Frailty Measures of Patient-reported Activity and Fatigue May Predict 1-year Outcomes in Ambulatory Advanced Heart Failure: A Report From the REVIVAL Registry.

BACKGROUND: The Fried Frailty Phenotype predicts adverse outcomes in geriatric populations, but has not been well-studied in advanced heart failure (HF). The Registry Evaluation of Vital Information for Ventricular Assist Devices (VADs) in Ambulatory Life (REVIVAL) study prospectively collected frailty measures in patients with advanced HF to determine relevant assessments and their impact on clinical outcomes. METHODS AND RESULTS: HF-Fried Frailty was defined by 5 baseline components (1 point each): (1) weakness: hand grip strength less than 25% of body weight; (2) slowness based on time to walk 15 feet; (3) weight loss of more than 10 lbs in the past year; (4) inactivity; and (5) exhaustion, both assessed by the Kansas City Cardiomyopathy Questionnaire. A score of 0 or 1 was deemed nonfrail, 2 prefrail, and 3 or greater was considered frail. The primary composite outcome was durable mechanical circulatory support implantation, cardiac transplant or death at 1 year. Event-free survival for each group was determined by the Kaplan-Meier method and the hazard of prefrailty and frailty were compared with nonfrailty with proportional hazards modeling. Among 345 patients with all 5 frailty domains assessed, frailty was present in 17%, prefrailty in 40%, and 43% were nonfrail, with 67% (n = 232) meeting the criteria based on inactivity and 54% (n = 186) for exhaustion. Frail patients had an increased risk of the primary composite outcome (unadjusted hazard ratio [HR] 2.82, 95% confidence interval [CI] 1.52-5.24; adjusted HR 3.41, 95% CI 1.79-6.52), as did prefrail patients (unadjusted HR 1.97, 95% CI 1.14-3.41; adjusted HR 2.11, 95% CI 1.21-3.66) compared with nonfrail patients, however, the predictive value of HF-Fried Frailty criteria was modest (Harrel's C-statistic of 0.603, P = .004). CONCLUSIONS: The HF-Fried Frailty criteria had only modest predictive power in identifying ambulatory patients with advanced HF at high risk for durable mechanical circulatory support, transplant, or death within 1 year, driven primarily by assessments of inactivity and exhaustion. Focus on these patient-reported measures may better inform clinical trajectories in this population.

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.

Novel dietary protocol prior to 18F-fluorodeoxyglucose positron emission tomography to evaluate for cardiac sarcoidosis.

The diagnosis of cardiac sarcoidosis (CS) is challenging. Recently, guidelines incorporated cardiac positron emission tomography (PET) with 18F-Fluorodeoxyglucose (F18-FDG) as a non-invasive diagnostic modality for the detection and follow-up of CS. However, this technique is dependent of patient dietary preparation to suppress physiological myocardial F18-FDG uptake. We present a case of possible CS which highlights a novel preparation protocol that facilitated appropriate myocardial suppression.

Comorbid Conditions and Health-Related Quality of Life in Ambulatory Heart Failure Patients: REVIVAL (Registry Evaluation of Vital Information for VADs in Ambulatory Life REVIVAL).

BACKGROUND: Patients with heart failure (HF) often have multiple chronic conditions that may impact health-related quality of life (HRQOL) despite HF therapy. We sought to determine the association between noncardiac comorbidities and HRQOL in ambulatory patients with advanced HF. METHODS: Baseline data from 373 subjects in REVIVAL (Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life) were analyzed using multivariable general linear models to evaluate the relationship between comorbidities and HRQOL (EuroQol Visual Analogue Scale, EQ-5D-3L Index Score, and Kansas City Cardiomyopathy Questionnaire). The primary independent variables were a comorbidity index (sum of 14 noncardiac conditions), a residual comorbidity index (without depression), and depression alone. The median (25th to 75th percentile) number of comorbidities was 3 (2-4). RESULTS: Increasing comorbidity burden was associated with a reduction in generic (EQ-5D Index, P=0.005) and HF-specific (Kansas City Cardiomyopathy Questionnaire, P=0.001) HRQOL. The residual comorbidity index was not associated with HRQOL when depression included in the model independently, while depression was associated with HRQOL across all measures. Participants with depression (versus without) scored on average 13 points (95% CI, 8-17) lower on the EuroQol Visual Analogue Scale, 0.15 points (95% CI, 0.12-0.18) lower on the EQ-5D Index, and 24.9 points (95% CI, 21.2-28.5) lower on the Kansas City Cardiomyopathy Questionnaire overall summary score. CONCLUSIONS: While noncardiac comorbidities were prevalent in ambulatory advanced HF patients, only depression was associated with decreased generic and HF-specific HRQOL. Other than depression, the presence of noncardiac comorbidities should not impact expected gains in HRQOL following ventricular assist device implantation, provided the conditions are not a contraindication to implant. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01369407.

Quality of life and treatment preference for ventricular assist device therapy in ambulatory advanced heart failure: A report from the REVIVAL study.

BACKGROUND: The Registry Evaluation of Vital Information for Ventricular Assist Devices (VADs) in Ambulatory Life study is a prospective multicenter cohort of 400 ambulatory patients with advanced chronic systolic heart failure (HF). The aim of the study is to better understand disease trajectory and optimal timing of advanced HF therapies. We examined patient health-related quality of life (HRQOL) data collected at enrollment and their association with patient treatment preferences for VAD placement. METHODS: Baseline assessment of HRQOL included the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the EuroQol EQ-5D-3L Visual Analogue Scale (VAS), along with patient self-assessment of remaining life (PSARL). Descriptive statistics were used to present baseline HRQOL data and Spearman correlation tests to assess the association between KCCQ, VAS, and VAD treatment preference with patient clinical characteristics of interest. RESULTS: The median age was 60 years, 75% were male, and the median left ventricular ejection fraction was 20%. The median (25th percentile, 75th percentile), baseline KCCQ summary score was 64 (48, 78), VAS score 65 (50, 75), and PSARL 7 years (5, 10). There were statistically significant associations of baseline KCCQ and VAS with New York Heart Association class and Interagency Registry of Mechanically Assisted Circulatory Support profile (p < 0.005 for all comparisons). Baseline KCCQ and VAS revealed a modest association with PSARL (correlation = 0.45 and 0.35, respectively; p < 0.001), and many patients were overly optimistic about their expected survival. VAD treatment preference was associated with KCCQ scores (p < 0.031), but the absolute differences were small. VAD treatment preference was independent of other key clinical characteristics such as subject age, VAS, and PSARL. CONCLUSIONS: We found a lack of strong association between HRQOL and patient preference for VAD therapy. Better understanding of patients' perceptions of their illness and how this relates to HRQOL outcomes, clinician risk assessment, and patient decision-making is needed. This may in turn allow better guidance toward available HF therapies in this vulnerable population.

Outcomes with ambulatory advanced heart failure from the Medical Arm of Mechanically Assisted Circulatory Support (MedaMACS) Registry.

BACKGROUND: The outlook for ambulatory patients with advanced heart failure (HF) and the appropriate timing for left ventricular assist device (LVAD) or transplant remain uncertain. The aim of this study was to better understand disease trajectory and rates of progression to subsequent LVAD therapy and transplant in ambulatory advanced HF. METHODS: Patients with advanced HF who were New York Heart Association (NYHA) Class III or IV and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profiles 4 to 7, despite optimal medical therapy (without inotropic therapy), were enrolled across 11 centers and followed for the end-points of survival, transplantation, LVAD placement, and health-related quality of life. A secondary intention-to-treat survival analysis compared outcomes for MedaMACS patients with a matched group of Profile 4 to 7 patients with LVADs from the INTERMACS registry. RESULTS: Between May 2013 and October 2015, 161 patients were enrolled with INTERMACS Profiles 4 (12%), 5 (32%), 6 (49%), and 7 (7%). By 2 years after enrollment, 75 (47%) patients had reached a primary end-point with 39 (24%) deaths, 17 (11%) undergoing LVAD implantation, and 19 (12%) receiving a transplant. Compared with 1,753 patients with Profiles 4 to 7 receiving LVAD therapy, there was no overall difference in intention-to-treat survival between medical and LVAD therapy, but survival with LVAD therapy was superior to medical therapy among Profile 4 and 5 patients (p = 0.0092). Baseline health-related quality of life was lower among patients receiving a LVAD than those enrolled on continuing oral medical therapy, but increased after 1 year for survivors in both cohorts. CONCLUSIONS: Ambulatory patients with advanced HF are at high risk for poor outcomes, with only 53% alive on medical therapy after 2 years of follow-up. Survival was similar for medical and LVAD therapy in the overall cohort, which included the lower severity Profiles 6 and 7, but survival was better with LVAD therapy among patients in Profiles 4 and 5. Given the poor outcomes in this group of advanced HF patients, timely consideration of transplant and LVAD is of critical importance.

Discordant Perceptions of Prognosis and Treatment Options Between Physicians and Patients With Advanced Heart Failure.

OBJECTIVES: This study assessed patient and physician perceptions of heart failure (HF) disease severity and treatment options. BACKGROUND: The prognosis for ambulatory patients with advanced HF on medical therapy is uncertain, yet has important implications for decision making regarding transplantation and left ventricular assist device (LVAD) placement. METHODS: Ambulatory patients with advanced HF (New York Heart Association functional class III to IV, Interagency Registry for Mechanically Assisted Circulatory Support profiles 4 to 7) on optimized medical therapy were enrolled across 11 centers. At baseline, treating cardiologists rated patients for perceived risk for transplant, LVAD, or death in the upcoming year. Patients were also surveyed about their own perceptions of life expectancy and willingness to undergo various interventions. RESULTS: At enrollment, physicians regarded 111 of 161 patients (69%) of the total cohort to be at high risk for transplant, LVAD, or death, whereas only 23 patients (14%) felt they were at high risk. After a mean follow-up of 13 months, 61 patients (38%) experienced an endpoint of 33 deaths (21%), 13 transplants (8%), and 15 LVAD implants (9%). There was poor discrimination between risk prediction among both patients and physicians. Among physician-identified high-risk patients, 77% described willingness to consider LVAD, but 63% indicated that they would decline 1 or more other simpler forms of life-sustaining therapy such as ventilation, dialysis, or a feeding tube. CONCLUSIONS: Among patients with advanced HF, physicians identified most to be at high risk for transplantation, LVAD, or death, whereas few patients recognized themselves to be at high risk. Patients expressed inconsistent attitudes toward lifesaving treatments, possibly indicating poor understanding of these therapies. Educational interventions regarding disease severity and treatment options should be introduced prior to the need for advanced therapies such as intravenous inotropic therapy, transplantation, or LVAD.

Optimal Timing of Heart Transplant After HeartMate II Left Ventricular Assist Device Implantation.

BACKGROUND: Optimal timing of heart transplantation in patients supported with second-generation left ventricular assist devices (LVADs) is unknown. Despite this, patients with LVADs continue to receive priority on the heart transplant waiting list. Our objective was to determine the optimal timing of transplantation for patients bridged with continuous-flow LVADs. METHODS: A total of 301 HeartMate II LVADs (Thoratec Corp, Pleasanton, CA) were implanted in 285 patients from October 2004 to June 2013, and 86 patients underwent transplantation through the end of follow-up. Optimal transplantation timing was the product of surviving on LVAD support and surviving transplant. RESULTS: Three-year survival after both HeartMate II implantation and heart transplantation was unchanged when transplantation occurred within 9 months of implantation. Survival decreased as the duration of support exceeded this. Preoperative risk factors for death on HeartMate II support were prior valve operation, prior coronary artery bypass grafting, low albumin, low glomerular filtration rate, higher mean arterial pressure, hypertension, and earlier date of implant. Survival for patients without these risk factors was lowest when transplant was performed within 3 months but was relatively constant with increased duration of support. Longer duration of support was associated with poorer survival for patients with many of these risk factors. Device reimplantation, intracranial hemorrhage, and postimplant dialysis during HeartMate II support were associated with decreased survival. CONCLUSIONS: Survival of patients supported by the HeartMate II is affected by preoperative comorbidities and postoperative complications. Transplantation before complications is imperative in optimizing survival.

Risk factors, mortality, and timing of ischemic and hemorrhagic stroke with left ventricular assist devices.

BACKGROUND: Stroke is a major cause of mortality after left ventricular assist device (LVAD) placement. METHODS: Prospectively collected data of patients with HeartMate II (n = 332) and HeartWare (n = 70) LVADs from October 21, 2004, to May 19, 2015, were reviewed. Predictors of early (during index hospitalization) and late (post-discharge) ischemic and hemorrhagic stroke and association of stroke subtypes with mortality were assessed. RESULTS: Of 402 patients, 83 strokes occurred in 69 patients (17%; 0.14 events per patient-year [EPPY]): early ischemic stroke in 18/402 (4%; 0.03 EPPY), early hemorrhagic stroke in 11/402 (3%; 0.02 EPPY), late ischemic stroke in 25/402 (6%; 0.04 EPPY) and late hemorrhagic stroke in 29/402 (7%; 0.05 EPPY). Risk of stroke and death among patients with stroke was bimodal with highest risks immediately post-implant and increasing again 9-12 months later. Risk of death declined over time in patients without stroke. Modifiable stroke risk factors varied according to timing and stroke type, including tobacco use, bacteremia, pump thrombosis, pump infection, and hypertension (all p < 0.05). In multivariable analysis, early hemorrhagic stroke (adjusted odds ratio [aOR] 4.3, 95% confidence interval [CI] 1.0-17.8, p = 0.04), late ischemic stroke (aOR 3.2, 95% CI 1.1-9.0, p = 0.03), and late hemorrhagic stroke (aOR 3.7, 95% CI 1.5-9.2, p = 0.005) predicted death, whereas early ischemic stroke did not. CONCLUSIONS: Stroke is a leading cause and predictor of death in patients with LVADs. Risk of stroke and death among patients with stroke is bimodal, with highest risk at time of implant and increasing risk again after 9-12 months. Management of modifiable risk factors may reduce stroke and mortality rates.

INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) Profiling Identifies Ambulatory Patients at High Risk on Medical Therapy After Hospitalizations for Heart Failure.

BACKGROUND: INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profiles provide important prognostic information for patients with advanced heart failure (HF) receiving mechanical support. The value of INTERMACS profiling has not been shown for patients followed on medical therapy for advanced HF at centers that also offer mechanical circulatory support. METHODS AND RESULTS: This prospective, observational study enrolled 166 patients with chronic New York Heart Association class III-IV HF, ejection fraction ≤30%, and ≥1 HF hospitalization in the previous year, excluding patients listed for transplant or receiving chronic intravenous inotropic therapy. Subjects were followed for at least 12 months or until death, mechanical support, or transplant. Baseline features, quality of life, and outcomes were compared according to INTERMACS profile. Mean age was 57 years, ejection fraction 18%, and 57% had HF >5 years, whereas 23% of subjects were INTERMACS profile 4, 32% profile 5, and 45% profile 6/7. At 1 year, only 47% of this ambulatory advanced HF cohort remained alive on medical therapy. Patients in INTERMACS profile 4 were more likely to die or require mechanical support, with only 52% of these patients alive without support after the first 6 months. Profile 6/7 patients had 1-year survival of 84%, similar to outcomes for contemporary destination left ventricular assist device recipients. Quality of life using the indexed EuroQol score was poor across profiles 4 to 7, although severe limitation was less common than for ambulatory patients enrolled in INTERMACS before ventricular assist device implantation. CONCLUSIONS: Ambulatory patients with systolic HF, a heavy symptom burden, and at least 1 recent HF hospitalization are at high risk for death or left ventricular assist device rescue. INTERMACS profiles help identify ambulatory patients with advanced HF who may benefit from current mechanical support devices under existing indications.

Recovery of Serum Cholesterol Predicts Survival After Left Ventricular Assist Device Implantation.

BACKGROUND: Advanced systolic heart failure is associated with myocardial and systemic metabolic abnormalities, including low levels of total cholesterol and low-density lipoprotein. Low cholesterol and low-density lipoprotein have been associated with greater mortality in heart failure. Implantation of a left ventricular assist device (LVAD) reverses some of the metabolic derangements of advanced heart failure. METHODS AND RESULTS: A cohort was retrospectively assembled from 2 high-volume implantation centers, totaling 295 continuous-flow LVAD recipients with ≥2 cholesterol values available. The cohort was predominantly bridge-to-transplantation (67%), with median age of 59 years and 49% ischemic heart failure cause. Total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels all significantly increased after LVAD implantation (median values from implantation to 3 months post implantation 125-150 mg/dL, 67-85 mg/dL, 32-42 mg/dL, and 97-126 mg/dL, respectively). On Cox proportional hazards modeling, patients achieving recovery of total cholesterol levels, defined as a median or greater change from pre implantation to 3 months post-LVAD implantation, had significantly better unadjusted survival (hazard ratio, 0.445; 95% confidence interval, 0.212-0.932) and adjusted survival (hazard ratio, 0.241; 95% confidence interval, 0.092-0.628) than those without cholesterol recovery after LVAD implantation. The continuous variable of total cholesterol at 3 months post implantation and the cholesterol increase from pre implantation to 3 months were also both significantly associated with survival during LVAD support. CONCLUSIONS: Initiation of continuous-flow LVAD support was associated with significant recovery of all 4 lipid variables. Patients with a greater increase in total cholesterol by 3 months post implantation had superior survival during LVAD support.

High early event rates in patients with questionable eligibility for advanced heart failure therapies: Results from the Medical Arm of Mechanically Assisted Circulatory Support (Medamacs) Registry.

BACKGROUND: The prognosis of ambulatory patients with advanced heart failure (HF) who are not yet inotrope dependent and implications for evaluation and timing for transplant or destination therapy with a left ventricular assist device (DT-LVAD) are unknown. We hypothesized that the characteristics defining eligibility for advanced HF therapies would be a primary determinant of outcomes in these patients. METHODS: Ambulatory patients with advanced HF (New York Heart Association class III-IV, Interagency Registry for Mechanically Assisted Circulatory Support profiles 4-7) were enrolled across 11 centers from May 2013 to February 2015. Patients were stratified into 3 groups: likely transplant eligible, DT-LVAD eligible, and ineligible for both transplant and DT-LVAD. Clinical characteristics were collected, and patients were prospectively followed for death, transplant, and left ventricular assist device implantation. RESULTS: The study enrolled 144 patients with a mean follow-up of 10 ± 6 months. Patients in the ineligible cohort (n = 43) had worse congestion, renal function, and anemia compared with transplant (n = 51) and DT-LVAD (n = 50) eligible patients. Ineligible patients had higher mortality (23.3% vs 8.0% in DT-LVAD group and 5.9% in transplant group, p = 0.02). The differences in mortality were related to lower rates of transplantation (11.8% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p = 0.02) and left ventricular assist device implantation (15.7% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p < 0.01). CONCLUSIONS: Ambulatory patients with advanced HF who were deemed ineligible for transplant and DT-LVAD had markers of greater HF severity and a higher rate of mortality compared with patients eligible for transplant or DT-LVAD. The high early event rate in this group emphasizes the need for timely evaluation and decision making regarding lifesaving therapies.

Outcomes for Patients With Diabetes After Continuous-Flow Left Ventricular Assist Device Implantation.

BACKGROUND: Diabetes mellitus (DM) is a risk factor for mortality among patients with heart failure as well as for patients who undergo cardiothoracic surgery. However it is unknown whether DM is associated with increased mortality or major complications during continuous-flow left ventricular assist device (CF-LVAD) support. METHODS AND RESULTS: We retrospectively reviewed 300 consecutive adults who received CF-LVADs at a single center in the years 2006-2013; 129 patients had DM before LVAD, as defined by American Diabetes Association criteria (HbA1c ≥6.5% and/or taking DM medications). Compared with the non-DM group, DM patients were older, with a higher pre-LVAD body mass index, more ischemic heart failure etiology, and higher pre-LVAD creatinine. Ninety-three patients died on LVAD support, 43 with DM and 50 without DM (P = .4526). After control for 9 covariates in a Cox proportional hazards model, DM was unassociated with all-cause mortality (hazard ratio 0.883, 95% confidence interval 0.571-1.366; P = .5768). Diabetes was also unassociated with the adverse event end points of stroke/transient ischemic attack, intracerebral hemorrhage, pump thrombosis, and device-related infections. CONCLUSIONS: Diabetes is common in LVAD recipients (43% of the present cohort) but does not increase mortality or rates of major adverse events during CF-LVAD support.

Replacement of the aortic valve with a bioprosthesis at the time of continuous flow ventricular assist device implantation for preexisting aortic valve dysfunction.

Left ventricular assist device (LVAD) implantation has become a mainstay of therapy for advanced heart failure patients who are either ineligible for, or awaiting, cardiac transplantation. Controversy remains over the optimal therapeutic strategy for preexisting aortic valvular dysfunction in these patients at the time of LVAD implant. In patients with moderate to severe aortic regurgitation, surgical approaches are center specific and range from variable leaflet closure techniques to concomitant aortic valve replacement (AVR) with a bioprosthesis. In the present study, we retrospectively analyzed our outcomes in patients who underwent simultaneous AVR and LVAD implantation secondary to antecedent aortic valve pathology. Between January 2004 and June 2010, 144 patients underwent LVAD implantation at a single institution. Of these, 7 patients (4.8%) required concomitant AVR. Five of the 7 patients (71%) survived to hospital discharge and suffered no adverse events in the perioperative period. One-year survival for the discharged patients was 80%, and no prosthetic valve-related adverse events were observed in long-term follow-up. Given our experience, we conclude that bioprosthetic AVR is a plausible alternative for end-stage heart failure patients at the time of LVAD implantation.

Caregivers and Left Ventricular Assist Devices as a Destination, Not a Journey.

BACKGROUND: The quality of life (QOL) of caregivers of patients with LVAD-DT (Left Ventricular Assist Device as Destination Therapy) has not been well explored. METHODS: We used a concurrent mixed methods design. Caregivers (n = 42; average 60 years old, 82% female, 75% white) of patients (n = 39; average 68.3 years old, 83% male, 90% white) and providers (n = 27) from 6 LVAD-DT programs were recruited. We used the City of Hope Quality of Life Family Caregiver instrument, modified for LVAD-DT. Lower scores indicate poorer QOL. We analyzed open-ended questions with the use of Nvivo 10.0, using a modified grounded theory approach. RESULTS: The Psychologic subscale had the lowest average QOL score, followed by Social, Spiritual, and then Physical subscales. The composite mean average QOL score across the subscales was highest in caregivers <40 years of age and ≥70 years of age. There was a nonsignificant trend toward better QOL in male caregivers (P = .06). We sorted QOL items into tertiles based on the percentage of responses <5 (10-point Likert scale). Scores <5 in the 2nd tertile (items from Social and Spiritual subscales) were reported by many fewer respondents than the 1st tertile (items from the Psychologic subscale). In the 3rd tertile, <10% of respondents scored <5 on 15 of the items. In qualitative interviews psychologic and social themes predominated in discussing requisites for competent caregivers, stress in pre-implantation decision making, lack of psychologic preparation, impact on freedom/independence, daily worry about pump performance, and value of psychologic and social support. CONCLUSION: Support interventions for caregivers of patients with LVAD-DT should address the psychologic and social aspects that lead to poor QOL.

S100A1 in human heart failure: lack of recovery following left ventricular assist device support.

BACKGROUND: We hypothesized that S100A1 is regulated during human hypertrophy and heart failure and that it may be implicated in remodeling after left ventricular assist device. S100A1 is decreased in animal and human heart failure, and restoration produces functional recovery in animal models and in failing human myocytes. With the potential for gene therapy, it is important to carefully explore human cardiac S100A1 regulation and its role in remodeling. METHODS AND RESULTS: We measured S100A1, the sarcoplasmic endoplasmic reticulum Ca(2+)ATPase, phospholamban, and ryanodine receptor proteins, as well as ß-adrenergic receptor density in nonfailing, hypertrophied (left ventricular hypertrophy), failing, and failing left ventricular assist device-supported hearts. We determined functional consequences of protein alterations in isolated contracting muscles from the same hearts. S100A1, sarcoplasmic endoplasmic reticulum Ca(2+)ATPase and phospholamban were normal in left ventricular hypertrophy, but decreased in failing hearts, while ryanodine receptor was unchanged in either group. Baseline muscle contraction was not altered in left ventricular hypertrophy or failing hearts. ß-Adrenergic receptor and inotropic response were decreased in failing hearts. In failing left ventricular assist device-supported hearts, S100A1 and sarcoplasmic endoplasmic reticulum Ca(2+)ATPase showed no recovery, while phospholamban, ß-adrenergic receptor, and the inotropic response fully recovered. CONCLUSIONS: S100A1 and sarcoplasmic endoplasmic reticulum Ca(2+)ATPase, both key Ca(2+)-regulatory proteins, are decreased in human heart failure, and these changes are not reversed after left ventricular assist device. The clinical significance of these findings for cardiac recovery remains to be addressed.