Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure.

OBJECTIVES: This study was undertaken to determine which exercise and radionuclide ventriculographic variables predict prognosis in advanced heart failure. BACKGROUND: Although cardiopulmonary exercise testing is frequently used to predict prognosis in patients with advanced heart failure, little is known about the prognostic significance of ventriculographic variables. METHODS: The results of maximal symptom-limited cardiopulmonary exercise testing and first-pass radionuclide ventriculography in patients with advanced heart failure referred for evaluation for cardiac transplantation were analyzed. RESULTS: Sixty-seven patients with advanced heart failure (mean [+/- SD]; age 51 +/- 10 years, New York Heart Association functional classes III (58%) and IV (18%); mean left ventricular ejection fraction 0.22 +/- 0.07) underwent simultaneous upright bicycle ergometric cardiopulmonary exercise testing and first-pass rest/exercise radionuclide ventriculography. Mean peak oxygen consumption (VO2) was 11.8 +/- 4.2 ml/kg per min, and mean peak age- and gender-adjusted percent predicted oxygen consumption (%VO2) was 38 +/- 11.9%. Univariate predictors of overall survival included right ventricular ejection fraction > or = 0.35 at rest and > or = 0.35 at exercise and %VO2 > or = 45% (all p < 0.05). In a multivariate proportional hazards survival model, right ventricular ejection fraction > or = 0.35 at exercise (p < 0.01) and %VO2 > or = 45% (p = 0.01) were selected as independent predictors of overall survival. Univariate predictors of event-free survival included right ventricular ejection fraction > or = 0.35 at rest (p = 0.01) and > or = 0.35 at exercise (p < 0.01), functional class II (p < 0.05) and %VO2 > or = 45% (p = 0.05). Right ventricular ejection fraction > or = 0.35 at exercise (p = 0.01) was the only independent predictor of event-free survival in a multivariate proportional hazards model. Cardiac index at rest, VO2, left ventricular ejection fraction at rest, and exercise-related increase or decrease > 0.05 in left or right ventricular ejection fraction were not predictive of overall or event-free survival in any univariate or multivariate analysis. CONCLUSIONS: 1) Right ventricular ejection fraction > or = 0.35 at rest and exercise is a more potent predictor of survival in advanced heart failure than VO2 or %VO2; 2) %VO2 rather than VO2 predicts survival in advanced heart failure; 3) neither %VO2 nor VO2 predicts survival to the combined end point of death or admission for inotropic or mechanical support in patients with advanced heart failure.

Inotropic effect of nicardipine in patients with heart failure: assessment by left ventricular end-systolic pressure-volume analysis.

Nicardipine, a new dihydropyridine calcium channel blocker, has been investigated for the treatment of coronary artery disease and heart failure. To assess the inotropic effect of nicardipine in humans independent of its vasodilator effect, equihypotensive doses of intravenous nitroprusside (mean infusion rate 65 +/- 13 micrograms/min) and nicardipine (mean dose 5.2 +/- 0.4 mg) were administered to 15 patients with heart failure (New York Heart Association functional classes II to IV, radionuclide left ventricular ejection fraction 0.15 +/- 0.02). Left ventricular micromanometer pressure and simultaneous radionuclide left ventricular volume were obtained at baseline, during nitroprusside infusion, during a second baseline period and during nicardipine infusion. Heart rate did not change significantly with either nitroprusside or nicardipine. Mean systemic arterial pressure decreased by an average of 21 mm Hg with both drugs. A greater decrease in left ventricular end-diastolic pressure occurred with nitroprusside (27 +/- 2 to 14 +/- 2 mm Hg, p less than 0.01) than with nicardipine (27 +/- 2 to 23 +/- 3 mm Hg, p less than 0.05), and pulmonary capillary wedge pressure decreased significantly only with nitroprusside. Cardiac index increased from 1.8 +/- 0.1 to 2.1 +/- 0.1 liters/min per m2 (p less than 0.05) with nitroprusside and to a greater extent from 1.7 +/- 0.1 to 2.4 +/- 0.1 liters/min per m2 (p less than 0.01) with nicardipine. Left ventricular ejection fraction increased with nicardipine (0.15 +/- 0.01 to 0.19 +/- 0.01, p less than 0.01), but not with nitroprusside. Peak positive first derivative of left ventricular pressure (dP/dt) decreased by 9% with both agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Positive inotropic and lusitropic effects of intravenous flosequinan in patients with heart failure.

OBJECTIVES: This study was designed to assess the direct effects of flosequinan on myocardial function. BACKGROUND: Flosequinan has been shown to improve symptoms and exercise tolerance in patients with heart failure. Although previous studies have established that flosequinan is a vasodilator, it is not known to what extent direct actions of the drug on myocardial contractility or diastolic properties contribute to its beneficial hemodynamic effects. METHODS: Nitroprusside and intravenous flosequinan were administered sequentially to 18 patients with severe heart failure (New York Heart Association functional class III or IV, left ventricular ejection fraction 0.14 +/- 0.02). Micromanometer left ventricular pressure and radionuclide volume data were combined to construct pressure-volume loops during 1) a baseline period, 2) nitroprusside infusion, 3) a second baseline period, and 4) flosequinan infusion. RESULTS: The peak rate of left ventricular pressure development increased from 899 +/- 84 to 1,070 +/- 94 mm Hg/s (p less than 0.05) with flosequinan. The baseline left ventricular end-systolic pressure-volume relation was constructed in 15 patients from the two baseline pressure-volume loops and from that obtained during afterload manipulation with nitroprusside. During flosequinan administration, the relation between end-systolic pressure and volume was shifted upward and leftward, indicating enhanced contractility, in 14 of 15 patients (p less than 0.001). The maximal rate of decrease in left ventricular pressure during isovolumetric relaxation increased in magnitude with flosequinan from 882 +/- 63 to 1,026 +/- 68 mm Hg/s (p less than 0.05). CONCLUSIONS: These results indicate that intravenous flosequinan has positive inotropic and lusitropic effects in patients with heart failure. Further studies are needed to assess the direct myocardial effects of oral flosequinan.

Hemodynamic effects of inhaled nitric oxide in heart failure.

OBJECTIVES: This study was performed to assess the utility of inhaled nitric oxide as a selective pulmonary vasodilator in patients with severe chronic heart failure and to compare its hemodynamic effects with those of nitroprusside, a nonselective vasodilator. BACKGROUND: Preoperative pulmonary vascular resistance is a predictor of right heart failure after heart transplantation. Non-selective vasodilators administered preoperatively to assess the reversibility of pulmonary vasoconstriction cause systemic hypotension, limiting their utility. METHODS: Systemic and pulmonary hemodynamic measurement were made at baseline, during oxygen inhalation and with the addition of graded doses of inhaled nitric oxide or intravenous nitroprusside in 16 patients with New York Heart Association class III or IV heart failure referred for heart transplantation. RESULTS: Pulmonary vascular resistance decreased to a greater extent with 80 ppm nitric oxide (mean +/- SEM 256 +/- 41 to 139 +/- 14 dynes.s.cm-5) than with the maximally tolerated dose of nitroprusside (264 +/- 49 to 169 +/- 30 dynes.s.cm-5, p < 0.05, nitric oxide vs. nitroprusside). Pulmonary capillary wedge pressure increased with 80 ppm nitric oxide (26 +/- 2 to 32 +/- 2 mm Hg, p < 0.05). Mean arterial pressure did not change with nitric oxide but decreased with nitroprusside. Seven of the 16 patients, including 1 patient who did not have an adequate decrease in pulmonary vascular resistance with nitroprusside but did with nitric oxide, have undergone successful heart transplantation. CONCLUSIONS: Inhaled nitric oxide is a selective pulmonary vasodilator in patients with pulmonary hypertension due to left heart failure and may identify patients with reversible pulmonary vasoconstriction in whom agents such as nitroprusside cause systemic hypotension. Inhaled nitric oxide causes an increase in left ventricular filling pressure by an unknown mechanism.

Exercise capacity and systolic and diastolic ventricular function after recovery from acute dilated cardiomyopathy.

OBJECTIVES: This study was undertaken to determine whether abnormalities in exercise capacity or ventricular function persist after recovery from acute dilated cardiomyopathy. BACKGROUND: Persistent ventricular structural abnormalities could cause abnormalities in exercise capacity or ventricular function. METHODS: The results of rest and exercise first-pass radionuclide ventriculography in 18 patients who were seen within 6 months of the onset of dilated cardiomyopathy and subsequently had a normal rest left ventricular ejection fraction were compared with those of age- and gender-matched control subjects. RESULTS: Patients were studied 144 +/- 34 (mean +/- SEM) days after the onset of left ventricular dysfunction at a time when heart failure symptoms had resolved. Patients with myocyte necrosis, as assessed by endomyocardial biopsy (n = 13) or antimyosin scintigraphy (n = 12), recovered more rapidly than did those without necrosis. Oxygen consumption both at peak exercise (17.7 +/- 1.2 vs. 26.1 +/- 1.5 ml/kg per min, p < 0.05) and at the anaerobic threshold (11.1 +/- 0.5 vs. 17.1 +/- 1.3 ml/kg per min, p < 0.05) was lower in the patients who had recovered from cardiomyopathy than in control subjects. Rest and exercise end-systolic and end-diastolic left ventricular volumes were greater in the patients than in the control subjects, although stroke volumes were similar. Left ventricular filling at rest was lower at diastolic filling intervals of 40% and 90%, and rest and exercise left ventricular early peak filling rate normalized for end-diastolic volume was slower in the patients than in the control subjects. At long-term follow-up of 1,082 +/- 206 days, two patients had a return of heart failure symptoms and a decrease in left ventricular ejection fraction. CONCLUSIONS: Despite the apparent normalization of rest left ventricular ejection fraction, patients who have recovered from dilated cardiomyopathy have abnormalities in aerobic exercise capacity and in left ventricular systolic and diastolic performance.

Cessation of platelet-mediated cyclic canine coronary occlusion after thrombolysis by combining nitric oxide inhalation with phosphodiesterase-5 inhibition.

OBJECTIVES: We sought to evaluate the ability of type 5 phosphodiesterase (PDE5) inhibitors to augment the antithrombotic effects of inhaled nitric oxide (NO) in a canine model of platelet-mediated coronary thrombosis after thrombolysis. BACKGROUND: Type 5 phosphodiesterase inhibitors potentiate the ability of NO to inhibit platelet aggregation in vitro by preventing platelet cyclic guanosine monophosphate catabolism. We previously reported that breathing low concentrations of NO gas attenuated, but did not prevent, cyclic flow reductions (CFRs) in a canine model of coronary thrombosis after thrombolysis. METHODS: Cyclic flow reductions were induced after creation of a left anterior descending coronary artery stenosis, endothelial injury, thrombus formation and thrombolysis. Dogs were either untreated or treated with inhaled NO (20 ppm by volume), intravenous zaprinast, intravenous dipyridamole or the combination of inhaled NO with either PDE5 inhibitor (n = 4 per group). RESULTS: Cyclic flow reductions ceased, and complete coronary patency was achieved in all dogs after they breathed NO combined with zaprinast (by 12.0+/-4.7 min [mean +/- SEM]) or dipyridamole (by 9.8+/-4.7 min). The frequency of CFRs was unaffected by NO, dipyridamole or zaprinast alone. Systemic arterial blood pressure and bleeding time were unchanged with any treatment. Ex vivo thrombin-induced platelet aggregation in dogs breathing NO and receiving dipyridamole was reduced by 75+/-7% (p < 0.05). CONCLUSIONS: The PDE5 inhibitors potentiated the antithrombotic properties of inhaled NO in a canine model of platelet-mediated coronary artery thrombosis after thrombolysis, without prolonging the bleeding time or causing systemic hypotension.

Coronary endothelial dysfunction in patients with acute-onset idiopathic dilated cardiomyopathy.

OBJECTIVES: This study sought to determine whether coronary endothelial dysfunction exists in patients with acute-onset idiopathic dilated cardiomyopathy (DCM) and to explore its relation to recovery of left ventricular systolic function in this patient population. BACKGROUND: Coronary endothelial dysfunction exists in chronic DCM, but its importance in the development and progression of ventricular dysfunction is not known. To address this issue we studied coronary endothelial function in patients with idiopathic DCM <6 months in duration and explored the relation between coronary endothelial function and subsequent changes in left ventricular ejection fraction (LVEF). METHODS: Ten patients with acute-onset idiopathic DCM (duration of heart failure symptoms 2.0 +/- 0.4 months [mean +/- SEM]) and 11 control patients with normal left ventricular function underwent assessment of coronary endothelial function during intracoronary administration of the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator adenosine. Coronary cross-sectional area (CSA) was determined by quantitative coronary angiography and coronary blood flow (CBF) by the product of coronary CSA and CBF velocity measured by an intracoronary Doppler catheter. Patients with DCM underwent assessment of left ventricular function before and several months after the study. RESULTS: Acetylcholine infusion produced no change in coronary CSA in control patients but significant epicardial constriction in patients with DCM (-36 +/- 11%, p < 0.01). These changes were associated with increases in CBF in control patients (+118 +/- 49%, p < 0.01) but no change in patients with DCM. Infusion of adenosine produced increases in coronary caliber and blood flow in both groups. Follow-up assessment of left ventricular function was obtained in nine patients with DCM 7.0 +/- 1.7 months after initial study, at which time LVEF had improved by > or =0.10 in four patients. Multiple linear regression revealed a positive correlation between both the coronary CSA (r2 = 0.57, p < 0.05) and CBF (r2 = 0.68, p < 0.01) response to acetylcholine and the subsequent improvement in LVEF. CONCLUSIONS: Coronary endothelial dysfunction exists at both the microvascular and the epicardial level in patients with acute-onset idiopathic DCM. The preservation of coronary endothelial function in this population is associated with subsequent improvement in left ventricular function.

Linearity of the left ventricular end-systolic pressure-volume relation in patients with severe heart failure.

The left ventricular end-systolic pressure-volume relation is a relatively load-independent measure of left ventricular contractile function. Linearity of the relation derived from full left ventricular pressure-volume loops has not previously been demonstrated for patients with severe heart failure. Therefore, nine patients with markedly depressed left ventricular systolic function (ejection fraction 0.14 +/- 0.08) were studied with micromanometer left ventricular pressure measurement and simultaneous radionuclide ventriculography. Afterload was reduced with graded infusions of nitroprusside, allowing construction of pressure-volume loops under four afterload conditions in four patients and three afterload conditions in the other five patients. The end-systolic pressure-volume relation derived from the pressure-volume loops was found to be linear for the range of pressures and volumes examined, with correlation coefficients in individual patients ranging from 0.936 to 0.999 (mean 0.981). The mean slope of the relation (or end-systolic elastance) was 0.71 mm Hg/ml (range 0.42 to 1.52), and the extrapolated volume intercept at zero pressure was positive in all patients. An exponential relation between end-systolic elastance and ejection fraction was demonstrated for this group of patients. Approximations of end-systolic elastance obtained from measurements other than the full pressure-volume loops correlated variably with "true" elastance obtained from the pressure-volume loops. The relation between stroke work and end-diastolic volume was nonlinear in most patients. Thus, the end-systolic pressure-volume relation is linear in the "physiologic" range in patients with severe heart failure. This finding should permit construction of the relation from two loading conditions in clinical studies, facilitating its use as an index of contractile function in patients with heart failure.

Effects of atrial natriuretic peptide on myocardial contractile and diastolic function in patients with heart failure.

Atrial natriuretic peptide alters left ventricular performance in patients with heart failure. To assess the direct effects of this hormone on myocardial function, its actions were compared with those of the pure vasodilator nitroprusside in 10 patients with heart failure. Simultaneous left ventricular micromanometer pressure and radionuclide volume were obtained during a baseline period, during nitroprusside infusion, during a second baseline period and during atrial natriuretic peptide infusion. The baseline end-systolic pressure-volume relation was generated in nine patients from pressure-volume loops obtained during the two baseline periods and during afterload reduction with nitroprusside. Mean arterial pressure decreased with atrial natriuretic peptide (89 +/- 3 to 80 +/- 2 mm Hg, p less than 0.05) and by a greater amount with nitroprusside (90 +/- 4 to 73 +/- 3 mm Hg, p less than 0.05). Left ventricular end-diastolic pressure also decreased with atrial natriuretic peptide (24 +/- 2 to 16 +/- 3 mm Hg, p less than 0.05) and by a greater amount with nitroprusside (24 +/- 2 to 13 +/- 3 mm Hg, p less than 0.05). Cardiac index increased during infusion of each agent from 2.0 +/- 0.2 to 2.4 +/- 0.2 liters/min per m2 (p less than 0.01). Heart rate increased slightly with nitroprusside but did not change with atrial natriuretic peptide. Peak positive first derivative of left ventricular pressure (dP/dt), ejection fraction and stroke work index were unchanged by either agent. The relation between end-systolic pressure and volume during atrial natriuretic peptide infusion was shifted slightly leftward from the baseline value in four patients, slightly rightward in four and not at all in one patient, indicating no consistent inotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of atrial natriuretic peptide on left ventricular function in hypertension.

Atrial natriuretic peptide (ANP) has natriuretic and vasodilator actions that lower arterial pressure and may be beneficial to hypertensive patients. To assess the effects of ANP on left ventricular function in patients with hypertension, we compared it with the pure vasodilator nitroprusside. Simultaneous left ventricular micromanometer pressure and radionuclide volume were obtained at baseline, during nitroprusside infusion, during a second baseline period, and during ANP infusion in 10 patients with hypertension. Mean arterial pressure fell during ANP and nitroprusside. Heart rate and plasma norepinephrine levels increased by similar amounts during the two agents, whereas cardiac index and stroke volume index were unchanged during both. Peak positive left ventricular dP/dt fell similarly during ANP and nitroprusside, but left ventricular dP/dt at a developed pressure of 40 mm Hg, a less load-dependent index of contractility, was unchanged during both. The relation between end-systolic pressure and volume during ANP infusion was not shifted leftward or rightward from that during nitroprusside infusion, indicating no inotropic effect. Both ANP and nitroprusside shortened at time constant of isovolumic relaxation calculated by the logarithmic method but did not change the time constant calculated by the derivative method. Peak filling rate was unchanged from baseline during both agents. ANP did not shift the end-diastolic pressure-volume point away from the relation constructed from baseline and nitroprusside points. We conclude that ANP has no direct effect on myocardial contractile or diastolic function in patients with hypertension.

Outcomes in recipients of combined heart-kidney transplantation: multiorgan, same-donor transplant study of the International Society of Heart and Lung Transplantation/United Network for Organ Sharing Scientific Registry.

In patients awaiting heart transplantation, end-stage disease of a second organ may occasionally require consideration of simultaneous multiorgan transplantation. Outcome statistics in multiorgan transplant recipients are needed to define optimal utilization of scarce donor resources. Incidence of cardiac allograft rejection, actuarial recipient survival, and cardiac allograft rejection-free survival were evaluated in 82 recipients of 84 simultaneous heart and kidney transplants. Twenty-three of the 82 dual-organ recipients have died with 1, 6, 12, and 24-month actuarial survival rates of 92%, 79%, 76%, and 67%, respectively. The actuarial survival rates in the heart-kidney recipients were similar to those observed in 14,340 isolated heart recipients (United Network for Organ Sharing Scientific Registry) during the same period (92%, 86%, 83%, and 79%, respectively; P=0.20). Clinical data on all episodes of treated rejection in either organ and on immunosuppressive regimens were available on 56 patients; 48% of these patients have had no rejection in either organ, 27% experienced heart rejection alone, 14% experienced kidney rejection alone, and 11% had both heart and kidney allograft rejection. Heart allograft rejection was less common in heart-kidney recipients, as compared with isolated heart transplant recipients; 0, 1, and > or = 2 treated cardiac allograft rejection episodes occurred in 63%, 20%, and 18% of heart-kidney recipients compared with 46%, 27%, and 28% of 911 isolated heart recipients reported by Transplant Cardiologists' Research Database (P=0.02). The rejection-free survival rates at 1, 3, and 6 months were 88%, 74%, and 71% in the double-organ recipients, as compared with 66%, 44%, and 39%, respectively, in the single-organ recipients. Compared with isolated heart transplantation, combined heart-kidney transplantation does not adversely affect intermediate survival and results in a lower incidence of treated cardiac allograft rejection. The findings suggest that combined heart-kidney transplantation may be an acceptable option in a small subset of potential heart transplant recipients with severe renal dysfunction.

Left ventricular diastolic function in patients with left ventricular systolic dysfunction due to coronary artery disease and effect of nicardipine.

To assess the effect of nicardipine on left ventricular (LV) diastolic function independent of concurrent effects on loading conditions in patients with LV systolic dysfunction due to coronary artery disease, equihypotensive doses of intravenous nitroprusside and nicardipine were administered to 12 patients with congestive heart failure due to previous myocardial infarction (LV ejection fraction less than 0.40). LV micromanometer pressure and simultaneous radionuclide volume were obtained during a baseline period, during nitroprusside infusion, during a second baseline period and during nicardipine infusion. Mean systemic arterial pressure decreased an average of 21 mm Hg with nitroprusside and 19 mm Hg with nicardipine. A greater decrease in LV end-diastolic pressure was observed with nitroprusside (29 +/- 2 to 15 +/- 2 mm Hg, p less than 0.01) than with nicardipine (29 +/- 2 to 25 +/- 3 mm Hg, p less than 0.05). There was a decrease in the time constant of relaxation during nitroprusside but not during nicardipine infusion. There was enough overlap in LV volumes in the baseline and nitroprusside periods to compare diastolic pressure-volume relations over a common range of volumes in 4 patients, and enough overlap in the baseline and nicardipine periods in 11 patients. The relation was shifted downward in 3 of 4 patients taking nitroprusside and in 6 of 11 patients taking nicardipine. The relation between end-diastolic pressure and volume was not shifted with nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Pattern of changes over time in myocardial blood flow and microvascular dilator capacity in patients with normally functioning cardiac allografts.

This study tests the hypothesis that myocardial blood flow and coronary microvascular dilator capacity vary as a function of time after orthotopic heart transplantation in humans. Positron emission tomography measurements of myocardial blood flow were obtained at rest and during adenosine in 24 patients between 1 and 86 months after heart transplantation. At the time of the study all patients were clinically well and had angiographically normal epicardial coronary artery vessels. Patients were divided into 3 groups based on time from transplant to positron emission tomography measurement of myocardial blood flow: group 1 to 12 months (n = 9); group 13 to 34 months (n = 8); and group > or = 37 months (n = 7). Basal myocardial blood flow in group 1 to 12 months (1.86+/-1.01 ml/min/g) exceeded (p <0.05) that of group 13 to 34 months (1.17+/-0.73) and group > or = 37 months (0.98+/-0.34). In group 13 to 34 months, basal myocardial blood flow and maximal dilator capacity (minimal coronary vascular resistance with adenosine 36+/-12 mm Hg/ml/min/g) were comparable to that of normal volunteers (1.01+/-0.20 and 37+/-, respectively). In group > or = 37 months, maximal flow response to adenosine was reduced (2.54+/-1.25 vs 3.16+/-0.52, respectively, p = 0.06). Maximal dilator capacity in group > or = 37 months (60+/-34) was impaired versus group 1 to 12 months (36+/-10) and group 13 to 34 months (36+/-12; both p <0.05) as well as normals (37+/-9, p <0.05). During the first year after cardiac transplantation basal myocardial blood flow is elevated out of proportion to external determinants of myocardial oxygen demand, but maximal dilator capacity of the coronary microcirculation is normal. Between 1 and 3 years both basal myocardial blood flow and microvascular function tend to normalize. After 3 years, although basal myocardial blood flow is normal, microvascular dilator capacity is impaired.

Usefulness of echocardiographic determined tricuspid regurgitation in predicting event-free survival in severe heart failure secondary to idiopathic-dilated cardiomyopathy or to ischemic cardiomyopathy.

Two-dimensional and color Doppler echocardiograms obtained in 117 patients during cardiac transplantation evaluation were reviewed. Right ventricular hypokinesia and dilation were more prevalent in patients with tricuspid regurgitation. In multivariate event-free survival analysis of 61 patients with complete clinical, echocardiographic, and cardiopulmonary exercise data, the absence of tricuspid regurgitation and New York Heart Association class were the only independent predictors of survival.

Biopsy-induced flail tricuspid leaflet and tricuspid regurgitation following orthotopic cardiac transplantation.

Damage to the tricuspid valve apparatus has been described after endomyocardial biopsy and may be associated with hemodynamically significant tricuspid regurgitation (TR). This study was performed to determine the prevalence of TR and flail tricuspid leaflet in cardiac transplant recipients and to evaluate the use of a 45 cm sheath placed directly in the right ventricle during endomyocardial biopsy to reduce the incidence of these complications. Echocardiograms and right heart catheterization data of 72 orthotopic cardiac transplant recipients were assessed for the presence of flail tricuspid leaflet, TR, and right-sided cardiac dysfunction 29 +/- 20 months (mean +/- SD) after transplantation. Moderate or severe TR was present in 23 patients (32%). Ten patients (14%) had flail tricuspid leaflet, with 7 of these having severe TR. Right atrial pressure (10 +/- 5 vs 6 +/- 5 mm Hg, p < 0.05) was higher, cardiac index (2.0 +/- 0.2 vs 2.5 +/- 0.7 L/min/m2, p < 0.05) was lower, and right-sided cardiac dimensions were greater in patients with flail leaflets than in those without flail leaflets. Both the prevalence of flail tricuspid leaflet (41% to 6%, p < 0.0001) and mean grade of TR (2 to 1, p < 0.0001) were reduced after the use of a 45 cm sheath. We conclude that TR secondary to biopsy-induced damage to the valve apparatus occurs in cardiac transplant recipients and is associated with signs of early right-sided heart failure. Use of a 45 cm sheath during endomyocardial biopsy reduces the prevalence of flail tricuspid leaflet and the severity of TR.

Inhaled nitric oxide improves exercise capacity in patients with severe heart failure and right ventricular dysfunction.

Fourteen cardiac transplant candidates were studied with cardiopulmonary exercise testing at baseline and while breathing nitric oxide (40 ppm). Oxygen consumption at the anaerobic threshold was improved by breathing nitric oxide in patients with pulmonary hypertension and in patients with an elevated left ventricular end-diastolic volume index.

Oxygen therapy improves cardiac index and pulmonary vascular resistance in patients with pulmonary hypertension.

STUDY OBJECTIVES: We tested the hypothesis that breathing 100% oxygen could result in selective pulmonary vasodilatation in patients with pulmonary hypertension, including those patients who would not meet current Health Care Finance Administration guidelines for long-term oxygen therapy. DESIGN, SETTING, AND PATIENTS: From 1996 to 1999, 23 adult patients (mean +/- SEM age, 51 +/- 4 years) with pulmonary arterial hypertension without left-heart failure underwent cardiac catheterization in a university teaching hospital while breathing air and then 100% oxygen. MEASUREMENTS AND RESULTS: Treatment with 100% oxygen increased arterial oxygen saturation (91 +/- 1% to 99 +/- 0.1%, p < 0.05) and PaO(2) (64 +/- 3 to 309 +/- 28 mm Hg, p < 0.05). Treatment with 100% oxygen also decreased mean pulmonary artery pressure (56 +/- 3 to 53 +/- 2 mm Hg, p < 0.05) and increased cardiac index (2.1 +/- 0.1 to 2.5 +/- 0.2 L/min/m(2), p < 0.05). Calculated mean pulmonary vascular resistance (PVR) decreased from 14.1 +/- 1.4 to 10.6 +/- 1.0 Wood units (p < 0.05). Vasodilatation with 100% oxygen occurred preferentially in the pulmonary circulation (PVR/systemic vascular resistance, 0.53 +/- 0.04 to 0.48 +/- 0.03; p < 0.05). The magnitude of the PVR response to oxygen therapy was correlated only with decreasing patient age (r = 0.45, p < 0.05). CONCLUSIONS: Treatment with 100% oxygen is a selective pulmonary vasodilator in patients with pulmonary hypertension, regardless of primary diagnosis, baseline oxygenation, or right ventricular function. Development of disease-specific oxygen prescription guidelines warrants consideration.

The six-minute walk test predicts peak oxygen uptake and survival in patients with advanced heart failure.

BACKGROUND: The 6-min walk test (6'WT) is a simple measure of functional capacity and predicts survival in patients with moderate heart failure (HF). METHODS: To assess the role of the 6'WT in the evaluation of patients with advanced HF, 45 patients (age 49 +/- 8 years, mean +/- SD; New York Heart Association class 3.3 +/- 0.6; left ventricular ejection fraction 0.20 +/- 0.06; right ventricular ejection fraction 0.31 +/- 0.11) underwent symptom-limited cardiopulmonary exercise testing and the 6'WT during cardiac transplant evaluation. RESULTS: Mean 6'WT distance ambulated was 310 +/- 100 m and peak oxygen uptake (peak Vo2) was 12.2 +/- 4.5 mL/kg/min. There was a significant correlation between 6'WT distance ambulated and peak Vo2 (r = 0.64, p < 0.001). Multivariate analysis of patient characteristics, resting hemodynamics, and 6'WT results identified the distance ambulated during the 6'WT as the strongest predictor of peak Vo2 (p < 0.001). 6'WT distance ambulated less than 300 m predicted an increased likelihood of death or pretransplant hospital admission for continuous inotropic or mechanical support within 6 months (p = 0.04), but did not predict long-term overall or event-free survival with a mean follow-up of 62 weeks. Peak Vo2 was the best predictor of long-term overall and event-free survival. CONCLUSIONS: In patients with advanced HF evaluated for cardiac transplantation, distance ambulated during the 6'WT predicts (1) peak Vo2 and (2) short-term event-free survival.

Comparison of the effects of nitric oxide, nitroprusside, and nifedipine on hemodynamics and right ventricular contractility in patients with chronic pulmonary hypertension.

STUDY OBJECTIVES: The effects of inhaled nitric oxide (NO) on hemodynamics and right ventricular (RV) contractility were compared with those of nitroprusside and nifedipine in 14 patients with severe chronic pulmonary hypertension. STUDY DESIGN: Micromanometer and balloon-tipped right heart catheterization were performed. Inhaled NO, IV nitroprusside, and sublingual nifedipine were administered sequentially while patients breathed > 90% oxygen. SETTING: Cardiac catheterization laboratory in a tertiary care teaching hospital. PATIENTS: Fourteen patients with severe pulmonary hypertension unrelated to left ventricular dysfunction. MEASUREMENTS AND RESULTS: During NO inhalation, mean systemic arterial pressure (MAP) was unchanged, but pulmonary artery (PA) pressure ([mean +/- SEM] 49 +/- 2 mm Hg vs 44 +/- 2 mm Hg; p < 0.01), pulmonary vascular resistance (PVR; 829 +/- 68 vs 669 +/- 64 dyne x s x cm(-5); p < 0.01) and RV end-diastolic pressure (RVEDP; 12 +/- 1 vs 10 +/- 1 mm Hg; p < 0.01) decreased. Stroke volume index (SVI; 31 +/- 2 vs 35 +/- 3 mL/m(2); p < 0.05) increased, and the first derivative of RV pressure at 15 mm Hg developed pressure (RV +dP/dt at DP15) was unchanged. During nitroprusside administration, MAP decreased (105 +/- 5 vs 76 +/- 5 mm Hg; p < 0.01), PA was unchanged (48 +/- 2 vs 45 +/- 3 mm Hg; p = not significant), and PVR decreased (791 +/- 53 vs 665 +/- 53 dyne x s x cm(-5); p < 0.01). RV +dP/dt at DP15 increased (425 +/- 22 vs 465 +/- 29 mm Hg/s; p < 0.05), but SVI was unchanged. Nifedipine decreased MAP (103 +/- 5 vs 94 +/- 5 mm Hg; p < 0.01), PA and PVR were unchanged, RVEDP increased (12 +/- 1 vs 14 +/- 2 mm Hg; p < 0.01), and RV +dP/dt at DP15 decreased (432 +/- 90 vs 389 +/- 21 mm Hg/s; p < 0.05). CONCLUSIONS: Inhaled NO is a selective pulmonary vasodilator in patients with chronic pulmonary hypertension that improves cardiac performance without altering RV contractility. Nitroprusside caused a similar degree of pulmonary vasodilation. In contrast to inhaled NO, nitroprusside caused systemic hypotension associated with an increase in RV contractility. Acute administration of nifedipine did not cause pulmonary vasodilation, but RVEDP increased and RV contractility decreased.

Evaluation of ischemic heart disease in potential lung transplant recipients.

BACKGROUND: The prevalence of coronary artery disease in potential lung transplant recipients has not been extensively studied. Given the limited donor supply, a high degree of sensitivity for detecting occult disease is essential. METHODS: This retrospective study examined both the clinical indications for coronary angiography and the extent of coronary arteriosclerotic disease in 105 consecutive potential lung transplant candidates. RESULTS: Fifty-one patients (49%) underwent angiography to either exclude asymptomatic atherosclerosis (n = 46) or define the extent of known symptomatic ischemic heart disease (n = 5). The perceived risk of occult disease according to a semiquantitative coronary risk assessment score that included hypertension, hyperlipidemia, diabetes, smoking, a family history of coronary artery disease, and electrocardiographic or echocardiographic abnormalities influenced the decision to perform angiography: 4 of 44 patients (9%) with two or fewer risk factors underwent angiography versus 42 of 56 patients (75%) with more than two risk factors (p < or = 0.05). A higher risk factor score also correlated with angiographic evidence of coronary artery disease. In the 46 patients without symptoms who were studied, two hemodynamically significant but unsuspected coronary lesions were identified. Six other patients without symptoms had noncritical (< 50%) lesions. Among the five patients with angina or a prior myocardial infarction, coronary angiography showed either minimal atherosclerosis (n = 2) or non-life threatening anatomy (n = 3). Angiographic findings did not exclude any patient from transplant listing. CONCLUSION: Coronary angiography appears most useful in patients without symptoms with multiple coronary risk factors and in a subset of patients who might otherwise be excluded from lung transplantation because of a history of symptomatic cardiovascular disease.