Elevated Body Mass Index Is Not a Risk Factor for Adverse Outcomes Following Ventricular Assist Device Implantation.

BACKGROUND: Despite ventricular assist devices (VADs) becoming more common in heart failure (HF) treatment, it is still uncertain which patients are more prone to complications. One potential risk factor is increased body mass index (BMI), which is known to increase both all-cause mortality and mortality from ischemic heart disease; however, the role of the BMI in predicting morbidity and mortality following device implantation is unclear. METHODS: The study population for this single-institution retrospective chart review consisted of 136 patients with HF, who underwent VAD implantation between 2004 and 2015. Patients were divided into 2 groups based on their BMI: a nonobese group (18.5 < BMI < 30.0; n = 82) or an obese group (BMI >30.0; n = 54). These groups were compared at baseline and after implantation for survival, hospital readmission, and adverse events. RESULTS: No significant difference was found in initial hospital length of stay, number or length of readmissions, or readmission diagnosis. At 1 year, rates of ongoing device support, orthotopic heart transplant (OHT), and death were not significantly different between groups ( P = .89, P = .90, and P = .70, respectively). Multivariate analysis did not identify obesity as an independent predictor of mortality ( P = .90); only biventricular assist device implantation was associated with decreased survival (hazard ratio [HR] = 5.90, P = .002). CONCLUSION: Obesity in itself should not preclude the use of VAD support in patients with HF, as carefully selected obese patients were shown to have similar rates of hospital readmission, 1-year outcomes, and survival following device implantation compared to nonobese patients.

GRK5-mediated exacerbation of pathological cardiac hypertrophy involves facilitation of nuclear NFAT activity.

RATIONALE: G protein-coupled receptor kinases (GRKs) acting in the cardiomyocyte regulate important signaling events that control cardiac function. Both GRK2 and GRK5, the predominant GRKs expressed in the heart, have been shown to be upregulated in failing human myocardium. Although the canonical role of GRKs is to desensitize G protein-coupled receptors via phosphorylation, it has been demonstrated that GRK5, unlike GRK2, can reside in the nucleus of myocytes and exert G protein-coupled receptor-independent effects that promote maladaptive cardiac hypertrophy and heart failure. OBJECTIVE: To explore novel mechanisms by which GRK5 acting in the nucleus of cardiomyocytes participates in pathological cardiac hypertrophy. METHODS AND RESULTS: In this study, we have found that GRK5-mediated pathological cardiac hypertrophy involves the activation of the nuclear factor of activated T cells (NFAT) because GRK5 causes enhancement of NFAT-mediated hypertrophic gene transcription. Transgenic mice with cardiomyocyte-specific GRK5 overexpression activate an NFAT-reporter in mice basally and after hypertrophic stimulation, including transverse aortic constriction and phenylephrine treatment. Complimentary to this, GRK5 null mice exhibit less NFAT transcriptional activity after transverse aortic constriction. Furthermore, the loss of NFATc3 expression in the heart protected GRK5 overexpressing transgenic mice from the exaggerated hypertrophy and early progression to heart failure seen after transverse aortic constriction. Molecular studies suggest that GRK5 acts in concert with NFAT to increase hypertrophic gene transcription in the nucleus via GRK5's ability to bind DNA directly without a phosphorylation event. CONCLUSIONS: GRK5, acting in a kinase independent manner, is a facilitator of NFAT activity and part of a DNA-binding complex responsible for pathological hypertrophic gene transcription.