Reduction In Left Ventricular End-systolic Volume Research Articles

Clinical effectiveness of a dedicated cardiac resynchronization therapy pre-assessment clinic incorporating cardiac magnetic resonance imaging and cardiopulmonary exercise testing on patient selection and outcomes.

BackgroundPre-procedural assessment of patients undergoing cardiac resynchronization therapy (CRT) is heterogenous and patients implanted with unfavorable characteristics may account for non-response. A dedicated CRT pre-assessment clinic (CRT PAC) was developed to standardize the review process and undertake structured pre-procedural evaluation. The aim of this analysis was to determine the effectiveness on patient selection and outcomes.MethodsA prospective database of consecutive patients attending the CRT PAC between 2013 and 2018 was analyzed. Pre-operative assessment included cardiac magnetic resonance (CMR) and cardiopulmonary exercise testing (CPET). Patients were considered CRT responders based on improvement in clinical composite score (CCS) and/or reduction in left ventricular end-systolic volume (LVESV) ≥ 15% at 6-months follow-up.ResultsOf 252 patients reviewed in the CRT PAC during the analysis period, 192 fulfilled consensus guidelines for implantation. Of the patients receiving CRT, 82% showed improvement in their CCS and 57% had a reduction in LVESV ≥ 15%. The presence of subendocardial scar on CMR and a peak VO2 ≤ 12 ml/kg/min on CPET predicted CRT non-response. Two patients were unsuitable for CRT as they had end-stage heart failure and died during follow-up. The majority of patients initially deemed unsuitable for CRT did not suffer from unexpected hospitalization for decompensated heart failure or died from cardiovascular disease; only 8 patients (13%) received CRT devices during follow-up because of symptomatic left ventricular systolic impairment.ConclusionA dedicated CRT PAC is able to appropriately select patients for CRT. Pre-procedural investigation/imaging can identify patients unlikely to respond to, or may not yet be suitable for CRT.

The physiological effects of cardiac resynchronization therapy on aortic and pulmonary flow and dynamic and static components of systemic impedance.

BackgroundPatients who improve following cardiac resynchronization therapy (CRT) have left ventricular (LV) remodeling and improved cardiac output (CO). Effects on the systemic circulation are unknown.ObjectiveTo explore the effects of CRT on aortic and pulmonary blood flow and systemic afterload.MethodsAt CRT implant patients underwent a noninvasive assessment of central hemodynamics, including wave intensity analysis (n = 28). This was repeated at 6 months after CRT. A subsample (n = 11) underwent an invasive electrophysiological and hemodynamic assessment immediately following CRT. CRT response was defined as reduction in LV end-systolic volume ≥15% at 6 months.ResultsIn CRT responders (75% of those in the noninvasive arm), there was a significant increase in CO (from 3 ± 2 L/min to 4 ± 2 L/min, P = .002) and LV dP/dtmax (from 846 ± 162 mm Hg/s to 958 ± 194 mm Hg/s, P = .001), immediately after CRT in those in the invasive arm. They demonstrated a significant increase in aortic forward compression wave (FCW) both acutely and at follow-up. The relative change in LV dP/dtmax strongly correlated with changes in the aortic FCW (Rs 0.733, P = .025). CRT responders displayed a significant reduction in afterload, and a decrease in systemic vascular resistance and pulse wave velocity acutely; there was a significant decrease in acute pulmonary afterload measured by the pulmonary FCW and forward expansion wave.ConclusionImproved cardiac function following CRT is attributable to a combination of changes in the cardiac and cardiovascular system. The relative importance of these 2 mechanisms may then be important for optimizing CRT.

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

BackgroundSeveral 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.MethodsWe 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).ResultsThe 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).ConclusionsThis 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.

The relationship between cardiac resynchronization therapy and serum levels of copeptin in patients with chronic heart failure

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): The present study was supported by a grant from Slovak Hearth Rhythm Association (Prognostic value of MR-proANP and MR-proADM in patients undergoing cardiac resynchronization therapy). Background Chronic heart failure (CHF) is a complex syndrome characterized by an abnormal neurohormonal activation, including arginine vasopressin (AVP). Copeptin is an indicator of AVP activation, which levels are elevated in CHF and have prognostic importance. Cardiac resynchronization therapy (CRT) is an important device therapy for patients with advanced CHF, left ventricular (LV) systolic dysfunction and evidence of electromechanical dyssynchrony. The aim of the present study was to determine the possible relationship between CRT and serum copeptin levels. Methods We have included CRT patients with ischemic as well as nonischemic etiology of CHF. The levels of copeptin were measured at baseline and 12 months respectively after CRT implantation. Echocardiography was also performed pre and 12 months post CRT implantation. A CRT response was defined as a ≥ 15 % reduction in LV end-systolic volume (LVESV). Results The study population consisted of 41 patients. The mean copeptin level was 20.50 ± 15.77 pmol/l. Copeptin levels positively correlated with New York Heart Association class, left atrial diameter, creatinine levels and NT-proBNP levels. CRT responders have significant reduction in copeptin levels from baseline to 12 months (from 16.96 ± 12.80 pmol/l to 6.20 ± 6.44 pmol/l, p &amp;lt; 0.001). No significant changes in copeptin levels were observed in CRT nonresponders. Reduction &amp;gt; 45 % in copeptin levels was predictor of CRT-response (OR 6.72, 95 % CI 1.01 - 18.11, p = 0.045). Conclusion The copeptin serum levels can be a useful biomarker in the evaluation of the CRT response.

Prognostic value of reverse remodelling criteria in heart failure with reduced or mid-range ejection fraction.

AimsReverse remodelling (RR) is the recovery from left ventricular (LV) dilatation and dysfunction. Many arbitrary criteria for RR have been proposed. We searched the criteria with the strongest prognostic yield for the hard endpoint of cardiovascular death.Methods and resultsWe performed a systematic literature search of diagnostic criteria for RR. We evaluated their prognostic significance in a cohort of 927 patients with LV ejection fraction (LVEF) < 50% undergoing two echocardiograms within 12 ± 2 months. These patients were followed for a median of 2.8 years (interquartile interval 1.3–4.9) after the second echocardiogram, recording 123 cardiovascular deaths. Two prognostic models were defined. Model 1 included age, LVEF, N‐terminal pro‐B‐type natriuretic peptide, ischaemic aetiology, cardiac resynchronization therapy, estimated glomerular filtration rate, New York Heart Association, and LV end‐systolic volume (LVESV) index, and Model 2 the validated Cardiac and Comorbid Conditions Heart Failure score. We identified 25 criteria for RR, the most used being LVESV reduction ≥15% (12 studies out of 42). In the whole cohort, two criteria proved particularly effective in risk reclassification over Model 1 and Model 2. These criteria were (i) LVEF increase >10 U and (ii) LVEF increase ≥1 category [severe (LVEF ≤ 30%), moderate (LVEF 31–40%), mild LV dysfunction (LVEF 41–55%), and normal LV function (LVEF ≥ 56%)]. The same two criteria yielded independent prognostic significance and improved risk reclassification even in patients with more severe systolic dysfunction, namely, those with LVEF < 40% or LVEF ≤ 35%. Furthermore, LVEF increase >10 U and LVEF increase ≥1 category displayed a greater prognostic value than LVESV reduction ≥15%, both in the whole cohort and in the subgroups with LVEF < 40% or LVEF ≤ 35%. For example, LVEF increase >10 U independently predicted cardiovascular death over Model 1 and LVESV reduction ≥15% (hazard ratio 0.40, 95% confidence interval 0.18–0.90, P = 0.026), while LVESV reduction ≥15% did not independently predict cardiovascular death (P = 0.112).ConclusionsLeft ventricular ejection fraction increase >10 U and LVEF increase ≥1 category are stronger predictors of cardiovascular death than the most commonly used criterion for RR, namely, LVESV reduction ≥15%.

The value of non-invasive myocardial work indices derived from left ventricular pressure-strain loops in predicting the response to cardiac resynchronization therapy.

Non-invasive left ventricular (LV) pressure-strain loops (PSLs), which are generated by combining LV longitudinal strain with brachial artery blood pressure, provide a novel method of quantifying global and segmental myocardial work (MW) indices with potential advantages over conventional echocardiographic strain data, which suffers from being load-dependent. This method has been recently introduced in echocardiographic software, enhancing the efficiency of MW calculations. This study aimed to evaluate the role of non-invasive MW indices derived from LV PSLs in predicting cardiac resynchronization therapy (CRT) response. A total of 106 heart failure (HF) patients scheduled for CRT were included in the MW analysis. Global and segmental (septal and lateral at the mid-ventricular level) MW indices were assessed before CRT and at a 6-month follow-up. Response to CRT was defined as ≥15% reduction in LV end-systolic volume and ≥1 NYHA functional class improvement at 6-month follow-up compared to baseline. CRT response was observed in 78 (74%) patients. At baseline, the global work index (GWI) and global constructive work (GCW) were significantly higher in CRT responders than in non-responders (both P<0.05). Furthermore, responders exhibited significantly higher mid lateral MW and mid lateral constructive work (CW) (both P<0.001), but significantly lower mid septal MWI and mid septal myocardial work efficiency (MWE) than non-responders (all P<0.01). Baseline mid septal MWE (OR 0.975, 95% CI: 0.959-0.990, P=0.002) and mid lateral MWI (OR 1.003, 95% CI: 1.002-1.004, P<0.001) were identified as independent predictors of CRT response in multivariate regression analysis. Mid septal MWE ≤42% combined with mid lateral MWI ≥740 mmHg% predicted CRT response, with an optimal sensitivity of 79% and specificity of 82% [area under the receiver operating characteristic curve (AUC) =0.830, P<0.001]. Assessment of MW indices before CRT could identify the marked imbalance in LV MW distribution and can be widely used as a reliable complementary tool for guiding patient selection for CRT in clinical practice.

Comparison between cardiac magnetic resonance and speckle-tracking echocardiography in prediction of cardiac resynchronization therapy outcomes

Background Cardiac resynchronization therapy (CRT) improves quality of life, exercise tolerance, and myocardial function in a considerable number of patients with heart failure (HF) and left bundle branch block. In addition, CRT decreases HF hospitalizations and overall mortality. However, structural, morbidity, and mortality improvements after CRT rate between 40 and 60%. Objective To compare the role of the cardiac magnetic resonance (CMR) and speckle-tracking echocardiography (STE) in expectation of response to CRT. Patients and methods We investigated the predictors of CRT response using CMR measurement of left ventricular (LV) volumes and function, CMR-derived mechanical dyssynchrony, scar percentage, and its relation to the site of LV lead implantation, in comparison with STE in prediction of CRT outcomes. Results A total of 35 patients with HF planned for CRT were included. Echocardiography was used to define the response to CRT (15% reduction in LV end-systolic volume 6 months after implantation). At follow-up, 18 (51.43%) patients were categorized as responders. Echocardiographic speckle-tracking radial strain analysis showed a significant LV dyssynchrony in responders versus nonresponders (radial mid-anteroseptal and posterior wall delays were 245.1 ms and 80.7 ms, respectively) (P&lt;0.0001). LV radial dyssynchrony, as measured by CMR-feature tracking, was significantly higher in responders versus nonresponders (mean of SDt-16 of radial strain were 232.7 ms vs. 180.4 ms, P&lt;0.0001), and median of radial mid-anteroseptal-to-inferolateral wall delay was 375 vs. 125.4 ms, P&lt;0.0001). Late contrast-enhanced CMR was performed for scar assessment. It was noticed that scar percentage of LV mass was much higher in nonresponders (median 6.2 vs. 0%) (P=0.005). Conclusion CMR imaging offers the unique opportunity to predict the CRT outcomes by measurement of LV volumes, LV mechanical dyssynchrony (that well correlated with that of STE), and the total scar percentage and distribution in a single examination.

Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study.

Remote ischemic conditioning (RIC) alleviates ischemia-reperfusion injury via several pathways, including micro-RNAs (miRs) expression and oxidative stress modulation. We investigated the effects of RIC on endothelial glycocalyx, arterial stiffness, LV remodelling, and the underlying mediators within the vasculature as a target for protection. We block-randomised 270 patients within 48h of STEMI post-PCI to either one or two cycles of bilateral brachial cuff inflation, and a control group without RIC. We measured: (a) the perfusion boundary region (PBR) of the sublingual arterial microvessels to assess glycocalyx integrity; (b) the carotid-femoral pulse wave velocity (PWV); (c) miR-144,-150,-21,-208, nitrate-nitrite (NOx) and malondialdehyde (MDA) plasma levels at baseline (T0) and 40min after RIC onset (T3); and (d) LV volumes at baseline and after one year. Compared to baseline, there was a greater PBR and PWV decrease, miR-144 and NOx levels increase (p < 0.05) at T3 following single- than double-cycle inflation (PBR:ΔT0-T3 = 0.249 ± 0.033 vs 0.126 ± 0.034μm, p = 0.03 and PWV:0.4 ± 0.21 vs -1.02 ± 0.24m/s, p = 0.03). Increased miR-150,-21,-208 (p < 0.05) and reduced MDA was observed after both protocols. Increased miR-144 was related to PWV reduction (r = 0.763, p < 0.001) after the first-cycle inflation in both protocols. After one year, single-cycle RIC was associated with LV end-systolic volume reduction (LVESV) > 15% (odds-ratio of 3.75, p = 0.029). MiR-144 and PWV changes post-RIC were interrelated and associated with LVESV reduction at follow-up (r = 0.40 and 0.37, p < 0.05), in the single-cycle RIC. RIC evokes "vascular conditioning" likely by upregulation of cardio-protective microRNAs, NOx production, and oxidative stress reduction, facilitating reverse LV remodelling. http://www.clinicaltrials.gov . Unique identifier: NCT03984123.

Reduction in the QRS area after cardiac resynchronization therapy is associated with survival and echocardiographic response.

IntroductionRecent studies have shown that the baseline QRS area is associated with the clinical response after cardiac resynchronization therapy (CRT). In this study, we investigated the association of QRS area reduction (∆QRS area) after CRT with the outcome. We hypothesize that a larger ∆QRS area is associated with a better survival and echocardiographic response.Methods and ResultsElectrocardiograms (ECG) obtained before and 2–12 months after CRT from 1299 patients in a multi‐center CRT‐registry were analyzed. The QRS area was calculated from vectorcardiograms that were synthesized from 12‐lead ECGs. The primary endpoint was a combination of all‐cause mortality, heart transplantation, and left ventricular (LV) assist device implantation. The secondary endpoint was the echocardiographic response, defined as LV end‐systolic volume reduction ≥ of 15%. Patients with ∆QRS area above the optimal cut‐off value (62 µVs) had a lower risk of reaching the primary endpoint (hazard ratio: 0.43; confidence interval [CI] 0.33–0.56, p < .001), and a higher chance of echocardiographic response (odds ratio [OR] 3.3;CI 2.4–4.6, p < .0001). In multivariable analysis, ∆QRS area was independently associated with both endpoints. In patients with baseline QRS area ≥109 µVs, survival, and echocardiographic response were better when the ∆QRS area was ≥62 µVs (p < .0001). Logistic regression showed that in patients with baseline QRS area ≥109 µVs, ∆QRS area was the only significant predictor of survival (OR: 0.981; CI: 0.967–0.994, p = .006).Conclusion∆QRS area is an independent determinant of CRT response, especially in patients with a large baseline QRS area. Failure to achieve a large QRS area reduction with CRT is associated with a poor clinical outcome.

The mechanism and prognosis of acute and late improvement in mitral regurgitation after cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) improves functional mitral regurgitation (MR); however, the mechanism and differences in acute and late improvement in MR are unclear. We aimed to evaluate the factors associated with the acute and late MR improvements and the prognosis of MR improvement after CRT. This retrospective study included 121 patients who underwent CRT implantation with full echocardiography assessment at baseline, 1week, and 6months after implantation. MR severity was classified into five grades (0: none to 4: severe). Two-dimensional speckle-tracking echocardiography with radial strain was used to assess dyssynchrony, and the time difference between the lateral and inferior segments at papillary muscle levels (TDlate-inf) was calculated. The MR improved 1week and 6months after CRT in 40 (33%) and 45 (37%) patients, respectively. On multivariate analyses, TDlate-inf (baseline-1week) and SPWMD were independently associated with acute MR improvement. The %reduction in left ventricular end-systolic volume (LVESV) (baseline-6months) and TDlate-inf (baseline-1week) were independently correlated with late MR improvement. The patients with pre-MR grades 2-4 and improved MR after CRT showed significantly better prognosis in heart failure hospitalization. Cutoff values of ≥ 19.5ms of the reduction of TDlate-inf and ≥ 30.8% of the %reduction of LVESV were significantly associated with the decrease in heart failure hospitalization. The improved interpapillary muscle activation time delay and volume reduction after CRT were associated with acute and late MR improvements. There may be different time course of recovery and distinct causes for late MR improvement.

A multicenter prospective randomized controlled trial of cardiac resynchronization therapy guided by invasive dP/dt.

BackgroundNo periprocedural metric has demonstrated improved cardiac resynchronization therapy (CRT) outcomes in a multicenter setting.ObjectiveWe sought to determine if left ventricular (LV) lead placement targeted to the coronary sinus (CS) branch generating the best acute hemodynamic response (AHR) results in improved outcomes at 6 months.MethodsIn this multicenter randomized controlled trial, patients were randomized to guided CRT or conventional CRT. Patients in the guided arm had LV dP/dtmax measured during biventricular (BIV) pacing. Target CS branches were identified and the final LV lead position was the branch with the best AHR and acceptable threshold values. The primary endpoint was the proportion of patients with a reduction in LV end-systolic volume (LVESV) of ≥15% at 6 months.ResultsA total of 281 patients were recruited across 12 centers. Mean age was 70.8 ± 10.9 years and 54% had ischemic etiology. Seventy-three percent of patients in the guided arm demonstrated a reduction in LVESV of ≥15% at 6 months vs 60% in the conventional arm (P = .02). Patients with AHR ≥ 10% were more likely to demonstrate a reduction of ESV ≥ 15% (84% of patients with an AHR ≥10% vs 28% with an AHR <10%; P < 0.001). Procedure duration and fluoroscopy times were longer in the pressure wire–guided arm (104 ± 39 minutes vs 142 ± 39 minutes; P < .001 and 20 ±16 minutes vs 28 ± 15 minutes; P = .002).ConclusionsAHR determined by invasively measuring LV dP/dtmax during BIV pacing predicts reverse remodeling 6 months after CRT. Patients in whom LV dP/dtmax was used to guide LV lead placement demonstrated better rates of reverse remodeling.

Clinical outcome of cardiac resynchronization therapy in patients randomized to an active fixation bipolar left ventricular lead versus a passive quadripolar lead

Objectives: To compare the clinical outcome of cardiac resynchronization therapy (CRT) in patients receiving a bipolar left ventricular (LV) lead with a side helix for active fixation to the outcome in patients receiving a quadripolar passive fixation LV lead. Design: Sixty-two patients (mean age 72 ± 11 years) were blindly and randomly assigned to the active fixation bipolar lead group (n = 31) or to the quadripolar lead group (n= 31). The LV leads were targeted to the basal LV segment in a vein concordant to the LV segment with the latest mechanical contraction chosen on the basis of preoperative radial strain (RS) echocardiography. Results: At the 6-month follow-up (FU), the reduction in LV end-systolic volume and LV reverse remodelling responder rate, defined as LV end-systolic volume reduction >15%, was 77% in the active fixation group and 83% in the quadripolar group, which was not significantly different. At the 12-month FU, the LV ejection fraction (LVEF) did not differ between the groups. There were no significant differences between the two groups in changes in New York Heart Association (NYHA) functional class or Minnesota Living with Heart Failure Questionnaire score. The occurrence of phrenic nerve stimulation (PNS) was 19% in the active fixation group versus 10% in the quadripolar group (p=.30), and all cases were resolved by reprogramming the device. All patients were alive at the 12-month FU. There was no device infection. Conclusions: There were no significant differences between the active fixation group of patients and the quadripolar group of patients concerning improvement in echocardiographic parameters or clinical symptoms. ClinicalTrials.gov number, NCT04632472

Factors associated with left ventricular reverse remodelling after percutaneous coronary intervention in patients with left ventricular systolic dysfunction

Percutaneous coronary intervention (PCI) is sometimes considered as an alternative therapeutic strategy to surgical revascularization in patients with coronary artery disease (CAD) and reduced left ventricular ejection fraction (LVEF). However, the types or conditions of patients that receive the clinical benefit of left ventricular reverse remodelling (LVRR) remain unknown. The purpose of this study was to investigate the determinants of LVRR following PCI in CAD patients with reduced LVEF. From 4394 consecutive patients who underwent PCI, a total of 286 patients with reduced LV systolic function (LVEF < 50% at initial left ventriculography) were included in the analysis. LVRR was defined as LV end-systolic volume reduction ≥ 15% and improvement of LVEF ≥ 10% at 6 months follow-up left ventriculography. Patients were divided into LVRR (n = 63) and non-LVRR (n = 223) groups. Multivariate logistic regression analysis revealed that unprotected left main coronary artery (LMCA) intervention was significantly associated with LVRR (P = 0.007, odds ratios [OR] 4.70, 95% confidence interval [CI] 1.54–14.38), while prior PCI (P = 0.001, OR 0.35, 95% CI 0.19–0.66), presence of in-stent restenosis (P = 0.016, OR 0.32, 95% CI 0.12–0.81), and presence of de-novo stenosis (P = 0.038, OR 0.36, 95% CI 0.14–0.95) were negatively associated with LVRR. These data suggest the potential prognostic benefit of unprotected LMCA intervention for LVRR and importance of angiographic follow-up in patients with CAD and LV systolic dysfunction.

Therapeutic effect of mesenchymal stem cell therapy in the LVEF, LVEDV, and LVESV after myocardial infarction.

The present study was aimed to investigate the therapeutic effect of mesenchymal Stem Cell Therapy in the left ventricular ejection fraction (LVEF), left ventricular enddiastolic volume (LVEDV), and left ventricular endsystolic volume (LVESV) after myocardial infarction (MI). Previous investigations propose that stem cell therapy may help treat myocardial infarction (MI). However, there are controversial data from different studies. We studied the relevant scientific literature available up to 2020. Comprehensive Meta-Analysis Software (CMAS) Version 2.0 were used for statistical analyses. Fixed or random-effect model was used to identify the weighted mean difference (WMD) with 95% confidence intervals (CI). The statistically significant level used for interpreting publication bias was less than 0.05. We identified 30 studies that met the inclusion criteria. In the overall pooled estimate, cell therapy had an effect on the LVEF change from baseline to follow-up (WMD: 2.98 mL, 95% CI: 1.66 to 4.29). The pooled WMD was found to be -4.16 (95% CI: -7.91 to -0.40) and -5.62 (95% CI: -9.20 to -2.00), for LVEDV, and LVESV, respectively. Thus, reduction in LVEDV and LVESV were significant in the treatment group participants. The present systematic review indicated that cell therapy in patients, who have MI could be effective and applicable clinically (Tab. 3, Fig. 7, Ref. 48). Text in PDF www.elis.sk Keywords: myocardial infarction, stem cell, systematic review, randomized clinical trials.

Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction

BackgroundLarge clinical trials established the benefits of sodium-glucose cotransporter 2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia. ObjectivesThe purpose of this study was to assess the effect of empagliflozin on left ventricular (LV) function and volumes, functional capacity, and quality of life (QoL) in nondiabetic HFrEF patients. MethodsIn this double-blind, placebo-controlled trial, nondiabetic HFrEF patients (n = 84) were randomized to empagliflozin 10 mg daily or placebo for 6 months. The primary endpoint was change in LV end-diastolic and -systolic volume assessed by cardiac magnetic resonance. Secondary endpoints included changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, 6-min walk test, and quality of life. ResultsEmpagliflozin was associated with a significant reduction of LV end-diastolic volume (−25.1 ± 26.0 ml vs. −1.5 ± 25.4 ml for empagliflozin vs. placebo, respectively; p < 0.001) and LV end-systolic volume (−26.6 ± 20.5 ml vs. −0.5 ± 21.9 ml for empagliflozin vs. placebo; p < 0.001). Empagliflozin was associated with reductions in LV mass (−17.8 ± 31.9 g vs. 4.1 ± 13.4 g, for empagliflozin vs. placebo, respectively; p < 0.001) and LV sphericity, and improvements in LV ejection fraction (6.0 ± 4.2 vs. −0.1 ± 3.9; p < 0.001). Patients who received empagliflozin had significant improvements in peak O2 consumption (1.1 ± 2.6 ml/min/kg vs. −0.5 ± 1.9 ml/min/kg for empagliflozin vs. placebo, respectively; p = 0.017), oxygen uptake efficiency slope (111 ± 267 vs. −145 ± 318; p < 0.001), as well as in 6-min walk test (81 ± 64 m vs. −35 ± 68 m; p < 0.001) and quality of life (Kansas City Cardiomyopathy Questionnaire-12: 21 ± 18 vs. 2 ± 15; p < 0.001). ConclusionsEmpagliflozin administration to nondiabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for sodium-glucose cotransporter 2 inhibitors in the treatment of HFrEF patients independently of their glycemic status. (Are the “Cardiac Benefits” of Empagliflozin Independent of Its Hypoglycemic Activity? [ATRU-4] [EMPA-TROPISM]; NCT03485222)

Change in QRS area by cardiac resynchronization therapy is associated with clinical outcomes and echocardiographic response

Abstract Background Cardiac Resynchronization Therapy (CRT) is the cornerstone of treatment in patients with dyssynchronous heart failure. Recently, baseline QRS area proved to predict outcomes after CRT better than QRS duration and morphology. Purpose It was the aim of the study to investigate whether the change in QRS area (ΔQRS area) by CRT-pacing further improves the prediction of CRT outcomes. Methods We conducted a retrospective analysis on 1,299 patients, who were included in a CRT-registry from three Dutch University hospitals with both pre- (baseline) and post-implantation 12-lead ECGs. ΔQRS area and ΔQRS duration were defined as the decrease in their respective values after CRT. Optimal cut offs for ΔQRS area and ΔQRS duration by means of Youden indices were found at 62μVs and −11ms, respectively. Primary endpoint was a combination of all-cause mortality, heart transplantation, and left ventricular assist device implantation. Secondary endpoint was the relative reduction in left ventricular end-systolic volume (LVESV), and echocardiographic response being defined as ≥15% LVESV reduction. Results The primary endpoint occurred in 408 patients (31%). ΔQRS area was superior to ΔQRS duration for the primary and secondary endpoints. Primary endpoint analysis showed a lower risk in the ΔQRS area ≥62μVs than in the &amp;lt;62μVs group (HR 0.43; 0.33–0.56, p&amp;lt;0.001). In the multivariable analysis, both baseline QRS area and ΔQRS area remained significantly associated with both primary and secondary endpoints. Clinical outcome (left panel of figure) and echocardiographic response (right panel) were significantly worse in patients with baseline QRS area &amp;lt;109μVs (group 3) than in those with QRS area ≥109μVs. Within the latter group, outcomes were significantly better in patients with ΔQRS area ≥62μVs (group 1) as compared to ΔQRS area &amp;lt;62μVs (group 2) (figure). Baseline QRS duration and ΔQRS duration were not independently associated with both clinical outcome and echocardiographic response. Conclusion The combination of baseline QRS area and ΔQRS area has a stronger association with CRT response than baseline QRS area alone, and (Δ)QRS duration. These results suggest that especially in patients with a good electrical substrate (large baseline QRS area) it is worthwhile to adjust CRT to achieve the largest decrease in QRS area. Funding Acknowledgement Type of funding source: None

Non-invasive myocardial workiIndices derived from left ventricular pressure-strain loops in predicting the response to cardiac resynchronization therapy

Abstract Background Non-invasive left ventricular (LV) pressure-strain loops (PSLs) which generated by combining LV longitudinal strain with brachial artery blood pressure, provide a novel method of quantifying global and segmental myocardial work (MW) indices with potential advantages over conventional echocardiographic strain which is load-dependent. The method has been introduced in echocardiographic software recently, making MW calculations more effectively and rapidly. The aim was to evaluate the role of non-invasive MW indices derived from LV PSLs in the prediction of cardiac resynchronization therapy (CRT) response. Methods 106 heart failure (HF) patients scheduled for CRT were included for MW analysis. Global and segmental (septal and lateral at the mid-ventricular level) MW indices were accessed before CRT. Response to CRT was defined as ≥15% reduction in LV end-systolic volume at 6-month follow-up in comparison with baseline value. Results CRT response was observed in 78 (74%) patients. At baseline, global work index (GWI) and global constructive work (GCW) were significant higher in CRT responders than in non-responders (both P&amp;lt;0.05). Besides, responders exhibited a significantly higher Mid Lateral MW and Mid Lateral constructive work (CW) (both P&amp;lt;0.001) but a significantly lower Mid Septal MW and Mid Septal myocardial work efficiency (MWE), as well as a significantly higher Mid Septal wasted work (WW) than non-responders (all P&amp;lt;0.01). Baseline Mid Septal MWE (OR 0.975, 95% CI 0.959–0.990, P=0.002) and Mid Lateral MW (OR 1.003, 95% CI 1.002–1.004, P&amp;lt;0.001) were identified as independent predictors of CRT response in multivariate regression analysis. Mid Septal MWE ≤42% combined with Mid Lateral MW ≥740 mm Hg% predicted CRT response with the optimal sensitivity of 79% and specificity of 82% (AUC = 0.830, P&amp;lt;0.001). Conclusion Mid Septal MWE and Mid Lateral MW can successfully predict response to CRT, and their combination can further improve the prediction accuracy. Assessment of MW indices before CRT could identify the marked misbalance in LV myocardial work distribution and has the potential to be widely used as a reliable complementary tool for guiding patient selection in clinical practice. Funding Acknowledgement Type of funding source: None

Time interval from left ventricular stimulation to QRS onset is a predictor of mortality in patients with cardiac resynchronization therapy

Abstract Introduction In our previous report, the time interval from left ventricular (LV) pacing to the earliest onset of QRS (S-QRS interval) has been found to be an independent predictor of mechanical response to cardiac resynchronization therapy (CRT). The S-QRS interval may indicate the conduction disturbance relevant to the localized tissue property such as scar or fibrotic lesion. Therefore, S-QRS interval longer than 37ms was associated with poor response to CRT, and proposed as suboptimal LV lead position. Then, we hypothesized that the longer S-QRS interval at the LV pacing site could be related to long term mortality and heart failure events in patients with CRT. Methods This retrospective study included 82 consecutive heart failure patients with sinus rhythm, reduced LV ejection fraction (≤35%), and a wide QRS complex (≥120ms), who undergone CRT implantation between 2012 January and 2017 December. Patients were divided into Short S-QRS group (&amp;lt;37ms, SS-QRS) and Long S-QRS group (≥37ms, LS-QRS) according to the previously reported optimal cut off value. A responder was defined as one with ≥15% reduction in LV end-systolic volume assessed by echocardiography at 6 months after CRT. The primary endpoint was total mortality, which included LV assist device implantation or heart transplantation. The secondary endpoints included the composite endpoint of total mortality or heart failure hospitalization. Results The study patients were divided into SS-QRS (N=43, age 65.9±13.2 years, 77% male) and LS-QRS (N=39, age 63.0±13.4, 85% male). In the electrocardiographic measurements, there were no significant differences in baseline QRS duration (162.4±30.3ms in SS-QRS vs. 154.5±31.6ms in LS-QRS, P=0.19) and LV local activation time assessed as Q-LV interval (118.3±34.3ms in SS-QRS vs. 115.3±32.0ms in LS-QRS, P=0.71). S-QRS interval was 25.9±5.3ms in SS-QRS and 51.5±13.7ms in LS-QRS (P&amp;lt;0.01), and the responder rate was significantly higher in SS-QRS compared with LS-QRS (79% vs. 29%, P&amp;lt;0.01). During mean follow up of 47.7±22.4 months, 24 patients (29%) reached to the primary endpoint, while the secondary endpoints were observed in 47 patients (57%). LS-QRS patients had significantly worse event-free survival for both primary and secondary endpoints (Figure). After the multivariate Cox regression analysis, LS-QRS (≥37ms) was an independent predictor of total mortality (HR=2.6, 95% CI: 1.11 to 6.12, P=0.03) and the secondary composite events (HR=2.4, 95% CI: 1.31 to 4.33, P&amp;lt;0.01). Conclusion The S-QRS interval longer than 37ms, which may reflect the conduction disturbance relevant to the scar or fibrotic lesion at the LV pacing site, was a significant predictor of the total mortality and heart failure hospitalization. These findings have implications for the optimal LV lead placement in patients with CRT device. Clinical outcomes according to S-QRS Funding Acknowledgement Type of funding source: None

Cardiac Inflammation Impedes Response to Cardiac Resynchronization Therapy in Patients With Idiopathic Dilated Cardiomyopathy.

Cardiac resynchronization therapy (CRT) is an established therapy in patients with dilated cardiomyopathy (DCM) and conduction disorders. Still, one-third of the patients with DCM do not respond to CRT. This study aims to depict the underlying cardiac pathophysiological processes of nonresponse to CRT in patients with DCM using endomyocardial biopsies. Within the Maastricht and Innsbruck registries of patients with DCM, 99 patients underwent endomyocardial biopsies before CRT implantation, with histological quantification of fibrosis and inflammation, where inflammation was defined as >14 infiltrating cells/mm2. Echocardiographic left ventricular end-systolic volume reduction ≥15% after 6 months was defined as response to CRT. RNA was isolated from cardiac biopsies of a representative subset of responders and nonresponders. Sixty-seven patients responded (68%), whereas 32 (32%) did not respond to CRT. Cardiac inflammation before implantation was negatively associated with response to CRT (25% of responders, 47% of nonresponders; odds ratio 0.3 [0.12-0.76]; P=0.01). Endomyocardial biopsies fibrosis did not relate to CRT response. Cardiac inflammation improved the robustness of prediction beyond well-known clinical predictors of CRT response (likelihood ratio test P<0.001). Cardiac transcriptomic profiling of endomyocardial biopsies reveals a strong proinflammatory and profibrotic signature in the hearts of nonresponders compared with responders. In particular, COL1A1, COL1A2, COL3A1, COL5A1, POSTN, CTGF, LOX, TGFβ1, PDGFRA, TNC, BGN, and TSP2 were significantly higher expressed in the hearts of nonresponders. Cardiac inflammation along with a transcriptomic profile of high expression of combined proinflammatory and profibrotic genes are associated with a poor response to CRT in patients with DCM.

Association of ECG characteristics with clinical and echocardiographic outcome to CRT in a non-LBBB patient population.

Effectiveness of cardiac resynchronization therapy (CRT) in patients without left bundle branch block (non-LBBB) QRS morphology is limited. Additional selection criteria are needed to identify these patients. Seven hundred ninety consecutive patients with non-LBBB morphology, who received a CRT-device in 3 university centers in the Netherlands, were selected. Pre-implantation 12-lead ECGs were evaluated on morphology, duration, and area of the QRS complex, as well as on PR interval, left ventricular activation time (LVAT), and the presence of fragmented QRS (fQRS). Association of these ECG features with the primary endpoint: a combination of left ventricular assist device (LVAD) implantation, cardiac transplantation and all-cause mortality, and secondary endpoint-echocardiographic reduction of left ventricular end-systolic volume (LVESV)-were evaluated. The primary endpoint occurred more often in non-LBBB patients with with PR interval ≥ 230ms, QRS area < 109μVs, and with fQRS. Multivariable regression analysis showed independent associations of QRS area (HR 2.33 [1.44, 3.77], p = 0.001) and PR interval (HR 2.03 [1.51, 2.74], p < 0.001) only. Mean LVESV reduction was significantly lower in patients with baseline RBBB, QRS duration < 150 ms, PR interval ≥ 230 ms, and in QRS area < 109 μVs. Multivariable regression analyses only showed significant associations between QRS area ≥ 109 μVs (OR 2.00 [1.09, 3.66] p = 0.025) and probability of echocardiographic response to CRT. In the heterogeneous non-LBBB patient population, QRS area and PR prolongation rather than traditional QRS duration and morphology are associated to both clinical and echocardiographic outcomes of CRT.