Personalized Screening Before Subcutaneous Cardioverter Defibrillator Implantation: Usefulness and Outcomes in Clinical Practice - The S-ICD Screening SIS Prospective Study.

BACKGROUND: Electrocardiographic (ECG) screening prior to S-ICD implantation is unsuccessful in around 10% of cases. A personalized screening method, by slightly moving the electrodes, to obtain a better R/T ratio has been described to overcome traditional screening failure. OBJECTIVE: To assess to what extent a personalized screening method improves eligibility for S-ICD implantation and evaluate the inappropriate shock rate after such screening success. METHODS: All consecutive patients eligible for an S-ICD implantation were prospectively recruited across 20 French centers between December 2019 to January 2022 (NCT04101253). In case of traditional screening failure, patients received a second personalized screening. If at least one vector was positive, the personalized screening was considered as successful, and the patient was eligible for implantation. RESULTS: 474 patients were included in the study (mean age 50.4 ±14.1 years; 77.4% men). Traditional screening was successful in 456 (96.2%) cases. This figure rose to 98.3% (n=466; P=.002) when personalized screening was performed. All patients implanted after successful personalized screening had correct signal detection on initial device interrogation. Nevertheless, after one year follow-up, 3 (43%) of the 7 patients implanted with personalized experienced inappropriate shock (vs 18 (4.2%) out of the 427 patients with traditional screening and S-ICD implantation P=.003). CONCLUSION: Traditional S-ICD screening was successful in our study in a very high proportion of patients. Considering the small improvement in success of screening and a higher rate of inappropriate shock, a strategy of personalized screening cannot be routinely recommended.

Evaluation of new predictive scores for sudden cardiac death in childhood hypertrophic cardiomyopathy in a French cohort.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is rare in children, and sudden cardiac death (SCD) is difficult to predict. Two prognostic scores - HCM Risk-Kids and Precision Medicine for Cardiomyopathy (PRIMaCY) - were developed to assess the risk of SCD in the next 5 years in children with HCM. AIMS: To test the ability of these scores to predict SCD in children with HCM. Also, to identify factors associated with a severe cardiac rhythmic event (SCRE) (ventricular fibrillation, sustained ventricular tachycardia, heart transplant for rhythmic reasons or SCD). METHODS: Retrospective, multicentre, observational study at 10 medical centres in the Nord-Pas-de-Calais region, France. RESULTS: This study included 72 paediatric patients with HCM during 2009-2019 who were followed for a median (interquartile range [IQR]) of 8.5 (5.0-16.2) years. Eleven patients (15.3%) presented with SCRE. HCM Risk-Kids was high, with a median (IQR) score of 6.2% (2.1-12.8%; significant threshold≥6.0%) and the PRIMaCY median (IQR) score was 7.1% (2.6-15.0%; significant threshold≥8.3%). The positive predictive value was only 27.1% (95% confidence interval [CI] 21.5-32.5%) for HCM Risk-Kids (with a threshold of≥6.0%) and 33.2% (95% CI 27.1-38.9%) for the PRIMaCY score (with a threshold of≥8.3%). The negative predictive values were 95.4% (95% CI 92.3-97.7%) and 93.0% (95% CI 89.8-96.2%), respectively. Three of 28 patients with an implantable cardioverter defibrillator (ICD) experienced complications (including inappropriate shocks). CONCLUSION: HCM Risk-Kids and the PRIMaCY score have low positive predictive values to predict SCD in paediatric patients. If used alone, they could increase the rate of ICD implantation and thus ICD complications. Therefore, the scores should be used in combination with other data (genetic and magnetic resonance imaging results).

Additive Prognostic Value of Left Ventricular Dispersion and Deformation in Patients With Severe Aortic Stenosis.

BACKGROUND: Speckle tracking strain echocardiography allows one to visualize the timing of maximum regional strain and quantifies left ventricular-mechanical dispersion (LV-MD). Whether LV-MD and LV-global longitudinal strain (LV-GLS) provide similar or complementary information in mortality risk stratification in patients with severe aortic stenosis (SAS) remains unknown. OBJECTIVES: The authors hypothesized that LV mechanical dyssynchrony assessed by LV-MD is associated with an increased risk of mortality and provides additional prognostic information on top of LV-GLS in patients with SAS. METHODS: A total of 364 patients with SAS (aortic valve area indexed ≤0.6 cm2/m2 and/or aortic valve area ≤1 cm2), LV ejection fraction ≥50% and no or mild symptoms were enrolled. The endpoint was overall mortality. RESULTS: During a median follow-up period of 41 months, 149 patients died. After adjustment, LV-MD ≥68 ms was significantly associated with an increased risk of mortality (adjusted HR: 1.41; 95% CI: 1.01-1.96; P = 0.044). Adding LV-MD ≥68 ms to a multivariable Cox regression model including LV-GLS ≥-15% improved predictive performance in terms of overall mortality, with improved global model fit, reclassification, and better discrimination. Patients with both criteria had an important increase in mortality compared to patients with none or one criterion (adjusted HR: 2.02; 95% CI: 1.34-3.03; P = 0.001). Interobserver reproducibility of LV-MD was good with an intraclass correlation coefficient of 0.90 (95% CI: 0.72-0.97). CONCLUSIONS: LV-MD is a reproducible parameter independently associated with an increased risk of mortality in SAS. Increased LV-MD associated with depressed LV-GLS identifies a subgroup of patients with an increased mortality risk. Whether early aortic valve replacement improves the outcome of these patients deserves further studies.

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).

Impact of peri-procedural management of direct oral anticoagulants on pocket haematoma after cardiac electronic device implantation: the StimAOD multicentre prospective study.

AIMS: The study aims to investigate the impact of direct oral anticoagulant (DOAC) management on the incidence of pocket haematoma in patients undergoing pacemaker or implantable cardioverter-defibrillator implantation. METHODS AND RESULTS: All consecutive patients receiving DOAC and undergoing cardiac electronic device implantation were included in a large multicentre prospective observational study (NCT03879473). The primary endpoint was clinically relevant haematoma within 30 days after implantation. Overall, 789 patients were enrolled [median age 80 (IQR 72-85) years old, 36.4% women, median CHA2DS2-VASc score 4 (IQR 0-8)], of which 632 (80.1%) received a pacemaker implantation. Antiplatelet therapy was combined with DOAC in 146 patients (18.5%). Direct oral anticoagulants (DOACs) were interrupted 52 (IQR 37-62) h before the procedure and resumed 31 (IQR 21-47) h later. Ninety-six percent of the patients had at least 12 h DOAC interruption before the procedure, and 78% had at least 12 h DOAC interruption after the procedure. Overall, anticoagulation was interrupted for 72 (IQR 48-96) h. Pre- or post-procedural heparin bridging was used in 8.2% and 3.9%, respectively. Timing of DOAC interruption of resumption was not associated with clinically relevant haematoma. Clinically relevant haematoma occurred in 26 patients (3.3%), and thromboembolic events occurred in 5 patients (0.6%). CONCLUSION: In this large real-life registry where most patients had DOAC interruption, clinically relevant haematoma was rare. Despite DOAC interruption and high CHA2DS2-VASc score, thromboembolic events occurred seldomly, highlighting that bleeding exceeds thromboembolic risk in this peri-procedural period. Future research is needed to identify risk factors for clinically relevant haematoma and meaningfully guide clinicians in optimizing DOAC management.

Improved diagnostic performance of insertable cardiac monitors by an artificial intelligence-based algorithm.

AIMS: The increasing use of insertable cardiac monitors (ICM) produces a high rate of false positive (FP) diagnoses. Their verification results in a high workload for caregivers. We evaluated the performance of an artificial intelligence (AI)-based ILR-ECG Analyzer™ (ILR-ECG-A). This machine-learning algorithm reclassifies ICM-transmitted events to minimize the rate of FP diagnoses, while preserving device sensitivity. METHODS AND RESULTS: We selected 546 recipients of ICM followed by the Implicity™ monitoring platform. To avoid clusterization, a single episode per ICM abnormal diagnosis (e.g. asystole, bradycardia, atrial tachycardia (AT)/atrial fibrillation (AF), ventricular tachycardia, artefact) was selected per patient, and analyzed by the ILR-ECG-A, applying the same diagnoses as the ICM. All episodes were reviewed by an adjudication committee (AC) and the results were compared. Among 879 episodes classified as abnormal by the ICM, 80 (9.1%) were adjudicated as 'Artefacts', 283 (32.2%) as FP, and 516 (58.7%) as 'abnormal' by the AC. The algorithm reclassified 215 of the 283 FP as normal (76.0%), and confirmed 509 of the 516 episodes as abnormal (98.6%). Seven undiagnosed false negatives were adjudicated as AT or non-specific abnormality. The overall diagnostic specificity was 76.0% and the sensitivity was 98.6%. CONCLUSION: The new AI-based ILR-ECG-A lowered the rate of FP ICM diagnoses significantly while retaining a > 98% sensitivity. This will likely alleviate considerably the clinical burden represented by the review of ICM events.

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.

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.

Deleterious effect of right ventricular pacing in patients with cardiac transthyretin amyloidosis: potential clinical benefit of cardiac resynchronization therapy.

BACKGROUND: Cardiac amyloidosis involvement is associated with a detrimental outcome including frequent arrhythmias, heart failure, and conduction disturbances which may need permanent pacing. CASES SUMMARY: We report two cases of patients with transthyretin amyloidosis (ATTR) who developed heart failure and depressed left ventricular ejection fraction (LVEF) following permanent right ventricular (RV) pacing but highly responded to cardiac resynchronization therapy (CRT). DISCUSSION: The impact of RV pacing and CRT in cardiac amyloidosis is not known. In our cases, the detrimental effect of permanent RV pacing on left ventricular (LV) systolic function and heart failure symptoms was suggested by both permanent RV pacing mediated functional and LV function decline and LV systolic dysfunction reversal following CRT along with QRS width reduction. Whether cardiac resynchronization should be readily recommended in ATTR patients who need ventricular pacing whatever the LVEF deserves further investigation.

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.

Subclinical Cardiac Dysfunction Is Associated With Extracardiac Organ Damages.

Background: Several studies conducted in America or Europe have described major cardiac remodeling and diastolic dysfunction in patients with sickle cell disease (SCD). We aimed at assessing cardiac involvement in SCD in sub-Saharan Africa where SCD is the most prevalent. Methods: In Cameroon, Mali and Senegal, SCD patients and healthy controls of the CADRE study underwent transthoracic echocardiography if aged ≥10 years. The comparison of clinical and echocardiographic features between patients and controls, and the associations between echocardiographic features and the vascular complications of SCD were assessed. Results: 612 SCD patients (483 SS or Sß0, 99 SC, and 19 Sß+) and 149 controls were included. The prevalence of dyspnea and congestive heart failure was low and did not differ significantly between patients and controls. While left ventricular ejection fraction did not differ between controls and patients, left and right cardiac chambers were homogeneously more dilated and hypertrophic in patients compared to controls and systemic vascular resistances were lower (p < 0.001 for all comparisons). Three hundred and forty nine SCD patients had extra-cardiac organ damages (stroke, leg ulcer, priapism, microalbuminuria or osteonecrosis). Increased left ventricular mass index, cardiac dilatation, cardiac output, and decreased systemic vascular resistances were associated with a history of at least one SCD-related organ damage after adjustment for confounders. Conclusions: Cardiac dilatation, cardiac output, left ventricular hypertrophy, and systemic vascular resistance are associated with extracardiac SCD complications in patients from sub-Saharan Africa despite a low prevalence of clinical heart failure. The prognostic value of cardiac subclinical involvement in SCD patients deserves further studies.

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.

Relationship between exercise pressure gradient and haemodynamic progression of aortic stenosis.

BACKGROUND AND AIMS: We hypothesized that large exercise-induced increases in aortic mean pressure gradient can predict haemodynamic progression during follow-up in asymptomatic patients with aortic stenosis. METHODS: We retrospectively identified patients with asymptomatic moderate or severe aortic stenosis (aortic valve area<1.5cm2 or<1cm2) and normal ejection fraction, who underwent an exercise stress echocardiography at baseline with a normal exercise test and a resting echocardiography during follow-up. The relationship between exercise-induced increase in aortic mean pressure gradient and annualised changes in resting mean pressure gradient during follow-up was investigated. RESULTS: Fifty-five patients (mean age 66±15 years; 45% severe aortic stenosis) were included. Aortic mean pressure gradient significantly increased from rest to peak exercise (P<0.001). During a median follow-up of 1.6 [1.1-3.2] years, resting mean pressure gradient increased from 35±13mmHg to 48±16mmHg, P<0.0001. Median annualised change in resting mean pressure gradient during follow-up was 5 [2-11] mmHg. Exercise-induced increase in aortic mean pressure gradient did correlate with annualised changes in mean pressure gradient during follow-up (r=0.35, P=0.01). Hemodynamic progression of aortic stenosis was faster in patients with large exercise-induced increase in aortic mean pressure gradient (≥20mmHg) as compared to those with exercise-induced increase in aortic mean pressure gradient<20mmHg (median annualised increase in mean pressure gradient 19 [6-28] vs. 4 [2-10] mmHg/y respectively, P=0.002). Similar results were found in the subgroup of 30 patients with moderate aortic stenosis. CONCLUSION: Large exercise-induced increases in aortic mean pressure gradient correlate with haemodynamic progression of stenosis during follow-up in patients with asymptomatic aortic stenosis. Further studies are needed to fully establish the role of ESE in the decision-making process in comparison to other prognostic markers in asymptomatic patients with aortic stenosis.

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.

Prognostic significance of left ventricular concentric remodelling in patients with aortic stenosis.

BACKGROUND: Four patterns of left ventricular (LV) geometry (normal, concentric remodelling, concentric hypertrophy and eccentric hypertrophy) have been described in aortic stenosis (AS). Although LV concentric remodelling (LVCR), characterized by normal LV mass despite increased LV wall thickness, is frequently observed in AS, its prognostic implication has been not specifically studied. AIM: We aimed to assess, using echocardiography, the prognostic implication of LVCR in asymptomatic or minimally symptomatic patients with AS. METHODS: Overall, 331 patients (mean age 73±13 years; 45% women) with AS (aortic valve area≤1.3cm2) and an ejection fraction >50% were enrolled. The endpoints were mortality with conservative management and mortality with conservative and/or surgical management. RESULTS: Sixty-three (19%) patients died under conservative management (follow-up 29±1 months). The highest risk of mortality under conservative management compared with patients with normal LV geometry was observed for LVCR (adjusted hazard ratio [HR]: 3.53, 95% confidence interval [CI]: 1.19-10.46; P=0.023), followed by concentric LVH (adjusted HR: 2.97, 95% CI: 1.02-8.60; P=0.045). Aortic valve replacement was performed in 96 patients (29%) during the entire follow-up (37±1 months); 72 (22%) patients died. Only LVCR remained independently associated with an increased risk of mortality when surgical management during the entire follow-up was considered (adjusted HR: 2.93, 95% CI: 1.19-7.23; P=0.020). CONCLUSIONS: Among the patterns of LV geometry in AS, LVCR portends the worst outcome. Patients with LVCR and AS have a considerable increased risk of mortality, regardless of clinical management.

Arterial Stiffness Impairment in Sickle Cell Disease Associated With Chronic Vascular Complications: The Multinational African CADRE Study.

BACKGROUND: Although a blood genetic disease, sickle cell disease (SCD) leads to a chronic vasculopathy with multiple organ involvement. We assessed arterial stiffness in SCD patients and looked for associations between arterial stiffness and SCD-related vascular complications. METHODS: The CADRE (Coeur Artères et Drepanocytose, ie, Heart Arteries and Sickle Cell Disease) study prospectively recruited pediatric and adult SCD patients and healthy controls in Cameroon, Ivory Coast, Gabon, Mali, and Senegal. Patients underwent clinical examination, routine laboratory tests (complete blood count, serum creatinine level), urine albumin/creatinine ratio measure, and a measure of carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AI) at a steady state. The clinical and biological correlates of cf-PWV and AI were investigated by using a multivariable multilevel linear regression analysis with individuals nested in families further nested in countries. RESULTS: Included were 3627 patients with SCD and 943 controls. Mean cf-PWV was lower in SCD patients (7.5±2.0 m/s) than in controls (9.1±2.4 m/s, P<0.0001), and lower in SS-Sß(0) than in SC-Sß(+) phenotypes. AI, corrected for heart rate, increased more rapidly with age in SCD patients and was higher in SCD than in control adults. cf-PWV and AI were independently associated with age, sex, height, heart rate, mean blood pressure, hemoglobin level, country, and hemoglobin phenotype. After adjustment for these correlates, cf-PWV and AI were associated with the glomerular filtration rate and osteonecrosis. AI was also associated with stroke, pulmonary hypertension, and priapism, and cf-PWV was associated with microalbuminuria. CONCLUSIONS: PWV and AI are deeply modified in SCD patients in comparison with healthy controls. These changes are independently associated with a lower blood pressure and a higher heart rate but also with the hemoglobin phenotype. Moreover, PWV and AI are associated with several SCD clinical complications. Their prognostic value will be assessed at follow-up of the patients.