Rationale and study design of the increase of vagal tone in heart failure study: INOVATE-HF.

BACKGROUND: Imbalance between the parasympathetic and sympathetic nervous systems is a recognized contributor to progression of chronic heart failure. Current therapy with beta adrenergic antagonists is designed to moderate the up-regulation of norepinephrine and sympathetic effects; however, to date, there are no therapies that specifically address the withdrawal of parasympathetic influences on cardiac function and structure. METHODS/RESULTS: In order to evaluate the impact of vagus nerve stimulation, an international multi-center randomized clinical trial (INOVATE-HF) has been designed to assess safety and efficacy of vagus nerve stimulation in symptomatic patients with heart failure on optimal medical therapy using the CardioFit System (BioControl Medical, Yehud, Israel). Up to 650 patients from 80 sites will be recruited and randomized in a 3:2 ratio to receive active treatment or standard optimal medical therapy. Inclusion criteria include left ventricular systolic dysfunction, the presence of New York Heart Association Class III symptoms, sinus rhythm, and QRS width less than 120 milliseconds. The study is powered to detect differences in the primary efficacy end point of all-cause mortality and heart failure hospitalization and 2 safety end points. CONCLUSION: Vagal nerve stimulation with CardioFit as a treatment for symptomatic heart failure is under active investigation as a novel approach to restore balance between the sympathetic and parasympathetic nervous systems. If shown to be safe and effective in decreasing heart failure events and mortality, this novel approach will impact the treatment paradigm for heart failure.

Electrophysiologic characteristics and catheter ablation of ventricular tachyarrhythmias among patients with heart failure on ventricular assist device support.

BACKGROUND: Ventricular tachyarrhythmias (VT) are common among ventricular assist device (VAD) recipients, yet electrophysiologic (EP) characteristics and catheter ablation outcomes remain uncharacterized. OBJECTIVE: To evaluate the EP characteristics and catheter ablation outcomes for VTs among heart failure patients on VAD support. METHODS: The Cleveland Clinic registry of consecutive patients undergoing VAD placement in 1991-2010 with medically refractory, symptomatic VT referred for EP study and catheter ablation. RESULTS: Among 611 recipients of VAD (mean age 53.3 ± 12.4 years, 80% men), 21 patients (3.4%) were referred for 32 EP procedures, including 11 patients (52%) presenting with implantable cardioverter-defibrillator therapy (13 shocks, 26 antitachycardia pacing). Data from 44 inducible tachycardias (mean cycle length 339 ± 59 ms) demonstrated monomorphic VT (n = 40, 91%; superior axis 52%, right bundle branch block morphology 41%) and polymorphic ventricular tachycardia (PMVT)/ventricular fibrillation (n = 4, 8%). Electroanatomic mapping of 28 tachycardias in 20 patients demonstrated reentrant VT related to intrinsic scar (n = 21 of 28, 75%) more commonly than the apical inflow cannulation site (n = 4 of 28, 14%), focal/microreentry VT (n = 2 of 28, 7%), or bundle branch reentry (n = 1 of 28, 3.5%). Catheter ablation succeeded in 18 of 21 patients (86%). VT recurred in 7 of 21 patients (33%) at a mean of 133 ± 98 days, and 6 patients (29%) required repeat procedures, with subsequent recurrence in 4 of 21 patients (19%). CONCLUSIONS: Catheter ablation of VT is effective among recipients of VAD. Intrinsic myocardial scar, rather than the apical device cannulation site, appears to be the dominant substrate.

Impact of dopamine infusion on renal function in hospitalized heart failure patients: results of the Dopamine in Acute Decompensated Heart Failure (DAD-HF) Trial.

BACKGROUND: Worsening renal function (WRF) and hypokalemia related to diuretic use for acute decompensated heart failure (ADHF) are common and associated with poor prognosis. Low-dose dopamine infusion improves renal perfusion; its effect on diuresis or renal function specifically in ADHF is not known. METHODS AND RESULTS: Sixty consecutive ADHF patients (age 75.7 ± 11.2 years; 51.7% female; left ventricular ejection fraction 35.3 ± 12.1%) were randomized, after receiving a 40 mg intravenous furosemide bolus, to either high-dose furosemide (HDF, 20 mg/h continuous infusion for 8 hours) or low-dose furosemide combined with low-dose dopamine (LDFD, furosemide 5 mg/h plus dopamine 5 µg kg(-1) min(-1) continuous infusion for 8 hours). Both strategies were compared for total diuresis, WRF (defined as a rise in serum creatinine of >0.3 mg/dL from baseline to 24 hours), electrolyte balance, and 60-day postdischarge outcomes. Mean hourly excreted urine volume (272 ± 149 mL in HDF vs 278 ± 186 mL in LDFD group; P = .965) and changes in dyspnea score (Borg index: -4.4 ± 2.1 in HDF group vs -4.7 ± 2.0 in LDFD group; P = .575) during the 8 hours of protocol treatment were similar in the two groups. WRF was more frequent in the HDF (n = 9; 30%) than in the LDFD group (n = 2; 6.7%; P = .042). Serum potassium changed from 4.3 ± 0.5 to 3.9 ± 0.4 mEq/L at 24 hours (P = .003) in the HDF group and from 4.4 ± 0.5 to 4.2 ± 0.5 mEq/L at 24 hours (P = .07) in the LDFD group. Length of stay and 60-day mortality or rehospitalization rates (all-cause, cardiovascular, and worsening HF) were similar in the two groups. CONCLUSIONS: In ADHF patients, the combination of low-dose furosemide and low-dose dopamine is equally effective as high-dose furosemide but associated with improved renal function profile and potassium homeostasis.

Impact of donor high-risk social behaviors on recipient survival in cardiac transplantation.

OBJECTIVE: To investigate the impact of cardiac donor participation in high-risk social behaviors (HRSBs) on recipient survival. METHODS: Retrospective chart review queried cardiac transplantations performed at our institution from August 1994 to November 2007 involving donors known to have engaged in HRSBs. Kaplan-Meier methodology was used to analyze survival rates, and a Cox proportional hazards regression was performed to determine the impact of donor HRSBs on survival. RESULTS: We identified 143 donors with social histories containing the following HRSBs: incarceration (n=69), unprofessional tattoos or piercings (n=44), alternative lifestyle practice (n=11), cocaine use (n=60), heroin smoking (n=6), marijuana use (n=79), oral narcotic abuse (n=20), and intravenous drug use (n=21). At the time of donation, viral screens detected 10 donors who were hepatitis B virus (HBV) positive, 11 donors who were hepatitis C virus (HCV) positive, and no donors who were positive for the HIV. One-year and 5-year survival were 92.2% and 84.4%, respectively. Cox regression analysis found only donor HCV infection to be associated with poorer recipient survival (P=0.14). CONCLUSION: Using cardiac allografts from high-risk donors who are serologically negative for viruses does not seem to impact recipient survival. There is a considerable risk for transmission of HBV and HCV when these are detected by pretransplant screens. However, if pretransplant screening does not discover donor HBV, HCV, or HIV infection, it is unlikely that subclinical disease transmission will occur.

Spirituality and well being among elders: differences between elders with heart failure and those without heart failure.

Heart failure is a chronic debilitating disease that affects all aspects of a person's life, including physical, mental and spiritual dimensions. The associations among these dimensions, and the relationship to overall health status, have not been clearly identified. The purpose of this quantitative, descriptive study was to explore differences between spirituality, depressive symptoms, and quality of life among elders with and without heart failure. A total of 44 elders with heart failure and 40 non-heart failure elders completed several questionnaires including: The Daily Spiritual Experiences Scale (DSES), Spirituality Index of Well-Being (SIWB), Center for Epidemiologic Studies Depression Scale (CES-D), and SF-12 Health Survey. There were significant differences in the groups on gender and ethnicity; thus these variables were controlled in the analyses related to the dependent variables. After controlling for gender and ethnicity, there were significant differences in the physical component of quality of life and spiritual well-being. The heart failure patients had significantly lower physical quality of life but more spiritual well-being than the non-heart failure patients. There were no significant differences in daily spiritual experiences, mental component of quality of life, and depressive symptoms between the two groups.