Time Of Cardiac Resynchronization Therapy Implantation Research Articles

Abstract 4122247: Impact of serum chloride levels for ventricular arrhythmias in patients with heart failure undergoing cardiac resynchronization therapy

Background: As previous reports of ventricular arrhythmia (VA) as a prognostic marker of mortality in heart failure (HF) patients included those with implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) devices, little is known about the risk factors of VA among patients undergoing cardiac resynchronization therapy (CRT), especially those without previous VA. The prognostic role of electrolyte abnormalities has been highlighted in HF patients. This study evaluated the impact of serum chloride levels for VA and all-cause death in patients with HF who underwent CRT without VA before CRT implantation. Methods: From the retrospective cohort of 397 HF patients (age 63+/-13, male 74%) who undergoing CRT implantation between 2010 and 2020, this study enrolled 175 patients (82% implanted CRT with a defibrillator) without a previous history of VA (sustained ventricular tachycardia (VT) of ventricular fibrillation (VF)). We studied the impact of serum chloride levels before CRT implantation. The primary endpoint was defined as VA, VA with ICD therapy and sudden cardiac death. The secondary endpoint was all-cause mortality. Results: During median follow-up of 35 months, 53 patients (30%) experienced VA. Patients with VA had a tendency toward high LVESV (172ml vs. 150ml, p<0.09) and low left ventricular ejection fraction (26 vs. 29, p<0.09), and significantly reduced rate of angiotensin converting enzyme inhibitors or angiotensin receptor blockers (30% vs. 70%, p<0.05) at the time of CRT implantation. The rate of CRT responders was significantly higher in patients without VA than with VA (59% vs. 40%, p<0.05). The cut-off value of chloride for VA was determined to be 102mEq/l using receiver operating characteristic analysis. The patients with chloride ≤102mEq/l had significantly higher rates of VA (41% vs. 25%, log-rank p<0.05) and mortality (33% vs. 18%, log-rank p<0.05) (Figure). By multivariate cox analysis, the level of chloride had an independent predictive value of VA in patients with CRT (hazard ratio [HR] 1.08 per 1mEq/l decrease, 95% confidence interval [CI] 1.00-1.16, p<0.05) (Table). Conclusions: The chloride level had a predictive value for VA after CRT implantation in HF patients without previous VA. The management of electrolytes, including chloride, might be important for preventing fatal arrhythmia in patients with HF undergoing CRT implantation.

Clinical Impact of Digitalis Therapy in a Large Multicenter Cohort of CRT-Recipients.

(1) Introduction: Digitalis use in patients with severe heart failure is controversial. We assessed the effects of digitalis therapy on mortality in a large, observational study in recipients of cardiac resynchronization therapy (CRT). (2) Methods: Consecutive patients receiving a CRT-defibrillator in three European tertiary referral centers were enrolled and followed-up for a mean 37 months ± 28 months. Digitalis use was assessed at the time of CRT implantation. A multivariate Cox-regression model and propensity score matching were used to determine all-cause mortality as the primary endpoint. CRT-response (defined as improvement of ≥1 NYHA class), echocardiographic improvement (defined as improvement of LVEF of ≥ 5%) and incidence of ICD shocks and rehospitalization were assessed as secondary endpoints in a subgroup of patients. (3) Results: The study comprised 552 CRT-recipients with standard indications, including 219 patients (40%) treated with digitalis. Compared to patients without digitalis, they had more often atrial fibrillation, poorer LVEF and a higher NYHA class (all p ≤ 0.002). Crude analysis of all-cause mortality demonstrated a similar relative risk of death for patients with and without digitalis (HR = 1.14; 95% CI 0.88-1.5; p = 0.40). After adjustment for independent predictors of mortality, digitalis therapy did not alter the risk for death (adjusted HR = 1.04; 95% CI 0.75-1.45; p = 0.82). Furthermore, in comparison to 286 propensity-score-matched patients, mortality was not affected by digitalis intake (propensity-adjusted HR = 1.11; 95% CI 0.72-1.70; p = 0.64). A CRT-response was predominant in digitalis non-users, concerning both improvement of HF symptoms and LVEF (NYHA p < 0.01; LVEF p < 0.01), while patients on digitalis had more often ventricular tachyarrhythmias requiring ICD shock (p = 0.01); although, rehospitalization for cardiac reasons was significantly lower among digitalis users compared to digitalis non-users (HR = 0.58; 95% C. I. 0.40-0.85; p = 0.01). (4) Conclusions: Digitalis therapy had no effect on mortality, but was associated with a reduced response to CRT and increased susceptibility to ventricular arrhythmias requiring ICD shock treatment. Although, digitalis administration positively altered the likelihood for cardiac rehospitalization during follow-up.

Prognostic impact of heart mate risk score among elderly heart failure patients with non-responder for cardiac resynchronization therapy

Abstract Background For patients with severe heart failure (HF) who are not eligible for transplantation, there is destination therapy (DT) that uses a continuous flow left ventricular assist device (LVAD). Implantation of LVAD improves HF and can be expected to improve the prognosis of life. Elderly refractory HF patients with non-responders for cardiac resynchronization therapy (CRT) may benefit from LVAD as DT. In considering indications of LVAD as DT for the elderly in Japan, conditions such as a low risk of Heart Mate Risk Score (HMRS) have been raised. HMRS has been shown to correlate with mortality in the cohort of LVAD patients enrolled in the Heartmate II trials. Purpose Because elderly CRT non-responder refractory HF patients are not indicated for transplantation and may benefit from LVAD as DT in Japan, we aimed to investigate the HMRS and prognosis among elderly CRT non-responders. Methods Of 467 patients underwent CRT implantation between 2000 and 2015, 157 were aged 65–75 years old. Of which 59 patients who could be determined to be non-responders based on echocardiographic data were included in this study. The primary endpoint was all-cause mortality, the secondary was readmission for HF and appropriate implantable cardioverter defibrillator (ICD) therapy. Results The patients' mean age was 68 years, males were 71%. The mean serum creatinine value was 1.1 mg/dl, albumin was 3.8 mg/dl, and BNP was 383 pg/ml. The mean left ventricular ejection fraction (LVEF) was 26%. The subjects were divided into 3 groups according to HMRS. The average of HMRS was 2.2, the low-risk group included 17 (29%) patients, the medium was 22 (37%), and the high was 20 (34%). There was no significant difference in age, LVEF, BNP, and NYHA functional classification at the time of CRT implantation between three groups. In the low-risk group, creatinine and INR were significantly lower, and albumin was significantly higher compared to the high-risk group. BNP tended to be lower in the low-risk group, but there was no significant difference. The mortality rate by HMRS was 12% in the low-risk group, 36% in the medium-risk group, and 50% in the high-risk group. On the Kaplan-Meier analysis, the low-risk group had a significantly lower mortality rate than the high-risk group (Figure). Furthermore, focusing on HF readmission, the rate of readmission was 59% in the low-risk group, 86% in the medium -risk group, and 65% in the high-risk group, and there was no significant difference between three groups. There was also no significant difference in appropriate ICD therapy between three groups. Conclusion Approximately 30% of elderly non-responders of CRT are in the low-risk group by HMRS and their mortality was lower than that of the other two groups. These elderly CRT non-responder patients might be considered a candidate for DT in Japan. Funding Acknowledgement Type of funding sources: None.

Electrocardiographic Model to Predict Cardiac Resynchronization Therapy Response among Chronic Heart Failure Patients

Background: Despite contemporary restrictive clinical and electrocardiographic selection criteria, up to one-third of chronic heart failure patients with implanted cardiac resynchronization therapy (CRT) are non-responders. Previous studies reported that some electrocardiographic patterns, such as the longer the intrinsicoid deflection (ID) in lead I, the higher the R wave amplitude in V₆, and other patterns may be helpful for CRT response prediction. Objective: To establish a simplified model using electrocardiographic parameters as predictors of CRT response among chronic heart failure patients. Materials and Methods: Eighty chronic heart failure patients meeting the current guideline recommendation for CRT implantation were enrolled in the present retrospective cohort study. The patients’ clinical and electrocardiographic parameters at the time of CRT implantation and during follow-up were analyzed. The response to CRT was evaluated after six months of implantation, defined as a decrease in the left ventricular end systolic volume (LVESV) of 15% or more or an increase in the left ventricular ejection fraction (LVEF) of 10% or more. Results: During a median follow-up period of 34 months, there were 45 (56.3%) responders. In multivariate analysis, the independent predictors for CRT response were the greater the reduction of the QRS complex duration after implantation (QRS post – QRS pre), the higher the time to ID in the lead I/QRS ratio (ID I/QRS), and the higher the difference in the amplitude of the R and S waves in lead V₁ and V₆ [(S1+R6) – (S6+R1)] (QRS post – QRS pre: adjusted odds ratio [OR] 0.97, 95% CI 0.94 to 0.99, p=0.004; ID I/QRS: OR 18.65, 95% CI 1.02 to 342.64, p=0.049; (S1+R6) – (S6+R1): OR 1.1, 95% CI 1.04 to 1.17, p=0.002). The new equation for calculating the predictive CRT response model, generated from multiple logistic regression analysis, was –3.414 – 0.035(QRS post – QRS pre) + 2.926(ID I/QRS) + 0.097[(S1+R6) – (S6+R1)]. The area under the receiver operating characteristic (ROC) curve for the new model for predicting CRT response was 0.853 (95% CI 0.767 to 0.939). A model score of more than 0.3 showed a sensitivity of 85.7% and specificity of 80% for the prediction of CRT response. Conclusion: The new electrocardiographic model achieved a high sensitivity and specificity for the prediction of CRT response among chronic heart failure patients, who met the current guideline recommendation for CRT implantation. Keywords: Cardiac resynchronization therapy, Electrocardiography, Heart failure, Responders, Model

Predictors of long‐term outcomes greater than 10 years after cardiac resynchronization therapy implantation

Cardiac resynchronization therapy (CRT) is indicated in patients with medically refractory heart failure and wide QRS duration. While much is known about predictors of left ventricular (LV) remodeling after CRT implantation and short-term mortality, limited data exist on long-term outcomes after CRT placement. We retrospectively reviewed all patients undergoing CRT implantation at our center between 2003 and 2008 and examined mortality using institutional electronic records, social security death index, and online obituary search. We included only patients with preimplant echoes with LV ejection fraction (LVEF) 35% or below. Variable selection was performed using stepwise regression and models were compared using goodness-of-fit criteria. A final model was validated with the bootstrap regression method. Out of the 877 CRT patients undergoing implantation during this time, 287 (32.7%) survived longer than 10 years. Significant (P < .05) predictors of survival in our multivariate model were age, left ventricular diastolic diameter, sex, presence of nonischemic vs ischemic cardiomyopathy, QRS duration, atrial fibrillation, BNP levels, and creatinine levels at the time of CRT implantation. A model using the odds ratios from these variables had a receiver operating curve with an area under the curve score of 0.816 (standard error, 0.019) at predicting survival or freedom from LVAD or heart transplant for longer than 10 years after CRT implantation. The specificity for factors 3 or above and 5 or above was 68% and 77%, respectively. A large proportion of patients are still alive 10 years after CRT implantation. Variables at the time of CRT implant can help provide prognostic information to patients and electrophysiologists to determine the long-term benefit and survival of patients after CRT implantation.

P5688Is renal dysfunction associated with the outcome of CRT patients?

Abstract Background The benefit of cardiac resynchronization therapy (CRT) in patients (pts) with chronic kidney disease (CKD) remains controversial despite frequent use. Pts with impaired renal function have systematically been excluded from randomized clinical trials and therefore specific recommendations for the use of CRT in these pts are still lacking. Purpose Study objectives were to assess long-term outcomes and clinical/echocardiographic response in a large population of patients with moderate-to-severe impaired renal function implanted with a CRT device in accordance with the current standard of care. Methods We prospectively analyzed clinical, instrumental data and survival of pts with CKD who received a CRT device in the CRT-MORE registry from 2011 to 2014. Adverse events for the analysis of clinical outcome comprised death from any cause and nonfatal HF events requiring hospitalization after CRT implantation. LV reverse remodeling and Clinical Response (CR) were also evaluated at 12-month follow-up. Patients were stratified according to current definition of CKD stage: low-moderate CKD with a GFR = 45–59 mL/min (stage 3A); moderate CKD with a GFR = 30–44 mL/min (stage 3B) and severe CKD with a GFR = 15–29 mL/min (stage 4). Results Of the 922 consecutive patients enrolled in the registry, 416 (45%) pts had a moderate-to-severe impaired renal function (43% Stage 3A, 43% Stage 3B and 14% Stage 4). The mean follow-up was 935±506 days. By the end of the study, 85 pts had died and 47 pts had been hospitalized for HF. The combined end-point of death or HF hospitalization was reached by 121 (29%) pts. After 12 months the absolute LVEF improvement was greater than 10% in 37% of pts and 58% of pts displayed a positive clinical response. The percentage of pts who died was higher in the group of pts with severe CKD (32.8% vs 18.4%; p=0.012, compared to the group of pts with moderate CKD). On the contrary the percentage of pts who had at least one HF hospitalization was lower in the group with more severe CKD (2% vs 13%; p=0.011). According to CKD stage both LV remodeling (LVEF improvement ranging from 43.7% - 3A - to 30.8% - 4) and CR (positive response ranging from 63.9% - 3A - to 50% - 4) were higher in low-moderate stage and decreased with CKD severity. At multivariate Cox regression analysis adjusted for baseline confounders, CKD class at implantation [HR=1.5; 95% CI: 1.06–2.14; p=0.0219], chronic obstructive pulmonary disease [HR=1.89; 1.18–3.01; p=0.0077], persistent/permanent AF [HR=1.86; 1.15–3.01; p=0.0115] and male gender [HR=1.92; 1.07–3.46; p=0.0301] remained associated with death. Conclusions Among CKD patients in the CRT-MORE registry, severity of renal dysfunction at the time of CRT implantation was associated with worse prognosis, lower clinical response and LV reverse remodeling. Acknowledgement/Funding None

The value of serum metabolomics analysis in predicting the response to cardiac resynchronization therapy.

ObjectiveTo construct a prediction model based on metabolic profiling for predicting the response to cardiac resynchronization therapy (CRT).MethodsPeripheral venous (PV) and coronary sinus (CS) blood samples were collected from 25 patients with heart failure (HF) at the time of CRT implantation, and PV blood samples were obtained from ten healthy controls. The serum samples were analyzed by liquid chromatography-mass spectrometry (LC-MS). As per the clinical and echocardiographic assessment at the 6-month follow-up, the HF patients were categorized as CRT responders and non-responders.ResultsHF patients had altered serum metabolomic profiles that were significantly different from those of the healthy controls. Differential metabolites were also observed between CRT responders and non-responders. A prediction model for CRT response (CRT-Re) was constructed using the concentration levels of the differential metabolites, L-arginine and taurine. The optimal cutoff value of the CRT-Re model was found to be 0.343 by ROC analysis (sensitivity, 88.2%; specificity, 87.5%; Area under curve (AUC) = 0.897, P = 0.002). The concentration levels of the differential metabolites, L-arginine and lysyl-gamma-glutamate, in PV serum were significantly correlated with that in CS serum (r = 0.945 and 0.680, respectively, all P < 0.001).ConclusionsOur results suggest that serum-based metabolic profiling may be a potential complementary screening tool for predicting the outcome of CRT.

Cardiac Resynchronization Therapy-Emerging Therapeutic Approaches.

Cardiac resynchronization therapy (CRT) is an important therapeutic tool in the management of patients with heart failure and electrical dyssynchrony. In appropriately selected patients, landmark randomized controlled trials have demonstrated morbidity and mortality benefit beyond standard goal-directed medical therapy. Current guidelines emphasize the greatest clinical efficacy of CRT in patients with symptomatic heart failure, left bundle branch block, and wide QRS duration (> 150ms). Other relevant considerations include the presence of atrial fibrillation, the presence of AV block, the etiology of cardiomyopathy, the presence of masked left-sided conduction delay, and the impact of comorbidities that might predict poor clinical response. At the time of CRT implantation, key considerations include targeting of the left ventricular (LV) lead to sites of greatest electrical and/or mechanical delay, the use of quadripolar versus bipolar LV pacing leads, evaluation of multiple pacing vectors to maximize electrical resynchronization, and in select instances pre-procedure imaging of the coronary venous anatomy to help guide decision-making at the time implant. Post-implant care includes the selective use of atrio-ventricular and inter-ventricular optimization algorithms, mitigation of right ventricular pacing, recognition, and treatment of suboptimal biventricular pacing, as well as management by a multi-disciplinary team of cardiovascular specialists. Emerging therapeutic strategies for patients eligible for CRT include the use of endocardial LV pacing, novel LV pacing options including multi-point pacing, His bundle pacing, and the integration of remote monitoring platforms that may identify patients at risk for clinical worsening.

Optimizationof coronary sinus lead placement targeted to the longest right-to-left delay in patients undergoing cardiac resynchronization therapy: The Optimal Pacing SITE 2 (OPSITE 2) acute study and protocol.

Left ventricular (LV) lead positioning at the site of delayed electrical activation is associated with better response to cardiac resynchronization therapy (CRT). We hypothesized that a long electrical conduction delay between right ventricular (RV) and coronary sinus (CS) leads during RV pacing (RLD index) is correlated with a better clinical outcome METHODS AND RESULTS: RLD is measured intraprocedurally, during RV pacing, as the time interval between the intracardiac electrograms of RV and CS leads. Initially, we did a prove-of-concept, feasibility, acute study in 97 patients who underwent CRT implantation. The CS lead position was assessed in the 40° right anterior oblique and 40° left anterior oblique views and assigned to one of 11 prespecified segments of a schematic eyeball depiction of the LV walls. Acute outcomes were QRS width during biventricular (BIV) pacing. The longest RLD were found in the basal and mid lateral segments; these accounted for 82% and 78%, respectively, of the total QRS width (%RLD). %RLD was inversely correlated with BIV-paced QRS (P=0.0001). A similar slope was present either in the 78 patients with preserved atrioventricular (AV) conduction and in the 19 without AV conduction (-0.34vs-0.27, P=0.7). We showed that RLD can be used to guide lead placement at the time of CRT implantation and that it is correlated with BIV-QRS width, an indirect predictor of clinical outcome. Based on these findings we started the prospective, multicenter Optimal Pacing SITE 2 (OPSITE 2) trial with the objective to demonstrate a relationship between RLD and clinical outcomes assessed as death, hospitalization for heart failure, New York Heart Association class, and clinical composite score. The protocol is provided.

Abstract 12650: Unexpected Response to Atrial Fibrillation Reduction in Patients With Cardiac Resynchronization Therapy

Background: Cardiac resynchronization therapy (CRT) is known to improve left ventricular (LV) systolic function and symptoms of systolic heart failure. The effect of CRT on atrial fibrillation (AF) burden is less clarified. Methods: 18 patients mean age of 77 ± 11 (72% male) underwent CRT implantations. There were no changes to concomitant anti-arrhythmic medication and permanent AF patients were excluded. Echocardiograms were obtained six month before and after device implantation. LV ejection fraction (LVEF), LV end diastolic dimension (LVEDd), left atrial (LA) dimension, and magnitude of mitral regurgitation (MR) were measured by echocardiogram before and after CRT. The burden of AF was evaluated by 24-hour Holter monitoring before and by device arrhythmic log after implantation. There were no concomitant medication changes. The results were later divided into presence (Group I) and absence (Group II) of paroxysmal or persistent AF. No patient was in permanent AF at the time of CRT implantation. Results: LVEF improved after CRT in both groups. Patients with AF showed the most beneficial effects of LVEF with average improvement of 41% (P-value=0.004) in comparison to 13% improvement in patients without AF (P-value=0.044). The LVEDd was improved by 11.9% in patients with AF (P-value=0.01) while it was improved by only 5.6% in patients without AF (P-value=0.08). LA Dimension was decreased by 4.4% in patients with AF (P-value=0.038). MR was reduced on average from moderate to mild for both groups. The number of AF episodes and duration of the AF were also decreased in all of our AF patients. The pre and post effect of CRT in patients with and without AF is shown in the table below: Conclusions: The AF burden in patients who received CRT was significantly reduced. There were excellent correlations between improvement of LVEF, LVEDd, LA dimension, and AF burden. This may be due to LV and LA remodeling. Further studies need to elaborate the mechanisms of this finding.

Clinical Impact of Off‐Label Cardiac Resynchronization Therapy in End‐Stage Heart Failure Patients on Continuous Intravenous Inotrope

Potential benefits of off-label cardiac resynchronization therapy (CRT) in end-stage heart failure (EHF) patients have not been fully investigated. Some EHF patients who are dependent on intravenous inotropes can benefit from CRT. We retrospectively enrolled 14 EHF patients who were dependent on intravenous inotropes at the time of CRT implantation. Mean duration of inotropic support was 51 ± 47 days before CRT device implantation. To identify the efficacy of CRT, we assessed the successful withdrawal rate from inotropic support and survival estimates after device implantation. We also tried to identify possible predictors for withdrawal by comparing patient demographics between successful withdrawal (SW) and nonwithdrawal (NW) groups. Successful withdrawal was achieved in 9 (64%) of 14 patients 46 ± 33 days after CRT device implantation. Event-free survival was longer in the SW group than in the NW group (810 ± 169 days vs 114 ± 34 days; P = 0.007). In addition, patients in the SW group showed a higher previous surgery rate (89% vs 20%; P = 0.010) and a lower grade of mitral regurgitation (median, 0 vs 2; P = 0.010) than those in the NW group. Our retrospective data showed potential benefits of CRT among EHFpatients. Treatment of mitral regurgitation might be an essential qualification for managing EHF patients with CRT.

Non-Responders to Cardiac Resynchronization Therapy - The Magnitude of the Problem and the Issues -

A variable proportion of cardiac resynchronization therapy (CRT) patients do not benefit from treatment (termed `non-responders'). The problem of non-response to CRT might become increasingly important, because it is anticipated that larger groups of heart failure patients are indicated to the therapy. This article will discuss the definition of response to CRT, the parameters related to response to CRT, and finally whether response to CRT might be predicted. The effort to improve patient selection in order to maximize human and financial resource utilization has fallen short so far. It is, however, conceivable that rather than the identification of a `universally' applicable cut-off value, risk strata-in which inclusion of method for determination of left ventricular volumes, etiology, QRS duration and morphology, etc-might better serve the goal of defining non-responders. Potentially simple clinical scores might help in refining outcome and by doing so, allow to more precisely measure response to CRT in daily practice in the individual patient at the time of CRT implantation. Although sophisticated cardiac imaging modalities have been intensively utilized for improving patient outcome, it seems that many mechanical dyssynchrony measures suffer from technical limitations and from difficult interpretation of the complex signals, which lack reproducibility outside highly specialized laboratories.