Decrease In End-systolic Volume Research Articles

Predictors of responders to cardiac resynchronization therapy in patients with non-left bundle branch block with mid-wide QRS duration

Abstract Background Cardiac resynchronization therapy (CRT) is useful for patients with severe heart failure with dyssynchrony of left ventricular contraction, significantly reducing total mortality or heart failure rehospitalization. In patient with left bundle branch block (LBBB) or QRS duration (QRSd) ≥ 150 ms, CRT is a well-established therapy at guidelines in Japan and other countries. However, CRT may be more useful and effective in Asian patients with middle range wide QRSd, because of smaller body size than in the West. Few reports have shown the usefulness and efficacy of CRT in patients with non-LBBB and middle range wide QRS duration (mid-wide QRSd). Purpose To evaluate the predictors of CRT responders in heart failure patients with non LBBB and mid wide QRSd. Methods We retrospectively studied 174 consecutive patients who underwent a denovo CRT device implantation at two institutions between September 2013 and March 2023. Follow up echocardiography examination could be performed after 150 days postoperatively. CRT responders were defined as a decrease in left ventricular end systolic volume ≥15% on echocardiography. We plotted thereceiver operating characteristic (ROC) curve for predicting CRT responders. The area under the curve (AUC) was calculated to determine the best cut off value. Results A total of 34 patients with non LBBB and 120≤ QRSd <150 ms were enrolled in this study. Sixteen of 34 (47%) patients were the responders for CRT. There was no significant difference in gender between the responder and non responder groups (p=0.274). Non ischemic cardiomyopathy was more prevalent in the responder group (p=0.046). The ROC curve analysis confirmed that 0.809 was the better optimal cut off value of QRSd/left ventricular end diastolic volume (LVEDV) for predicting CRT responders (AUC = 0.688). The multivariate analysis demonstrated that QRSd/LVEDV was significantly associated with CRT responders [odds ratio (OR) 9.88, 95% confidence interval 1.51 64.90, p = 0.017]. Conclusion The corrected QRSd for heart size using LVEDV could be the independent predictor of CRT responders in Japanese patients with non LBBB and mid wide QRSd.

Impact of left bundle branch block morphology in predicting response to left bundle branch area pacing for cardiac resynchronization therapy

Abstract Background Left bundle branch area pacing (LBBAP) is a novel pacing technique with an emerging role in resynchronization therapy [1-4]. QRS morphology has shown to significantly influence cardiac resynchronization therapy (CRT) response [5-6]. Purpose The aim of this study was to assess whether different left bundle branch block (LBBB) definitions are associated with response to LBBAP resynchronization therapy. Methods 40 consecutive CRT candidates with previously unsuccessful biventricular (BiV) pacing or in which effective CRT could not be achieved with BiV pacing based on anatomical or functional criteria were selected for this study. Both ischemic and non-ischemic heart failure (HF) patients were included. Patients were divided into two groups according to LBBB morphology. Group 1 included 20 patients (45% ischemic HF) with strict LBBB definition according to Strauss criteria [7], while 20 patients in Group 2 (55% ischemic HF) had conventional LBBB morphology. Response to CRT was defined for (1) reduction in QRS duration; (2) increase in left ventricular ejection fraction (LVEF) ≥ 5% and (3) decrease in left ventricular end systolic volume (LVESV) ≥ 15%. Results LBBAP was successfully achieved in all patients (mean age: 72.0 years; male: 29). The mean baseline QRS duration before implantation was 178.6±13.8 in the Group 1 and 170.8±29.4 in the Group 2, without a statistically significant difference. Over a mean follow-up of 5.6 months, LBBAP resulted in QRS narrowing in both groups, with a greater reduction in Group 1 (-40.6 ms) compared to Group 2 (-15.1 ms), (p 0.002). Pre-implantation ventricular systolic function did not show significant differences between the two groups, with a mean of 30.1±3.5% in the Strauss LBBB group and 31.0±6.0% in the conventional LBBB group. After implantation LVEF was 42.1±8.5 % in the true LBBB patients and 33.2±7.5 in the conventional LBBB group. Echocardiographic response was observed in 65% of patients with a statistically significant difference between Group 1 (90% of responders) and Group 2 (40% of responders), (p 0,001). HF etiology did not impact the response to LBBAP CRT. Conclusions Strict LBBB definition is associated to a greater electrocardiographic and echocardiographic response in patients receiving LBBAP CRT compared to conventional LBBB criteria.\

Association of ventricular-arterial interaction with left ventricular remodelling after acute myocardial infarction: a 2-year follow-up study

Abstract Background/Introduction Adverse left ventricular (LV) remodelling after ST-segment elevation myocardial infarction (STEMI) is associated with heart failure. Purpose We aimed to investigated the association of ventricular-arterial interaction with LV remodelling in patients with STEMI. Methods In 109 patients within 48 hours of myocardial infarction post-primary percutaneous coronary intervention and after 2 years, we measured: (1) pulse wave velocity (PWV-Complior), (2) LV global longitudinal strain (GLS) and left atrial strain, (3) PWV/GLS ratio as a marker of ventricular-arterial interaction, and (4) LV end-diastolic and end-systolic volumes. A >15% decrease in LV end-systolic volume at 2-years follow-up was considered as a criterion of reverse LV remodelling. Results Compared with baseline, all patients had reduced PWV, PWV/GLS, LV end-diastolic and end-systolic volumes, while GLS and reservoir left atrial strain were increased (p<0.05) after 2 years. Both baseline and percentage change of PWV/GLS ratio were associated with LV end-systolic volume percentage change at 2 years (r=0.43, p=0.012 and r=0.35, p=0.038, respectively). Patients with LV end-systolic volume reduction >15% had lower baseline PWV and PWV/GLS and higher GLS and left atrial strain than patients with LV end-systolic volume reduction <15% (p<0.05). Multivariable analysis revealed that PWV and PWV/GLS were independently associated with LV remodelling. A baseline value of PWV of 8.1m/s and PWV/GLS of -0.52m/s% had a sensitivity of 84% and 82% and a specificity of 80% and 77% respectively for prediction of LV remodelling (area under the curve: 0.751, p=0.001 and 0.779, p<0.001). Conclusion Ventricular-arterial interaction is an independent predictor of LV remodelling after 2 years of the ischemic event.

Outcomes of Upgrading to LBBP in CRT Nonresponders: A Prospective, Multicenter, Nonrandomized, Case-Control Study

BackgroundCardiac resynchronization therapy (CRT) nonresponders account for nearly 30% of CRT candidates. Left-bundle branch pacing (LBBP) is an alternative to CRT. ObjectivesThis study aimed to evaluate the feasibility, clinical efficacy, and outcomes of upgrading to LBBP in CRT nonresponders, using propensity-score matching (PSM) analysis. MethodsCRT nonresponders were defined as those with an implantable CRT-pacemaker or CRT-defibrillator for more than 12 months who remained nonresponsive (a decrease in left ventricular end-systolic volume of <15% or a left ventricular ejection fraction [LVEF] absolute increase of <5%) after optimal medical therapy and device optimization compared with baseline. In total, 145 CRT nonresponders were prospectively enrolled and randomly divided into 2 groups: upgraded to LBBP (n = 48), and continuing biventricular pacing (BVP) (control; n = 97). PSM was performed at a 1:1 ratio, and clinical evaluation and echocardiographic assessments were compared at baseline and follow-up in paired cohorts. The primary composite endpoint for clinical outcomes (heart failure-related rehospitalization events, all-cause death, or heart transplantation) was analyzed. ResultsSuccessful upgrading to LBBP was achieved in 48/49 patients (97.96%), with a significant decrease in QRS duration (P < 0.001). In the paired LBBP group, LVEF significantly increased (baseline: 29.75% ± 7.79%; 6 months: 37.78% ± 9.25% [P < 0.001]; 12 months: 38.84% ± 12.13% [P < 0.001]) with 21/44 patients (47.73%) classified as echocardiographically responsive, whereas in the BVP control group, no significant improvement was observed (29.55% ± 6.74% vs 29.22% ± 8.10%; P = 0.840). In a multivariate logistic regression model, LV end-diastolic volume and baseline LBBB QRS morphology were independent predictors of echocardiographic response after upgrading to LBBP. At a median 24 months, the primary composite endpoint was significantly lower in the LBBP group (HR: 0.31; 95% CI: 0.14-0.72; log-rank P = 0.007). ConclusionsUpgrading to LBBP is feasible and effective in achieving significant heart function improvement and better clinical outcomes in CRT nonresponders, making it a reasonable and promising pacing strategy. (LBBP in CRT Non-Response patients; ChiCTR1900028131)

Abstract 18159: Cardiac Resynchronization Therapy Response Predicted by Tissue Characterization Using Cardiac Magnetic Resonance Imaging in Non-Ischemic Dilated Cardiomyopathy

Introduction: Tissue characterization using cardiac magnetic resonance (CMR) is helpful for risk stratification in non-ischemic dilated cardiomyopathy (NIDCM). Hypothesis: This study aimed to investigate the predictive role of tissue characterization identified by CMR on cardiac resynchronization therapy (CRT) response. Methods: We retrospectively reviewed the patients who underwent CMR within 1 year before CRT implantation in NIDCM patients at a single tertiary center from January 2018 to September 2022. Late gadolinium enhancement (LGE), native T1, T2 and extracellular volume (ECV) were analyzed. CRT response was defined as a decrease in left ventricular end-systolic volume (LVESV) &gt; 15% or an increase in left ventricular ejection fraction &gt; 5% on TTE after at least 3 months after CRT implantation. Results: Among a total of 101 patients (mean age 66 years, 52.5% of male), 76 (75.2%) patients were defined as CRT responders. CRT responders had more LBBB (96.1% vs. 60.0%, p&lt;0.001) and longer QRS duration (156.0±178.5 vs. 167.0±176.5ms, p=0.005) compared with CRT non-responders. However, LGE burden (34.3 vs. 13.3%, p&lt;0.001), native T1 (1371.6 vs. 1336.8ms, p=0.033), T2 (45.9 vs. 42.1ms, p&lt;0.001), and extracellular volume (ECV, 36.8 vs. 31.0%, p&lt;0.001) were significantly higher in CRT non-responders. The area under the curve (AUC) to predict CRT response is the highest in LGE burden (0.817, 95% confidence interval [CI]: 0.710-0.925), followed by ECV (0.808, 95% CI: 0.711-0.905), T2 (0.779, 95% CI: 0.663-0.895), and native T1 (0.643, 95% CI: 0.520-0.766). After adjustment, LGE burden&gt;20% (odds ratio [OR]: 0.15, 95% CI: 0.02-0.71, p=0.024) and ECV &gt; 34% (OR: 0.13, 95% CI: 0.01-0.78, p=0.037) were independently poor CRT response predictors. Conclusions: The tissue characterization by using CMR is helpful to predict CRT response and clinical outcomes in patients with NIDCM, independently of conventional CRT response predictors.

Abstract 14836: Left Ventricular Extracellular Volume on Computed Tomography is Useful for Predicting Reverse Remodeling After Catheter Ablation for Atrial Fibrillation

Introduction: In the CAMERA-MRI study, restoring sinus rhythm with catheter ablation (CA) for atrial fibrillation (AF) significantly improved left ventricular (LV) ejection fraction (EF), particularly in the absence of LV myocardial fibrosis, determined by magnetic resonance imaging (MRI). LV extracellular volume fraction (ECV) on MRI correlates with myocardial fibrosis. Recently analysis of LVECV on computed tomography (CT) has been feasible and LVECV on CT and MRI correlate well. Little is known about what predicts achieving LV reverse remodeling (LVRR) after CA. Hypothesis: LVECV on pre-ablation planning CT could predict LVRR after CA in patients with AF and reduced LVEF. Methods: One thousand three hundred twenty patients underwent CA for AF in our institutions from Apr 2014 to Aug 2022. Of these, 50 patients (4%) with LVEF under 50% on transthoracic echocardiography (TTE) were included. All patients underwent cardiac CT using 320-detector or 256-detector row CT before the CA. LVECV was measured by CT using non-contrast and late-phase cardiac images (Figure A). We defined LVRR as an LV end-systolic volume decrease of 15% or more, an increase in LVEF to 50% or more, or an absolute LVEF increase of 15% or more. We evaluated the utility of LVECV for the prediction of LVRR after CA. Results: LVRR was achieved in 31 patients (62%) after CA, and LVECV was significantly lower in them than in the others (31.3 ± 3.3% vs. 35.9 ± 6.6%, P &lt; 0.01) (Figure B). On receiver operating characteristic curve analysis, the best cut-off of LVECV for the prediction of LVRR was 34.8%, and the sensitivity and specificity of LVECV for the prediction of RR were 90 and 68% (the area under the curve was 0.72, Figure C). On multivariate logistic regression analysis, LVECV less than or equal to 34.8% was the only significant predictor of LVRR. Conclusion: LVECV on CT is useful for predicting LVRR in patients with AF after CA.

Beneficial effects of upgrading to His-Purkinje system pacing in patients with pacing-induced cardiomyopathy: a systematic review and meta-analysis.

The purpose of this study was to evaluate the effectiveness of His-Purkinje system pacing (HPSP) in the management of patients with pace-induced cardiomyopathy (PICM). PubMed, Embase, Web of Science, and the Cochrane Library were searched comprehensively to collect related studies published from the inception of databases to June 1, 2022. R 4.04 software, including the Metafor package, matrix package, and the Meta package, was utilized to conduct the singe-arm meta-analysis. The methodology index for non-randomized studies (MINORS) was used to assess the methodological quality of the included studies. A total of seven studies were included, involving 164 PICM patients. The meta-analysis showed that HPSP ameliorated the left ventricular ejection fraction (LVEF) by 13.41% (95% CI [11.21-15.61]), improved the New York Heart Association (NYHA) classification by 1.02 (95% CI [-1.41 to -0.63]), and shortened the QRS duration (QRSd) by 60.85 ms (95% CI [-63.94 to -57.75]), resulting in improved cardiac functions in PICM patients. Besides, HPSP reversed the ventricular remodeling, with a 32.46 ml (95% CI [-53.18 to -11.75]) decrease in left ventricular end systolic volume (LVESV) and a 5.93 mm (95% CI [-7.68 to -4.19]) decrease in left ventricular end-diastolic dimension (LVEDD). HPSP also showed stable electrical parameters of pacemakers, with a 0.07 V (95% CI [0.01-0.13]) increase in pacing threshold, a 0.02 mV (95% CI [-0.85 to 0.90]) increase in sensed R-wave amplitude, and a 31.12 Ω reduction in impedance (95% CI [-69.62 to 7.39]). Compared with LBBP, HBP improved LVEF by 13.28% (95% CI [-11.64 to 14.92]) vs 14.43% (95% CI [-13.01 to 15.85]), ameliorated NHYA classification by 1.18 (95% CI [-1.97 to -0.39]) vs 0.95 (95% CI [-1.33 to -0.58]), shortened QRSd by 63.16 ms (95% CI [-67.00 to -59.32]) vs 57.98 ms (95% CI [-62.52 to -53.25]), and decreased LVEDD by 4.12 mm (95% CI [-5.79 to -2.45]) vs 6.26 mm (95% CI [-62.52 to -53.25]). The electrical parameters of the pacemaker were stable in both groups. This meta-analysis showed that HPSP could significantly improve cardiac function, promote reverse remodeling, and provide stable electrical parameters of pacemakers for PICM patients.

The Interaction Between Tricuspid Regurgitation and Cardiac Resynchronization Therapy Response in Patients with Congestive Heart Failure

Background: Aggravation of tricuspid regurgitation (TR) is a predictable issue following cardiac device implantation, while its clinical importance is subject to debate. Objectives: We aimed to recognize the alteration of TR following cardiac resynchronization therapy (CRT) and its effect on the response to CRT. Methods: In this prospective study, 70 candidates were recruited for CRT from those who visited two university hospitals in Tehran and Ahvaz (Iran) from January 2012 to March 2013. Baseline specifications were recorded for all the participants. All the patients underwent echocardiography before and 6 months after CRT administration. They were then divided into two categories for further comparison: (1) Patients with no or mild TR and (2) patients with moderate-to-severe TR. The echocardiographic response to CRT was defined as a left ventricular end-systolic volume (LVESV) decrease of &gt;15% or left ventricular ejection fraction (LVEF) advancement of &gt;5%. The clinical response to CRT was one class improvement based on the New York Heart Association (NYHA) class. Results: Of the patients, 24 had moderate-to-severe TR. Although the increase in cases with moderate-to-severe TR after CRT was not significant, the aggravation of TR degree after the procedure was significant (P = 0.002). Moreover, the NYHA class significantly improved after the CRT (P = 0.02). The number of cases with a clinical response to CRT based on improvement of the NYHA class was significantly greater in patients with no TR or mild TR at baseline (P = 0.003). There was no significant variation in response to CRT among patients who experienced TR exacerbation after CRT compared with those who had no change or a reduction in TR. Conclusions: This study demonstrated that TR severity was exacerbated following CRT, but this alternation in TR severity had no significant effect on the response to CRT. Therefore, the presence and development of TR before and after CRT must not affect the criteria for choosing cardiac resynchronization therapy for appropriate patients.

Sex-specific Evaluation of Ventricular Ejection Fraction and End-Systolic Volume Applied to Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) can decrease the risk of heart failure (HF) events in relatively asymptomatic patients with a reduced ejection fraction (EF) and wide QRS complex. However, individual response to this type of therapy varies widely. Often based on either EF increase or end-systolic volume (ESV) decrease as criterion, a subgroup of super-responders has been described. Therefore, it is important to determine factors that can predict a favorable response and identify those patients who may benefit from CRT. With this goal in mind we explored the possible role of ESV.To improve insight in ventricular pump function we previously introduced the volume regulation graph (VRG), relating ESV to end-diastolic volume (EDV). An individual patient is uniquely defined by the prevailing working point in the volume domain. The traditional metric EF can be graphically derived for each working point. The nonlinear association between EF and ESV is given by EF = 1 + γ {ESV / (δ - ESV)}, with empirical constants γ and δ. The impact of CRT super-responders on EF can be evaluated, taking into account sex-specific ESV values. Based on available regression equations we modeled the impact on EF (as percent points) resulting from CRT-induced fractional ESV changes expressed as % of baseline ESV. Our analysis confirms clinical findings, indicating that CRT super-responders are likely to be women, and clarify why a specific reduction of ESV cannot be directly translated into EF improvement. We propose that the EF as CRT criterion should be abandoned and replaced by sex-specific ESV evaluations.Clinical Relevance- Response to CRT should be evaluated in a sex-specific manner. The smaller heart size in women has implications for the interpretation of percentwise reductions of ESV and their translation into an associated increase of EF.

Relationship between left ventricular mechanical dyssynchrony with cardiac resynchronization therapy response in chronic heart failure patients with left bundle branch block

Aim. To investigate the relationship between left ventricular (LV) mechanical dyssynchrony with cardiac resynchronization therapy (CRT) response in chronic heart failure (CHF) pts with left bundle branch block.Methods. Forty-nine pts (male - 34 [69.4%], average age 58.3±11.4 years) with sinus rhythm, permanent left bundle branch block with QRS duration ≥150 ms and New York Heart Association (NYHA) II-III functional class of CHF were included in the study. In addition to full examination, myocardial perfusion scintigraphy (MPS) and gated blood pool single-photon emission computed tomography (gBPS) were performed before and 6 months after CRT devices with cardioverter-defibrillator function implantation. Pts were considered as responders to CRT if they fulfilled after 6-month follow-up the following combined criteria: NYHA FC improvement ≥1 class + LV end systolic volume decrease &gt;15% or NYHA FC improvement ≥1 class + LV ejection fraction improvement &gt;5%.Results. The 1st and 2nd groups included 35 (71.4%) and 14 (28.6%) pts with and without response to CRT respectively. Groups were comparable in terms of pre-CRT implantation clinical and instrumental parameters, except for MPS and gBPS parameters. The multivariate logistic regression had shown that only ∆interventricular dyssynchrony (adjusted odds ratio [OR] 1,0349; 95% confidence interval [CI] 1.0075-1,0631; р=0.01) and phase standard deviation of the anterior LV wall (OR 1.0669; 95% CI 1.0118-1.1251; p=0.01) were independently related with CRT response. An increase in the prognostic coefficient, calculated using the ∆interventricular dyssynchrony and phase standard deviation of the anterior LV wall, more than 0.67 was a predictor of CRT response (area under the curve 0.918; sensitivity 85.71; specificity 85.71; p &lt;0.001).Conclusion. The mechanical dyssynchrony assessed by MPS and gBPS is associated with CRT response. According to our predictive model, an increase in prognostic coefficient more than 0.67 is a predictor of CRT response.

Establishing minimally important differences for cardiac MRI end-points in pulmonary arterial hypertension.

Cardiac magnetic resonance (CMR) is the gold standard technique to assess biventricular volumes and function, and is increasingly being considered as an end-point in clinical studies. Currently, with the exception of right ventricular (RV) stroke volume and RV end-diastolic volume, there is only limited data on minimally important differences (MIDs) reported for CMR metrics. Our study aimed to identify MIDs for CMR metrics based on US Food and Drug Administration recommendations for a clinical outcome measure that should reflect how a patient "feels, functions or survives". Consecutive treatment-naïve patients with pulmonary arterial hypertension (PAH) between 2010 and 2022 who had two CMR scans (at baseline prior to treatment and 12 months following treatment) were identified from the ASPIRE registry. All patients were followed up for 1 additional year after the second scan. For both scans, cardiac measurements were obtained from a validated fully automated segmentation tool. The MID in CMR metrics was determined using two distribution-based (0.5sd and minimal detectable change) and two anchor-based (change difference and generalised linear model regression) methods benchmarked to how a patient "feels" (emPHasis-10 quality of life questionnaire), "functions" (incremental shuttle walk test) or "survives" for 1-year mortality to changes in CMR measurements. 254 patients with PAH were included (mean±sd age 53±16 years, 79% female and 66% categorised as intermediate risk based on the 2022 European Society of Cardiology/European Respiratory Society risk score). We identified a 5% absolute increase in RV ejection fraction and a 17 mL decrease in RV end-diastolic or end-systolic volumes as the MIDs for improvement. Conversely, a 5% decrease in RV ejection fraction and a 10 mL increase in RV volumes were associated with worsening. This study establishes clinically relevant CMR MIDs for how a patient "feels, functions or survives" in response to PAH treatment. These findings provide further support for the use of CMR as a clinically relevant clinical outcome measure and will aid trial size calculations for studies using CMR.

Cardiac shear wave elastography can detect myocardial remodelling in LBBB patients undergoing CRT

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac shear wave elastography (SWE) allows for the non-invasive assessment of myocardial stiffness via the detection of shear waves travelling through the heart after e.g. mitral valve closure (MVC). The propagation speed of these waves is directly related to myocardial stiffness. Myocardial stiffness depends on the intrinsic properties of the myocardium. Therefore, processes that alter these intrinsic properties, such as cardiac remodelling, could influence shear wave speed. In this way, SWE could be an interesting tool to directly and non-invasively monitor cardiac remodelling over time. Purpose To evaluate the effect of reverse remodelling on myocardial stiffness in left bundle branch block (LBBB) patients undergoing cardiac resynchronization therapy (CRT). Methods Fourteen non-ischemic patients with LBBB undergoing CRT were included. SWE was performed 1 day after CRT implantation and repeated after 6 and 12 months. Eleven age-matched healthy volunteers served as controls. Volumetric response was defined as ≥15% decrease in end-systolic volume after 1 year of CRT. Echocardiographic images were taken during biventricular (BiV) pacing ON (resynchronized) and BiV pacing OFF (native LBBB conduction), both with a conventional ultrasound machine and an experimental high frame rate ultrasound scanner (999 ± 134 frames/s). For SWE, LV parasternal long-axis views were acquired. Shear waves were visualized in M-modes of the septum, colour coded for tissue acceleration. The slope of the shear waves in the M-mode represents their propagation speed (Figure 1A). Results All included patients were volumetric responders. LV ejection fraction and global longitudinal strain improved significantly over time. LV volumes decreased significantly in all patients during one year of CRT (Table 1), reflecting reverse remodelling. Shear wave speed was significantly higher immediately after implantation compared to healthy controls during BiV ON (5.9±1.5 vs 4.6±1.1 m/s; p = 0.02; Figure 1B), but not at 6 months (5.3±1.5 vs 4.6±1.1 m/s; p = 0.19) and 12 months (5.1±1.1 vs 4.6±1.1 m/s; p = 0.39) after implantation (Figure 1B), indicating that myocardial stiffness normalized over time due to reverse remodelling. Moreover, shear wave speed was significantly higher during BiV OFF compared to BiV ON immediately after implantation (5.9±1.5 vs 6.7±1.4 m/s; p = 0.022) and at 6 months (5.3±1.5 vs 6.1±1.4 m/s; p = 0.048), indicating that the reintroduction of dyssynchrony increases shear wave speed after MVC (Figure 1B). One year after implantation shear wave speed was not significantly different between BiV ON and OFF (5.1±1.1 vs 5.2±0.4 m/s; p = 0.78; Figure 1B). This could imply that dyssynchrony decreases over time as a result of reverse remodelling. Conclusion SWE can non-invasively detect changes in myocardial properties during reverse remodelling under CRT. Myocardial stiffness gradually decreases towards the range of age-matched healthy hearts after CRT.

The prognostic value of non-invasively estimated left atrial pressure in patients undergoing cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 research and innovative program under the Marie Sklodowska -Curie grant agreement No. 860745. Background The impact of non-invasively estimated left atrial pressure (LAP) on cardiac resynchronization therapy (CRT) outcome has been previously investigated, yet with inconsistent results. Aim We aim at investigating the association between baseline LAP and CRT outcome applying both the standard guideline approach (Nagueh et al 2016) and the integrated guideline + LA strain approach. Methods Datasets of 219 CRT patients were retrospectively analyzed. All patients had full echocardiographic diastolic function assessment before CRT and were classified based on the guidelines approach for estimation of LAP into normal LAP (nLAP = 40%), elevated LAP (eLAP = 49%) and undetermined LAP (uLAP = 11%, when classification was not possible due to missing data, Figure A, solid bars). All baseline characteristics, comorbidities, and ECG data in addition to LA strain components before CRT were collected and analyzed. The amount of CRT-induced LV reverse remodeling was assessed at 12±6 months after CRT and was defined as percentage decrease of LV end-systolic volume (LVESV) compared to baseline. Patients were followed up for a mean of 4.8 years (interquartile range (IQR): 2.7–6.0) for all-cause mortality. Results Compared to patients with eLAP, patients with nLAP were more of female sex (40% vs. 21%) and they had lower serum creatinine (1.1 ± 0.4 vs. 1.5 ± 0.6 mg/dl). ECG data showed that they had less prevalence of AF (9 vs. 15%). All LA strain indices were better in patients with nLAP (23 ± 9 vs. 12 ± 7% for reservoir strain, 10 ± 4 vs. 7 ± 5% for conduit strain and 11 ± 7 vs. 4 ± 4% for pump strain, P &amp;lt; 0.01 for all comparisons). At follow-up, LVESV was reduced more in patients with nLAP than in patients with eLAP (47 ± 28 vs. 30 ± 30%, P &amp;lt; 0.01, figure B solid bars). Survival rates of patients with nLAP was significantly higher than patients with eLAP (Hazard ratio (HR): 0.40; confidence interval (CI): 0.22–0.27; P &amp;lt; 0.01, figure C solid lines). In the subgroup of uLAP an LA reservoir strain was used to further identify patients with nLAP (LA reservoir strain ≥ 18%). Accordingly, the integrated guideline+LA strain approach improved the feasibility for classification from 89% to 97%, where the percentage of the uLAP dropped from 11% to 3% (only patients with no baseline LA strain remained classified as uLAP, figure A). Patients with nLAP according to the integrated approach showed very similar CRT-induced LV reverse remodeling (figure B dashed bars) and long-term survival as compared to patients with nLAP according to the standard approach (figure C dashed lines). Conclusion Applying the standard guideline approach for LAP, patients with nLAP before CRT show more LV reverse remodeling and better long-term survival after CRT, as compared to patients with eLAP. The guideline + LA strain approach markedly improves the feasibility of LAP estimation, while not influencing the association between LAP and outcome after CRT.

Baseline mechanical dyssynchrony is associated with better diastolic function in patients undergoing cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 research and innovative program under the Marie Sklodowska -Curie grant agreement No. 860745. Background Outcome after cardiac resynchronization therapy has been shown to be worse in patients with diastolic dysfunction. Aim We aim at investigating the association between baseline mechanical dyssynchrony (Dyss) and diastolic function, both assessed using conventional 2D echocardiography in heart failure patients undergoing cardiac resynchronization therapy (CRT). Methods Datasets of 219 patients were retrospectively analyzed, including full echocardiographic diastolic function assessment before CRT implantation. Using the guideline approach (Nagueh et al 2016) for estimating left atrial pressure (LAP), patients were classified as elevated LAP (eLAP = 49%), normal LAP (nLAP = 40%), and undetermined LAP (uLAP = 11%). Patients with nLAP and uLAP together were referred to as non-elevated LAP (non-eLAP = 51%). Dyss was defined as the presence of apical rocking (ApRock) and /or septal flash (SF). All baseline characteristics, comorbidities, ECG data and left atrial (LA) strain components (reservoir, conduit, and pump strains) were collected and analyzed. The amount of CRT-induced LV reverse remodeling was assessed at 12±6 months after CRT and was defined as percentage decrease of LV end-systolic volume (LVESV) compared to baseline. Patients were followed up for a mean of 4.8 years (interquartile range (IQR): 2.7–6.0) for all-cause mortality. Results Compared to patients without Dyss, patients with Dyss were significantly more of female sex (39% vs. 14%), had less diabetes mellitus (21 vs. 34%), had lower serum creatinine (1.2±0.5 vs. 1.4±0.6 mg/dl) and less prevalence of ischemic cardiomyopathy, 43% vs. 68%). They used significantly more ACEi (91% vs. 76%). ECG data showed that they had less prevalence of AF (8 vs. 22%) and had wider QRS complex (158±18 vs. 152±18 msec), P-values &amp;lt;0.05 for all comparisons. Baseline LV volumes and EF were not significantly different between patients with and without Dyss. Patients with Dyss show less prevalence of eLAP compared to patients without Dyss (30% vs. 60%, P &amp;lt;0.001, figure A). Additionally, they had better LA function on all LA strain indices (Figure B). In the multivariable analysis for predicting the association with eLAP, the presence of Dyss was independently associated with less eLAP after adjusting for most of the baseline variables (HR: 0.31, CI: 0.1–0.7, P &amp;lt;0.01). At follow up, patients who had both Dyss and non-eLAP before CRT showed the largest amount of LV reverse remodeling compared to other patients. Similarly, the patients with Dyss and non-eLAP showed the best survival compared to other groups (figure C). Conclusion The presence of mechanical dyssynchrony is associated with better diastolic function and lower estimated LAP before CRT. Additionally, the combination of Dyss and non-eLAP before CRT was associated with the most CRT-induced LV reverse remodeling and best long-term survival.

Characterisation of responder profiles for cardiac resynchronisation therapy based on explainable machine-learning and virtual patient approaches

Abstract Funding Acknowledgements Type of funding sources: None. Context Cardiac resynchronisation therapy (CRT) is an implant-based therapy applied to patients with a specific heart failure (HF) profile. The characterisation and identification of CRT candidates is challenging since the application of current guidelines still induces a non-responder rate of about 30%. Recently, the assessment of left ventricular mechanics by speckle tracking echocardiography has been shown to provide useful information for patient’s selection. However, the interpretation of stain curves remains difficult due to the great heterogeneities in dyssynchrony patterns. The objective of this study is to propose a characterisation of HF patient profiles considering their responses to CRT, based on unsupervised machine-learning and virtual patient approaches. Methods The prospective database includes 250 patients. Before implantation of CRT, transthoracic echocardiography were performed in order to extract regional myocardial longitudinal strain curves. At 6-month follow-up, response to CRT were defined as 15 % decrease in LV end-systolic volume. Feature extraction was performed from clinical, electrocardiographic, and echocardiographic data, leading to a set of 70 features per patient. The set of all features was clustered by applying the K-Means method. Virtual patients were defined from patient-specific computational models for patients associated with the barycenter of each cluster. The proposed model includes the cardiac electrical system, right and left atria, multi-segment representation of the right and left ventricles, systemic and pulmonary circulations. Contractility, stiffness and electrical activation delays are identified from each virtual patient and each LV cardiac segment. Results Five clusters were identified from clinical, original and classical echocardiographic features with response rates ranging from 50% to 93%. Virtual patients were defined for the 5 patients associated with each cluster barycenter visualised by a principal component analysis. Patient-specific simulated strain curves were provided for the 16 LV segments of these 5 patients. A close match was observed between experimental and simulated curves pattern. The mean RMSE on the five patients is 3.97% ± 1.74. Cluster 1 and 2, which are the two groups with below-average rate, are associated with low contractility of myocardial segments. The other clusters with normal or elevated response rates present higher contractility and delayed electrical activation of the lateral wall. Conclusions A new pipeline, combining personalised cardiovascular modelling and unsupervised machine-learning algorithms, was proposed to provide a phenotyping of HF patient profiles in the context of CRT. This novel approach appears a promising tool to improve understanding of LV mechanics, patient characterisation and selection before CRT.

Should we use a semi-quantitative assessment of apical rocking to predict outcome in CRT patients?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Apical rocking (AR) is a systolic septal-to-lateral motion of the apex observed on echocardiography in the apical 4-chamber view in some patients with a ventricular conduction delay. It is a strong predictor for outcome after cardiac resynchronization therapy (CRT) and has been suggested as selection criterion for CRT. Critics argue that simple visual assessment of AR may be too subjective for clinical use. Speckle-tracking based myocardial motion analysis may allow to objectify AR and may reduce a potential observer dependence. Purpose To compare the visual assessment of AR (VAR) to the semi-quantitative assessment of AR (QAR) in patients for the prediction of (i) volume response and (ii) all-cause death after CRT. To assess interobserver agreement for VAR and QAR. Methods We retrospectively analyzed data from 166 patients with a first CRT implantation. All patients had an echo before CRT implantation and approximately 1 year after implantation. VAR and QAR analysis were performed by three experienced observers on echocardiographic apical 4-chamber views before CRT implantation. QAR was obtained by performing speckle-tracking in the apical segments of the lateral and septal wall. A negative lateral displacement with a positive septal displacement during systole was considered as AR (Figure). Areas under the ROC-curves (AUC) for prediction of volume response were determined and compared using the DeLong method. Volume response was defined as a ≥15% decrease in left ventricular end-systolic volume (LVESV) within 1 year. Patients were followed for a mean duration of 5.2 years. Hazard ratios (HR) for all-time all-cause death after CRT were calculated using an univariate Cox proportional-hazards regression model. Interobserver agreement was analysed using the intraclass correlation coefficient (ICC) based on an average measurement, absolute agreement, two-way mixed effects model. Results 77% (n = 122) of patients were volume responders. Seven patients died before follow-up echocardiography. 31% (n = 52) of patients died during follow-up. AUC for volume response were similar for VAR and QAR (0.73 vs 0.72, p = 0.782). HR for all-time all-cause death were similar for VAR (0.39, 0.25–0.61; p&amp;lt;0.001) and QAR (0.37, 0.23–0.59; p&amp;lt;0.001). ICC was good for VAR (0.78; 0.55–0.90) and QAR (0.84; 0.67–0.93). Conclusion Semi-quantification of AR (QAR) using speckle-tracking technology achieves comparable results as the simple visual assessment of AR (VAR) when performed by an experienced reader for prediction of volume response and prediction of all-cause death in patients eligible for CRT. Interobserver agreement for VAR and QAR was similarly good. QAR could be used as confirmation of the visual assessment and may support clinicians less familiar with the visual assessment.

Delta 9-tetrahydrocannabinol conserves cardiovascular functions in a rat model of endotoxemia: Involvement of endothelial molecular mechanisms and oxidative-nitrative stress.

In endotoxemic models, the inflammatory parameters are altered to a favorable direction as a response to activation of cannabinoid receptors 1 and 2. The phytocannabinoid Δ9-tetrahydrocannabinol (THC) is an agonist/partial antagonist of both cannabinoid receptors. This report targets the effects of THC on the cardiovascular system of endotoxemic rats. In our 24-hour endotoxemic rat model (E. coli derived lipopolysaccharide, LPS i.v. 5mg/kg) with THC treatment (LPS+THC 10 mg/kg i.p.), we investigated cardiac function by echocariography and endothelium-dependent relaxation of the thoracic aorta by isometric force measurement compared to vehicle controls. To evaluate the molecular mechanism, we measured endothelial NOS and COX-2 density by immunohistochemistry; and determined the levels of cGMP, the oxidative stress marker 4-hydroxynonenal, the nitrative stress marker 3-nitrotyrosine, and poly(ADP-ribose) polymers. A decrease in end-systolic and end-diastolic ventricular volumes in the LPS group was observed, which was absent in LPS+THC animals. Endothelium-dependent relaxation was worsened by LPS but not in the LPS+THC group. LPS administration decreased the abundance of cannabinoid receptors. Oxidative-nitrative stress markers showed an increment, and cGMP, eNOS staining showed a decrement in response to LPS. THC only decreased the oxidative-nitrative stress but had no effect on cGMP and eNOS density. COX-2 staining was reduced by THC. We hypothesize that the reduced diastolic filling in the LPS group is a consequence of vascular dysfunction, preventable by THC. The mechanism of action of THC is not based on its local effect on aortic NO homeostasis. The reduced oxidative-nitrative stress and the COX-2 suggest the activation of an anti-inflammatory pathway.

Response to cardiac resynchronization therapy and treatment with ARNi and iSGLT2

Abstract Funding Acknowledgements Type of funding sources: None. Background Heart failure with reduced ejection fraction (HFrEF) is associated in about one third of patients with abnormal conduction of the cardiac electrical impulse, resulting in asynchronous activation of the ventricles and worsening of cardiac pump function. Cardiac resynchronization therapy via biventricular pacing (CRT) has demonstrated improvement in cardiac mechanical function. The pharmacological treatment of HFrEF with sacubitril/valsartan (ARNi) and glyphozines (iSGLT2) have been shown to significantly reduce mortality. Purpose The objective of our study was 1) to evaluate the effect of therapy with ARNi and iSGLT2 on the recovery of left ventricular ejection fraction (LVEF %) in a population affected by HFrEF and with CRT 2) to evaluate whether there are any differences in terms of improvement in LVEF among patients who introduced these drugs into therapy before CRT implantation and those who introduced them after. Methods This single-center retrospective study analyzed patients with HFrEF and CRTD. These patients in our center undergo regular follow-up with cardiology visit, ECG and echocardiography every 6 months. We analyzed clinical features, drug therapy, and echocardiographic data including LVEF. Patients were considered responders they had an increase in LVEF ≥ 5% or a decrease in end-systolic volume of 15% at 6 months. The data analysis was performed with the R software. Results 258 patients were included, 202 males (78%) with a mean age of 69.4 years, and 67.4% of them with ischemic HFrEF. Diabetes mellitus (68%), dyslipidemia (87%) and arterial hypertension (73%) were the most frequent comorbidities. Fifty-two percent of patients (133) were CRT responders and there was no difference in the proportion of responders between patients receiving ARNi and/or iSGLT2 therapy and those without (55% vs 47%; p=ns). The mean increase of LVEF was also similar between the two groups (+7.7% vs +10.3%; p=ns). In the group of patients taking ARNi or iSGLT2, no significant differences were found between patients taking these drugs already before CRT compared to those who started after. Conclusions In this population, HFrEF patients with CRT, therapy with ARNi or iSGLT2 does not affect the response to CRT.

Safety and Efficacy of Istaroxime 1.0 and 1.5 µg/kg/min for Patients With Pre-Cardiogenic Shock

Istaroxime was shown, in a small study, to increase systolic blood pressure (SBP) in patients with pre-cardiogenic shock (CS) due to acute heart failure (AHF). In the current analysis, we describe the effects of 2 doses of istaroxime 1.0 (Ista-1) and 1.5 µg/kg/min (Ista-1.5). The target dose of istaroxime, administered in a double-blind, placebo-controlled fashion, was 1.5 µg/kg/min in the first cohort (n = 24), and it was reduced to 1.0 µg/kg/min in subsequent patients (n = 36). Ista-1 was associated with numerically larger effects on SBP area under the curve, with a 93.6% relative increase from baseline during the first 6 hours with Ista-1 vs 39.5% for Ista-1.5, and with a 49.4% and 24.3% relative increase, respectively, at 24 hours. Compared to placebo, Ista-1.5 had more worsening HF events until day 5 and fewer days alive out of hospital (DAOH) through day 30. Ista-1 had no worsening HF events, and DAOH to day 30 were significantly increased. Effects on echocardiographic measures were similar, although decreases in left ventricular end systolic and diastolic volumes were numerically larger in the Ista-1 group. Ista-1, but not Ista-1.5, showed numerically smaller creatinine increases and larger decreases in natriuretic peptides as compared to placebo. There were 5 serious adverse events in Ista-1.5 (4 of which were cardiac) but only 1 in Ista-1. In patients with pre-CS due to AHF, istaroxime 1.0 µg/kg/min induced beneficial effects on SBP and DAOH. Clinical benefits appear to be reached at dosages less than 1.5 ug/kg/min.

Dyssynchrony and Response to Cardiac Resynchronization Therapy in Heart Failure Patients With Unfavorable Electrical Characteristics

BackgroundAmong heart failure (HF) patients undergoing cardiac resynchronization therapy (CRT), those with unfavorable electrical characteristics (UEC) are less frequently CRT responders. ObjectivesIn this study, the authors sought to evaluate the relationship between preprocedural echocardiographic parameters of electromechanical dyssynchrony (EMD) and outcome following CRT. MethodsAmong 551 patients receiving CRT, 121 with UEC, defined as atypical left bundle branch, presence of right bundle branch block, or unspecified intraventricular conduction disturbance, were enrolled. Indices of EMD were presence of septal flash, apical rocking, septal deformation patterns, and global wasted work (GWW), determined with the use of speckle-tracking strain echocardiography. Endpoints were response to CRT, defined as a relative decrease in left ventricular end-systolic volume ≥15% at 9-month postoperative follow-up, and all-cause death or HF hospitalization during follow-up. ResultsAmong the 121 patients, 68 (56%) were CRT responders. In multivariate analysis, GWW ≥200 mm Hg% (adjusted odds ratio [aOR]: 4.17 [95% CI: 1.33-14.56]; P = 0.0182) and longitudinal strain septal contraction patterns 1 and 2 (aOR: 10.05 [95% CI: 2.82-43.97]; P < 0.001) were associated with CRT response. During a 46-month follow-up (IQR: 42-55 months), survival free from death or HF hospitalization increased with the number of positive criteria (87% for 2, 59% for 1, and 27% for 0). After adjustment for established predictors of outcome in patients receiving CRT, absence of either of the 2 criteria remained associated with a considerable increased risk of death and/or HF hospitalization (adjusted HR: 4.83 [95% CI: 1.84-12.68]; P = 0.001). ConclusionsIn patients with UEC, echocardiographic assessment of EMD may help to select patients who will derive benefit from CRT. (Echocardiography in Cardiac Resynchronization Therapy [Echo-CRT]; NCT02986633)