Haqeel A. Jamil

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)

Cardiac resynchronization therapy in pacemaker-dependent patients with left ventricular dysfunction

AIMS Heart failure and left ventricular (LV) systolic dysfunction (LVSD) are common in patients with permanent pacemakers. The aim was to determine if cardiac resynchronization therapy (CRT) at the time of pulse generator replacement (PGR) is of benefit in patients with unavoidable RV pacing and LVSD. METHODS AND RESULTS Fifty patients with unavoidable RV pacing, LVSD, and mild or no symptoms of heart failure, listed for PGR were randomized 1 : 1 to either standard RV-PGR (comparator) or CRT. The primary endpoint was the difference in change in LV ejection fraction (LVEF) between RV-PGR and CRT groups from baseline to 6 months. Secondary endpoints included peak oxygen consumption, quality of life, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. At 6 months there was a difference in change in median (interquartile range) LVEF [9 (6-12) vs. -1.5 (-4.5 to -0.8)%; P < 0.0001] between the CRT and RV-PGR arms. There were also improvements in exercise capacity (P = 0.007), quality of life (P = 0.03), and NT-proBNP (P = 0.007) in those randomized to CRT. After 809 (729-880) days, 17 patients had died or been hospitalized (6 in CRT group and 11 in the comparator RV-PGR group) and two patients in the RV-PGR arm had required CRT for deteriorating heart failure. Patients with standard RV-PGR had more days in hospital during follow-up than those in the CRT group [4 (2-7) vs. 11 (6-16) days; P = 0.047]. CONCLUSION Performing CRT in pacemaker patients with unavoidable RV pacing and LVSD but without severe symptoms of heart failure, at the time of PGR, improves cardiac function, exercise capacity, quality of life, and NT-pro-BNP levels.

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).

Ambulatory heart rate range predicts mode-specific mortality and hospitalisation in chronic heart failure

Objective We aimed to define the prognostic value of the heart rate range during a 24 h period in patients with chronic heart failure (CHF). Methods Prospective observational cohort study of 791 patients with CHF associated with left ventricular systolic dysfunction. Mode-specific mortality and hospitalisation were linked with ambulatory heart rate range (AHRR; calculated as maximum minus minimum heart rate using 24 h Holter monitor data, including paced and non-sinus complexes) in univariate and multivariate analyses. Findings were then corroborated in a validation cohort of 408 patients with CHF with preserved or reduced left ventricular ejection fraction. Results After a mean 4.1 years of follow-up, increasing AHRR was associated with reduced risk of all-cause, sudden, non-cardiovascular and progressive heart failure death in univariate analyses. After accounting for characteristics that differed between groups above and below median AHRR using multivariate analysis, AHRR remained strongly associated with all-cause mortality (HR 0.991/bpm increase in AHRR (95% CI 0.999 to 0.982); p=0.046). AHRR was not associated with the risk of any non-elective hospitalisation, but was associated with heart-failure-related hospitalisation. AHRR was modestly associated with the SD of normal-to-normal beats (R2=0.2; p<0.001) and with peak exercise-test heart rate (R2=0.33; p<0.001). Analysis of the validation cohort revealed AHRR to be associated with all-cause and mode-specific death as described in the derivation cohort. Conclusions AHRR is a novel and readily available prognosticator in patients with CHF, which may reflect autonomic tone and exercise capacity.

Patients with long-term permanent pacemakers have a high prevalence of left ventricular dysfunction.

Introduction Patients with right ventricular pacemakers are at increased risk of left ventricular systolic dysfunction (LVSD). We aimed to establish the prevalence, degree and associations of LVSD in patients with long-term right ventricular pacemakers listed for pulse generator replacement (PGR). Methods All patients listed for PGR at Leeds General Infirmary were invited to attend for an assessment during which we recorded medical history, symptomatic status, medical therapy, date and indication of first implantation, the percentage of right ventricular pacing (% RVP) and an echocardiogram. Results We collected data on 491 patients. A left ventricular ejection fraction less than 50% was observed in 40% of our cohort, however, this was much higher (59%) in those with more than 80% RVP than in those with less than 80% RVP (22%) (P < 0.0001). Multivariable analysis revealed % RVP, (but not complete heart block at baseline), serum creatinine and previous myocardial infarction to be independently related to the presence of LVSD. A model combining % RVP and previous myocardial infarction has a c-statistic of 0.74 for predicting LVSD. After a mean follow-up time of 668 days, 56 patients (12%) were dead or had been hospitalized for heart failure. In multivariable analysis, previous myocardial infarction and high % RVP were independently associated with a worse survival. Conclusion Patients with right ventricular pacemakers have a high prevalence of LVSD, and this is greater in those exposed to more RVP. Those with LVSD and high amounts of RVP are at higher risk of hospitalization or death. Simple variables can identify those patients who might benefit from a more comprehensive review.

Pacing-associated left ventricular dysfunction? Think reprogramming first!

Objective Heart failure and left ventricular systolic dysfunction (LVSD) are common in patients with permanent pacemakers, but whether right ventricular (RV) pacing is contributory or merely a bystander in patients with more severe cardiac disease is controversial. The aim of the present study was to determine whether reprogramming of existing pacemakers to reduce RV pacing is safe and leads to improvements in cardiac function. Methods This was a prospective service evaluation of the effects of optimising pacemaker programming to avoid RV pacing in 66 consecutive attendees of a teaching hospital pacemaker clinic without complete heart block. The main outcome measures were left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels, quality of life and cardiopulmonary exercise testing at baseline and after 6 months. Results At 6 months, the protocol reduced absolute RV pacing by a mean of 49% (95% CI 41% to 57%) (p<0.0001 from baseline) and resulted in a mean absolute improvement in LVEF of 6% (4% to 8%) (p<0.0001 from baseline) but no reduction in exercise capacity, NT-pro-BNP or quality of life. There was a relationship between the magnitude of change in EF and the reduction in RV pacing (p=0.04) and changes in NT-pro-BNP seemed to relate to change in RV pacing (p=0.07). Conclusions Programming standard pacemakers to avoid RV pacing is safe, does not adversely affect patients’ symptoms or quality of life and is associated with improved LV function, related to the reductions in RV pacing percentage.

Hypertension in the Young Adult

Hypertension is the most common cardiovascular condition to be seen in primary care. It also represents the strongest single modifiable risk factor with regards to future morbidity and mortality. The incidence of hypertension is predicted to continue to increase, being contributed to by an ageing population.

47 Using Natriuretic Peptide Levels to Diagnose Heart Failure in Primary Care: An Evaluation of the 2010 United Kingdom National Institute of Clinical Excellence Guidelines on the Diagnosis of Chronic Heart Failure

Introduction Chronic heart failure (HF) due to left ventricular systolic dysfunction (LVSD) is common and associated with high morbidity and mortality. The 2010 UK National Institute for Health and Care Excellence (NICE) guideline (CG-108) advises the measurement of natriuretic peptides (NP) in patients presenting to primary care with symptoms possibly due to HF without previous myocardial infarction (MI); with elevated concentrations triggering referral to a HF clinic. The aim of this study was to describe the results of implementation of the 2010 NP-based diagnostic guidelines for HF. Methods We prospectively collected demographic data from all patients in Leeds who underwent an NP test between 1st May 2012 and 1st May 2013. In those referred to the Leeds Integrated HF Service we collected clinical variables, electrocardiography and echocardiography data. Results Of the 4415 NT-pro-B-type NP tests performed in the twelve months to May 1st 2013, 543 (12%) returned a ‘high’ result (>2000 ng/L), and 1067 (24%) an ‘intermediate’ result (400–2000 ng/L). Of 1610 patients with an elevated result and no previous MI, 820 (51%) were referred to secondary care. Patients with a previous MI or a ‘high’ result were more likely to have LVSD (83/173, 48% and 131/245, 53% respectively), than those with ‘intermediate’ concentrations (112/447, 25%). Overall, the yield from 4263 NP tests (in patients without a previous MI) was 243 new diagnoses of LVSD. Conclusion Comprehensive implementation of the 2010 NICE guidelines for the diagnosis and management of HF has led to a large number of NT-pro-BNP tests and few new diagnoses.

56 The Influence of Chronotropic Incompetence on Exercise Capacity in Chronic Heart Failure

Introduction Increased cardiac output during exercise is the result of greater stroke volume and an increase in heart rate. It is therefore assumed that a limitation to heart rate rise (HRR) in response to activity, chronotropic incompetence (CI), could contribute to the exercise intolerance that is characteristic of chronic heart failure (CHF). However, HRR is closely related to workload and subjects with impaired exercise capacity have a lower peak heart rate (PHR) and a lower HRR. Hence, whether a limited increase in heart rate (HR) during exercise in patients with CHF is aetiological in their exercise limitation or merely a bystander remains unproven. The aim of this study was to examine the effects of correcting CI in patients with CHF on peak and submaximal exercise capacity. Methods We enrolled 50 subjects with CHF due to left ventricular systolic dysfunction (LVSD), (left ventricular ejection fraction <45%, and symptoms of breathlessness or fatigue), on optimal medical therapy with cardiac pacing devices, into a randomised double blind cross-over study of rate adaptive versus fixed rate pacing. At baseline, each participant underwent a full echocardiographic assessment, and performed a peak, symptom-limited treadmill-based familiarisation cardiopulmonary exercise test with breath-by-breath metabolic gas analysis. After at least one week, subjects were invited back for two further exercise tests (at least one week apart) immediately prior to which, the pacemaker was either programmed to rate-adaptive or fixed rate pacing, with the maximum paced HR determined using the age-predicted peak HR equation (220-age). Results Rate-adaptive pacing led to higher mean (SE) peak HR (128 (21) vs 107 (28) bpm; p < 0.0001, Figure 1) but no difference in mean peak oxygen consumption (16.6(4.7) v 15.9(4.5) ml/kg/min, p = 0.24), anaerobic threshold (11.7 (2.7) vs 11.3 (2.6) ml/kg/min; p = 0.24), exercise time (470 (239) v 451 (222)s; p = 0.33, Figure 2), stage-by-stage HR or perceived exertion levels. Abstract 56 Figure 1 Rate-adaptive (RR on) versus fixed-rate (RR off) pacing in CHF patients showing increased heart rates (HR) at submaximal and peak exercise Abstract 56 Figure 2 Rate-adaptive (RR on) versus fixed-rate (RR off) pacing in CHF patients showing no benefit on oxygen consumption with increased heart rate Conclusions Exercise intolerance due to breathlessness and fatigue is a cardinal feature of CHF and remains a problem for many patients despite optimal medical and device therapy. Agents that lower HR and induce CI are proven to improve outcomes for patients with CHF due to LVSD yet traditional models of heart failure suggest that a lower cardiac output, potentially the consequence of CI, reduces blood supply to exercising muscles thereby limiting work. By demonstrating that higher HR throughout exercise is not associated with greater exercise capacity in CHF patients, we propose that CI does not play a major role in exercise intolerance in CHF.

Thromboprophylaxis in heart failure patients with sinus rhythm: aspirin and warfarin lead to similar cardiovascular outcomes

Commentary on: Homma S, Thompson JL, Pullicino PM, et al. WARCEF Investigators. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med 2012;366:1859–69.[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Chronic heart failure (CHF) is common, affecting 1–2% of the population and 10% of people >70 years. Patients with CHF have an increased risk of thromboembolism. Those with atrial fibrillation (AF) should receive warfarin but whether CHF patients with sinus rhythm (SR), whose risk is 1.5–3.5%,1 should receive thromboprophylaxis is unclear. Previous studies, Warfarin/Aspirin Study in Heart failure (warfarin, aspirin 300 mg daily, placebo),2 Heart failurE Long-term Antithrombotic Study (aspirin 325 mg daily or warfarin for patients with ischaemic heart disease (IHD) or warfarin or placebo in the non-ischaemics)3 and Warfarin and Antiplatelet Therapy in Chronic Heart failure (WATCH: warfarin, clopidogrel 75 mg daily, … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DHomma%26rft.auinit1%253DS.%26rft.volume%253D366%26rft.issue%253D20%26rft.spage%253D1859%26rft.epage%253D1869%26rft.atitle%253DWarfarin%2Band%2Baspirin%2Bin%2Bpatients%2Bwith%2Bheart%2Bfailure%2Band%2Bsinus%2Brhythm.%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa1202299%26rft_id%253Dinfo%253Apmid%252F22551105%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa1202299&link_type=DOI [3]: /lookup/external-ref?access_num=22551105&link_type=MED&atom=%2Febmed%2F18%2F2%2F69.atom [4]: /lookup/external-ref?access_num=000304083000005&link_type=ISI