Cardiac Resynchronization Therapy Nonresponders Research Articles

Outcomes of mitral TEER in non-responders to cardiac resynchronization therapy: A systematic review and meta-analysis

BackgroundSecondary mitral regurgitation (MR) worsens in 10–15 % of heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). Transcatheter edge-to-edge repair (TEER) with Mitra-Clip (Abbot Vascular, Santa Clara, CA, USA) therapy is associated with improved survival and decreased rates of hospitalization for HF in selected patients with secondary MR. Data on TEER outcomes in CRT-non-responders are limited. The purpose of this meta-analysis was to evaluate outcomes of mitral TEER with Mitra-Clip in CRT-non-responders. MethodsCochrane, Scopus, MEDLINE, and EMBASE were searched for studies discussing outcomes of Mitra-Clip in CRT non-responders. Two reviewers were independently involved in screening studies and extracting relevant data. Individual study incidence rate estimates underwent logit transformation to calculate the weighted summary proportion under the random effect model. ResultsA total of eight reports met the inclusion criteria (439 patients). Mitra-Clip improved MR grade to ≤2+ in 83.8 % and 86.8 % of CRT non-responders at six months and one year, respectively. Symptomatic improvement (New York Heart Association class ≤II) was also found in 71 % and 78.1 % of CRT non-responders at six months and one year, respectively. The pooled overall incidence estimates of mortality at 30 days, 6 months, 1 year, and 2 years were 3.6 %, 9.2 %, 17.8 %, and 25.9 %, respectively. ConclusionTEER with Mitra-Clip in patients with significant secondary MR who do not respond to CRT was associated with MR improvement, alleviation of symptoms, and mortality rates similar to those in the COAPT trial.

The Prognostic Role of Global Longitudinal Strain and NT-proBNP in Heart Failure Patients Receiving Cardiac Resynchronization Therapy.

We aimed to evaluate whether baseline GLS (global longitudinal strain), NT-proBNP, and changes in these after cardiac resynchronization therapy (CRT) can predict long-term clinical outcomes and the echocardiographic-based response to CRT (defined by 15% relative reduction in left ventricular end-systolic volume). We enrolled 143 patients with stable ischemic heart failure (HF) undergoing CRT-D implantation. NT-proBNP and echocardiography were obtained before and 6 months after. The patients were followed up (median: 58 months) for HF-related deaths and/or HF hospitalizations (primary endpoint) or HF-related deaths (secondary endpoint). A total of 84 patients achieved the primary and 53 the secondary endpoint, while 104 patients were considered CRT responders and 39 non-responders. At baseline, event-free patients had higher absolute GLS values (p < 0.001) and lower NT-proBNP serum levels (p < 0001) than those achieving the primary endpoint. A similar pattern was observed in favor of CRT responders vs. non-responders. On Cox regression analysis, baseline absolute GLS value (HR = 0.77; 95% CI, 0.51-1.91; p = 0.002) was beneficially associated with lower primary endpoint incidence, while baseline NT-proBNP levels (HR = 1.55; 95% CI, 1.43-2.01; p = 0.002) and diabetes presence (HR = 1.27; 95% CI, 1.12-1.98; p = 0.003) were related to higher primary endpoint incidence. In HF patients undergoing CRT-D, baseline GLS and NT-proBNP concentrations may serve as prognostic factors, while they may predict the echocardiographic-based response to CRT.

Abstract 18159: Cardiac Resynchronization Therapy Response Predicted by Tissue Characterization Using Cardiac Magnetic Resonance Imaging in Non-Ischemic Dilated Cardiomyopathy

Introduction: Tissue characterization using cardiac magnetic resonance (CMR) is helpful for risk stratification in non-ischemic dilated cardiomyopathy (NIDCM). Hypothesis: This study aimed to investigate the predictive role of tissue characterization identified by CMR on cardiac resynchronization therapy (CRT) response. Methods: We retrospectively reviewed the patients who underwent CMR within 1 year before CRT implantation in NIDCM patients at a single tertiary center from January 2018 to September 2022. Late gadolinium enhancement (LGE), native T1, T2 and extracellular volume (ECV) were analyzed. CRT response was defined as a decrease in left ventricular end-systolic volume (LVESV) &gt; 15% or an increase in left ventricular ejection fraction &gt; 5% on TTE after at least 3 months after CRT implantation. Results: Among a total of 101 patients (mean age 66 years, 52.5% of male), 76 (75.2%) patients were defined as CRT responders. CRT responders had more LBBB (96.1% vs. 60.0%, p&lt;0.001) and longer QRS duration (156.0±178.5 vs. 167.0±176.5ms, p=0.005) compared with CRT non-responders. However, LGE burden (34.3 vs. 13.3%, p&lt;0.001), native T1 (1371.6 vs. 1336.8ms, p=0.033), T2 (45.9 vs. 42.1ms, p&lt;0.001), and extracellular volume (ECV, 36.8 vs. 31.0%, p&lt;0.001) were significantly higher in CRT non-responders. The area under the curve (AUC) to predict CRT response is the highest in LGE burden (0.817, 95% confidence interval [CI]: 0.710-0.925), followed by ECV (0.808, 95% CI: 0.711-0.905), T2 (0.779, 95% CI: 0.663-0.895), and native T1 (0.643, 95% CI: 0.520-0.766). After adjustment, LGE burden&gt;20% (odds ratio [OR]: 0.15, 95% CI: 0.02-0.71, p=0.024) and ECV &gt; 34% (OR: 0.13, 95% CI: 0.01-0.78, p=0.037) were independently poor CRT response predictors. Conclusions: The tissue characterization by using CMR is helpful to predict CRT response and clinical outcomes in patients with NIDCM, independently of conventional CRT response predictors.

CRT non-responder to responder conversion rate in the MORE-CRT MPP Trial.

To assess the impact of MultiPoint™ Pacing (MPP) in cardiac resynchronization therapy (CRT) non-responders after six months of standard biventricular pacing (BiVP). The trial enrolled 5,850 patients who planned to receive a CRT device. The echocardiography core laboratory assessed CRT response before implant and after six months of BiVP; non-response to BiVP was defined as < 15% relative reduction in left ventricular end-systolic volume (LVESV). Echocardiographic non-responders were randomized in a 1:1 ratio to receive MPP (541 patients) or continued BiVP (570 patients) for an additional six months and evaluated the conversion rate to the echocardiographic response. The characteristics of both groups at randomization were comparable. The percentage of non-responder patients who became responders to CRT therapy was 29.4% in the MPP arm and 30.4% in the BIVP arm (p=0.743). In patients with > 30 mm spacing between the two left ventricular pacing sites (MPP-AS), identified during the first phase as a potential beneficial subgroup, no significant difference in the conversion rate was observed. Our trial shows that approximately 30% of patients, who do not respond to CRT in the first six months, experience significant reverse remodeling in the following six months. This finding suggests that CRT benefit may be delayed or slowly incremental in a relevant proportion of patients and that the percentage of CRT responders may be higher than what has been described in short/middle-term studies. MPP does not improve CRT response in non-responders to BiVP, even with MPP-AS.

Adaptive CRT algorithm and electrical synchrony

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): United Hospital Medical Education and Research Committee, United Hospital Foundation. Background We have previously shown that optimization of cardiac resynchronization therapy (CRT) nonresponders using a novel electrical dyssynchrony mapping (EDM) system significantly improves electrical dyssynchrony, left ventricle (LV) size and systolic function. Whether this methodology can improve electrical dyssynchrony (and potentially LV function) in nonresponder patients programmed with the adaptive CRT (aCRT) algorithm is not known. Purpose To quantify electrical dyssynchrony in CRT nonresponders programmed using aCRT and determine if it can be improved using EDM. Methods We studied 97 patients programmed with the aCRT algorithm at multiple device settings with an ECG system of 9 anterior and 9 posterior electrodes. We quantified electrical dyssynchrony using a measure of wavefront fusion, cardiac resynchronization index (CRI), calculated as % change in area under the curve between all combinations of anterior and posterior electrodes as compared to native LBBB (CRT off). CRI results were displayed on an electrical dyssynchrony map (EDM) showing atrial-to-right ventricle-paced intervals (A-RVp) on the y-axis and atrial-to-left ventricle-paced intervals (A-LVp) on the x-axis. Results Figure 1 shows an EDM for a typical patient with CRI values marked at different programmed settings. Figure 2 shows CRI for 58 patients programmed LV-only by aCRT at baseline (red bars) and 39 patients programmed biventricular (BiV) by aCRT at baseline (blue bars). CRI at baseline was significantly (p≤0.001) higher in patients programmed LV-only vs. those programmed BiV. In both groups programming to LV-only at the optimal atrial-ventricular delay (AVD) and to sequential BiV pacing at the optimal ventricular-ventricular delay (VVD) produced significantly and markedly better CRI as compared to CRI at aCRT baseline settings. In the patients programmed by aCRT at baseline to LV-only, BiV VV=0 at standard device setting (SAV 120 ms) had significantly worse CRI than baseline. Conclusions Electrical dyssynchrony as measured by CRI is better in patients programmed aCRT LV-only than those programmed aCRT BiV. CRI can be improved by 20% or more by using EDM to program patients to LV-only pacing at the optimal AVD or to BiV pacing at the optimal VVD. EDM technology offers the possibility of substantially improving electrical synchrony in nonresponder patients programmed with aCRT.

PO-02-019 PREDICTION OF RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY USING IN SILICO HEART MODELS: COMPARISON OF IN SILICO AND REAL-WORLD CRT OUTCOMES

Cardiac resynchronization therapy (CRT) is a treatment option for patients with heart failure and left ventricular (LV) dyssynchrony. However, one-third of the patients are a CRT non-responder. We predicted CRT outcomes using in silico CRT simulation model and compared the in silico CRT outcomes with real-world CRT outcomes. Three-dimensional (3D) heart geometries of 11 patients (age, 64.0 ± 10.7 years, 4 men) with CRT were constructed from cardiac computed tomography. Finite element method was used to simulate the electrical wave propagation and mechanics in the heart. We coupled the cardiac electrical excitation and mechanical contraction with vascular hemodynamics by using the lumped parameter model. We predicted LV end-diastolic and end-systolic volume (LVEDV and LVESV) and ejection fraction (LVEF) after CRT implantation using the in silico CRT simulation model. A CRT responder was defined as absolute increase in LVEF ≥ 5%. We compared the in silico CRT outcomes with real-world CRT outcomes Two patients were in silico CRT responders and these 2 patients were real-world CRT responders. Nine patients were in silico CRT non-responders. Among these 9 patients, 8 patients were real-world CRT non-responders and 1 patient was real-world CRT responder. The in silico CRT outcomes agreed with real-world CRT outcomes in 10 out of 11 patients. The positive and negative predictive values and the accuracy of the response of in silico CRT model were 100%, 88.9%, and 90.9%, respectively. The in silico CRT simulation model is feasible for prediction of real-world CRT outcomes.

PO-02-016 PHYSIOLOGIC SIGNALS FROM CRT DEVICES ARE INDICATIVE OF CRT RESPONSE IN SMART-MSP STUDY

Cardiac resynchronization therapy (CRT) is a well-established treatment for some heart failure patients with reduced ejection fraction, but a subset of these patients does not respond to CRT. Multi-site pacing (MSP) is proposed to improve clinical response to CRT, but it is unclear which CRT subset would benefit from MSP. Physiologic sensor data from CRT devices may provide insights into this question. To determine whether device based physiologic parameters are indicative of CRT response/non-response and thus identify potential candidates for MSP. SMART-MSP study evaluated 6-month CRT response, defined by improved Clinical Composite Score, in patients with CRT defibrillators (CRT-D). Device parameters considered for this analysis included third (S3) and first (S1) heart sounds, thoracic impedance (ITTI), respiration rate, rapid shallow breathing index (RSBI), activity, and the multi-sensor HeartLogic index. From a randomly selected 60% development set of patients (183 CRT responders and 40 non-responders) with at least 150 days of data, the following statistical measures were calculated for each parameter based on the first 60- and 150-day epoch after CRT-D implant: mean (μ), standard deviation (σ) and change from first 30-day mean to last 30-day mean (Δ). To evaluate the effect of each measure on CRT response, odds ratios were calculated and tested for significance via univariable and multivariable logistic regression. The 60-day analysis (Fig 1A) shows that increases in σ60 for S3, S3/S1, RSBI, respiration rate, and HeartLogic index as well as μ60 for RSBI were significantly associated with reduced odds of CRT response in the univariable model. The only signal to survive multivariate elimination was respiration rate σ60. The 150-day analysis (Fig 1B) shows the same indications and that increases in μ150 for RSBI and HeartLogic index were associated with reduced odds while increases in μ150 and Δ150 for activity were associated with increased odds of CRT response. Both respiration rate σ150 and activity Δ150 survived multivariate elimination. Multiple device-based physiologic parameters significantly differed between CRT responders versus non-responders in the SMART-MSP study. 60-day results indicate that there is potential for device-based parameters to identify patients who may benefit from switching to MSP sooner. However, while useful parameters are apparent early on (60-day window), more parameters become significant over a longer follow-up (150 days).

Hemodynamic forces from 4D flow magnetic resonance imaging predict left ventricular remodeling following cardiac resynchronization therapy

BackgroundPatients with heart failure and left bundle branch block (LBBB) may receive cardiac resynchronization therapy (CRT), but current selection criteria are imprecise, and many patients have limited treatment response. Hemodynamic forces (HDF) have been suggested as a marker for CRT response. The aim of this study was therefore to investigate left ventricular (LV) HDF as a predictive marker for LV remodeling after CRT. MethodsPatients with heart failure, EF < 35% and LBBB (n = 22) underwent CMR with 4D flow prior to CRT. LV HDF were computed in three directions using the Navier–Stokes equations, reported in median N [interquartile range], and the ratio of transverse/longitudinal HDF was calculated for systole and diastole. Transthoracic echocardiography was performed before and 6 months after CRT. Patients with end-systolic volume reduction ≥ 15% were defined as responders. ResultsNon-responders had smaller HDF than responders in the inferior-anterior direction in systole (0.06 [0.03] vs. 0.07 [0.03], p = 0.04), and in the apex-base direction in diastole (0.09 [0.02] vs. 0.1 [0.05], p = 0.047). Non-responders had larger diastolic HDF ratio compared to responders (0.89 vs. 0.67, p = 0.004). ROC analysis of diastolic HDF ratio for identifying CRT non-responders had AUC of 0.88 (p = 0.005) with sensitivity 57% and specificity 100% for ratio > 0.87. Intragroup comparison found higher HDF ratio in systole compared to diastole for responders (p = 0.003), but not for non-responders (p = 0.8). ConclusionHemodynamic force ratio is a potential marker for identifying patients with heart failure and LBBB who are unlikely to benefit from CRT. Larger-scale studies are required before implementation of HDF analysis into clinical practice. Graphical Abstract [Display omitted]

Pacing interventions in non-responders to cardiac resynchronization therapy.

Non-responders to Cardiac Resynchronization Therapy (CRT) represent a high-risk, and difficult to treat population of heart failure patients. Studies have shown that these patients have a lower quality of life and reduced life expectancy compared to those who respond to CRT. Whilst the first-line treatment for dyssynchronous heart failure is "conventional" biventricular epicardial CRT, a range of novel pacing interventions have emerged as potential alternatives. This has raised the question whether these new treatments may be useful as a second-line pacing intervention for treating non-responders, or indeed, whether some patients may benefit from these as a first-line option. In this review, we will examine the current evidence for four pacing interventions in the context of treatment of conventional CRT non-responders: CRT optimization; multisite left ventricular pacing; left ventricular endocardial pacing and conduction system pacing.

The effectiveness of ARNI medication in patients, non-responder to cardiac resynchronization therapy

Abstract Introduction Almost 30% of patients are non-responders to cardiac resynchronization therapy (CRT) with no improvement of heart failure (HF) symptoms and left ventricular ejection fraction (LVEF). Angiotensin Receptor Neprilysin Inhibitor (ARNI), a novel class of medication resulted in a significant improvement in HF with reduced ejection fraction (HFrEF) in recent trials. No data has been reported on the clinical effectiveness of ARNI in the specific HF patient cohort of CRT non-responders (CRT-NR). Objective Herein, we compared the efficacy of ARNI medication in a general HF patient population and in CRT-NR patients. Method CRT-NR patients on ARNI therapy initiated at least 6 months after CRT implantation in years 2019–2021 were enrolled. Criterium for CRT-NR was a no, or less than 10% improvement in LVEF measured with echocardiography 6 months post-implantation. HF patients on ARNI therapy from our HF Clinic were used as controls. Changes in LVEF, in NYHA functional class and in the level of NT-proBNP were compared before ARNI therapy initiation and 6 months thereafter in both groups. Results 70 patients (age: 66,03±9.06 years, 9 women) were enrolled in the CRT-NR and 135 patients (age 62,36±11.26 years; 31 women) in the control group. LVEF increased from 25,25±5.70% to 29,47±6.73% (p&amp;lt;0.001), NYHA class decreased from 2,74±0.55 to 2.03±0.68 (p&amp;lt;0.001) and NT-proBNP from 3884.21±2503.95 to 2676,16±1745.94 (p&amp;lt;0.001) in CRT-NR patients after a 6-month treatment with ARNI. Similar improvement was demonstrated in all parameters in the control group: LVEF increased from 26,64±6.47% to 29,91±6.64% (p&amp;lt;0,001), NYHA class decreased from 2,97±0.54 to 2,18±0.58% (p&amp;lt;0,001) and NT-proBNP from 5355,17±1731.71 to 2062,66±1919.07 (p&amp;lt;0,001). During a mean follow-up of 20,55±11,36 months mortality rates were 17,14% in the CRT-NR group, and 18,51% in the control group. Conclusion ARNI therapy resulted in significant improvement in functional class, LVEF and HF biomarker level in CRT-NR patients, similarly to what was observed in a general HF patient cohort with no CRT. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Project no. TKP2021-EGA-18 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme.

Impact of long-term optimizing atrioventricular delay using device-based algorithms on cardiac resynchronization therapy

Sub-optimal atrioventricular delay (AVD) is one of the main causes of non-responder for cardiac resynchronization therapy (CRT). Recently, device-based algorithms (DBAs) that provide optimal AVD based on intracardiac electrograms, have been developed. However, their long-term effectiveness is still unknown. This study aims to investigate the effect of optimizing AVD using DBAs over a long period, on the prognosis of patients undergoing CRT. A total of 118 patients who underwent CRT at our hospital between April 2008 and March 2018, were retrospectively reviewed; 61 of them with optimizing AVD using DBAs were classified into the treated group (group 1), and the remaining 57 were classified into the control group (group 2). The median follow-up period was 46.0 months. The responder and survival rate in group 1 were significantly better than those in group 2 (group 1 vs. group 2: responder rate = 64% vs. 46%, p = 0.046; survival rate: 85.2% vs. 64.9%, p = 0.02). Moreover, investigating only the non-responder population showed that group 1 had an improved survival rate compared to group 2 (group 1 vs. group 2 = 72.7% vs. 45.1%, p = 0.02). Optimizing AVD using DBAs was a significant contributor to the improved survival rate in CRT non-responders in multivariate analysis (HR 3.6, p = 0.01). In conclusion, the long-term optimizing AVD using DBAs improved the survival rate in CRT and the prognosis of CRT non-responders, as well.

Stratification of Destination Therapy Candidates by J-HeartMate Risk Score Among Elderly Non-Responders to Cardiac Resynchronization Therapy

Background: For elderly patients with refractory heart failure (HF), destination therapy (DT) with a continuous-flow left ventricular assist device (LVAD) is a possible treatment. The aim of DT is for long-term, satisfying quality of life on LVAD support. Previously, elderly non-responders to cardiac resynchronization therapy (CRT) were primarily destined for palliative care, but DT has been available in Japan since April 30, 2021. This study investigated the prognosis of elderly CRT non-responders and assessed the feasibility of DT in these patients based on the J-HeartMate Risk Score (J-HMRS).Methods and Results: Of the 559 patients who underwent CRT at Tokyo Women’s Medical University between 2000 and 2018, 198 were aged 65–75 years. Among these, 76 were identified as non-responders based on echocardiographic data, and were included in this study. We calculated patients’ J-HMRS and investigated associations between the J-HMRS and cardiac events after CRT. Patients were divided into 3 groups according to the J-HMRS: low (n=23), medium (n=29), and high (n=24) risk. Patients in the low-risk group experienced as many HF rehospitalizations and ventricular arrhythmia events as those in the other groups. However, survival analysis revealed that, after CRT, survival was higher for patients in the low- compared with high-risk group (P=0.04).Conclusions: The J-HMRS classified 30% of elderly CRT non-responders as low risk and as suitable candidates for DT in Japan.

The Role of the Systemic Immune-Inflammation Index in Predicting Response to Cardiac Resynchronization Therapy

Objective: Cardiac resynchronization therapy (CRT) is a reliable treatment modality in patients with systolic dysfunction. However, not every patient appears to benefit from CRT. The systemic immune inflammation index (SII) is closely linked to the poor prognosis of various cardiovascular disorders. However, there is no study investigating whether SII has predictive value in determining response to CRT in dilated cardiomyopathy patients. Therefore, we intend to investigate the association between SII and response to CRT.&#x0D; Methods: A total of 220 patients (mean age 61.2±10.8 years; 120 men) implanted with CRT were involved in this study. Echocardiographic and laboratory measurements were evaluated prior to CRT. Response to CRT was determined as a≥ 15% decrease in left ventricular end-systolic volume at one-year follow-up.&#x0D; Results: Patients grouped as CRT responders and non-responders. Of these, 143 (64.6%) were considered to be CRT responders, while the remaining 77 (33.4%) were non-responders. Female sex (OR: 3.823, CI: 1.568-9.324 p=0.003), QRS duration (OR: 1.224, CI: 1.158-1.335 p

Treatment of cardiac resynchronization therapy non-responders: current approaches and new frontiers

ABSTRACT Introduction Cardiac resynchronization therapy (CRT) has developed into a very effective technology for patients with decreased systolic function and has substantially improved patients’ clinical course. However, non-responsiveness to CRT, described as lack of reverse cardiac chamber remodeling, leading to lack to improve symptoms, heart failure hospitalizations or mortality, is common, rather unpredictable, and not fully understood. Areas covered This article aims to discuss key factors that are impacting CRT response, from patient selection to LV lead position, to structured follow-up in CRT clinics. Secondly, common causes and interventions for CRT non-responsiveness are discussed. Next, insight is given into technologies representing new and feasible interventions as well as pacing strategies in this group of patients that remain challenging to treat. Finally, an outlook is given into future scientific development. Expert opinion Despite the progress that has been made, CRT non-response remains a significant and complex problem. Patient management in interdisciplinary teams including heart failure, imaging, and cardiac arrhythmia experts appears critical as complexity is increasing and CRT non-response often is a multifactorial problem. This will allow optimization of medical therapy, and the use of new integrated sensor technologies and telemedicine to ultimately optimize outcomes for all patients in need of CRT.

What Have We Learned in the Last 20Years About CRT Non-Responders?

Although cardiac resynchronization therapy (CRT) has become well established in the treatment of heart failure, the management of patients who do not respond after CRT remains a key challenge. This review will summarize what we have learned about non-responders over the last 20years and discuss methods for optimizing response, including the introduction of novel therapies.

The importance of early evaluation after cardiac resynchronization therapy to redefine response: Pooled individual patient analysis from 5 prospective studies

Cardiac resynchronization therapy (CRT) reduces mortality and improves outcomes in appropriately selected patients with heart failure (HF); however, response may vary. We sought to correlate 6-month CRT response assessed by clinical composite score (CCS) and left ventricular end-systolic volume index (LVESVi) with longer-term mortality and HF-related hospitalizations. Individual patient data from 5 prospective CRT studies-Multicenter InSync Randomized Clinical Evaluation (MIRACLE), Multicenter InSync ICD Randomized Clinical Evaluation(MIRACLE ICD), InSync III Marquis, predictors of response to cardiac resynchronization therapy(PROSPECT), and Adaptive CRT-were pooled. Classification of CRT response status using CCS and LVESVi were made at 6 months. Kaplan-Meier analyses were used to assess time to mortality. Cox proportional hazards regression models were used to compute hazard ratios (HRs) for the 3 levels of CRT response: improved, stabilized, and worsened. Adjusted models controlled for baseline factors known to influence both CRT response and mortality. HF-related hospitalization was compared between CRT response categories using incidence rate ratios. Among a total of 1603 patients, 1426 and 1165 were evaluated in the CCS and LVESVi outcome assessments, respectively. Mortality was significantly lower for patients in the improved (CCS: HR 0.22; 95% confidence interval [CI] 0.15-0.31; LVESVi: HR 0.40; 95% CI 0.27-0.60) and stabilized (CCS: HR 0.38; 95% CI 0.24-0.61; LVESVi: HR 0.41; 95% CI 0.25-0.68) groups than in the worsened group for both measures after adjusting for potential confounders. Patients with a worsened CRT response status have a high mortality rate and HF-related hospitalizations. Stabilized patients have a more favorable prognosis than do worsened patients and thus should not be considered CRT nonresponders.

Ten-year follow-up of cardiac resynchronization therapy patients with non-ischemic dilated cardiomyopathy assessed by radionuclide angiography: a single-center cohort study.

Relatively few data are available on long-term survival and incidence of ventricular arrhythmias in cardiac resynchronization therapy (CRT) patients. We investigated long-term outcomes of CRT patients with non-ischemic dilated cardiomyopathy stratified as responders or non-responders according to radionuclide angiography. Fifty patients with non-ischemic dilated cardiomyopathy undergoing CRT were assessed by equilibrium Tc99 radionuclide angiography with bicycle exercise at baseline and after 3months. Intra- and interventricular dyssynchrony were derived by Fourier phase analysis. Patient clinical outcome was assessed after 10years. At 3months, 50% of patients were identified as CRT responders according to an increase in LV ejection fraction ≥ 5%. During a follow-up of 109 ± 48months, 30% of patients died and 6% underwent heart transplantation. Age and history of paroxysmal atrial fibrillation were found to be predictors of all-cause mortality. CRT responders showed lower risk of death from cardiac causes than non-responders. At follow-up, 38% of patients presented at least one episode of sustained ventricular tachycardia, with a similar percentage between responders and non-responders. At long-term follow-up, non-ischemic CRT recipients identified as responders by radionuclide angiography were found to be at lower risk of worsening heart failure death than non-responders. Long-term risk for sustained ventricular arrhythmia was similar between CRT responders and non-responders.

Comparison of Speckle Tracking Echocardiography During Different Pacing Modalities for Cardiac Resynchronization Therapy Response Prediction.

Background: The aim of this study was to evaluate left ventricular mechanical activation pattern by speckle tracking echocardiography (STE) as a predictor of response to cardiac resynchronization therapy (CRT) in patients with heart failure. Methods: Echocardiography was performed during no pacing, right ventricular pacing (RVP), biventricular pacing (BVP) and multipolar pacing (MPP) immediately after CRT implantation in 16 patients at a single centre. Seven patients were diagnosed as responders and 9 patients as non-responders after 6 months of standard CRT pacing. All had adequate short axis views, and 1 CRT responder and 2 CRT non-responders had limited longitudinal views. Results: Longitudinal and circumferential global strain (GS) and global strain rate (GSR) or their change analysis, did not yield any CRT response prediction. However, the longitudinal BVP/RVP GS ratio was significantly higher in the responder group (1.32 ± 0.2%, 2.0 ± 0.4% and 1.9 ± 0.4%), compared with the non-responder group (1.06 ± 0.2%, 1.1 ± 0.4% and 1.2 ± 0.4%) in the apical two-chamber, APLAX and four-chamber views, respectively. Similarly, the longitudinal BVP/RVP GSR at active systolic phase (GSRs) was significantly higher in the responder group (1.9 ± 0.9% and 1.7 ± 0.4%) compared with the non-responder group (1.0 ± 0.4% and 1.1 ± 0.2%) in the apical APLAX and four-chamber views, respectively. Measurements of the strain delay index showed predictive power regarding CRT response in non-paced patients. Conclusion: Post implantation, longitudinal BVP/RVP GS and GSRs ratios of 1.4% and above may be useful as a CRT response prediction tool. Furthermore, our findings support the usefulness of strain delay index prior to CRT implantation in non-paced patients.

Usefulness of Multisite Ventricular Pacing in Nonresponders to Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) is an established treatment for heart failure patients with myocardial dysfunction and delayed ventricular activation, but approximately 25% to 40% of patients do not respond to CRT. Left ventricular (LV) multisite pacing (MSP) has been proposed as a tool to improve CRT response. The goal of this study is to examine the safety and efficacy of LV MSP in CRT nonresponders. Between January 2018, and September 2019, the Strategic Management to Improve CRT Using Multi-Site Pacing trial prospectively enrolled 584 CRT-defibrillator recipients for established indications at 52 sites across the United States and evaluated their response at 6 months using the clinical composite score (CCS). Of the nonresponders, 102 patients had the LV MSP feature turned on and 78 patients completed the 12-month CCS evaluation. The LV MSP feature-related complication-free rate was 99.0% with a lower 95% confidence interval limit of 94.9%, which was higher than the performance goal of 90%. The proportion of nonresponders with an improved CCS from 6 to 12 months was 51.3% with a lower 95% confidence interval limit of 41.4%, which was higher than the performance goal of 5%. The estimated mean reduction in battery longevity with the LV MSP feature was about 3.6 months (estimated battery longevity of 8.87 ± 2.08 years at 6 months and 8.07 ± 2.23 years at 12 months). In conclusion, in CRT nonresponders, the use of the LV MSP feature is safe and associated with a ∼50% conversion rate with a small projected reduction in CRT-defibrillator battery longevity. LV MSP should be considered in the management of CRT nonresponders.

Prognostic impact of heart mate risk score among elderly heart failure patients with non-responder for cardiac resynchronization therapy

Abstract Background For patients with severe heart failure (HF) who are not eligible for transplantation, there is destination therapy (DT) that uses a continuous flow left ventricular assist device (LVAD). Implantation of LVAD improves HF and can be expected to improve the prognosis of life. Elderly refractory HF patients with non-responders for cardiac resynchronization therapy (CRT) may benefit from LVAD as DT. In considering indications of LVAD as DT for the elderly in Japan, conditions such as a low risk of Heart Mate Risk Score (HMRS) have been raised. HMRS has been shown to correlate with mortality in the cohort of LVAD patients enrolled in the Heartmate II trials. Purpose Because elderly CRT non-responder refractory HF patients are not indicated for transplantation and may benefit from LVAD as DT in Japan, we aimed to investigate the HMRS and prognosis among elderly CRT non-responders. Methods Of 467 patients underwent CRT implantation between 2000 and 2015, 157 were aged 65–75 years old. Of which 59 patients who could be determined to be non-responders based on echocardiographic data were included in this study. The primary endpoint was all-cause mortality, the secondary was readmission for HF and appropriate implantable cardioverter defibrillator (ICD) therapy. Results The patients' mean age was 68 years, males were 71%. The mean serum creatinine value was 1.1 mg/dl, albumin was 3.8 mg/dl, and BNP was 383 pg/ml. The mean left ventricular ejection fraction (LVEF) was 26%. The subjects were divided into 3 groups according to HMRS. The average of HMRS was 2.2, the low-risk group included 17 (29%) patients, the medium was 22 (37%), and the high was 20 (34%). There was no significant difference in age, LVEF, BNP, and NYHA functional classification at the time of CRT implantation between three groups. In the low-risk group, creatinine and INR were significantly lower, and albumin was significantly higher compared to the high-risk group. BNP tended to be lower in the low-risk group, but there was no significant difference. The mortality rate by HMRS was 12% in the low-risk group, 36% in the medium-risk group, and 50% in the high-risk group. On the Kaplan-Meier analysis, the low-risk group had a significantly lower mortality rate than the high-risk group (Figure). Furthermore, focusing on HF readmission, the rate of readmission was 59% in the low-risk group, 86% in the medium -risk group, and 65% in the high-risk group, and there was no significant difference between three groups. There was also no significant difference in appropriate ICD therapy between three groups. Conclusion Approximately 30% of elderly non-responders of CRT are in the low-risk group by HMRS and their mortality was lower than that of the other two groups. These elderly CRT non-responder patients might be considered a candidate for DT in Japan. Funding Acknowledgement Type of funding sources: None.