Leadless Ultrasound-Based Cardiac Resynchronization System in Heart Failure

The left atrium (LA) has a pivotal role in cardiac performance and LA deformation is a well-known prognostic predictor in several clinical conditions including heart failure with reduced ejection fraction. The aim of this study is to investigate the effect of cardiac resynchronization therapy (CRT) on both LA morphology and function and to assess the impact of LA reservoir strain (LARS) on left ventricular (LV) systolic and diastolic remodelling after CRT. Two hundred and twenty-one CRT-candidates were prospectively included in the study in four tertiary centres and underwent echocardiography before CRT-implantation and at 6-month follow-up (FU). CRT-response was defined by a 15% reduction in LV end-systolic volume. LV systolic and diastolic remodelling were defined as the percent reduction in LV end-systolic and end-diastolic volume at FU. Indexed LA volume (LAVI) and LV-global longitudinal (GLS) strain were the main parameters correlated with LARS, with LV-GLS being the strongest determinant of LARS (r = -0.59, P < 0.0001). CRT induced a significant improvement in LAVI and LARS in responders (both P < 0.0001). LARS was an independent predictor of both LV systolic and diastolic remodelling at follow-up (r = -0.14, P = 0.049 and r = -0.17, P = 0.002, respectively). CRT induces a significant improvement in LAVI and LARS in responders. In CRT candidates, the evaluation of LARS before CRT delivery is an independent predictor of LV systolic and diastolic remodelling at FU.

A multicenter prospective randomized controlled trial of cardiac resynchronization therapy guided by invasive dP/dt

Examine the impact of acute changes in left heart strain and volumes with percutaneous edge-to-edge MitraClip repair on improvement in health status assessed using Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) score. Changes in left atrial strain, left ventricular (LV) global longitudinal strain (LVGLS), LV end-systolic volume (LVESV), and end-diastolic volume (LVEDV) were evaluated in 50 patients undergoing MitraClip repair for symptomatic primary mitral regurgitation (PMR) and secondary mitral regurgitation (SMR) on transthoracic echocardiography before and 1 month after MitraClip. Multivariable regression was used to evaluate changes in left heart strain and volumes as predictors of change in KCCQ-12 scores, adjusting for baseline clinical and echocardiographic characteristics. Both PMR and SMR patients had significant increase in LVGLS and reduction in LVEDV and LVESV ( P < 0.05) after MitraClip, reduction trend in left atrial conduit strain (PMR P = 0.053; SMR P = 0.12) but no significant change in LV ejection fraction. KCCQ-12 score improved significantly in both PMR ( P < 0.001) and SMR cohorts ( P < 0.001). Higher delta KCCQ-12 tertiles were associated with greater reduction in LVEDV ( P = 0.022) after MitraClip. On multiple regression analysis, lower preprocedural Society of Thoracic Surgeons for Mitral Valve Replacement and KCCQ-12 score, and greater reduction in LVESV and left atrial strain conduit phase were associated with KCCQ-12 score improvement ( P < 0.001). There is a significant increase in LVGLS and reduction in LVEDV, LVESV and left atrial strain conduit after edge-to-edge MitraClip repair in both PMR and SMR. Lower preprocedural Society of Thoracic Surgeons for Mitral Valve Replacement and KCCQ-12 score, and greater reduction in LVESV and left atrial conduit strain were associated with KCCQ-12 score improvement after MitraClip. Further studies are warranted to understand the mechanism and significance of our findings.

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Clinical or echocardiographic mid-term responses to cardiac resynchronization therapy (CRT) may have a different influence on a long-term prognosis of heart failure patients treated with CRT. The aim of the evaluation was to establish which definition of response to CRT, clinical or echocardiographic, best predicts long-term prognosis. A total of 679 heart failure patients treated with CRT were included. All the patients underwent a complete history and physical examination and transthoracic echocardiogram prior to CRT implantation and at 6-month follow-up. The clinical and echocardiographic responses to CRT were defined based on clinical improvement (≥1 NYHA class) and LV reverse remodelling (reduction in LV end-systolic volume ≥15%) at 6-month follow-up, respectively. All the patients were prospectively followed up for the occurrence of death. The mean age was 65 ± 11 years and 79% of the patients were male. At 6-month follow-up, 510 (77%) patients showed clinical response to CRT and 412 (62%) patients showed echocardiographic response to CRT. During a mean follow-up of 37 ± 22 months, 140 (21%) patients died. Clinical and echocardiographic responses to CRT were both significantly related to all-cause mortality on univariable analysis. However, on multivariable Cox-regression analysis only echocardiographic response to CRT was independently associated with superior survival (hazard ratio: 0.38; 95% CI: 0.27-0.50; P < 0.001). In a large population of heart failure patients treated with CRT, the reduction in LV end-systolic volume at the mid-term follow-up demonstrated to be a better predictor of long-term survival than improvement in the clinical status.

Left ventricular end-systolic volume (LVESV) changes at 6 months and clinical status are useful for assessing responses to cardiac resynchronization therapy (CRT). Regression of the LVESV following CRT has not been described beyond 6 months. This study aimed to assess the proportion, predictors, and clinical outcomes of responders whose LVESVs had regressed. We retrospectively analyzed 104 consecutive CRT patients. A responder was defined as a patient with a relative reduction in the LVESV ≥15% at 6 months after CRT. Fifty-six responders participated in this study. A transient responder was defined as a responder without a relative reduction in the LVESV ≥15% at 2 years after CRT or who died of cardiac events during the 24-month follow-up period. Of the 56 responders, 16 (29%) were transient responders. Multivariable logistic regression analysis showed that chronic atrial fibrillation (odds ratio [OR] = 19.2, 95% confidence interval [CI] [1.93, 190], P = 0.012) and amiodarone usage (OR = 60.9, 95% CI [4.18, 886], P = 0.003) were independent predictors of transient responses. Hospitalizations for heart failure were significantly higher among the transient responders than among the lasting responders during a mean follow-up period of 7.6 years (log-rank P < 0.001), and all-cause mortality tended to be higher among the transient responders (log-rank P = 0.093). One-third of the responders were transient responders at 2 years after CRT, and their long-term prognoses were poor. Careful attention should be paid to maintain the reduction in LVESV especially in patients with chronic AF.

Cardiac resynchronization therapy (CRT) was shown to improve heart failure (HF) prognosis. But many patients do not benefit from CRT. Optimization of left ventricular (LV) lead position to the latest activated LV area is important to increase CRT response. We aimed to detect the relationship between LV lead sensing delay and echocardiographic and electrocardiographic response to CRT treatment. We prospectively included 156 consecutive patients with HF diagnosis, QRS ≥ 120 ms, left bundle branch block, New York Heart Association II-IV, LV ejection fraction (LVEF) < 35%, and scheduled for CRT (100 male, 56 female; mean age 65.8 ± 10.06 years). Echocardiographic CRT response was defined as ≥15% reduction in LV end-systolic volume (LVESV). LV lead sensing delay was calculated as the time interval from the onset of surface QRS wave to the onset of depolarization wave recorded from the LV lead by using the LV pacing lead as a bipolar electrode. LVESV reduction was associated with baseline QRS width (r = 0.292, P = 001), QRS narrowing (r = 0.332, P < 001), and LV lead sensing delay (r = 0.454, P < 001) in bivariate analysis. In logistic regression analysis, LV lead sensing delay was found to be the only independent parameter for predicting significant LVESV reduction (β = 0.423, P < 0.001). LV lead sensing delay was also found to be significantly associated with LVEF increase (r = 0.320, P < 0.001) and QRS narrowing (r = 0.345, P < 0.001). LV lead sensing delay is the only independent predictor for significant reduction in LVESV and was found to be significantly associated with LVEF increase and QRS narrowing after CRT treatment. We suggest that LV lead sensing delay may be used as a marker to predict the favorable response to CRT.

Background. Cardiac resynchronization therapy (CRT) results in improved left ventricular (LV) systolic function expressed by reduction in LV end-systolic volume (ESV). However, it is still not well known whether this reduction in LVESV occurs immediately after CRT (acute response) or whether some pts need more time to improve in LVESV. Aim of the study was to evaluate the time course of response (improvement in LVESV) to CRT. Particularly, the time course of response was compared between pts with ischemic and non-ischemic cardiomyopathy. Methods. 95 consecutive heart failure pts (84 men; 65±10yrs, 60 pts with ischemic cardiomyopathy and 35 pts with non-ischemic cardiomyopathy) scheduled for CRT, were included. 2D echocardiography was performed before, immediately after CRT and at 6 months follow-up (6MFU) to evaluate LVESV and LV ejection fraction (EF). Results. Immediately after CRT, a significant reduction in LVESV was observed combined with a significant increase in LVEF. At 6MFU a further improvement in LVESV and LVEF was noted (Table ).When a reduction in LVESV&gt;15% was used to define response to CRT, 38% exhibited an acute response, with an additional 18% at 6MFU resulting in a total of 56% responders to CRT. In pts with ischemic cardiomyopathy (63%), 28% exhibited an acute response, with an additional 17% at 6MFU resulting in 45% responders. In non-ischemic pts, 54% (P&lt;0.05 vs ischemic pts) exhibited acute response, with an additional 20% at 6MFU resulting in 74% responders. Conclusions. The beneficial effect of CRT on LV systolic function occurs immediately after CRT implantation, with an additional improvement at 6MFU. Pts with ischemic cardiomyopathy need more time to respond to CRT.

Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy: The TARGET Study: A Randomized, Controlled Trial

Interatrial Conduction Time and Left Atrial Function in Patients With Left Ventricular Systolic Dysfunction: Effects of Cardiac Resynchronization Therapy

BackgroundLeft bundle branch block (LBBB) causes left atrial (LA) dyssynchrony. It is unknown if LA dyssynchrony impacts long-term prognosis. ObjectivesThe purpose of this study was to determine mechanisms of LA dyssynchrony in LBBB and if LA dyssynchrony impacts long-term prognosis. MethodsIn a prospective multicenter study of 168 heart failure patients with LBBB, echocardiographic strain imaging was done before and after 6 months with cardiac resynchronization therapy (CRT). Outcome was assessed after 6 years. Dyssynchrony was measured relative to septum as delay in left ventricular (LV) lateral wall shortening and LA lateral wall stretch. Response to CRT was defined as at least 15% reduction in LV end-systolic volume. ResultsBefore CRT, there was marked LA dyssynchrony of 105 ± 76 ms, which decreased to 37 ± 68 ms in CRT-responders (P < 0.001), whereas nonresponders showed only a modest reduction in LA dyssynchrony (P < 0.05). There was strong association between LA and LV dyssynchrony (r = 0.70), consistent with direct LV-LA mechanical interaction. CRT caused modest increase in LA reservoir strain (P < 0.01) and marked increase of LV filling time (P < 0.001) in responders. Mortality after 6 years was 21% (35 deaths). LA dyssynchrony did not independently predict mortality. However, the combination of preserved LA reservoir strain (≥18%) and resolved LA dyssynchrony (≤53 ms) after 6 months with CRT was associated with excellent long term-prognosis: HR: 0.11 (95% CI: 0.03-0.42) vs preserved reservoir strain and persistent LA dyssynchrony. ConclusionsLA dyssynchrony in LBBB was attributed to direct LV-LA mechanical interactions. CRT improved diastolic function by increasing LV filling time. Patients with preserved LA reservoir strain and resolution of LA dyssynchrony by CRT had excellent long-term prognosis. (Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy [CRID-CRT]; NCT02525185)

Prevalence and characteristics of patients with clinical improvement but not significant left ventricular reverse remodeling after cardiac resynchronization therapy

This study aims to evaluate the feasibility, efficacy, procedural complications, and long-term outcomes of left ventricular (LV) endocardial pacing lead implantation at the latest activation site of the LV. This procedure is guided by three-dimensional (3D) mapping and performed via transseptal puncture, and targets heart failure (HF) patients who either do not respond to conventional cardiac resynchronization therapy (CRT) or face challenges in lead implantation. A retrospective analysis of clinical data was performed on 11 patients with dilated cardiomyopathy who were treated with LV endocardial pacing. Compared to conventional CRT, this procedure required longer operation and fluoroscopy times and higher radiation dose. Clinical improvements, as evidenced by at least one New York Heart Association class improvement, were achieved in 63.6% of the patients, with an average decrease in Minnesota Living with Heart Failure Questionnaire score of 33.8 ± 2.2 points (p < 0.05). However, complications and adverse events were noted in 3 patients (27.3%) one month postoperatively, including pocket hematomas in 3 patients (27.3%), a pocket infection in 1 patient (9.1%), and a thromboembolic event in 1 patient (9.1%). In addition, 3 patients (27.3%) had worsening HF after implantation. The estimated mortality rates at 1, 3, and 5 years post-implantation were 9.1%, 18.2%, and 27.3%, respectively. Implanting the LV endocardial pacing lead at the latest activation site under 3D mapping guidance via transseptal puncture offers a viable alternative for patients eligible for CRT who face challenges with LV epicardial lead implantation due to anatomical issues or CRT non-response. However, this procedure is associated with a relatively high incidence of complications, requires careful patient selection, and may necessitate lifelong anticoagulation after implantation.

Background:Routine atrioventricular optimization (AVO) has not been shown to improve outcomes with cardiac resynchronization therapy (CRT). However, more recently subgroup analyses of multicenter CRT trials have identified electrocardiographic or lead positions associated with benefit from AVO. Therefore, the purpose of this analysis was to evaluate whether interventricular electrical delay modifies the impact of AVO on reverse remodeling with CRT.Methods:This substudy of the SMART-AV trial (SMARTDELAY Determined AV Optimization) included 275 subjects who were randomized to either an electrogram-based AVO (SmartDelay) or nominal atrioventricular delay (120 ms). Interventricular delay was defined as the time between the peaks of the right ventricular (RV) and left ventricular (LV) electrograms (RV-LV duration). CRT response was defined prospectively as a >15% reduction in LV end-systolic volume from implant to 6 months.Results:The cohort was 68% men, with a mean age of 65±11 years and LV ejection fraction of 28±8%. Longer RV-LV durations were significantly associated with CRT response (P<0.01) for the entire cohort. Moreover, the benefit of AVO increased as RV-LV duration prolonged. At the longest quartile, there was a 4.26× greater odds of a remodeling response compared with nominal atrioventricular delays (P=0.010).Conclusions:Baseline interventricular delay predicted CRT response. At long RV-LV durations, AVO can increase the likelihood of reverse remodeling with CRT. AVO and LV lead location optimized to maximize interventricular delay may work synergistically to increase CRT response.Clinical Trial Registration:URL: https://www.clinicaltrials.gov. Unique identifier: NCT00874445.

125 Left Ventricular Systolic Mechanics is not the only determinant of response to Cardiac resynchronization Therapy