Caregiver Health-Related Quality of Life, Burden, and Patient Outcomes in Ambulatory Advanced Heart Failure: A Report From REVIVAL.

Background Heart failure (HF) imposes significant burden on patients and caregivers. Longitudinal data on caregiver health-related quality of life (HRQOL) and burden in ambulatory advanced HF are limited. Methods and Results Ambulatory patients with advanced HF (n=400) and their participating caregivers (n=95) enrolled in REVIVAL (Registry Evaluation of Vital Information for VADs [Ventricular Assist Devices] in Ambulatory Life) were followed up for 24 months, or until patient death, left ventricular assist device implantation, heart transplantation, or loss to follow-up. Caregiver HRQOL (EuroQol Visual Analog Scale) and burden (Oberst Caregiving Burden Scale) did not change significantly from baseline to follow-up. At time of caregiver enrollment, better patient HRQOL by Kansas City Cardiomyopathy Questionnaire was associated with better caregiver HRQOL (P=0.007) and less burden by both time spent (P<0.0001) and difficulty (P=0.0007) of caregiving tasks. On longitudinal analyses adjusted for baseline values, better patient HRQOL (P=0.034) and being a married caregiver (P=0.016) were independently associated with better caregiver HRQOL. Patients with participating caregivers (versus without) were more likely to prefer left ventricular assist device therapy over time (odds ratio, 1.43; 95% CI, 1.03-1.99; P=0.034). Among patients with participating caregivers, those with nonmarried (versus married) caregivers were at higher composite risk of HF hospitalization, death, heart transplantation or left ventricular assist device implantation (hazard ratio, 2.99; 95% CI, 1.29-6.96; P=0.011). Conclusions Patient and caregiver characteristics may impact their HRQOL and other health outcomes over time. Understanding the patient-caregiver relationship may better inform medical decision making and outcomes in ambulatory advanced HF.

Oral Anticoagulation and Adverse Outcomes after Ischemic Stroke in Heart Failure Patients without Atrial Fibrillation.

BACKGROUND: The safety and effectiveness of oral anticoagulation (OAC) after an ischemic stroke in older patients with heart failure (HF) without atrial fibrillation remains uncertain. METHODS: Utilizing Get With The Guidelines Stroke national clinical registry data linked to Medicare claims from 2009-2014, we assessed the outcomes of eligible patients with a history of HF who were initiated on OAC during a hospitalization for an acute ischemic stroke. The cumulative incidences of adverse events were calculated using Kaplan-Meier curves and adjusted Cox proportional hazard ratios were compared between patients discharged on or off OAC. RESULTS: A total of 8,261 patients from 1,370 sites were discharged alive after an acute ischemic stroke and met eligibility criteria. Of those, 747 (9.0%) were initiated on OAC.  Patients on OAC were younger (77.2±8.0 vs. 80.5±8.9 years, p<0.01). After adjustment for clinical covariates, the likelihood of 1 year mortality was higher in those on OAC (aHR: 1.22, 95% CI 1.05-1.41, p<0.01), while no significant differences were noted for ICH (aHR: 1.34, 95% CI 0.69-2.59, p=0.38) and recurrent ischemic stroke (aHR: 0.78, 95% CI 0.54-1.15, p = 0.21).  The likelihood of all-cause bleeding (aHR: 1.59, 95% CI 1.29-1.96, p<0.01) and all-cause re-hospitalization (aHR: 1.14, 95% CI 1.02-1.27, p = 0.02) was higher for those on OAC. CONCLUSION: Initiation of OAC after an ischemic stroke in older patients with HF in the absence of atrial fibrillation is associated with death, bleeding and re-hospitalization without an associated reduction in recurrent ischemic stroke. If validated, these findings raise caution for prescribing OAC to such patients.

Etiologies, Predictors, and Economic Impact of 30-Day Readmissions Among Patients With Peripartum Cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a pregnancy-associated cause of heart failure. Given the significant impact of heart failure on healthcare, we sought to identify etiologies and predictive factors for readmission in PPCM. We queried the 2013 to 2014 National Readmissions Database to identify patients admitted with a diagnosis of PPCM. Patients who were readmitted within 30 days were evaluated to identify etiologies and predictors of readmission. We identified 6,977 index admissions with PPCM. Of the 6,880 (98.6%) patients who survived the index hospitalization, 30-day readmission rate was 13%. Seventy-six percent of readmitted patients were admitted once, and the other 24% were readmitted at least twice within 30 days of discharge. Length of stay was ≥8 days (adjusted odds ratio [aOR] 2.80, 95% confidence interval [CI] 2.08 to 3.77), multiparity (aOR 2.07, 95% CI 1.09 to 3.92), coronary artery disease (aOR 2.28, 95% CI 1.42 to 3.67), and long-term anticoagulation use (aOR 2.51, 95% CI 1.73 to 3.64) were independently associated with increased risk of 30-day readmission. Among the readmissions, 48% were due to cardiac causes, where PPCM and related complications (24%) were the most common cardiac cause followed by heart failure (16%). The annual cost of stay for index admissions was $64.2 million (average cost for index admission was $16,892). The annual charges attributed to readmission within 30 days were ≈$9 million. Cardiac etiologies were the most common cause for 30-day readmissions in PPCM patients, with a readmission rate of 13%. Long-term anticoagulation use, multiparity, coronary disease and length of stay predicted higher 30-day readmission.

The Relationship Between Psychological Symptoms and Ventricular Assist Device Implantation.

CONTEXT: Ventricular assist devices (VADs) improve quality of life in advanced heart failure patients, but there are little data exploring psychological symptoms in this population. OBJECTIVE: This study examined the prevalence of psychiatric symptoms and disease over time in VAD patients. METHODS: This prospective multicenter cohort study enrolled patients immediately before or after VAD implant and followed them up to 48 weeks. Depression and anxiety were assessed with Patient-Reported Outcomes Measurement Information System Short Form 8a questionnaires. The panic disorder, acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) modules of the Structured Clinical Interview for the DSM were used. RESULTS: Eighty-seven patients were enrolled. After implant, depression and anxiety scores decreased significantly over time (P = 0.03 and P < 0.001, respectively). Two patients met criteria for panic disorder early after implantation, but symptoms resolved over time. None met criteria for ASD or PTSD. CONCLUSIONS: Our study suggests VADs do not cause serious psychological harms and may have a positive impact on depression and anxiety. Furthermore, VADs did not induce PTSD, panic disorder, or ASD in this cohort.

Frailty Assessment in Advanced Heart Failure.

BACKGROUND: Several studies have recently demonstrated the value of frailty assessment in a general heart failure (HF) population; however, it is unknown whether these findings are also applicable in advanced HF. We investigated the utility of frailty assessment and its prognostic value in elderly patients with advanced HF. METHODS: Forty consecutive elderly subjects aged ≥65 years, with left ventricular ejection fraction ≤35%, New York Heart Association class III or IV, and a 6-minute walk test <300 m were enrolled from the HF clinic at Montefiore Medical Center between October 2012 and July 2013. Subjects were assessed for frailty with the Fried Frailty Index, consisting of 5 components: hand grip strength, 15-foot walk time, weight loss, physical activity, and exhaustion. All subjects were prospectively followed for death or hospitalization. RESULTS: At baseline, the mean age of the cohort was 74.9 ± 6.5 years, 58% female, left ventricular ejection fraction 25.6 ± 6.4%, 6-minute walk test 195.8 ± 74.3 m and length of follow-up 454 ± 186 days. Thirty-five percent were prefrail and 65% were frail. Frailty status was associated with the combined primary endpoint of mortality and all-cause hospitalization (hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.15-3.25, P = .013). On individual analysis, frailty was associated with all-cause hospitalizations (HR 1.92, 95% CI 1.12-3.27, P = .017) and non-HF hospitalizations (HR 3.31, 95% CI 1.14- 9.6, P = .028), but was not associated with HF hospitalizations alone (HR 1.31, 95% CI 0.68-2.49, P = .380). CONCLUSIONS: Frailty assessment in patients with advanced HF is feasible and provides prognostic value. These findings warrant validation in a larger cohort.

Pre-operative mortality risk assessment in patients with continuous-flow left ventricular assist devices: application of the HeartMate II risk score.

BACKGROUND: Survival with left ventricular assist device (LVAD) therapy is dependent on appropriate patient selection. The HeartMate II risk score (HMRS) was recently derived and validated to predict 90-day mortality in clinical trial patients with continuous-flow LVADs. The aim of this study was to test HMRS validity in predicting survival at our institution. METHODS: We performed a retrospective analysis of patients implanted with HeartMate II (HMII; Thoratec, Pleasanton, CA) LVADs from March 31, 2004 to September 20, 2012 at the Columbia University Medical Center (CUMC). Patients were stratified according to HMRS profiles (HMRS Low < 1.58, 1.58 ≤ HMRS Medium ≤ 2.48, HMRS High > 2.48) calculated using age, albumin, creatinine, international normalized ratio (INR) and center volume. Outcome was defined as survival at 90 days after device implantation. RESULTS: HeartMate II LVADs were implanted in 205 patients. Pre-operative data from 201 patients were categorized into HMRS Low (n = 101; 1.04 [0.64 to 1.31]), HMRS Medium (n = 73; 1.98 [1.78 to 2.25]) and HMRS High (n = 27, 3.07 [2.70 to 3.43]) (p < 0.0001). Kaplan-Meier survival estimates at 90 days (HMRS Low 91.0 ± 2.9%, HMRS Medium 91.7 ± 3.2%, HMRS High 88.7 ± 6.1%) and at 1 year (HMRS Low 85.5 ± 3.8%, HMRS Medium 79.3 ± 5.5%, HMRS High 82.4 ± 8.4%) after LVAD implantation were not statistically different (p = 0.43). Prediction of 90-day mortality by receiver operating characteristic was poor (AUC = 0.56). CONCLUSION: HMRS stratification poorly discriminates 90-day mortality after HMII LVAD implantation at our institution. Its generalizability as a universal prognostic score may be limited.

Prevalence, significance, and management of aortic insufficiency in continuous flow left ventricular assist device recipients.

BACKGROUND: Aortic insufficiency (AI) is increasingly recognized as a complication of continuous flow left ventricular assist device support; however, its long-term prevalence, clinical significance, and efficacy of potential interventions are not well known. METHODS AND RESULTS: We studied the prevalence and management of AI in 232 patients with continuous flow left ventricular assist device at our institution. Patients with aortic valve (AV) surgery before left ventricular assist device implantation were excluded from analysis. To examine the prevalence of de novo AI, patients without preoperative AI were divided into a retrospective and a prospective cohort based on whether a dedicated speed optimization study had been performed at the time of discharge. Forty-three patients underwent AV repair at the time of implant, and 3 subsequently developed greater than mild AI. In patients without surgical AV manipulation and no AI at the time of implant, Kaplan-Meier analysis revealed that freedom from greater than mild de novo AI at 1 year was 77.6±4.2%, and that at least moderate AI is expected to develop in 37.6±13.3% after 3 years. Nonopening of the AV was strongly associated with de novo AI development in patients without prospective discharge speed optimization. Seven of 21 patients with at least moderate AI developed symptomatic heart failure requiring surgical intervention. CONCLUSIONS: AI is common in patients with continuous flow left ventricular assist devices and may lead to clinical decompensation requiring surgical correction. The prevalence of AI is substantially less in patients whose AV opens, and optimized loading conditions may reduce AI prevalence in those patients in whom AV opening cannot be achieved.

Preoperative assessment of high-risk candidates to predict survival after heart transplantation.

BACKGROUND: Alternate waiting list strategies expand listing criteria for patients awaiting heart transplantation (HTx). We retrospectively analyzed clinical events and outcome of patients listed as high-risk recipients for HTx. METHODS AND RESULTS: We analyzed 822 adult patients who underwent HTx of whom 111 patients met high-risk criteria. Clinical data were collected from medical records and outcome factors calculated for 61 characteristics. Significant factors were summarized in a prognostic score. Age >65 years (67%) and amyloidosis (19%) were the most common reasons for alternate listing. High-risk recipients were older (63.2±10.2 versus 51.4±11.8 years; P<0.001), had more renal dysfunction, prior cancer, and smoking. Survival analysis revealed lower post-HTx survival in high-risk recipients (82.2% versus 87.4% at 1-year; 59.8% versus 76.3% at 5-year post-HTx; P=0.0005). Prior cerebral vascular accident, albumin <3.5 mg/dL, re-HTx, renal dysfunction (glomerular filtration rate <40 mL/min), and >2 prior sternotomies were associated with poor survival after HTx. A prognostic risk score (CARRS [CVA, albumin, re-HTx, renal dysfunction, and sternotomies]) derived from these factors stratified survival post-HTx in high-risk (3+ points) versus low-risk (0-2 points) patients (87.9% versus 52.9% at 1-year; 65.9% versus 28.4% at 5-year post-HTx; P<0.001). Low-risk alternate patients had survival comparable with regular patients (87.9% versus 87.0% at 1-year and 65.9% versus 74.5% at 5-year post-HTx; P=0.46). CONCLUSIONS: High-risk patients had reduced survival compared with regular patients post-HTx. Among patients previously accepted for alternate donor listing, application of the CARRS score identifies patients with unacceptably high mortality after HTx and those with a survival similar to regularly listed patients.

High-risk aortic valve replacement: are the outcomes as bad as predicted?

BACKGROUND: Percutaneous aortic valve replacement (PAVR) trials are ongoing in patients with an elevated European System for Cardiac Operative Risk Evaluation (EuroSCOREs), patients believed to have high mortality rates and poor long-term prognoses with valve replacement surgery. It is, however, uncertain that the EuroSCORE model is well calibrated for such high-risk AVR patients. We evaluated EuroSCORE prediction vs a single institution's surgical results in this target population. METHODS: From January 1996 through March 2006, 731 patients with EuroSCOREs of 7 or higher underwent isolated AVR. In this cohort, 313 (42.8%) were septuagenarians, 322 (44.0%) were octogenarians or nonagenarians, 233 (31.9%) had had previous cardiac procedures, 237 (32.4%) had atheromatous aortas, and 127 (17.4%) had cerebrovascular disease. A minimally invasive approach was used in 469 (64.2%). Data collection was prospective. Long-term survival was computed from the Social Security Death Benefit Index. RESULTS: The mean EuroSCORE was 9.7 (median, 10), and the mean logistic EuroSCORE was 17.2%. Actual hospital mortality was 7.8% (57 of 731). Multivariate analysis showed ejection fraction of less than 0.30 (p = 0.002; odds ratio [OR], 3.13), chronic obstructive pulmonary disease (p = 0.019; OR, 2.14), and peripheral vascular disease (p = 0.048; OR, 2.13) were significant predictors of hospital mortality. Complication(s) occurred in 73 patients (9.9%). Freedom from all-cause death (including hospital mortality) was 72.4% at 5 years (n = 152). Age (p < 0.001), previous cardiac operations (p < 0.014; OR, 1.51), renal failure (p < 0.002; OR, 2.37), and chronic obstructive pulmonary disease (p < 0.007; OR, 1.30) were predictors of worse survival. CONCLUSIONS: Logistic EuroSCORE greatly overpredicts mortality in these patients. Five-year survival is good, unlike suggestions from earlier EuroSCORE analyses. This raises concern about unknown long-term percutaneous prosthesis function. Clinical trials for these patients must include randomized surgical controls and have long-term end points.

Impact of moderate functional mitral insufficiency in patients undergoing surgical revascularization.

BACKGROUND: Mild and moderate functional ischemic mitral insufficiency present at the time of surgical revascularization present clinical uncertainty. It is unclear whether the relatively poor outcomes in this cohort are dependent on valvular function or related to left ventricular dysfunction. The purpose of this study was to examine the early and late outcomes in patients with less-than-severe functional ischemic mitral insufficiency at the time of isolated coronary artery bypass grafting (CABG). METHODS AND RESULTS: From 1996 through 2004, 2242 consecutive patients undergoing isolated CABG were identified as having none to moderate mitral regurgitation (MR) and no valve leaflet pathology. All of the patients at this single institution routinely had an intraoperative transesophageal echocardiography, prospectively quantified MR, and ejection fraction (EF). The New York State Cardiac Surgery Reporting System infrastructure was used to prospectively collect in-hospital patient variables and outcomes. Social Security Death Benefit Index was used to determine long-term survival. Odds ratio and significance (P value) are presented for each determined risk factor. There were 841 patients (37.5%) with no MR, 1137 (50.7%) with mild MR, and 264 (11.8%) with moderate MR. The patients with moderate MR were more likely to be older, female, and have more renal disease, previous MI, congestive heart failure, previous cardiac surgery, and lower EFs. Hospital mortality was independently and significantly associated with renal disease, decreasing EF, increasing age, previous cardiac operation, and cerebral vascular disease. Multivariable analysis revealed decreased survival with increasing age, previous operation, congestive heart failure, diabetes, nonelective operation, decreasing EF, and the presence of moderate MR (expbeta = 1.49; P=0.007) and mild MR (expbeta = 1.34; P=0.033). CONCLUSIONS: Independent of ventricular function, mild and moderate functional mitral insufficiency are associated with significantly decreased survival in patients undergoing CABG. Whether correction of moderate functional MR at the time of CABG improves outcome still needs to be determined.

Suppression of the renin-angiotensin-aldosterone system in chronic heart failure: choice of agents and clinical impact.

Chronic heart failure (CHF) has taken on epidemic proportions in the United States, with approximately 550,000 new cases annually. With the evolution of pharmacotherapy targeting neurohormonal pathways over the past 2 decades, the annual mortality in subjects with New York Heart Association (NYHA) class IV has dramatically improved from 52% in the seminal CONSENSUS trial to less than 20% in more recent trials in CHF. Suppression of the renin-angiotensin system (RAS) with various angiotensin-converting enzyme (ACE) inhibitors has been proven to save lives in several large-scale trials of CHF, and all of them can be used at doses tested in clinical trials without clear preference of one over another. Angiotensin receptor blockers (ARBs) can be used in place of ACE inhibitors in the case of ACE inhibitor intolerance with comparable results. However, some inconsistencies exist between trials with ARBs, and it is uncertain if the ARBs tested in clinical trials provide comparable clinical benefit whether used in place of or in combination with ACE inhibitors. Once ACE inhibition has been started, beta blockade should follow for all subjects with symptomatic CHF. Triple neurohormonal blockade can then be accomplished with the addition of an aldosterone receptor or ARB. Regardless of the exact agent used or sequence of initiation, the critical importance of careful monitoring of neurohormonal blockade cannot be overstated. Renal failure and hyperkalemia are the most important complications of suppression of the renin-angiotensin-aldosterone system (RAAS), and an increase in hospital admissions and death from hyperkalemia after publication of the RALES trial illustrates the danger of "casual" use of neurohormonal blockers. In light of the tremendous benefits of neurohormonal blockade, the only conclusion from these data is to initiate RAAS-blocking agents following the safety precautions tested in the respective clinical trials.