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.

Cardiac resynchronization therapy following Carillon® annuloplasty device for symptomatic heart failure and functional mitral regurgitation: a case report.

BACKGROUND: Symptomatic patients with significant left ventricular systolic dysfunction (LVSD) require a tailored treatment approach. Both functional mitral regurgitation (FMR) and left bundle branch block (LBBB) can develop, contributing to clinical deterioration, and worse prognosis despite optimal medical therapy (OMT). CASE SUMMARY: We report the case of a symptomatic 60-year-old man on OMT with LVSD and significant FMR. His symptoms and FMR initially improved following transvenous mitral annuloplasty using the Carillon® Mitral Contour System® annuloplasty device. However, he subsequently developed LBBB with associated reduction in exercise capacity, for which he underwent cardiac resynchronization therapy, and ensuing symptom improvement and stabilization. DISCUSSION: Our case describes how targeted device interventions can be combined synergistically to optimize patient symptoms.

Prognostic Significance of Incidental Nonsustained Ventricular Tachycardia Detected on Pacemaker Interrogation.

Symptomatic sustained ventricular tachycardia is a life threatening arrhythmia requiring prompt treatment. However, the risk associated with asymptomatic nonsustained ventricular tachycardia (NSVT) detected on routine permanent pacemaker (PPM) interrogation in patients with known cardiac conduction disease is unknown. Our aim is to determine if asymptomatic NSVT detected on PPM interrogation is associated with increased mortality. As part of a prospective observational cohort study, 582 patients with long-term pacemakers were recruited at a tertiary cardiac centre, and followed for 4 ± 1.96 years (mean ± standard deviation). At each subsequent pacemaker check, any symptoms and ventricular high-rate episodes were recorded. We excluded 17 patients due to incomplete data. In the remaining 565 patients (57% male, age 74.5 ± 19.2 years, left ventricular ejection fraction 50.0 ± 11.3%), NSVT was found in 125 (22.1%) patients with a higher prevalence in males (65% vs 54%; p = 0.033). Those with NSVT were more likely to have had coronary artery disease (p = 0) or previous myocardial infarction (p = 0.015). After correction for baseline variables, NSVT had no impact on survival (n = 52 [42%] vs n = 162 [37%]; log-rank p = 0.331, hazard ratio: 0.927, 95% confidence interval: 0.678 to 1.268, p = 0.697). In conclusion, asymptomatic NSVT identified on PPM interrogation does not appear to be associated with increased mortality, thus whether treatment to suppress this arrhythmia is of benefit remains unproven.

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.

Prospective evaluation and long-term follow-up of patients referred to secondary care based upon natriuretic peptide levels in primary care.

AIMS: The UK National Institute for Health and Care Excellence (UK-NICE) and European Society of Cardiology (ESC) guidelines advise natriuretic peptide (NP) assessment in patients presenting to primary care with symptoms possibly due to chronic heart failure (HF), to determine need for specialist involvement. This prospective service evaluation aimed to describe the diagnostic and prognostic utility of these guidelines. METHODS AND RESULTS: We prospectively collected clinical, echocardiography and outcomes data (minimum 5 years) from all patients referred to the Leeds HF Service for 12 months of following the initiation of the NP-guideline-directed pathway. Between 1 May 2012 and 1 August 2013, 1020 people with symptoms possibly due to HF attended either with a raised NT-pro-BNP or a previous myocardial infarction (MI) with an overall rate of left ventricular systolic dysfunction (LVSD) of 33%. Of these, 991 satisfied the ESC criteria (NT-pro-BNP ≥125 pg/mL) in whom the rate of LVSD was 32%, and 821 the UK-NICE criteria in whom the rate of LVSD was 49% in those with a previous MI, 25% in those with NT-pro-BNP concentration 400-2000 pg/mL, and 54% in those with NT-pro-BNP concentration of >2000 pg/mL. An NT-pro-BNP concentration 125-400 pg/mL had a 12% risk of LVSD. Specificity was poor in women >70 years, who made up the largest proportion of attendees. Elevated NT-pro-BNP levels were associated with lower survival even in the absence of LVSD. CONCLUSION: In people referred through the ESC and UK-NICE guidelines, elevated NT-pro-BNP is a marker of increased mortality risk, but there is wide variation in specificity for LVSD. Age- and sex-adjusted criteria might improve performance.

Rate-Response Programming Tailored to the Force-Frequency Relationship Improves Exercise Tolerance in Chronic Heart Failure.

OBJECTIVES: This study sought to examine whether the heart rate (HR) at which the force-frequency relationship (FFR) slope peaks (critical HR) could be used to tailor HR response in chronic heart failure (CHF) patients with cardiac pacemakers and whether this favorably influences exercise capacity. BACKGROUND: CHF secondary to left ventricular (LV) systolic dysfunction is characterized by blunting of the positive relationship between HR and LV contractility known as the FFR. METHODS: This observational study was carried out in patients with CHF and healthy subjects with pacemaker devices. The study assessed the 3 important features of the FFR (critical HR, peak contractility, and the FFR slope), and their reproducibility was measured noninvasively using echocardiography. The investigators then undertook a double-blind, randomized, controlled crossover study comparing the effects of tailored pacemaker rate-response programming on the basis of the FFR with conventional rate-response programming on exercise time and maximal oxygen consumption. RESULTS: The study enrolled 90 patients with CHF into the observational cohort study: mean age, 73.6 ± 8.9 years; mean left ventricular ejection fraction (LVEF), 33.5 ± 10.9%. The study investigated 15 control subjects with normal LV function (LVEF, 55.6 ± 5.3%). The critical HR (103 ± 22 beats/min vs. 126 ± 15 beats/min; p = 0.0002), peak contractility (3.8 ± 3.7 SBP/LVESVI vs. 9.8 ± 4.1 SBP/LVESVI; p = 0.0001), and the slope of the FFR (p < 10-15) were lower in patients with CHF than in control subjects. A total of 52 patients, with a mean LVEF of 32 ± 11% on optimal therapy, took part in the crossover study. Rate-response settings limiting HR rise to below the critical HR led to greater exercise time (475 ± 189 s vs. 425 ± 196 s; p = 0.003) and higher peak oxygen consumption (17.3 ± 4.6 ml/kg/min vs. 16.6 ± 4.7 ml/kg/min; p = 0.01). CONCLUSIONS: A personalized approach to rate-response programming, determined using a reproducible noninvasive method for assessing the FFR, improves exercise time in patients with CHF and pacemaker devices. (Bowditch Revisited: Defining the Optimum Heart Rate Range in Chronic Heart Failure; NCT02563873).

Cardiac resynchronization therapy outcomes in patients with chronic heart failure: cardiac resynchronization therapy with pacemaker versus cardiac resynchronization therapy with defibrillator.

AIMS: Cardiac resynchronization therapy (CRT) for chronic heart failure with left ventricular systolic dysfunction (LVSD) consistently improves survival against optimal medical therapy alone. Limited data exist comparing the outcomes between CRT with pacemaker (CRT-P) and with defibrillator (CRT-D). We aimed to investigate the long-term prognosis of patients who received CRT-P or CRT-D. METHODS AND RESULTS: Data were prospectively collected from consecutive patients with standard indications for CRT, who were implanted at a single large tertiary centre between 2008 and 2012. All-cause mortality was compared between those patients who received either CRT-P or CRT-D. A subgroup analysis was performed in patients with ischaemic cardiomyopathy. During the period in question, 795 patients received CRT devices: 544 (68.4%) CRT-P and 251 (31.6%) CRT-D. The mean follow-up was 1072 ±â€Š(SD 556) days. Overall, there was no survival benefit in those patients implanted with a CRT-D compared with CRT-P (hazard ratio 1.09, 95% confidence interval 0.84-1.41, P = 0.51). In patients with ischaemic chronic heart failure [n = 530 (66.7%)], there was a trend for improved survival with CRT-D; however, this was not significant after adjustment. In a subgroup analysis, there were no differences in mode-specific mortality in those patients implanted with CRT-D compared with CRT-P. CONCLUSION: In this large consecutive patient cohort, we did not find a survival benefit of CRT-D compared with CRT-P. Patients indicated for CRT devices may not reliably benefit from the addition of a defibrillator.

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).

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).

Calcium, phosphate and calcium phosphate product are markers of outcome in patients with chronic heart failure.

BACKGROUND: Serum calcium (Ca) and inorganic phosphate (Pi) concentrations and calcium-phosphate product (CPP) levels are positively associated with worse outcomes in patients with chronic kidney disease, but there are few data for Pi or Ca and none for CPP in patients with chronic heart failure (CHF). METHODS: Unselected, consecutive patients with CHF (left ventricular ejection fraction, LVEF ≤45%) were enrolled in a prospective observational study for the occurrence of hospitalisation and mortality. Blood samples were collected at the time of recruitment and analysed immediately. RESULTS: Patients (n = 713) were on contemporary optimal treatment and mean (standard error, SE) follow-up was 765 (18.9) days. Mean (SE) Ca was 2.29 (0.004) mmol/l. Median (interquartile range, IQR) Pi was 1.11 (0.98-1.23) mmol/l and median CPP 2.53 (2.21-2.88) mmol(2)/l(2). LVEF correlated inversely with Ca, natural log-transformed (Ln)Pi, and LnCPP. There was no difference in CPP between classes of symptom severity or diabetes status. Ca and LnCPP (but not LnPi) were associated with total mortality. Ca was significantly associated with progressive HF and non-cardiovascular death but not with sudden death. Binary logistic regression analyses showed that LnPi and LnCPP were associated with risk of hospitalisation. CONCLUSIONS: Ca, Pi and CPP could be useful additional variables in determining risk in CHF patients. Further work is required to elucidate the mechanisms underlying the adverse influence and determine whether lowering phosphate levels per se in CHF patients is of benefit.

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.

Prosthetic valve thrombosis: keeping the valve ticking!

Prosthetic valve thrombosis is a serious acute complication of mechanical valvular replacement, with significant mortality and morbidity. This case highlights the key diagnostic features and the role of thrombolysis in treatment.