Indication For Cardiac Resynchronization Therapy Research Articles

The role of fibrosis and inflammation for response and outcome prediction in candidates to cardiac resynchronization therapy: is response the right answer?

Abstract Background Cardiac resynchronization therapy (CRT) is an established treatment in selected patients suffering from heart failure with reduced ejection fraction (HFrEF). It has been proposed that myocardial fibrosis and inflammation could influence CRT "response" and outcome. Purpose Our study investigated the long-term prognostic significance of cardiac biomarkers in HFrEF patients with an indication for CRT. Methods 86 consecutive patients referred for CRT implantation were retrospectively evaluated. The soluble suppression of tumorigenicity 2 (sST2), galectin-3 (Gal-3), N-terminal portion of the B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR) were measured at baseline and after 1 year of follow-up. An echocardiographic reduction of LV end-systolic volume ≥15% was used to define a patient as responder to CRT. Multivariate analyses were performed to evaluate their correlation with the primary composite outcome of cardiovascular mortality and heart failure hospitalizations at a mean follow-up of 9 ± 2 years. Results 44% of patients experienced the primary outcome. the mean baseline values of NT-proBNP, Gal-3, and sST2 were significantly higher compared with the patients without cardiovascular events. At the multivariate analyses, baseline Gal-3 [cut-off: 38.5 ng/ml, AUC: 0.63, p=0.03, (OR 7.13 [1.12;45.41], p=0.03), together with TAPSE>17.5 mm (OR 10.86 [3.15;37.44], p<0.001) significantly correlated with the structural response to CRT in several prediction models. Baseline Gal-3 [cut-off: 16.6 ng/ml, AUC: 0.91, p<0.001, HR 8.33 (1.88–33.33), p = 0.005] and sST2 [cut-off: 35.6 ng/ml AUC: 0.91, p<0.001, HR 333 (250–1,000), p = 0.003] significantly correlated with the composite outcome in the prediction models with high likelihood (Table). At Kaplan-Meyer curve patients with both high baseline sST2 and Gal-3 had the lowest survival probability (Figure). Among the parameters evaluated at 1-year follow-up, sST2, eGFR, and the variation from baseline to 1-year of Gal-3 levels showed a strong association with the primary outcome [HR 1.15 (1.08–1.22), p < 0.001; HR: 0.84 (0.74–0.91), p = 0.04; HR: 1.26 (1.10–1.43), p ≤ 0.001, respectively]. Conversely, the echocardiographic definition of CRT response did not correlate with any outcome. Conclusion In HFrEF patients with CRT, sST2, Gal-3, and renal function were associated with the combined endpoint of cardiovascular death and HF hospitalizations at long term follow-up, while the echocardiographic CRT response did not seem to influence the outcome of the patients.

Prospective assessment of risk factors for appropriate ICD intervention in patients with ischemic cardiomyopathy: results of PARCADIA trial

Abstract Background There is still a big unmet need for better risk stratification tools to identify patients at high risk for sudden cardiac death in the era of primary prevention ICD therapy. Scar burden on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging may be a risk marker for the prediction of ventricular arrhythmia in post-myocardial infarction (MI) patients. Purpose The aim of the PARCADIA trial was to assess whether scar characteristics, determined via LGE-CMR, or other baseline risk markers are associated with appropriate ICD therapy. Methods In this prospective, multi-center, clinical trial, we enrolled post-MI patients with an indication for de novo primary prevention ICD. Main exclusion criteria were indication for cardiac resynchronization therapy and NYHA class IV. Prior to the ICD implantation, LGE-CMR was performed to analyze the amount of scar tissue (LGE core mass + grey zone mass) and LV function / volumes. A 24h Holter recording was performed to collect information on potential triggers like premature ventricular beats (PVB) and sympathetic-vagal balance based on heart rate variability (HRV). Follow-ups were performed in-office every 6 months, including remote monitoring. Appropriate ICD therapy was used as primary endpoint and adjudicated by a clinical event committee. Results 199 patients were enrolled at 5 investigational sites in Europe. Patients mean age was 64.3 years, with a mean LVEF of 27.7 %, timing from the index MI was 9.1 years, and 42.7% received a primary PCI on index MI. After a median follow-up duration of 47.7 months, 23.1% of patients received appropriate ICD therapy. In 135 patients (67.8%), quality of LGE-CMR was sufficient for detailed analysis. The mean LGE core mass (20.5 vs. 19,7 g) and grey zone mass (10.5 vs. 11.4 g) was not different in patients with or without appropriate ICD therapy, also not when corrected for LV mass. However, LVEF (28.5 vs. 32.9 %) was lower, while diastolic myocardial mass (141 vs. 125 g), and end-diastolic volume (265.0 vs. 226.7 ml) were significantly higher in patients with appropriate ICD therapy. On 24h Holter the mean PVB burden (3695 vs. 1643 beats), and non-sustained ventricular tachycardia (12 vs. 0.9), were higher in patients with appropriate ICD therapy, while the HRV (96.1 vs. 113.1 SDNN) was lower. In univariate analysis the variables LVEF, timing to index MI, primary PCI on index MI, PVB burden and HRV appeared to be predictors for appropriate ICD intervention, while in multivariate analysis LVEF and PVB burden remained predictive. Conclusion In post-MI patients with appropriate ICD therapy, scar burden was not different from patients without appropriate ICD therapy. Only LVEF and PVB burden were independent predictors of increased arrhythmogenicity. Improved CMR analysis on scar characteristics (conduction channels) to identify potential arrhythmogenic regions might be the topic for future research.

Comparison of acute hemodynamic effect of prioritizing ventricular resynchronization vs left ventricular filling during optimization of cardiac resynchronization therapy

BackgroundTargeting maximal ventricular resynchronization, with the shortest QRS duration (QRSd), is commonly implemented after cardiac resynchronization therapy (CRT). ObjectiveThe purpose of this study was to compare optimization of ventricular resynchronization with optimization of left ventricular (LV) filling during CRT by measuring their acute hemodynamic effects. MethodsPatients with standard CRT indications, recruited from 2 centers, underwent biventricular pacing (BVP) and left bundle branch pacing (LBBP). We performed a within-patient comparison of acute hemodynamic response of systolic blood pressure (SBP) at the atrioventricular delay (AVD) with the shortest QRSd against the AVD with the most efficient LV filling. In a validation substudy, we also performed electrical assessment using QRS area (QRSa) and hemodynamic assessment with the maximum rate of LV pressure rise (dP/dtmax). ResultsThirty patients (age 65 ± 10 years; 53% male) were recruited. The AVD producing maximal ventricular resynchronization was associated with a significantly shorter QRSd (difference 15 ± 12 ms for BVP and 18 ± 13 ms for LBBP, both P <.01) and a significantly smaller improvement in SBP (difference −3 ± 4 mm Hg for BVP and −2 ± 2 mm Hg for LBBP, both P <.01) compared with the AVD that optimized filling. Similar findings were observed in the substudy, with a significantly smaller improvement in dP/dtmax assessed with QRSd and QRSa (difference −9% ± 7% and −6% ± 4% during BVP, and −5% ± 6% and −3% ± 3% during LBBP, all P <.01). ConclusionTargeting the maximal ventricular resynchronization results in suboptimal acute hemodynamic performance with both BVP and LBBP as CRT. These findings support prioritizing LV filling when programming AVD for CRT.

A predictive model of super response to cardiac resynchronization therapy in short-term period.

The left bundle branch block, nonischemic heart failure (HF) and female gender are the most powerful predictors of a super response to cardiac resynchronization therapy (CRT). It is important to identify super responders who can derive most benefits from CRT. We aimed to establish a predicting model that could be used for prognosis of a super response to CRT in short-term period. Patients with QRS ≥ 130ms, New York Heart Association (NYHA) II-III class of HF, left ventricle ejection fraction (LVEF) ≤ 35% and indications for CRT were included in the study. Before and 6month after CRT the electrocardiography, echocardiography and cardiac scintigraphy were performed. The study's primary endpoint was the NYHA class improvement ≥ 1 and left ventricle end systolic volume decrease > 30% or LVEF improvement > 15% after 6month CRT. Based on collected data, we developed a predictive model regarding a super response to CRT. Of 49 (100.0%) patients, 32 (65.3%) had a super response to CRT. Patients with a super response were likelier to have a lower cardiac index (p = 0.007), higher rates of interventricular delay (IVD) (p = 0.003), phase standard deviation of left ventricle anterior wall (PSD LVAW) (p = 0.009) and ∆QRS (p = 0.02). Only IVD and PSD LVAW were independently associated with a super response to CRT in univariate and multivariate logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.812 (sensitivity 90.62%; specificity 70.59%). Our predictive model is able to distinguish patients with a super response to CRT.

Predictors of failed left bundle branch pacing implant in heart failure with reduced ejection fraction: Importance of left ventricular diameter and QRS morphology

BackgroundLeft bundle branch pacing (LBBP) is considered an alternative to cardiac resynchronization therapy (CRT). However, LBBP is not suitable for all patients with heart failure. ObjectiveThe aim of our study was to identify predictors of unsuccessful LBBP implantation in CRT candidates. MethodsA cohort of consecutive patients with indications for CRT were included. Clinical, echocardiographic, and electrocardiographic variables were prospectively recorded. ResultsA total of 187 patients were included in the analysis. LBBP implantation was successful in 152 of 187 patients (81.2%) and failed in 35 of 187 patients (18.7%). The causes of unsuccessful implantation were unsatisfactory paced QRS morphology (28 of 35 [80%]), inability to screw the helix (4 of 35 [11.4%]), lead instability (2 of 35 [5.7%]), and high pacing thresholds (1 of 35 [2.8%]). The left ventricular end-diastolic diameter (LVEDD), non-LBBB (left bundle branch block) QRS morphology, and QRS width were predictors of failed implantation according to the univariate analysis. According to the multivariate regression analysis, LVEDD (odds ratio 1.31 per 5-mm increase; 95% confidence interval 1.05–1.63 per 5-mm increase; P = .02) and non-LBBB (odds ratio 3.07; 95% confidence interval 1.08–8.72; P = .03) were found to be independent predictors of unsuccessful LBBP implantation. An LVEDD of 60 mm has 60% sensitivity and 71% specificity for predicting LBBP implant failure. ConclusionWhen LBBP was used as CRT, LVEDD and non-LBBB QRS morphology predicted unsuccessful implantation. Non-LBBB triples the likelihood of failed implantation independent of LVEDD. Caution should be taken when considering these parameters to plan the best pacing strategy for patients.

Implant failure predictors of left bundle branch pacing used as cardiac resynchronization therapy: importance of left ventricular diameter and QRS morphology

Abstract Background Left bundle branch pacing (LBBP) is considered an alternative to cardiac resynchronization therapy (CRT). However, LBBP is not suitable for all heart failure patients. Purpose The aim of our study was to identify predictors of unsuccessful LBBP implantation in CRT candidates. Methods A cohort of consecutive patients with indications for CRT were included. Clinical, echocardiography and electrocardiographic variables were prospectively recorded. Results A total of 157 patients were included in the analysis. The LBBP implant was successful in 129/157 (82.2%) patients, and the implant failed in 28/157 patients (17.8%). The causes of failed implantation were as follows: unsatisfactory paced QRS (21/28; 75%); impossibility of screwing the helix (4/28; 14.3%); lead instability (2/28; 7.1%); and high pacing thresholds (1/28; 3.6%). Left ventricular end diastolic diameter (LVEDD), nonspecific intraventricular conduction delay morphology (IVCD), and QRS width were predictors of failed implants according to the univariate analysis. In a multivariable regression analysis, LVEDD [OR 1.44 per 5 mm increase (95% CI 1.13, 1.82) p=0.003] and IVCD [OR 2.96 (95% CI 0.74, 11.84) p=0.09] were independent predictors of unsuccessful LBBP implantation. An LVEDD of 60 mm has 75% sensitivity and 67% specificity to predict LBBP implant failure. Conclusions When LBBP was used as CRT, LVEDD and IVCD predicted unsuccessful implantation. IVCD triples the possibility of failed implantation independently of LVEDD. Caution should be exercised when considering these parameters to plan the best pacing strategy in patients.

Absence of late gadolinium enhancement and outcomes of cardiac resynchronization therapy in non-ischemic dilated cardiomyopathy

Abstract Background Among patients with non-ischemic dilated cardiomyopathy (DCM) with indication for cardiac resynchronization therapy (CRT), there are no clear recommendations about who should receive a CRT-defibrillator (CRT-D) and who should have CRT-pacemaker (CRT-P). Absence of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has a high negative predictive value for ventricular arrhythmias (VA) and sudden death (SD) in DCM and is a predictor of reverse remodelling in several scenarios. Purpose To evaluate the association between absence of LGE and VA/SD or echocardiographic response to CRT in DCM patients treated with CRT. Methods Multicenter retrospective observational cohort study including consecutive DCM patients with de-novo CRT implant and with available CMR. The primary endpoints were: 1) a combined arrhythmic endpoint including appropriate defibrillator therapies, sustained VA and sudden death. 2) echocardiographic response to CRT, intended as an increase ≥10% in left ventricular ejection fraction (LVEF). Results We included 167 patients, 55% males, with median QRS duration of 160ms and median LVEF of 25%. LGE was present in 46% of cases (LGE+). A CRT-D was implanted in 73% of patients. Median follow-up was 63 months. Of note, among patients without LGE (LGE-) we did not record any event of the combined arrhythmic endpoint. The cumulative incidence of the arrhythmic endpoint was significantly higher in LGE+ than in LGE- patients (25% vs 0%, p&amp;lt;0.001) and LGE was an independent predictor of this endpoint (adjusted HR 42, p&amp;lt;0.001). The proportion of responders to CRT was significantly higher in LGE- than in LGE+ cases (81% vs 53%, p&amp;lt;0.001); absence of LGE was the strongest predictor of echocardiographic response to CRT at multivariate analysis (adjusted OR 4.1, p=0.001). Super-responders (i.e. those with LVEF≥50% at follow-up) were also more frequent among LGE- than LGE+ patients (46% vs 21%, p=0.001) and absence of LGE was an independent predictor of LVEF normalization (HR 2.6, p=0.03). Conclusions Among DCM patients who receive CRT, those without LGE have an extremely low (or null in this case) arrhythmic risk and, at the same time, they have a high probability of echocardiographic response to CRT. Thus, LGE- patients could be ideal candidates for CRT-P instead of CRT-D.

ECG imaging as a real time tool to guide left bundle branch pacing implant in patients with left bundle branch block and resynchronization therapy indication

Abstract Background Left bundle branch pacing (LBBP) has emerged as a promising alternative technique for cardiac resynchronization therapy (CRT). ECG imaging (ECGI) may provide an accurate assessment of electrical resynchronization using real-time maps during LBBP implant. Purpose To evaluate the usefulness of ECGI to guide LBBP implant, by analyzing the ventricular activation times and the degree of resynchronization at each screwing step during the lead implant. Methods Four patients with CRT indication and left bundle branch block (LBBB) referred for LBBP were prospectively enrolled. ECGI was performed during the implant procedure. Cardiac signals were recorded using ECGI and projected into an artificial intelligence-derived geometric model. Thus, generating imageless and non-invasive activation maps at defined stages during lead screwing: basal rhythm (LBBB), right ventricular (RV) septum, mid-septal, deep-septal, and finally pacing from the left bundle branch (according with guidelines ECG criteria). The following parameters were measured: a) total activation time (TAT); b) left ventricular activation time (LVAT); c) left ventricular dyssynchrony index (LVDI) (as a quantifier of intraventricular dyssynchrony); d) ventricular electrical uncoupling (VEU); and e) histogram overlap between LV and RV distribution (the last 2 markers of interventricular dyssynchrony). Results The study cohort comprised men with a median age of 68 [Q1 59- Q3 79], with a median basal LBBB QRS duration of 175 ms [160-188] and a median LVEF of 32% [28-39]. A shortening of the activation times and a decrease in intra and interventricular dyssynchrony was achieved when the final lead position was reached. See the results in Figure 2. Conclusion Real-time and imageless ECGI system may offer a novel approach for guiding LBBP and it is useful to ensure left ventricular resynchronization.ECGI to guide LBBP implantActivation and dyssynchrony measurements

Left-ventricular-only cardiac resynchronization therapy with electrocardiographic optimization: 100-day follow-up

Abstract Background LV-only (LVo) cardiac resynchronization therapy (CRT) was recognized in 2013 as a non-inferior alternative to bi-ventricular (biV) CRT [1]. In a triple-chamber device it can extend service life, reduce atrial fibrillation risk. A number of LVo systems have been proposed but have not been shown to be superior to biV [2] due to a lack of individualized optimization of the LV atrio-ventricular delay. Purpose An LVo algorithm with an electrocardiographic optimization for each patient along general principles was developed and successfully implanted in a dozen patients with triple-chamber devices. The algorithm has been reported earlier. Since the RV lead is redundant, a dual chamber CRT (dcCRT) version was developed, with just the RA and LV leads. A preliminary series of 8 dcCRT implants were performed with good results. Methods A 2-week training class on LV lead implantation was held in July 2023. Fourteen dcCRT’s were implanted. Inclusion criteria: CRT indications, Left-bundle-branch block, good A-RV conduction, mostly sinus rhythm. 100-day follow-ups were performed on 15 patients (including 2 earlier patients) and reported here. Results In Fig.1 Implant LVEFs (Simpson): 16% to 38%. At the 100-day follow-ups, the LVEFs range from 24% to 62%. 6 (40%) remained below LVEF 35%, 9 (60%) exceeded the 35% threshold, 3 (20%) exceeded 45%, including 2 (13%) with 56% and 62%. Only 3 patients with small 2-3% LVEF improvements. All others were &amp;gt;5%, up to 29%. Since the devices can measure thoracic impedance, Z, 1024 times/hour, with the hourly average combined for a daily average, the 100-day daily Z trends were analyzed. The implant and 100-day Z’s are plotted in Fig.2. Except for the 2 patients whose Z measurements were left off, the universal upward Z trend is an indication of improved LV blood flow in all patients, helping reduced excessive lung fluid. Z changes range from 14 to 34 Ohms. Of the 2 patients in Fig.1 with only 2% LVEF improvements, their Z improvements were meaningful 23 Ohms increases! The Z and LVEF trends indicate that the therapy had a 100% success. Conclusions The 100-day follow-ups of the ECG optimized LVo CRT of 15 patients with dcCRTs show results superior to what have been reported in previous biV studies, thanks to the ECG optimization. This indicates that this may be a superior alternative to biV CRT. While the study was done with dcCRT, it should be applicable to all triple chamber CRT (-P/-D) devices which can support LVo pacing. Unlike other CRT algorithms, if the device supports LVo, it can be applied. It is safe since the programming can be reverted to biV at any time! This opens the possibility for improving the health of current CRT patients and extending the service lives of their devices, in addition to improved de novo results. The dcCRT is no longer viable since bipolar LV leads have been discontinued in favor of quadripolar leads, but the results apply to all CRT systems.Fig 1. LVEF @ implant &amp; 100 dayFig 2. Thoracic Z @implant &amp; 100 day

Comparison of long-term risk of device-related complications between left bundle branch area pacing and biventricular pacing in candidates for resynchronization therapy

Abstract Introduction Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well established therapy in patients with reduced left ventricular ejection fraction (LVEF), heart failure, and wide QRS. Left bundle branch area pacing (LBBAP) has recently been shown to be a feasible and effective alternative to BVP. Comparative data on the risk of complications between LBBAP and BVP among CRT candidates are lacking. Purpose The aim of this study was to compare the long-term risk of device-related complications between LBBAP and BVP in a cohort of patients undergoing CRT. Methods Prospective, multicenter, observational study enrolling 668 consecutive patients (71.2±10.0 years, 52.2% male, 59.4% NYHA class &amp;gt;II), with LVEF ≤35% (mean 33.4±4.3%) who underwent BVP (n=560) or LBBAP (n=108) for the first time for Class I or II indications for CRT from January 2020 to June 2023 at 6 Italian centers. Propensity matching for baseline characteristics yielded 90 matched pairs. Rate and nature of device-related complications occurring during follow-up were prospectively collected and compared between the two groups. Results During a mean follow-up of 18 months, device-related complications were observed in 14 patients: 11 in BVP (12.2%), and in 3 in LBBAP (3.3%) (p=0.026). Compared to BVP patients, LBBAP patients showed a higher cumulative survival free from first device–related complication (Figure). Complications related to coronary sinus lead were most frequently observed in BVP patients (36.4% of all complications). The rate of overall lead-related complications was 6.7 and 2.2% in BVP and LBBAP patients, respectively (p=0.149). Conclusion LBBAP was associated with a lower long-term risk of device-related complications compared with BVP in patients with CRT indications.

A Comparison of the Association of Septal Scar Burden on Responses to LBBAP-CRT and BVP-CRT

BackgroundLeft bundle branch area pacing (LBBAP) is an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). However, despite the presence of left bundle branch block, whether cardiac substrate may influence the effect between the 2 strategies is unclear. ObjectivesThis study aims to assess the association of septal scar on reverse remodeling and clinical outcomes of LBBAP compared with BVP. MethodsWe analyzed patients with nonischemic cardiomyopathy who had CRT indications undergoing preprocedure cardiac magnetic resonance examination. Changes in left ventricular ejection fraction (LVEF) and echocardiographic response (ER) (≥5% absolute LVEF increase) were assessed at 6 months. The clinical outcome was the composite of all-cause mortality, heart failure hospitalization, or major ventricular arrhythmia. ResultsThere were 147 patients included (51 LBBAP and 96 BVP). Among patients with low septal scar burden (below median 5.7%, range: 0% to 5.3%), LVEF improvement was higher in the LBBAP than the BVP group (17.5% ± 10.9% vs 12.3% ± 11.8%; P = 0.037), with more than 3-fold increased odds of ER (OR: 4.35; P = 0.033). In high sepal scar subgroups (≥5.7%, range: 5.7%-65.9%), BVP trended towards higher LVEF improvement (9.2% ± 9.4% vs 6.4% ± 12.4%; P = 0.085). Interaction between septal scar burden and pacing strategy was significant for ER (P = 0.002) and LVEF improvement (P = 0.011) after propensity score adjustment. During median follow-up of 33.7 (Q1-Q3: 19.8-42.1) months, the composite clinical outcome occurred in 34.7% (n = 51) of patients. The high-burden subgroups had worse clinical outcomes independent of CRT method. ConclusionsRemodeling response to LBBAP and BVP among nonischemic cardiomyopathy patients is modified by septal scar burden. High septal scar burden was associated with poor clinical prognosis independent of CRT methods.

Relationship between left ventricular mechanical dyssynchrony and accelerated 99mTc-MIBI clearance in patients with heart failure

Aim. To evaluate 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) washout rate and its relationship with contractility and left ventricular (LV) mechanical dyssynchrony in patients with heart failure (HF) of non-ischemic origin.Material and methods. The study included 20 patients with HF of non-ischemic origin with indications for cardiac resynchronization therapy (CRT). Ten patients without HF were included in the comparison group. All patients underwent 99mTc-MIBI myocardial perfusion scintigraphy (MPS). We assessed the 99mTc-MIBI washout rate, as well as LV perfusion, contractility, and mechanical dyssynchrony using phase analysis data (phase standard deviation, histogram bandwidth (HBW), asymmetry, and gradient). Six months after CRT, all patients with HF underwent MPS to assess the changes of studied parameters.Results. According to MPS, patients with HF had a higher 99mTc-MIBI washout rate from the LV myocardium compared with the comparison group (10,9 (8,49-13,8) vs 3,98 (0,9-9,8)%, p=0,0001), as well as severe LV mechanical dyssynchrony (standard deviation: 66 (55,11-73,24) vs 13,1 (10,1-19,6), p&lt;0,0001; HBW: 207 (165-246) vs 40 (33-66), p&lt;0,0001). The 99mTc-MIBI washout rate was positively correlated with LV end-diastolic (r=0,46, p&lt;0,001) and LV end-systolic volumes (r=0,44, p&lt;0,001) and negatively correlated with LV ejection fraction (r=0,41, p&lt;0,001). A moderate correlation was found between the 99mTc-MIBI washout rate and following LV mechanical dyssynchrony and contractility parameters: HBW (r=0,412, p&lt;0,001), asymmetry (r=-0,41, p&lt;0,001), gradient (r=-0,44, p&lt;0,001), wall motion (r=-0,45, p=0,001), wall thickening (r=-0,54, p&lt;0,001). Six months after CRT, all patients showed a significant decrease in the 99mTc-MIBI washout rate from 12,4 (10,3-14,9) to 8,14 (3,37-8,88)%, p=0,0006.Conclusion. In patients with HF of non-ischemic origin, an increase in the 99mTc-MIBI washout rate from the LV myocardium is associated with the severity of impaired cardiac contractility and mechanical dyssynchrony.

Atrioventricular optimization improves cardiac resynchronization response in patients with long interventricular electrical delays: A pooled analysis of the SMART-AV and SMART-CRT trials

BackgroundThe utility of atrioventricular (AV) optimization (AVO) algorithms remains in question. A substudy of the SMART-AV trial found that patients with prolonged interventricular delays ≥70 ms were more likely to benefit from cardiac resynchronization therapy (CRT) with AVO. The SMART-CRT trial evaluated AVO on the basis of these results, but the study was underpowered. ObjectiveTo increase statistical power, data from SMART-AV patients meeting the inclusion criterion of interventricular delay ≥70 ms were pooled with data from SMART-CRT to reassess AVO. MethodsSMART-CRT and SMART-AV were prospective, randomized, multicenter clinical trials. Patients in both studies were randomized to be programmed with an AVO algorithm (SmartDelay) or fixed AV delay (120 ms). Paired echocardiograms obtained at baseline and 6 months were compared, with CRT response defined as ≥15% reduction in left ventricular end-systolic volume. ResultsA total of 451 complete patient data sets were pooled and analyzed. The baseline demographics between studies did not differ statistically in terms of age, sex, left ventricular ejection fraction, or left ventricular end-systolic volume. The AVO group had a greater proportion of CRT responders (SmartDelay, 73.9%; fixed, 63.1%; P = .014) and greater changes in measures of reverse remodeling. SmartDelay patients with a recommended sensed AV delay outside the nominal range (100–120 ms) had 2.3 greater odds of CRT response than fixed AV delay patients. ConclusionGreater CRT response and measures of reverse remodeling were observed in patients with SmartDelay enabled vs a fixed AV delay. This study supports the use of SmartDelay in patients with a CRT indication and interventricular delay ≥70 ms.

Baroreflex activation therapy in patients with heart failure and a reduced ejection fraction: Long-term outcomes.

Carotid baroreflex activation therapy (BAT) restores baroreflex sensitivity and modulates the imbalance in cardiac autonomic function in patients with heart failure with reduced ejection fraction (HFrEF). We tested the hypothesis that treatment with BAT significantly reduces cardiovascular mortality and heart failure morbidity and provides long-term safety and sustainable symptomatic improvement. BeAT-HF was a prospective, multicentre, randomized, two-arm, parallel-group, open-label, non-implanted control trial. New York Heart Association (NYHA) class III subjects, ejection fraction ≤35%, previous heart failure hospitalization or N-terminal pro-B-type natriuretic peptide (NT-proBNP) >400 pg/ml, no class I indication for cardiac resynchronization therapy and NT-proBNP <1600 pg/ml were randomized to BAT plus optimal medical management (BAT group) or optimal medical management alone (control). The primary endpoint was cardiovascular mortality and HF morbidity; additional pre-specified endpoints included durability of safety, quality of life (QOL), exercise capacity (6-min hall walk distance [6MHWD]), functional status (NYHA class), hierarchical composite win ratio, freedom from all-cause death, left ventricular assists device (LVAD) implantation, heart transplant. Overall, 323 patients had 332 primary events, median follow-up was 3.6 years/patient. Both primary endpoint (rate ratio 0.94, 95% confidence interval [CI] 0.57-1.57; p = 0.82) and components of the primary endpoints were not significantly different between BAT and control. The system- and procedure-related major adverse neurological and cardiovascular event-free rate remained 97% throughout the trial. Symptom improvement (QOL, 6MHWD, NYHA class, all nominal p < 0.001) in the BAT group was durable in time, sustainable in extent. Win ratio (1.26, 95% CI 1.02-1.58) and freedom from all-cause death, LVAD implantation, heart transplant (hazard ratio 0.66, 95% CI 0.43-1.01) favoured the BAT group but did not reach statistical significance. The BeAT-HF primary endpoint was neutral; however, BAT provided safe, effective, and sustainable improvements in HFrEF patient's functional status, 6MHWD and QOL.

Landmark Evolutions in Time and Indication for Cardiac Resynchronization Therapy: Results from a Multicenter Retrospective Registry.

Background: Cardiac resynchronization therapy (CRT) has evolved into an established therapy for patients with chronic heart failure and a wide QRS complex. Data on long-term outcomes over time are scarce and the criteria for implantation remain a subject of investigation. Methods: An international, multicenter, retrospective registry includes 2275 patients who received CRT between 30 November 2000 and 31 December 2019, with a mean follow-up of 3.6 ± 2.7 years. Four time periods were defined, based on landmark trials and guidelines. The combined endpoint was a composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Results: The composite endpoint occurred in 656 patients (29.2%). The mean annual implantation rate tripled from 31.5 ± 17.4/year in the first period to 107.4 ± 62.4/year in the last period. In the adjusted Cox regression analysis, the hazard ratio for the composite endpoint was not statistically different between time periods. When compared to sinus rhythm with left bundle branch block (LBBB), a non-LBBB conduction pattern (sinus rhythm: HR 1.51, 95% CI 1.12-2.03; atrial fibrillation: HR 2.08, 95% CI 1.30-3.33) and a QRS duration below 130 ms (HR 1.64, 95% CI 1.29-2.09) were associated with a higher hazard ratio. Conclusions: Despite innovations, an adjusted regression analysis revealed stable overall survival over time, which can at least partially be explained by a shift in patient characteristics.

Cardiac contractility modulation in patients with heart failure - A review of the literature.

Experimental in vivo and in vitro studies showed that electric currents applied during the absolute refractory period can modulate cardiac contractility. In preclinical studies, cardiac contractility modulation (CCM) was found to improve calcium handling, reverse the foetal myocyte gene programming associated with heart failure (HF), and facilitate reverse remodeling. Randomized control trials and observational studies have provided evidence about the safety and efficacy of CCM in patients with HF. Clinically, CCM therapy is indicated to improve the 6-min hall walk, quality of life, and functional status of HF patients who remain symptomatic despite guideline-directed medical treatment without an indication for cardiac resynchronization therapy (CRT) and have a left ventricular ejection fraction (LVEF) ranging from 25 to 45%. Although there are promising results about the role of CCM in HF patients with preserved LVEF (HFpEF), further studies are needed to elucidate the role of CCM therapy in this population. Late gadolinium enhancement (LGE) assessment before CCM implantation has been proposed for guiding the lead placement. Furthermore, the optimal duration of CCM application needs further investigation. This review aims to present the existing evidence regarding the role of CCM therapy in HF patients and identify gaps and challenges that require further studies.

Real-time three-dimensional transthoracic echocardiography in quantification of left ventricular dyssynchrony

Aim. To compare endocardial and epicardial left ventricular (LV) pacing using real-time electrocardiography (ECG)-synchronized three-dimensional echocardiography (3DE).Methods. Experimental intraoperative study included 88 points obtained from 12 patients with compensated heart failure of II-IV functional class NYHA (LV ejection fraction &lt; 35%) and cardiac resynchronization therapy indications - ECG pattern of complete left bundle branch block (LBBB) and QRS complex duration &gt; 150 ms. During isolated LV pacing as part of cardiac resynchronization therapy implantation procedure endocardial and epicardial stimulation points matched under fluoroscopic control using quadripolar coronary sinus leads and endocardial electrodes for temporary pacing were obtained. The overall number of corresponding pacing sites included 44 endocardial and 44 epicardial stimulation positions. The mean age of patients was 68.5 [63; 73.5] years, 83% males (n=10). Before study enrollment, 12-channel ECG, echocardiography, and a six-minute walk test were performed for all participants along with cardiac magnetic resonance imaging and control coronary angiography if indicated. The prevalence of coronary heart disease was 50% (n=6) while dilated cardiomyopathy was the most common etiology of chronic heart failure in other cases. Intraoperative ECG with estimation of paced QRS complex morphology at each point was registered via LabSystem Pro Electrophysiological Recording System (Bard Electrophysiology, USA). 3DE was performed using TomTec and Philips Qlab 3DQ Advanced software (Philips Medical Systems, USA).Results. Three-dimensional parametric imaging of LV regional segmental excursion and myocardial contractility using 3DE revealed statistically significant difference in semi-quantative parameters such as ExcAvg (p&lt;0.001), ExcMax (p=0.001), ExcMin (p&lt;0.001) and LV ejection fraction based on 3D modelling (p=0.003) while endocardial pacing was more beneficial. During the course of endocardial stimulation, the 3DE dyssynchrony index estimated at the 2nd stimulation site was also significantly lower (p=0.03). Identical dyssynchrony parameters valid for the 16 and 12-segment 3D models (SDI-16, Tmsv-12SD) (at p=0.06) demonstrated only a tendency for significant difference. The duration of QRS complex at the time of endocardial pacing was significantly shorter (&lt;190 [179;215] ms) (p=0.0008). Semi-quantitative and quantitative 3DE parameters showed the benefit of endocardial pacing resulting in cardiac contractility improvement with less dyssynchrony and LV volume reducing during intraoperative period.Conclusion. Endocardial pacing has potential benefit over the epicardial pacing represented by intraoperative dynamics of LV global and local contractility, intraventricular dyssynchrony estimated by 3DE and also ECG criteria. 3DE is helpful in more precise and reproducibile determing of late activation zone for target LV lead placement that is more manoeuvrable in case of endocardial stimulation.

Cardiac resynchronization therapy in acute heart failure and left bundle-branch block in a real-life registry.

To determine the prevalence, characteristics, timing of implementation and prognosis of patients with left bundle branch block (LBBB) and acute heart failure (AHF) treated with cardiac resynchronization therapy (CRT) in a real-life registry. We analysed the characteristics of patients with AHF and LBBB at the time of inclusion in the EAHFE (Epidemiology Acute Heart Failure Emergency) cohort to determine the indication for CRT, the timing of implementation and its impact on 10-year all-cause mortality. 729 patients with a median age of 82 years and there was a high burden of comorbidities and functional dependence. The median left-ventricle ejection fraction (LVEF) was 40%. Forty-six (6%) patients were treated with CRT at some point during follow-up, with a median time of delay for CRT implementation of 960 (IQR=1,147 days) and at least 108 more untreated patients fulfilled criteria for CRT. Patients receiving CRT were younger, had different comorbidities, less functional dependence (higher Barthel index) and lower LVEF values. The median follow-up was 5.7 years (95% CI: 5.6-5.8) and CRT was not associated with changes in 10-year mortality (adjusted HR 1.33, 95% CI: 0.72-2.48; p-value 0.4). When compared with untreated patients fulfilling criteria for CRT, very similar results were observed (adjusted HR 1.34, 95% CI: 0.67-2.68). CRT implementation was delayed and underused in patients with AHF and LBBB. Under these circumstances, CRT is not associated with a reduction in all-cause mortality in the long term.

Visualization of Left Ventricular Endocardium Activation Time during Cardiac Conduction System Pacing

Introduction. Right ventricular myocardial pacing leads to asynchronous contraction of the left ventricle (LV) and can impair its contractility over time. Stimulation of the conduction system of the heart ensures physiological activation of the ventricles.&#x0D; The aim. To visualize the pattern of propagation of the electrical front on the activation map of the LV endocardium during conduction system pacing and during right ventricular myocardial pacing.&#x0D; Materials and methods. In two patients with the conduction system pacing, who were operated at the National Amosov Institute of Cardiovascular Surgery, invasive LV activation mapping was performed on various options of cardiac pacing using the EnSite Precision TM navigation system. One patient with complete atrioventricular block had nonselective His bundle pacing. The second patient had dilated cardiomyopathy and indications for cardiac resynchronization therapy and ablation of the atrioventricular junction due to chronic tachyform of atrial fibrillation. After an unsuccessful attempt to place LV lead in coronary sinus, a lead for left bundle branch pacing was implanted. Different activation maps of the LV endocardium were built in two patients with two types of cardiac pacing: right ventricular myocardial pacing and cardiac conduction system pacing.&#x0D; Results. The total LV endocardial activation time was significantly different in the two studied patients with different pacing options. In a patient with non-selective stimulation of His bundle, the total LV endocardial activation time was 43 ms (QRS width 126 ms, the interval from the stimulus to the peak of the R wave in lead V6 78 ms). After switching to right ventricular myocardial pacing with a decrease in the pacing amplitude, the total LV endocardial activation time prolonged to 90 ms (QRS width 165 ms, the interval from the stimulus to the peak of the R wave in lead V6 117 ms). In a patient with left bundle branch pacing, total LV endocardial activation time was 51 ms (QRS width 160 ms, the interval from the stimulus to the peak of the R wave in lead V6 66 ms). With switching exclusively to right ventricular pacing the total LV endocardial activation time prolonged to 93 ms (stimulated QRS width 180 ms). At the same time, the activation pattern of the LV endocardium was significantly different, since the right ventricular lead was located closer to the apex.&#x0D; Conclusions. Conduction system pacing provides rapid physiological LV activation and potentially avoids the negative consequences of asynchronous slow ventricular activation during right ventricular pacing.

Indications for Cardiac Resynchronization Therapy in Patients with Congenital Heart Disease.

Heart failure in patients with congenital heart disease (CHD) stems from unique causes compared with the elderly. Patients with CHD face structural abnormalities and malformations present from birth, leading to altered cardiac function and potential complications. In contrast, elderly individuals primarily experience heart failure due to age-related changes and underlying cardiovascular conditions. Cardiac resynchronization therapy (CRT) can benefit patients with CHD, although it presents numerous challenges. The complexities of CHD anatomy and limited access to appropriate venous sites for lead placement make CRT implantation demanding.