Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure.

PURPOSE: Low 25-hydroxyvitamin D (25[OH]D) concentrations have been associated with adverse outcomes in selected populations with established chronic heart failure (CHF). However, it remains unclear whether 25[OH]D deficiency is associated with mortality and hospitalisation in unselected patients receiving contemporary medical and device therapy for CHF. METHODS: We prospectively examined the prevalence and correlates of 25[OH]D deficiency in 1802 ambulatory patients with CHF due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤ 45%) attending heart failure clinics in the north of England. RESULTS: 73% of patients were deficient in 25[OH]D (< 50 nmol/L). 25[OH]D deficiency was associated with male sex, diabetes, lower serum sodium, higher heart rate, and greater diuretic requirement. During a mean follow-up period of 4 years, each 2.72-fold increment in 25[OH]D concentration (for example from 32 to 87 nmol/L) is associated with 14% lower all-cause mortality (95% confidence interval (CI) 1, 26%; p = 0.04), after accounting for potential confounding factors. CONCLUSIONS: Low 25-hydroxyvitamin D deficiency is associated with increased mortality in patients with chronic heart failure due to left ventricular systolic dysfunction. Whether vitamin D supplementation will improve outcomes is, as yet, unproven.

Echocardiographic screening for heart failure and optimization of the care pathway for individuals with pacemakers: a randomized controlled trial.

Individuals with pacemakers are at increased risk of left ventricular systolic dysfunction (LVSD). Whether screening for and optimizing the medical management of LVSD in these individuals can improve clinical outcomes is unknown. In the present study, in a multicenter controlled trial (OPT-PACE), we randomized 1,201 patients (717 men) with a pacemaker to echocardiography screening or usual care. In the screening arm, LVSD was detected in 201 of 600 (34%) patients, who then received management in either primary care or a specialist heart failure (HF) and devices clinic. The primary outcome of the trial was the difference in a composite of time to first HF hospitalization or death. Over 31 months (interquartile range = 30-40 months), the primary outcome occurred in 106 of 600 (18%) patients receiving echocardiography screening, which was not significantly different compared with the occurrence of the primary outcome in 115 of 601 (19%) patients receiving the usual care (hazard ratio = 0.89; 95% confidence interval = 0.69, 1.17). In a prespecified, nonrandomized, exploratory analysis, patients with LVSD managed by the specialist clinic experienced the primary outcome event less frequently than those managed in primary care. The results of this trial indicate that echocardiography screening commonly identifies LVSD in individuals with pacemakers but alone does not alter outcomes. ClinicalTrials.gov registration: NCT01819662 .

Personalised reprogramming to prevent progressive pacemaker-related left ventricular dysfunction: A phase II randomised, controlled clinical trial.

BACKGROUND: Pacemakers are widely utilised to treat bradycardia, but right ventricular (RV) pacing is associated with heightened risk of left ventricular (LV) systolic dysfunction and heart failure. We aimed to compare personalised pacemaker reprogramming to avoid RV pacing with usual care on echocardiographic and patient-orientated outcomes. METHODS: A prospective phase II randomised, double-blind, parallel-group trial in 100 patients with a pacemaker implanted for indications other than third degree heart block for ≥2 years. Personalised pacemaker reprogramming was guided by a published protocol. Primary outcome was change in LV ejection fraction on echocardiography after 6 months. Secondary outcomes included LV remodeling, quality of life, and battery longevity. RESULTS: Clinical and pacemaker variables were similar between groups. The mean age (SD) of participants was 76 (+/-9) years and 71% were male. Nine patients withdrew due to concurrent illness, leaving 91 patients in the intention-to-treat analysis. At 6 months, personalised programming compared to usual care, reduced RV pacing (-6.5±1.8% versus -0.21±1.7%; p<0.01), improved LV function (LV ejection fraction +3.09% [95% confidence interval (CI) 0.48 to 5.70%; p = 0.02]) and LV dimensions (LV end systolic volume indexed to body surface area -2.99mL/m2 [95% CI -5.69 to -0.29; p = 0.03]). Intervention also preserved battery longevity by approximately 5 months (+0.38 years [95% CI 0.14 to 0.62; p<0.01)) with no evidence of an effect on quality of life (+0.19, [95% CI -0.25 to 0.62; p = 0.402]). CONCLUSIONS: Personalised programming in patients with pacemakers for bradycardia can improve LV function and size, extend battery longevity, and is safe and acceptable to patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03627585.

Optimising pacemaker therapy and medical therapy in pacemaker patients for heart failure: protocol for the OPT-PACE randomised controlled trial.

INTRODUCTION: Permanent artificial pacemaker implantation is a safe and effective treatment for bradycardia and is associated with extended longevity and improved quality of life. However, the most common long-term complication of standard pacemaker therapy is pacemaker-associated heart failure. Pacemaker follow-up is potentially an opportunity to screen for heart failure to assess and optimise patient devices and medical therapy. METHODS AND ANALYSIS: The study is a multicentre, phase-3 randomised trial. The 1200 participants will be people who have a permanent pacemaker for bradycardia for at least 12 months, randomly assigned to undergo a transthoracic echocardiogram with their pacemaker check, thereby tailoring their management directed by left ventricular function or the pacemaker check alone, continuing with routine follow-up. The primary outcome measure is time to all-cause mortality or heart failure hospitalisation. Secondary outcomes include external validation of our risk stratification model to predict onset of heart failure and quality of life assessment. ETHICS AND DISSEMINATION: The trial design and protocol have received national ethical approval (12/YH/0487). The results of this randomised trial will be published in international peer-reviewed journals, communicated to healthcare professionals and patient involvement groups and highlighted using social media campaigns. TRIAL REGISTRATION NUMBER: NCT01819662.

A portable prototype magnetometer to differentiate ischemic and non-ischemic heart disease in patients with chest pain.

BACKGROUND: Magnetocardiography (MCG) is a non-invasive technique used to measure and map cardiac magnetic fields. We describe the predictive performance of a portable prototype magnetometer designed for use in acute and routine clinical settings. We assessed the predictive ability of the measurements derived from the magnetometer for the ruling-out of healthy subjects and patients whose chest pain has a non-ischemic origin from those with ischemic heart disease (IHD). METHODS: MCG data were analyzed from a technical performance study, a pilot clinical study, and a young healthy reference group. Participants were grouped to enable differentiation of those with IHD versus non-IHD versus controls: Group A (70 IHD patients); Group B (69 controls); Group C (37 young healthy volunteers). Scans were recorded in an unshielded room. Between-group differences were explored using analysis of variance. The ability of 10 candidate MCG predictors to predict normal/abnormal cases was analyzed using logistic regression. Predictive performance was internally validated using repeated five-fold cross-validation. RESULTS: Three MCG predictors showed a significant difference between patients and age-matched controls (P<0.001); eight predictors showed a significant difference between patients and young healthy volunteers (P<0.001). Logistic regression comparing patients with controls yielded a specificity of 35.0%, sensitivity of 95.4%, and negative predictive value for the ruling-out of IHD of 97.8% (area under the curve 0.78). CONCLUSION: This analysis represents a preliminary indication that the portable magnetometer can help rule-out healthy subjects and patients whose chest pain has a non-ischemic origin from those with IHD.

Effects of Vitamin D on Cardiac Function in Patients With Chronic HF: The VINDICATE Study.

BACKGROUND: Patients with chronic heart failure (HF) secondary to left ventricular systolic dysfunction (LVSD) are frequently deficient in vitamin D. Low vitamin D levels are associated with a worse prognosis. OBJECTIVES: The VINDICATE (VitamIN D treatIng patients with Chronic heArT failurE) study was undertaken to establish safety and efficacy of high-dose 25 (OH) vitamin D3 (cholecalciferol) supplementation in patients with chronic HF due to LVSD. METHODS: We enrolled 229 patients (179 men) with chronic HF due to LVSD and vitamin D deficiency (cholecalciferol <50 nmol/l [<20 ng/ml]). Participants were allocated to 1 year of vitamin D3 supplementation (4,000 IU [100 µg] daily) or matching non-calcium-based placebo. The primary endpoint was change in 6-minute walk distance between baseline and 12 months. Secondary endpoints included change in LV ejection fraction at 1 year, and safety measures of renal function and serum calcium concentration assessed every 3 months. RESULTS: One year of high-dose vitamin D3 supplementation did not improve 6-min walk distance at 1 year, but was associated with a significant improvement in cardiac function (LV ejection fraction +6.07% [95% confidence interval (CI): 3.20 to 8.95; p < 0.0001]); and a reversal of LV remodeling (LV end diastolic diameter -2.49 mm [95% CI: -4.09 to -0.90; p = 0.002] and LV end systolic diameter -2.09 mm [95% CI: -4.11 to -0.06 p = 0.043]). CONCLUSIONS: One year of 100 µg daily vitamin D3 supplementation does not improve 6-min walk distance but has beneficial effects on LV structure and function in patients on contemporary optimal medical therapy. Further studies are necessary to determine whether these translate to improvements in outcomes. (VitamIN D Treating patIents With Chronic heArT failurE [VINDICATE]; NCT01619891).