Clinical Impact of Digitalis Therapy in a Large Multicenter Cohort of CRT-Recipients.

(1) Introduction: Digitalis use in patients with severe heart failure is controversial. We assessed the effects of digitalis therapy on mortality in a large, observational study in recipients of cardiac resynchronization therapy (CRT). (2) Methods: Consecutive patients receiving a CRT-defibrillator in three European tertiary referral centers were enrolled and followed-up for a mean 37 months ± 28 months. Digitalis use was assessed at the time of CRT implantation. A multivariate Cox-regression model and propensity score matching were used to determine all-cause mortality as the primary endpoint. CRT-response (defined as improvement of ≥1 NYHA class), echocardiographic improvement (defined as improvement of LVEF of ≥ 5%) and incidence of ICD shocks and rehospitalization were assessed as secondary endpoints in a subgroup of patients. (3) Results: The study comprised 552 CRT-recipients with standard indications, including 219 patients (40%) treated with digitalis. Compared to patients without digitalis, they had more often atrial fibrillation, poorer LVEF and a higher NYHA class (all p ≤ 0.002). Crude analysis of all-cause mortality demonstrated a similar relative risk of death for patients with and without digitalis (HR = 1.14; 95% CI 0.88-1.5; p = 0.40). After adjustment for independent predictors of mortality, digitalis therapy did not alter the risk for death (adjusted HR = 1.04; 95% CI 0.75-1.45; p = 0.82). Furthermore, in comparison to 286 propensity-score-matched patients, mortality was not affected by digitalis intake (propensity-adjusted HR = 1.11; 95% CI 0.72-1.70; p = 0.64). A CRT-response was predominant in digitalis non-users, concerning both improvement of HF symptoms and LVEF (NYHA p < 0.01; LVEF p < 0.01), while patients on digitalis had more often ventricular tachyarrhythmias requiring ICD shock (p = 0.01); although, rehospitalization for cardiac reasons was significantly lower among digitalis users compared to digitalis non-users (HR = 0.58; 95% C. I. 0.40-0.85; p = 0.01). (4) Conclusions: Digitalis therapy had no effect on mortality, but was associated with a reduced response to CRT and increased susceptibility to ventricular arrhythmias requiring ICD shock treatment. Although, digitalis administration positively altered the likelihood for cardiac rehospitalization during follow-up.

Cardiac resynchronization therapy for pacing induced cardiomyopathy: Role of baseline right ventricular pacing burden.

BACKGROUND: Cardiac resynchronization therapy (CRT) is indicated for patients with heart failure with reduced left ventricular ejection fraction (LVEF) and chronic right ventricular (RV) pacing burden ≥40% (pacing-induced cardiomyopathy, PICM). It is uncertain whether baseline RV pacing burden impacts response to CRT. METHODS: We conducted a retrospective study of all CRT upgrades for PICM at our hospital from January 2017 to December 2018. Univariate and multivariable-adjusted changes in LVEF, and echocardiographic response (≥10% improvement in LVEF) at 3-12 months post-CRT upgrade were compared in those with RV pacing burden ≥90% versus <90%. RESULTS: We included 75 patients (age 74 ± 11 years, 71% male) who underwent CRT upgrade for PICM. The baseline RV pacing burden was ≥90% in 56 patients (median 99% [IQR 98%-99%]), and <90% in 19 patients (median 79% [IQR 73%-87%]). Improvement in LVEF was greater in those with baseline RV pacing burden ≥90% versus <90% (15.7 ± 9.3% vs. 7.5 ± 9.6%, p = .003). Baseline RV pacing burden ≥90% was a strong predictor of an improvement in LVEF ≥10% after CRT upgrade both in univariate and multivariate-adjusted models (p = .005 and .02, respectively). CONCLUSION: A higher baseline RV pacing burden predicts a greater improvement in LVEF after CRT upgrade for PICM.

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 > 18 years 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 3 months. 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.

Comparative efficacy of image-guided techniques in cardiac resynchronization therapy: a meta-analysis.

BACKGROUND: Several studies have illustrated the use of echocardiography, magnetic resonance imaging, and nuclear imaging to optimize left ventricular (LV) lead placement to enhance the response of cardiac resynchronization therapy (CRT) in heart failure patients. We aimed to conduct a meta-analysis to determine the incremental efficacy of image-guided CRT over standard CRT. METHODS: We searched PubMed, Cochrane library, and EMBASE to identify relevant studies. The outcome measures of cardiac function and clinical outcomes were CRT response, concordance of the LV lead to the latest sites of contraction (concordance of LV), heart failure (HF) hospitalization, mortality rates, changes of left ventricular ejection fraction (LVEF), and left ventricular end-systolic volume (LVESV). RESULTS: The study population comprised 1075 patients from eight studies. 544 patients underwent image-guided CRT implantation and 531 underwent routine implantation without imaging guidance. The image-guided group had a significantly higher CRT response and more on-target LV lead placement than the control group (RR, 1.33 [95% CI, 1.21 to 1.47]; p < 0.01 and RR, 1.39 [95% CI, 1.01 to 1.92]; p < 0.05, respectively). The reduction of LVESV in the image-guided group was significantly greater than that in the control group (weighted mean difference, - 12.46 [95% CI, - 18.89 to - 6.03]; p < 0.01). The improvement in LVEF was significantly higher in the image-guided group (weighted mean difference, 3.25 [95% CI, 1.80 to 4.70]; p < 0.01). Pooled data demonstrated no significant difference in HF hospitalization and mortality rates between two groups (RR, 0.89 [95% CI, 0.16 to 5.08]; p = 0.90, RR, 0.69 [95% CI, 0.37 to 1.29]; p = 0.24, respectively). CONCLUSIONS: This meta-analysis indicates that image-guided CRT is correlated with improved CRT volumetric response and cardiac function in heart failure patients but not with lower hospitalization or mortality rate.

Feasibility of intraprocedural integration of cardiac CT to guide left ventricular lead implantation for CRT upgrades.

BACKGROUND: Optimal positioning of the left ventricular (LV) lead is an important determinant of cardiac resynchronization therapy (CRT) response. OBJECTIVE: Evaluate the feasibility of intraprocedural integration of cardiac computed tomography (CT) to guide LV lead implantation for CRT upgrades. METHODS: Patients undergoing LV lead upgrade underwent ECG-gated cardiac CT dyssynchrony and LV scar assessment. Target American Heart Association segment selection was determined using latest non-scarred mechanically activating segments overlaid onto real-time fluoroscopy with image co-registration to guide optimal LV lead implantation. Hemodynamic validation was performed using a pressure wire in the LV cavity (dP/dtmax) ). RESULTS: 18 patients (male 94%, 55.6% ischemic cardiomyopathy) with RV pacing burden 60.0 ± 43.7% and mean QRS duration 154 ± 30 ms underwent cardiac CT. 10/10 ischemic patients had CT evidence of scar and these segments were excluded as targets. Seventeen out of 18 (94%) patients underwent successful LV lead implantation with delivery to the CT target segment in 15 out of 18 (83%) of patients. Acute hemodynamic response (dP/dtmax ≥ 10%) was superior with LV stimulation in CT target versus nontarget segments (83.3% vs. 25.0%; p = .012). Reverse remodeling at 6 months (LV end-systolic volume improvement ≥15%) occurred in 60% of subjects (4/8 [50.0%] ischemic cardiomyopathy vs. 5/7 [71.4%] nonischemic cardiomyopathy, p = .608). CONCLUSION: Intraprocedural integration of cardiac CT to guide optimal LV lead placement is feasible with superior hemodynamics when pacing in CT target segments and favorable volumetric response rates, despite a high proportion of patients with ischemic cardiomyopathy. Multicentre, randomized controlled studies are needed to evaluate whether intraprocedural integration of cardiac CT is superior to standard care.

Intracardiac conduction time as a predictor of cardiac resynchronization therapy response: Results of the BIO|SELECT pilot study.

BACKGROUND: Quadripolar left ventricular (LV) leads are capable of sensing and pacing the left ventricle from 4 different electrodes, which may potentially improve patient response to cardiac resynchronization therapy (CRT). OBJECTIVE: We measured 3 different time intervals: right ventricular (RV)-sensed to LV-sensed during intrinsic rhythm (RVs-LVs), RV-paced to LV-sensed (RVp-LVs), and LV-paced to LV-sensed (LVp-LVs, between distal [LV1] and proximal pole on a quadripolar LV lead), and assessed their association with CRT response in terms of LV end-systolic volume (LVESV) and a composite benefit index (CBI) comprising LVESV, LV ejection fraction (LVEF), brain natriuretic peptide level, and NYHA class. METHODS: A CRT-defibrillator system with quadripolar LV lead was implanted in 196 patients (mean age 69 years, mean LVEF 30%, left bundle-branch block [LBBB] 58%). Conduction intervals were measured before hospital discharge. At baseline and 7-month follow-up, echocardiographic and other components of CBI were determined. RESULTS: The mean RVs-LV1s, RVp-LV1s, and LVp-LVs delays were 68 ± 38 ms, 132 ± 34 ms, and 99 ± 31 ms, respectively. From baseline to 7 months, LVESV decreased by 17.3% ± 28.6%. The RVs-LV1s interval correlated stronger with CBI (R2 = 0.12, P < .00001) than with LVESV change (R2 = 0.05, P = .006). In contrast, RVp-LV1s did not correlate and LVp-LVs correlated only weakly with CRT response. The subgroup of patients (44%) with LBBB and RVs-LV1s above the lower quartile (≥34 ms) showed the greatest response to CRT. CONCLUSION: The RVs-LVs interval during intrinsic rhythm is relevant for CRT success, whereas RVp-LVs and LVp-LVs intervals did not predict CRT response.

Acute correction of electromechanical dyssynchrony and response to cardiac resynchronization therapy.

AIMS: Echocardiographic measures of dyssynchrony at baseline have not demonstrated a good ability to predict response to cardiac resynchronization therapy (CRT). The purpose of this study was to determine if the acute correction of electromechanical dyssynchrony, assessed by the change in simple pulsed-Doppler measures, was related to CRT response at 6 months. METHODS AND RESULTS: Echocardiography was performed at baseline and at pre-discharge after CRT implantation. Intraventricular, interventricular, and atrioventricular dyssynchrony were evaluated by the left pre-ejection interval (LPEI), the interventricular mechanical delay, and the ratio of left ventricular filling time to RR interval, respectivelxy. A patient was considered responder if he/she was alive without hospitalization for heart failure and had an absolute increase of left ventricular ejection fraction (LVEF) >5 points. Forty-eight patients (mean age 67 ± 11 years, 73% male, mean LVEF 30 ± 5%) were included. CRT led to an acute correction of intraventricular and interventricular dyssynchrony but not to an acute correction of atrioventricular dyssynchrony. There were 31 (65%) responders at 6 months. Two factors were independently associated with CRT response in multivariate analysis: ischemic cardiomyopathy (odds ratio 0.19, 95% confidence interval 0.04-0.87; P= 0.032) and delta LPEI (odds ratio 1.03 per 1 ms decrease, 95% confidence interval 1.01-1.05; P = 0.007). By receiver operating characteristic analysis, the optimal cut-off value of delta LPEI was -16 ms. The proportion of responders in patients without ischemic cardiomyopathy and with a delta LPEI greater than -16 ms was 85%. CONCLUSIONS: Acute correction of intraventricular electromechanical dyssynchrony evaluated by the LPEI predicted CRT response at 6 months.

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.

Benchmarking Belgian CRT practice against the rest of Europe: insights from the ESC-CRT survey II.

This subanalysis of the Euro-CRT survey II specifically focus on Belgian practice for CRT implantation. It explores Belgian adherence with the guidelines but also benchmark CRT practice in Belgium against the other European countries. Overall, Belgian management of CRT implantation is performed with great agreement with guidelines. This report could be used to provide guidance for both practical and economical approaches.

Association of QRS narrowing with response to cardiac resynchronization therapy-a systematic review and meta-analysis of observational studies.

Prolonged QRS duration, which reflects a higher degree of mechanical dysynchrony, is a predictor of response to CRT. However, the association of QRS narrowing after biventricular pacing with CRT response rates is not clear. Our aim was to conduct a systematic review and meta-analysis on the association between QRS narrowing after cardiac resynchronization therapy (CRT) and clinical and echocardiographic response to CRT in patients with heart failure. Two independent investigators searched MedLine and EMBASE databases through July 2018 without any limitations. Studies providing estimates (continuous data) on the association of QRS shortening with either clinical (defined as New York Heart Association (NYHA) reduction ≥ 1) or echocardiographic (defined as left ventricular end-systolic volume (LVESV) reduction ≥ 15%) response to CRT were finally included in the quantitative synthesis. We included 32 studies (14 studies (1274 patients mean age 64 years old, males 79.3%) using clinical CRT response and 18 studies (1270 patients, mean age 64 years old, males 69.1%) using echocardiographic CRT response). A significant association between QRS narrowing and shorter attained QRS duration with clinical and echocardiographic CRT response was observed. The observed association was independent of the timing of QRS width measurement after CRT implantation. Acute and late improvement of electrical dysynchrony as depicted by QRS narrowing following biventricular pacing is associated with clinical and echocardiographic response to CRT. However, large prospective studies are needed to further examine our findings.

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

BACKGROUND: 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. OBJECTIVE: 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). METHODS: 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. RESULTS: 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). CONCLUSION: An S wave in lead V6 can predict poor response to CRT and long-term outcome.

The Evolving Role of Electrocardiography in Cardiac Resynchronization Therapy.

PURPOSE OF REVIEW: This study aims to summarize the literature on the role of electrocardiography (ECG) in (i) patient selection for cardiac resynchronization therapy (CRT), (ii) predicting clinical response after CRT system is implanted, and (iii) optimizing CRT programming. RECENT FINDINGS: Progress has been made in interpreting ECG beyond QRS duration and left bundle branch (LBBB) morphology to select patients for CRT. We now understand a higher chance of response to CRT in patients with atypical right bundle branch block and lower response rates in subgroups with atypical LBBB. QRS area has emerged as a novel marker to quantify baseline electrical dyssynchrony to improve patient selection. After CRT, the resultant QRS narrowing remains the most validated predictor of long-term favorable outcome. There is increasing awareness of prolonged left ventricular pacing latency hindering the desired response to CRT. There is active interest in using ECG beyond minimizing QRS duration to optimize CRT programming for maximal resynchronization. Novel strategies include fusion of paced and/or conducted wavefronts and minimization of paced QRS area. ECG remains the ubiquitous method for ventricular electrical mapping in context of CRT. The role of ECG in elucidating baseline electrical dyssynchrony to aptly select patients for this treatment continues to evolve, and ECG is increasingly being evaluated as a reliable endpoint for optimal CRT programming.

Biomarkers to predict the response to cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is an established non-pharmacological treatment for selected heart failure patients with wide QRS duration. However, there is a persistent number of non-responders throughout. The prediction of the CRT response is paramount to adequately select the correct patients for CRT. One of the expanding fields of research is the development of biomarkers that predict the response to CRT. A review of the available literature on biomarkers in CRT patients has been performed to formulate a critical appraisal of the available data. The main conclusion of our review is that biomarker research in this patient population is very fragmented and broad. This results in the use of non-uniform endpoints to define the CRT response, which precludes an in-depth comparison of the available data. To improve research development in this field, a uniform definition of the CRT response and relevant endpoints is necessary to better predict the CRT response.

Multipoint left ventricular pacing improves response to cardiac resynchronization therapy with and without pressure-volume loop optimization: comparison of the long-term efficacy of two different programming strategies.

PURPOSE: Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP]) improves long-term LV reverse remodeling, though questions persist about how to program LV pacing vectors and delays. We evaluated if an empirical method of programming MPP vectors and delays between pacing pulses improved CRT response similar to pressure-volume loop (PVL) optimized MPP programming. METHODS: Patients undergoing CRT implant (Quadra Assura MP™ CRT-D and Quartet™ LV lead) received MPP with programmed settings optimized either by PVL measurements at implant (PVL-OPT group) or empirically determined by maximizing the spatial separation between the two cathodes and minimal delays between the three ventricular pacing pulses (MAX-SEP group). CRT response was prospectively defined as a reduction in end-systolic volume (ESV) of ≥ 15% relative to baseline at 6 months as determined by a blinded observer. RESULTS: Patient characteristics at baseline (NYHA II-III, ejection fraction [EF] 27 ± 6%, QRS 151 ± 17 ms) were not significantly different between the PVL-OPT (n = 27) and MAX-SEP (n = 26) groups. During the follow-up period, there were no differences in the number of patients requiring reprogramming due to phrenic nerve stimulation or a high threshold for PVL-OPT vs. MAX-SEP (5/27 [19%] vs. 7/26 [27%], p = 0.53). After 6 months, ESV reduction, EF increase, and CRT response rate (RR) were similar for PVL-OPT vs. MAX-SEP (ESV - 20 ± 11 vs. - 22 ± 11%, p = 0.59; EF + 10 ± 4 vs. + 9 ± 7%, p = 0.53; RR 20/27 [74%] vs. 21/26 [81%], p = 0.74), while fewer patients in the PVL-OPT group experienced NYHA class reduction ≥ 2 (4/27 [15%] vs.15/26 [58%], p = 0.002). CONCLUSIONS: Both evaluated methods of MPP programming resulted in similar CRT outcomes. Empirical MPP programming by maximum spatial separation of LV cathodes may be an effective, simple, and non-invasive alternative to pressure-volume optimization.

Non-response to Cardiac Resynchronization Therapy.

PURPOSE OF REVIEW: Cardiac resynchronization therapy (CRT) is an effective treatment option for therapy-refractory mild to severe heart failure (HF) patients with reduced ejection fraction and left ventricular (LV) conduction delay. Multiple clinical trials have shown that CRT improves cardiac function and overall quality of life, as well as reduces HF hospitalizations, health care costs, and mortality. RECENT FINDINGS: Despite its effectiveness, the "non-response" rate to CRT is around 30%, remaining a major challenge that faces electrophysiologists and researchers. It has been recently suggested that the etiology of CRT non-response is multifactorial, and it requires a multifaceted approach to address it. In this focused review, we will summarize the definitions of CRT non-response, identify key factors for CRT non-response, and offer a simplified framework to address CRT non-response with the main goal of improving CRT outcomes.

Right heart function interacts with left ventricular remodeling after CRT: A pressure volume loop study.

BACKGROUND: Right ventricular (RV) dysfunction is recognized as a cardinal prognostic marker in systolic heart failure patients. Conflicting data exist on the interaction of RV function and left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). This prospective monocentric trial was set up to assess the predictive value of baseline RV function and corresponding RV-pulmonary artery (PA) coupling on LV reverse remodeling after CRT. METHODS: 110 patients with a CRT indication were prospectively enrolled. RV function and RV-PA interaction were analyzed at baseline using echocardiographic and invasive pressure-volume loop catheter approach. The primary endpoint was reverse LV remodeling (CRT-responder) defined as a reduction in LV end-systolic volume of ≥15% at 6 months. RESULTS: Responders had higher RV-PA coupling ratios (single-beat end-systolic elastance/PA elastance: Ees/Ea) at baseline, which corresponded to smaller RVs with better ejection fraction and lower afterload. After multivariate adjustment, the baseline Ees/Ea remained an independent predictor for LV response (OR 14.0 [1.5-130.8], p = 0.021). Normal coupling (Ees/Ea ≥ 1) was associated with higher responder rates (RR) (86%). Progressive uncoupling was associated with lower LV-RR (Ees/Ea ≤ 1-0.5: 57%, and Ees/Ea < 0.5: 32%, p < 0.001), corresponded with higher degrees of LV impairment and severity of mitral regurgitation, and was independently associated with an adverse outcome. CONCLUSIONS: A higher baseline RV-PA coupling, reflecting a lower degree of LV-induced pulmonary hypertension and secondary RV-dysfunction, is associated with an improved LV-reverse remodeling and is independently associated with better prognosis. The value of RV-PA ratio as potential guide for CRT patient selection warrants further investigation. Clinical Trial Registration - URL: http://www.drks.de. Unique Identifier: DRKS00011133.

Coronary sinus lead delay index for optimization of coronary sinus lead placement.

AIM: Optimization of coronary sinus (CS) lead position to the latest activated left ventricular (LV) area is important to increase cardiac resynchronization therapy (CRT) response. We aimed to detect the relationship between coronary sinus lead delay index (CSDI) and echocardiographic, electrocardiographic response to CRT treatment. METHODS: We prospectively included 137 consecutive patients with heart failure (HF) diagnosis, QRS ≥ 120 ms, left bundle branch block (LBBB), New York Heart Association score (NYHA) II-IV, LV ejection fraction (LVEF) <35% and scheduled for CRT (84 male, 53 female; mean age 65.1 ± 10.1 years). Echocardiographic CRT response was defined as ≥15% reduction in LV end-systolic volume (LVESV). CS lead sensing delay was calculated as the time interval from the onset of surface QRS wave to the onset of depolarization wave recorded from the CS lead by using the CS pacing lead as a bipolar electrode. CSDI was calculated by dividing the CS lead sensing delay by the QRS duration. RESULTS: LVESV reduction was associated with baseline QRS width (r = .257, p = .002), QRS narrowing (r = .396, p < .001), CSDI (r = .357, p < .001), and NT-proBNP (r = -0.213, p = .022) in bivariate analysis. In logistic regression analysis, CSDI was found to be only independent parameter for predicting significant LVESV reduction (Beta = 0.318, p < .001). CSDI was also found to be significantly associated with LVEF increase (r = .244, p = .004) and QRS narrowing (r = .178, p = .046). CONCLUSION: CSDI may be used as a marker to predict the favorable response to CRT. It may be useful to integrate CSDI to CRT implantation procedure in order to minimize nonresponders.

A Low-Normal Free Triiodothyronine Level Is Associated with Adverse Prognosis in Euthyroid Patients with Heart Failure Receiving Cardiac Resynchronization Therapy.

Thyroid dysfunction is prevalent in patients with heart failure (HF) and hypothyroidism is related to the adverse prognosis of HF subjects receiving cardiac resynchronization therapy (CRT). We aim to investigate whether low-normal free triiodothyronine (fT3) level is related to CRT response and the prognosis of euthyroid patients with HF after CRT implantation.One hundred and thirteen euthyroid patients who received CRT therapy without previous thyroid disease and any treatment affecting thyroid hormones were enrolled. All of patients were evaluated for cardiac function and thyroid hormones (serum levels of fT3, free thyroxine [fT4] and thyroid-stimulating hormone [TSH]). The end points were overall mortality and hospitalization for HF worsening. During a follow-up period of 39 ± 3 weeks, 36 patients (31.9%) died and 45 patients (39.8%) had hospitalization for HF exacerbation. A higher rate of NYHA III/IV class and a lower fT3 level were both observed in death group and HF event group. Multivariate Cox regression analyses disclosed that a lower-normal fT3 level (HR = 0.648, P = 0.009) and CRT response (HR = 0.441, P = 0.001) were both independent predictors of overall mortality. In addition, they were also both related to HF re-hospitalization event (P < 0.01 for both). Patients with fT3 < 3.00 pmol/L had a significantly higher overall mortality than those with fT3 ≥ 3.00 pmol/L (P = 0.027). Meanwhile, a higher HF hospitalization event rate was also found in patients with fT3 < 3.00 pmol/L (P < 0.001).A lower-normal fT3 level is correlated with a worse cardiac function an adverse prognosis in euthyroid patients with HF after CRT implantation.

Ventricular pacing site separation by cardiac computed tomography: validation for the prediction of clinical response to cardiac resynchronization therapy.

Cardiac Resynchronization Therapy (CRT) fails to provide benefit in up to one-third of patients. Maximizing the geographic separation of right and left ventricular pacing lead sites has been suggested as one way to improve response. Cardiac CT provides an opportunity to explore 3-dimensional inter-lead distance (ILD) measures for the prediction of CRT response. The objective of this study was to investigate associations between standardized measures of ILD by cardiac CT and echocardiographic response to CRT. Forty-two consecutive patients undergoing CRT had serial clinical and echocardiographic evaluations performed in addition to a post-procedural cardiac-gated CT with blinded measurement of direct and circumferential (via the myocardium) ILD measures. Clinical response to CRT, the primary clinical outcome, was defined as a ≥15% reduction in LVESV using echocardiography at 6-months. The mean age and ejection fraction was 63.6 ± 8.9 years and 25.2 ± 7.8%, respectively. The primary outcome occurred in 35 of 42 patients (83%). Both direct and circumferential CT-based ILD measures were associated with the primary outcome by univariate analysis. Receiver Operator Characteristic analysis identified Circumferential ILD to have the strongest predictive accuracy (AUC 0.78). Inter- and intra-observer reproducibility of CT-derived ILD measures was excellent. Circumferential ILD measures on cardiac CT are predictive of clinical response to CRT. Incorporation of these measures into the selection of optimal pacing targets, particularly from pre-procedural CT coronary vein imaging may be of therapeutic benefit and warrants further investigation.