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

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.; 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.; 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.; 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).; 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

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

International audienceThe 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 blocktypical 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 (120ms). 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 (120-150ms)

From evidence-based medicine to personalized medicine, with particular emphasis on drug-safety monitoring

International audienceNowadays, guidelines are derived from the findings of randomized controlled therapeutic trials. However, an overall significant P value does not exclude that some patients may be harmed by or will not respond to the therapeutic agent being studied. Trials in patients with a low risk of events and/or a limited chance of providing significant differences in therapeutic effects require a large patient population to demonstrate a beneficial effect. Composite efficacy endpoints are often employed to obviate the need for a large patient population when low rates of events or limited therapeutic efficacy are anticipated. Results of randomized controlled therapeutic trials are commonly expressed in terms of relative risk reduction, whereas absolute risk reduction allows the calculation of the ``number needed to treat'' to prevent an adverse outcome. The number needed to treat is a far more clinically relevant variable than relative risk reduction. The clinician's mission is to match treatment to patient with the goal of achieving optimal therapeutic response. Drug-safety monitoring is also of major importance to avoid exposing patients to irreversible adverse effects. Unfortunately, drug-safety monitoring is often overlooked in routine clinical practice. Finally, the lack of long-term therapeutic data (> 5-10 years) is an unsolved dilemma, as most trials are limited to a duration of a few months or years. (C) 2017 Elsevier Masson SAS. All rights reserved

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

International audienceAims 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 = 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 (120150 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

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

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.; 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.; 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).; 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