Advanced Systolic Heart Failure Research Articles

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

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. 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. 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. 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.

2678 To the Heart of the Matter: A Case of Left Ventricular Assist Device Erosion at the Texas Heart Institute

INTRODUCTION: Left ventricular assist devices (LVADs) are used in patients with advanced systolic heart failure as a bridge to cardiac transplant or as destination therapy. LVADs provide a survival benefit in this population but pose a significant risk of infection, typically of the driveline. Gastrointestinal-related infectious complications of LVADs, including erosion into the GI tract, or a device-related enteric fistula are less common. Here we present a case of enteric LVAD erosion discovered while investigating unusual blood culture results. CASE DESCRIPTION/METHODS: A 52 year old man with history of alcohol-related cardiomyopathy now with LVAD and chronic driveline infections with Stenotrophomonas, E. cloacae, MRSA, and MSSA on suppressive antibiotics was admitted to our hospital after outpatient blood cultures grew C. albicans. He reported fatigue and forty-pound weight loss during the previous three months. He denied fevers, abdominal pain, nausea, vomiting, change in appetite or early satiety. On admission, the patient was afebrile. On physical exam, he was in no distress, the abdomen was soft and not tender. There was purulent drainage from the driveline site, unchanged from prior admissions. Given his unusual history of bloodstream infections with Lactobacillus, Enterobacter, E. coli, and now Candida, there was concern for a bowel connection to the LVAD. Cross-sectional imaging with PO contrast revealed expected positioning of the LVAD abutting the gastric body and significant hardware scatter artifact, limiting the examination (Figure 1). The patient therefore underwent bidirectional endoscopy and EGD revealed two areas of ulceration and exposed LVAD hardware eroding into the greater curvature of the gastric body (Figure 2). The patient underwent subsequent explant and replacement of the LVAD. Two defects in the gastric body, one near the cardia and the other near the antrum were repaired by omental flap placement and gastrorrhaphy. A peri-gastric abscess was also drained. DISCUSSION: LVADs have revolutionized the management of advanced heart failure, however one-half of patients will develop a device-related infection within nine months of implantation. Although less common, GI-related LVAD infections, including enteric erosion and fistula formation, require a high index of suspicion. Non-invasive testing is suboptimal given limitations of current imaging modalities. Therefore, these patients should undergo upper and lower endoscopy for direct visualization and timely diagnosis.

Registry Evaluation of Vital Information for VADs in Ambulatory Life (REVIVAL): Rationale, design, baseline characteristics, and inclusion criteria performance

Improved understanding of the clinical course of ambulatory advanced chronic systolic heart failure may improve the provision of appropriate care and is central to the design of clinical trials in this population. Twenty-one implanting ventricular assist device (VAD) centers enrolled 400 subjects in the Registry Evaluation of Vital Information for VADs in Ambulatory Life (REVIVAL),a prospective, observational study in ambulatory, chronic, advanced systolic heart failure, designed to identify a cohort with an approximately 25% 1-year risk of the primary composite outcome of death, urgent transplant, or durable mechanical circulatory support. Inclusion criteria utilized only information collected during routine clinical care. Exclusion criteria identified patients with contraindications to VAD. Study inclusion required at least 1 of 10 high-risk criteria derived from established hospitalization and non-hospitalization markers of increased mortality risk. We evaluated the test performance characteristics of the high-risk criteria. Data on 373 subjects evaluable for the primary composite outcome at the 1-year visit are presented. Baseline data were consistent with a less advanced cohort than Medical Arm for Mechanically Assisted Circulatory Support or Risk Assessment (MedaMACS) and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients (ROADMAP). Freedom from the primary composite outcome was 75.9%. Non-hospitalization inclusion criteria identified 89% of patients with events. Using routinely obtained clinical information for enrollment, REVIVAL successfully recruited an ambulatory chronic systolic heart failure cohort with an approximately 25% annual risk of the primary composite outcome. Information from this registry will be relevant to the planning of future trials of earlier VAD use and of other interventions in this population.

Percutaneous Intervention for Left Ventricular Assist Device Outflow Obstruction

Left ventricular assist devices (LVADs) are used to support patients with advanced systolic heart failure (HF). These patients might develop LVAD dysfunction and consequent HF symptoms. Occasionally, outflow graft obstruction is responsible for LVAD dysfunction. Here, we describe percutaneous techniques to repair the outflow graft and avoid re-sternotomy.

Sex-Based Differences in Left Ventricular Assist Device Utilization

Women comprise approximately one-third of the advanced heart failure population but may receive fewer advanced heart failure therapies including left ventricular assist devices (LVADs). During the early pulsatile-flow device era, women had higher post-LVAD mortality and increased complications. However, knowledge about these differences in the continuous-flow device era is limited. Therefore, we sought to explore temporal trends in LVAD utilization and post-LVAD mortality by sex. Patients with LVAD implantation from 2004 to 2016 were identified using the Nationwide Inpatient Sample. Trends in LVAD utilization and post-LVAD inpatient mortality were compared by sex and device era. Although LVADs are being increasingly utilized for patients with advanced systolic heart failure, women continue to represent a smaller proportion of LVAD recipients-25.8% in 2004 to 21.9% in 2016 (P for trend, 0.91). Women had increased inpatient mortality after LVAD implantation compared with men in the pulsatile-flow era (46.9% versus 31.1%, P<0.0001) but not in the continuous-flow era (13.3% versus 12.1%, P=0.27; P for interaction=0.0002). Inpatient mortality decreased for both sexes over time after LVAD, with a sharp fall in 2008 to 2009. Female sex was independently associated with increased post-LVAD inpatient mortality beyond adjustment for demographics and risk factors during the pulsatile-flow era (odds ratio, 2.13; 95% CI, 1.45-3.10; P<0.0001) but not during the continuous-flow era (1.18; 0.93-1.48; P=0.16). Although utilization of LVAD therapy increased over time for both sexes, LVAD implantation remains stably lower in women, which may suggest a potential underutilization of this potentially life-saving therapy. Prospective studies are needed to confirm these findings.

Macro- and Micronutrient Dietary Quality in Patients with Advanced Systolic Heart Failure Receiving Left Ventricular Assist Devices

Introduction Macro- and micronutrient insufficiencies are common in patients with ambulatory systolic heart failure (HF) and are associated with adverse clinical outcomes. Less is known about dietary quality in advanced systolic HF, particularly the adequacy of protein intake. It is also unknown if dietary quality improves during mechanical support and so we sought to determine nutrient intake changes early after left ventricular assist device (LVAD) implantation. Methods We recruited adults with advanced systolic HF ±21 days from LVAD implantation. Weight and appendicular lean mass (ALM) were assessed by whole-body dual X-ray absorptiometry (DXA). Food intake was assessed with 3-day facilitated food records and entered into the Food Processor Nutrition Analysis Software. Study procedures were repeated after 3 months ±14 days of LVAD support. The Institute of Medicine's Estimated Average Requirement values (EARs, age and sex-specific ranges) were tabulated beside the median (quartile 1-3) results from the baseline and 3-month food records.Comparisons were made between baseline and 3-month intakes using Wilcoxon matched-pairs signed rank tests. Results The cohort (n=18) was 78% male, with median age 60 years, weight 77.5 kg, BMI 25.2 kg/m2 and serum albumin 3.4 g/dL. Baseline dietary quality was poor as compared to general population EARs (Table 1), with a high prevalence of vitamin A, B1, B6, D, E, folate, calcium, magnesium, zinc and selenium insufficiencies. Protein supplementation products were used by 78% at baseline and 39% at 3 months. Despite no changes in average daily calorie or carbohydrate intake from baseline to 3 months, and only a non-significant upward trend in protein and fat intake, there was an increase in total body weight and appendicular lean mass (Table). Micronutrient intakes did not significantly improve at 3 months, and intake of calcium and vitamin D decreased. Conclusions Baseline micronutrient dietary quality was poor amongst patients with systolic HF undergoing LVAD implantation. Micronutrient changes at 3 months were variable, with some intakes including calcium and vitamin D decreasing, possibly secondary to reduced use of supplementation products after the LVAD implantation hospitalization. Protein intake was sufficient per estimated average requirements and non-significantly trended upwards during the first 3 months of LVAD support.

Home Inotropic Therapy Post Left Ventricular Assist Device Placement

Purpose Left ventricular assist device (LVAD) therapy improves survival and quality of life in patients with advanced systolic heart failure. Right heart failure (RHF) is not uncommon following LVAD implantation and is associated with poor prognosis. Management of RHF post LVAD often involves inotropic therapy. Refractory RHF may require discharge on home inotropes. Outcomes in LVAD patients discharged on inotropic therapy has not been well studied. We report our experience with LVAD patients discharged home on inotropic therapy. Methods We retrospectively reviewed 520 durable LVAD implants at our center between 1/1/13 and 4/1/18. All patients discharged on home inotropic therapy following LVAD implantation were included. Age, device type, duration of inotropic therapy, infection, ICD shocks, rehospitalizations, and outcomes were recorded. Results 39 LVAD patients were discharged on inotropic therapy and included in this analysis. The average age was 56.7±13.6 years. 31 (79%) were male. 20 (51%) patients were implanted as destination therapy (DT). We included 16 (41%) patients with HeartWare LVADs and 28 with HeartMate2 LVADs. Average time on device support was 950±523 days. Average time on inotropes was 319±236 days. 6 patients (15%) had initiation of inotropes during index admission (early RHF), while the remaining patients had late RHF. Average time from implant to initiation of inotropes was 474±453 days. 18 (46%) patients developed PICC line site infections and 29 (74%) patients developed bacteremia. 21 (54%) patients developed driveline infections. There was a total of 246 readmissions following inotrope initiation. 18 (46%) patients received ICD shocks while on inotropic therapy. 11 (28%) patients died on inotropes at an average of 325±251 days from initiation of inotropes with RHF being the primary cause of death in 9 (81%) patients. Nine (23%) patients underwent successful heart transplantation. Conclusion Home inotropic therapy following LVAD implantation is associated with significant risk. Infections, including PICC line infections and bacteremia occurred at high rates. Late RHF was more common than early RHF. Overall, there is a high morbidity and mortality associated with home inotropic therapy post-LVAD. Further analysis of post-LVAD care may provide insight regarding opportunities to avoid late RHF given the lack of viable options for its management.

Outpatient Weaning of Inotropes is Achievable in Patients with Advanced Heart Failure

Purpose Patients admitted with advanced decompensated systolic heart failure (ADHF) typically require inotropes . Those who cannot be bridged to advanced heart failure therapies are discharged home on inotropes (as a palliative measure or until eligible for advanced therapies). Continuous inotrope infusion exposes patients to increased risk of arrhythmias and mortality. It is unknown whether such patients can be weaned off inotropic support in an outpatient setting. Methods In a single-center observational study of patients admitted with ADHF between 2016-2018, we studied demographics, clinical history, physical exam data, and laboratory data. We determined functional status and compliance with medical therapies of patients who were successfully weaned off inotropes. Creatinine , electrolytes, vital signs, and physical exam findings were followed weekly/biweekly during weaning and followed post-wean for ≥60 days. Results 9 patients (mean age 49 y; 5 males) were successfully weaned off inotropes in an outpatient setting. All had been discharged home on milrinone or dobutamine infusion. Only 1 patient had ischemic cardiomyopathy ; 2 had required mechanical support during hospitalization. Median length of stay after inotrope initiation was 8 days with median 78 days on inotropes prior to weaning. 6 patients were started on sacubitril/valsartan, which was uptitrated during weaning, of whom 3 tolerated the maximum dose. The other patients were uptitrated on angiotensin converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARB). 60 days post-wean, all 9 patients reported doing well with NYHA Class IIIa (n=5), Class IV (n=1), and Class II (n=3) symptoms. On longitudinal follow-up, 1 patient was hospitalized 1-year post-wean, was subsequently restarted on inotropes and required heart transplantation . Conclusion With close monitoring and gentle uptitration of afterload-reducing agents, it is feasible to wean patients with ADHF off inotropes in an outpatient setting.

Abstract 16800: Sarcopenia in Advanced Systolic Heart Failure Patients Receiving Left Ventricular Assist Devices

Introduction: Sarcopenia is the age-related deterioration in skeletal muscle mass and function, which can be accelerated by chronic comorbidities. The prevalence in advanced systolic heart failure (HF) and impact on HF health status are currently uncertain. Sarcopenia diagnostic criteria from the Foundation for the National Institutes of Health (FNIH) and European Working Group on Sarcopenia in Older People (EWGSOP) have not been applied to HF cohorts. Hypothesis: We hypothesized that at the time of left ventricular assist device (LVAD) implantation systolic HF patients have prevalent sarcopenia, and that sarcopenia is associated with poorer nutritional and HF health status. Methods: We recruited 18 adults with systolic HF ±21 days from LVAD implantation. All underwent whole-body dual X-ray absorptiometry (DXA) to calculate appendicular lean mass (ALM). Subjects also underwent a 3-day food recall, Simplified Nutritional Appetite Questionnaire (SNAQ), Kansas City Cardiomyopathy Questionnaire (KCCQ) for HF health status, handgrip strength and blood testing. Sarcopenia was defined by 2 ALM criteria: FNIH – males &lt;19.75kg, females &lt;15.02kg; EWGSOP – males &lt;7.26kg/m 2 , females &lt;5.5kg/m 2 . Linear regression determined relationships between appendicular lean mass and age, weight, handgrip strength, KCCQ summary score, SNAQ score, 24-hour protein intake, and key blood variables, without/with adjustment for sex and height. Results: Sarcopenia was diagnosed in 5 subjects (28%) by FNIH criteria and an additional 5 (10 total, 56%) by EWGSOP criteria (Figure). There were unadjusted associations between lower appendicular lean mass and lower handgrip strength; higher SNAQ score (higher malnutrition risk); lower sodium; and lower hemoglobin. After adjustment for sex and height, lower lean mass remained associated with lower hemoglobin. Lower appendicular lean mass was also independently associated with higher (more favorable) KCCQ scores. Conclusions: As many as half of advanced systolic HF patients meet standard DXA criteria for sarcopenia. Lower appendicular lean mass is independently associated with lower hemoglobin but does not appear to be associated with poorer HF status.

Transient elevation of high-sensitive troponinT after Cardioband implantation.

The Cardioband system enables percutaneous surgical-like direct mitral valve annuloplasty and, thereby, repair of severe functional mitral valve regurgitation (MR) in patients with advanced systolic heart failure (HF) and dilation of the left ventricular (LV) annulus. Since the device is anchored by screws in the LV annulus, limited myocardial injury is likely to occur. Five patients (Society of Thoracic Surgeons score: 2.7 ± 0.7%) with severe HF (LV ejection fraction [LVEF]: 17 ± 1%; LV end-diastolic diameter [LVEDD]: 71 ± 3 mm) were treated with the Cardioband (sizes C-F) receiving 14-17screws in the LV annulus region. Myocardial injury was monitored by measuring high-sensitive cardiac troponinT (hsTnT) levels and by echocardiography. All patients showed significant periprocedural increase in hsTnT levels. Peak hsTnT concentration was reached between day1 and day6 (593 ± 141 pg/ml). None of the patients showed clinical signs of myocardial infarction, ST-segment elevation, new onset of deteriorated myocardial wall motion, or new ventricular tachycardia. hsTnT levels normalized in all patients after 14days (hsTnT on day0: 34 ± 6 pg/ml vs. hsTnT on day14: 36 ± 6 pg/ml; p = 0.604). This nonischemic hsTnT kinetics was compared to asixth patient who experienced proximal damage of the left circumflex artery (LCX) and ST-segment elevation during the Cardioband procedure, followed by immediate repair of the LCX, avoiding structural damage of the LV. Cardioband implantation is accompanied by significant elevation of hsTnT without causing structural myocardial damage or clinical symptoms such as worsening of LV function, new-onset LV regions exhibiting reduced wall motion, or ventricular tachycardia.

The Metabolic Syndrome, Cardiovascular Fitness and Survival in Patients With Advanced Systolic Heart Failure

The metabolic syndrome (MetS), which incorporates insulin resistance, visceral adiposity, and dyslipidemia, is an independent risk factor for incident heart failure (HF), but the impact on survival is uncertain. We sought to determine the relation between the metabolic syndrome and survival in ambulatory systolic HF patients and the impact of MetS on cardiopulmonary exercise test (CPET). We identified adults with ejection fraction ≤40% who underwent CPETs between 2000 and 2011. Baseline MetS status was defined by 3 or more of: (1) Triglycerides ≥150 mg/dl; (2) High density lipoprotein <40 mg/dl males or <50 mg/dl females; (3) Diabetes mellitus; (4) Hypertension; (5) Body mass index ≥35 kg/m2. Minimally-adjusted (for age, sex, transplantation and left ventricular assist device implantation) and fully-adjusted Cox proportional hazards models were constructed for all-cause mortality. MetS prevalence was 37% (716 of 1,953) and median follow-up 5 years. Mortality was 36% for +MetS and 29% for -MetS (p = 0.006), with highest mortality in the subgroup with both MetS plus diabetes (39%). The minimally-adjusted hazard ratio for mortality with MetS was 1.27 (95% confidence interval, 1.08 to 1.49, p = 0.004). After adjustment, MetS was no longer independently associated with mortality (hazard ratio 1.01, 95% confidence interval 0.85 to 1.19, p = 0.921). Patients with MetS achieved poorer CPET performance compared and MetS was independently associated with a lower peak VO2. MetS was associated with a higher hazard of mortality in the minimally-adjusted model, which was primarily driven by the unfavorable impact of diabetes on mortality, but this association was no longer significant after full adjustment. In conclusion, there was no independent association between MetS and survival in an ambulatory systolic HF population.

Neopterin as a novel marker; well correlated with mortality and morbidity in patients with advanced systolic heart failure

Objective: The aim of this study is research relation of serum neopterin level with mortality and morbidity due to systolic HF and also its role in diagnosis of patients with systolic HF. Material and methods: Eighty-one patients with systolic heart failure (HF group) and eighty-one age- and gender-matched healthy subjects (the control group) were enrolled in the study. Echocardiographic examination was performed accordingly. At the beginning of the study, serum B type natriuretic peptide (BNP), neopterin, and high sensitive C-reactive protein (hs-CRP) were measured accordingly. The subjects were followed for one year then after. Mortality rate and number of hospitalisation due to HF were recorded. Results: Age and gender distribution over the groups were statistically similar (p > .05). LVEF of the control and HF groups were 62 ± 3 and 27 ± 3%, respectively (p < .001). Average neopterin value of HF group was significantly higher than that of the control group (p < .001). Both hs-CRP and BNP values were well correlated to neopterin values (p = .667 and .778, respectively). There was a significant correlation between number of hospitalisation and neopterin values among patients in HF group (p = .008). Also among HF group, neopterin value of patients died within first year of follow-up (n = 29) was higher than that of patients survived beyond first year (n = 52 and p = .011). Conclusions: Neopterin is a biomarker reflecting ongoing inflammatory process in deteriorating heart. High level of serum neopterin concentrations was associated with mortality and morbidity in systolic HF.

Daily non-invasive haemodynamic telemonitoring for efficacy evaluation of MitraClip® implantation in patients with advanced systolic heart failure.

AimPatients with advanced systolic chronic heart failure frequently suffer from progressive functional mitral regurgitation. We report our initial experience in patients with an implanted pulmonary artery pressure (PAP) sensor, who developed severe mitral regurgitation, which was treated with the MitraClip system. We non‐invasively compared changes in PAP values in patients after MitraClip with PAP changes in patients without MitraClip.Methods and resultsAmong 28 patients with New York Heart Association III heart failure with implanted PAP sensor for haemodynamic telemonitoring from a single centre, four patients (age 66 ± 6 years, left ventricular ejection fraction 21 ± 3%, and cardiac index 1.8 ± 0.3) received a MitraClip procedure and were compared with 24 patients (age 72 ± 8 years, left ventricular ejection fraction 26 ± 9.9%, and cardiac index 2.0 ± 1.0) without MitraClip procedure in a descriptive manner. Ambulatory PAP values were followed for 90 days in both groups. In comparison with the PAP values 4 weeks before MitraClip procedure, PAP was profoundly reduced in all four patients after 30 days (ΔPAPmean −11 ± 5, ΔPAPdiast −7 ± 3 mmHg, P < 0.02) as well as after 90 days (ΔPAPmean −6.3 ± 6, ΔPAPdiast −1 ± 3 mmHg). Reductions in PAP were accompanied by a profound reduction in N terminal pro brain natriuretic peptide as well as clinical and echocardiographic improvement. When analysing the dynamics with a regression model, reductions in all PAP values were significantly greater after MitraClip compared with conservative haemodynamic monitoring (P < 0.001).ConclusionsThe efficacy of the interventional MitraClip procedure on clinical symptoms can be confirmed by haemodynamic telemonitoring. Thus, daily non‐invasive haemodynamic telemonitoring allows, for the first time, for a continuous assessment of the haemodynamic efficacy of novel therapies in patients with chronic heart failure.

Cryoballoon ablation of atrial fibrillation in patients with advanced systolic heart failure and cardiac implantable electronic devices.

Pulmonary vein isolation with cryoballoon catheter ablation (CCB) is an effective method of treatment in patients with atrial fibrillation (AF), but in patients with heart failure (HF) the role of CCB remains unknown. The aim of the study was to assess the feasibility, effectiveness, and safety of CCB in patients with HF and cardiac im-plantable electronic devices (CIEDs), the impact of the procedure on symptoms, and echocardiographic parameters. Thirty consecutive HF patients with left ventricular ejection fraction (LVEF) ≤ 40% and CIED, referred for CCB of AF, were included. Procedural parameters were compared to a group of 59 consecutive patients without cardiac diseases referred for CCB (control group). The number of veins ablated per patient was smaller and application was performed less frequently in the right inferior pulmonary vein in the HF group compared with the control group (66.7% vs. 88.1%; p = 0.01, respectively). In two (6.7%) patients from the HF group and in five (8.5%) from the control group procedure-related complications occurred (p = 0.76). After six months 21 HF patients (70%), after one year 13 (43%), and after 625 days only three (10%) were free from arrhythmia. AF burden was significantly reduced after six months compared to the pre-ablation period (18.5% vs. 52.9%; p = 0.001). New York Heart Association and European Heart Rhythm Association classes were both significantly (p < 0.001) reduced and LVEF was higher after six months in the HF patients. Safety and feasibility of CCB for AF in HF patients with CIED are comparable to subjects with structurally nor-mal heart; however, stable positioning of the balloon in the right inferior pulmonary vein may be more challenging. Although late recurrences are common, ablation reduces arrhythmia burden and leads to a long-term improvement of symptoms and echocardiographic indices.

Efficacy and safety of intermittent intravenous outpatient administration of levosimendan in patients with advanced heart failure: the LION-HEART multicentre randomised trial.

The LION-HEART study was a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial evaluating the efficacy and safety of intravenous administration of intermittent doses of levosimendan in outpatients with advanced chronic heart failure. Sixty-nine patients from 12 centres were randomly assigned at a 2:1 ratio to levosimendan or placebo groups, receiving treatment by a 6-hour intravenous infusion (0.2 μg/kg/min without bolus) every 2 weeks for 12 weeks. The primary endpoint was the effect on serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) throughout the treatment period in comparison with placebo. Secondary endpoints included evaluation of safety, clinical events and health-related quality of life (HRQoL). The area under the curve (AUC, pg.day/mL) of the levels of NT-proBNP over time for patients who received levosimendan was significantly lower than for the placebo group (344 × 103 [95% Confidence Interval (CI) 283 × 103 -404 × 103 ] vs. 535 × 103 [443 × 103 -626 × 103 ], p = 0.003). In comparison with the placebo group, the patients on levosimendan experienced a reduction in the rate of heart failure hospitalisation (hazard ratio 0.25; 95% CI 0.11-0.56; P = 0.001). Patients on levosimendan were less likely to experience a clinically significant decline in HRQoL over time (P = 0.022). Adverse event rates were similar in the two treatment groups. In this small pilot study, intermittent administration of levosimendan to ambulatory patients with advanced systolic heart failure reduced plasma concentrations of NT-proBNP, worsening of HRQoL and hospitalisation for heart failure. The efficacy and safety of this intervention should be confirmed in larger trials.

Can a Left Ventricular Assist Device in Individuals with Advanced Systolic Heart Failure Improve or Reverse Frailty?

Frailty, characterized by low physiological reserves, is strongly associated with vulnerability to adverse outcomes. Features of frailty overlap with those of advanced heart failure, making a distinction between them difficult. We sought to determine whether implantation of a left ventricular assist device (LVAD) would decrease frailty. Prospective, cohort study. Five academic medical centers. Frail individuals (N = 29; mean age 70.6 ± 5.5, 72.4% male). Frailty, defined as having 3 or more of the Fried frailty criteria, was assessed before LVAD implantation and 1, 3, and 6 months after implantation. Other domains assessed included quality of life, using the Kansas City Cardiomyopathy Questionnaire; mood, using the Patient Health Questionnaire; and cognitive function, using the Trail-Making Test Part B. After 6 months, three subjects had died, and one had undergone a heart transplant; of 19 subjects with serial frailty measures, the average number of frailty criteria decreased from 3.9 ± 0.9 at baseline to 2.8 ± 1.4 at 6 months (P = .003). Improvements were observed after 3 to 6 months of LVAD support, although 10 (52.6%) participants still had 3 or more Fried criteria, and all subjects had at least one at 6 months. Changes in frailty were associated with improvement in QOL but not with changes in mood or cognition. Higher estimated glomerular filtration rate at baseline was independently associated with a decrease in frailty. Frailty decreased in approximately half of older adults with advanced heart failure after 6 months of LVAD support. Strategies to enhance frailty reversal in this population are worthy of additional study.

Bleeding and thrombosis associated with ventricular assist device therapy

Over the past decade, continuous-flow rotary pumps have dramatically improved survival for patients with advanced systolic heart failure. Bleeding and thrombosis, however, continue to be the Achilles heel of left ventricular assist device (LVAD) therapy. There is a dynamic and complex interaction between the patient and pump. The net effect of a variety of hematologic derangements, such as hemolysis, high-molecular-weight von Willebrand degradation, platelet activation and diminished pulsatility, is poorly understood. A combination of these factors mediates the common adverse events of gastrointestinal bleeding, device thrombosis and stroke. In this review we incorporate information from translational investigations in LVAD patients to understand how continuous-flow pumps activate the coagulation system and platelets predisposing to thrombosis, while, in parallel, degrade high-molecular-weight von Willebrand factor and trigger abnormal angiogenesis predisposing to bleeding. Finally, we propose novel strategies to develop a personalized approach to anti-thrombotic monitoring and titration of anti-coagulants to minimize the bleeding and thrombotic event rates of future LVAD recipients.

Frailty and Advanced Heart Failure in Older Adults

Purpose of Review Advances in medical therapy have resulted in a growing population of older adults with advanced heart failure. Frailty is a clinical syndrome that increases in prevalence with age and is highly prevalent in patients with heart failure. This paper reviews the complex relationship between frailty and advanced systolic heart failure in older adults, including the potential for reversal of frailty following advanced cardiac interventions.

Does aortic pulse wave velocity have any prognostic significance in advanced heart failure patients?

Introduction: Noninvasive measurement of arterial stiffness by pulse-wave velocity (PWV) has prognostic value in different sub groups of cardiovascular disorders. We aimed to measure the PWV in advanced heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF) and investigate whether it has any prognostic significance in this group of patients. Methods: Between 2013 to 2015 patients with a diagnosis of advanced HF (LVEF ≤ 30%) scheduled for right heart catheterization (RHC) were included in our study. PWV was measured before RHC in each patient using vascular explorer device (Enverdis GmbH) in catheterization laboratory. The patients were subsequently followed for 6 months and their hospitalization or death (composite of all-cause death/hospitalization) were recorded. Results: A total of 50 patients (38 men) were enrolled. The mean (SD) of age was 45 (16) years. The mean PWV was 6.8 m/s. There was no statistically significant correlation between the PWV and the clinical, echocardiographic and RHC data. The PWV was not different in patients with or without composite of all-cause death/hospitalization (7.3 versus 6.3, P > 0.05). In this study cardiac output (CO) (beta = -0.53, P = 0.02, odds ratio = 0.6, 95% CI = 0.4-0.9), pulse pressure (PP) (beta = -0056, P = 0.03, odds ratio=0.95, 95% CI = 0.89-0.99) and age (beta = -0.045, P = 0.05, odds ratio = 0.96, 95% CI = 0.9-1.001) were independent predictors of composite of all-cause death/ hospitalization. Conclusion: In patients with advanced systolic HF, PWV may not be a good prognostic factor and does not have any added value over previous well known prognostic factors.

Positive Impact of Continuous-Flow Left Ventricular Assist Device Implantation on Glycemic Control in Patients with Type 2 Diabetes Mellitus and Advanced Chronic Systolic Heart Failure.

To evaluate the impact of continuous-flow left ventricular assist device (LVAD) implantation on glycemic control in patients with type 2 diabetes mellitus and advanced chronic systolic heart failure. Retrospective medical record review. Large academic tertiary and quaternary care hospital. Eighty-three adults with type 2 diabetes mellitus and advanced chronic systolic heart failure who underwent implantation of a continuous-flow LVAD between July 1, 2008, and June 30, 2013. Baseline demographic data and laboratory values pertinent to glycemic control (hemoglobin A1c [A1C], total daily insulin requirements, noninsulin antidiabetic medication use, and body mass index [BMI]) were collected for each patient. Pre-LVAD data were compared with data obtained during the 24 months after LVAD implantation. The mean age of the study population was 61.3 years, 70% were men, and 63% had ischemic cardiomyopathy. The first available mean ± SD A1C after LVAD implantation was 6.21 ± 1.5% at a median of 4.8 months (interquartile range 3.3-8.9), which represented a significant decrease from the pre-LVAD A1C of 7.46 ± 1.5% (p<0.001). Average daily insulin requirements decreased by 22.9 units at the end of 24 months (p<0.001). Over half of patients with prescriptions for noninsulin antidiabetic medications were able to discontinue therapy by the end of the study. Of note, BMI increased in the second year after LVAD implantation from a baseline of 32.3 kg/m2 to 34.9 kg/m2 (p=0.004). Regression analysis revealed that baseline A1C was the only independent predictor of change in A1C. LVAD implantation was associated with a significant improvement in glycemic control. Further prospective studies are needed to evaluate the long-term impact of LVAD implantation on the clinical course of diabetes.