident vertebral fractures occurred in two group A patients, whereas 17 group B patients sustained 30 incident vertebral fractures, one hip fracture and three episodes of rib fractures (P < .02; test of proportions). With respect to markers of bone resorption, urinary deoxypyridinoline fell by 51% +/- 9% in group A patients and increased by 65% +/- 22% in group B patients by 3 months after transplantation (P < .0001). CONCLUSION: In summary, heart transplant recipients treated with bisphosphonates and replacement doses of calcitriol sustained less bone loss and fewer fractures than those treated with calcium and vitamin D. We conclude that bisphosphonate therapy, in conjunction with calcitriol, shows promise for prevention of transplantation-related osteoporosis.

Absorptiometry, Photon↗
PubMed1997

Nonselective beta-adrenergic blockade with carvedilol does not hinder the benefits of exercise training in patients with congestive heart failure.

BACKGROUND: Long-term beta-adrenergic blockade does not appear to be associated with drug-induced training in patients with congestive heart failure (CHF); whether exercise training can increase peak aerobic capacity in patients with CHF who are treated with beta-adrenergic blockers is currently unknown. METHODS AND RESULTS: We studied 23 patients with CHF who were treated with carvedilol or propranolol in addition to ACE inhibitors, furosemide, and digoxin. Of the patients treated with carvedilol, 8 underwent exercise training and 8 remained sedentary. All 7 patients treated with propranolol underwent exercise training. Peak oxygen consumption (mL.kg-1.min-1) was serially measured in trained and sedentary patients. Peak reactive hyperemia (mL.min-1.100 mL-1) was determined in the calf and forearm immediately before and after 12 weeks of training. The peak oxygen consumption of trained patients treated with either carvedilol or propranolol increased from 12.9 +/- 1.4 to 16.0 +/- 1.6 (P < .001) and 12.4 +/- 1.0 to 15.7 +/- 0.9 (P < .001) mL.kg-1.min-1, respectively, whereas it did not change in the sedentary patients. Peak reactive hyperemia increased significantly in the calves but not the forearms of trained patients. CONCLUSIONS: Long-term, nonselective beta-adrenergic blockade with carvedilol or propranolol does not prevent patients with CHF from deriving systemic and regional benefits from physical training.

Adaptation, Physiological↗
PubMed1997

Acute unloading of the work of breathing extends exercise duration in patients with heart failure.

OBJECTIVES: This study investigated whether maximal exercise performance can be improved by acutely decreasing the work of breathing in these patients. BACKGROUND: Exertional dyspnea is a frequent limiting symptom in patients with heart failure. It may result from increased work of breathing. METHODS: Fifteen patients with heart failure and nine age-matched normal subjects underwent two maximal exercise tests. Subjects exercised twice in randomized, single-blind manner using room air (RA) and a 79% helium/21% oxygen mixture (He). Respiratory gas analysis, Borg scale recordings of perceived dyspnea and near infrared spectroscopy of an accessory respiratory muscle were obtained during exercise. RESULTS: In normal subjects there was no significant difference in peak oxygen uptake (Vo2) ([mean +/- SD] RA 38 +/- 8 vs. He 35 +/- 7 ml/kg per min), exercise duration (RA 724 +/- 163 vs. He 762 +/- 123 s) or peak minute ventilation (RA 97 +/- 27 vs. He 97 +/- 28 liters/min, all p = NS). Only three of nine control subjects thought that exercise with the He mixture was subjectively easier. In contrast, patients with heart failure exercised an average of 146 s longer with the He mixture (RA 868 +/- 293 vs. He 1,014 +/- 338, p < 0.01). Peak Vo2 (RA 19 +/- 4 vs. He 18 +/- 5 ml/kg per min) and peak minute ventilation (RA 53 +/- 12 vs. He 53 +/- 15 liters/min) were unchanged (both p = NS). The respiratory quotient at peak exercise was lower with the He mixture (RA 1.05 +/- 0.08 vs. He 0.98 +/- 0.06, p < 0.05). Thirteen of the 15 patients thought that exercise with the He mixture was subjectively easier (p < 0.02 vs. control group). CONCLUSIONS: In patients with heart failure, pulmonary factors, including respiratory muscle work and airflow turbulence, contribute to limiting exercise performance. Therapeutic interventions aimed at attenuating work of breathing may be beneficial.

Adult↗
PubMed1997

Chronic congestive heart failure elicits adaptations of endurance exercise in diaphragmatic muscle.

BACKGROUND: During rest and exercise, patients with heart failure hyperventilate; therefore, the diaphragm can be viewed as undergoing constant moderate-intensity exercise. Accordingly, we hypothesized that heart failure elicits adaptations in the diaphragm similar to those elicited by endurance exercise in the limb muscles of normal subjects. METHODS AND RESULTS: Costal diaphragmatic biopsy samples were obtained from 7 normal subjects (age, 36 +/- 20 years) and 10 patients (age, 50 +/- 6 years; left ventricular ejection fraction, 18 +/- 8%) at the time of transplant or left ventricular assist-device placement. We measured the distribution of myosin heavy chain isoforms I, IIa, and IIb by SDS gel electrophoresis. We also measured the activities of the following enzymes: citrate synthase, a marker of oxidative metabolism; beta-hydroxyacyl-CoA dehydrogenase, a marker of lipolytic metabolism; and lactate dehydrogenase, a marker of glycolytic metabolism. In normal subjects, the distribution of myosin heavy chain isoforms I, IIa, and IIb was 43 +/- 2%, 40 +/- 2%, and 17 +/- 1%, respectively. In contrast, in heart failure subjects, the fiber distribution was 55 +/- 2%, 38 +/- 2%, and 7 +/- 2% for types I, IIa, and IIb, respectively. Therefore, in heart failure, myosin heavy chain I is increased (P < .0001) and myosin heavy chain IIb decreased from normal levels (P < .001). Additionally, citrate synthase activity (normal, 0.33 +/- 0.14; heart failure, 0.54 +/- 0.21 mumol.min-1.mg protein-1; P < .05) and beta-hydroxyacyl-CoA dehydrogenase activity (normal, 0.27 +/- 0.04; heart failure, 0.38 +/- 0.02 mumol.min-1.mg protein-1; P < .05) were greater in heart failure patients than in normal subjects, whereas lactate dehydrogenase activity was significantly less in heart failure patients than in normal subjects (normal, 11.6 +/- 4.6; heart failure,: 4.3 +/- 2.2 mumol.min-1.mg protein-1; P < .01). CONCLUSIONS: In the diaphragm in heart failure, there is a shift from fast to slow myosin heavy chain isoforms with an increase in oxidative capacity and a decrease in glycolytic capacity. These diaphragmatic muscle changes are consistent with those elicited by endurance training of the limb muscles in normal subjects.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1997

Bone mass, vitamin D deficiency, and hyperparathyroidism in congestive heart failure.

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

Constitutively methylated CpG dinucleotides as mutation hot spots in the retinoblastoma gene (RB1).

A wide spectrum of mutations, ranging from point mutations to large deletions, have been described in the retinoblastoma gene (RB1). Mutations have been found throughout the gene; however, these genetic alterations do not appear to be homogeneously distributed. In particular, a significant proportion of disease-causing mutations results in the premature termination of protein synthesis, and the majority of these mutations occur as C-->T transitions at CpG dinucleotides (CpGs). Such recurrent CpG mutations, including those found in RB1, are likely the result of the deamination of 5-methylcytosine within these CpGs. In the present study, we used the sodiumbisulfite conversion method to detect cytosine methylation in representative exons of RB1. We analyzed DNA from a variety of tissues and specifically targeted CGA codons in RB1, where recurrent premature termination mutations have been reported. We found that DNA methylation within RB1 exons 8, 14, 25, and 27 appeared to be restricted to CpGs, including six CGA codons. Other codons containing methylated cytosines have not been reported to be mutated. Therefore, disease-causing mutations at CpGs in RB1 appear to be determined by several factors, including the constitutive presence of DNA methylation at cytosines within CpGs, the specific codon within which the methylated cytosine is located, and the particular region of the gene within which that codon resides.

DNA↗
PubMed1997

Angiotensin II-receptor blockade further reduces afterload safely in patients maximally treated with angiotensin-converting enzyme inhibitors for heart failure.

Combined therapy with an angiotensin-II type I receptor (AT1) antagonist and an angiotensin-converting enzyme (ACE) inhibitor results in more complete suppression of the renin-angiotensin system. Accordingly, the blood-pressure response and safety of combining AT1-receptor blockade with losartan for ACE inhibition were evaluated in patients with congestive heart failure who were already treated with maximally recommended or tolerated doses of an ACE inhibitor. Forty-three patients with symptomatic congestive heart failure were evaluated biweekly for 1 month before addition of losartan and weekly during administration of losartan at a daily dose of 25 mg for the first week and 50 mg for the second week. Systolic blood pressure, which remained unchanged before addition of losartan, decreased from 122 +/- 18 mm Hg to 112 +/- 17 and 107 +/- 17 mm Hg (p < 0.001) after 1 week of 25 mg and 1 week of 50 mg losartan, respectively. Diastolic blood pressure also significantly decreased. The decreases in blood pressure were well tolerated by all patients, even by those in whom symptomatic hypotension developed during uptitration of ACE inhibition. Serum potassium and sodium and parameters of renal function remained unchanged. Combining AT1-receptor blockade with losartan to maximally recommended or tolerated ACE inhibition appears safe and leads to further vasodilatation in symptomatic patients with congestive heart failure.

Aged↗
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↗
PubMed1996

Assessment of submaximal exercise capacity in patients with left ventricular assist devices.

BACKGROUND: Long-term implantable left ventricular assist devices (LVADs) are increasingly used as a bridge to cardiac transplantation and may be used as long-term therapy for end-stage heart failure. After insertion of an LVAD, patients frequently become ambulatory. Sensors contained within these devices can measure the hemodynamic demands of submaximal exercise. In this study, we performed serial assessment of submaximal exercise capacity in patients with LVADs early (< 3 months), mid (3 to 6 months), and late (> 6 months) after device implantation to determine whether submaximal exercise capacity increased over time and whether this was related to improvements in the cardiac output response. Moreover, we compared the sub-maximal exercise capacities of these patients with those of normal subjects and patients with mild to severe heart failure. METHODS AND RESULTS: An encouraged 6-minute walk test with metabolic measurements was used to assess submaximal exercise capacity in 14 patients with LVADs, 20 patients with mild to moderate congestive heart failure (CHF), 14 patients with severe heart failure dependent on dobutamine (DB), and 6 normal subjects. Cardiac output measurements at rest and during exercise were obtained in the patients with devices. Distance walked was significantly greater for LVAD patients than DB patients and was similar to that for patients with mild CHF (LVAD, 1562 +/- 404; DB, 948 +/- 241; and CHF, 1358 +/- 278 ft; P < .01). Vo2 was also greater in the LVAD than DB or CHF patients (LVAD, 16.3 +/- 6.5; DB, 9.8 +/- 4.8; and CHF, 11.2 +/- 2.0 mL.kg-1.min-1; P < .05). Vo2 (23.4 +/- 7.4 mL.kg-1.min-1) and distance walked (2142 +/- 408 ft) in normal subjects was significantly greater than for all patient groups (all P < .01). Serial assessment of submaximal exercise capacity in LVAD patients demonstrated continued sustained improvement over time (early, 1261 +/- 341; mid, 1538 +/- 345; and late, 1867 +/- 265 ft; P < .05). However, peak cardiac output response was unchanged (early, 8 +/- 1.3; mid, 8.6 +/- 1.4; and late, 8.6 +/- 1.4 L/min; P = NS). CONCLUSIONS: The submaximal exercise capacity of LVAD patients is comparable to that of patients with mild CHF but significantly better than that of dobutamine-dependent patients. Hemodynamic and metabolic assessment during 6-minute walk tests demonstrates that in patients with heart failure and LVAD, cardiovascular demands are generally > 85% of maximum. A significant sustained improvement in submaximal exercise capacity occurs with chronic LVAD therapy. Lack of alteration of the cardiac output response to exercise suggests that this functional improvement results from peripheral mechanisms.

Adult↗