Refining success of cardiac resynchronization therapy using a simple score predicting the amount of reverse ventricular remodelling: results from the Markers and Response to CRT (MARC) study.

Aims: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in systolic heart failure patients with ventricular conduction delay. Variability of individual response to CRT warrants improved patient selection. The Markers and Response to CRT (MARC) study was designed to investigate markers related to response to CRT. Methods and results: We prospectively studied the ability of 11 clinical, 11 electrocardiographic, 4 echocardiographic, and 16 blood biomarkers to predict CRT response in 240 patients. Response was measured by the reduction of indexed left ventricular end-systolic volume (LVESVi) at 6 months follow-up. Biomarkers were related to LVESVi change using log-linear regression on continuous scale. Covariates that were significant univariately were included in a multivariable model. The final model was utilized to compose a response score. Age was 67 ± 10 years, 63% were male, 46% had ischaemic aetiology, LV ejection fraction was 26 ± 8%, LVESVi was 75 ± 31 mL/m2, and QRS was 178 ± 23 ms. At 6 months LVESVi was reduced to 58 ± 31 mL/m2 (relative reduction of 22 ± 24%), 130 patients (61%) showed ≥ 15% LVESVi reduction. In univariate analysis 17 parameters were significantly associated with LVESVi change. In the final model age, QRSAREA (using vectorcardiography) and two echocardiographic markers (interventricular mechanical delay and apical rocking) remained significantly associated with the amount of reverse ventricular remodelling. This CAVIAR (CRT-Age-Vectorcardiographic QRSAREA -Interventricular Mechanical delay-Apical Rocking) response score also predicted clinical outcome assessed by heart failure hospitalizations and all-cause mortality. Conclusions: The CAVIAR response score predicts the amount of reverse remodelling after CRT and may be used to improve patient selection. Clinical Trials: NCT01519908.

The concept of triple wavefront fusion during biventricular pacing: Using the EGM to produce the best acute hemodynamic improvement in CRT.

BACKGROUND: Previous reports suggest that biventricular pacing (BiVp) fused with intrinsic conduction (BiVp-fusion, triple wavefront fusion) is associated with improved resynchronization compared to pure-BiVp in cardiac resynchronization therapy (CRT). This study aimed to assess the association between acute hemodynamic benefit of CRT and signs of BiVp-fusion by using a novel electrogram (EGM)-based method. METHODS: In 17 patients undergoing CRT implantation, 28 combinations of atrioventricular (AV) and interventricular (VV) delays were applied while invasively measuring acute hemodynamic response based on maximum rate of left ventricular (LV) pressure rise (LV dP/dtmax ) to assess optimal BiVp settings. BiVp-fusion was noted if farfield signal (caused by first intrinsic ventricular depolarization) was seen prior to right ventricular (RV) pacing (RVp) artifact on integrated bipolar RV EGM, or QRS morphology changed compared to pure-BiVp (short AV-delay) as seen on electrocardiogram (ECG). RESULTS: Mean optimal RVp timing was at 98 ± 17% of intrinsic right atrial (RA)-RVfarfield (interval from right atrial pace or sense to RV farfield signal) interval, while preactivating the LV at 50 ± 11% of RA-RVsense (interval from right atrial pace or sense to RV sense interval) interval. BiVp-fusion was noted in 16 of 17 (94%) patients on ECG during optimal BiVp. Eight of these patients showed intrinsic farfield signal prior to RVp artifact on RV EGM. In the remaining eight, the RVp was paced just within the RA-RVfarfield interval with a mean of 25 ± 14 ms prior to the onset; therefore, the intrinsic farfield was masked. CONCLUSION: Optimal hemodynamic BiVp facilitates triple wavefront fusion, by pacing the RV around the onset of intrinsic farfield signal on RV EGM, while preactivating the LV. Aiming at BiVp-fusion could be a target for noninvasive EGM-based CRT device setting optimization.

Volumetric Response beyond Six Months of Cardiac Resynchronization Therapy and Clinical Outcome.

AIMS: Response to cardiac resynchronization therapy (CRT) is often assessed six months after implantation. Our objective was to assess the number of patients changing from responder to non-responder between six and 14 months, so-called late non-responders, and compare them to patients who were responder both at six and 14 months, so-called stable responders. Furthermore, we assessed predictive values of six and 14-month response concerning clinical outcome. METHODS: 105 patients eligible for CRT were enrolled. Clinical, laboratory, ECG, and echocardiographic parameters and patient-reported health status (Kansas City Cardiomyopathy Questionnaire [KCCQ]) were assessed before, and six and 14 months after implantation. Response was defined as ≥15% LVESV decrease as compared to baseline. Major adverse cardiac events (MACE) were registered until 24 months after implantation. Predictive values of six and 14-month response for MACE were examined. RESULTS: In total, 75 (71%) patients were six-month responders of which 12 (16%) patients became late non-responder. At baseline, late non-responders more often had ischemic cardiomyopathy and atrial fibrillation, higher BNP and less dyssynchrony compared to stable responders. At six months, late non-responders showed significantly less LVESV decrease, and higher creatinine levels. Mean KCCQ scores of late non-responders were lower than those of stable responders at every time point, with the difference being significant at 14 months. The 14 months response was a better predictor of MACE than six months response. CONCLUSIONS: The assessment of treatment outcomes after six months of CRT could be premature and response rates beyond might better correlate to long-term clinical outcome.