Predicting the response to cardiac resynchronization therapy using in silico heart models: pilot study of comparison between in silico and real cardiac resynchronization therapy outcomes

Contemporary and future trends in cardiac resynchronization therapy to enhance response

The absence of clinical response in 30% to 40% of patients receiving cardiac resynchronization therapy (CRT) poses a great challenge to heart failure clinicians and device implanters.It is well documented that positioning of the left ventricular (LV) lead in areas of myocardial scar in patients with ischemic cardiomyopathy is associated with a diminished response to CRT.Regions of slow conduction exist in both nonischemic and ischemic cardiomyopathy that can be delineated using noncontact mapping, whereby the electrophysiological properties of a chamber can be characterized using a multielectrode array.Using this technique, the authors evaluated the effect of pacing inside and outside regions of slow conduction on acute hemodynamic response to CRT.Procedures were performed in a combined x-ray and MRI environment so that tissue characterization by delayed-enhancement cardiac MRI could be correlated with electrophysiological assessment.Both endocardial and transvenous epicardial LV pacing were performed with the hypothesis that endocardial pacing may be more effective as a result of reproducing the physiological pattern of activation of the LV myocardium as well as a lack of constraint by the coronary venous anatomy.The authors found that zones of slow conduction could be identified using delayed-enhancement cardiovascular magnetic resonance in patients with an ischemic heart failure etiology but not in patients with nonischemic cardiomyopathy.The short-term effect of CRT was superior in response to endocardial compared with epicardial pacing.Stimulation within zones of slow conduction was associated with a diminished response to CRT.This is a potential explanation for lack of response to CRT and reinforces the need for positioning the LV lead on an individual basis. Conclusions:Endocardial LV pacing appears superior to conventional CRT, although the optimal site varies among patients and is influenced by pacing within areas of slow conduction.Delayedenhancement cardiovascular magnetic resonance was a poor predictor of zones of slow conduction in patients without ischemia. 1 Relative Merits of Left Ventricular Dyssynchrony, Left Ventricular Lead Position, and Myocardial Scar to Predict Long-Term Survival of Ischemic Heart Failure Patients Undergoing Cardiac Resynchronization TherapySummary: The beneficial effects of cardiac resynchronization therapy on long-term survival are influenced by several pathophysiolog-ical factors.The present study demonstrated the relative merits of left ventricular (LV) dyssynchrony, LV lead position, and myocardial scar to predict long-term outcome of patients with ischemic heart failure treated with cardiac resynchronization therapy.With speckletracking radial strain analysis, the extent of LV dyssynchrony, site of latest mechanical activation, and presence of myocardial scar at the LV segment where the LV pacing lead is placed were evaluated.In addition, the LV lead position was derived from chest radiograph and was defined as concordant when the LV pacing lead coincided with the site of latest mechanical activation.Mean baseline LV radial dyssynchrony was 133Ϯ98 ms.A concordant LV lead position was reported in 271 (68%) patients, and the mean value of peak radial strain at the targeted segment was 18.9Ϯ12.6%.During a median follow-up of 21 months, 88 (22%) patients died.Larger LV radial dyssynchrony at baseline was an independent predictor of superior long-term survival (hazard ratio, 0.995 per 1-ms increment; Pϭ0.001), whereas a discordant LV lead position (hazard ratio, 2.086; Pϭ0.001) and myocardial scar in the segment targeted by the LV lead (hazard ratio, 2.913; PϽ0.001) were independent predictors of worse outcome.Addition of these 3 parameters yielded incremental prognostic value over the combination of clinical parameters.These data underscore the need for integrated evaluation that includes assessment of these 3 parameters to further improve patient selection and survival after cardiac resynchronization therapy.Conclusions: Baseline LV radial dyssynchrony, discordant LV lead position, and myocardial scar in the region of the LV pacing lead were independent determinants of long-term prognosis in patients with ischemic heart failure treated with cardiac resynchronization therapy.Larger baseline LV dyssynchrony predicted superior longterm survival, whereas discordant LV lead position and myocardial scar predicted worse outcome. 2 Prediction of Cardiac Resynchronization Therapy Response: Value of Calibrated Integrated Backscatter ImagingSummary: According to current guidelines, candidates for cardiac resynchronization therapy (CRT) are patients in New York Heart Association functional class III to IV heart failure with left ventricular (LV) ejection fraction Յ35% and QRS duration Ն120 ms.However, by applying these selection criteria, more than one third of the patients do not show clinical response or LV reverse remodeling.Among several factors that determine a favorable response to CRT, the amount of LV fibrosis as assessed, for example, with cardiovascular magnetic resonance has been shown to be an important issue.This study demonstrated that myocardial ultrasound reflectivity is an important determinant of CRT response in the overall heart failure

Background Cardiac resynchronization therapy (CRT) is treatment for patients with heart failure and left ventricular (LV) dyssynchrony. The objective of this study is to evaluate the feasibility of an in silico electromechanical heart model to predict CRT outcomes. Methods The three-dimensional heart geometries of 11 patients (age, 64.0±10.7 years, 4 men) with CRT were constructed from cardiac computed tomography images. We coupled cardiac electrical excitation and mechanical contraction with vascular hemodynamics using a lumped parameter model. We predicted the LV end-diastolic and end-systolic volumes and LV ejection fraction (LVEF) after CRT implantation using the in silico CRT simulation model. We compared the in silico CRT outcomes with the real CRT outcomes. Results Two patients were in silico CRT responders, and those 2 patients were also real CRT responders. Nine patients were in silico CRT non-responders, 8 who were real CRT non-responders, and 1 who was a real CRT responder. The in silico CRT outcomes agreed with the real CRT outcomes in 10 of 11 patients. The positive and negative predictive values and accuracy of the in silico CRT model were 100%, 88.9%, and 90.9%, respectively. Conclusion The in silico CRT simulation model is feasible for predicting real CRT outcomes.In silico CRT simulation model generatioAn example (patient No. 2) of LV (black

Managing atrial fibrillation in the CRT patient: Controversy or consensus?

We investigated the impact of baseline left atrial (LA) strain data and estimated left atrial pressure (LAP) by applying the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging (ASE/EACVI) guidelines on cardiac resynchronization therapy (CRT) outcomes. Datasets of 219 CRT patients were retrospectively analysed. All patients had full echocardiographic diastolic function assessment before CRT and were classified based on the guideline algorithm into normal LAP (nLAP = 40%), elevated LAP (eLAP = 49%) and indeterminate LAP (iLAP = 11%). All relevant baseline characteristics were analysed. CRT-induced left ventricular (LV) reverse remodeling was measured as the relative change of LV end-systolic volume (LVESV) at 12 ± 6 months after CRT compared to baseline. Patients were followed up for all-cause mortality for a mean of 4.8 years [interquartile range (IQR): 2.7-6.0 years]. At follow-up, CRT resulted in more pronounced reduction of LVESV in patients with nLAP than in patients with eLAP. In univariate analysis, nLAP was associated with LV reverse remodelling (p < 0.001), as well as long-term survival after CRT (p < 0.01). However, multivariable analysis showed that only the association between nLAP and LV reverse remodelling after CRT is independent (p < 0.01). Adding LA strain analysis to the guideline algorithm improved the feasibility of LAP estimation without affecting the association between estimated LAP and CRT outcome. Normal LAP before CRT, estimated using the 2016 ASE/EACVI guideline algorithm, is associated with LV reverse remodelling and long-term survival after CRT. Albeit non-independent, it can serve as a non-invasive imaging-based predictor of effective therapy. Furthermore, the inclusion of LA reservoir strain in the guideline algorithm can enhance the feasibility of LAP estimation without affecting the association between LAP and CRT outcome.

Does cardiac resynchronization therapy benefit patients with right bundle branch block: cardiac resynchronization therapy has a role in patients with right bundle branch block.

AimsTo evaluate in patients with heart failure with reduced ejection fraction (HFrEF) the association between patient characteristics and likelihood of receiving cardiac resynchronization therapy (CRT), as well as between CRT and clinical outcomes, according to comorbid atrial fibrillation (AF).Methods and resultsPatients in the Swedish Heart Failure (HF) Registry who met the guidelines’ recommendation for CRT between 2014 and 2022 were included. The primary endpoint was the composite of time to first HF hospitalization or cardiovascular (CV) death. Secondary endpoints were its individual components, all-cause death, and the total number of HF hospitalizations. Out of 3530 patients with HFrEF and an indication for CRT, 24.7% received a CRT. A history of or concomitant AF were observed in 51.6% of patients. AF was not associated with the likelihood of receiving a CRT, and the patient characteristics independently associated with CRT were consistent regardless of AF, except for CRT being less likely implanted in patients with valvular disease without AF, and more likely among those with AF and university (vs. compulsory) education. Regardless of AF, CRT use was associated with a lower adjusted risk of CV death/first HF hospitalization [hazard ratio (HR): 0.71, 95% confidence interval (CI) 0.64–0.79], of its individual components, and of all-cause death (HR: 0.72, 95% CI 0.64–0.81), but not with total number of HF hospitalizations.ConclusionA diagnosis of AF was not associated with the likelihood of receiving CRT in real-world HF care, nor did it affect the association between CRT and lower risk of clinical outcomes.

PO-02-019 PREDICTION OF RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY USING IN SILICO HEART MODELS: COMPARISON OF IN SILICO AND REAL-WORLD CRT OUTCOMES

First-Phase Ejection Fraction Predicts Response to Cardiac Resynchronization Therapy and Adverse Outcomes

There are ongoing efforts to optimize patient selection criteria for cardiac resynchronization therapy (CRT). In this regard, the relationship between acute change in left ventricular synchrony (LV) after CRT and patient outcome remains undefined. A novel protocol was designed to evaluate acute change in left LV synchrony after CRT using phase analysis of standard gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging with a single injection of radiotracer and prospectively applied to 44 patients undergoing CRT. Immediately after CRT, 18 (41%), 11 (25%), and 15 (34%) patients had an improvement, no change, or a worsening in LV synchrony. An algorithm incorporating the presence of baseline dyssynchrony, myocardial scar burden, and lead concordance predicted acute improvement or no change in LV synchrony with 72% sensitivity, 93% specificity, 96% positive predictive value, and 64% negative predictive value and had 96% negative predictive value for acute deterioration in synchrony. Over a follow-up period of 9.6 ± 6.8 months, patients who had an acute deterioration in synchrony after CRT had a higher composite event rate of death, heart failure hospitalizations, appropriate defibrillator discharges, and CRT device deactivation for worsening heart failure symptoms, compared with patients who had an improvement or no change [hazard ratio, 4.6 (1.3 to 16.0); log rank test; P=0.003]. In this single-center pilot study, phase analysis of gated SPECT was successfully used to predict acute change in LV synchrony and patient outcome after CRT.

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Left bundle branch–optimized cardiac resynchronization therapy: Pursuing the optimal resynchronization in severe (distal) conduction system disease

We aimed to investigate the impact of the 2021 European Society of Cardiology(ESC) guideline changes in left bundle branch block (LBBB) definition on cardiac resynchronization therapy (CRT) patient selection and outcomes. The MUG (Maastricht, Utrecht, Groningen)registry, consisting of consecutive patients implanted with a CRT device between 2001 and 2015 was studied. For this study, patients with baseline sinus rhythm and QRS duration ≥ 130ms were eligible. Patients were classified according to ESC 2013 and 2021 guideline LBBB definitions and QRS duration. Endpoints were heart transplantation, LVAD implantation or mortality (HTx/LVAD/mortality) and echocardiographic response (LVESV reduction ≥15%). The analyses included 1.202, typical CRT patients. The ESC 2021 definition resulted in considerably less LBBB diagnoses compared to the 2013 definition (31.6% vs. 80.9%, respectively). Applying the 2013 definition resulted in significant separation of the Kaplan-Meier curves of HTx/LVAD/mortality (p < .0001). A significantly higher echocardiographic response rate was found in the LBBB compared to the non-LBBB group using the 2013 definition. These differences in HTx/LVAD/mortality and echocardiographic response were not found when applying the 2021 definition. The ESC 2021 LBBB definition leads to a considerably lower percentage of patients with baseline LBBB then the ESC 2013 definition. This does not lead to better differentiation of CRT responders, nor does this lead to a stronger association with clinical outcomes after CRT. In fact, stratification according to the 2021 definition is not associated with a difference in clinical or echocardiographic outcome, implying that the guideline changes may negatively influence CRT implantation practice with a weakened recommendation in patients that will benefit from CRT.

BackgroundThe objective of this international multicenter study was to investigate both early and late outcomes of cardiac resynchronization therapy (CRT) in patients with a systemic right ventricle (SRV) and to identify predictors for congestive heart failure readmissions and mortality.Methods and ResultsThis retrospective international multicenter study included 13 centers. The study population comprised 80 adult patients with SRV (48.9% women) with a mean age of 45±14 (range, 18–77) years at initiation of CRT. Median follow‐up time was 4.1 (25th–75th percentile, 1.3–8.3) years. Underlying congenital heart disease consisted of congenitally corrected transposition of the great arteries and dextro‐transposition of the great arteries in 63 (78.8%) and 17 (21.3%) patients, respectively. CRT resulted in significant improvement in functional class (before CRT: III, 25th–75th percentile, II–III; after CRT: II, 25th–75th percentile, II–III; P=0.005) and QRS duration (before CRT: 176±27; after CRT: 150±24 milliseconds; P=0.003) in patients with pre‐CRT ventricular pacing who underwent an upgrade to a CRT device (n=49). These improvements persisted during long‐term follow‐up with a marginal but significant increase in SRV function (before CRT; 30%, 25th–75th percentile, 25–35; after CRT: 31%, 25th–75th percentile, 21–38; P=0.049). In contrast, no beneficial change in the above‐mentioned variables was observed in patients who underwent de novo CRT (n=31). A quarter of all patients were readmitted for heart failure during follow‐up, and mortality at latest follow‐up was 21.3%.ConclusionsThis international experience with CRT in patients with an SRV demonstrated that CRT in selected patients with SRV dysfunction and pacing‐induced dyssynchrony yielded consistent improvement in QRS duration and New York Heart Association functional status, with a marginal increase in SRV function.

Impact of atrial septal pacing in left ventricular–only pacing in patients with a first-degree atrioventricular block: A case series