Maria F. Paton

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)

Chronotropic Incompetence Does Not Limit Exercise Capacity in Chronic Heart Failure.

BACKGROUND Limited heart rate (HR) rise (HRR) during exercise, known as chronotropic incompetence (CI), is commonly observed in chronic heart failure (CHF). HRR is closely related to workload, the limitation of which is characteristic of CHF. Whether CI is a causal factor for exercise intolerance, or simply an associated feature remains unknown. OBJECTIVES This study sought to clarify the role of the HR on exercise capacity in CHF. METHODS This series of investigations consisted of a retrospective cohort study and 2 interventional randomized crossover studies to assess: 1) the relationship between HRR and exercise capacity in CHF; and 2) the effect of increasing and lowering HR on exercise capacity in CHF as assessed by symptom-limited treadmill exercise testing and measurement of peak oxygen consumption in patients with CHF due to left ventricular systolic dysfunction. RESULTS The 3 key findings were: 1) the association of exercise capacity and HRR is much weaker in severe CHF compared to normal left ventricular function; 2) increasing HRR using rate-adaptive pacing (versus fixed-rate pacing) in unselected patients with CHF does not improve peak exercise capacity; and 3) acutely lowering baseline and peak HR by adjusting pacemaker variables in conjunction with a single dose of ivabradine does not adversely affect exercise capacity in unselected CHF patients. CONCLUSIONS The data refute the contention that CI contributes to impaired exercise capacity in CHF. This finding has widespread implications for pacemaker programming and the use of heart-rate lowering agents. (The Influence of Heart Rate Limitation on Exercise Tolerance in Pacemaker Patients [TREPPE]; NCT02247245).

Mortality Reduction Associated With β-Adrenoceptor Inhibition in Chronic Heart Failure Is Greater in Patients With Diabetes

OBJECTIVE Diabetes increases mortality in patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction. Studies have questioned the safety of β-adrenoceptor blockers (β-blockers) in some patients with diabetes and reduced left ventricular ejection fraction. We examined whether β-blockers and ACE inhibitors (ACEIs) are associated with differential effects on mortality in CHF patients with and without diabetes. RESEARCH DESIGN AND METHODS We conducted a prospective cohort study of 1,797 patients with CHF recruited between 2006 and 2014, with mean follow-up of 4 years. β-Blocker dose was expressed as the equivalent dose of bisoprolol (mg/day) and ACEI dose as the equivalent dose of ramipril (mg/day). Cox regression analysis was used to examine the interaction between diabetes and drug dose on all-cause mortality. RESULTS Patients with diabetes were prescribed larger doses of β-blockers and ACEIs than were patients without diabetes. Increasing β-blocker dose was associated with lower mortality in patients with diabetes (8.9% per mg/day; 95% CI 5–12.6) and without diabetes (3.5% per mg/day; 95% CI 0.7–6.3), although the effect was larger in people with diabetes (interaction P = 0.027). Increasing ACEI dose was associated with lower mortality in patients with diabetes (5.9% per mg/day; 95% CI 2.5–9.2) and without diabetes (5.1% per mg/day; 95% CI 2.6–7.6), with similar effect size in these groups (interaction P = 0.76). CONCLUSIONS Increasing β-blocker dose is associated with a greater prognostic advantage in CHF patients with diabetes than in CHF patients without diabetes.

Performance of 2014 NICE defibrillator implantation guidelines in heart failure risk stratification

Objective Define the real-world performance of recently updated National Institute for Health and Care Excellence guidelines (TA314) on implantable cardioverter-defibrillator (ICD) use in people with chronic heart failure. Methods Multicentre prospective cohort study of 1026 patients with stable chronic heart failure, associated with left ventricular ejection fraction (LVEF) ≤45% recruited in cardiology outpatient departments of four UK hospitals. We assessed the capacity of TA314 to identify patients at increased risk of sudden cardiac death (SCD) or appropriate ICD shock. Results The overall risk of SCD or appropriate ICD shock was 2.1 events per 100 patient-years (95% CI 1.7 to 2.6). Patients meeting TA314 ICD criteria (31.1%) were 2.5-fold (95% CI 1.6 to 3.9) more likely to suffer SCD or appropriate ICD shock; they were also 1.5-fold (95% CI 1.1 to 2.2) more likely to die from non-cardiovascular causes and 1.6-fold (95% CI 1.1 to 2.3) more likely to die from progressive heart failure. Patients with diabetes not meeting TA314 criteria experienced comparable absolute risk of SCD or appropriate ICD shock to patients without diabetes who met TA314 criteria. Patients with ischaemic cardiomyopathy not meeting TA314 criteria experienced comparable absolute risk of SCD or appropriate ICD shock to patients with non-ischaemic cardiomyopathy who met TA314 criteria. Conclusions TA314 can identify patients with reduced LVEF who are at increased relative risk of sudden death. Clinicians should also consider clinical context and the absolute risk of SCD when advising patients about the potential risks and benefits of ICD therapy.

Reply: The Paradox of Heart Failure and Atrial Fibrillation

We are grateful for the comments raised by Dr. Cerit in response to our recently published paper describing the remodeling effects of 1-year of high-dose vitamin D therapy in patients with chronic heart failure (CHF) due to left ventricular systolic dysfunction [(1)][1]. We agree that suppression of