Dyssynchrony and Response to Cardiac Resynchronization Therapy in Heart Failure Patients With Unfavorable Electrical Characteristics.

BACKGROUND: Among heart failure (HF) patients undergoing cardiac resynchronization therapy (CRT), those with unfavorable electrical characteristics (UEC) are less frequently CRT responders. OBJECTIVES: In this study, the authors sought to evaluate the relationship between preprocedural echocardiographic parameters of electromechanical dyssynchrony (EMD) and outcome following CRT. METHODS: Among 551 patients receiving CRT, 121 with UEC, defined as atypical left bundle branch, presence of right bundle branch block, or unspecified intraventricular conduction disturbance, were enrolled. Indices of EMD were presence of septal flash, apical rocking, septal deformation patterns, and global wasted work (GWW), determined with the use of speckle-tracking strain echocardiography. Endpoints were response to CRT, defined as a relative decrease in left ventricular end-systolic volume ≥15% at 9-month postoperative follow-up, and all-cause death or HF hospitalization during follow-up. RESULTS: Among the 121 patients, 68 (56%) were CRT responders. In multivariate analysis, GWW ≥200 mm Hg% (adjusted odds ratio [aOR]: 4.17 [95% CI: 1.33-14.56]; P = 0.0182) and longitudinal strain septal contraction patterns 1 and 2 (aOR: 10.05 [95% CI: 2.82-43.97]; P < 0.001) were associated with CRT response. During a 46-month follow-up (IQR: 42-55 months), survival free from death or HF hospitalization increased with the number of positive criteria (87% for 2, 59% for 1, and 27% for 0). After adjustment for established predictors of outcome in patients receiving CRT, absence of either of the 2 criteria remained associated with a considerable increased risk of death and/or HF hospitalization (adjusted HR: 4.83 [95% CI: 1.84-12.68]; P = 0.001). CONCLUSIONS: In patients with UEC, echocardiographic assessment of EMD may help to select patients who will derive benefit from CRT. (Echocardiography in Cardiac Resynchronization Therapy [Echo-CRT]; NCT02986633).

CRT-D replacement strategy: results of the BioCONTINUE study.

BACKGROUND: In patients with cardiac resynchronization therapy defibrillators (CRT-Ds), the need for implantable cardioverter-defibrillator (ICD) back-up may be questionable at time of CRT-D replacement (REP) if ICD implant criteria are no longer met due to an improved left ventricular ejection fraction (LVEF) and if no major ventricular arrhythmic event (VAE) occurred during the CRT-D lifetime. The aim of our study was to assess the relevance of ICD back-up and predictors of VAE after REP in primary prevention CRT-D patients. METHODS: The prospective, observational, international BioCONTINUE study investigated the rate of patients with at least 1 sustained VAE (sVAE) post-REP and searched for predictive factors of sVAE. RESULTS: Two hundred seventy-six patients (70 ± 10 years, 77% men, mean LVEF 40.6 ± 12.6%) were followed for 28.4 ± 10.2 months. The rate of patients with sVAE was 8.3%, 10.3%, and 21.2% at 1, 2, and 4 years post-REP. Patients without persistent ICD indication at REP still had a sVAE rate of 5.7% (95% CI 2.3-11.5%) at 2 years. In multivariate analysis, predictive factors of subsequent sVAE were (i) persistent ICD indication (hazard ratio (HR) 3.6; 95% CI 1.6-8.3; p = 0.003); (ii) 64-72 years of age as compared to ≥ 79 years (HR 3.7; 95% CI 1.4-9.7; p = 0.008); and (iii) ischemic heart disease (HR 4.4; 95% CI 2.1-9.3; p < 0.0001). CONCLUSIONS: The risk of sVAE (21.2% at 4 years post-REP) depends on age, ischemic heart disease, and ICD indication at the time of REP. A non-trivial risk of sVAE remains in patients without persistent ICD indication. CLINICAL TRIAL REGISTRATION: NCT02323503.

Artificial intelligence software standardizes electrogram-based ablation outcome for persistent atrial fibrillation.

INTRODUCTION: Multiple groups have reported on the usefulness of ablating in atrial regions exhibiting abnormal electrograms during atrial fibrillation (AF). Still, previous studies have suggested that ablation outcomes are highly operator- and center-dependent. This study sought to evaluate a novel machine learning software algorithm named VX1 (Volta Medical), trained to adjudicate multipolar electrogram dispersion. METHODS: This study was a prospective, multicentric, nonrandomized study conducted to assess the feasibility of generating VX1 dispersion maps. In 85 patients, 8 centers, and 17 operators, we compared the acute and long-term outcomes after ablation in regions exhibiting dispersion between primary and satellite centers. We also compared outcomes to a control group in which dispersion-guided ablation was performed visually by trained operators. RESULTS: The study population included 29% of long-standing persistent AF. AF termination occurred in 92% and 83% of the patients in primary and satellite centers, respectively, p = 0.31. The average rate of freedom from documented AF, with or without antiarrhythmic drugs (AADs), was 86% after a single procedure, and 89% after an average of 1.3 procedures per patient (p = 0.4). The rate of freedom from any documented atrial arrhythmia, with or without AADs, was 54% and 73% after a single or an average of 1.3 procedures per patient, respectively (p < 0.001). No statistically significant differences between outcomes of the primary versus satellite centers were observed for one (p = 0.8) or multiple procedures (p = 0.4), or between outcomes of the entire study population versus the control group (p > 0.2). Interestingly, intraprocedural AF termination and type of recurrent arrhythmia (i.e., AF vs. AT) appear to be predictors of the subsequent clinical course. CONCLUSION: VX1, an expertise-based artificial intelligence software solution, allowed for robust center-to-center standardization of acute and long-term ablation outcomes after electrogram-based ablation.

EASI™ 12­lead ECG with a handheld computer refines cardiovascular diagnosis in general practice.

BACKGROUND: Electrocardiogram (ECG) is used to a small extent in general medicine, because of general practitioner (GP) apprehension about interpretation and time consumption. AIM: This study tested the hypothesis that user-friendly EASI ECG improves GP diagnosis of cardiovascular symptoms. METHOD: Patients over 18 years with recent cardiovascular symptoms or auscultation rhythm abnormalities were included in this prospective, multicentric study (10 practices, 17 GPs). ECG recordings were made with Cardiosecur® (4­lead ECG connected to a handheld computer for EASI™ processing). Besides clinical data, diagnosis/patient referral were noted before and after ECG and interpretation. GP diagnosis and ECG interpretation were compared with a reference diagnosis made by ECG specialist. RESULTS: There were 338 patients; 66% had cardiovascular risk factors. ECGs were performed for chest pain (41%), auscultation rhythm abnormalities (33%) or palpitations (19%). Average time to perform ECG was 4.7 ± 2.1 min, with possible home recordings. Compared with standard ECG, improvement provided by Cardiosecur® was scored 9/10 (range 7-10) by GPs. GPs correctly interpreted ECG normality/abnormality in 77% of patients. Diagnosis was correctly changed for 14% of patients thanks to the ECG, and wrongly changed for 2%. One new appropriate final diagnosis was achieved for 9 ECG recordings (p < 0.001). Diagnostic certainty increased 1.9 ± 2.1/10 (p < 0.001). ECG brought about changes in GP decision making: referral or treatment changed for 82 patients (24%) and complementary test for 69 patients (20%). CONCLUSION: The EASI™ algorithm coupled with a handheld computer facilitates ECG recordings in the primary care setting, providing improved diagnosis.

Clinical Significance of Global Wasted Work in Patients with Heart Failure Receiving Cardiac Resynchronization Therapy.

BACKGROUND: The relationship between myocardial work assessment using pressure-strain loops by echocardiography before cardiac resynchronization therapy (CRT) and response to CRT has been recently revealed. Among myocardial work parameters, the impact of left ventricular myocardial global wasted work (GWW) on response to CRT and outcome following CRT has been seldom studied. Hence, the authors evaluated the relationship between preprocedural GWW and outcome in a large prospective cohort of patients with heart failure (HF) and reduced ejection fraction receiving CRT. METHODS: The study included 249 patients with HF. Myocardial work indices including GWW were calculated using speckle-tracking strain two-dimensional echocardiography using pressure-strain loops. End points of the study were (1) response to CRT, defined as left ventricular reverse remodeling and/or absence of hospitalization for HF, and (2) all-cause death during follow-up. RESULTS: Median follow-up duration was 48 months (interquartile range, 43-54 months). Median preoperative GWW was 281 mm Hg% (interquartile range, 184-388 mm Hg%). Preoperative GWW was associated with CRT response (area under the curve, 0.74; P < .0001), and a 200 mm Hg% threshold discriminated CRT nonresponders from responders with 85% specificity and 50% sensitivity, even after adjustment for known predictors of CRT response (adjusted odds ratio, 4.03; 95% CI, 1.91-8.68; P < .001). After adjustment for established predictors of outcome in patients with HF with reduced ejection fraction receiving CRT, GWW < 200 mm Hg% remained associated with a relative increased risk for all-cause death compared with GWW ≥ 200 mm Hg% (adjusted hazard ratio, 2.0; 95% CI, 1.1-3.9; P = .0245). Adding GWW to a baseline model including known predictors of outcome in CRT resulted in an improvement of this model (χ2 to improve 4.85, P = .028). The relationship between GWW and CRT response and outcome was stronger in terms of size effect and statistical significance than for other myocardial work indices. CONCLUSIONS: Low preoperative GWW (<200 mm Hg%) is associated with absence of CRT response in CRT candidates and with a relative increased risk for all-cause death. GWW appears to be a promising parameter to improve selection for CRT of patients with HF with reduced ejection fraction.

Clinical and prognostic implications of phenomapping in patients with heart failure receiving cardiac resynchronization therapy.

BACKGROUND: Despite having an indication for cardiac resynchronization therapy according to current guidelines, patients with heart failure with reduced ejection fraction who receive cardiac resynchronization therapy do not consistently derive benefit from it. AIM: To determine whether unsupervised clustering analysis (phenomapping) can identify distinct phenogroups of patients with differential outcomes among cardiac resynchronization therapy recipients from routine clinical practice. METHODS: We used unsupervised hierarchical cluster analysis of phenotypic data after data reduction (55 clinical, biological and echocardiographic variables) to define new phenogroups among 328 patients with heart failure with reduced ejection fraction from routine clinical practice enrolled before cardiac resynchronization therapy. Clinical outcomes and cardiac resynchronization therapy response rate were studied according to phenogroups. RESULTS: Although all patients met the recommended criteria for cardiac resynchronization therapy implantation, phenomapping analysis classified study participants into four phenogroups that differed distinctively in clinical, biological, electrocardiographic and echocardiographic characteristics and outcomes. Patients from phenogroups 1 and 2 had the most improved outcome in terms of mortality, associated with cardiac resynchronization therapy response rates of 81% and 78%, respectively. In contrast, patients from phenogroups 3 and 4 had cardiac resynchronization therapy response rates of 39% and 59%, respectively, and the worst outcome, with a considerably increased risk of mortality compared with patients from phenogroup 1 (hazard ratio 3.23, 95% confidence interval 1.9-5.5 and hazard ratio 2.49, 95% confidence interval 1.38-4.50, respectively). CONCLUSIONS: Among patients with heart failure with reduced ejection fraction with an indication for cardiac resynchronization therapy from routine clinical practice, phenomapping identifies subgroups of patients with differential clinical, biological and echocardiographic features strongly linked to divergent outcomes and responses to cardiac resynchronization therapy. This approach may help to identify patients who will derive most benefit from cardiac resynchronization therapy in "individualized" clinical practice.

Wearable cardioverter-defibrillator in patients with a transient risk of sudden cardiac death: the WEARIT-France cohort study.

AIMS: We aimed to provide contemporary real-world data on wearable cardioverter-defibrillator (WCD) use, not only in terms of effectiveness and safety but also compliance and acceptability. METHODS AND RESULTS: Across 88 French centres, the WEARIT-France study enrolled retrospectively patients who used the WCD between May 2014 and December 2016, and prospectively all patients equipped for WCD therapy between January 2017 and March 2018. All patients received systematic education session through a standardized programme across France at the time of initiation of WCD therapy and were systematically enrolled in the LifeVest Network remote services. Overall, 1157 patients were included (mean age 60 ± 12 years, 16% women; 46% prospectively): 82.1% with ischaemic cardiomyopathy, 10.3% after implantable cardioverter-defibrillator explant, and 7.6% before heart transplantation. Median WCD usage period was 62 (37-97) days. Median daily wear time of WCD was 23.4 (22.2-23.8) h. In multivariate analysis, younger age was associated with lower compliance [adjusted odds ratio (OR) 0.97, 95% confidence interval (CI) 0.95-0.99, P < 0.01]. A total of 18 participants (1.6%) received at least one appropriate shock, giving an incidence of appropriate therapy of 7.2 per 100 patient-years. Patient-response button allowed the shock to be aborted in 35.7% of well-tolerated sustained ventricular arrhythmias and in 95.4% of inappropriate ventricular arrhythmia detection, finally resulting in an inappropriate therapy in eight patients (0.7%). CONCLUSION: Our real-life findings reinforce previous studies on the efficacy and safety of the WCD in the setting of transient high-risk group in selected patients. Moreover, they emphasize the fact that when prescribed appropriately, in concert with adequate patient education and dedicated follow-up using specific remote monitoring system, compliance with WCD is high and the device well-tolerated by the patient.

Periprocedural, early, and long-term risks of pacemaker implantation after atrioventricular nodal re-entry tachycardia ablation: a French nationwide cohort.

AIMS: Pacemaker implantation (PI) after atrioventricular nodal re-entry tachycardia (AVNRT) ablation is a dreadful complication. We aimed to assess periprocedural, early, and late risks for PI. METHODS AND RESULTS: All 27 022 patients who underwent latest AVNRT ablation in France from 2009 to 2017, were identified in the nationwide medicalization database. A control group of 305 152 patients hospitalized for arm, leg, or skin injuries with no history of AVNRT or supraventricular tachycardia were selected. After propensity score matching, both groups had mean age of 53 ± 18 years and were predominantly female (64%). During this 9-year period, 822 of 27 022 (3.0%) AVNRT patients underwent PI, with significant higher risk in propensity-matched AVNRT patients compared to propensity-matched controls [2.9% vs. 0.9%; hazard ratio 3.4 (2.9-3.9), P < 0.0001]. This excess risk was significant during all follow-up, including periprocedural (1st month), early (1-6 months), and late (>6 months) risk periods. Annualized late risk per 100 AVNRT patients was 0.2%. In comparison to controls, excess risk was 0.2% in <30-year-old AVNRT patients; 0.7% in 30-50-year-old; 1.1% in 50-70-year-old and 6.5% over 70-year-olds. Risk for PI was also significantly different according to three procedural factors: centres, experience, and ablation date, with a 30% decrease since 2015. CONCLUSION: Periprocedural, early, and late risks for PI were higher after AVNRT ablation compared to propensity-matched controls. Longer follow-up is needed as the excess risk seems to persist late after AVNRT ablation.

Clinical Significance of Electromechanical Dyssynchrony and QRS Narrowing in Patients With Heart Failure Receiving Cardiac Resynchronization Therapy.

BACKGROUND: We hypothesized that preoperative electromechanical dyssynchrony amenable to cardiac resynchronization therapy (CRT) and QRS narrowing immediately after CRT are both correlated and have a cumulative impact on response and outcome after CRT. METHODS: A total of 233 CRT candidates (heart failure New York Heart Association classes II-IV, ejection fraction < 35%, QRS ≥ 120 milliseconds, 44% women, 71 ± 11 years old) were prospectively included. Preoperative electromechanical dyssynchrony amenable to CRT was assessed by septal deformation patterns using speckle tracking echocardiography. QRS narrowing was calculated from 12-lead electrocardiograms before and immediately after CRT implantation. The primary endpoint was overall mortality during long-term follow-up. The NTC clinical trial number is NCT02986633. RESULTS: Eighty-seven percent of patients with preoperative electromechanical dyssynchrony experienced QRS narrowing after CRT (118/136), whereas 69% of patients without preoperative electromechanical dyssynchrony (67/97) experienced QRS narrowing after CRT (P < 0.001). By Cox multivariate analysis, both preoperative electromechanical dyssynchrony and lack of postoperative QRS narrowing were independently associated with an increased risk of mortality during follow-up (adjusted hazards ratio [HR] 2.24, 95% confidence interval [CI] 1.43-3.50 and HR 1.90, 95% CI 1.06-3.38, respectively). Compared with patients with preoperative electromechanical dyssynchrony, patients without both electromechanical dyssynchrony and postoperative QRS narrowing experienced a considerable increased risk of mortality during follow-up (adjusted HR 3.70, 95% CI 1.96-6.97). CONCLUSIONS: Lack of postoperative QRS narrowing after CRT is associated with preoperative electromechanical dyssynchrony. Both preoperative electromechanical dyssynchrony and postoperative QRS narrowing have a favourable cumulative impact on outcome after CRT.

Impact of Increased Right Atrial Size on Long-Term Mortality in Patients With Heart Failure Receiving Cardiac Resynchronization Therapy.

The ability to visualize the right atrium (RA) by echocardiography allows a quantitative, highly reproducible assessment of the RA volume (RAV). The aim of this study is to evaluate the relation between RAV and long-term mortality in a prospective cohort of heart failure and reduced ejection fraction patients in sinus rhythm receiving cardiac resynchronization therapy. 172 patients were included. The right atrium volume index (RAVI) was calculated using Simpson's method from the apical four-chamber view and indexed to body surface area. The relation between RAVI and mortality during follow up was studied. Median follow up was 68 months (interquartile range 62 to 73 months). Mean RAVI was 27 ± 14 mL/m² (IQR 22 to 33 mL/m²). Cumulative 5-year all-cause mortality was 22 ± 6% in patients with RAVI ≤ 19 mL/m², 24 ± 6% for RAVI 19 to 29 mL/m² and 58 ± 7% for RAVI >29 mL/m² (p for trend <0.001). After adjustment on clinical and echocardiographic predictors of outcome including indices of right ventricular function, there was a significant increase in overall mortality risk with increasing RAVI (adjusted hazard ratio 1.02 [95% confidence interval, 1.00 to 1.03], per 1 mL/m2 increment; p = 0.042). Patients in the highest tertile (RAVI >29 mL/m²) had significantly greater risk of death compared with those with RAVI ≤29 mL/m² (adjusted hazard ratio 2.01 [95% confidence interval, 1.15 to 3.50]; p = 0.014). In conclusion, RA enlargement is a powerful and highly reproducible independent predictor of long-term mortality in patients with heart failure and reduced ejection fraction in sinus rhythm receiving cardiac resynchronization therapy.

Time course of secondary mitral regurgitation in patients with heart failure receiving cardiac resynchronization therapy: Impact on long-term outcome beyond left ventricular reverse remodelling.

BACKGROUND: The prognostic value of secondary mitral regurgitation (MR) at baseline versus immediately after and several months after cardiac resynchronization therapy (CRT), beyond left ventricular (LV) reverse remodelling, has yet to be investigated. AIM: To evaluate the clinical significance of secondary MR before and at two timepoints after CRT in a large cohort of consecutive patients with heart failure (HF) and reduced LV ejection fraction. METHODS: A total of 198 patients were recruited prospectively into a registry, and underwent echocardiography at baseline and immediately after CRT (on the day of hospital discharge). Echocardiography was also performed 9 months after CRT in 172 patients. The impact of significant secondary MR (≥moderate) on all-cause death, cardiovascular death and hospitalization for HF was studied at each stage. RESULTS: The frequency of significant secondary MR decreased from 23% (n=45) to 8% (n=16) immediately after CRT. Among the 172 patients who underwent echocardiography 9 months after CRT, 17 (10%) had significant secondary MR. During a median follow-up of 48 months, 49 patients died and 36 were hospitalized for HF. Patients with significant secondary MR immediately after or 9 months after CRT had an increased risk of all-cause death, cardiovascular death and hospitalization for HF during follow-up (P<0.05 for all endpoints). After adjustment for LV reverse remodelling, significant secondary MR 9 months after CRT remained associated with an increased risk of all-cause death (adjusted hazard ratio [HR] 3.77; P=0.014), cardiovascular death (adjusted HR 5.36; P=0.037), and hospitalization for HF (adjusted HR 7.33; P=0.001). CONCLUSIONS: Significant secondary MR despite CRT provides important prognostic information beyond LV reverse remodelling. Further studies are needed to evaluate the potential role of new percutaneous procedures for mitral valve repair in improving outcome in these very high-risk patients.

Predicting Clinical and Echocardiographic Response After Cardiac Resynchronization Therapy With a Score Combining Clinical, Electrocardiographic, and Echocardiographic Parameters.

The L2ANDS2 score was previously found to be able to assess the probability of left ventricular (LV) remodeling. We sought to evaluate this score in terms of clinical outcomes: 275 patients with heart failure, from 2 centers, implanted with a cardiac resynchronization therapy (CRT) device were followed at least 2 years after implantation. Baseline clinical, electrocardiographic, and echocardiographic characteristics including left bundle branch block, age >70 years, nonischemic etiology, LV end-diastolic diameter <40 mm/m2, and septal flash by echocardiography were integrated in 4 scoring systems. Nonresponse to CRT was LV reverse remodeling <15% at 6 months' follow-up and/or occurrence of major cardiovascular event (cardiovascular death or transplantation or assistance) during a clinical follow-up of at least 2 years. Ninety-seven patients (36%) demonstrated nonresponse to CRT. The L2ANDS2 score demonstrated the best predictive value (C statistic of 0.783) for predicting absence of LV reverse remodeling and/or occurrence of major cardiovascular event during the 2 years follow-up compared with other scoring systems that do not include septal flash. A L2ANDS2 score ≤4 was associated with a worse outcome (38% survival vs 81% survival, hazard ratio 4.19, 95% CI 2.70 to 6.48, p <0.0001). In conclusion, the L2ANDS2 score is able to assess the probability of nonresponse to CRT in terms of no reverse LV remodeling and/or major cardiovascular event at long-term follow-up. Integrating septal flash in a scoring system adds value over left bundle branch block only.

Clinical significance of septal deformation patterns in heart failure patients receiving cardiac resynchronization therapy.

AIMS: Specific septal motion related to dyssynchrony is strongly linked to reverse remodelling, in patients with systolic heart failure (HF) receiving cardiac resynchronization therapy (CRT). We aimed to investigate the relationship between septal deformation patterns studied by longitudinal speckle tracking and clinical outcome following CRT. METHODS AND RESULTS: A total of 284 CRT candidates from two centres (HF NYHA classes II-IV, ejection fraction < 35%, QRS ≥ 120 ms) were prospectively included. Longitudinal strain of the septum in the apical four-chamber view determined three patterns of septal contraction. The endpoints were overall mortality, cardiovascular mortality, and hospitalization for HF. Compared with patterns 1 or 2, pattern 3 was associated with an increased risk for both overall and cardiovascular mortality [hazard ratio (HR) = 3.78, 95% confidence interval (CI): 1.85-7.75, P < 0.001 and HR = 3.84, 95% CI: 1.45-10.16, P = 0.007, respectively] and HF hospitalization (HR = 4.41, 95% CI: 2.18-8.90, P < 0.001). Addition of septal patterns to multivariable models, including baseline QRS width and presence of left bundle branch block, improved risk prediction, and discrimination. In patients with intermediate QRS duration (120-150 ms), pattern 3 remained associated with a worse outcome than pattern 1 or 2 (P < 0.05 for all endpoints). CONCLUSION: The identification of septal deformation patterns provides important prognostic information in CRT candidates in addition to ordinary clinical, electrocardiographic, and echocardiographic predictors of outcome in HF patients. This parameter may be particularly useful in patients with intermediate QRS duration in whom the benefit of CRT remains uncertain.

Role of echocardiography before cardiac resynchronization therapy: new advances and current developments.

The role of echocardiography in improving the selection of patients who will benefit from cardiac resynchronization therapy (CRT) remains a source of debate. Although previous landmark reports have demonstrated a link between mechanical dyssynchrony, assessed by delays between left ventricle (LV) walls and response to CRT, the predictive value of these findings has not yet been confirmed in multicenter trials. Indeed, recent studies demonstrated that the classical assessment of LV mechanical dyssynchrony using delay between walls by echocardiography depends not only on LV electrical activation delay (electrical dyssynchrony), but also on abnormalities in regional contractility of the LV and/or loading conditions, which do not represent an appropriate target for CRT. Recent reports highlighted the value of new indices of electromechanical dyssynchrony obtained by echocardiography, to predict LV response and outcome after CRT including septal flash, left bundle branch block-typical pattern by longitudinal strain, apical rocking, septal strain patterns, and systolic stretch index. This was achieved using a mechanistic approach, based on the contractile consequences of electrical dyssynchrony. These indices are rarely found in patients with narrow QRS (<120 ms), whereas their frequency rises in patients with an increase in QRS duration (>120 ms). Theses indices should improve candidate selection for CRT in clinical practice, especially for patients in whom the benefit of CRT remains uncertain, for example, patients with intermediate QRS width (120-150 ms).

Prognostic importance of postoperative QRS widening in patients with heart failure receiving cardiac resynchronization therapy.

BACKGROUND: Landmark reports have suggested that patients with QRS widening immediately after cardiac resynchronization therapy (CRT) experienced less frequently reverse left ventricular remodeling during follow-up. OBJECTIVE: We sought to investigate the relationship between postoperative QRS widening relative to baseline and mortality in a prospective cohort of heart failure patients receiving CRT. METHODS: A 12-lead electrocardiogram was recorded for 237 heart failure patients (New York Heart Association class II to IV, left ventricular ejection fraction ≤35%, and QRS width ≥120 ms) before and immediately after CRT device implantation. The relationships between QRS widening, all-cause and cardiovascular mortality, and echocardiographic response to CRT were studied. RESULTS: During a median follow-up of 24 months, 39 patients died. Fifty patients (21%) experienced QRS widening after CRT [QRS(+) group]. During follow-up, all-cause mortality was higher in QRS(+) patients than in QRS(-) patients (36-month survival free from death 81% ± 7% vs 64% ± 16%; log rank, P = .029). After adjustment for important prognostic confounders, QRS(+) patients remained associated with an excess overall mortality (adjusted hazard ratio [HR] 2.67; 95% confidence interval 1.07-6.65; P = .035) and cardiovascular mortality (adjusted hazard ratio 3.63; 95% confidence interval 1.13-11.65; P = .03). QRS(+) patients were less frequent responders to CRT than were QRS(-) patients (20 [47%] vs 136 [83%]; P < .0001). CONCLUSION: Postoperative QRS widening relative to baseline after CRT is associated with a considerable increased mortality risk during follow-up. Whether QRS narrowing should be achieved to optimize CRT placement, and thereby increase the rate of CRT responders and improve outcome, deserves further research.

Prognostic value of left ventricular reverse remodeling and performance improvement after cardiac resynchronization therapy: A prospective study.

BACKGROUND: The present study was designed to evaluate the respective value of left ventricular (LV) reverse remodeling (changes in LV end-systolic volume relative to baseline (ΔLVESV)) or LV performance improvement (ΔLV ejection fraction (ΔLVEF) or ΔGlobal longitudinal strain (GLS)) to predict long-term outcome in a prospective cohort of consecutive patients receiving routine cardiac resynchronization therapy (CRT). METHODS: One hundred and seventy heart failure patients (NYHA classes II-IV, LVEF ≤ 35%, QRS width ≥ 120 ms) underwent echocardiography before and 9 months after CRT. The relationships between ΔLVESV, ΔLVEF, ΔGLS and outcome (all-cause mortality and/or CHF hospitalization, overall mortality, cardiovascular mortality, CHF hospitalization) were investigated. RESULTS: During a median follow-up of 32 months, 20 patients died and 27 were hospitalized for heart failure. ΔLVESV, ΔLVEF or ΔGLS were significantly associated with all-cause mortality or CHF hospitalization (adjusted hazard's ratio (HR) per standard deviation 0.58 (0.43-0.77), 0.39 (0.27-0.57) or 0.55 (0.37-0.83) respectively, all p < 0.01) and all other endpoints (all p < 0.01). Patients with ΔLVESV≥15%, ΔLVEF ≥ 10% and ΔGLS ≥ 1% had a reduced risk of mortality or CHF hospitalization (adjusted HR=0.25 (0.12-0.51), p < 0.001, adjusted HR = 0.26 (0.13-0.54), p < 0.001 and adjusted HR 0.38 (0.19-0.75), p = 0.006 respectively). Overall performance of multivariate models was better using ΔLVESV or ΔLVEF compared with ΔGLS. Interobserver agreement was excellent for ΔLVESV (Intraclass correlation coefficient - ICC-0.91) and ΔGLS (ICC 0.90) but modest for ΔLVEF (ICC 0.76) in a sample of 20 patients from the study population. CONCLUSIONS: LV reverse remodeling assessed by ΔLVESV is a strong and reproducible predictor of outcome following CRT. Compared with ΔLVESV, ΔLVEF and ΔGLS have important shortcomings: poorer reproducibility or lower predictive value.

Is mechanical dyssynchrony a therapeutic target in heart failure with preserved ejection fraction?

BACKGROUND: Previous studies have found a high frequency of mechanical dyssynchrony in patients with heart failure (HF) with preserved ejection fraction (HFpEF), hence suggesting that cardiac resynchronization therapy (CRT) may be considered in HFpEF. The present study was designed to compare the amount of mechanical dyssynchrony between HFpEF patients and (1) HF with reduced EF (HFrEF) patients with an indication for CRT (HFrEF-CRT(+)) group, (2) HFrEF patients with QRS duration < 120 ms (HFrEF-QRS < 120 ms) group, and (3) hypertensive controls (HTN). METHODS: Electrical (ECG) and mechanical dyssynchrony (atrio-ventricular dyssynchrony, interventricular dyssynchrony, intraventricular dyssynchrony) were assessed using conventional, tissue Doppler, and Speckle Tracking strain echocardiography in 40 HFpEF patients, 40 age- and sex-matched HTN controls, 40 HFrEF-QRS < 120 ms patients, and 40 HFrEF-CRT(+) patients. RESULTS: The frequency of left bundle branch block was low in HFpEF patients (5%) and similar to HTN controls (5%, P = 0.85). Indices of dyssynchrony were similar between HFpEF and HTN patients or HFrEF-QRS < 120 ms patients. In contrast, most indices of dyssynchrony differed between HFpEF and HFrEF-CRT(+) patients. The principal components analysis on the entire cohort of 160 patients yielded 2 homogeneous groups of patients in terms of dyssynchrony, the first comprising HFrEF-CRT(+) patients and the second comprising HTN, HFrEF-QRS < 120 ms and HFpEF patients. CONCLUSIONS: Mechanical dyssynchrony in HFpEF does not differ from that of patients with HTN or patients with HFrEF and a narrow QRS. This data raises concerns regarding the role of dyssynchrony in the pathophysiology of HFpEF and thereby the potential usage of CRT in HFpEF.

Role of patient education in the perception and acceptance of home monitoring after recent implantation of cardioverter defibrillators: the EDUCAT study.

BACKGROUND: Much attention is being paid to the education of and provision of medical information to patients, to optimize their understanding and acceptance of their disease. AIMS: To ascertain the impact of educating recent recipients of an implantable cardioverter defibrillator (ICD) on their perception and acceptance of a home monitoring (HM) system. METHODS: Questionnaire 1, completed one month after ICD implantation, was designed to assess: the quality of patient preparation for HM; patient comprehension of HM; and patient anxiety experienced during its installation. The comprehension questions were assigned a score of -2 for an incorrect answer, +1 for a correct answer and 0 for neither (total score ranging from -40 to +20). Questionnaire 2, completed six months after ICD implantation, assessed patient acceptance of and anxiety about HM. RESULTS: The registry included 571 patients (mean age 63.9±12.8 years; 83% men; 76% of ICDs implanted for primary prevention) followed by HM for 6.2±1.2 months. Questionnaire 1 was completed by 430 (75.3%) patients and questionnaire 2 by 398 (69.7%) patients. Younger patients had a better comprehension of HM than older patients. High-quality training conditions improved the comprehension score, and a positive association was observed between anxiety and acceptance levels and the comprehension score. The 80±20% mean data transmission rate (days of transmission/days of follow-up ratio) was unrelated to the comprehension scores. CONCLUSION: A clear understanding was associated with a higher acceptance of HM, although it was unrelated to the data transmission rate.

Relationship between two-dimensional speckle-tracking septal strain and response to cardiac resynchronization therapy in patients with left ventricular dysfunction and left bundle branch block: a prospective pilot study.

BACKGROUND: Previous studies have demonstrated variable patterns of longitudinal septal deformation in patients with left ventricular (LV) dysfunction and left bundle branch block. This prospective single center study was designed to assess the relationship between septal deformation patterns obtained by two-dimensional speckle-tracking echocardiography and response to cardiac resynchronization therapy (CRT). METHODS: One hundred one patients with New York Heart Association class II to IV heart failure, LV ejection fractions ≤ 35%, and left bundle branch block underwent echocardiography before CRT. Longitudinal two-dimensional speckle-tracking strain analysis in the apical four-chamber view identified three patterns: double-peaked systolic shortening (pattern 1), early pre-ejection shortening peak followed by prominent systolic stretch (pattern 2), and pseudonormal shortening with a late systolic shortening peak and less pronounced end-systolic stretch (pattern 3). CRT response was defined as a relative reduction in LV end-systolic volume of ≥ 15% at 9-month follow-up. CRT super-response was defined as an absolute LV ejection fraction of ≥ 50% associated with a relative reduction in LV end-systolic volume of ≥ 15% and an improvement in New York Heart Association functional class. Cardiac death or hospitalization for heart failure during follow-up was systematically investigated. RESULTS: Ninety-two percent of patients with pattern 1 or 2 were responders to CRT compared with 59% with pattern 3 (P < .0001). Thirty-six percent of patients with pattern 1 were super-responders compared with 15% of those with pattern 2 and 12% of those with pattern 3 (P = .037). The improvement in LV volumes, LV ejection fraction, and global longitudinal strain after CRT was better in patients with pattern 1 or 2 compared with those with pattern 3 (P < .0001 for all). Eighteen-month outcomes were excellent in patients with pattern 1 or 2, with event-free survival of 95 ± 3% compared with 75 ± 7% in patients with pattern 3 (P = .010). CONCLUSIONS: Septal deformation strain pattern 1 or 2 is highly predictive of CRT response. Further studies are needed to identify predictors of "nonresponse" in patients with a pattern 3.

Cardiac resynchronization therapy as rescue therapy in end-stage heart failure: illustration by three-dimensional speckle tracking strain echocardiography.

We report the case of a 73-year-old man admitted for refractory heart failure following implantation of a dual-chamber pacemaker. Three-dimensional (3D) echocardiography with speckle tracking area strain identified severe left ventricular (LV) dysfunction and LV dyssynchrony following right ventricular pacing. As the patient's clinical condition rapidly worsened despite optimal medical treatment, a cardiac resynchronization therapy (CRT) pacemaker was successfully implanted as rescue therapy. Symptoms rapidly regressed and echocardiographic assessment following CRT demonstrated an immediate improvement in LV systolic function, confirmed at 9-month follow-up with evidence of reverse remodeling. New imaging technologies such as 3D echocardiography with speckle tracking area strain may help to identify and follow up patients who will benefit from CRT as rescue therapy.