The Interaction of Amiodarone and Continuous-flow Left Ventricular Assist Device Use in Risk of Severe Primary Graft Dysfunction Following Heart Transplantation.

BACKGROUND: Primary graft dysfunction (PGD) increases morbidity and mortality after heart transplant. Here we investigated (1) the association of continuous-flow left ventricular assist device (CF-LVAD), amiodarone, and severe PGD and (2) the safety of amiodarone discontinuation in CF-LVAD patients. METHODS: Retrospective, single-center study of heart transplant recipients was conducted to investigate the association of risk factors and severe PGD. Patients were grouped into 4 groups based on the presence (denoted +) or absence (denoted -) of amiodarone and CF-LVAD. Prospective amiodarone discontinuation was undertaken to investigate its safety in a cohort of CF-LVAD patients. Study endpoints were severe PGD and recurrence of arrhythmia. RESULTS: Severe PGD was strongly associated with CF-LVAD and amiodarone use, and its prevalence is highest if both risk factors were present (CF-LVAD-/amiodarone - 1.5%, CF-LVAD -/amiodarone+ 4.5%, CF-LVAD+/amiodarone - 7.1%, CF-LVAD+/amiodarone+ 21.8%; P < 0.01). The product of every 1-y additional CF-LVAD support by every 100 mg amiodarone was associated with severe PGD (adjusted odds ratio, 1.43; 95% confidence interval, 1.15-1.78; P < 0.01). Amiodarone was prospectively discontinued in 28 CF-LVAD patients. Of them, 6 patients had recurrence of arrhythmia requiring treatment or heart failure admission. There were no deaths. Nine patients in whom amiodarone had been discontinued had heart transplants with no severe PGD. CONCLUSIONS: Amiodarone and CF-LVAD were independently associated with severe PGD. The combination of both risk factors was associated with a higher prevalence of severe PGD. Amiodarone discontinuation was associated with recurrence of arrhythmia in 6 CF-LVAD patients. There was no mortality associated with amiodarone discontinuation.

Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmia in Continuous-Flow Left Ventricular Assist Device.

Cardiac sympathetic denervation has been shown to reduce sustained ventricular arrhythmias and implantable cardioverter-defibrillator shocks by inhibiting sympathetic outflow to the heart. We describe the first case to our knowledge of cardiac sympathetic denervation in the left ventricular assist device population. (Level of Difficulty: Advanced.).

Feasibility of high-intensity interval training in patients with left ventricular assist devices: a pilot study.

AIMS: Patients with left ventricular assist device (LVAD) suffer from persistent exercise limitation despite improvement of their heart failure syndrome. Exercise training (ET) programmes to improve aerobic capacity have shown modest efficacy. High-intensity interval training (HIIT), as an alternative to moderate continuous training, has not been systematically tested in this population. We examine the feasibility of a short, personalized HIIT programme in patients with LVAD and describe its effects on aerobic capacity and left ventricular remodelling. METHODS AND RESULTS: Patients on durable LVAD support were prospectively enrolled in a 15-session, 5 week HIIT programme. Turndown echocardiogram, Kansas City Cardiomyopathy Questionnaire, and cardiopulmonary exercise test were performed before and after HIIT. Training workloads for each subject were based on pretraining peak cardiopulmonary exercise test work rate (W). Percentage of prescribed training workload completed and adverse events were recorded for each subject. Fifteen subjects were enrolled [10 men, age = 51 (29-71) years, HeartMate II = 12, HeartMate 3 = 3, and time on LVAD = 18 (3-64) months]. Twelve completed post-training testing. HIIT was well tolerated, and 90% (inter-quartile range: 78, 99%) of the prescribed workload (W) was completed with no major adverse events. Improvements were seen in aV̇O2 at ventilatory threshold [7.1 (6.5, 9.1) to 8.5 (7.7, 9.3) mL/kg/min, P = 0.04], work rate at ventilatory threshold [44 (14, 54) to 55 (21, 66) W, P = 0.05], and left ventricular end-diastolic volume [168 (144, 216) to 159 (124, 212) mL, n = 7, P = 0.02]. HIIT had no effect on maximal oxygen consumption (V̇O2peak ) or Kansas City Cardiomyopathy Questionnaire score. CONCLUSIONS: Cardiopulmonary exercise test-guided HIIT is feasible and can improve submaximal aerobic capacity in stable patients with chronic LVAD support. Further studies are needed on its effects on the myocardium and its potential role in cardiac rehabilitation programmes.

Relation of Peripheral Venous Pressure to Central Venous Pressure in Patients With Heart Failure, Heart Transplant, and Left Ventricular Assist Device.

Peripheral venous pressure (PVP) monitoring is a noninvasive method to assess volume status. We investigated the correlation between PVP and central venous pressure (CVP) in heart failure (HF), heart transplant (HTx), and left ventricular assist device (LVAD) patients undergoing right heart catheterization (RHC). A prospective, cross-sectional study examining PVP in 100 patients from October 2018 to January 2020 was conducted. The analysis included patients undergoing RHC admitted for HF, post-HTx monitoring, or LVAD hemodynamic testing. Sixty percent of patients had HF, 30% were HTx patients, and 10% were LVAD patients. The mean PVP was 9.4 ± 5.3 mm Hg, and the mean CVP was 9.2 ± 5.8 mm Hg. The PVP and CVP were found to be highly correlated (r = 0.93, p < 0.00001). High correlation was also noted when broken down by HF (r = 0.93, p < 0.00001), HTx (r = 0.93, p < 0.00001), and LVAD groups (r = 0.94, p < 0.00005). In conclusion, there is a high degree of correlation between PVP and CVP in HF, HTx, and LVAD patients. PVP measurements can be used as a rapid, reliable, noninvasive estimate of volume status in these patient populations.

Association of centre volume and in-hospital mortality in heart failure hospitalisations.

BACKGROUND: Centre volume is an important determinant of outcomes in patients requiring complex medical treatments or surgical procedures. Heart failure hospitalisation (HFH) has become an increasingly complex and resource intensive clinical event. We evaluated the effect of centre volume on mortality and costs in patients with HFH. METHODS: This was a retrospective registry-based analysis of adult patients discharged with a primary diagnosis of HF from hospitals across New York (NY) State over a 5-year period, between January 2009 and December 2013, using the Statewide Planning and Research Cooperative System inpatient discharge files. The primary outcome of interest was in-hospital mortality. All patients were followed from the day of admission to either in-hospital death or discharge alive. RESULTS: 300 972 HFHs from 198 facilities across NY State were included. Five-year centre volume was associated with a decrease in in-hospital mortality in unadjusted (HR=0.872, 95% CI 0.863 to 0.881, p<0.001) and adjusted Cox models (HR=0.869, 95% CI 0.859 to 0.879, p<0.001). After dividing the overall cohort into three groups based on 5-year centre volume, groups with medium and high volume centres had lower in-hospital mortality when compared with the group with low volume centres. The results were consistent in various subgroup analyses. Furthermore, hospitals in the higher centre volume groups had increased HFH costs across different severity of illness categories and involved increased use of cardiac procedures. CONCLUSIONS: Higher centre volume was associated with lower HFH mortality but increased HFH costs and increased cardiac procedures in a cohort of Medicare and non-Medicare beneficiaries.

Readmissions after ventricular assist device: etiologies, patterns, and days out of hospital.

BACKGROUND: Scarce literature exists describing the patterns of readmission after continuous flow left ventricular assist device (CF-LVAD) implantation. These carry significant cost and quality of life implications. We sought to describe the etiology and pattern of readmission among patients receiving CF-LVADs. METHODS: Frequency, reason, urgency, and duration of readmission as well as freedom from readmission were examined in a retrospective review of our institutional experience. As an indirect means of quality of life, the ratio of days out of hospital (OOH)/days alive with device was calculated. RESULTS: From 2006 to 2011, 71 adult patients implanted with a CF device were included. Indication for device implantation was bridge to transplant (n=19), potential bridge to transplant (n=25), or destination therapy (n=27). Length of support averaged 359 days. Total support time was 69.7 patient years. One hundred fifty-five readmissions accounted for a total of 1,659 hospital days. Fifty-six patients were readmitted during the study period. Median time to first readmission was 48 days (range 2 to 663 days). Median length of stay was 5 days. The single most common etiology for readmission was gastrointestinal bleeding accounting for 14% of readmissions. Readmissions were urgent (87%), elective (10%), or life-threatening (3%). Patients on the average enjoyed 92% of their time OOH. CONCLUSIONS: Patients undergoing CF-LVAD support are often readmitted within 6 months of discharge. Readmissions tend to be of short duration and the most common reason is for gastrointestinal bleeding. Importantly, following discharge after implant procedure, 51 patients spent at least 90% of days OOH.

Combining neurohormonal blockade with continuous-flow left ventricular assist device support for myocardial recovery: a single-arm prospective study.

BACKGROUND: Combining mechanical unloading by a continuous-flow left ventricular assist device (CF-LVAD) and neurohormonal blockade with heart failure medications (HFMED) is an underexplored clinical strategy to promote recovery of cardiac function in patients with advanced heart failure (HF). METHODS: We implemented a clinical protocol to achieve maximal neurohormonal blockade after placement of a CF-LVAD and assessed its utility in an LVAD weaning (6,200 rpm) study. Thirty-four subjects were enrolled after CF-LVAD and were managed with aggressive, bi-weekly up-titration of HFMED. RESULTS: Twenty-one subjects (8 with coronary artery disease, 13 with idiopathic dilated cardiomyopathy) were included in this LVAD weaning investigation. Overall, combined CF-LVAD and HFMED resulted in significant reverse remodeling with a decrease in left atrial volume index (44.7±16.0 to 31.6±12.1 ml/m(2), p < 0.001) and LV internal diastolic diameter (6.7±1.5 to 6.0±1.6 cm, p = 0.003) and an increase in LV ejection fraction (17.4±6.5 to 33.1±16.2%, p < 0.001) during LVAD weaning (6,200 rpm). Five of 21 (24%) subjects demonstrated recovery of biventricular function. Exploratory analysis showed that recovered subjects had shorter duration HF, less myocardial fibrosis and less myocyte hypertrophy, and were supported at higher LVAD speeds. CONCLUSIONS: CF-LVAD support in combination with HFMED leads to significant reverse remodeling in patients with advanced HF. Using this approach, one quarter of patients demonstrated complete recovery of cardiac function. Our results suggest that bridge to recovery in the current device era is a clinically meaningful phenomenon and merits further investigation.

Outcomes of cardiac transplantation in septuagenarians.

BACKGROUND: Cardiac transplantation in many centers is programmatically limited to patients aged younger than 70 years. We investigated the trends and outcomes for cardiac transplantation in recipients aged 70 years and older in the United States. METHODS: De-identified data were provided by United Network of Organ Sharing. Transplant recipients were grouped by age 60-69 years and 70 years and older. Univariate comparisons were performed using Student's t-test or the Pearson chi-square test. Survival was estimated using the Kaplan-Meier technique and compared with the log-rank test. Cox regression was used to determine predictors of death after transplant. Statistical significance was assigned to p < 0.05. RESULTS: Between January 1, 1998, and June 15, 2010, 5,807 sexagenarians and 332 septuagenarians received allografts. The septuagenarian cohort had more men, less diabetes, was less likely to have a ventricular assist device, and more likely to be status II. Donors for septuagenarians were older and died more frequently from intracranial hemorrhage. Median unadjusted survival was 9.8 years for sexagenarians vs 8.5 years for septuagenarians (p = 0.003). There was no difference in the incidence of cerebrovascular accident, length of stay, or pacemaker need between groups. Septuagenarians were less likely to be treated for rejection the first year (p = 0.001). Age was a multivariate predictor of death (hazard ratio, 1.289; 95% confidence interval, 1.039-1.6; p = 0.021). CONCLUSIONS: Selected septuagenarians with advanced heart failure can derive great benefit from cardiac transplantation, although survival is inferior to that of an immediately younger sexagenarian cohort. Most of the mortality risk is seen in the first year after transplantation. A reduced incidence of rejection was observed and warrants further study.

Improved exercise performance and skeletal muscle strength after simulated altitude exposure: a novel approach for patients with chronic heart failure.

BACKGROUND: Adaptation to altitude leads to beneficial physiologic changes that improve oxygen delivery and utilization by the periphery. Athletes have used simulated altitude enclosures as part of their training regimen to improve exercise performance. We hypothesized that changes due to acclimatization would also be beneficial for patients with heart failure (HF). We report the results of a pilot study of altitude exposure in patients with chronic HF. METHODS AND RESULTS: Subjects with chronic stable HF, left ventricular ejection fraction (LVEF) ≤35%, on optimal medical therapy were enrolled and underwent simulated altitude exposure for 10 sessions, each 3-4 hours, over a period of 22 days. Starting altitude was 1,500 m and was increased by 300 m with each subsequent session to a maximum altitude of 2,700 m. Peak oxygen consumption, 6-minute walk distance (6MW), skeletal muscle strength, quality of life scores, LVEF, and hematologic parameters were measured at baseline and 48 hours and 4 weeks after the final session. Twelve subjects (median age 52.5 y, ejection fraction 31.7%) successfully completed the protocol without any adverse effects. Peak oxygen consumption significantly improved after altitude sessions from 13.5 ± 1.8 to 14.2 ± 1.9 mL kg(-1) min(-1) (P = .036) and remained elevated after 4 weeks. There were significant improvements in exercise time, 6MW, skeletal muscle strength, and quality of life scores and a trend toward improvement in LVEF after completion of altitude sessions, which were sustained after 1 month. CONCLUSIONS: Simulated altitude exposure up to 2,700 m is safe and well tolerated in patients with chronic stable HF and may have beneficial effects on exercise performance, muscular strength, and quality of life.