Electrical Reverse Remodeling of the Native Cardiac Conduction System after Cardiac Resynchronization Therapy.
ABSTRACT: Background: Little is known about electrical remodeling of the native conduction systems, particularly how the PR interval changes, after cardiac resynchronization therapy (CRT). We investigated the effects of CRT on the intrinsic PR interval (i-PRi) and QRS duration (i-QRSd). Methods and results: In 100 consecutive CRT recipients with sinus rhythm and long-term follow-up (>1 year), the i-PRi and i-QRSd were measured at baseline and at the last echocardiographic follow-up (33.4 ± 17.9 months) with biventricular pacing temporarily withdrawn. The relative decrease in the left ventricular end-systolic volume (LVESV) was measured to define CRT-responders (?15%) and super-responders (?30%). Following CRT, the left ventricular (LV) ejection fraction increased significantly (p < 0.001). In CRT-responders (n = 71), the LVESV and i-QRSd decreased markedly (170 ± 39 to 159 ± 24 ms, p = 0.012). However, the i-PRi was not shortened with CRT response and was actually likely to increase, even in the super-responder group (n = 33). Moreover, lengthening of the i-PRi was observed consistently irrespective of the CRT response status, beta-blocker use, or amiodarone use. CRT non-responders were associated with a remarkable PR prolongation (p = 0.005) and QRS widening (p = 0.001), along with positive ventricular remodeling. Conclusion: LV volume and i-QRSd decreased markedly with CRT response. However, the i-PRi was not shortened, but rather increased regardless of the degree of CRT response. CRT non-response was associated with a considerable increase in the i-PRi and i-QRSd, along with positive ventricular remodeling. CRT-induced electrical reverse remodeling might occur preferentially in the intraventricular, but not the atrioventricular, conduction system.
Project description:BACKGROUND:Although QRS duration (QRSd) is an important determinant of cardiac resynchronization therapy (CRT) response, non-responder rates remain high. QRS fragmentation can also reflect electrical dyssynchrony. We hypothesized that quantification of abnormal QRS peaks (QRSp) would predict CRT response. METHODS:Forty-seven CRT patients (left ventricular ejection fraction = 23±7%) were prospectively studied. Digital 12-lead ECGs were recorded during native rhythm at baseline and 6 months post-CRT. For each precordial lead, QRSp was defined as the total number of peaks detected on the unfiltered QRS minus those detected on a smoothed moving average template QRS. CRT response was defined as >5% increase in left ventricular ejection fraction post-CRT. RESULTS:Sixty-percent of patients responded to CRT. Baseline QRSd was similar in CRT responders and non-responders, and did not change post-CRT regardless of response. Baseline QRSp was greater in responders than non-responders (9.1±3.5 vs. 5.9±2.2, p = 0.001) and decreased in responders (9.2±3.6 vs. 7.9±2.8, p = 0.03) but increased in non-responders (5.5±2.3 vs. 7.5±2.8, p = 0.049) post-CRT. In multivariable analysis, QRSp was the only independent predictor of CRT response (Odds Ratio [95% Confidence Interval]: 1.5 [1.1-2.1], p = 0.01). ROC analysis revealed QRSp (area under curve = 0.80) to better discriminate response than QRSd (area under curve = 0.67). Compared to QRSd ?150ms, QRSp ?7 identified response with similar sensitivity but greater specificity (74 vs. 32%, p<0.05). Amongst patients with QRSd <150ms, more patients with QRSp ?7 responded than those with QRSp <7 (75 vs. 0%, p<0.05). CONCLUSIONS:Our novel automated QRSp metric independently predicts CRT response and decreases in responders. Electrical dyssynchrony assessed by QRSp may improve CRT selection and track structural remodeling, especially in those with QRSd <150ms.
Project description:Response to cardiac resynchronization therapy (CRT) is commonly assessed after 6 or 12 months. We evaluated subsequent echocardiographic changes, serial QRS duration, and clinical outcomes in patients showing delayed responses to CRT after 12 months.Among all patients who received CRT in Seoul St. Mary's Hospital, 36 one-year survivors were enrolled. Indicators of a positive CRT response were ≥ 15% reduction in left ventricular end-systolic volume (LVESV) or ≥ 10% increase in left ventricular ejection fraction (LVEF) on any follow up echocardiogram. We defined the early responders as patients responding before one year, the late responders as patients responding after one year, and the non-responders as patients who did not respond on any follow-up echocardiogram.We identified 17 early responders, 10 late responders, and 9 non-responders. The late responders showed modest improvement in LVESV and LVEF at two years after CRT. QRS duration was shortened the day after CRT in all three groups. Narrowed QRS was maintained for two years in early and late responders, whereas it was continuously prolonged over time in non-responders. Incidence of all-cause death or heart failure hospitalization was comparable between early and late responders, while non-responders showed worst prognosis.Patients responding to CRT after one year show modest echocardiographic improvement but clinical outcome is similar to early responders. Shorter baseline QRS duration and long-term maintenance of QRS duration shortening are important features of the late responders to CRT.
Project description:Background:Approximately 20-40% of recipients of cardiac resynchronization therapy (CRT) do not respond to it based on the current patient selection criteria. The purpose of this study was to identify baseline parameters that can predict CRT response and to evaluate the effect of those predictive parameters on long-term prognosis. Methods:This was a retrospective, nonrandomized, noncontrolled cohort study. Patients who received CRT in our centre were divided into responders and nonresponders by the definition of CRT response (an increase in left ventricular ejection fraction (LVEF) of ?5% and improvement of ?1 New York Heart Association (NYHA) class from baseline to the 6-month follow-up). Results:Of the 101 patients, 68 were responders and 33 were nonresponders. Left ventricular end-diastolic diameter (LVEDD; OR: 0.88, 95% CI: 0.81-0.95, P=0.001) and QRS duration (OR: 1.07, 95% CI: 1.04-1.10, P < 0.001) were independent predictors of CRT response. The combination of LVEDD and QRS duration was more valuable for predicting CRT response (AUC 0.836; 95% CI: 0.76-0.91; P < 0.001). Moreover, the combination of LVEDD???71?mm and QRS duration???170?ms had a low incidence of all-cause mortality, HF hospitalisation, and the composite endpoint. In addition, baseline LVEDD had a positive correlation with QRS duration (R=0.199, P=0.046). Responders to CRT had better LV reverse remodeling. Conclusion:The combination of LVEDD and QRS duration provided more robust prediction of CRT response. Moreover, the combination of LVEDD???71?mm and QRS duration???170?ms was associated with a low incidence of all-cause mortality, HF hospitalisation, and the composite endpoint. Our results may be useful to provide individualized patient selection for CRT.
Project description:Despite an intensive search for predictors of the response to cardiac resynchronization therapy (CRT), the QRS duration remains the simplest and most robust predictor of a positive response. QRS duration of???130 ms is considered to be a prerequisite for CRT; however, some studies have shown that CRT may also be effective in heart failure (HF) patients with a narrow QRS (<130 ms). Since CRT can now be performed by pacing the left ventricle from multiple vectors via a single quadripolar lead, it is possible that multipoint pacing (MPP) might be effective in HF patients with a narrow QRS. This article reports the design of the MPP Narrow QRS trial, a prospective, randomized, multicenter, controlled feasibility study to investigate the efficacy of MPP using two LV pacing vectors in patients with a narrow QRS complex (100-130 ms).Fifty patients with a standard ICD indication will be enrolled and randomized (1:1) to either an MPP group or a Standard ICD group. All patients will undergo a low-dose dobutamine stress echo test and only those with contractile reserve will be included in the study and randomized. The primary endpoint will be the percentage of patients in each group that have reverse remodeling at 12 months, defined as a reduction in left ventricular end-systolic volume (LVESV) of >15% from the baseline.This feasibility study will determine whether MPP improves reverse remodeling, as compared with standard ICD, in HF patients who have a narrow QRS complex (100-130 ms).ClinicalTrials.gov, NCT02402816 . Registered on 25 March 2015.
Project description:Cardiac resynchronization therapy (CRT) is associated with reverse left atrial (LA) remodeling. The aim of this meta-analysis was to assess the relationship between clinical response to CRT and LA function changes. We conducted a systematic search of all electronic databases up to September 2019 which identified 488 patients from seven studies. At (mean) 6 months follow-up, LA systolic strain and emptying fraction (EF) were increased in CRT responders, with a -5.70% weighted mean difference (WMD) [95% confidence interval (CI) -8.37 to -3.04, p < 0.001 and a WMD of -8.98% [CI -15.1 to -2.84, p = 0.004], compared to non-responders. The increase in LA strain was associated with a fall in left ventricle (LV) end-systolic volume (LVESV) r = -0.56 (CI -0.68 to -0.40, p < 0.001) and an increase in the LV ejection fraction (LVEF) r = 0.58 (CI 0.42 to 0.69, p < 0.001). The increase in LA EF correlated with the fall in LVESV r = -0.51 (CI -0.63 to -0.36, p < 0.001) and the increase in the LVEF r = 0.48 (CI 0.33 to 0.61, p = 0.002). The increase in LA strain correlated with the increase in the LA EF, r = 0.57 (CI 0.43 to 0.70, p < 0.001). Thus, the improvement of LA function in CRT responders reflects LA reverse remodeling and is related to its ventricular counterpart.
Project description:Cardiac resynchronization therapy (CRT) is an important treatment for heart failure. Low female enrollment in clinical trials means that current CRT guidelines may be biased toward males. However, females have higher response rates at lower QRS duration (QRSd) thresholds. Sex differences in the left ventricle (LV) size could provide an explanation for the improved female response at lower QRSd. We aimed to test if sex differences in CRT response at lower QRSd thresholds are explained by differences in LV size and hence predict sex-specific guidelines for CRT. We investigated the effect that LV size sex difference has on QRSd between male and females in 1093 healthy individuals and 50 CRT patients using electrophysiological computer models of the heart. Simulations on the healthy mean shape models show that LV size sex difference can account for 50-100% of the sex difference in baseline QRSd in healthy individuals. In the CRT patient cohort, model simulations predicted female-specific guidelines for CRT, which were 9-13 ms lower than current guidelines. Sex differences in the LV size are able to account for a significant proportion of the sex difference in QRSd and provide a mechanistic explanation for the sex difference in CRT response. Simulations accounting for the smaller LV size in female CRT patients predict 9-13 ms lower QRSd thresholds for female CRT guidelines.
Project description:BACKGROUND:QRS narrowing following cardiac resynchronization therapy with biventricular (BiV) or left ventricular (LV) pacing is likely affected by patient-specific conduction characteristics (PR, qLV, LV-paced propagation interval), making a universal programming strategy likely ineffective. We tested these factors using a novel, device-based algorithm (SyncAV) that automatically adjusts paced atrioventricular delay (default or programmable offset) according to intrinsic atrioventricular conduction. METHODS AND RESULTS:Seventy-five patients undergoing cardiac resynchronization therapy (age 66±11 years; 65% male; 32% with ischemic cardiomyopathy; LV ejection fraction 28±8%; QRS duration 162±16 ms) with intact atrioventricular conduction (PR interval 194±34, range 128-300 ms), left bundle branch block, and optimized LV lead position were studied at implant. QRS duration (QRSd) reduction was compared for the following pacing configurations: nominal simultaneous BiV (Mode I: paced/sensed atrioventricular delay=140/110 ms), BiV+SyncAV with 50 ms offset (Mode II), BiV+SyncAV with offset that minimized QRSd (Mode III), or LV-only pacing+SyncAV with 50 ms offset (Mode IV). The intrinsic QRSd (162±16 ms) was reduced to 142±17 ms (-11.8%) by Mode I, 136±14 ms (-15.6%) by Mode IV, and 132±13 ms (-17.8%) by Mode II. Mode III yielded the shortest overall QRSd (123±12 ms, -23.9% [P<0.001 versus all modes]) and was the only configuration without QRSd prolongation in any patient. QRS narrowing occurred regardless of QRSd, PR, or LV-paced intervals, or underlying ischemic disease. CONCLUSIONS:Post-implant electrical optimization in already well-selected patients with left bundle branch block and optimized LV lead position is facilitated by patient-tailored BiV pacing adjusted to intrinsic atrioventricular timing using an automatic device-based algorithm.
Project description:AIMS:Various strain parameters and multiple imaging techniques are presently available including cardiovascular magnetic resonance (CMR) tagging (CMR-TAG), CMR feature tracking (CMR-FT), and speckle tracking echocardiography (STE). This study aims to compare predictive performance of different strain parameters and evaluate results per imaging technique to predict cardiac resynchronization therapy (CRT) response. METHODS AND RESULTS:Twenty-seven patients were prospectively enrolled and underwent CMR and echocardiographic examination before CRT implantation. Strain analysis was performed in circumferential (CMR-TAG, CMR-FT, and STE-circ) and longitudinal (STE-long) orientations. Regional strain values, parameters of dyssynchrony, and discoordination were calculated. After 12 months, CRT response was measured by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). Twenty-six patients completed follow-up; mean LVESV change was -29 ± 27% with 17 (65%) patients showing ?15% LVESV reduction. Measures of dyssynchrony (SD-TTPLV ) and discoordination (ISFLV ) were strongly related to CRT response when using CMR-TAG (R2 0.61 and R2 0.57, respectively), but showed poor correlations for CMR-FT and STE (all R2 ? 0.32). In contrast, the end-systolic septal strain (ESSsep ) parameter showed a consistent high correlation with LVESV change for all techniques (CMR-TAG R2 0.60; CMR-FT R2 0.50; STE-circ R2 0.43; and STE-long R2 0.43). After adjustment for QRS duration and QRS morphology, ESSsep remained an independent predictor of response per technique. CONCLUSIONS:End-systolic septal strain was the only parameter with a consistent good relation to reverse remodelling after CRT, irrespective of assessment technique. In clinical practice, this measure can be obtained by any available strain imaging technique and provides predictive value on top of current guideline criteria.
Project description:BACKGROUND:Because 20% to 40% of patients undergoing cardiac resynchronization therapy (CRT) do not respond to it, identification of potential factors predicting response is a relevant research topic. HYPOTHESIS:There is a possible association between right ventricular function and response to CRT. METHODS:We analyzed 227 patients from the Cardiac Resynchronization Therapy Modular Registry (CRT-MORE) who received CRT according to current guidelines from March to December 2013. Response to therapy was defined as a decrease of ?15% in left ventricular end-systolic volume (LVESV) at 6 months. RESULTS:The tricuspid annular plane systolic excursion (TAPSE) value that best predicted improvement in LVESV (sensitivity 68%, specificity 54%) was 17 mm. Stratifying patients according to TAPSE, LVESV decreased ?15% in 78% of patients with TAPSE >17 mm (vs 59% in patients with TAPSE ?17 mm; P = 0.006). At multivariate analysis, TAPSE >17 mm was independently associated with LVESV improvement (odds ratio: 1.97, 95% confidence interval: 1.03-3.80, P < 0.05), together with ischemic etiology (odds ratio: 0.39, 95% confidence interval: 0.20-0.75, P < 0.01). These results were confirmed for New York Heart Association class III to IV patients (79% echocardiographic response rate in patients with TAPSE >17 mm vs 55% in patients with TAPSE <17 mm; P = 0.012). CONCLUSIONS:Baseline signs of right ventricular dysfunction suggest possible remodeling after CRT. A TAPSE value of 17 mm was identified as a good cutoff for predicting a better response to CRT in patients with both mildly symptomatic and severe heart failure.
Project description:Patients with non-ischemic heart failure etiology and left bundle branch block (LBBB) show better response to cardiac resynchronization therapy (CRT). While these patients have the most pronounced left ventricular (LV) dyssynchrony, LV dyssynchrony assessment often fails to predict outcome. We hypothesized that patients with favorable outcome from CRT can be identified by a characteristic strain distribution pattern.From 313 patients who underwent CRT between 2003 and 2006, we identified 10 patients who were CRT non-responders (no LV end-systolic volume [LVESV] reduction) with non-ischemic cardiomyopathy and LBBB and compared with randomly selected CRT responders (n = 10; LVESV reduction ≥15%). Longitudinal strain (εlong) data were obtained by speckle tracking echocardiography before and after (9 ± 5 months) CRT implantation and standardized segmental εlong-time curves were obtained by averaging individual patients.In responders, ejection fraction (EF) increased from 25 ± 9 to 40 ± 11% (p = 0.002), while in non-responders, EF was unchanged (20 ± 8 to 21 ± 5%, p = 0.57). Global εlong was significantly lower in non-responders at pre CRT (p = 0.02) and only improved in responders (p = 0.04) after CRT. Pre CRT septal εlong -time curves in both groups showed early septal contraction with mid-systolic decrease, while lateral εlong showed early stretch followed by vigorous mid to late contraction. Restoration of contraction synchrony was observed in both groups, though non-responder remained low amplitude of εlong.CRT non-responders with LBBB and non-ischemic etiology showed a similar improvement of εlong pattern with responders after CRT implantation, while amplitude of εlong remained unchanged. Lower εlong in the non-responders may account for their poor response to CRT.