Real-world validation of smartphone-based photoplethysmography for rate and rhythm monitoring in atrial fibrillation.

AIMS: Photoplethysmography- (PPG) based smartphone applications facilitate heart rate and rhythm monitoring in patients with paroxysmal and persistent atrial fibrillation (AF). Despite an endorsement from the European Heart Rhythm Association, validation studies in this setting are lacking. Therefore, we evaluated the accuracy of PPG-derived heart rate and rhythm classification in subjects with an established diagnosis of AF in unsupervised real-world conditions. METHODS AND RESULTS: Fifty consecutive patients were enrolled, 4 weeks before undergoing AF ablation. Patients used a handheld single-lead electrocardiography (ECG) device and a fingertip PPG smartphone application to record 3907 heart rhythm measurements twice daily during 8 weeks. The ECG was performed immediately before and after each PPG recording and was given a diagnosis by the majority of three blinded cardiologists. A consistent ECG diagnosis was exhibited along with PPG data of sufficient quality in 3407 measurements. A single measurement exhibited good quality more often with ECG (93.2%) compared to PPG (89.5%; P < 0.001). However, PPG signal quality improved to 96.6% with repeated measurements. Photoplethysmography-based detection of AF demonstrated excellent sensitivity [98.3%; confidence interval (CI): 96.7-99.9%], specificity (99.9%; CI: 99.8-100.0%), positive predictive value (99.6%; CI: 99.1-100.0%), and negative predictive value (99.6%; CI: 99.0-100.0%). Photoplethysmography underestimated the heart rate in AF with 6.6 b.p.m. (95% CI: 5.8 b.p.m. to 7.4 b.p.m.). Bland-Altman analysis revealed increased underestimation in high heart rates. The root mean square error was 11.8 b.p.m. CONCLUSION: Smartphone applications using PPG can be used to monitor patients with AF in unsupervised real-world conditions. The accuracy of AF detection algorithms in this setting is excellent, but PPG-derived heart rate may tend to underestimate higher heart rates.

No Effect of Continued Antiarrhythmic Drug Treatment on Top of Optimized Pulmonary Vein Isolation in Patients With Persistent Atrial Fibrillation: Results From the POWDER-AF2 Trial.

BACKGROUND: In patients with persistent atrial fibrillation (PersAF), catheter ablation aiming for pulmonary vein isolation (PVI) is associated with moderate clinical effectiveness. We investigated the benefit of continuing previously ineffective class 1C or 3 antiarrhythmic drug therapy (ADT) in the setting of a standardized PVI-only ablation strategy. METHODS: In this multicenter, randomized controlled study, patients with PersAF (≥7 days and <12 months) despite ADT were prospectively randomized 1:1 to PVI with ADT continued versus discontinued beyond the blanking period (ADT ON versus ADT OFF). Standardized catheter ablation was performed aiming for durable isolation with stable, contiguous, and optimized radio frequency applications encircling the pulmonary veins (CLOSE protocol). Clinical visits and 1-to-7-day Holter were performed at 3, 6, and 12 months. The primary end point was any documented atrial tachyarrhythmia lasting >30 seconds beyond 3 months. Prospectively defined secondary end points included repeat ablations, unscheduled arrhythmia-related visits, and quality of life among groups. RESULTS: Of 200 PersAF patients, 98 were assigned to ADT OFF and 102 to ADT ON. The longest atrial fibrillation episode qualifying for PersAF was 28 (10-90) versus 30 (11-90) days. Clinical characteristics and procedural characteristics were similar. Recurrence of atrial tachyarrhythmia was comparable in both groups (20% OFF versus 21.2% ON). No differences were observed in repeat ablations and unscheduled arrhythmia-related visits. Marked improvement in quality of life was observed in both groups. CONCLUSIONS: In patients with PersAF, there is no benefit in continuing previously ineffective ADT beyond the blanking period after catheter ablation. The high success rate of PVI-only might be explained by the high rate of durable isolation after optimized PVI and the early stage of PersAF (POWDER-AF2). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03437356.

The MADIT-ICD benefit score helps to select implantable cardioverter-defibrillator candidates in cardiac resynchronization therapy.

AIMS: The aim of this study is to evaluate whether the MADIT-ICD benefit score can predict who benefits most from the addition of implantable cardioverter-defibrillator (ICD) to cardiac resynchronization therapy (CRT) in real-world patients with heart failure with reduced ejection fraction (HFrEF) and to compare this with selection according to a multidisciplinary expert centre approach. METHODS AND RESULTS: Consecutive HFrEF patients who received a CRT for a guideline indication at a tertiary care hospital (Ziekenhuis Oost-Limburg, Genk, Belgium) between October 2008 and September 2016, were retrospectively evaluated. The MADIT-ICD benefit groups (low, intermediate, and high) were compared with the current multidisciplinary expert centre approach. Endpoints were (i) sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and (ii) non-arrhythmic mortality. Of the 475 included patients, 165 (34.7%) were in the lowest, 220 (46.3%) in the intermediate, and 90 (19.0%) in the highest benefit group. After a median follow-up of 34 months, VT/VF occurred in 3 (1.8%) patients in the lowest, 9 (4.1%) in the intermediate, and 13 (14.4%) in the highest benefit group (P < 0.001). Vice versa, non-arrhythmic death occurred in 32 (19.4%) in the lowest, 32 (14.6%) in the intermediate, and 3 (3.3%) in the highest benefit group (P = 0.002). The predictive power for ICD benefit was comparable between expert multidisciplinary judgement and the MADIT-ICD benefit score: Uno's C-statistic 0.69 vs. 0.69 (P = 0.936) for VT/VF and 0.62 vs. 0.60 (P = 0.790) for non-arrhythmic mortality. CONCLUSION: The MADIT-ICD benefit score can identify who benefits most from CRT-D and is comparable with multidisciplinary judgement in a CRT expert centre.

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 fibrillation screening with photo-plethysmography through a smartphone camera.

AIMS: This cross-sectional study was set up to assess the feasibility of mass screening for atrial fibrillation (AF) with only the use of a smartphone. METHODS AND RESULTS: A local newspaper published an article, allowing to subscribe for a 7-day screening period to detect AF. Screening was performed through an application that uses photo-plethysmography (PPG) technology by exploiting a smartphone camera. Participants received instructions on how to perform correct measurements twice daily, with notifications pushed through the application's software. In case of heart rhythm irregularities, raw PPG signals underwent secondary offline analysis to confirm a final diagnosis. From 12 328 readers who voluntarily signed up for screening (49 ± 14 years; 58% men), 120 446 unique PPG traces were obtained. Photo-plethysmography signal quality was adequate for analysis in 92% of cases. Possible AF was detected in 136 individuals (1.1%). They were older (P < 0.001), more frequently men (P < 0.001), and had higher body mass index (P = 0.004). In addition, participants who strictly adhered to the recommended screening frequency (i.e. twice daily) were more often diagnosed with possible AF (1.9% vs. 1.0% in individuals who did not adhere; P = 0.008). Symptoms of palpitations, confusion, and shortness of breath were more frequent in case of AF (P < 0.001). The cumulative diagnostic yield for possible AF increased from 0.4% with a single heart rhythm assessment to 1.4% with screening during the entire 7-day screening period. CONCLUSION: Mass screening for AF using only a smartphone with dedicated application based on PPG technology is feasible and attractive because of its low cost and logistic requirements.

Sacubitril/valsartan reduces ventricular arrhythmias in parallel with left ventricular reverse remodeling in heart failure with reduced ejection fraction.

BACKGROUND: Sacubitril/valsartan reduced the occurrence of sudden cardiac death in the PARADIGM-HF trial. However, limited information is available about the mechanism. METHODS: Heart failure (HF)-patients receiving sacubitril/valsartan for a class-I indication equipped with an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) with remote tele-monitoring were retrospectively analyzed. Device-registered arrhythmic-events were determined [ventricular tachycardia/fibrillation (VT/VF), appropriate therapy, non-sustained VT (NsVT; > 4beats and < 30 s), hourly premature ventricular contraction (PVC)-burden], following sacubitril/valsartan initiation (incident-analysis) and over an equal time period before initiation (antecedent-analysis). Reverse remodeling to sacubitril/valsartan was defined as an improvement of left ventricular ejection fraction of ≥ 5% between baseline and follow-up. RESULTS: A-total of 151 HF-patients with reduced LVEF (29 ± 9%) were included. Patients were switched from ACE-I or ARB to equal doses of sacubitril/valsartan (expressed as %-target-dose; before = 58 ± 30% vs. after = 56 ± 27%). The mean follow-up of both the incident and antecedent analysis was 364 days. Following the initiation, VT/VF-burden dropped (individual patients with VT/VF pre_n = 19 vs. post_n = 10, total-episodes of VT/VF pre_n = 51 vs. post_n = 14, both p < 0.001), resulting in reduced occurrence of appropriate therapy (pre_n = 16 vs. post_n = 6; p < 0.001). NsVT-burden per patient also dropped (mean episodes pre_n = 7.7 ± 11.8 vs. post_n = 3.7 ± 5.4; p < 0.001). There was no impact on atrial-fibrillation burden. PVC-burden dropped significantly which was associated with an improvement in BiV-pacing in patients with < 90% BiV-pacing at baseline. A higher degree of reverse remodeling was associated with a lower burden of NsVT and PVCs (both p < 0.05). CONCLUSION: Initiation of sacubitril/valsartan is associated with a lower degree of VT/VF, resulting in less ICD-interventions. This beneficial effect on ventricular arrhythmias might be related to cardiac reverse remodeling.

Cardiac sarcoidosis: a diagnostic and therapeutic challenge.

OBJECTIVE: Cardiac involvement in sarcoidosis can present in various ways, with atrioventricular (AV) block and ventricular arrhythmias being the most common signs. Because of initial non-specific findings, diagnosis can be a challenge. Very few data can support treatment decisions as cardiac manifestations of this systemic disorder are rare. METHODS AND RESULTS: We reviewed current guidelines, cohort studies, and expert opinions concerning diagnosis and treatment of cardiac sarcoidosis. CONCLUSIONS: Longitudinal follow-up studies are necessary to improve the diagnostic process and risk stratification of cardiac sarcoidosis. The optimal dose of steroids, indications for internal cardioverter-defibrillator (ICD), and technique and optimal timing of ablation are still under debate.

Incremental benefit of cardiac resynchronisation therapy with versus without a defibrillator.

OBJECTIVE: To determine the incremental value of implantable cardioverter defibrillators (ICD) in contemporary optimally treated patients with heart failure (HF) undergoing cardiac resynchronisation therapy (CRT). METHODS: Consecutive patients with HF undergoing CRT-pacemaker (CRT-P) or CRT-defibrillator (CRT-D) implantation in a single tertiary care centre between October 2008 and August 2015 were retrospectively evaluated. For patients with a primary prevention indication of the CRT-D, no benefit of the ICD was defined as absence of appropriate therapy (device analysis) or lethal ventricular tachyarrhythmias (mode of death analysis) during follow-up. RESULTS: 687 patients (CRT-P/CRT-D; n=361/326) were followed for 38±22 months. CRT-P recipients were older (75.7±9.1 vs 71.8±9.3 years; p<0.001) and had a higher comorbidity burden. Five patients with CRT-P (1%) experienced episodes of sustained ventricular-tachycardia vs 64 (20%) patients with CRT-D (p<0.001). Remote tele-monitoring detected the episodes of sustained ventricular tachycardia in four patients with CRT-P, allowing for elective upgrade to CRT-D. All-cause mortality was higher in patients with CRT-P versus CRT-D (21% vs 12%, p=0.003), even after adjusting for baseline characteristics (HR 2.5; 95% CI 1.36 to 4.60; p=0.003). However, mode of death analysis revealed a predominant non-cardiac mode of death in CRT-P recipients (n=47 (71%) vs n=13 (38%) in CRT-D, p=0.002). Multivariate analysis revealed that age >80 years, New York Heart Association class IV, intolerance to beta-blockers and underlying non-ischaemic cardiomyopathy were independently associated with little incremental value of a primary prevention ICD on top of CRT. CONCLUSIONS: The majority of patients with contemporary HF as currently selected for CRT-P exhibit mainly non-cardiac-driven mortality. Weighing risk of ventricular-tachyarrhythmic death versus risk of all-cause mortality helps to address the incremental value of an ICD to CRT-P.

Long-Term Performance of the Riata/ST Implantable Cardioverter-Defibrillator Lead.

Riata and Riata ST implantable cardioverter-defibrillator leads are prone to structural and electrical failure (EF). Our objective was to evaluate Riata/ST lead performance over a long-term follow-up. Of 184 patients having undergone Riata/ST and Riata ST Optim lead implantation from September 2003 to June 2008, 154 patients were evaluated for EF and radiographic conductor externalization (CE). Survival analysis for EF was performed for Riata/ST leads, both for failure-free lead survival and cumulative hazard. Subanalysis on 7Fr leads was performed to evaluate EF and CE rates both for different Riata ST lead management (monitoring vs proactive) and between Riata ST and Riata ST Optim leads. During a mean follow-up of 7 years, Riata/ST lead EF rate was 13% overall. Similar failure-free survival rate was noted for 7Fr as for 8Fr leads (log-rank, p = 0.63). Of all failed leads, 64% failed only after 5 years of follow-up. Compared with the absolute failure rate of 1.84% per device year, cumulative hazard analysis for leads surviving past 5 years revealed an estimated failure rate of 7% per year. No clinical or procedural predictors for EF were found. The subanalysis on 7Fr leads showed an excellent outcome both for a proactive lead management approach as for Optim leads. In conclusion, long-term survival of the Riata/ST lead is impaired with an accelerating EF risk over time. An initial exponential trend was followed by a linear lead failure pattern for leads surviving past 5 years, corresponding to an estimated 7% annual EF rate. These findings may have repercussions on the lead management strategy in patients currently surviving with a Riata/ST lead to prevent significant clinical events like inappropriate shocks or failed device interventions.

The figure-of-eight artifact in the echocardiographic assessment of percutaneous disc occluders: impact of imaging depth and device type.

PURPOSE: Echocardiography is increasingly important in the guidance and follow-up of percutaneous transcatheter device closures. It was recently shown that the Amplatzer left atrial appendage occluder frequently presents as a figure-of-eight artifact due to interaction of device mesh and ultrasound waves. It remains unknown whether this can be translated to other types of disc occluders. Furthermore, the morphology of this figure-of-eight artifact appears to be different in the transesophageal and transthoracic image of the same device. The aim of this study was to evaluate the echocardiographic appearance of different types of disc occluders, and to clarify differences in morphology of the figure-of-eight artifact. METHODS: A mathematical model of an epitrochoid curve was used for numerical simulation of disc occluder appearance at various imaging depths. In addition, an in vitro setup was used for echocardiographic analysis of different types of disc occluders at adjustable imaging depth and position. RESULTS: Mathematically, decreasing the imaging depth resulted in a more asymmetric figure-of-eight, i.e. with small upper part and wide lower part. In vitro results were in close agreement with the mathematical results. In addition, in vitro a figure-of-eight artifact was obtained in all different types of disc occluder devices. CONCLUSIONS: Different types of percutaneous disc occluders all present as a figure-of-eight artifact on echocardiography when imaged from a coronal imaging position. The morphology of the artifact depends on the imaging depth, with a more asymmetric figure-of-eight morphology at smaller probe-to-device distance. This clarifies the differences observed between transesophageal and transthoracic imaging.

EuroEco (European Health Economic Trial on Home Monitoring in ICD Patients): a provider perspective in five European countries on costs and net financial impact of follow-up with or without remote monitoring.

AIM: Remote follow-up (FU) of implantable cardiac defibrillators (ICDs) allows for fewer in-office visits in combination with earlier detection of relevant findings. Its implementation requires investment and reorganization of care. Providers (physicians or hospitals) are unsure about the financial impact. The primary end-point of this randomized prospective multicentre health economic trial was the total FU-related cost for providers, comparing Home Monitoring facilitated FU (HM ON) to regular in-office FU (HM OFF) during the first 2 years after ICD implantation. Also the net financial impact on providers (taking national reimbursement into account) and costs from a healthcare payer perspective were evaluated. METHODS AND RESULTS: A total of 312 patients with VVI- or DDD-ICD implants from 17 centres in six EU countries were randomised to HM ON or OFF, of which 303 were eligible for data analysis. For all contacts (in-office, calendar- or alert-triggered web-based review, discussions, calls) time-expenditure was tracked. Country-specific cost parameters were used to convert resource use into monetary values. Remote FU equipment itself was not included in the cost calculations. Given only two patients from Finland (one in each group) a monetary valuation analysis was not performed for Finland. Average age was 62.4 ± 13.1 years, 81% were male, 39% received a DDD system, and 51% had a prophylactic ICD. Resource use with HM ON was clearly different: less FU visits (3.79 ± 1.67 vs. 5.53 ± 2.32; P < 0.001) despite a small increase of unscheduled visits (0.95 ± 1.50 vs. 0.62 ± 1.25; P < 0.005), more non-office-based contacts (1.95 ± 3.29 vs. 1.01 ± 2.64; P < 0.001), more Internet sessions (11.02 ± 15.28 vs. 0.06 ± 0.31; P < 0.001) and more in-clinic discussions (1.84 ± 4.20 vs. 1.28 ± 2.92; P < 0.03), but with numerically fewer hospitalizations (0.67 ± 1.18 vs. 0.85 ± 1.43, P = 0.23) and shorter length-of-stay (6.31 ± 15.5 vs. 8.26 ± 18.6; P = 0.27), although not significant. For the whole study population, the total FU cost for providers was not different for HM ON vs. OFF [mean (95% CI): €204 (169-238) vs. €213 (182-243); range for difference (€-36 to 54), NS]. From a payer perspective, FU-related costs were similar while the total cost per patient (including other physician visits, examinations, and hospitalizations) was numerically (but not significantly) lower. There was no difference in the net financial impact on providers [profit of €408 (327-489) vs. €400 (345-455); range for difference (€-104 to 88), NS], but there was heterogeneity among countries, with less profit for providers in the absence of specific remote FU reimbursement (Belgium, Spain, and the Netherlands) and maintained or increased profit in cases where such reimbursement exists (Germany and UK). Quality of life (SF-36) was not different. CONCLUSION: For all the patients as a whole, FU-related costs for providers are not different for remote FU vs. purely in-office FU, despite reorganized care. However, disparity in the impact on provider budget among different countries illustrates the need for proper reimbursement to ensure effective remote FU implementation.

Asymptomatic episodes of device-registered atrial tachyarrhythmia are not associated with worse cardiac resynchronization therapy response.

AIMS: To assess the influence of device-registered episodes of atrial tachyarrhythmia (AT) on the response to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Consecutive CRT patients without history of atrial fibrillation (AF; n = 118) were followed prospectively. AT was defined as a device-registered episode of atrial rate >190 b.p.m. for ≥30 s. Episodes of electrocardiographically documented AF, accompanied by symptoms, or need for cardioversion, were classified as clinical AF. During mean follow-up of 26 ± 9 months, 39 patients (33%) had ≥1 episode of asymptomatic device-registered AT. Twenty-one patients (18%) developed clinical AF of whom seven had previously experienced episodes of asymptomatic device-registered AT. Patients with asymptomatic AT or AF had a higher body mass index, but otherwise similar baseline characteristics, compared with the subjects without AT. Reverse remodelling after CRT was similar among the groups. While clinical AF was significantly associated with the composite endpoint of all-cause mortality or unplanned hospital admission (hazard ratio = 2.43, 95% confidence interval: 1.40-4.24), this correlation was not observed in patients with asymptomatic device-registered AT (P value = 0.540). CONCLUSION: Episodes of asymptomatic device-registered AT are frequent in CRT patients, but are not associated with impaired reverse remodelling. In contrast to clinical AF, such episodes are not associated with worse clinical outcome.

Etiology and relevance of the figure-of-eight artifact on echocardiography after percutaneous left atrial appendage closure with the Amplatzer Cardiac Plug.

BACKGROUND: The Amplatzer Cardiac Plug (ACP) device, used for percutaneous left atrial appendage closure, frequently presents as an unexplained figure-of-eight on echocardiography. The aim of this study was to clarify the figure-of-eight display of the ACP device during echocardiography and to relate this finding to device position and function. METHODS: A mathematical model was developed to resemble device geometry and predict the echocardiographic appearance of the ACP device. In addition, an in vitro setup was used to validate the model. Finally, echocardiographic images of consecutive patients referred for percutaneous left atrial appendage closure (n = 24) were analyzed for the presence of a figure-of-eight display. RESULTS: Because the ACP device resembles an epitrochoid curve, those points with tangent vector perpendicular to the ultrasound waves are emphasized, resulting in a figure-of-eight display, which can be replicated in vitro in the coronal imaging position. We found the figure-of-eight display in 100% (11 of 11) of three-dimensional periprocedural transesophageal images and in 87% (34 of 39) of postprocedural transthoracic echocardiographic images. CONCLUSIONS: The figure-of-eight display of the ACP device during echocardiography is the result of the specific epitrochoid geometry of the device mesh and its interaction with ultrasound waves. It is important to recognize the figure-of-eight as being a normal imaging artifact of a correctly deployed device in the coronal imaging position on both transesophageal and transthoracic echocardiography. In the future, this could be used during follow-up to aid clinical practitioners in assessing device position and function.

Fragmented QRS as a predictor of arrhythmic events in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: This study aims to determine whether fragmented QRS (fQRS) in the surface electrocardiogram (ECG) at implantable cardioverter defibrillator (ICD) implant can predict arrhythmic events using appropriate therapy delivered by the ICD as a surrogate. BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is a genetic disorder associated with life-threatening arrhythmias frequently requiring an ICD. Seeking a noninvasive method of risk stratification remains a challenge. METHODS: This paper is a retrospective, multicenter study of patients with HOCM and ICD. Surface 12-lead ECGs were analyzed. Appropriate therapy was validated by a blinded Core Lab. Univariate and multivariate analyses were performed. A p value of <0.05 was considered significant. RESULTS: We included 102 patients from 13 centers. Mean age at implant was 41.16 ± 18.25 years, 52% were male. Mean left ventricular ejection fraction was 61.56 ± 9.46% and two thirds had heart failure according to the New York Heart Association class I. Secondary prophylaxis ICD implantation was the indication for implant in 40.2% of cases. About half received a single-chamber ICD. fQRS was present at the time of diagnosis in 21 and in 54% at ICD implant. At a mean follow-up of 47.8 ± 39.3 months, 41 patients (40.2%) presented with appropriate therapy. In a multivariate logistic regression, predictors of appropriate therapy included fQRS at implant (odds ratio [OR], 16.4; 95% confidence interval [CI], 3.6-74.0; p = 0.0003), history of combined ventricular tachycardia/fibrillation/sudden death (OR, 14.3; 95% CI, 3.2-69.3; p = 0.001) and history of syncope (OR, 5.5; 95% CI, 1.5-20.4; p = 0.009). Ten deaths (9.8%) occurred during the follow-up. fQRS in the lateral location increased the risk of appropriate therapy (p < 0.0001). CONCLUSIONS: fQRS predicts arrhythmic events in patients with HOCM and should be considered in a model of risk stratification.

Revisiting diastolic filling time as mechanistic insight for response to cardiac resynchronization therapy.

AIMS: Intraventricular dyssynchrony and commonly associated prolonged atrioventricular conduction both reduce diastolic filling time (DFT), which can be improved by cardiac resynchronization therapy (CRT). Our aim was to investigate whether change in DFT corrected for RR interval (DFTC) after CRT might serve to assess the mechanistic response to CRT. METHODS AND RESULTS: Echocardiography data of consecutive patients in sinus rhythm (n = 91) were studied before and 6 months after implantation. Mortality and heart failure hospitalization data were collected. Patients with vs. without DFTC increase after 6 months were compared. The programmed atrioventricular delay, percentage of biventricular pacing, and change in PR interval were similar in both groups. DFTC increase after 6 months reflected favourable reverse left ventricular remodelling and was significantly associated with freedom from death or heart failure admission (P = 0.008). In multivariate analysis including guideline criteria for CRT (i.e. QRS width, presence of left bundle branch block, and ejection fraction), interventricular mechanical delay, and Tei index, baseline DFTC was the strongest predictor of adverse outcome. Notably, while patients with impaired relaxation had a large and highly significant reduction in all-cause mortality and heart failure admissions when DFTC increased [hazard ratio (HR), 95% confidence interval (CI) = 0.24, 0.08-0.73; P = 0.012], this benefit was less pronounced and did not reach statistical significance in patients with pseudonormal or restrictive filling (HR, 95% CI = 0.64, 0.23-1.77; P = 0.388). CONCLUSION: DFTC increase after CRT reflects favourable reverse remodelling and is associated with better clinical outcome.

Cardiac resynchronization therapy with or without defibrillator: experience from a high-volume Belgian implantation centre.

OBJECTIVE: Cardiac resynchronization therapy (CRT) is an important treatment modality for heart failure with reduced ejection fraction and ventricular conduction delay. Considering limited health care budgets in an aging population, adding a defibrillator function to CRT remains a matter of debate. Our aim was to describe the experience of a high-volume Belgian implantation centre with CRT with/without defibrillator (CRT-D/P). METHODS AND RESULTS: Consecutive CRT patients (n = 221), implanted between October 2008 and April 2011 in Ziekenhuis Oost-Limburg (Genk), were reviewed. From 209 primo-implantations, 74 CRT-D and 98 CRT-P patients with complete follow-up inside the centre, were analysed. Despite differences in baseline characteristics, both groups demonstrated similar reverse left ventricular remodelling, improvement in New York Heart Association functional class and maximal aerobic capacity. During mean follow-up of 18 +/- 9 months, 21 patients died and 83 spent a total of 1200 days in hospital. Annual mortality was 8% and equal among the groups. The mode of death differed between CRT-D (predominantly pump failure) and CRT-P patients (pump failure, comorbidity and sudden death). The yearly population attributable risk of malignant ventricular arrhythmia was 8.16% in CRT-D and 1.38% in CRT-P patients. CONCLUSIONS: With current guidelines applied to the Belgian reimbursement criteria and at physicians'discretion, patient selection for CRT-D/ CRT-P was appropriate, with similar reverse remodelling, functional capacity improvement and good clinical outcome in both groups. High-risk patients for malignant ventricular arrhythmia were more likely to receive CRT-D, although the yearly attributable risk remained 1.38% in CRT-P patients.

Response to cardiac resynchronization therapy in elderly patients (≥70 years) and octogenarians.

AIMS: Cardiac resynchronization therapy (CRT) leads to reverse ventricular remodelling, improved functional capacity, and better clinical outcome in patients with advanced chronic heart failure, reduced ejection fraction, and evidence of ventricular conduction delay, who are under optimal medical therapy. This study investigated whether these benefits can be extrapolated to older patients, typically not included in randomized clinical trials. METHODS AND RESULTS: Consecutive patients who received a CRT device between October 2008 and June 2011, including optimization afterwards in a dedicated clinic, were stratified into 3 pre-specified groups, according to age: <70 years (n = 76); 70-79 years (n = 95); and ≥80 years (n = 49). Left ventricular remodelling, functional capacity, heart failure hospitalization, and mortality data were assessed during follow-up. Reverse left ventricular remodelling and improvement in New York Heart Association functional class were similar in all groups at 6 months after implantation. During mean follow-up of 20 months, 32 patients died and 66 were admitted for heart failure. Annualized mortality rates were significantly higher in elderly patients (6% vs. 8% vs. 15% in all groups, respectively; P < 0.001), but time to death or first heart failure admission was similar among age groups (P = 0.531). Progressive pump failure was the major cause of death (50%), with co-morbidity-related deaths also being frequent (41%). CONCLUSION: Reverse left ventricular remodelling and functional capacity improvement after CRT are sustained at advanced age. Moreover, time to all-cause mortality or heart failure admission was similar, irrespective of age, in a context of maximized optimization including optimal medical therapy.

Comorbidity significantly affects clinical outcome after cardiac resynchronization therapy regardless of ventricular remodeling.

BACKGROUND: The influence of comorbid conditions on ventricular remodeling, functional status, and clinical outcome after cardiac resynchronization therapy (CRT) is insufficiently elucidated. METHODS AND RESULTS: The influence of different comorbid conditions on left ventricular remodeling, improvement in New York Heart Association (NYHA) functional class, hospitalizations for heart failure, and all-cause mortality after CRT implantation was analyzed in 172 consecutive patients (mean age 71 ± 9 y), implanted from October 2008 to April 2011 in a single tertiary care hospital. During mean follow-up of 18 ± 9 months, 21 patients died and 57 were admitted for heart failure. Left ventricular remodeling and improvement in NYHA functional class were independent from comorbidity burden. However, diabetes mellitus (hazard ratio [HR] 3.45, 95% confidence interval [CI] 1.24-9.65) and chronic kidney disease (HR 3.11, 95% CI 1.10-8.81) were predictors of all-cause mortality, and the presence of chronic obstructive pulmonary disease (HR 1.89, 95% CI 1.02-3.53) was independently associated with heart failure admissions. Importantly, those 3 comorbid conditions had an additive negative impact on survival and heart failure admissions, even in patients with reverse left ventricular remodeling. CONCLUSIONS: Reverse ventricular remodeling and improvement in functional status after CRT implantation are independent from comorbidity burden. However, comorbid conditions remain important predictors of all-cause mortality and heart failure admissions.