The VITAH Trial-Vitamin D Supplementation and Cardiac Autonomic Tone in Patients with End-Stage Kidney Disease on Hemodialysis: A Blinded, Randomized Controlled Trial

End-stage kidney disease (ESKD) patients are at increased cardiovascular risk. Vitamin D deficiency is associated with depressed heart rate variability (HRV), a risk factor depicting poor cardiac autonomic tone and risk of cardiovascular death. Vitamin D deficiency and depressed HRV are highly prevalent in the ESKD population. We aimed to determine the effects of oral vitamin D supplementation on HRV ((low frequency (LF) to high frequency (HF) spectral ratio (LF:HF)) in ESKD patients on hemodialysis. Fifty-six subjects with ESKD requiring hemodialysis were recruited from January 2013-March 2015 and randomized 1:1 to either conventional (0.25 mcg alfacalcidol plus placebo 3×/week) or intensive (0.25 mcg alfacalcidol 3×/week plus 50,000 international units (IU) ergocalciferol 1×/week) vitamin D for six weeks. The primary outcome was the change in LF:HF. There was no difference in LF:HF from baseline to six weeks for either vitamin D treatment (conventional: p = 0.9 vs. baseline; intensive: p = 0.07 vs. baseline). However, participants who remained vitamin D-deficient (25-hydroxyvitamin D < 20 ng/mL) after treatment demonstrated an increase in LF:HF (conventional: n = 13, ∆LF:HF: 0.20 ± 0.06, p < 0.001 vs. insufficient and sufficient vitamin D groups; intensive: n = 8: ∆LF:HF: 0.15 ± 0.06, p < 0.001 vs. sufficient vitamin D group). Overall, six weeks of conventional or intensive vitamin D only augmented LF:HF in ESKD subjects who remained vitamin D-deficient after treatment. Our findings potentially suggest that while activated vitamin D, with or without additional nutritional vitamin D, does not appear to improve cardiac autonomic tone in hemodialysis patients with insufficient or sufficient baseline vitamin D levels, supplementation in patients with severe vitamin D deficiency may improve cardiac autonomic tone in this higher risk sub-population of ESKD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01774812

Programmed inappropriate ICD ventricular defibrillation for cardioversion of persistent atrial fibrillation

In this report we briefly describe a patient with a dual chamber implantable cardioverter defibrillator in the context of severe ischemic cardiomyopathy who developed persistent atrial fibrillation. After appropriate anticoagulation and under mild sedation the patient was successfully cardioverted to sinus rhythm after a programmed ventricular synchronized defibrillation using his defibrillator. Programmed internal cardioversion of persistent atrial fibrillation in patients who have an implantable cardioverter defibillator without atrial defibrillation capabilities could be an effective and safe therapeutic option. Unlike external electrical cardioversion, this strategy does not interfere with the implantable cardioverter defibrillator, is more effective, and obviates the need of general anesthesia. This strategy should be further evaluated in clinical trials

Adrenergic Alpha-1 Pathway Is Associated with Hypertension among Nigerians in a Pathway-focused Analysis

The pathway-focused association approach offers a hypothesis driven alternative to the agnostic genome-wide association study. Here we apply the pathway-focused approach to an association study of hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in 1614 Nigerians with genome-wide data.Testing of 28 pathways with biological relevance to hypertension, selected a priori, containing a total of 101 unique genes and 4,349 unique single-nucleotide polymorphisms (SNPs) showed an association for the adrenergic alpha 1 (ADRA1) receptor pathway with hypertension (p<0.0009) and diastolic blood pressure (p<0.0007). Within the ADRA1 pathway, the genes PNMT (hypertension P(gene)<0.004, DBP P(gene)<0.004, and SBP P(gene)<0.009, and ADRA1B (hypertension P(gene)<0.005, DBP P(gene)<0.02, and SBP P(gene)<0.02) displayed the strongest associations. Neither ADRA1B nor PNMT could be the sole mediator of the observed pathway association as the ADRA1 pathway remained significant after removing ADRA1B, and other pathways involving PNMT did not reach pathway significance.We conclude that multiple variants in several genes in the ADRA1 pathway led to associations with hypertension and DBP. SNPs in ADRA1B and PNMT have not previously been linked to hypertension in a genome-wide association study, but both genes have shown associations with hypertension through linkage or model organism studies. The identification of moderately significant (10(-2)>p>10(-5)) SNPs offers a novel method for detecting the "missing heritability" of hypertension. These findings warrant further studies in similar and other populations to assess the generalizability of our results, and illustrate the potential of the pathway-focused approach to investigate genetic variation in hypertension

The A's, G's, C's, and T's of health disparities

In order to eliminate health disparities in the United States, more efforts are needed to address the breadth of social issues directly contributing to the healthy divide observed across racial and ethnic groups. Socioeconomic status, education, and the environment are intimately linked to health outcomes. However, with the tremendous advances in technology and increased investigation into human genetic variation, genomics is poised to play a valuable role in bolstering efforts to find new treatments and preventions for chronic conditions and diseases that disparately affect certain ethnic groups. Promising studies focused on understanding the genetic underpinnings of diseases such as prostate cancer or beta-blocker treatments for heart failure are illustrative of the positive contribution that genomics can have on improving minority health