Feasibility and safety of left atrial posterior wall isolation with a new Cryoballoon technology in patients with persistent atrial fibrillation.

BACKGROUND: Left atrial posterior wall isolation (LAPWI) is often performed in addition to pulmonary vein isolation (PVI) in the setting of persistent atrial fibrillation (AF) ablation. The aim of this study was to evaluate the feasibility and safety of a new cryoballoon ablation system in achieving PVI + LAPWI isolation. METHODS: The study was a prospective, non-randomized, single center study. Forty consecutive patients, undergoing PVI + LAPWI with the novel POLARx™, were compared to 40 consecutive patients who underwent the same procedure with the established Arctic Front Advance PRO™. RESULTS: Acute isolation was achieved in all PVs in both groups and left posterior wall isolation (LAPWI) was achieved in 38 patients (95%) in the POLARx group and in 36 patients (90%) in Arctic Front group. Procedural outcomes were similar between both groups, except for lower temperatures during cryoenergy in the POLARx group, for both pulmonary vein isolation (PVI) and LAPWI. CONCLUSION: LAPWI + PVI with the novel POLARx™ Cryoballoon is feasible and safe; the results are comparable with the Arctic Front Advance PRO™ system.

Catheter Ablation for Atrial Fibrillation with Heart Failure.

BACKGROUND: Mortality and morbidity are higher among patients with atrial fibrillation and heart failure than among those with heart failure alone. Catheter ablation for atrial fibrillation has been proposed as a means of improving outcomes among patients with heart failure who are otherwise receiving appropriate treatment. METHODS: We randomly assigned patients with symptomatic paroxysmal or persistent atrial fibrillation who did not have a response to antiarrhythmic drugs, had unacceptable side effects, or were unwilling to take these drugs to undergo either catheter ablation (179 patients) or medical therapy (rate or rhythm control) (184 patients) for atrial fibrillation in addition to guidelines-based therapy for heart failure. All the patients had New York Heart Association class II, III, or IV heart failure, a left ventricular ejection fraction of 35% or less, and an implanted defibrillator. The primary end point was a composite of death from any cause or hospitalization for worsening heart failure. RESULTS: After a median follow-up of 37.8 months, the primary composite end point occurred in significantly fewer patients in the ablation group than in the medical-therapy group (51 patients [28.5%] vs. 82 patients [44.6%]; hazard ratio, 0.62; 95% confidence interval [CI], 0.43 to 0.87; P=0.007). Significantly fewer patients in the ablation group died from any cause (24 [13.4%] vs. 46 [25.0%]; hazard ratio, 0.53; 95% CI, 0.32 to 0.86; P=0.01), were hospitalized for worsening heart failure (37 [20.7%] vs. 66 [35.9%]; hazard ratio, 0.56; 95% CI, 0.37 to 0.83; P=0.004), or died from cardiovascular causes (20 [11.2%] vs. 41 [22.3%]; hazard ratio, 0.49; 95% CI, 0.29 to 0.84; P=0.009). CONCLUSIONS: Catheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy. (Funded by Biotronik; CASTLE-AF ClinicalTrials.gov number, NCT00643188 .).

Feasibility of His-bundle pacing in patients with conduction disorders following transcatheter aortic valve replacement.

BACKGROUND: Conduction disorders requiring permanent pacemaker implantation occur frequently after transcatheter aortic valve replacement (TAVR). This multicenter study explored the feasibility and safety of His bundle pacing (HBP) in TAVR patients with a pacemaker indication to correct a TAVR-induced left bundle branch block (LBBB). METHODS: Patients qualifying for a permanent pacemaker implant after TAVR were planned for HBP implant. HBP was performed using the Select Secure (3830; Medtronic) pacing lead, delivered through a fixed curve or deflectable sheath (C315HIS or C304; Medtronic). Successful HBP was defined as selective or nonselective HBP, irrespective of LBB recruitment. Successful LBBB correction was defined as selective or nonselective HBP resulting in paced QRS morphology similar to pre-TAVR QRS and paced QRS duration (QRSd) less than 120 milliseconds with thresholds less than 3.0 V at 1.0-millisecond pulse width. RESULTS: The study enrolled 16 patients requiring a permanent pacemaker after TAVR (age 85 ± 4 years, 31% female, all LBBB; QRSd: 161 ± 14 milliseconds). Capture of the His bundle was achieved in 13 of 16 (81%) patients. HBP with LBBB correction was achieved in 11 of 16 (69%) and QRSd narrowed from 162 ± 14 to 99 ± 13 milliseconds and 134 ± 7 milliseconds during S-HBP and NS-HBP, respectively (P = .005). At implantation, mean threshold for LBBB correction was 1.9 ± 1.1 V at 1.0 millisecond. Thresholds remained stable at 11 ± 4 months follow-up (1.8 ± 0.9 V at 1.0 millisecond, P = .231 for comparison with implant thresholds). During HBP implant, one temporary complete atrioventricular block occurred. CONCLUSION: Permanent HBP is feasible in the majority of patients with TAVR requiring a permanent pacemaker with the potential to correct a TAVR-induced LBBB with acceptable pacing thresholds.

In-hospital and 12-month follow-up outcome from the ESC-EORP EHRA Atrial Fibrillation Ablation Long-Term registry: sex differences.

AIM: The purpose of this study was to compare sex differences of atrial fibrillation (AF) catheter ablation (CA) and to analyse the opportunities for improved outcomes. METHODS AND RESULTS: All data were collected from the Atrial Fibrillation Ablation Long-Term registry, a prospective, multinational study conducted by the ESC-EORP European Heart Rhythm Association (EHRA) under the EURObservational Research Programme (ESC-EORP). A total of 104 centres in 27 European countries participated. Of 3593 included patients, 1146 (31.9%) were female. Female patients were older (61.0 vs. 56.4 years; P < 0.001), had more comorbidities (hypertension, diabetes, and obesity), more episodes of arrhythmias per month (6.9 vs. 6.2; P < 0.001), and a higher average EHRA score (2.6 vs. 2.4; P < 0.001). The duration of the procedure was shorter in females (160.1 min vs. 167.9 min; P < 0.001), irrespective of additional ablation lesions added to pulmonary vein isolation. Overall cardiovascular complications were more frequent in women than in men (5.7% vs. 3.4%; P < 0.001). Furthermore, cardiac perforations (3.8% vs. 1.3%; P = 0.011) and neurological complications (2.2% vs. 0.3%; P = 0.004) were found in females in less experienced centres than in experienced ones. On a final note, at 12 months, AF recurrence rate was similar in females and males (34.4% vs. 34.2%; P = 0.897), but more females were still on antiarrhythmic drugs (50.6% vs. 44.1%; P < 0.001) when compared with men. CONCLUSION: Females underwent CA procedures for AF less frequently than males throughout Europe, despite more recurrent symptoms. With the same success rate, severe acute complications remained considerable in females, especially in less experienced centres.

Biventricular Paced QRS Area Predicts Acute Hemodynamic CRT Response Better Than QRS Duration or QRS Amplitudes.

INTRODUCTION: Vectorcardiographic (VCG) QRS area of left bundle branch block (LBBB) predicts acute hemodynamic response in cardiac resynchronization therapy (CRT) patients. We hypothesized that changes in QRS area occurring with biventricular pacing (BV) might predict acute hemodynamic CRT response (AHR). METHODS AND RESULTS: VCGs of 624 BV paced electrocardiograms (25 LBBB patients with 35 different pacing configurations) were calculated according to Frank's orthogonal lead system. Maximum QRS vector amplitudes (XAmpl , YAmpl , ZAmpl , and 3DAmp ) and QRS areas (XArea , YArea , ZArea , and 3DArea ) in the orthogonal leads (X, Y, and Z) and in 3-dimensional projection were measured. Volume of the 3D vector loop and global QRS duration (QRSD) on the surface electrocardiogram were assessed. Differences (Δ) in VCG parameters between BV paced and LBBB QRS complexes were calculated. An increase of 10% in dP/dt max was considered as AHR. LBBB conduction is characterized by a large ZArea (109 µVs, interquartile range [IQR]:75;135), significantly larger than XArea (22 µVs, IQR:10;57) and YArea (44 µVs, IQR:32;62, P < 0.001). Overall, QRS duration, amplitudes, and areas decrease significantly with BV pacing (P < 0.001). Of all VCG parameters, 3DAmpl , Δ3DAmpl , ZArea, ΔZArea , Δ3DArea , and ΔQRSD differentiate AHR response from nonresponse (P < 0.05). ΔZArea predicted best positive AHR (area under the curve = 0.813) and outperformed any other VCG parameter or QRSD measurement. CONCLUSION: Of all VCG parameters, reduction in QRS area, calculated in Frank's Z lead, predicts acute hemodynamic response best. This method might be an easy, noninvasive tool to guide CRT implantation and optimization.

Different Methods to Measure QRS Duration in CRT Patients: Impact on the Predictive Value of QRS Duration Parameters.

BACKGROUND: Measurements of QRS duration (QRSD) in patients undergoing cardiac resynchronization therapy (CRT) are not standardized. We hypothesized that both the measurement of QRSD and its predictive value on CRT response are sensitive to the method by which QRSD is measured. METHODS: Electrocardiograms (ECGs) pre- and post-CRT from 52 CRT patients (66 ± 12 years, 65% male) were retrospectively analyzed. Custom-made software was developed to measure global QRSD (QRSDglobal ) and lead-specific QRSD (QRSDI,II,III,aVR,aVL,aVF,V1,V2,V3,V4,V5,V6 ). QRSD was also assessed automatic by a routinely used ECG device. For each method we measured QRSD pre- and post-CRT and shortening of QRSD (∆QRSD). Response to CRT at 6 months was defined as an improvement of ≥1 class in New York Heart Association classification and an increase by >7.5% in left ventricular ejection fraction. RESULTS: The CRT response rate was 77% (n = 40). Different methods to measure QRSD show divergent nominal values before (median range 152-172 ms, P < 0.001) and after CRT (130-152 ms, P < 0.001). The predictive value of QRSD measurements for CRT response also varies significantly according to the method used (range AUC pre-CRT QRSD 0.400-0.580, P < 0.05; AUC post-CRT QRSD 0.447-0.768, P < 0.05; AUC ΔQRSD 0.540-0.858, P < 0.05). Global QRSD measurements revealed lower variability compared to lead-specific QRSD. CONCLUSION: Different methods to measure QRSD yield not only different nominal values but also influence the value of QRSD in predicting CRT response. Measuring QRSD by a global method can help to standardize QRSD measurements in future studies.

Unique cardiac Purkinje fiber transient outward current ß-subunit composition: a potential molecular link to idiopathic ventricular fibrillation.

RATIONALE: A chromosomal haplotype producing cardiac overexpression of dipeptidyl peptidase-like protein-6 (DPP6) causes familial idiopathic ventricular fibrillation. The molecular basis of transient outward current (I(to)) in Purkinje fibers (PFs) is poorly understood. We hypothesized that DPP6 contributes to PF I(to) and that its overexpression might specifically alter PF I(to) properties and repolarization. OBJECTIVE: To assess the potential role of DPP6 in PF I(to). METHODS AND RESULTS: Clinical data in 5 idiopathic ventricular fibrillation patients suggested arrhythmia origin in the PF-conducting system. PF and ventricular muscle I(to) had similar density, but PF I(to) differed from ventricular muscle in having tetraethylammonium sensitivity and slower recovery. DPP6 overexpression significantly increased, whereas DPP6 knockdown reduced, I(to) density and tetraethylammonium sensitivity in canine PF but not in ventricular muscle cells. The K(+)-channel interacting ß-subunit K(+)-channel interacting protein type-2, essential for normal expression of I(to) in ventricular muscle, was weakly expressed in human PFs, whereas DPP6 and frequenin (neuronal calcium sensor-1) were enriched. Heterologous expression of Kv4.3 in Chinese hamster ovary cells produced small I(to); I(to) amplitude was greatly enhanced by coexpression with K(+)-channel interacting protein type-2 or DPP6. Coexpression of DPP6 with Kv4.3 and K(+)-channel interacting protein type-2 failed to alter I(to) compared with Kv4.3/K(+)-channel interacting protein type-2 alone, but DPP6 expression with Kv4.3 and neuronal calcium sensor-1 (to mimic PF I(to) composition) greatly enhanced I(to) compared with Kv4.3/neuronal calcium sensor-1 and recapitulated characteristic PF kinetic/pharmacological properties. A mathematical model of cardiac PF action potentials showed that I(to) enhancement can greatly accelerate PF repolarization. CONCLUSIONS: These results point to a previously unknown central role of DPP6 in PF I(to), with DPP6 gain of function selectively enhancing PF current, and suggest that a DPP6-mediated PF early-repolarization syndrome might be a novel molecular paradigm for some forms of idiopathic ventricular fibrillation.

Ventricular tachyarrhythmias and mortality in patients with an implantable cardioverter defibrillator: impact of depression in the MIDAS cohort.

OBJECTIVE: We examined whether depression is independently associated with implantable cardioverter defibrillator (ICD) therapy for ventricular tachyarrhythmias and mortality. METHODS: A cohort of 430 consecutive patients with a first-time ICD (79% men; mean [standard deviation] age = 57.8 [12.1] years) completed the Hospital Anxiety and Depression Scale 1 day before implantation. During follow-up, the ICD was interrogated at 3-month intervals. Cox proportional hazard regression analyses were used to examine the impact of depression on time to first appropriate ICD therapy and all-cause mortality during a median follow-up period of 3.8 years. RESULTS: Of all patients, 108 (25.1%) were depressed. Depression was not associated with time to first appropriate ICD therapy (unadjusted hazard ratio [HR] = 1.07, 95% confidence interval [CI] = 0.73-1.56). However, depression was associated with an increased risk for all-cause mortality (unadjusted HR = 2.18, 95% CI = 1.36-3.49). Depression remained independently associated with all-cause mortality (HR = 1.94, 95% CI = 1.06-3.54, p = .031), after adjusting for demographic and clinical characteristics. Patients who remained depressed during the first 3 months after implantation were at greatest risk for dying (HR = 2.88, 95% CI = 1.29-6.45, p = .010). CONCLUSIONS: The current study showed that depression at the time of implant is not associated with time to first appropriate ICD therapy but almost doubled the risk for all-cause mortality in patients with an ICD. Patients with persistent depression during the first 3 months after implantation face the greatest risk of dying. Current evidence indicates that multifactorial interventions are likely to be the most successful in terms of reducing distress. Whether this translates into enhanced survival has yet to be determined.

Early mortality in prophylactic implantable cardioverter-defibrillator recipients: development and validation of a clinical risk score.

AIMS: To reduce sudden cardiac death, implantable cardioverter-defibrillators (ICDs) are indicated in patients with ischaemic and non-ischaemic dilated cardiomyopathy and a left ventricular ejection fraction (LVEF) ≤35%. Current guidelines do not recommend device therapy in patients with a life expectancy <1 year since benefit in these patients is low. In this study, we evaluated the incidence and predictors of early mortality (<1 year after implantation) in a consecutive primary prevention population. METHODS AND RESULTS: Analysis was performed on a prediction and validation cohort. The primary endpoint was all-cause mortality at 1 year. The prediction cohort comprised 861 prophylactic ICD recipients with ischaemic cardiomyopathy or dilated cardiomyopathy from the Academic Medical Center (Amsterdam) and Thorax Center Twente (Enschede). Detailed clinical data were collected. After multivariate analysis, a risk score was developed based on age ≥75 years, LVEF ≤ 20%, history of atrial fibrillation, and estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73 m(2). Using these predictors, a low (≤1 factor), intermediate (2 factors), and high (≥3 factors) risk group could be identified with 1-year mortality of, respectively, 3.4, 10.9, and 38.9% (P< 0.01). Afterwards, the risk score was validated in 706 primary prevention patients from the Erasmus Medical Center (Rotterdam). One-year mortality was, respectively, 2.5, 13.2, and 46.3% (all P< 0.01). CONCLUSION: A simple risk score based on age, LVEF, eGFR, and atrial fibrillation can identify patients at low, intermediate, and high risk for early mortality after ICD implantation. This may be helpful in the risk assessment of ICD candidates.

The cost-effectiveness of primary prophylactic implantable defibrillator therapy in patients with ischaemic or non-ischaemic heart disease: a European analysis.

AIMS: It remains unclear whether primary prophylactic implantable cardioverter-defibrillator (ICD) therapy is cost-effective compared with a 'no ICD strategy' in the European health care setting. We performed a cost-effectiveness analysis for a cohort of patients with a left ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease. METHODS AND RESULTS: A Markov decision analytic model was used to evaluate long-term survival, quality-adjusted life years (QALYs), and lifetime costs for a cohort of patients with a reduced left ventricular function without previous arrhythmias, managed with a prophylactic ICD. Input data on effectiveness were derived from a meta-analysis of primary prophylactic ICD-only therapy randomized trials, from a prospective cohort study of ICD patients, from a health care utilization survey, and from the literature. Input data on costs were derived from a micro-cost analysis. Data on quality-of-life were derived from the literature. Deterministic and probabilistic sensitivity analysis was performed to assess the uncertainty. Probabilistic sensitivity analysis demonstrated a mean lifetime cost of €50 685 ± €4604 and 6.26 ± 0.64 QALYs for patients in the 'no ICD strategy'. Patients in the 'ICD strategy' accumulated €86 759 ± €3343 and an effectiveness of 7.08 ± 0.71 QALYs yielding an incremental cost-effectiveness ratio of €43 993/QALY gained compared with the 'no ICD strategy'. The probability that ICD therapy is cost-effective was 65% at a willingness-to-pay threshold of €80 000/QALY. CONCLUSION: Our results suggest that primary prophylactic ICD therapy in patients with a left ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease is cost-effective in the European setting.

An entirely subcutaneous implantable cardioverter-defibrillator.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) prevent sudden death from cardiac causes in selected patients but require the use of transvenous lead systems. To eliminate the need for venous access, we designed and tested an entirely subcutaneous ICD system. METHODS: First, we conducted two short-term clinical trials to identify a suitable device configuration and assess energy requirements. We evaluated four subcutaneous ICD configurations in 78 patients who were candidates for ICD implantation and subsequently tested the best configuration in 49 additional patients to determine the subcutaneous defibrillation threshold in comparison with that of the standard transvenous ICD. Then we evaluated the long-term use of subcutaneous ICDs in a pilot study, involving 6 patients, which was followed by a trial involving 55 patients. RESULTS: The best device configuration consisted of a parasternal electrode and a left lateral thoracic pulse generator. This configuration was as effective as a transvenous ICD for terminating induced ventricular fibrillation, albeit with a significantly higher mean (+/-SD) energy requirement (36.6+/-19.8 J vs. 11.1+/-8.5 J). Among patients who received a permanent subcutaneous ICD, ventricular fibrillation was successfully detected in 100% of 137 induced episodes. Induced ventricular fibrillation was converted twice in 58 of 59 patients (98%) with the delivery of 65-J shocks in two consecutive tests. Clinically significant adverse events included two pocket infections and four lead revisions. After a mean of 10+/-1 months, the device had successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. CONCLUSIONS: In small, nonrandomized studies, an entirely subcutaneous ICD consistently detected and converted ventricular fibrillation induced during electrophysiological testing. The device also successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. (ClinicalTrials.gov numbers, NCT00399217 and NCT00853645.)

Implantable cardioverter-defibrillators in hypertrophic cardiomyopathy: patient outcomes, rate of appropriate and inappropriate interventions, and complications.

BACKGROUND: Sudden cardiac death (SCD) is the most devastating complication of hypertrophic cardiomyopathy (HCM), but this can be prevented by an implantable cardioverter-defibrillator (ICD). The aim of this study is to evaluate HCM patients with ICDs for primary or secondary prevention of SCD. METHODS: The study population consisted of all HCM patients with an ICD in 2 tertiary referral clinics. End points during follow-up were total and cardiac mortality, appropriate and inappropriate ICD intervention, and device-related complications. Cox-regression analysis was performed to identify predictors of outcome. RESULTS: ICDs were implanted in 134 patients with HCM (mean age 44 ± 17 years, 34% women, 4.2 ± 4.8 years follow-up). Annualized cardiac mortality rate was 3.4% per year and associated with New York Heart Association class III or IV (HR 5.2 [2.0-14, P = .002]) and cardiac resynchronization therapy (HR 6.3 [2.1-20, P = .02]). Appropriate ICD interventions occurred in 38 patients (6.8%/year) and was associated with implantation for secondary prevention of SCD (HR 4.0 [1.8-9.1], P = .001) and male gender (HR 3.3 [1.2-9.0], P = .02). Inappropriate ICD intervention occurred in 21 patients (3.7%/year) and in 20 patients device related complications were documented (3.6%/year). CONCLUSION: ICDs successfully abort life-threatening arrhythmias in HCM patients at increased risk of SCD with an annualized intervention rate of 6.8% per year. End-stage heart failure is the main cause of mortality in these patients. The annualized rate of inappropriate ICD intervention was 3.7% per year, whereas device-related complications occurred 3.6% per year.

Anxiety and risk of ventricular arrhythmias or mortality in patients with an implantable cardioverter defibrillator.

OBJECTIVE: A subgroup of patients with an implantable cardioverter defibrillator (ICD) experiences anxiety after device implantation. The purpose of the present study was to evaluate whether anxiety is predictive of ventricular arrhythmias and all-cause mortality 1 year post ICD implantation. METHODS: A total of 1012 patients completed the state version of the State-Trait Anxiety Inventory at baseline. The end points were ventricular arrhythmias and mortality the first year after ICD implantation. RESULTS: Within the first year after ICD implantation, 19% of patients experienced a ventricular arrhythmia, and 4% died. Anxiety was associated with an increased risk of ventricular arrhythmias (hazard ratio [HR] = 1.017; 95% confidence interval [CI] = 1.005-1.028; p = .005) and mortality (HR = 1.038; 95% CI = 1.014-1.063; p = .002) in adjusted analysis. Patients with anxiety (highest tertile) had a 1.9 increased risk for ventricular arrhythmias (95% CI = 1.329-2.753; p =.001) and a 2.9 increased risk for mortality (95% CI = 1.269-6.677; p = .01) compared with patients with low anxiety (lowest tertile). Among 257 patients with cardiac resynchronization therapy, anxiety was associated with mortality (HR = 5.381; 95% CI = 1.254-23.092; p = .02) after adjusting for demographic and clinical covariates. CONCLUSIONS: Anxiety was associated with an increased risk of ventricular arrhythmias and mortality 1 year after ICD implantation, independent of demographic and clinical covariates. Monitoring and treatment of anxiety may be warranted in a selected subgroup of high-risk patients with an ICD.

Comorbidity burden is associated with poor psychological well-being and physical health status in patients with an implantable cardioverter-defibrillator.

AIMS: Comorbidity burden has been linked to survival in patients with an implantable cardioverter-defibrillator (ICD), but no study has examined the influence on psychological well-being and health status. We examined the relationship between comorbidity burden and anxiety, depression, and health status in patients with an ICD during the first 12 months post-implantation using a prospective study design. METHODS AND RESULTS: Consecutively, implanted ICD patients (N = 401; 78% men) completed the Hospital Anxiety and Depression Scale and the Short Form Health Survey 36 (SF-36) at baseline, 3, 6, and 12 months post-implantation. Data were analysed using general linear mixed modelling repeated measures multivariable analysis of variance. The mean Charlson comorbidity index score was 3.5 (± 2.4). In adjusted analyses, comorbidity burden was significantly associated with depression (P = 0.003) and the physical health status domains of the SF-36 (Physical Functioning: P < 0.001; Role Limitations-Physical: P = 0.023; Bodily Pain: P = 0.004; and General Health: P = 0.025) but not with anxiety (P = 0.62) and the mental health status domains of the SF-36 (all P's > 0.05). Chronic heart failure, chronic obstructive pulmonary disease, cerebrovascular disease, and renal failure were the comorbidities with the most impact on depression and physical health status. CONCLUSION: Comorbidity burden was a significant predictor of poorer psychological well-being and physical health status in ICD patients during the first 12 months post-implantation. In the care and management of ICD patients, it is important to recognize the impact of comorbidity burden on patients' mood and health status, and that adjunctive intervention may be warranted to enhance well-being.

Poor health status and distress in cardiac patients: the role of device therapy vs. underlying heart disease.

AIMS: Implantable cardioverter defibrillator (ICD) therapy, which includes the risk of shocks, is considered the primary culprit of reductions in patient reported outcomes (PROs; e.g. health status and distress), thereby negating the role of underlying disease severity. We examined the relative influence of living with an ICD vs. congestive heart failure (CHF) on PROs and compared (i) ICD patients without CHF (ICD only), (ii) CHF patients without an ICD (CHF-only), and (iii) CHF patients with an ICD (ICD + CHF). METHODS AND RESULTS: Separate cohorts of ICD and CHF patients (N = 435; 75% men) completed PROs at baseline, 6 and 12 months. Groups differed on physical health status only at baseline (F((2,415)) = 7.15, P = 0.001) and on anxiety at 12 months (F((2,415)) = 4.04, P = 0.01); ICD + CHF patients had the most impaired physical health status but the lowest anxiety level followed by the ICD only and CHF only patients. Congestive heart failure only patients had the most impaired mental health status and reported the highest level of anxiety as compared to the ICD only (P < 0.001) and ICD + CHF groups (P = 0.009), while the two latter groups did not differ. The effect sizes ranged from very small (0.03) to moderate-large (0.69). Groups did not differ in depression scores. CONCLUSION: Congestive heart failure patients reported worse PROs as compared to ICD patients, although the magnitude of the differences was relatively small. This suggests that the well being of patients is not necessarily negatively influenced by the implantation of an ICD, and that underlying heart disease may have at least an equal if not greater influence on PROs.

Outcomes of repeat catheter ablation using magnetic navigation or conventional ablation.

AIMS: After initial catheter ablation, repeat procedures could be necessary. This study evaluates the efficacy of the magnetic navigation system (MNS) in repeat catheter ablation as compared with manual conventional techniques (MANs). METHODS AND RESULTS: The results of 163 repeat ablation procedures were analysed. Ablations were performed either using MNS (n = 84) or conventional manual ablation (n = 79). Procedures were divided into four groups based on the technique used during the initial and repeat ablation procedure: MAN-MAN (n = 66), MAN-MNS (n = 31), MNS-MNS (n = 53), and MNS-MAN (n = 13). Three subgroups were analysed: supraventricular tachycardias (SVTs, n = 68), atrial fibrillation (AF, n = 67), and ventricular tachycardias (VT, n = 28). Recurrences were assessed during 19 ± 11 months follow-up. Overall, repeat procedures using MNS were successful in 89.0% as compared with 96.2% in the MAN group (P = ns). The overall recurrence rate was significantly lower using MNS (25.0 vs. 41.4%, P = 0.045). Acute success and recurrence rates for the MAN-MAN, MAN-MNS, MNS-MNS, and MNS-MAN groups were comparable. For the SVT subgroup a higher acute success rate was achieved using MAN (87.9 vs. 100.0%, P = 0.049). The use of MNS for SVT is associated with longer procedure times (205 ± 82 vs. 172 ± 69 min, P = 0.040). For AF procedure and fluoroscopy times were longer (257 ± 72 vs. 185 ± 64, P = 0.001; 59.5 ± 19.3 vs. 41.1 ± 18.3 min, P < 0.001). Less fluoroscopy was used for MNS-guided VT procedures (22.8 ± 14.7 vs. 41.2 ± 10.9, P = 0.011). CONCLUSION: Our data suggest that overall MNS is comparable with MAN in acute success after repeat catheter ablation. However, MNS is related to fewer recurrences as compared with MAN.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy: pathogenic desmosome mutations in index-patients predict outcome of family screening: Dutch arrhythmogenic right ventricular dysplasia/cardiomyopathy genotype-phenotype follow-up study.

BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an autosomal dominant inherited disease with incomplete penetrance and variable expression. Causative mutations in genes encoding 5 desmosomal proteins are found in ≈50% of ARVD/C index patients. Previous genotype-phenotype relation studies involved mainly overt ARVD/C index patients, so follow-up data on relatives are scarce. METHODS AND RESULTS: One hundred forty-nine ARVD/C index patients (111 male patients; age, 49±13 years) according to 2010 Task Force criteria and 302 relatives from 93 families (282 asymptomatic; 135 male patients; age, 44±13 years) were clinically and genetically characterized. DNA analysis comprised sequencing of plakophilin-2 (PKP2), desmocollin-2, desmoglein-2, desmoplakin, and plakoglobin and multiplex ligation-dependent probe amplification to identify large deletions in PKP2. Pathogenic mutations were found in 87 index patients (58%), mainly truncating PKP2 mutations, including 3 cases with multiple mutations. Multiplex ligation-dependent probe amplification revealed 3 PKP2 exon deletions. ARVD/C was diagnosed in 31% of initially asymptomatic mutation-carrying relatives and 5% of initially asymptomatic relatives of index patients without mutation. Prolonged terminal activation duration was observed more than negative T waves in V(1) to V(3), especially in mutation-carrying relatives <20 years of age. In 45% of screened families, ≥1 affected relatives were identified (90% with mutations). CONCLUSIONS: Pathogenic desmosomal gene mutations, mainly truncating PKP2 mutations, underlie ARVD/C in the majority (58%) of Dutch index patients and even 90% of familial cases. Additional multiplex ligation-dependent probe amplification analysis contributed to discovering pathogenic mutations underlying ARVD/C. Discovering pathogenic mutations in index patients enables those relatives who have a 6-fold increased risk of ARVD/C diagnosis to be identified. Prolonged terminal activation duration seems to be a first sign of ARVD/C in young asymptomatic relatives.

Rationale and design of the PRAETORIAN trial: a Prospective, RAndomizEd comparison of subcuTaneOus and tRansvenous ImplANtable cardioverter-defibrillator therapy.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are widely used to prevent fatal outcomes associated with life-threatening arrhythmic episodes in a variety of cardiac diseases. These ICDs rely on transvenous leads for cardiac sensing and defibrillation. A new entirely subcutaneous ICD overcomes problems associated with transvenous leads. However, the role of the subcutaneous ICD as an adjunctive or primary therapy in patients at risk for sudden cardiac death is unclear. STUDY DESIGN: The PRAETORIAN trial is an investigator-initiated, randomized, controlled, multicenter, prospective 2-arm trial that outlines the advantages and disadvantages of the subcutaneous ICD. Patients with a class I or IIa indication for ICD therapy without an indication for bradypacing or tachypacing are included. A total of 700 patients are randomized to either the subcutaneous or transvenous ICD (1:1). The study is powered to claim noninferiority of the subcutaneous ICD with respect to the composite primary endpoint of inappropriate shocks and ICD-related complications. After noninferiority is established, statistical analysis is done for potential superiority. Secondary endpoint comparisons of shock efficacy and patient mortality are also made. CONCLUSION: The PRAETORIAN trial is a randomized trial that aims to gain scientific evidence for the use of the subcutaneous ICD compared with the transvenous ICD in a population of patients with conventional ICD with respect to major ICD-related adverse events. This trial is registered at ClinicalTrials.gov with trial ID NCT01296022.