Multicenter evaluation of left ventricular assist device implantation with or without ECMO bridge in cardiogenic shock.

BACKGROUND: The efficacy of extracorporeal membrane oxygenation (ECMO) as a bridge to left ventricular assist device (LVAD) remains unclear, and recipients of the more contemporary HeartMate 3 (HM3) LVAD are not well represented in previous studies. We therefore undertook a multicenter, retrospective study of this population. METHODS AND RESULTS: INTERMACS 1 LVAD recipients from five U.S. centers were included. In-hospital and one-year outcomes were recorded. The primary outcome was the overall mortality hazard comparing ECMO versus non-ECMO patients by propensity-weighted survival analysis. Secondary outcomes included survival by LVAD type, as well as postoperative and one-year outcomes. One hundred and twenty-seven patients were included; 24 received ECMO as a bridge to LVAD. Mortality was higher in patients bridged with ECMO in the primary analysis (HR 3.22 [95%CI 1.06-9.77], p = 0.039). Right ventricular assist device was more common in the ECMO group (ECMO: 54.2% vs non-ECMO: 11.7%, p < 0.001). Ischemic stroke was higher at one year in the ECMO group (ECMO: 25.0% vs non-ECMO: 4.9%, p = 0.006). Among the study cohort, one-year mortality was lower in HM3 than in HeartMate II (HMII) or HeartWare HVAD (10.5% vs 46.9% vs 31.6%, respectively; p < 0.001) recipients. Pump thrombosis at one year was lower in HM3 than in HMII or HVAD (1.8% vs 16.1% vs 16.2%, respectively; p = 0.026) recipients. CONCLUSIONS: Higher mortality was observed with ECMO as a bridge to LVAD, likely due to higher acuity illness, yet acceptable one-year survival was seen compared with historical rates. The receipt of the HM3 was associated with improved survival compared with older generation devices.

Hospitalization epidemic in patients with heart failure: risk factors, risk prediction, knowledge gaps, and future directions.

Patients with heart failure (HF) are hospitalized over a million times annually in the United States. Hospitalization marks a fundamental change in the natural history of HF, leading to frequent subsequent rehospitalizations and a significantly higher mortality compared with nonhospitalized patients. Three-fourths of all HF hospitalizations are due to exacerbation of symptoms in patients with known HF. One-half of hospitalized HF patients experience readmission within 6 months. Preventing HF hospitalization and rehospitalization is important to improve patient outcomes and curb health care costs. To implement cost-effective strategies to contain the HF hospitalization epidemic, optimal schemes to identify high-risk individuals are needed. In this review, we describe the risk factors that have been associated with hospitalization risk in HF and the various multimarker risk prediction schemes developed to predict HF rehospitalization. We comment on areas that represent gaps in our knowledge or difficulties in interpretation of the current literature, representing opportunities for future research. We also discuss issues with using HF readmission rate as a quality indicator.

Incremental value of renal function in risk prediction with the Seattle Heart Failure Model.

BACKGROUND: Impaired renal function portends poor heart failure (HF) outcomes. The Seattle Heart Failure Score (SHFS), a multimarker risk assessment tool, however does not incorporate renal function. In this study, we assessed the incremental value of renal function over the SHFS in patients with advanced HF on contemporary optimal treatment. METHODS: Blood urea nitrogen (BUN), serum creatinine (sCr), BUN/sCr ratio, and estimated glomerular filtration rate were assessed in survival models with SHFS as the base model among 443 patients with HF (52 +/- 12 years, male 68.5%, white 52.4%, ejection fraction 0.18 +/- 0.08). Incremental value of renal function was assessed by changes in the likelihood ratio chi(2) and the area under the receiver operating characteristic curves for 1-, 2-, and 3-year event prediction. RESULTS: During a median follow-up of 21 months, 108 (24.5%) of 443 patients had an event (death [n = 92], urgent transplantation [n = 13], or ventricular assist device implantation [n = 3]). All renal parameters individually were associated with outcome (BUN, P < .001; sCr, P < .001; BUN/sCr ratio, P = .006; and estimated glomerular filtration rate, P = .006); however, only BUN was an independent predictor of events in multivariable analyses. Addition of BUN improved the predictive ability of SHFS (Deltalikelihood ratio chi(2) 5.03, P = .025); however, the increase in the area under the receiver operating characteristic curve was marginal (year 1, 0.786 to 0.791; year 2, 0.732 to 0.741; year 3, 0.745 to 0.754; all P > .2). CONCLUSION: Among the various renal function parameters, BUN had the strongest association with outcomes in patients with advanced HF. However, the incremental value of renal function over the SHFS for risk determination was marginal.

Echocardiography and risk prediction in advanced heart failure: incremental value over clinical markers.

BACKGROUND: Incremental value of echocardiography over clinical parameters for outcome prediction in advanced heart failure (HF) is not well established. METHODS AND RESULTS: We evaluated 223 patients with advanced HF receiving optimal therapy (91.9% angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, 92.8% beta-blockers, 71.8% biventricular pacemaker, and/or defibrillator use). The Seattle Heart Failure Model (SHFM) was used as the reference clinical risk prediction scheme. The incremental value of echocardiographic parameters for event prediction (death or urgent heart transplantation) was measured by the improvement in fit and discrimination achieved by addition of standard echocardiographic parameters to the SHFM. After a median follow-up of 2.4 years, there were 38 (17.0%) events (35 deaths; 3 urgent transplants). The SHFM had likelihood ratio (LR) chi(2) 32.0 and C statistic 0.756 for event prediction. Left ventricular end-systolic volume, stroke volume, and severe tricuspid regurgitation were independent echocardiographic predictors of events. The addition of these parameters to SHFM improved LR chi(2) to 72.0 and C statistic to 0.866 (P < .001 and P=.019, respectively). Reclassifying the SHFM-predicted risk with use of the echocardiography-added model resulted in improved prognostic separation. CONCLUSIONS: Addition of standard echocardiographic variables to the SHFM results in significant improvement in risk prediction for patients with advanced HF.

Patient perception versus medical record entry of health-related conditions among patients with heart failure.

A shared understanding of medical conditions between patients and their health care providers may improve self-care and outcomes. In this study, the concordance between responses to a medical history self-report (MHSR) form and the corresponding provider documentation in electronic health records (EHRs) of 19 select co-morbidities and habits in 230 patients with heart failure were evaluated. Overall concordance was assessed using the κ statistic, and crude, positive, and negative agreement were determined for each condition. Concordance between MHSR and EHR varied widely for cardiovascular conditions (κ = 0.37 to 0.96), noncardiovascular conditions (κ = 0.06 to 1.00), and habits (κ = 0.26 to 0.69). Less than 80% crude agreement was seen for history of arrhythmias (72%), dyslipidemia (74%), and hypertension (79%) among cardiovascular conditions and lung disease (70%) and peripheral arterial disease (78%) for noncardiovascular conditions. Perfect agreement was observed for only 1 of the 19 conditions (human immunodeficiency virus status). Negative agreement >80% was more frequent than >80% positive agreement for a condition (15 of 19 [79%] vs 8 of 19 [42%], respectively, p = 0.02). Only 20% of patients had concordant MSHRs and EHRs for all 7 cardiovascular conditions; in 40% of patients, concordance was observed for ≤5 conditions. For noncardiovascular conditions, only 28% of MSHR-EHR pairs agreed for all 9 conditions; 37% agreed for ≤7 conditions. Cumulatively, 39% of the pairs matched for ≤15 of 19 conditions. In conclusion, there is significant variation in the perceptions of patients with heart failure compared to providers' records of co-morbidities and habits. The root causes of this variation and its impact on outcomes need further study.

Usefulness of cardiac index and peak exercise oxygen consumption for determining priority for cardiac transplantation.

Decisions regarding cardiac transplantation listing are difficult in patients with heart failure who have relatively discordant peak exercise oxygen consumption (Vo(2)) and cardiac index (CI) values. One hundred five patients with heart failure who underwent cardiopulmonary exercise testing and right-sided cardiac catheterization for transplantation evaluation were studied. Patients were divided into 4 groups on the basis of peak Vo(2) and CI: group 1, Vo(2) > or = 12 ml/min/kg, CI > or = 1.8 L/min/m(2) (n = 30); group 2, Vo(2) > or = 12 ml/min/kg, CI <1.8, L/min/m(2) (n = 27); group 3, Vo(2) <12 ml/min/kg, CI > or = 1.8 L/min/m(2) (n = 25); and group 4, Vo(2) <12 ml/min/kg, CI <1.8 L/min/m(2) (n = 23). Groups were compared for event-free (death or ventricular assist device) survival. The overall CI was 1.9 + or - 0.4 L/min/m(2) and peak Vo(2) was 12.4 + or - 2.8 ml/min/kg; values in the 4 groups were as follows: group 1, peak Vo(2) 14.7 + or - 2.1 ml/min/kg, CI 2.2 + or - 0.3 L/min/m(2); group 2, peak VO(2) 14.2 + or - 1.3 ml/min/kg, CI 1.5 + or - 0.2 L/min/m(2); group 3, peak Vo(2) 10.2 + or - 1.3 ml/min/kg, CI 2.1 + or - 0.3 L/min/m(2); and group 4, peak Vo(2) 9.7 + or - 2.0 ml/min/kg, CI 1.6 + or - 0.2 L/min/m(2). After a median follow-up period of 3.7 years, 28 patients (26.0%) had events. Event-free survival was 96%, 95%, 96%, and 79% for 6 months (p = 0.04); 88%, 81%, 90%, and 73% for 12 months (p = 0.09); 88%, 73%, 85%, and 65% for 18 months (p = 0.11); and 83%, 73%, 79%, and 53% for 24 months (p = 0.06) for groups 1 to 4, respectively. Median survival was 5.1, 3.0, 3.9, and 2.6 years, respectively, in groups 1 to 4 (p = 0.052). In conclusion, almost half the patients had relatively discordant peak Vo(2) and CI measurements. Patients with lower peak Vo(2) values but relatively preserved CI values had survival comparable to post-transplantation survival, whereas those with low CI but preserved Vo(2) had a lower survival rate. These results suggest that the former group may be safely monitored on medical therapy, whereas the latter may benefit from early listing.

Digoxin therapy does not improve outcomes in patients with advanced heart failure on contemporary medical therapy.

BACKGROUND: The impact of digoxin on outcomes of patients with advanced heart failure (HF) receiving optimal contemporary therapy is not known. METHODS AND RESULTS: We retrospectively reviewed data of 455 advanced HF patients referred for transplant evaluation (age, 52+/-12 years; ejection fraction, 18.3+/-8%); 227 (49.9%) were on digoxin at baseline. Primary outcome was death (n=101), urgent transplantation (n=14), or ventricular assist device implantation (n=4); secondary outcomes included HF and all-cause hospitalizations. Digoxin use was evaluated (1) in the original cohort; (2) in a propensity score-matched subset (n=322); (3) as a time-dependent covariate; and (4) after adjustment for Seattle Heart Failure Score. Patients were on optimal therapy: angiotensin-II modulation, 92.5%; beta-blockers, 91.2%; aldosterone antagonists, 45.6%; and devices, 71.0%. After a median of 27 months, 83 of 277 (36.6%) patients treated with digoxin versus 36 of 228 (15.8%) patients without digoxin met primary outcome (hazard ratio [HR], 2.28; 95% CI, 1.51 to 3.43; P<0.001). This risk persisted in the matched subset (HR, 1.73; 95% CI, 1.09 to 2.75; P=0.021) and with time-varying digoxin use (HR, 2.05; 95% CI, 1.23 to 3.41; P=0.011). Digoxin was associated with higher risk among patients in sinus rhythm compared with atrial fibrillation. Digoxin was not associated with improvement in either all-cause or HF hospitalization rates. These results were similar across sex and race and when adjusted for Seattle Heart Failure Score and renal function. CONCLUSIONS: This study suggests that digoxin therapy may be of no benefit in patients with advanced HF referred for cardiac transplantation who received optimal medical therapy. Treatment with digoxin should be used cautiously in such patients because of risk for adverse outcomes.

Utility of the Seattle Heart Failure Model in patients with advanced heart failure.

OBJECTIVES: The aim of this study was to validate the Seattle Heart Failure Model (SHFM) in patients with advanced heart failure (HF). BACKGROUND: The SHFM was developed primarily from clinical trial databases and extrapolated the benefit of interventions from published data. METHODS: We evaluated the discrimination and calibration of SHFM in 445 advanced HF patients (age 52 +/- 12 years, 68.5% male, 52.4% white, ejection fraction 18 +/- 8%) referred for cardiac transplantation. The primary end point was death (n = 92), urgent transplantation (n = 14), or left ventricular assist device (LVAD) implantation (n = 3); a secondary analysis was performed on mortality alone. RESULTS: Patients were receiving optimal therapy (angiotensin-II modulation 92.8%, beta-blockers 91.5%, aldosterone antagonists 46.3%), and 71.0% had an implantable device (defibrillator 30.4%, biventricular pacemaker 3.4%, combined 37.3%). During a median follow-up of 21 months, 109 patients (24.5%) had an event. Although discrimination was adequate (c-statistic >0.7), the SHFM overall underestimated absolute risk (observed vs. predicted event rate: 11.0% vs. 9.2%, 21.0% vs. 16.6%, and 27.9% vs. 22.8% at 1, 2, and 3 years, respectively). Risk underprediction was more prominent in patients with an implantable device. The SHFM had different calibration properties in white versus black patients, leading to net underestimation of absolute risk in blacks. Race-specific recalibration improved the accuracy of predictions. When analysis was restricted to mortality, the SHFM exhibited better performance. CONCLUSIONS: In patients with advanced HF, the SHFM offers adequate discrimination, but absolute risk is underestimated, especially in blacks and in patients with devices. This is more prominent when including transplantation and LVAD implantation as an end point.