Zuheir Abrahams

Importance of Venous Congestion for Worsening of Renal Function in Advanced Decompensated Heart Failure

OBJECTIVES To determine whether venous congestion, rather than impairment of cardiac output, is primarily associated with the development of worsening renal function (WRF) in patients with advanced decompensated heart failure (ADHF). BACKGROUND Reduced cardiac output is traditionally believed to be the main determinant of WRF in patients with ADHF. METHODS A total of 145 consecutive patients admitted with ADHF treated with intensive medical therapy guided by pulmonary artery catheter were studied. We defined WRF as an increase of serum creatinine >/=0.3 mg/dl during hospitalization. RESULTS In the study cohort (age 57 +/- 14 years, cardiac index 1.9 +/- 0.6 l/min/m(2), left ventricular ejection fraction 20 +/- 8%, serum creatinine 1.7 +/- 0.9 mg/dl), 58 patients (40%) developed WRF. Patients who developed WRF had a greater central venous pressure (CVP) on admission (18 +/- 7 mm Hg vs. 12 +/- 6 mm Hg, p < 0.001) and after intensive medical therapy (11 +/- 8 mm Hg vs. 8 +/- 5 mm Hg, p = 0.04). The development of WRF occurred less frequently in patients who achieved a CVP <8 mm Hg (p = 0.01). Furthermore, the ability of CVP to stratify risk for development of WRF was apparent across the spectrum of systemic blood pressure, pulmonary capillary wedge pressure, cardiac index, and estimated glomerular filtration rates. CONCLUSIONS Venous congestion is the most important hemodynamic factor driving WRF in decompensated patients with advanced heart failure.

Elevated intra-abdominal pressure in acute decompensated heart failure: a potential contributor to worsening renal function?

OBJECTIVES This study sought to determine whether changes in intra-abdominal pressure (IAP) with aggressive diuretic or vasodilator therapy are associated with improvement in renal function in acute decompensated heart failure (ADHF). BACKGROUND Elevated IAP (>or=8 mm Hg) is associated with intra-abdominal organ dysfunction. There is potential for ascites and visceral edema causing elevated IAP in patients with ADHF. METHODS Forty consecutive patients admitted to a specialized heart failure intensive care unit for management of ADHF with intensive medical therapy were studied. The IAP was measured using a simple transvesical technique at time of admission and before removal of the pulmonary artery catheter. RESULTS In our study cohort (mean age 59 +/- 13 years, mean left ventricular ejection fraction 19 +/- 9%, baseline serum creatinine 2.0 +/- 0.9 mg/dl), the mean baseline IAP was 8 +/- 4 mm Hg, with 24 (60%) patients having elevated IAP. Elevated IAP was associated with worse renal function (p = 0.009). Intensive medical therapy resulted in improvement in both hemodynamic measurements and IAP. A strong correlation (r = 0.77, p < 0.001) was observed between reduction in IAP and improved renal function in patients with baseline elevated IAP. However, changes in IAP or renal function did not correlate with changes in any hemodynamic variable. CONCLUSIONS Elevated IAP is prevalent in patients with ADHF and is associated with impaired renal function. In the setting of intensive medical therapy for ADHF, changes in IAP were better correlated with changes in renal function than any hemodynamic variable.

Sodium Nitroprusside for Advanced Low-Output Heart Failure

OBJECTIVES This study was designed to examine the safety and efficacy of sodium nitroprusside (SNP) for patients with acute decompensated heart failure (ADHF) and low-output states. BACKGROUND Inotropic therapy has been predominantly used in the management of patients with ADHF presenting with low cardiac output. METHODS We reviewed all consecutive patients with ADHF admitted between 2000 and 2005 with a cardiac index < or =2 l/min/m(2) for intensive medical therapy including vasoactive drugs. Administration of SNP was chosen by the attending clinician, nonrandomized, and titrated to a target mean arterial pressure of 65 to 70 mm Hg. RESULTS Compared with control patients (n = 97), cases treated with SNP (n = 78) had significantly higher mean central venous pressure (15 vs. 13 mm Hg; p = 0.001), pulmonary capillary wedge pressure (29 vs. 24 mm Hg; p = 0.001), but similar demographics, medications, and renal function at baseline. Use of SNP was not associated with higher rates of inotropic support or worsening renal function during hospitalization. Patients treated with SNP achieved greater improvement in hemodynamic measurements during hospitalization, had higher rates of oral vasodilator prescription at discharge, and had lower rates of all-cause mortality (29% vs. 44%; odds ratio: 0.48; p = 0.005; 95% confidence interval: 0.29 to 0.80) without increase in rehospitalization rates (58% vs. 56%; p = NS). CONCLUSIONS In patients with advanced, low-output heart failure, vasodilator therapy used in conjunction with optimal current medical therapy during hospitalization might be associated with favorable long-term clinical outcomes irrespective of inotropic support or renal dysfunction and remains an excellent therapeutic choice in hospitalized ADHF patients.

Prompt Reduction in Intra-Abdominal Pressure Following Large-Volume Mechanical Fluid Removal Improves Renal Insufficiency in Refractory Decompensated Heart Failure

BACKGROUND Our group recently reported that elevated intra-abdominal pressure (IAP, defined as > or = 8 mm Hg) can be associated with renal dysfunction in patients with advanced decompensated heart failure (ADHF). We hypothesize that in the setting of persistently elevated IAP and progressive renal insufficiency refractory to intensive medical therapy, mechanical fluid removal can be associated with improvements in IAP and renal function. METHODS AND RESULTS The renal and hemodynamic profiles of 9 consecutive, volume-overloaded subjects with ADHF and elevated IAP, refractory to intensive medical therapy, were prospectively collected. All subjects experienced progressive elevation of serum creatinine and IAP in response to intravenous loop diuretics. Within 12 hours after mechanical fluid removal via paracentesis (n = 5, mean volume removed 3187 +/- 1772 mL) or ultrafiltration (n = 4, mean volume removed 1800 +/- 690 mL), there was a significant reduction in IAP (from 13 +/- 4 mm Hg to 7 +/- 2 mm Hg, P = .001), with corresponding improvement in renal function (serum creatinine from 3.4 +/- 1.4 mg/dL to 2.4 +/- 1.1 mg/dL, P = .01) without significantly altering any hemodynamic measurement. CONCLUSION In volume-overloaded patients admitted with ADHF refractory to intensive medical therapy, we observed a reduction of otherwise persistently elevated IAP with corresponding improvement in renal function after mechanical fluid removal.

Prognostic Role of Pulmonary Arterial Capacitance in Advanced Heart Failure

Background—Right ventricular (RV) dysfunction frequently occurs and independently prognosticates in left-sided heart failure. It is not clear which RV afterload measure has the greatest impact on RV function and prognosis. We examined the determinants, prognostic role, and response to treatment of pulmonary arterial capacitance (PAC, ratio of stroke volume over pulmonary pulse pressure), in relation to pulmonary vascular resistance (PVR) in heart failure. Methods and Results—We reviewed 724 consecutive patients with heart failure who underwent right heart catheterization between 2000 and 2005. Changes in PAC were explored in an independent cohort of 75 subjects treated for acute decompensated heart failure. PAC showed a strong inverse relation with PVR (r=−0.64) and wedge pressure (r=−0.73), and provides stronger prediction of significant RV failure than PVR (area under the curve ROC 0.74 versus 0.67, respectively, P=0.003). During a mean follow-up of 3.2±2.2 years, both lower PAC (P<0.0001) and higher PVR (P<0.0001) portend more adverse clinical events (all-cause mortality and cardiac transplantation). In multivariate analysis, PAC (but not PVR) remains an independent predictor (Hazard ratio=0.92 [95% CI: 0.84–1.0, P=0.037]). Treatment of heart failure resulted in a decrease in PVR (270±165 to 211±88 dynes·s–1·cm–5, P=0.002), a larger increase in PAC (1.65±0.64 to 2.61±1.42 mL/mm Hg, P<0.0001), leading to an increase in pulmonary arterial time constant (PVR×PAC) (0.29±0.12 to 0.37±0.15 second, P<0.0001). Conclusions—PAC bundles the effects of PVR and left-sided filling pressures on RV afterload, explaining its strong relation with RV dysfunction, poor long-term prognosis, and response to therapy.

Usefulness of Isosorbide Dinitrate and Hydralazine as Add-on Therapy in Patients Discharged for Advanced Decompensated Heart Failure

Data supporting the use of oral isosorbide dinitrate and/or hydralazine (I/H) as add-on therapy to standard neurohormonal antagonists in advanced decompensated heart failure (ADHF) are limited, especially in the non-African-American population. Our objective was to determine if addition of I/H to standard neurohormonal blockade in patients discharged from the hospital with ADHF is associated with improved hemodynamic profiles and improved clinical outcomes. We reviewed consecutive patients with ADHF admitted from 2003 to 2006 with a cardiac index < or =2.2 L/min/m(2) admitted for intensive medical therapy. Patients discharged with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers (control group) were compared with those receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers plus I/H (I/H group). The control (n = 97) and I/H (n = 142) groups had similar demographic characteristics, baseline blood pressure, and renal function. Patients in the I/H group had a significantly higher estimated systemic vascular resistance (1,660 vs 1,452 dynes/cm(5), p <0.001) and a lower cardiac index (1.7 vs 1.9 L/min/m(2), p <0.001) on admission. The I/H group achieved a similar decrease in intracardiac filling pressures and discharge blood pressures as controls, but had greater improvement in cardiac index and systemic vascular resistance. Use of I/H was associated with a lower rate of all-cause mortality (34% vs 41%, odds ratio 0.65, 95% confidence interval 0.43 to 0.99, p = 0.04) and all-cause mortality/heart failure rehospitalization (70% vs 85%, odds ratio 0.72, 95% confidence interval 0.54 to 0.97, p = 0.03), irrespective of race. In conclusion, the addition of I/H to neurohormonal blockade is associated with a more favorable hemodynamic profile and long-term clinical outcomes in patients discharged with low-output ADHF regardless of race.

Tricuspid Regurgitation After Cardiac Transplantation: An Old Problem Revisited

Tricuspid regurgitation (TR) is the most common valvular abnormality after orthotopic heart transplantation (OHT), with a reported incidence of up to 84%, depending on the definition of significant regurgitation and surgical methods of OHT employed. While multiple etiologies are implicated in the development of TR after OHT, endomyocardial biopsy (EMB), performed to detect allograft rejection, is the single most important contributor to significant TR by causing anatomic disruption of the tricuspid valvular structure. Although the clinical course of TR is heterogeneous, hemodynamically significant regurgitation generally leads to progressive right-heart dysfunction and symptoms. In cases refractory to diuretic-based medical therapy, surgical correction of TR has been shown to effectively alleviate the condition and provide symptomatic and organ function improvement. Tricuspid valve repair and replacement are viable surgical options, the application of which often depends on the institutions experience and underlying valve pathology. A non-invasive surveillance technique to detect allograft rejection is on the horizon, and may reduce the number of EMBs performed as well as the procedure-related tissue damage that leads to TR.

Prognostic Evaluation of Ambulatory Patients With Advanced Heart Failure

Previous heart failure (HF) risk models have included clinical and noninvasive variables and have been derived largely from clinical trial databases or decompensated HF registries. The importance of hemodynamic assessment is less established, particularly in ambulatory patients with advanced HF. In this study, 513 consecutive ambulatory patients (mean age 54+/-11 years, mean left ventricular ejection fraction 20+/-9%) with symptomatic HF who underwent diagnostic right-sided cardiac catheterization as part of outpatient assessment from 2000 to 2005 were reviewed. After a total of 1,696 patient-years of follow-up, 139 (27%) patients had died and 116 (23%) had undergone cardiac transplantation. The 1- and 2-year overall survival rates (defined as freedom from death or cardiac transplantation) were 77% and 67%, respectively. Overall, 65% of patients had elevated intracardiac filling pressures, and 40% had cardiac indexes<2.2 L/min/m2. In multivariate analysis, mean pulmonary arterial pressure, cardiac index, and the severity of mitral regurgitation were the 3 strongest predictors of all-cause mortality and cardiac transplantation. Renal dysfunction was also an independent predictor of all-cause mortality. When a clinical model for Cox multivariate analysis of all-cause mortality was compared with a model that also included cardiac index and mean pulmonary arterial pressure, the chi-square score increased from 45 to 69 (p<0.0001). In conclusion, in ambulatory patients with advanced HF, hemodynamic and renal function assessments remain strong independent predictors of all-cause mortality.

Gender Differences in Patients Admitted With Advanced Decompensated Heart Failure

Broad population studies of patients with stable ambulatory heart failure have associated female gender with better age-adjusted survival. This study investigated whether there are gender-specific differences in clinical presentation, response to intensive medical therapy, and outcomes in patients admitted with advanced (cardiac index <2.4 L/min/m(2)) decompensated heart failure (ADHF). We reviewed 278 consecutive patients (age 54 +/- 12 years, cardiac index 1.7 +/- 0.4 L/kg/m(2), pulmonary capillary wedge pressure 26 +/- 9 mm Hg, serum creatinine 1.4 +/- 0.8 mg/dl) with ADHF treated with intensive medical therapy guided by pulmonary artery catheter in a dedicated heart failure intensive care unit from 2000 to 2006. Compared with men (n = 226), women (n = 52) had similar baseline characteristics with the exception of a higher prevalence of nonischemic cause. No differences in medical therapy on admission, during intensive medical therapy, or at discharge were observed. Intensive medical therapy was associated with significant hemodynamic improvement independent of gender. All-cause mortality and heart failure rehospitalization rates were similar between genders. However, adjusted for cause, women with ischemic cardiomyopathy had higher all-cause mortality rates (50% vs 37%, hazard ratio 1.95, 95% confidence interval 0.98 to 3.90, p = 0.05) and those with nonischemic cardiomyopathy had lower all-cause mortality rates (19% vs 40%, hazard ratio 0.40, 95% confidence interval 0.17 to 0.96, p = 0.01) than men. In conclusion, women presenting with ADHF had baseline characteristics and response to therapy similar to men. Overall outcomes were similar between men and women, although subgroup analysis suggested better survival for women with a nonischemic cause.

Conivaptan: Potential Therapeutic Implications in Heart Failure

Conivaptan, a dual vasopressin receptor antagonist, is a member of an emerging class of medications for the treatment of euvolemic hyponatremia. These agents induce a free-water diuresis as compared to the natriuretic effect of loop diuretics and make them an intriguing prospect for the treatment of congestive heart failure. Article also includes recent patents on this topic.