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.

Relationship Between Reverse Remodeling and Cardiopulmonary Exercise Capacity in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy.

BACKGROUND: Studies on the relationship between left ventricular reverse remodeling and cardiopulmonary exercise capacity in heart failure patients undergoing cardiac resynchronization therapy (CRT) are scarce and inconclusive. METHODS AND RESULTS: Eighty-four patients with a 1st-time CRT-defibrillator (mean age 65 ± 11; 73% male) underwent echocardiography and cardiopulmonary exercise testing (CPX) before implantation (baseline) and 6 months after implantation. At baseline, patients also completed a set of questionnaires measuring mental and physical health. The association between echocardiographic response (left ventricular end-systolic volume decrease ≥15%) and a comprehensive set of CPX results was examined. Echocardiographic responders (54%) demonstrated higher peak oxygen consumption and better exercise performance than nonresponders at baseline and at 6-month follow-up. Furthermore, only echocardiographic responders showed improvements in ventilatory efficiency during follow-up. Multivariable repeated measures analyses revealed that, besides reverse remodeling, New York Heart Association functional class II and good patient-reported health status before implantation were the most important correlates of higher average oxygen consumption during exercise, and that nonischemic etiology and smaller pre-implantation QRS width were associated with better ventilatory efficiency over time. CONCLUSIONS: During the first 6 months of CRT there was a significant positive association between reverse remodeling and cardiopulmonary exercise capacity.

Regional Left Ventricular Electrical Activation and Peak Contraction Are Closely Related in Candidates for Cardiac Resynchronization Therapy.

OBJECTIVES: This study determined the relationship between the timing of left ventricular (LV) electrical activation and peak contraction at potential LV pacing locations in candidates for cardiac resynchronization therapy (CRT). BACKGROUND: Targeting the LV lead to the region of latest electrical activation or the segment of latest peak contraction has both been shown to improve CRT response. Whether these regions correspond within CRT patients is uncertain. METHODS: Twenty-eight consecutive CRT candidates underwent intraprocedural coronary venous electroanatomic mapping using EnSite NavX. Peak contraction time of the mapped LV regions was determined using longitudinal strain derived from speckle tracking echocardiography. Electrical activation and peak contraction times were correlated on a per patient basis, and the regions of latest electrical activation and latest peak contraction were compared. RESULTS: Successful measurements by both techniques allowed analysis in 23 of 28 patients. There was a strong positive correlation between electrical activation and peak contraction times within each patient (R2 = 0.85 ± 0.09). However, the magnitude of the electrical activation-peak contraction relationship varied greatly among patients (slope of regression line: 4.05 ± 3.23). The regions of latest electrical activation and latest peak contraction corresponded in 19 of 23 (83%) patients and were adjacent in 4 patients. CONCLUSIONS: There is a close relationship between the timing of LV electrical activation and peak contraction in CRT candidates. This finding suggests that a strategy of determining the latest activated LV region based on speckle tracking echocardiography corresponds to that based on intracardiac measurements of electrical activation.

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.

Discrepancy between echocardiographic and patient-reported health status response to cardiac resynchronization therapy: results of the PSYHEART-CRT study.

AIMS: The current study examined the degree of agreement between echocardiographic and patient-reported health status response to CRT 6 months after implantation, and evaluated the differences in pre-implantation characteristics of patients with concordant and discordant echocardiographic and health status responses. METHODS AND RESULTS: Consecutively implanted CRT-defibrillator patients (n = 109, mean age = 65.4 ± 10.1 years, 74 men) were recruited from the University Medical Center Utrecht, The Netherlands. Prior to implantation and 6 months post-implantation, all patients underwent echocardiography and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). Echocardiographic response was defined as a relative reduction of ≥15% in LV end-systolic volume; an improvement of ≥10 points in KCCQ score indicated a health status response. In the 54 patients with discordant responses, 25 (22.9%) had an echocardiographic response but no health status response and 29 (26.6%) had a health status response but no echocardiographic response. Patients with concordant and discordant responses differed on various pre-implantation characteristics, including sex, employment status, LV volumes, and pre-implantation KCCQ score. In multivariable analysis, pre-implantation KCCQ score [odds ratio (OR) = 0.91, 95% confidence interval (CI) = 0.88-0.95, P < 0.001] and QRS duration (OR = 1.03, 95% CI = 1.01-1.06, P = 0.009) were the only characteristics associated with health status response to CRT. CONCLUSIONS: Our results show a large discrepancy between echocardiographic and patient-reported health status response to CRT. The most important predictor of health status response was the pre-implantation health status score. These results emphasize that disease-specific health status measures may have additional value over 'objective' measures of CRT response and should be incorporated in clinical practice.