Congestive Heart Failure Trial Research Articles

Implications of Renin-Angiotensin-System Blocker Discontinuation in Advanced Decompensated Heart Failure

Introduction: The impact of renin-angiotensin-system blocker (RASB) use, or lack of, on renal function, blood pressure, and clinical outcomes during treatment for acute decompensated heart failure (ADHF) needs further clarification. Hypothesis: In comparison to patients with RASB use, discontinuing or non-use of a RASB will associate with worsening renal function, hypotension, and adverse long-term outcomes. Methods: Participants with an LVEF ≤ 40% in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization (ESCAPE) trial were included. Mixed effects models compared RASB use on serial serum creatinine and systolic blood pressure (SBP) measurements. Cox-proportional hazard models tested the association between RASB use and outcomes adjusted for age, male sex, potassium, SBP < 140 mmHg and baseline creatinine. Outcomes were validated in an independent ADHF cohort admitted to the Cleveland Clinic (n = 253). Results: Patients in the ESCAPE cohort (N = 402, age 56 ± 14 y, 74% male, 49% ischemic, LVEF 19 ± 6 %, and creatinine 1.5 ± 0.6 mg/dL) were separated into 4 groups based on RASB use at baseline and discharge: continued (n = 316), discontinued (n = 21), initiated (n = 42), and non-use (n = 23). RASB discontinuation or non-use was associated with higher serial serum creatinine levels than RASB continuation or initiation (P < .001 for both) but not with SBP measurements (P > .3 for both). In comparison to RASB continuation, RASB discontinuation and non-use was associated with ~75% increased risk of a 180-day composite of death, transplant, or re-hospitalization (HR 1.87, 95% CI 1.09–3.20, P = .02 and HR 1.72 1.04–2.82, P = .03, respectively, Figure A). Similarly in the validation cohort, RASB discontinuation and non-use versus RASB continuation were associated with ~65% and ~75% risk for 180-day death, transplant, LVAD, or re-hospitalization (HR 1.85, 95% CI 1.02–3.34, P = .04 and HR 95% CI 1.64, 95% CI 1.03–2.5, P = .04, respectively, Figure B). Conclusions: In comparison to RASB continuation, RASB discontinuation and non-use was associated with higher baseline and serial serum creatinine levels during treatment for ADHF, but not with changes in SBP. Furthermore, RASB discontinuation and non-use in ADHF were associated with an increased risk of adverse clinical outcomes. Given the persistent elevation of serum creatinine and unchanged blood pressures these findings question the practice of withholding RASB in the setting of renal insufficiency and marginal blood pressure in ADHF.

Clinical Impact of Changes in Hemodynamic Indices of Contractile Function During Treatment of Acute Decompensated Heart Failure

BackgroundThe objective of this work was to determine the impact of improving right ventricular versus left ventricular stroke work indexes (RVSWI vs LVSWI) during therapy for acute decompensated heart failure (ADHF). Methods and ResultsCox proportional hazards regression and logistic regression were used to analyze key factors associated with outcomes in 175 patients (mean age 56.7 ± 13.6 years, 29.1% female) with hemodynamic data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial. In this cohort, 28.6% and 69.7%, respectively, experienced the outcomes of death, transplantation, or ventricular assist device implantatation (DVADTX) and DVADTX or HF rehospitalization (DVADTXHF) during 6 months of follow-up. Increasing RVSWI (ΔRVSWI) from baseline to discharge was associated with a decrease in DVADTXHF (hazard ratio [HR] 0.923, 95% confidence interval [CI] 0.871–0.979) per 0.1 mm Hg⋅L⋅m−2 increase); however, increasing LVSWI (ΔLVSWI) had only a nonsignificant association with decreased DVADTXHF (P = .11) In a multivariable model, patients with ΔRVSWI ≤1.07 mm Hg⋅L⋅m−2 and ΔLVSWI ≤4.57 mm Hg⋅L⋅m−2 had a >2-fold risk of DVADTXHF (HR 2.05, 95% CI 1.23–3.41; P = .006). ConclusionCompared with left ventricular stroke work, increasing right ventricular stroke work during treatment of ADHF was associated with better outcomes. The results promise to inform optimal hemodynamic targets for ADHF.

Prognostic Significance of Discharge Hyponatremia in Heart Failure Patients With Normal Admission Sodium (from the ESCAPE Trial)

Hyponatremia in acute decompensated heart failure (HF) is indicative of a poor prognosis and predicts morbidity and mortality. We explored the predictive utility of hyponatremia at the time of hospital discharge among HF patients with normal admission sodium (Na). Characteristics and outcomes of HF patients enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial, who had normal Na on admission, were compared between those who were hyponatremic (Na <135 meq/L) or normonatremic on discharge. Three hundred six patients with normal admission Na had either hyponatremia (n= 86) or normal Na (n= 220) on discharge. Compared with patients with normal Na on discharge, hyponatremic patients were younger (p= 0.004), with lower discharge systolic (p <0.001) and diastolic (p= 0.004) blood pressure, higher discharge blood urea nitrogen (p= 0.011) despite similar creatinine (p= 0.566), lower ejection fraction (p= 0.007), and higher left ventricular end-diastolic (p= 0.028) and end-systolic (p= 0.007) dimensions. Despite comparable congestion on hospital admission, patients with discharge hyponatremia had a higher degree of decongestion throughout hospitalization evident in the significantly greater admission to discharge weight loss (p=0.044) and admission to discharge reduction in inferior vena cava diameter (p=0.014). Despite longer initial hospitalization (p= 0.004), total duration in hospital at 30 days (p= 0.004) and 6 months (p= 0.045), there were no significant differences between patients with discharge hyponatremia versus normal Na on discharge regarding rehospitalization (p= 0.386), all-cause mortality (p= 0.440), and composite of death, cardiac rehospitalization, and cardiac transplant (p= 0.799), all up to 6-month following randomization. Restricted cubic spline analysis also showed no significant relationships between discharge Na and the aforementioned 3 outcomes. Cox proportional hazards regressions showed that discharge hyponatremia did not significantly predict any of the 3 outcomes after adjustment for imbalances at baseline. Among patients with discharge hyponatremia, a poor outcome was more likely if they were also hyponatremic on admission: the composite end point occurred in 69.2% of those also hyponatremic on admission versus 51.2% of those with normal Na on admission but decreased Na on discharge (p= 0.045). Because the median discharge Na level in the discharge hyponatremia group was 132 meq/L, our findings suggest a benign nature of mild discharge hyponatremia in HF patients with normal admission Na.

Ratio of Systolic Blood Pressure to Right Atrial Pressure, a Novel Marker to Predict Morbidity and Mortality in Acute Systolic Heart Failure

Congestion is the main contributor to heart failure (HF) morbidity and mortality. We assessed the combined role of congestion and decreased forward flow in predicting morbidity and mortality in acute systolic HF. The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial data set was used to determine if the ratio of simultaneously measured systolic blood pressure (SBP)/right atrial pressure (RAP) on admission predicted HF rehospitalization and 6-month mortality. One hundred ninety-five patients (mean age 56.5years, 75% men) who received pulmonary artery catheterization were studied. The RAP, SBP, and SBP/RAP had an area under the curve (AUC) of 0.593 (p= 0.0205), 0.585 (p= 0.0359), and 0.621 (p= 0.0026), respectively, in predicting HF rehospitalization. The SBP/RAP was a superior marker of HF rehospitalization compared with RAP alone (difference in AUC 0.0289, p= 0.0385). The optimal criterion of SBP/RAP <11 provided the highest combined sensitivity (77.1%) and specificity (50.9%) in predicting HF rehospitalization. The SBP/RAP had an AUC 0.622, p= 0.0108, and a cut-off value of SBP/RAP <8 had a sensitivity of 61.9% and specificity 64.1% in predicting mortality. Multivariate analysis showed that an SBP/RAP <11 independently predicted rehospitalization for HF (estimated odds ratio 3.318, 95% confidence interval 1.692 to 6.506, p= 0.0005) and an SBP/RAP <8 independently predicted mortality (estimated hazard ratio 2.025, 95% confidence interval 1.069 to 3.833, p= 0.030). In conclusion, SBP/RAP ratio is a marker that identifies a spectrum of complications after hospitalization of patients with decompensated systolic HF, starting with increased incidence of HF rehospitalization at SBP/RAP <11 to increased mortality with SBP/RAP <8.

Abstract 13478: Increased Changes in Calculated Plasma Volume Predict Poor Prognosis in Heart Failure

Introduction: Plasma volume (PV) is contracted in stable patients with heart failure (HF) due to the effects of therapy aimed at reducing congestion, while increased PV can complicate the progression of HF. We sought to determine the prognostic implications of calculated PV in patients with HF. Hypothesis: Increased changes in PV predict mortality after hospital discharge in HF patients. Methods: We used data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial for our analysis. The outcome in our study was all-cause mortality after hospital discharge. We used the hemoglobin and 1-hematocrit method to calculate the percentage change in PV (%ΔPV) between baseline and hospital discharge. We used Kaplan-Meier curves to compare 180-day (6-month) survival for patients that had increased %ΔPV to patients that had reduced or no %ΔPV. We used Cox proportional hazard regression analysis to adjust for age and gender, and obtained adjusted hazard ratios (AHR) and 95% confidence intervals (CI) of the association between mortality and %ΔPV. Results: There were 315 patients with complete data on PV that were included, of which 231 (73.3%) were men. The mean age was 56 years (range: 22-88 years). Of these 315 patients, 59 (18.7%) died after discharge during 4365.3 person days (PDs) of observation from baseline; mortality incidence rate was 1.4 deaths/100 PDs. Patients with reduced or no %ΔPV were more likely to survive than those with increased %ΔPV at the end of follow-up (Log rank test p=0.0042). Patients with increased %ΔPV had a statistically significant increased risk of mortality compared to patients with reduced or no %ΔPV (AHR 1.9, 95% CI: 1.1-3.2). Conclusions: Increased changes in calculated plasma volume predicted 6-month mortality in HF patients enrolled in the ESCAPE trial. Plasma volume changes during hospitalization for acute decompensated HF could guide risk stratification and prognosis in HF patients.

Usefulness of the Sum of Pulmonary Capillary Wedge Pressure and Right Atrial Pressure as a Congestion Index that Prognosticates Heart Failure Survival (from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness Trial)

In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial, use of a pulmonary artery catheter did not significantly affect advanced heart failure outcomes. However, the success of achieving the targeted hemodynamic goals of pulmonary capillary wedge pressure (PCWP) of 15mm Hg and right atrial pressure (RAP) of 8mm Hg and the association of these goals with clinical outcomes were not addressed. Furthermore, goals with 2 independent variables, PCWP and RAP, left room for uncertainties. We assessed the ability of a single hemodynamic target to achieve a threshold sum of PCWP and RAP as a predictor of all-cause mortality, death-or-transplantation (DT), or death-or-rehospitalization (DR) at 6months in the pulmonary artery catheter-guided treatment arm of ESCAPE (n= 206). Patients with a posttreatment PCWP+ RAP of <30mm Hg had characteristics similar to those of the population who achieved the ESCAPE hemodynamic goals. This group had 8.7% mortality, 13.0% DT, and 58.7% DR at 6months. The contrasting cohort with PCWP+ RAP of ≥30mm Hg had 45.3% mortality, 54.7% DT, and 84.9% DR at 6months, with greater relative risk (RR) of death (RR 5.76), DT (RR 4.92), and DR (RR 1.80) and higher prevalence of jugular venous pulsation, edema, hepatomegaly, and ascites at admission and discharge. In conclusion, PCWP+ RAP of 30mm Hg posttreatment, obtained early in the index hospitalization, may represent as a simple congestion index that has prognostic value for heart failure survival and readmission rates at 6months and as a warning signal for more aggressive intervention, thus warranting further validation.

Decreased Pulmonary Arterial Proportional Pulse Pressure After Pulmonary Artery Catheter Optimization for Advanced Heart Failure Is Associated With Adverse Clinical Outcomes

BackgroundThis study evaluated the novel index pulmonary arterial proportional pulse pressure (PAPP) in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. Methods and ResultsMultivariable Cox proportional hazards and logistical regression were used to model 6-month death; death, transplantation, or left ventricular assist device (DTLVAD); and DTLVAD or heart failure rehospitalization (DTLVADHF) with respect to PAPP. Among 175 patients with final hemodynamic data, 15.5% and 33.9%, respectively, died in optimal PAPP (PAPP >0.50) and nonoptimal PAPP (PAPP ≤0.50) groups (P = .008), and PAPP was independently associated with death, DTLVAD, and DTLVADHF (P < .01 for all outcomes). The hypothesized logistic regression model with pulmonary capillary wedge pressure, creatinine, and nonoptimal PAPP had an area under the curve of 0.818 (P < .0001) for death. Furthermore, PAPP as a continuous variable was the most powerful predictor of DTLVADHF (hazard ratio 0.793 per 0.1 increase in PAPP [95% confidence interval 0.659–0.955], chi square 8.80; P = .01) in the Cox model, with no other clinical, laboratory, or hemodynamic parameters significant after adjustment for PAPP. ConclusionsPAPP, a novel parameter for right-sided proportional pulse pressure, is an independent and powerful predictor of adverse clinical outcomes in advanced HF. Increased PAPP promises to be a useful therapeutic target in patients with pulmonary arterial pressure assessment.

Abstract 16043: Pulmonary Artery Proportional Pulse Pressure Predicts Adverse Clinical Outcomes in Advanced Heart Failure

Introduction: There is increasing interest in ventriculo-arterial hemodynamics in heart failure (HF). Hypothesis: Based on the normal physiological distribution of Pulmonary artery (PA) systolic pressure (PASP) being more than twice the PA diastolic pressure (PADP), we hypothesized that PA proportional pressure (PAPP), defined as (PASP-PADP)/PASP, would be associated with clinical outcomes using data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. Methods: Multivariable Cox proportional hazards and logistic regression was performed using independent covariates of creatinine at discharge, PAPP, and pulmonary capillary wedge pressure (PCWP) (based on final hemodynamic measurement) for the 6-month outcome of death, transplant, left ventricular assist device (LVAD), or rehospitalization (DTxLVADHF), as well as secondary outcomes of death alone and death, transplant, or LVAD (DTxLVAD). Results: Among n=175 patients, there were 110 (62.9 %) and 65 (37.1%), respectively, with optimal PAPP (&gt; 0.50) and non-optimal PAPP (&lt;=0.50). During 6 months of follow-up, 15.5% and 33.9%, respectively, died in these 2 groups (p=0.008). In Cox models adjusted for final PCWP and creatinine at discharge, an increase of 0.10 in the final PAPP (continuous variable, range 0-1) was associated with a 26.4% reduction in DTxLVADHF (HR 0.736, 95% CI = 0.592-0.913). Furthermore, non-optimal PAPP status was associated with increased risk for the outcomes of DTxLVADHF, DTxLVAD, and death alone with hazard ratios of 1.82 (95% CI 1.22-2.73), 2.09 (95% CI 1.09-4.02), and 2.72 (95% CI 1.29-5.72), respectively. The AUC obtained with multivariable logistic regression for the outcome of death with the model containing final PAPP, final PCWP, and creatinine at discharge was 0.804 (p&lt;0.0001), with p&lt; 0.05 for the odds ratios of each covariate in the model. Conclusions: PAPP at final hemodynamic measurement in patients undergoing hemodynamically guided therapy for ADHF is strongly associated with adverse clinical outcomes even after adjustment for final PCWP and creatinine at discharge. These results have important clinical implications for hemodynamic targets in patients treated for ADHF.

Severity of Remodeling, Myocardial Viability, and Survival in Ischemic LV Dysfunction After Surgical Revascularization

ObjectivesThis study sought to test the hypothesis that end-systolic volume (ESV), as a marker of severity of left ventricular (LV) remodeling, influences the relationship between myocardial viability and survival in patients with coronary artery disease and LV systolic dysfunction. BackgroundRetrospective studies of ischemic LV dysfunction suggest that the severity of LV remodeling determines whether myocardial viability predicts improved survival with surgical compared with medical therapy, with coronary artery bypass grafting (CABG) only benefitting patients with viable myocardium who have smaller ESV. However, this has not been tested prospectively. MethodsInteractions of end-systolic volume index (ESVI), myocardial viability, and treatment with respect to survival were assessed in patients in the prospective randomized STICH (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease) trial of CABG versus medical therapy who underwent viability assessment (n = 601; age 61 ± 9 years; ejection fraction ≤35%), with a median follow-up of 5.1 years. Median ESVI was 84 ml/m2. Viability was assessed by single-photon emission computed tomography or dobutamine echocardiography using pre-specified criteria. ResultsMortality was highest among patients with larger ESVI and nonviability (p < 0.001), but no interaction was observed between ESVI, viability status, and treatment assignment (p = 0.491). Specifically, the effect of CABG versus medical therapy in patients with viable myocardium and ESVI ≤84 ml/m2 (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.56 to 1.29) was no different than in patients with viability and ESVI >84 ml/m2 (HR: 0.87; 95% CI: 0.57 to 1.31). Other ESVI thresholds yielded similar results, including ESVI ≤60 ml/m2 (HR: 0.87; 95% CI: 0.44 to 1.74). ESVI and viability assessed as continuous rather than dichotomous variables yielded similar results (p = 0.562). ConclusionsAmong patients with ischemic cardiomyopathy, those with greater LV ESVI and no substantial viability had worse prognosis. However, the effect of CABG relative to medical therapy was not differentially influenced by the combination of these 2 factors. Lower ESVI did not identify patients in whom myocardial viability predicted better outcome with CABG relative to medical therapy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595)

Tolvaptan in Patients Hospitalized With Acute Heart Failure: Rationale and Design of the TACTICS and the SECRET of CHF Trials.

Congestion is a primary reason for hospitalization in patients with acute heart failure (AHF). Despite inpatient diuretics and vasodilators targeting decongestion, persistent congestion is present in many AHF patients at discharge and more severe congestion is associated with increased morbidity and mortality. Moreover, hospitalized AHF patients may have renal insufficiency, hyponatremia, or an inadequate response to traditional diuretic therapy despite dose escalation. Current alternative treatment strategies to relieve congestion, such as ultrafiltration, may also result in renal dysfunction to a greater extent than medical therapy in certain AHF populations. Truly novel approaches to volume management would be advantageous to improve dyspnea and clinical outcomes while minimizing the risks of worsening renal function and electrolyte abnormalities. One effective new strategy may be utilization of aquaretic vasopressin antagonists. A member of this class, the oral vasopressin-2 receptor antagonist tolvaptan, provides benefits related to decongestion and symptom relief in AHF patients. Tolvaptan may allow for less intensification of loop diuretic therapy and a lower incidence of worsening renal function during decongestion. In this article, we summarize evidence for decongestion benefits with tolvaptan in AHF and describe the design of the Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure Study (TACTICS) and Study to Evaluate Challenging Responses to Therapy in Congestive Heart Failure (SECRET of CHF) trials.

Towards destination therapy with left ventricular assist devices in Japan.

Medical and electrical therapies for systolic heart failure have improved outcomes and altered the natural history of the disease. Although heart transplantation remains the most successful treatment option for patients with advanced heart failure refractory for these treatment, cardiac transplantation is available for only a minority of patients because of the lack of suitable donor hearts. As a consequence of limited donor availability, left ventricular assist device (LVAD) therapy has become an established treatment for patients with advanced heart failure as either a bridge to transplantation (BTT) or as a permanent alternative to transplantation, i.e., destination therapy (DT). The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial provided a firm albeit inauspicious proof of concept for the use of blood pumps as an alternative to medical therapy in patients not eligible for transplantation. Small continuous-flow LVADs improved the probability of survival and reduced the risk of device failure compared to larger pulsatile-flow LVADs. Axialflow LVADs have been the most popular option for mechanical circulatory support. Along with axial-flow blood pumps, some centrifugal blood pumps have also been developed aiming at achieving mechanical circulatory support as well as long-term durability.

Minute Ventilation-Targeted Adaptive Servo Ventilation Protects Renal Function In Acute Decompensated Heart Failure Patients

Introduction: Findings from The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial, published in October 2005, suggested that use of swan-ganz catheterization in patients with acute decompensated heart failure was not associated with an improvement in clinical outcomes. However, the temporal trends in national utilization of swan-ganz catheterization among heart failure patients in the post-ESCAPE era are not known. In this study, we aim to determine the temporal trends in use of swan-ganz catheterization among hospitalized heart failure patients between 2004 and 2012. Methods: The 2004-2012 Nationwide Inpatient Sample (NIS), the largest database of in-patient hospital stays in the US, was used to identify hospitalizations with primary diagnosis of heart failure among patients $16 years using ICD-9 codes 402.xx, 404.xx, and 428.xx. Use of swan-ganz catheterization for monitoring among these patients was identified using the clinical classification software procedure code 204. Primary outcome of interest was annual swan ganz catheterization per 1000 heart failure admissions during the study period. Results: There were 9.2 million hospitalizations with a principal diagnosis of heart failure from 2004 2012 (mean age 72.6 years, 51% were women). The overall rate of utilization of swan-ganz catheterization was 6.2 per 1000 heart failure hospitalizations. There was a significant increase in the proportional utilization of swan-ganz catheterization from 5.7 per 1000 heart failure admissions in 2004 to 8.9 per 1000 heart failure admissions in 2012 (p!0.001 for linear trend). In contrast, among patients who died during hospitalization, a group whose disease severity may be consistent across time, there was a relative decline in proportional utilization of swan ganz catheterization (3.05 per 1000 heart failure admissions in 2004 to 2.54 per 1000 heart failure admissions in 2012 (P-trend 5 0.02). Conclusions: Proportional utilization of swan-ganz catheters among patients hospitalized for heart failure has increased over time in the post ESCAPE era. This increase is likely due to its greater use in patients with less severe disease.

CARDIAC POWER INDEX IN ADVANCED DECOMPENSATED HEART FAILURE: INSIGHTS FROM THE ESCAPE TRIAL

Cardiac power (CP) is the rate of hydraulic work done by the heart. It is prognostic in acute ischemia, but its role advanced decompensated heart failure (ADHF) is unclear. We analyzed the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial

Abstract 16202: Changes in Hemoglobin After Pulmonary Artery Catheterization: Results From the ESCAPE Trial

Introduction: We sought to investigate the association between hemoglobin (Hgb) changes in patients with ADHF (with and without PACs) to mortality and clinical outcomes. Methods: We examined 433 patients enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. Change of Hgb (g/dL) was defined as at least 1 (g/dL) drop by hospital discharge. Quartiles of % change of Hgb (g/dL) were calculated. We used multivariable Cox regression analysis to evaluate the effect Hgb change on mortality and composite end points of death, cardiac re-hospitalization, or cardiac transplant. Results: Of the 433 patients, 324 (75%) had baseline and discharge Hgb available for analysis. Of those, 64 (20%) had at least 1 (g/dL) drop of Hgb by time of discharge. Patients in the Hgb drop group were older than those without Hgb changes (59 vs. 55, p = 0.011). There were no baseline differences in gender, race, and etiology of HF between groups. Compared to patients without Hgb changes, patients with Hgb drop had lower systolic BP (99 vs. 106, p = 0.017), lower sodium (136 vs. 137, p =0.025), higher BUN (37 vs. 26, p &lt;0.001), and higher Creatinine (1.6 vs. 1.3, p &lt;0.001), respectively. Higher Hgb drop was observed in the PACs (vs. no PACs) randomized arm of the trial (2 g/dL: PACs 10% versus 3%, p =0.010; 3 g/dL: PACs 5% versus 0%, p =0.005). After adjustments, higher in-hospital Hgb was associated with lower mortality (HR 0.79, p =0.003). In addition, patients in the Hgb drop group had increased risk of mortality (Adjusted HR 2.38, p =0.003) and composite endpoints (Adjusted HR 1.43, p =0.055). PACs insertion was not associated with adverse clinical outcomes by quartiles of % change of hemoglobin (Mortality: Q1: HR 0.80, p 0.601, Q2 HR 0.79, p = 0.706, Q3 HR 0.34, p =0.101, Q4 HR 2.23, p =0.357). Conclusion: In-hospital decrease in Hgb is independently associated with increased long-term mortality and adverse cardiovascular events in severe HF. The ideal Hgb levels in ADHF patients should be investigated and the insertion of PACs to direct therapy should be weighed against bleeding risks.

Bud Frazier Has Pioneered Mechanical Circulatory Support

In celebrating the 1,000th implantation of a left ventricular assist device (LVAD) at the Texas Heart Institute (THI), we find it particularly appropriate to recognize the contributions of Dr. O.H. (Bud) Frazier. As important as Bud's contributions have been to THI, they have been that much more important to the entire field of cardiac replacement therapy. Early in his career, Bud was inspired by the vision of Dr. Michael DeBakey and the energy of Dr. Denton Cooley, who pioneered mechanical circulatory support (MCS) and replacement in the 1960s. The early attempts to replace the human heart have been compared to the first manned mission to the moon, which took place during the same era; both of these heroic endeavors were fraught with danger and difficulty. By the 1980s, most cardiac surgeons had turned away from MCS and replacement. Instead, they had committed themselves to the boom in reparative heart operations, including coronary artery bypass grafting, valve replacement and repair, and aneurysm surgery. Bud was one of the few who remained committed to developing a surgical approach to benefit the sickest of the sick: patients with end-stage heart disease. His diligent, systematic approach entailed the creation of one of the world's most sophisticated large-animal surgical laboratories, as well as a clinical program for heart transplantation and MCS. In collaboration with industry pioneers, including Victor Poirier, of Thoratec Corporation, and John Watson, of the National Institutes of Health (NIH)—the “godfather” of MCS—Bud pioneered the use of mechanical devices as bridges to heart transplantation. Most important, he perceived the important role of bridging to transplantation as a “clinical laboratory” for developing MCS devices that could be used for long-term destination therapy (DT). In the late 1980s, the dismal results obtained with the Jarvik 7 Total Artificial Heart caused attention to be focused on left ventricular support as a simpler alternative. While the leading NIH-supported MCS researchers focused on mock circulatory loop studies and the durability of potential LVADs, Drs. Frazier, Poirier, and Watson focused on reducing the risk of stroke and creating a wearable pulsatile device rather than a fully implantable one. The results of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial,1 reported in 2001, proved that, compared with maximal medical therapy, this wearable device dramatically reduced the mortality rate of patients with end-stage heart disease who were not eligible for transplantation. More important, the quality of life of DT patients was superior to that of medically treated (control) patients, despite a high incidence of bleeding, cardiovascular accident, device failure, and infection. This validation of DT was followed by U.S. Food and Drug Administration approval of the first DT device and Medicare approval of reimbursement for DT. Clearly, because of his pioneering work, Bud Frazier was largely responsible for the current era of MCS. Whereas the 1,000th LVAD implantation at THI is certainly a cause for celebration, the continuing progress in this field—combined with the increasing incidence of severe heart failure—leads us to envision a future characterized by tens of thousands, if not hundreds of thousands, of LVAD implants.

Assessment and Management of Heart Failure After Left Ventricular Assist Device Implantation

Case Presentation: A 56-year-old man with a history of ischemic cardiomyopathy and New York Heart Association functional class IV heart failure (HF) requiring intravenous inotropic therapy underwent uncomplicated implantation of a continuous-flow left ventricular assist device (LVAD) as bridge to heart transplantation (HT). The patient was weaned off inotropic support during the first week after surgery and had progressive improvement in functional status. He was discharged home on maintenance antithrombotic therapy with aspirin 325 mg once daily and warfarin targeted to an international normalized ratio of 2.0 to 3.0. Eight weeks after LVAD implantation, he developed progressive dyspnea on exertion, recurrent pedal edema, and a 7-pound weight gain. Physical examination revealed conjunctival pallor, a palpable carotid pulse, jugular venous pressure of 14 cm H2O, and 2+ pitting edema bilaterally. A rapid and targeted assessment of recurrent HF is essential in this LVAD patient because of multiple, potentially life-threatening causes that necessitate divergent treatments. The US Food and Drug Administration first approved implantable LVADs as a bridge to transplantation in 1994.1 Although HT remains the gold standard therapy for selected patients with end-stage HF, the stable donor base of <2500 hearts per year in North America limits its widespread applicability.2 The landmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial established the first-generation, pulsatile-flow HeartMate (HM) XVE LVAD as a viable, life-prolonging treatment in patients who were not candidates for HT, a strategy known as destination therapy (DT). However, survival 2 years after implantation was still only 23%, in part because of the high rates of mechanical pump failure. The advent of continuous-flow LVADs has provided a more durable long-term treatment that improves quality of life and survival.3 The continuous-flow HM II LVAD has a markedly lower rate of device …

Cardiorenal Syndrome

Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research.

Atrial Fibrillation and Congestive Heart Failure: A Cost Analysis of Rhythm-Control vs Rate-Control Strategies

BackgroundAtrial fibrillation (AF) is common in patients with heart failure. Rhythm- and rate-control strategies are associated with similar efficacy outcomes. We compared the economic impact of the 2 treatment strategies in patients with AF and heart failure from the province of Québec, Canada. MethodsIn a substudy of the Atrial Fibrillation and Congestive Heart Failure trial, health care expenditures of patients from Québec randomized to rhythm and rate-control treatment strategies were compared from a single-payer perspective using a cost-minimization approach. In-trial resource utilization and unit costs were estimated from Québec Health Insurance Board databases supplemented by disease-specific costs from the Ontario Case Costing Initiative. ResultsIn all, 304 patients were included, aged 68 ± 9 years; 86% male; ejection fraction, 26% ± 6%. Baseline characteristics were similar in rhythm-control (n = 149) and rate-control (n = 155) groups. Arrhythmia-related costs accounted for 45% of total expenditures. Rate-control patients had fewer cardiac procedures (146 vs 238, P < 0.001), driven by fewer cardioversions, and lower costs related to antiarrhythmic drugs (CAD$48 per patient [95% confidence interval {CI}, $21-$96] vs $1319 per patient [95% CI, $1124-$1522]). However, these differences were offset by higher expenditures due to hospitalizations for noncardiovascular diagnoses, implantable cardiac arrhythmia devices, and noncardiovascular drugs in the rate-control group. The total cost per patient was not significantly different between rhythm-control ($72,764 [95% CI, $61,575-$85,145]) and rate-control ($78,767 [95% CI, $67,101-$92,139]) strategies. ConclusionIn the study population, the therapeutic strategy used to manage AF in patients with severe heart failure appears to have little influence on the overall financial burden, which remains substantial.

Atrial fibrillation in heart failure: drug therapies for rate and rhythm control

Pharmacological treatment of atrial fibrillation in the context of heart failure poses numerous challenges. Management decisions are limited by contraindications to several drugs and the paucity of robust clinical trials that provide evidence-based guidance. This review proposes a structured action plan for managing atrial fibrillation coexisting with heart failure that considers published clinical guidelines and integrates recent data derived from substudies of randomized trials, including the atrial fibrillation and congestive heart failure (AF-CHF) trial. Areas of uncertainty, such as target heart rates in atrial fibrillation and upstream therapies, are also discussed.

Goldilocks and the importance of AV intervals in cardiac resynchronization—How to best find the AV interval that is not too long, not too short, but just right for patients

Long before cardiac resynchronization (CRT) became standard therapy for patients with QRS prolongation and drug-refractory heart failure, standard dual chamber pacing in the right atrium and right ventricle using short atrioventricular (AV) delays was undertaken. The proponents of this procedure performed in patients without traditional bradycardia indications for pacing theorized that a shortened AV delay would decrease symptoms of heart failure by decreasing mitral and tricuspid valve regurgitation. Several case reports and case studies demonstrated favorable outcomes of improvement in cardiac output and decrease in symptoms of breathlessness in patients randomized to right ventricular pacing with short AV intervals. 1,2 Right ventricular pacing solely to improve symptomatic heart failure in patients without bradycardia was no longer thought useful after the publication of a double-blind randomized crossover trial of 12 patients, which demonstrated no difference in hemodynamic parameters or symptoms of heart failure between the times spent in the backup VVI 40 beats/min mode vs the VDD mode with an AV delay of 100 ms. The importance of AV intervals was realized even in the early days of left ventricular pacing for the treatment of heart failure. In a substudy of the Pacing Therapies in Congestive Heart Failure (PATH-CHF) trial, patients with a left bundle branch block treated with an epicardial left ventricular lead had significant differences in acute hemodynamic parameters as the AV interval was varied. There were significant variations in the optimal AV interval among individual patients, but the greatest benefit was seen as improvements in aortic pulse pressure, aortic systolic pressure, and left ventricular contractility if the AV interval was not too short and not too long. 3