Cardiac Resynchronization Therapy Response Rate Research Articles

CRT with triple fusion: results of the multicentric, randomized, doble-blinded CRUSTY trial

Abstract Background The possible benefit in terms of cardiac resynchronization therapy (CRT) response using a dynamic automatic algorithm designed to provide triple fusion as compared to conventional optimized biventricular pacing (CBP) is not known. Methods In this randomized, doble blinded, multicentric (13 centers) clinical trial we assigned patients with heart failure, reduced left ventricular ejection fraction and left bundle branch block, who underwent CRT implantation to be optimized using the SyncAV dynamic algorithm or through a conventional method. The primary endpoint was the rate of echocardiographic CRT responders at 6-month follow-up defined as a reduction of the left ventricular end diastolic volume (LVEDV) >15%. Results The study had to be stopped for slow recruitment in the context of the COVID-19 pandemic after enrolling 56 patients; 54 patients were finally analyzed. Patients’ basal characteristics are shown in TABLE. Patients assigned to the SyncAV group presented a narrowest paced QRS (128±16 ms vs. 145±19 ms; p <0.01) and a greater reduction in QRS duration (FIGURE A). Furthermore, more patients in the SyncAV group achieved a paced QRSd <120 mseg (7% vs 35%, p = 0.02). 21 (81%) patients in the SyncAV group and 19 (68%) in the CBP group were classified as CRT responders (OR = 1.99; 95% CI 0.57–7). While patients in the SyncAV group demonstrated a trend towards superior reverse remodeling across all secondary endpoints, statistical significance was not reached (FIGURE B). In the SyncAV group, 2 (8%) patients were categorized as negative responders, and 4 (16%) in the CBP group. A total of 43% of patients improved by at least one category in the NYHA functional classification, while 2 patients experienced worsening, both in the CBP group (clinical negative responders) (FIGURE C). No adverse events directly associated with device programming or the activation of the SyncAV algorithm were reported. Conclusions In this multicenter randomized controlled trial comparing CRT with triple fusion pacing using the SyncAV algorithm to conventional optimized biventricular pacing, there was not reached adequate statistical power to draw a conclusion regarding a potential increase in the CRT response rate. Nevertheless, the use of the SyncAV algorithm resulted in a high proportion of CRT responders. A significant greater reduction of the QRS duration was observed when employing the SyncAV algorithm, leading to a high percentage of cases achieving QRS width normalization. Nonetheless, further investigations are warranted to thoroughly assess the possible clinical benefits associated with triple fusion of LV pacing, RV pacing and intrinsic conduction in HF patients with LBBB.FIGURE

LBBB and heart failure-Relationships among QRS amplitude, duration, height, LV mass, and sex.

Height, left ventricular (LV) size, and sex were proposed as additional criteria for patient selection for cardiac resynchronization therapy (CRT) but their connections with the QRS complex in left bundle branch block (LBBB) are little investigated. We evaluated these. Among patients with "true" LBBB, QRS duration (QRSd) and amplitude, and LV hypertrophy indices, were correlated with patient's height and LV mass, and compared between sexes. In this study cohort (n = 220; 60 ± 12 years; left ventricular ejection fraction [LVEF] 21 ± 7%; mostly New York Heart Association II-III, QRSd 165 ± 19 ms; 57% female; 70% responders [LVEF increased ≥5%]), LV mass was increased in all patients. QRS amplitude did not correlate with LV mass or height in any individual lead or with Sokolow-Lyon or Cornell-Lyon indices. QRSd did not correlate with height. In contrast, QRSd correlated strongly with LV mass (r = .51). CRT response rate was greater in women versus men (84% vs. 58%, p < .001) despite shorter QRSd [7% shorter (p < .0001)]. QRSd normalized for height resulted in a 2.7% and for LV mass 24% greater index in women. True LBBB criteria do not exclude HF patients with increased LV mass. QRS amplitudes do not correlate with height or LV mass. Height does not affect QRSd. However, QRSd correlates with LV size. QRSd normalized for LV mass results in 24% greater value in women in the direction of sex-specific responses. LV mass may be a significant nonelectrical modifier of QRSd for CRT.

Cardiac CT in CRT as a Singular Imaging Modality for Diagnosis and Patient-Tailored Management.

Between 30-40% of patients with cardiac resynchronization therapy (CRT) do not show an improvement in left ventricular (LV) function. It is generally known that patient selection, LV lead implantation location, and device timing optimization are the three main factors that determine CRT response. Research has shown that image-guided CRT placement, which takes into account both anatomical and functional cardiac properties, positively affects the CRT response rate. In current clinical practice, a multimodality imaging approach comprised of echocardiography, cardiac magnetic resonance imaging, or nuclear medicine imaging is used to capture these features. However, with cardiac computed tomography (CT), one has an all-in-one acquisition method for both patient selection and the division of a patient-tailored, image-guided CRT placement strategy. This review discusses the applicability of CT in CRT patient identification, selection, and guided placement, offering insights into potential advancements in optimizing CRT outcomes.

Effects of Atrioventricular Optimization on Left Ventricular Reverse Remodeling With Cardiac Resynchronization Therapy: Results of the SMART-CRT Trial.

The role of atrioventricular optimization (AVO) to improve cardiac resynchronization therapy outcomes remains controversial. Previous post hoc analyses of a multicenter trial showed that measures of electrical dyssynchrony (right ventricular-left ventricular [LV] or QLV durations) are associated with patients who benefit from AVO. This was a global, multicenter, prospective, randomized trial of de novo cardiac resynchronization therapy implant patients with an right ventricular-LV duration ≥70 ms to determine whether AVO results in greater reverse remodeling. Patients were randomized 1:1 for either an AVO algorithm (SmartDelay) that determines atrioventricular delay and pacing chamber, biventricular or LV only, or a fixed atrioventricular delay of 120 ms with biventricular pacing. Paired echocardiograms performed at baseline and 6 months were evaluated. The primary end point was echocardiographic cardiac resynchronization therapy response, defined dichotomously as a >15% reduction in LV end-systolic volume. A total of 310 patients (n=120 women) were randomized and had completed 6 months of follow-up. The echocardiographic cardiac resynchronization therapy response rate did not statistically differ between the groups (SmartDelay, 74.8%; fixed, 67.7%; P=0.17). Analyses of prespecified secondary end points demonstrated significant improvements in the absolute (median: SmartDelay, -41.0 mL; fixed, -33.0 mL; P=0.01) and relative change in LV end-systolic volume (SmartDelay, -38.3%; fixed, -27.8%; P=0.03) for patients with SmartDelay optimization. Similar results were observed for the relative improvement in LV ejection fraction (SmartDelay, 46.7%; fixed, 32.1%; P=0.050); absolute improvement in LV ejection fraction trended to be higher with SmartDelay (P=0.06). Analysis of reverse remodeling parameters demonstrated that AVO via SmartDelay, relative to the nonoptimized fixed atrioventricular delay comparator group, improved absolute and relative changes in LV function in patients with longer right ventricular-LV duration. URL: https://www. gov; Unique identifier: NCT03089281.

Response rate in cardiac resynchronization therapy patients implanted with a left ventricular quadripolar lead and the MultiPoint™ pacing feature early activated. QUARTO III.

Although cardiac resynchronization therapy (CRT) is beneficial in most heart failure patients, up to 40% do not respond to CRT. It has been suggested that multipoint left ventricle pacing (MPP) would increase the response rate. To assess the CRT response rate at 6months in patients implanted with a CRT device with the MPP feature activated early after the implant. This was a multicentre, prospective, open-label and non-randomized study. The primary endpoint was response to biventricular pacing defined as >15% relative reduction in left ventricular end-systolic volume (LVESV) comparing echocardiography measurements performed at baseline and 6months by a core laboratory. Among secondary endpoints the combined endpoint of mortality or all-cause hospitalizations was evaluated. Primary study endpoint and clinical outcomes were compared to a Quarto II control cohort. Totally, 105 patients were included. The response rate was 64.6% (97.5% lower confidence bound 53%). Mean relative reduction in LVESV was 25.3%, and mean absolute increase in LVEF was 9.4%. The subjects with device programmed using anatomical approach showed a trend towards higher responder rate than those using the electrical approach (72% vs. 61.1%, p= 0.32). Finally, the combined incidence of mortality and or all-cause hospitalizations at 6month was 12.4%. Early activation of MPP was not associated to an advantage increasing echocardiography responders to CRT at 6months of follow-up. Nevertheless, patients programmed using widest pacing cathodes had a numerically higher responder rate. Finally, early activation of MPP was associated to a low incidence of clinical endpoints at 6months of follow-up.

Why does CRT work better in women?

Abstract Introduction It has been recently postulated that cardiac resynchronization therapy (CRT) might have a higher efficacy in women, with a greater reverse cardiac remodeling in this population. The reasons for these differences are not yet completely understood. We aimed to detect sex differences in the degree of ventricular asynchrony (VA) and mitral regurgitation (MR) in patients undergoing CRT implantation. Methods We analyzed baseline characteristics of a prospective international clinical trial that compared CRT response rate in a HF population with a comparable distribution of men and women (BIOWOMEN). A total of 408 patients were analyzed. The degree of mitral regurgitation and intra and inter-ventricular asynchrony was assessed by independent echocardiographers in a core lab. Inter-ventricular asynchrony was defined as an interventricular mechanical delay greater than 40ms and intra-ventricular asynchrony as differences greater than 50ms among regional pre-ejection periods. Multivariable logistic regression was performed using commercial data analysis software. Results As expected, ventricular asynchrony was dependent on QRS duration and the presence of LBBB (p&amp;lt;0.01). Baseline QRS duration was significantly shorter in women than men (155.85±19.0 in women vs 160.4±21.6, p=0.02). However, for a similar QRS duration, there were no differences in asynchrony parameters between the two groups (p=0.43; Figure 1). Female sex was associated with a significantly higher proportion of mitral regurgitation for a given QRS duration, which was independent of the etiology (p=0.05). Conclusions In our analysis, for a given QRS duration there was not a higher degree of asynchrony in women with HF. However, female sex was associated with a significantly higher proportion of mitral regurgitation for a given QRS duration irrespective of baseline HF etiology. Further investigations are needed to establish a possible link between these findings and better CRT outcomes in women. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): BIOTRONIK SE &amp; Co. KG

The role of cardiac magnetic resonance in identifying appropriate candidates for cardiac resynchronization therapy - a systematic review of the literature.

Despite the strict indications for cardiac resynchronization therapy (CRT) implantation, a significant proportion of patients will fail to adequately respond to the treatment. This systematic review aims to present the existing evidence about the role of cardiac magnetic resonance (CMR) in identifying patients who are likely to respond better to the CRT. A systematic search in the MedLine database and Cochrane Library from their inception to August 2021 was performed, without any limitations, by two independent investigators. We considered eligible observational studies or randomized clinical trials (RCTs) that enrolled patients &gt; 18years old with heart failure (HF) of ischaemic or non-ischaemic aetiology and provided data about the association of baseline CMR variables with clinical or echocardiographic response to CRT for at least 3months. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA Statement). Following our search strategy, 47 studies were finally included in our review. CMR appears to have an additive role in identifying the subgroup of patients who will respond better to CRT. Specifically, the presence and the extent of myocardial scar were associated with increased non-response rates, while those with no scar respond better. Furthermore, existing data show that scar location can be associated with CRT response rates. CMR-derived markers of mechanical desynchrony can also be used as predictors of CRT response. CMR data can be used to optimize the position of the left ventricular lead during the CRT implantation procedure. Specifically, positioning the left ventricular lead in a branch of the coronary sinus that feeds an area with transmural scar was associated with poorer response to CRT. CMR can be used as a non-invasive optimization tool to identify patients who are more likely to achieve better clinical and echocardiographic response following CRT implantation.

Determinants of Response to Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) is a well-established treatment modality for ambulatory patients with heart failure (HF) who have prolonged QRS, left bundle branch block, reduced left ventricular (LV) ejection fraction, and New York Heart Association class II–IV. CRT has been shown to induce reverse LV remodeling and improve HF symptoms and clinical outcomes. About one-third of CRT recipients are considered non-responders. Patient selection, LV lead location, LV lead selection, multipoint pacing, and optimization of the atrioventricular and ventriculo-ventricular intervals were all shown to be associated with a better CRT response rate. Herein, we review the determinants of CRT response.

Clinical significance of the albumin-bilirubin score in patients with heart failure undergoing cardiac resynchronization therapy.

Despite emerging recognition of interactions between heart failure (HF) and liver dysfunction, the impact of cardiac hepatopathy on patients with HF undergoing cardiac resynchronization therapy (CRT) has not been fully elucidated. Albumin-bilirubin (ALBI) score is a new assessment of liver function. The relationship between liver dysfunction severity based on ALBI score and clinical outcomes of patients with HF receiving CRT is unclear. Clinical records of 274 patients who underwent CRT device implantation between March 2003 and October 2020 were retrospectively investigated. ALBI score was calculated based on serum albumin and total bilirubin levels obtained before CRT device implantation. Patients were divided into three groups based on ALBI score: first tertile (ALBI ≤ - 2.62, n = 91)), second tertile (- 2.62 < ALBI < - 2.13, n = 92), and third tertile (ALBI ≥ - 2.13, n = 91). The study endpoint was all-cause mortality. The third tertile group had more advanced NYHA functional class, lower hemoglobin levels, and higher total bilirubin, aspartate aminotransferase, γ-glutamyl transferase, and N-terminal Pro-B-type natriuretic peptide levels (all p < 0.05). The third tertile group also had a higher prevalence of moderate or severe tricuspid regurgitation and higher tricuspid regurgitation pressure gradient (all p < 0.05). CRT response rates were significantly lower in the third tertile group. During a median (interquartile range) follow-up of 30 (9-60) months, 104 (37.9%) patients died. The third tertile group had significantly higher rates of all-cause mortality (log-rank p < 0.001). Higher ALBI score was significantly associated with all-cause mortality, even after adjusting for clinically relevant factors, a conventional validated risk score, and echocardiographic parameters related to right HF (all p < 0.01). Higher ALBI score before CRT device implantation is associated with HF severity, hepatic congestion and impairment due to right HF, lower CRT response, and higher all-cause mortality in CRT recipients.

Prognostic value of the MELD-XI score in patients undergoing cardiac resynchronization therapy.

AimsMulti‐organ dysfunction was recently reported to be a common condition in patients with heart failure (HF). The Model for End‐stage Liver Disease eXcluding International normalized ratio (MELD‐XI) score reflects liver and kidney function. The prognostic relevance of this score has been reported in patients with a variety of cardiovascular diseases who are undergoing interventional therapies. However, the relationship between the severity of hepatorenal dysfunction assessed by the MELD‐XI score and the long‐term clinical outcomes of HF patients receiving cardiac resynchronization therapy (CRT) has not been evaluated.Methods and resultsClinical records of 283 patients who underwent CRT implantation between March 2003 and October 2020 were retrospectively evaluated (mean age 67 ± 12, 22.6% female). Blood samples were collected before CRT implantation. Patients were divided into three groups based on tertiles of the MELD‐XI score: first tertile (MELD‐XI = 9.44, n = 95), second tertile (9.44 < MELD‐XI < 13.4, n = 94), and third tertile (MELD‐XI ≥ 13.4, n = 94). The primary endpoint was all‐cause mortality. Compared with the other groups, the third tertile group exhibited significantly older age, higher prevalence of diabetes mellitus and hypertension, lower haemoglobin level, and higher N‐terminal pro‐brain natriuretic peptide level (all P < 0.05). The functional CRT response rate was also significantly lower in the third tertile group (P = 0.011). During a median follow‐up of 30 months (inter‐quartile range, 9–67), 105 patients (37.1%) died. Kaplan–Meier analysis revealed that patients with a higher MELD‐XI score had a greater risk of all‐cause mortality (log‐rank test: P < 0.001). Even after adjustment for clinically relevant factors and a conventional risk score, the MELD‐XI score was still associated with mortality (adjusted hazard ratio: 1.04, 95% confidence interval: 1.00–1.07, P = 0.014, and adjusted hazard ratio: 1.04, 95% confidence interval: 1.01–1.09, P = 0.005, respectively). A higher MELD‐XI score was associated with a greater risk of all‐cause mortality than a lower MELD‐XI score regardless of whether a pacemaker or defibrillator was implanted (log‐rank test: P = 0.010 and P < 0.001, respectively).ConclusionsImpaired hepatorenal function assessed by the MELD‐XI score was associated with older age, higher prevalence of multiple co‐morbidities, severity of HF, lower CRT response rates, and subsequent all‐cause mortality in HF patients undergoing CRT implantation. These results suggest that the MELD‐XI score can provide additional prognostic information and may be useful for improving risk stratification in this population.

A rapid electromechanical model to predict reverse remodeling following cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is an effective therapy for patients who suffer from heart failure and ventricular dyssynchrony such as left bundle branch block (LBBB). When it works, it reverses adverse left ventricular (LV) remodeling and the progression of heart failure. However, CRT response rate is currently as low as 50-65%. In theory, CRT outcome could be improved by allowing clinicians to tailor the therapy through patient-specific lead locations, timing, and/or pacing protocol. However, this also presents a dilemma: there are far too many possible strategies to test during the implantation surgery. Computational models could address this dilemma by predicting remodeling outcomes for each patient before the surgery takes place. Therefore, the goal of this study was to develop a rapid computational model to predict reverse LV remodeling following CRT. We adapted our recently developed computational model of LV remodeling to simulate the mechanics of ventricular dyssynchrony and added a rapid electrical model to predict electrical activation timing. The model was calibrated to quantitatively match changes in hemodynamics and global and local LV wall mass from a canine study of LBBB and CRT. The calibrated model was used to investigate the influence of LV lead location and ischemia on CRT remodeling outcome. Our model results suggest that remodeling outcome varies with both lead location and ischemia location, and does not always correlate with short-term improvement in QRS duration. The results and time frame required to customize and run this model suggest promise for this approach in a clinical setting.

Abstract 13731: Randomized Trial of CMR Guidance for Cardiac Resynchronization Therapy: Findings in Nonischemic Cardiomyopathy From an Interim Analysis

Introduction: Cardiac resynchronization therapy (CRT) response rates in unselected cohorts are suboptimal. Cardiac magnetic resonance (CMR) provides high-quality imaging of strain and scar, and post-CRT CMR offers reliable assessment of left ventricular (LV) reverse remodeling. Hypothesis: Cardiac magnetic resonance (CMR) guidance for CRT will increase CRT response rates, particularly in nonischemic cardiomyopathy (NICM). Methods: Patients were randomized 1:1 to standard CRT or CMR guidance for CRT using circumferential strain from Displacement Encoding with Stimulated Echoes (DENSE) and scar (late gadolinium enhancement [LGE]) by CMR. The primary endpoint is the percent change in LV end-systolic volume (LVESV) calculated from CMRs before CRT and 6 months after CRT. A pre-specified interim analysis by cardiomyopathy type was performed after completion of enrollment of 45 of the projected 90 patients needed for adequate power. Results: Of 45 patients enrolled (age 65.9 +/- 10.3 years, 29% female), two patients did not undergo a CRT procedure, and the LV lead could not be placed in one patient. Of the remaining 42 patients, 26/42 had NICM and 21/42 were randomized to CMR guidance. In a linear regression model for the primary endpoint adjusted for baseline QRS duration (p=0.04) and cardiomyopathy type (p=0.01), a favorable trend for the intervention on response was noted (p=0.06). Box plots demonstrate a significant difference in the primary endpoint among NICM patients (p=0.03) and a favorable trend for QRS shortening (0.07) in NICM patients (Figure). In all patients (including ICM patients), the overall p-value for the intervention relative to the primary endpoint was 0.08. Conclusion: An interim analysis in CRT patients with NICM demonstrated a favorable effect of CMR guidance on LV reverse remodeling after CRT, as assessed with post-CRT CMRs. Enrollment is continuing to evaluate the effect of the intervention on the entire cohort and other endpoints.

Right ventricular dilatation and systolic dysfunction and relationship to QRS duration in patients with left bundle branch block and cardiomyopathy.

Marked QRS widening in patients with left bundle branch block (LBBB) may reduce efficacy of cardiac resynchronization therapy (CRT). We hypothesized that extreme QRS prolongation may accompany right ventricular (RV) dilatation/systolic dysfunction (RVD/RVsD) as well as left ventricular dilatation/systolic dysfunction (LVD/LVsD). We assessed rates of both ventricular dilatation and systolic dysfunction according to widening of QRS duration (QRSd) in 100 consecutive cardiomyopathy patients with true LBBB (QRSd≥130ms in female or ≥140ms in male, QS or rS in leads V1/V2, and mid-QRS notching/slurring in ≥2 contiguous leads of I, aVL, and V1/V2/V5/V6). Ventricular dimensions and function were measured by cardiac magnetic resonance imaging. There was a trend toward an increase in the prevalence of LVD (13%, 20%, and 90%), LVsD (67%, 77%, and 90%), RVD (23%, 27%, and 50%), RVsD (27%, 27%, and 40%), RVD plus RVsD (13%, 17%, and 40%), or RVD/RVsD (37%, 37%, and 50%) according to the degree of QRS prolongation (<150ms, n=30; 150-180ms, n=60; and ≥180ms, n=10). Similarly, patients in the highest quartile of QRSd (QRSd≥168ms, n=26) showed greater rates of RVD (23% vs. 44%, p=.069), RVsD (22% vs. 48%, p=.032), RVD plus RVsD (10% vs. 30%, p=.040), or RVD/RVsD (33% vs. 57%, p=.050) compared to those in the remaining quartiles (n=74). QRSd≥180ms was identified as an independent predictor for the presence of RVD plus RVsD. The rates of RVD and/or RVsD increased with QRS widening, particularly when QRSd exceeded 180ms. This may diminish anticipated CRT response rates in cardiomyopathy patients with LBBB.

Efficacy of Cardiac Resynchronization Therapy in Patients with a Narrow QRS Complex

Aims. In the guidelines for cardiac resynchronization therapy (CRT), there is a gap between the Japanese Circulation Society (JCS) criteria, which specify a QRS duration of ≥120 ms, and other countries, with a QRS ≥ 130 ms. The efficacy of CRT remains controversial in patients with a narrow QRS &lt;130 ms. The aims of this study are to evaluate the response to CRT in patients with a narrow QRS and to identify predictors of mortality. Methods. We retrospectively studied 212 patients who received CRT. They were divided into narrow QRS (&lt;130 ms) and wide QRS (≥130 ms) groups. We compared CRT response rates and investigated whether age, gender, baseline New York Heart Association (NYHA) class, ischemic etiology, atrial fibrillation, and ventricular arrhythmias are associated with response and also predictive of mortality. Results. The CRT response rate was not significantly different between the wide QRS group and the narrow QRS group (74.6% versus 77.2%, p = 0.6876), and the response rate in the narrow QRS group was as good as that reported worldwide. NYHA class IV was shown to be a predictor of mortality (HR 9.38, 95% CI 5.35–16.3, p &lt; 0.0001). Conclusions. The present study demonstrated that patients with a narrow QRS complex responded well to CRT. Even with QRS &lt;130 ms, CRT should be tried if no other effective treatment is available.

Cardiac Resynchronization Therapy Response Assessment with Electromechanical Activation Mapping within 24 Hours of Device Implantation: A Pilot Study

Cardiac resynchronization therapy (CRT) response assessment relies on the QRS complex narrowing criterion. Yet one third of patients do not improve despite narrowed QRS after implantation. Electromechanical wave imaging (EWI) is a quantitative echocardiography-based technique capable of noninvasively mapping cardiac electromechanical activation in three dimensions. The aim of this exploratory study was to investigate the EWI technique, sensitive to ventricular dyssynchrony, for informing CRT response on the day of implantation. Forty-four patients with heart failure with left bundle branch block or right ventricular (RV) paced rhythm and decreased left ventricular ejection fraction (LVEF; mean, 25.3±9.6%) underwent EWI without and with CRT within 24hours of device implantation. Of those, 16 were also scanned while in left ventricular (LV) pacing. Improvement in LVEF at 3-, 6-, or 9-month follow-up defined (1) super-responders (ΔLVEF≥20%), (2) responders (10%≤ΔLVEF<20%), and (3) nonresponders (ΔLVEF≤5%). Three-dimensionally rendered electromechanical maps were obtained under RV, LV, and biventricular CRT pacing conditions. Mean RV free wall and LV lateral wall activation times were computed. The percentage of resynchronized myocardium was measured by quantifying the percentage of the left ventricle activated within 120 msec of QRS onset. Correlations between percentage of resynchronized myocardium and type of CRT response were assessed. LV lateral wall activation time was significantly different (P≤.05) among all three pacing conditions in the 16 patients: LV lateral wall activation time with CRT in biventricular pacing (73.1±17.6 msec) was lower compared with LV pacing (89.5±21.5 msec) and RV pacing (120.3±17.8 msec). Retrospective analysis showed that the percentage of resynchronized myocardium with CRT was a reliable response predictor within 24hours of implantation for significantly (P≤.05) identifying super-responders (n=7; 97.7±1.9%) from nonresponders (n=17; 89.9±9.9%). Electromechanical activation mapping constitutes a valuable three-dimensional visualization tool within 24hours of implantation and could potentially aid in the timely assessment of CRT response rates, including during implantation for adjustment of lead placement and pacing outcomes.

The therapeutic effects of upgrade to cardiac resynchronization therapy in pacing-induced cardiomyopathy or chronic right ventricular pacing patients: a meta-analysis.

Pacing-induced cardiomyopathy (PICM) or heart failure accompanied with chronic right ventricular pacing (CRVP-HF) has no established treatments. We aimed to carry out a meta-analysis of published studies about the therapeutic effects of the upgrade to cardiac resynchronization therapy (CRT) in patients of PICM/CRVP-HF. The PUBMED, EMBASE, MEDLINE, OVID databases, and Cochrane Library were systemically searched for relevant publications. Data about the improvements of left ventricular ejection fraction (LVEF), NYHA functional class (NYHA-FC), and the CRT response rate was extracted and synthesized. Mean difference (MD), odds ratio, and standard mean difference (SMD) with 95% confidence interval (CI) were calculated as the effect size by both fixed and random effect models. We included sixteen studies (four about PICM and twelve about CRVP-HF). The total sample size of PICM/CRVP-HF patients was 924. Upgrade to CRT improved the LVEF by 10.87% (95%CI, 8.90 to 12.84%) and reduce the NYHA-FC by around one class (MD, -1.25; 95%CI, -1.43 to -1.06) in PICM/CRVP-HF patients overall. Upgrade to CRT seemed to improve LVEF no less than de-novo CRT (SMD 0.24; 95%CI 0.05 to 0.43; P<0.05). This meta-analysis suggested that upgrade CRT could improve the cardiac function in PICM/CRVP-HF patients. This strategy may be considered in these patients but require more evidence about the efficacy and procedure-related complications from prospective studies or randomized controlled trials.

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

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

Application and efficacy of the adjustment on left ventricular electrical delay and the distance between right and left ventricular pacing polar in optimizing the left ventricular pacing polar

Objective: To investigate the application and efficacy of left ventricular (LV) electrical delay (LVED) and the distance of right ventricular(RV) pacing polar to LV(DRLV) in optimizing LV pacing polar. Methods: Heart failure (HF) patients who implanted cardiac resynchronization therapy (CRT) device with a LV quadripolar lead from January 2014 to January 2018 at General Hospital of Northern Theater Command were enrolled in the study. Measurements of LVED and DRLV of each polar of the lead were performed in patients with HF who underwent CRT with LV quadripolar lead. The principle in turn for polar selecting used for clinical LV pacing was the pacing polar: (1)without phrenic nerve stimulation(PNS); (2)with appropriate capture threshold; (3)not located in apical; (4)with maximal LVED; (5)with maximal DRLV. The LV pacing polar was selected for CRT according to the procedure. The distribution of target veins implanted with LV quadripolar lead were calculated. The percentage of biventricular pacing at 6-month follow-up was recorded. The following indexes were compared before and 6-month after surgery, including QRS duration, LV end-systolic volume(LVESV), LV ejection fraction(LVEF), LV end-diastolic dimension(LVEDD), 6 minute walking distance(6MWD), New York Heart Association(NYHA) class. The efficacy and echocardiographic efficacy of CRT was evaluated. Results: There were twenty-nine HF patients enrolled. The mean age of enrolled patients was(61.7±7.6)years old, nineteen (66%)of them were male. There were seventeen(59%) patients diagnosed as dilated cardiomyopathy and twelve(41%) patients as ischemic cardiomyopathy. All patients were successfully implanted with LV quadripolar lead into target veins, and all four pacing sites were also in target veins. Target veins were located in lateral veins in 15 patients (52%), anterior veins in 2 patients (7%), posterior veins in 11 patients (38%), and lateral branches of great cardiac veins in 1 patient (3%). After 6-month of follow-up, the percentage of biventricular pacing was greater than 95%.There were nineteen(66%) patients optimized LV pacing polar by the largest LVED and four (14%) patients by the DRLV. Of the 29 patients, 5(17%) patients used D1 as the pacing polar, 5(17%) patients used M2 as the pacing polar, 7(24%) patients used M3 as the pacing polar, and 12(41%) patients used P4 as the pacing polar. The pacing polars (D1, M2) of traditional bipolar lead were used in 10(34%) patients, and the LV quadripolar lead specific pacing polars (M3, P4) were used in 19(66%) patients.Compared to a LV quadripolar lead, the LV pacing polar (M3, P4) selected in 19(66%) patients were not achievable with the traditional LV bipolar lead (D1, M2). Preoperative QRS duration, LVESV, LVEF, LVEDD, 6MWD and NYHA class were (171±24)ms, (231±79)ml, (28±5)%, (74±11)mm, (294±103)m, (3.2±1.0)class and the postoperative 6-month were (130±12)ms, (158±73)ml, (36±10)%, (66±12)mm, (371±86)m, (1.9±0.5)class. These indexes were significantly improved after 6 months operation(P<0.001). 97% and 83% patients were responders of CRT as assessed by 6-month efficacy and echocardiographic efficacy. Conclusion: The maximal LVED and DRLV can be used to select LV pacing polar with a high rate of CRT response rate.

Narrower QRS may be enough to respond to cardiac resynchronization therapy in lightweight patients

A prolonged QRS duration (QRSd) is promising for a response to cardiac resynchronization therapy (CRT). The variation in human body sizes may affect the QRSd. We hypothesized that conduction disturbances may exist in Japanese even with a narrow (< 130 ms)-QRS complex; such patients could be CRT candidates. We investigated the relationships between QRSd and sex and body size in Japanese. We retrospectively analyzed the values of 338 patients without heart failure (HF) (controls) and 199 CRT patients: 12-lead electrocardiographically determined QRSd, left ventricular diastolic and systolic diameters (LVDd and LVDs), body surface area (BSA), body mass index (BMI), and LVEF. We investigated the relationships between the QRSd and BSA, BMI, and LVD. The men’s and women’s BSA values were 1.74 m2 and 1.48 m2 in the controls (p < 0.0001), and 1.70 m2 and 1.41 m2 in the CRT patients (p < 0.0001). The men’s and women’s QRSd values were 96.1 ms and 87.4 ms in the controls (p < 0.0001), and 147.8 ms and 143.9 ms in the CRT group (p = 0.4633). In the controls, all body size and LVD variables were positively associated with QRSd. The CRT response rate did not differ significantly among narrow-, mid-, and wide-QRS groups (83.6%, 91.3%, 92.4%). An analysis of the ROC curve provided a QRS cutoff value of 114 ms for CRT responder. The QRSd appears to depend somewhat on body size in patients without HF. The CRT response rate was better than reported values even in patients with a narrow QRSd (< 130 ms). When patients are considered for CRT, a QRSd > 130 ms may not be necessary, and the current JCS guidelines appear to be appropriate.

An S wave in ECG lead V6 predicts poor response to cardiac resynchronization therapy and long-term outcome

Cardiac resynchronization therapy (CRT) is a standard treatment for selected patients with chronic heart failure(HF). However, up to 30%-50% of patients still do not respond to CRT. Our aim was to identify the predictive value of an S wave in lead V6 in CRT response in patients with complete left bundle branch block (CLBBB). The CLBBB definition included the Strauss left bundle branch block criteria and the absence of q waves in leads I, V5, and V6. According to the electrocardiogram at baseline, CLBBB patients were divided into 3 groups: T-CLBBB group (CLBBB without an S wave in lead V5 or V6), V5S group (CLBBB with an S wave in lead V5 and no S wave in lead V6), and V5&V6S group (CLBBB with S waves in leads V5 and V6). CRT response was defined as left ventricular end-systolic volume reduction ≥ 15% at 6-month follow-up. The combined end point included HF rehospitalization or all-cause death. Of 181 patients with left bundle branch block-like pattern, 112 patients with CLBBB were included into 3 groups: 54 in the T-CLBBB group, 32 in the V5S group, and 26 in the V5&V6S group. The CRT response rate was 85.2% (46), 65.6% (21), and 38.5% (10), respectively (P < .001). Kaplan-Meier curves demonstrated that patients in the V5&V6S group had a higher incidence of HF rehospitalization or all-cause death than those in the other 2 groups (P < .001). In a multivariate logistic regression model analysis, an S wave in lead V6 was significantly associated with CRT nonresponse (hazard ratio 0.33; 95% confidence interval 0.11-0.96; P = .042). An S wave in lead V6 can predict poor response to CRT and long-term outcome.