Wilfried Mullens

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

OBJECTIVESnTo 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).nnnBACKGROUNDnReduced cardiac output is traditionally believed to be the main determinant of WRF in patients with ADHF.nnnMETHODSnA 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.nnnRESULTSnIn 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.nnnCONCLUSIONSnVenous congestion is the most important hemodynamic factor driving WRF in decompensated patients with advanced heart failure.

Tissue Doppler Imaging in the Estimation of Intracardiac Filling Pressure in Decompensated Patients With Advanced Systolic Heart Failure

Background— The ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity (E/Ea) has been correlated with pulmonary capillary wedge pressure (PCWP) in a wide variety of cardiac conditions. The objective of this study was to determine the reliability of mitral E/Ea for predicting PCWP in patients admitted for advanced decompensated heart failure. Methods and Results— Prospective consecutive patients with advanced decompensated heart failure (ejection fraction ≤30%, New York Heart Association class III to IV symptoms) underwent simultaneous echocardiographic and hemodynamic evaluation on admission and after 48 hours of intensive medical therapy. A total of 106 patients were included (mean age, 57±12 years; ejection fraction, 24±8%; PCWP, 21±7 mm Hg; mitral E/Ea ratio, 20±12). No correlation was found between mitral E/Ea ratio and PCWP, particularly in those with larger left ventricular volumes, more impaired cardiac indexes, and the presence of cardiac resynchronization therapy. Overall, the mitral E/Ea ratio was similar among patients with PCWP >18 and ≤18 mm Hg, and sensitivity and specificity for mitral E/Ea ratio >15 to identify a PCWP >18 mm Hg were 66% and 50%, respectively. Contrary to prior reports, we did not observe any direct association between changes in PCWP and changes in mitral E/Ea ratio. Conclusion— In decompensated patients with advanced systolic heart failure, tissue Doppler–derived mitral E/Ea ratio may not be as reliable in predicting intracardiac filling pressures, particularly in those with larger LV volumes, more impaired cardiac indices, and the presence of cardiac resynchronization therapy.

Insights From a Cardiac Resynchronization Optimization Clinic as Part of a Heart Failure Disease Management Program

OBJECTIVESnOur aim was to determine the feasibility and value of a protocol-driven approach to patients with cardiac resynchronization therapy (CRT) who did not exhibit a positive response long after implant.nnnBACKGROUNDnUp to one-third of patients with advanced heart failure do not exhibit a positive response to CRT.nnnMETHODSnA total of 75 consecutive ambulatory patients with persistent advanced heart failure symptoms and/or adverse reverse remodeling and CRT implanted >6 months underwent a comprehensive protocol-driven evaluation to determine the potential reasons for a suboptimal response. Recommendations were made to maximize the potential of CRT, and adverse events were documented.nnnRESULTSnAll patients (mean left ventricular [LV] ejection fraction 23 +/- 9%, LV end-diastolic volume 275 +/- 127 ml) underwent evaluation. Eighty-eight percent of patients had significantly better echocardiographic indexes of LV filling and LV ejection with optimal setting of their CRT compared with a temporary VVI back-up setting. Most patients had identifiable reasons for suboptimal response, including inadequate device settings (47%), suboptimal medical treatment (32%), arrhythmias (32%), inappropriate lead position (21%), or lack of baseline dyssynchrony (9%). Multidisciplinary recommendations led to changes in device settings and/or other therapy modifications in 74% of patients and were associated with fewer adverse events (13% vs. 50%, odds ratio: 0.2 [95% confidence interval: 0.07 to 0.56], p = 0.002) compared with those in which no recommendation could be made.nnnCONCLUSIONSnRoutine protocol-driven approach to evaluate ambulatory CRT patients who did not exhibit a positive response is feasible, and changes in device settings and/or other therapies after multidisciplinary evaluation may be associated with fewer adverse events.

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

OBJECTIVESnThis 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).nnnBACKGROUNDnElevated 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.nnnMETHODSnForty 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.nnnRESULTSnIn 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.nnnCONCLUSIONSnElevated 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

OBJECTIVESnThis 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.nnnBACKGROUNDnInotropic therapy has been predominantly used in the management of patients with ADHF presenting with low cardiac output.nnnMETHODSnWe 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.nnnRESULTSnCompared 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).nnnCONCLUSIONSnIn 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.

Right Ventricular Response to Intensive Medical Therapy in Advanced Decompensated Heart Failure

Background—Right ventricular (RV) systolic dysfunction is a strong predictor of adverse outcomes in heart failure, yet quantitatively assessing the impact of therapy on this condition is difficult. Our objective was to compare the clinical significance of changes in RV echocardiographic indices in response to intensive medical treatment in patients admitted to the hospital with acute decompensated heart failure (ADHF). Methods and Results—Serial comprehensive echocardiography was performed in 62 consecutive patients with ADHF, and adverse events (death, cardiac transplantation, assist device, heart failure rehospitalization) were prospectively documented. RV peak systolic strain was assessed using speckle-tracking longitudinal strain analysis as the average of the basal, mid-, and apical segment of the RV free wall. Other conventional parameters of RV function (RV fractional area change, RV myocardial performance index, tricuspid annular peak systolic excursion, and tissue Doppler peak tricuspid annular systolic velocity) were measured for comparison. In our study cohort [left ventricular ejection fraction, 26±10%; cardiac index, 2.0±0.6 L/(min · m2)], overall mean RV peak systolic strain was −14±4% at baseline and −15±4% at 48 to 72 hours (P=0.27). Among all the RV functional indices measured, only RV peak systolic strain at 48 to 72 hours was associated with adverse events (P=0.02). In particular, improvement in RV peak systolic strain after intensive medical treatment was associated with lower adverse events in this patient population (26% versus 78%; hazard ratio, 0.13; 95% CI, 0.02 to 0.84; P=0.02). Conclusion—Dynamic improvement in RV mechanics in response to intensive medical therapy was associated with lower long-term adverse events in patients with ADHF than in patients not showing improvement.

Persistent Hemodynamic Benefits of Cardiac Resynchronization Therapy With Disease Progression in Advanced Heart Failure

OBJECTIVESnOur aim was to determine the potential hemodynamic contributions of cardiac resynchronization therapy (CRT) in patients admitted for advanced decompensated heart failure.nnnBACKGROUNDnCRT restores synchrony of the heart resulting in hemodynamic support that can facilitate the reversal of left ventricular (LV) remodeling in some patients.nnnMETHODSnA total of 40 consecutive patients with advanced decompensated heart failure and CRT implanted >3 months, admitted due to hemodynamic derangements, underwent simultaneous comprehensive echocardiographic and invasive hemodynamic evaluation under different CRT settings.nnnRESULTSnAll patients (mean LV ejection fraction 22 +/- 7%, LV end-diastolic volume 323 +/- 140 ml, 40% ischemic) had experienced progressive cardiac remodeling despite adequate LV lead positions and continuous biventricular pacing. A significant worsening of hemodynamics was observed immediately when CRT was programmed OFF in the majority (88%) of patients (systolic blood pressure: 105 +/- 12 mm Hg to 98 +/- 13 mm Hg; pulmonary capillary wedge pressure: 17 +/- 6 mm Hg to 21 +/- 7 mm Hg; cardiac output: 4.6 +/- 1.4 l/min.m(2) to 4.0 +/- 1.1 l/min.m(2); all p < 0.001). Worsening of hemodynamics coincided with reappearance of significant electrical (QRS width 161 +/- 29 ms to 202 +/- 39 ms, p < 0.001) and intraventricular mechanical dyssynchrony (15 +/- 26 ms to 57 +/- 41 ms, p < 0.001), together with a significant reduction in diastolic filling time (377 +/- 138 ms to 300 +/- 118 ms, p < 0.001).nnnCONCLUSIONSnDespite progressive cardiac remodeling and decompensation, chronic CRT continues to provide hemodynamic augmentation in the failing heart in most patients. Our data suggest that disease progression may not be explained by diminished beneficial hemodynamic contributions of successful resynchronization.

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.

Mechanical dyssynchrony in advanced decompensated heart failure: Relation to hemodynamic responses to intensive medical therapy

BACKGROUNDnIn patients with heart failure, the degree of intraventricular mechanical dyssynchrony (intra-VMD) at baseline may predict reversal of cardiac remodeling with cardiac resynchronization therapy (CRT).nnnOBJECTIVEnThe purpose of this study was to determine the prevalence and clinical significance of intra-VMD in patients admitted for advanced decompensated heart failure (ADHF).nnnMETHODSnWe prospectively enrolled 50 patients with ADHF without previous CRT implantation who had been admitted to a specialized heart failure intensive care unit because of hemodynamic derangements. All patients underwent comprehensive echocardiographic evaluation within 12 hours of admission and after 48 hours from baseline evaluation after intensive medical therapy. Intra-VMD was assessed by the opposing wall time-to-peak myocardial velocity intervals in a four-segment model using color-tissue Doppler imaging.nnnRESULTSnIn our study cohort (mean age 57 +/- 11 years, left ventricular ejection fraction 26 +/- 10%, QRS width 127 +/- 31 ms, cardiac index 2.0 +/- 0.6 L/min/m(2)), significant intra-VMD (>or=65 ms) was present in 44% of subjects at baseline, and 56% of patients presented with QRS >120 ms. There was no correlation between QRS width and extent of intra-VMD. Intensive medical therapy was associated with a significant reduction in intra-VMD (85 +/- 23 ms vs. 39 +/- 19 ms; P <.001). Significant hemodynamic improvement in cardiac index, filling pressures, and systemic and pulmonic vascular resistance was seen only in patients with intra-VMD.nnnCONCLUSIONnA substantial subset of patients admitted with ADHF and hemodynamic derangements demonstrate evidence of intra-VMD, which is reduced at follow-up and independent of underlying QRS width. Nevertheless, the presence of significant intra-VMD is associated with a more reversible hemodynamic profile.