Reassessment of clinical variables in cardiac resynchronization defibrillator patients at the time of first replacement: Death after replacement of CRT (DARC) score.

INTRODUCTION: Cardiac resynchronization defibrillator (CRT-D) as primary prevention is known to reduce mortality. At the time of replacement, higher age and comorbidities may attenuate the benefit of implantable cardioverter-defibrillator (ICD) therapy. The purpose of this study was to evaluate the progression of comorbidities after implantation and their association with mortality following CRT-D generator replacement. In addition, a risk score was developed to identify patients at high risk for mortality after replacement. METHODS AND RESULTS: We identified patients implanted with a primary prevention CRT-D (n = 648) who subsequently underwent elective generator replacement (n = 218) from two prospective ICD registries. The cohort consisted of 218 patients (median age: 70 years, male gender: 73%, mean left ventricular ejection fraction [LVEF]: 36 ± 11% at replacement). Median follow-up after the replacement was 4.2 years during which 64 patients (29%) died and 11 patients (5%) received appropriate ICD shocks. An increase in comorbidities was observed in 77 patients (35%). The 5-year mortality rate was 41% in patients with ≥2 comorbidities at the time of replacement. A risk score incorporating age, gender, LVEF, atrial fibrillation, anemia, chronic kidney disease, and history of appropriate ICD shocks at time of replacement accurately predicted 5-year mortality (C-statistic 0.829). Patients with a risk score of greater than 2.5 had excess mortality at 5-year postreplacement compared with patients with a risk score less than 1.5 (57% vs. 6%; p < .001). CONCLUSION: A simple risk score accurately predicts 5-year mortality after replacement in CRT-D patients, as patients with a risk score of greater than 2.5 are at high risk of dying despite ICD protection.

Application of the heart failure meta-score to predict prognosis in patients with cardiac resynchronization defibrillators.

BACKGROUND: The Heart Failure (HF) Meta-score may be useful in predicting prognosis in patients with primary prevention cardiac resynchronization defibrillators (CRT-D) considering the competing risk of appropriate defibrillator shock versus mortality. METHODS: Data from 648 consecutive patients from two centers were used for the evaluation of the performance of the HF Meta-score. The primary endpoint was mortality and the secondary endpoint was time to first appropriate implantable cardioverter-defibrillator (ICD) shock or death without prior appropriate ICD shock. Fine-Gray model was used for competing risk regression analysis. RESULTS: In the entire cohort, 237 patients died over a median follow-up of 5.2 years. Five-year cumulative incidence of mortality ranged from 12% to 53%, for quintiles 1 through 5 of the HF Meta-score, respectively (log-rank P < 0.001). Compared with the lowest quintile, mortality risk was higher in the highest quintile (HR 6.9; 95%CI 3.7-12.8). The HF Meta-score had excellent calibration, accuracy, and good discrimination in predicting mortality (C-statistic 0.76 at 1-year and 0.71 at 5-year). The risk of death without appropriate ICD shock was higher in risk quintile 5 compared to quintile 1 (sub HR 5.8; 95%CI 3.1-11.0, P < 0.001). CONCLUSIONS: Our study demonstrated a good ability of the HF Meta-score to predict survival in HF patients treated with CRT-D as primary prevention. The HF Meta-score proved to be useful in identifying a subgroup with a significantly poor prognosis despite a CRT-D.

Automated electrocardiographic quantification of myocardial scar in patients undergoing primary prevention implantable cardioverter-defibrillator implantation: Association with mortality and subsequent appropriate and inappropriate therapies.

BACKGROUND: Myocardial scarring from infarction or nonischemic fibrosis forms an arrhythmogenic substrate. The Selvester QRS score has been developed to estimate myocardial scar from the 12-lead electrocardiogram. OBJECTIVE: We aimed to assess the value of an automated version of the Selvester QRS score for the prediction of implantable cardioverter-defibrillator (ICD) therapy and death in patients undergoing primary prevention ICD implantation. METHODS: Unselected patients undergoing primary prevention ICD implantation were included in this retrospective, observational, multicenter study. The QRS score was calculated automatically from a digital standard preimplantation 12-lead electrocardiogram and was correlated to the occurrence of death and appropriate and inappropriate shocks during follow-up. Analyses were performed in groups defined by QRS duration < 130 ms vs ≥ 130 ms. RESULTS: Overall, 1047 patients (872 [83%] men; median age 64 years IQR [55-71]) with ischemic (648, 62%) or nonischemic (399, 38%) cardiomyopathy were included. The median QRS duration was 123 ms (interquartile range [IQR] 111-157 ms), and the median QRS score was 5 (IQR 2-8). The QRS duration was <130 ms in 59% and ≥130 ms in 41%. During a median follow-up of 45 months (IQR 24-72 months), a QRS score of ≥5 was independently associated with a significantly higher risk of mortality (hazard ratio [HR] 1.67; 95% confidence interval [CI] 1.05-2.66; P = .031) and appropriate (HR 1.83; 95% CI 1.07-3.14; P = .028) and inappropriate (HR 2.32; 95% CI 1.04-5.17; P = .039) shocks in patients with QRS duration ≥ 130 ms. No association of the QRS score and outcome was observed in patients with QRS duration < 130 ms (P > .05). CONCLUSION: The automatically calculated Selvester QRS score, an indicator of myocardial scar burden, predicts mortality and appropriate and inappropriate shocks in patients undergoing primary prevention ICD implantation with a prolonged QRS duration.

Predicting Early Mortality Among Implantable Defibrillator Patients Treated With Cardiac Resynchronization Therapy.

BACKGROUND: The beneficial effects of a cardiac resynchronization defibrillator (CRT-D) in patients with heart failure, low left ventricular ejection fraction (LVEF), and wide QRS have clearly been established. Nevertheless, mortality remains high in some patients. The aim of this study was to develop and validate a risk score to identify patients at high risk for early mortality who are implanted with a CRT-D. METHODS AND RESULTS: For predictive modelling, 1282 consecutive patients from 5 centers (74% male; median age 66 years; median LVEF 25%; New York Heart Association class III-IV 60%; median QRS-width 160 ms) were randomly divided into a derivation and validation cohort. The primary endpoint is mortality at 3 years. Model development was performed using multivariate logistic regression by checking log likelihood, Akaike information criterion, and Bayesian information criterion. Model performance was validated using C statistics and calibration plots. The risk score included 7 independent mortality predictors, including myocardial infarction, LVEF, QRS duration, chronic obstructive pulmonary disease, chronic kidney disease, hyponatremia, and anemia. Calibration-in-the-large was suboptimal, reflected by a lower observed mortality (44%) than predicted (50%). The validated C statistic was 0.71 indicating modest performance. CONCLUSION: A risk score based on routine, readily available clinical variables can assist in identifying patients at high risk for early mortality within 3 years after CRT-D implantation.

Atrial electrogram quality in single-pass defibrillator leads with floating atrial bipole in patients with permanent atrial fibrillation and cardiac resynchronization therapy.

Many patients receiving cardiac resynchronization therapy (CRT) suffer from permanent atrial fibrillation (AF). Knowledge of the atrial rhythm is important to direct pharmacological or interventional treatment as well as maintaining AV-synchronous biventricular pacing if sinus rhythm can be restored. A single pass single-coil defibrillator lead with a floating atrial bipole has been shown to obtain reliable information about the atrial rhythm but has never been employed in a CRT-system. The purpose of this study was to assess the feasibility of implanting a single coil right ventricular ICD lead with a floating atrial bipole and the signal quality of atrial electrograms (AEGM) in CRT-defibrillator recipients with permanent AF. METHODS AND RESULTS: Seventeen patients (16 males, mean age 73 ±â€¯6 years, mean EF 25 ±â€¯5%) with permanent AF and an indication for CRT-defibrillator placement were implanted with a designated CRT-D system comprising a single pass defibrillator lead with a atrial floating bipole. They were followed-up for 103 ±â€¯22 days using remote monitoring for AEGM transmission. All patients had at last one AEGM suitable for atrial rhythm diagnosis and of 100 AEGM 99% were suitable for visual atrial rhythm assessment. Four patients were discharged in sinus rhythm and one reverted to AF during follow-up. CONCLUSION: Atrial electrograms retrieved from a single-pass defibrillator lead with a floating atrial bipole can be reliably used for atrial rhythm diagnosis in CRT recipients with permanent AF. Hence, a single pass ventricular defibrillator lead with a floating bipole can be considered in this population.

Sex differences in outcomes of primary prevention implantable cardioverter-defibrillator therapy: combined registry data from eleven European countries.

Aims: Therapy with an implantable cardioverter defibrillator (ICD) is established for the prevention of sudden cardiac death (SCD) in high risk patients. We aimed to determine the effectiveness of primary prevention ICD therapy by analysing registry data from 14 centres in 11 European countries compiled between 2002 and 2014, with emphasis on outcomes in women who have been underrepresented in all trials. Methods and results: Retrospective data of 14 local registries of primary prevention ICD implantations between 2002 and 2014 were compiled in a central database. Predefined primary outcome measures were overall mortality and first appropriate and first inappropriate shocks. A multivariable model enforcing a common hazard ratio for sex category across the centres, but allowing for centre-specific baseline hazards and centre specific effects of other covariates, was adjusted for age, the presence of ischaemic cardiomyopathy or a CRT-D, and left ventricular ejection fraction ≤25%. Of the 5033 patients, 957 (19%) were women. During a median follow-up of 33 months (IQR 16-55 months) 129 women (13%) and 807 men (20%) died (HR 0.65; 95% CI: [0.53, 0.79], P-value < 0.0001). An appropriate ICD shock occurred in 66 women (8%) and 514 men (14%; HR 0.61; 95% CI: 0.47-0.79; P = 0.0002). Conclusion: Our retrospective analysis of 14 local registries in 11 European countries demonstrates that fewer women than men undergo ICD implantation for primary prevention. After multivariate adjustment, women have a significantly lower mortality and receive fewer appropriate ICD shocks.

Comparison of Multivariate Risk Estimation Models to Predict Prognosis in Patients With Implantable Cardioverter Defibrillators With or Without Cardiac Resynchronization Therapy.

Several multivariate risk score models were developed to predict prognosis of patients with heart failure (HF). We compared 3 models with regard to prediction of mortality in patients with HF who received an implantable defibrillator (ICD) or a cardiac resynchronization therapy defibrillator (CRT-D), as primary prevention of sudden death. The study cohort consisted of 823 patients (ICD = 410; CRT-D = 413). The evaluated models were the Seattle Heart Failure Model (SHFM), the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) score, and an adjusted Charlson Comorbidity Index (aCCI). End point was the performance of the models to predict all-cause mortality at 5 years. This was determined by c-statistics, for both subgroups. Multivariate analysis was used to analyze the relations between the risk score models, their individual components and mortality, and its applicability to the entire population. Cumulative mortality was 4.9% at 1 year and 21.1% at 5 years. Discriminatory power for 5-year mortality was highest for the SHFM (0.73; p <0.001) compared with the MADIT II score and the aCCI for the entire population. SHFM performed better than the MADIT II score for CRT-D group. In the entire population, the SHFM and the aCCI were significant predictors of mortality in multivariate analysis (hazard ratio 1.90, 95% confidence interval 1.49 to 2.43 vs hazard ratio 1.11, 95% confidence interval 1.01 to 1.22). The strongest individual components were age, HF, impaired renal function, and cancer, whereas CRT-D use was no predictor. In conclusion, the SHFM has the best discriminatory power for 5-year mortality in patients with HF with an ICD or CRT-D. The aCCI and MADIT II scores are less powerful but viable alternatives.

Longevity of implantable cardioverter defibrillators: a comparison among manufacturers and over time.

AIMS: Longevity of implantable cardioverter defibrillators (ICDs) is crucial for patients and healthcare systems as replacements impact on infection rates and cost-effectiveness. Aim was to determine longevity using very large databases of two teaching hospitals with a high number of replacements and a rather homogeneous distribution among manufacturers. METHODS AND RESULTS: The study population consists of all patients in whom an ICD was inserted in. All ICD manufacturers operating in Switzerland and the Netherlands and all implanted ICDs were included. Implantable cardioverter defibrillator replacements due to normal battery depletion were considered events, and other replacements were censored. Longevity was assessed depending on manufacturers, pacing mode, implant before/after 2006, and all parameters combined. We analysed data from 3436 patients in whom 4881 ICDs [44.2% VVI-ICDs, 27.4% DDD-ICDs, 26.3% cardiac resynchronization therapy (CRT)-ICDs, 2.0% subcutaneous ICDs] were implanted. The four major manufacturers had implant shares between 18.4 and 31.5%. Replacement due to battery depletion (27.4%) was performed for 1339 ICDs. Patient survival at 5 years was 80.1%. Longevity at 5 years improved in contemporary compared with elderly ICDs [63.9-80.6% across all ICDs, of 73.7-92.1% in VVIs, 58.2-76.1% in DDDs, and of 47.1-66.3% in CRT defibrillators, all P value < 0.05]. Remarkable differences were seen among manufacturers, and those with better performance in elderly ICDs were not those with better performance in contemporary ones. CONCLUSION: Implantable cardioverter defibrillator longevity increased in contemporary models independent of manufacturer and pacing mode. Still, significant differences exist among manufacturers. These results might impact on device selection.

Concurrent Cardioversion of Atrial Fibrillation during ICD Shock Testing.

BACKGROUND: Many patients receiving an implantable cardioverter-defibrillator (ICD) also have atrial fibrillation (AF). Shock testing during ICD implantation carries a potential risk of cardioversion to sinus rhythm (SR) and thrombembolic events. We aimed to analyze the recurrence of AF after cardioversion to SR during ICD shock testing. METHODS: A total of 555 consecutive patients referred to a tertiary hospital in Switzerland for ICD implantation or generator exchange between 02/2002 and 03/2010 were screened for AF. Fifty-seven patients who were in AF at the time of ICD shock testing were included. RESULTS: Forty-four patients (77%) were successfully cardioverted from AF to SR. Type of AF (persistent, not permanent 64 vs 31% of cardioverted patients) was the only predictor. Thirty-nine patients (89%) experienced a recurrence of AF/atrial flutter after a median of 54 days (interquartile range 35-251 days). The only predictor for recurrence of AF was previous AF declared as permanent. No ischemic stroke occurred during hospitalization for the procedure. CONCLUSIONS: For patients in AF undergoing shock testing at the time of ICD implant, there is a high chance of cardioversion from AF to SR, but there is also a high risk of early recurrence. Decisions regarding long-term anticoagulation should not be based on the heart rhythm immediately following shock testing.

Evaluation of the need of elective implantable cardioverter-defibrillator generator replacement in primary prevention patients without prior appropriate ICD therapy.

OBJECTIVE: It is not clear whether patients who received an implantable cardioverter-defibrillator (ICD) for primary prevention should undergo device replacement if they never experienced an appropriate ICD therapy during the first generator longevity. This study evaluated the incidence and predictors of appropriate ICD therapy after device replacement in this specific population. METHODS: From two large prospective ICD registries, we identified all primary prevention patients who had a first ICD replacement without previous appropriate ICD therapy. Cox regression analysis was used to identify predictors of appropriate ICD therapy. RESULTS: Of 403 primary prevention patients needing first ICD replacement, 275 patients (68%) had not received previous appropriate ICD therapy. Patients without previous appropriate ICD therapy before first ICD replacement (mean age at replacement 62 ± 12 years, 75% male) had a mean follow-up of 86 ± 24 months after the initial implantation and 30 ± 24 months after device replacement. Following replacement, 3-year cumulative incidence of appropriate ICD therapy was 13.7% (95% CI 8.6 to 18.8%). No predictive factors associated with appropriate ICD therapy after replacement could be identified in spite of including seven clinically relevant factors. CONCLUSIONS: A considerable number of primary prevention patients without previous appropriate ICD therapy before first ICD replacement received appropriate ICD therapy after replacement. As there were no predictors of appropriate ICD therapy after replacement, replacing an ICD is still recommended in all primary prevention patients despite the lack of appropriate ICD therapy during first battery service life.

Application of a mortality risk score in a general population of patients with an implantable cardioverter defibrillator (ICD).

OBJECTIVE: The implantable cardioverter defibrillator (ICD) is very effective in the prevention of sudden cardiac death, but its benefit is impaired by competing risks. A simple risk model to predict mortality was designed for patients with primary prevention and ischaemic cardiomyopathy. We aimed to apply this score to a general ICD population. METHODS: This retrospective registry study included all patients in whom an ICD was implanted at a tertiary referral hospital. Risk factors were age >70 years, QRS width >120 ms, atrial fibrillation, New York Heart Association Functional Classification class >2 and glomerular filtration rate <60 mL/min/1.73 m(2). Kaplan-Meier curves were constructed according to the presence of 0, 1, 2 and >2 risk factors. RESULTS: The cohort consists of 1032 patients, 881 (86%) were men, mean age was 61±14 years and mean follow-up 66±46 months. 256 patients (25%) died 58±41 months after implant. The setting was secondary prevention in 498 patients (48%). No risk factors was present in 32% of patients, 1 in 27%, 2 in 20% and >2 in 21%, respectively. There was a significant and comprehensible relation between risk score and mortality. Cumulative survival was 82% in patients with 0 risk factors, 63% in those with 1, 41% in those with 2 and 23% in those with >2 risk factors (p < 0.0001). ICD therapies were documented in 421 patients (41%) without correlation to risk factors. CONCLUSIONS: In a mixed population of primary and secondary preventive ICD carriers, application of a simple risk score predicts long-term mortality but not appropriate use of the ICD.

Changes in renal function over time in patients with cardiac resynchronisation therapy.

QUESTION UNDER STUDY: Cardiac resynchronisation therapy (CRT) with defibrillator back-up (CRT-D) is widely used in selected patients with moderate/severe heart failure. Renal failure is common in these patients. Data on the impact of CRT on renal function are controversial and limited by short follow-up. The aim of this study was to describe changes in glomerular filtration rate (GFR) from baseline compared with 1 and 2 years after CRT implantation. METHODS: A total of 284 CRT-D patients with creatinine levels at baseline and after 1 year were identified in two prospective registries. In 149 patients, levels after 2 years were available. GFR in ml/min/1.73 m2 was estimated with the Modification Diet in Renal Disease equation and patients stratified into GFR stages 1 to 4. RESULTS: The population was predominantly male (75%), mean (± standard deviation) age was 61 ± 7 years and ejection fraction 24% ± 8 %. GFR was 63 ± 24 ml/min/1.73 m2 at implantation and 60 ± 24 ml/min/1.73 m2 after 1 year (p = 0.26). At the 2-year follow-up, GFR had decreased from 60 ± 21 to 56 ± 21 ml/min/1.73 m2 (p = 0.04). Mean GFR decreased in stages 1 and 2, remained stable in stage 3 and improved in stage 4 patients. After 2 years, GFR had decreased ≥10 ml/min/1.73 m2 in 42%, but improved in only 15% (p = 0.04). CONCLUSIONS: Overall, mean GFR in CRT-D patients decreases at 1 and 2 years after implantation, depending in part on the initial degree of renal function. However, the chance of further substantial deterioration (≥10 ml/min/1.73 m2) is considerable.

Role of defibrillation threshold testing in the contemporary defibrillator patient population.

INTRODUCTION: Defibrillation threshold (DFT) testing has been performed to prove functionality of the implantable cardioverter defibrillator (ICD). Over the past years it has become increasingly controversial because of possible morbidity and mortality. The goal of this study was to determine unsuccessful shock testing and report strategies used to overcome these problems. METHODS AND RESULTS: A total of 314 patients with a de novo implantation of an ICD and 127 patients receiving a generator exchange were identified retrospectively. All patients underwent defibrillation threshold testing after induction of VF using a low-energy T-wave shock during the intervention, 2 shock tests after de novo implantations, 1 after generator change. A safety margin of 10 J or more was requested. Seven (2.3%) patients in the de novo group and 2 patients (1.4%) in the generator exchange group could not be defibrillated using the standard approach. All of those patients had either chronic amiodarone therapy, secondary prevention or a cardiac resynchronization therapy device (CRT). In univariate analysis, amiodarone therapy, dilated cardiomyopathy, and lower ejection fraction were predictors of failure. CONCLUSION: Our study's results as well as a review of the current literature favor shock testing, especially in patients with specific risk factors as mentioned above.

Performance of the Seattle Heart Failure Model in implantable defibrillator patients treated with cardiac resynchronization therapy.

The Seattle Heart Failure Model (SHFM) is a validated multivariate risk prediction model for mortality in patients with heart failure, using widely available clinical variables. The aim of this study was to assess the performance of the SHFM when applied to patients with heart failure who received cardiac resynchronization therapy devices with defibrillation. A total of 413 patients were identified from 2 prospective implantable cardioverter-defibrillator registries who received cardiac resynchronization therapy devices with defibrillation for the primary prevention of sudden death. Baseline laboratory and clinical data were entered in the SHFM to calculate predicted survival. The end point was all-cause mortality. During a median follow-up period of 2.8 years, 78 patients died and 9 underwent heart transplantation. Observed versus predicted 5-year mortality rates were 11.6% versus 11.4%, 21.5% versus 22.1%, and 41.4% versus 46.1% by ascending tertile of Seattle Heart Failure Score, respectively. No systematic or substantial errors of risk estimation were observed. Discrimination was excellent; the C-statistic ranged from 0.78 at 1-year follow-up to 0.70 at 5-year follow-up, and the Hosmer-Lemeshow chi-square statistic was 0.87 (p = 0.65). In conclusion, in patients with heart failure who received cardiac resynchronization therapy devices with defibrillation, the SHFM offers adequate discrimination of risk for all-cause mortality and estimation of mortality risk without substantial or systematic errors.

Clinical impact of screening for sleep related breathing disorders in atrial fibrillation.

OBJECTIVE: The aim of this study was to quantify daytime symptoms in atrial fibrillation (AF) patients with and without sleep related breathing disorders (SRBD). BACKGROUND: SRBD are common in patients with AF but little is known about daytime symptoms among those with SRBD. METHODS: Patients with AF admitted to clinics of two tertiary referral hospitals for a variety of different cardiovascular diseases were screened with a trans-nasal airflow measurement device allowing measurement of the apnea-hypopnea-index. Data on cardiac risk factors, left ventricular ejection fraction (LVEF) and cardiac medication were collected. Presence of SRBD was defined as an AHI ≥ 15/h. The Epworth sleepiness scale (ESS) was used to quantify daytime symptoms. RESULTS: Of 102 screened patients 8 were excluded due to device malfunction (n=1), dislocation of nasal cannula (n=6), or hyperthyroidism (n=1). Among the remaining 94 patients, 40 (43%) were diagnosed with SRBD. Patients with and without SRBD had similar age, body mass index, LVEF and cardiac medication. The prevalence of coronary artery disease was higher in patients with SRBD than in those without (50 vs. 17%; p=0.0007). ESS score was low and similar in both groups (no SRBD: median 4, interquartile range (IQR) 2-4 vs. SRBD: 5, IQR 3-8; p=0.14). Only 6/40 (5%) of the patients underwent overnight polysomnography and 2 (5%) started CPAP ventilation during follow-up. CONCLUSIONS: Even though SRBD are common in patients with AF, the prevalence of daytime symptoms is rare. Consequently, most patients will not initiate CPAP ventilation after positive SRBD screening.

[Device therapy in chronic heart failure]. / Device-Therapie der chronischen Herzinsuffizienz.

Besides optimal drug therapy, cardiac resynchronisation therapy offers a further therapy option for selected patients. Additional ICD implantation should be evaluated as well to prevent sudden cardiac death.

The prognosis of implantable defibrillator patients treated with cardiac resynchronization therapy: comorbidity burden as predictor of mortality.

AIMS: Comorbidity, such as myocardial infarction, diabetes, and renal failure, plays a pivotal role in the prognosis of a patient with arrhythmias. However, data on the prognostic impact of comorbiditiy in heart failure patients with cardiac resynchronization therapy and defibrillation (CRT-D) are scarce. The purpose of this study was to determine the impact of comorbidity on survival in CRT-D patients. METHODS AND RESULTS: The study population consisted of 463 heart failure patients who received a CRT-D between 1999 and 2008 in Rotterdam and Basel. The Charlson comorbidity index (CCI) is often used as an adjusting variable in prognostic models. The Cox proportional hazards analysis was performed to determine the independent effect of comorbidity on survival. During a median follow-up of 30.5 months, 85 patients died. Mortality rates at 1 and 7 years were 6.3 and 32.3%. Cumulative incidence of implantable cardioverter defibrillator (ICD) therapy at 7 years was 50%, and death without ICD therapy was observed in 9% of patients. At least three comorbid conditions were observed in 81% of patients. Patients who died had a higher CCI score compared with those who survived (3.9 ± 1.5 vs. 2.9 ± 1.5; P < 0.001). An age-adjusted CCI score ≥ 5 was a predictor of mortality (hazard ratio 3.69, 95% CI 2.06-6.60; P < 0.001) independent from indication for ICD therapy, and from ICD interventions during the clinical course. CONCLUSION: Comorbidity is often present in heart failure patients, and a high comorbidity burden was a significant predictor of mortality in CRT-D recipients. Comorbidity cannot predict appropriate ICD therapy. Death without prior ICD therapy occurs in a minor proportion of patients.

Close connection between improvement in left ventricular function by cardiac resynchronization therapy and the incidence of arrhythmias in cardiac resynchronization therapy-defibrillator patients.

AIMS: The aim of this study was to determine the relationship between improved ejection fraction (EF) and occurrence of arrhythmias in patients with cardiac resynchronization therapy devices with defibrillator function (CRT-D). The hypothesis was that patients who experienced a marked improvement in EF also had fewer appropriate defibrillator interventions. METHODS AND RESULTS: We analysed data of 270 patients from 2 prospective registries with follow-up of ≥12 months and echocardiography performed ≥8 months after CRT-D implantation. The discriminator was whether left ventricular ejection fraction (LVEF) improved to >35% [cut-off for primary prevention implantable cardioverter-defibrillator (ICD) implantation]. Mean age was 61±11 years, LVEF 22±5%, and follow-up 40±22 months. Ischaemic cardiomyopathy was present in 48%, and secondary prevention indication was present in 25%. Implantable cardioverter-defibrillator interventions were delivered to 35% of patients. Echocardiography (20±15 months after implantation) showed an improvement in LVEF from 22% (SD 5.4%) to 30% (SD 9.8%). Improvement to >35% was seen in 21% of patients. Those who improved to >35% had fewer ICD interventions than those who did not (23 vs.38%; P-value 0.03). Analysing only patients with a primary prevention indication and stratifying again in patients with and without improvement of LVEF to >35%, the latter had highly significant more ICD-therapies (6 vs. 31%; P-value 0.0008). CONCLUSION: Patients with CRT-D for primary prevention, whose LVEF improved to >35% during mid-term follow-up, are at low risk of first ICD therapies beyond year 1. If similar findings are reported in other patient cohorts, this might impact on decision-making at the time of battery depletion.

Risk for incident atrial fibrillation in patients who receive antihypertensive drugs: a nested case-control study.

BACKGROUND: Different antihypertensive drug classes may alter risk for atrial fibrillation. Some studies suggest that drugs that interfere with the renin-angiotensin system may be favorable because of their effect on atrial remodeling. OBJECTIVE: To assess and compare the relative risk for incident atrial fibrillation among hypertensive patients who receive antihypertensive drugs from different classes. DESIGN: Nested case-control analysis. SETTING: The United Kingdom-based General Practice Research Database, a well-validated primary care database comprising approximately 5 million patient records. PATIENTS: 4661 patients with atrial fibrillation and 18,642 matched control participants from a population of 682,993 patients treated for hypertension. MEASUREMENTS: A comparison of the risk for atrial fibrillation among hypertensive users of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II-receptor blockers (ARBs), or beta-blockers with the reference group of users of calcium-channel blockers. Patients with clinical risk factors for atrial fibrillation were excluded. RESULTS: Current exclusive long-term therapy with ACE inhibitors (odds ratio [OR], 0.75 [95% CI, 0.65 to 0.87]), ARBs (OR, 0.71 [CI, 0.57 to 0.89]), or beta-blockers (OR, 0.78 [CI, 0.67 to 0.92]) was associated with a lower risk for atrial fibrillation than current exclusive therapy with calcium-channel blockers. LIMITATION: Blood pressure changes during treatment courses could not be evaluated, and risk for bias by indication cannot be fully excluded in an observational study. CONCLUSION: In hypertensive patients, long-term receipt of ACE inhibitors, ARBs, or beta-blockers reduces the risk for atrial fibrillation compared with receipt of calcium-channel blockers. PRIMARY FUNDING SOURCE: None.