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.

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.

Unexpected abrupt increase in left ventricular assist device thrombosis.

BACKGROUND: We observed an apparent increase in the rate of device thrombosis among patients who received the HeartMate II left ventricular assist device, as compared with preapproval clinical-trial results and initial experience. We investigated the occurrence of pump thrombosis and elevated lactate dehydrogenase (LDH) levels, LDH levels presaging thrombosis (and associated hemolysis), and outcomes of different management strategies in a multi-institutional study. METHODS: We obtained data from 837 patients at three institutions, where 895 devices were implanted from 2004 through mid-2013; the mean (±SD) age of the patients was 55±14 years. The primary end point was confirmed pump thrombosis. Secondary end points were confirmed and suspected thrombosis, longitudinal LDH levels, and outcomes after pump thrombosis. RESULTS: A total of 72 pump thromboses were confirmed in 66 patients; an additional 36 thromboses in unique devices were suspected. Starting in approximately March 2011, the occurrence of confirmed pump thrombosis at 3 months after implantation increased from 2.2% (95% confidence interval [CI], 1.5 to 3.4) to 8.4% (95% CI, 5.0 to 13.9) by January 1, 2013. Before March 1, 2011, the median time from implantation to thrombosis was 18.6 months (95% CI, 0.5 to 52.7), and from March 2011 onward, it was 2.7 months (95% CI, 0.0 to 18.6). The occurrence of elevated LDH levels within 3 months after implantation mirrored that of thrombosis. Thrombosis was presaged by LDH levels that more than doubled, from 540 IU per liter to 1490 IU per liter, within the weeks before diagnosis. Thrombosis was managed by heart transplantation in 11 patients (1 patient died 31 days after transplantation) and by pump replacement in 21, with mortality equivalent to that among patients without thrombosis; among 40 thromboses in 40 patients who did not undergo transplantation or pump replacement, actuarial mortality was 48.2% (95% CI, 31.6 to 65.2) in the ensuing 6 months after pump thrombosis. CONCLUSIONS: The rate of pump thrombosis related to the use of the HeartMate II has been increasing at our centers and is associated with substantial morbidity and mortality.

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.

Optimizing Triage of Ambulatory Patients With Advanced Heart Failure: 2-Year Outcomes From REVIVAL.

BACKGROUND: Left ventricular assist device (LVAD) use remains uncommon in advanced heart failure (HF) patients not dependent on inotropes. OBJECTIVES: Before considering a randomized trial comparing a strategy of earlier use of LVAD to continued medical therapy, a better understanding is needed of the clinical trajectory of ambulatory patients with advanced systolic HF on optimal guideline-directed medical therapy (GDMT). METHODS: REVIVAL enrolled 400 patients with advanced ambulatory systolic HF, ≥1 HF mortality risk marker (≥2 HF hospitalizations past year; or HF hospitalization and high natriuretic peptide; or no HF hospitalizations but low peak oxygen consumption, 6-minute walk, serum sodium, HF survival score or Seattle HF model predicted survival), and no LVAD contraindication at 21 LVAD centers from July 2015 to June 2016. Patients were followed for 2 years or until a primary outcome (death, durable ventricular assist device, or urgent transplant). Clinical outcomes and health-related quality of life were evaluated. RESULTS: Mean baseline left ventricular ejection fraction was 21%, median 6-minute walk was 341 m, and 92% were Interagency Registry for Mechanically Assisted Circulatory Support profiles 5 to 7. Adherence to GDMT and electrical device therapies was robust. Composite primary outcome occurred in 22% and 37% at 1 and 2 years, with death alone in 8% and 16%, respectively. Patients surviving for 2 years maintained GDMT intensity and had no decline in health-related quality of life. CONCLUSION: Structured, serial follow-up at programs with expertise in caring for advanced ambulatory systolic HF patients facilitates triage for advanced therapies. Better strategies are still needed to avoid deaths in a small but significant group of patients who die without advanced therapies. REVIVAL patients not selected for VAD or transplant have robust survival and patient-reported outcomes, which challenges advocacy for earlier VAD implantation. (Registry Evaluation of Vital Information for VADs in Ambulatory Life [REVIVAL]; NCT01369407).

Inflow graft interruption as a simple method for left ventricular assist device removal after successful bridge to recovery.

In this report we provide another method of ventricular assist device separation by simply transecting the inflow graft of a Heart Mate II LVAD without the need of dissecting the left ventricular apex for cases of myocardial recovery.

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.

Management of left ventricular assist devices after surgery: bridge, destination, and recovery.

PURPOSE OF REVIEW: As the use and understanding of mechanical circulatory support (MCS) increases, the management of these devices has become more conventional. The purpose of this review is to discuss the perioperative and long-term management of MCS patients. RECENT FINDINGS: With the advent of axial flow pumps, both perioperative and long-term management are more standardized. The issues of nutrition, physical therapy, drive line care, and readiness to transition to home are becoming more mainstream and are readily accepted into the community. However, many factors remain that are not well defined in dealing with anticoagulation, weaning of MCS, achieving optimal device settings, and end-of-life care. SUMMARY: Care for the MCS patient provided in a multidisciplinary team approach is imperative to allow for a seamless transition from the hospital and into the community and successful long-term outcomes.

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.

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.

Unplanned hospital readmissions after HeartMate II implantation: frequency, risk factors, and impact on resource use and survival.

OBJECTIVES: The purpose of this study was to identify potential areas for quality improvement and cost containment. We investigated readmissions after HeartMate II left ventricular assist device (LVAD) implantation by characterizing their type, temporal frequency, causative factors, and resource use and survival after readmission. BACKGROUND: The HeartMate II LVAD provides enhanced survival and quality of life to end-stage heart failure patients. Whether these improved outcomes are accompanied by a similar reduction in unplanned hospital readmissions is largely unknown. METHODS: From October 2004 to January 2010, 118 patients received a HeartMate II, of whom 92 were discharged on device support. Subsequent readmissions were analyzed using prospectively maintained clinical and financial databases. RESULTS: Forty-eight patients (52%) had 177 unplanned hospital readmissions, 87 non-LVAD- and 90 LVAD-associated. Reasons for non-LVAD-associated readmissions included medical management of comorbidities and progression of cardiac pathology (n = 48), neuropsychiatric/psychosocial issues (n = 22), and infections (n = 17). Those for LVAD-associated readmissions included device component infection (n = 51), management of nontherapeutic anticoagulation or device malfunction (n = 22), and bleeding (n = 15). Cumulative incidence of unplanned readmissions was higher (p < 0.0001) for destination therapy than bridge-to-transplant patients (9/patient vs. 4/patient at 24 months). Cumulative hospital days overall were 25 and 42 at 12 and 18 months, respectively, and the costs were 18% and 29% of initial implantation costs. Increased number of unplanned readmissions was predictive of mortality. CONCLUSIONS: Unplanned readmissions are common during HeartMate II support and negatively affect resource use and survival. Refining patient selection, especially in destination therapy patients, reducing infectious and bleeding complications, and increasing awareness about these devices might reduce unnecessary readmissions.

Major bleeding during HeartMate II support.

OBJECTIVES: The aim of this study was to characterize a single-center experience of major bleeding complications during HeartMate II (HMII) (Thoratec Corp., Pleasanton, California) left ventricular assist device support, with focus on the subtypes and temporal patterns of post-operative bleeding. BACKGROUND: Bleeding complications are the most common post-operative adverse events after HMII implantation. The timing of bleeding events, relationship to coagulation status, and effect on post-operative survival are incompletely understood. METHODS: From October 2004 to June 2010, 139 HMII recipients at the Cleveland Clinic received 145 devices as a bridge to transplant or destination therapy for advanced heart failure. Major bleeding was defined using Interagency Registry for Mechanically Assisted Circulatory Support criteria, with an additional category created to maximize sensitivity for events. Pre-operative variables, coagulation status, and bleeding recurrence were assessed for correlation to primary events using modulated renewal within a multivariable analysis. RESULTS: The cumulative occurrence of major bleeding was 58% during 171 patient-years of follow-up. There were 1.14 major bleeds per patient-year, with 44% occurring as repeat bleeding events. A first bleed did not predict subsequent bleeding. The greatest risk of bleeding was noted within 2 weeks post-implantation. The international normalized ratio profile correlated poorly with the risk of bleeding. Bleeding early after surgery was associated with reduced survival while on HMII support. CONCLUSIONS: The risk of bleeding peaks early after HMII implantation. Bleeding of thoracic and gastrointestinal sources dominates these events, although many patients undergo transfusions for anemia without an apparent source of hemolysis or bleeding.

Heartmate II outflow graft ligation and driveline excision without pump removal for left ventricular recovery.

We report interruption of left ventricular assist device (VAD) support by way of outflow graft ligation and driveline excision while leaving the pump in situ. In this case, the indication for mechanical assist device separation was myocardial recovery, which occurred following 9 months of support. This case report demonstrates the feasibility of separating a patient from a VAD without the need for a major reoperative intervention.