Myocardial Scar on Surface ECG: Selvester Score, but Not Fragmentation, Predicts Response to CRT.

PURPOSE: Myocardial scar is directly related to the response to CRT after implantation. The extent of myocardial scar can be detected not only by cardiac magnetic resonance but also by two electrocardiographic scores: fragmented QRS (fQRS) and Selvester score (SSc). The aim of our study is to compare the role of baseline SSc and fQRS in predicting response to CRT in a cohort of heart failure patients with true left bundle branch block (LBBB). As a secondary endpoint, we assessed the association of both scores with overall and cardiac mortality, heart failure hospitalizations, ventricular arrhythmias requiring ICD intervention, and major adverse cardiovascular event (MACE). METHODS: We evaluated fQRS and SSc of 178 consecutive HF patients with severe systolic dysfunction (LVEF ≤ 35%), NYHA class II-III despite optimal medical treatment, and true-LBBB. Response to CRT was defined as the improvement of LVEF of at least 10% or as the reduction of LVESV of at least 15% at a 6-month follow-up. Each endpoint was related to fQRS and SSc. RESULTS: SSc ≥7 was significantly associated with the absence of echocardiographic response to CRT (OR: 0.327; 95% C.I. 0.155-0.689; p=0.003), while the presence of fQRS at baseline ECG was not (OR: 1.133; 95% C.I. 0.539-2.381; p=0.742). No correlation was found between SSc and overall mortality, cardiac death, ventricular arrhythmias, hospitalizations due to heart failure, or for MACE. Similar results were observed between fQRS and all secondary endpoints. CONCLUSION: In HF patients with true-LBBB and LVEF ≤35% eligible for CRT, myocardial scar assessed by calculating the SSc on preimplant ECG is an independent predictor of nonresponse after multiple adjustments. Neither SSc nor fQRS is associated with overall and cardiac death, ventricular arrhythmias, or hospitalization for heart failure at a 24-month follow-up.

Severe Spontaneous Echo Contrast/Auricolar Thrombosis in "Nonvalvular" AF: Value of Thromboembolic Risk Scores.

BACKGROUND: Patients with atrial fibrillation (AF) have an increased thromboembolic risk that can be estimated with risk scores and sometimes require oral anticoagulation therapy (OAT). Despite correct anticoagulation, some patients still develop left atrial spontaneous echo contrast (SEC) or thrombosis. The value of traditional risk scores (R2 CHADS2 , CHADS2 , and CHA2 DS2 -VASc) in predicting such events remains controversial. METHODS AND RESULTS: The aim of our study was to explore variables linked to severe SEC or atrial thrombosis and evaluate the performance of traditional risk scores in identifying these patients. In order to do this, we retrospectively analyzed 568 patients with nonvalvular nonparoxysmal AF who underwent electrical cardioversion from January 2011 to December 2016 after OAT for a minimum of 4 weeks. A transesophageal echocardiogram was performed in 265 patients for various indications, and 24 exhibited left atrial SEC or thrombosis. Female gender, history of heart failure or left ventricular ejection fraction <40%, and high levels (>1 mg/dL) of C-reactive protein (CRP) were independently associated with left atrial SEC/thrombosis. A score composed by these factors (denominated HIS [Heart Failure, Inflammation, and female Sex]) showed a sensitivity of 79% and a specificity of 60% (area under receiver operating characteristic curve 0.695, P = 0.002) in identifying patients with a positive transesophageal echo; traditional risk scores did not perform as well. CONCLUSIONS: In patients with persistent AF and suboptimal anticoagulation, a risk score composed by history of heart failure, high CRP, and female gender identifies patients at high risk of left atrial SEC/thrombosis when its value is >1.

Cardiac resynchronization therapy improves functional status and cognition.

BACKGROUND: Many trials demonstrated the beneficial effects on hospitalizations and mortality of cardiac resynchronization therapy (CRT). The purpose of this study was to evaluate CRT effects on functional performance and cognition, two determinants of disability, frailty development and survival. METHODS: All consecutive patients receiving a CRT device were evaluated at baseline and at the 6-month follow-up. Functional profile was assessed with the Short Physical Performance Battery (SPPB), a measure exploring balance, gait, strength and endurance, highly predictive of incident disability and mortality. The Mini-Mental State Examination (MMSE) was used to study the cognitive profile. RESULTS: We enrolled 54 patients; two of them died during the follow-up, two refused to continue the study. Age was 67±10years (men: 80%, LVEF: 28±5%); medical therapy was optimized (ACE-I/ARB: 84%, beta-blockers: 80%). After 6months, CRT was associated with the improvement of LVEF (35±8 vs. 28±5%, p<0.001) and NYHA Class (1.8±0.6 vs. 2.6±0.5, p<0.001), and with the reduction of left ventricular end-systolic diameter (50±9 vs. 57±9mm, p<0.001). SPPB improved in its total score (10.3±2.0 vs. 9.1±2.7, p<0.001) and in the scores exploring gait speed and strength and endurance. These changes were associated with a better cognitive profile (MMSE score: 27.0±3.5 vs. 25.9±4.8, p=0.009). Advanced age was an independent predictor of improved functional performance and cognition. CONCLUSIONS: CRT is associated with higher functional and cognitive profile after only 6months of therapy. These findings let us hypothesize a powerful effect of treatment to slow disability and frailty development in heart failure.

Prognostic Impact of QRS Axis Deviation in Patients Treated With Cardiac Resynchronization Therapy.

INTRODUCTION: QRS duration and morphology are currently recognized as recommended criteria for the selection of CRT candidates. It has recently been shown that patients with left bundle branch block (LBBB) derive substantial clinical benefit from CRT. The aim of this study is to investigate the prognostic impact of QRS axis deviation (AD) in HF patients with LBBB undergoing CRT. METHODS AND RESULTS: We retrospectively evaluated 707 HF patients with LBBB who underwent CRT at five centers. Baseline QRS axis was defined as normal (NA: -30° to 90°), right axis deviation (RAD: 90° to 180°) and left axis deviation (LAD: <-30°). The primary endpoint was a composite of all cause death/HF hospitalization. The risk of endpoint by AD was evaluated with both Kaplan-Meier and Cox proportional hazard analysis. Among 707 patients (73% M, median age: 71 [62,77] years), 323 (46%) had NA, 359 (51%) LAD, and 25 (3.5%) RAD. Baseline clinical characteristics were similar between the three groups. Over a mean follow-up of 32 ± 25 months, 141 deaths occurred (21%) and 36% (n = 255) met with the composite endpoint. A significantly higher proportion of RAD patients (52%) reached the endpoint (LAD 40%, NA 30%). KM analysis showed that RAD and LAD patients had worse event free survival and in multivariate analysis both LAD (HR: 1.40; 95% CI: 1.05-1.86; P = 0.021) and RAD (HR: 2.49; 95% CI: 1.31-4.74; P = 0.005) were independently associated with worse clinical outcome. CONCLUSIONS: Right or left axis deviation in the presence of LBBB in HF patients undergoing CRT are independent predictors of poor prognosis.

[Acute results of left ventricular endocardial pacing for cardiac resynchronization therapy obtained with a transapical approach]. / Risultati in acuto della stimolazione endocardica sinistra per la terapia di resincronizzazione cardiaca ottenuta mediante approccio transapicale.

Although cardiac resynchronization therapy (CRT) is considered a milestone in the treatment of patients affected with chronic congestive heart failure, reduced left ventricular ejection fraction and enlarged QRS, up to 30% of patients can be considered clinical non-responders to this treatment. In these patients, optimization of atrioventricular and interventricular intervals could be of some help, but results of trials are not univocal on the benefit of this procedure. In the last years, left ventricular endocardial pacing for CRT has emerged as a possible solution in non-responders. Several studies have demonstrated its feasibility and safety, and some reports suggest its incremental efficacy in comparison with traditional epicardial pacing, both obtained transvenously or surgically. We describe the cases of two patients already implanted with a CRT device who came to our attention for clinical non-responsiveness to CRT and who have been successfully treated with the addition of a left endocardial lead. A brief literature review on this topic is also reported.

Simplified Selvester Score: a practical electrocardiographic instrument to predict response to CRT.

AIMS: To investigate the LBBB Selvester Scoring System (LBBB-SSc) and the Simplified-SSc prognostic impact in predicting response to CRT, all cause and cardiac mortality, heart failure (HF) hospitalizations and onset of arrhythmias in HF patients undergoing CRT. METHODS: We retrospectively evaluated LBBB-SSc and Simplified-SSc of 172 consecutive HF patients with true-LBBB who underwent CRT. Response to CRT was defined as the improvement of LVEF of at least 10% or as the reduction of LVESV of at least 15% at 6-month follow-up. Logistic regression analysis and Cox proportional hazard analysis were performed to evaluate each endpoint related risk according to LBBB-SSc and Simplified-SSc. RESULTS: The LBBB-SSc and the Simplified-SSc were inversely correlated with response to CRT. Myocardial scar at both scores was independently associated to non-response to CRT. No correlation was observed between LBBB-SSc or Simplified-SSc and other endpoints. CONCLUSIONS: In HF patients with true-LBBB, Simplified-SSc is able to predict response to CRT.

Relation of QRS duration to response to cardiac resynchronization therapy.

Left bundle branch block (LBBB) is the most reliable electrocardiographic predictor of responsiveness to cardiac resynchronization therapy (CRT). However, not all patients with LBBB will respond to CRT. Our aim was to investigate the interaction between QRS duration, LBBB-type morphology, and the responsiveness to CRT. We retrospectively analyzed electrocardiograms of 243 patients who underwent CRT implantation according to current clinical indications. A 6-month reduction of left ventricular end-systolic volume >15% was used to identify CRT responders. The clinical end point consisted of death, hospitalization for heart failure and sustained rapid ventricular tachyarrhythmias. An LBBB morphology was present in 169 patients (70%) and 101 of these (60%) were responders to CRT. Analyzing the interaction between QRS duration and CRT responsiveness in patients with LBBB, a "U shaped" distribution resulted, with nonresponders clustered between 120 and 130 ms and above 180 ms. The receiver operating characteristic curve analysis identified 178 ms as the optimal cut-off value of QRS to predict a nonresponsiveness to CRT (area under the curve = 0.67 [95% confidence interval 0.57 to 0.76]). At multivariate analysis, only an ischemic cause and a QRS ≥178 ms were independent predictors of nonresponsiveness to CRT (area under the curve = 0.75). Patients with LBBB with QRS ≥178 ms had greater likelihood of adverse clinical events during a mean follow-up of 32 months (p = 0.049). In conclusion, in patients with LBBB undergoing CRT, a marked QRS widening (i.e., ≥178 ms) is related to worse echocardiographic responsiveness and lower event free survival rate compared with patients with an intermediate QRS widening.

CHADS2 and CHA2DS2-VASc scores to predict morbidity and mortality in heart failure patients candidates to cardiac resynchronization therapy.

AIMS: CHADS2 and CHA2DS2-VASc scores are pivotal in assessing the risk of stroke in atrial fibrillation patients, and were recently proved to predict hospitalizations and mortality in specific clinical settings. Aim of this study was to evaluate whether these scores could predict clinical outcomes [first hospitalization for heart failure (HF) and a combined event of HF hospitalization and death for any cause] in patients candidates to cardiac resynchronization therapy and implantable defibrillator (CRT-D). METHODS AND RESULTS: In a retrospective multicentre Italian study, we enrolled 559 consecutive HF patients candidates to CRT-D, and we grouped them in three pre-specified risk classes: low (CHADS2/CHA2DS2-VASc 1-2), moderate (CHADS2/CHA2DS2-VASc 3-4), and high (CHADS2 5-6/CHA2DS2-VASc 5-8). All patients underwent regular follow-up at implanting centres every 6 months; data collection was extended till the 72th month of follow-up. At a median FU of 30 months, 143 patients (25.4%) were hospitalized for HF and 110 (19.5%) died. Event-free survival analysis showed a significant difference according to baseline CHADS2 and CHA2DS2-VASc scores (Log-Rank for HF P < 0.001 for CHADS2 and CHA2DS2-VASc; Log-Rank for combined end-point P = 0.001 for CHADS2, P < 0.001 for CHA2DS2-VASc). At multivariate analysis, independent predictors of endpoints were: previous atrial fibrillation (AF) or AF at implant, NYHA class, QRS duration and the CHA2DS2-VASc score (for HF hospitalization P = 0.013; for the combined event, P = 0.007), while the CHADS2 score was not independently associated with either the end-points. CONCLUSION: In CRT-D patients, pre-implant CHA2DS2-VASc score is an independent predictor of major clinical events at 30-month follow-up.

Effects of smoking in patients treated with cardiac resynchronization therapy.

Smoking is associated with increased morbidity and mortality in cardiac patients. However, data on the prognostic impact of smoking in heart failure (HF) patients on cardiac resynchronization therapy with defibrillator (CRT-D) are absent. We investigated the effects of smoking on all-cause mortality and on a composite endpoint (all-cause death/appropriate device therapy), appropriate and inappropriate device therapy, in 649 patients with HF who underwent CRT-D between January 2003 and October 2011 in 6 Centers (4 in Italy and 2 in USA). 68 patients were current smokers, 396 previous-smokers (patients who had smoked in the past but who had quit before the CRT-D implant), and 185 had never smoked. The risk of each endpoint by smoking status was evaluated with both Kaplan-Meier and Cox proportional-hazard analysis. After adjusting for age, left ventricular ejection fraction, QRS width and ischemic etiology, both current and previous smoking were independent predictors of all-cause death [HR = 5.07 (95 % CI 2.68-9.58), p < 0.001 and HR = 2.43 (95 % CI 1.38-4.29), p = 0.002, respectively) and of composite endpoint [HR = 1.63 (1.04-2.56); p = 0.033 and HR = 1.46 (1.04-2.04) p = 0.027]. In addition, current smokers had a significantly higher rate of inappropriate device therapy compared to never smokers [HR = 21.74 (4.53-104.25), p = 0.005]. Our study indicates that in patients with HF who received a CRT-D device, current and previous smoking increase the event rate per person-time of death and of appropriate and inappropriate ICD therapy more than other known negative prognostic factors such as age, left ventricular dysfunction, prolonged QRS duration and ischemic etiology.

Discordant electrical and mechanical atrial delays affect intracavitary electrogram-based cardiac resynchronization therapy optimization.

AIMS: It has been shown that atrioventricular (AV) delay optimization improves cardiac resynchronization therapy (CRT) response. Recently, an automatic algorithm (QuickOpt™, St Jude Medical), able to quickly identify the individual optimal AV interval, has been developed. The algorithm suggests an AV delay based on atrial intracavitary electrogram (IEGM) duration. We hypothesized that the difference between electrical and mechanical atrial delays could affect the effectiveness of QuickOpt method. The aim of this study was to test this hypothesis in 23 CRT patients who were recipients of St. Jude Medical devices. METHODS AND RESULTS: Using echocardiography, aortic flow velocity time integral (VTI) was evaluated at baseline, at QuickOpt suggested AV delay and after reducing it by 25 and 50%. Mechanical inter-atrial delay (MIAD) derived from echo/Doppler and electrical inter-atrial delay (EIAD) derived from IEGM were also analysed. Optimal AV delay was identified by the maximal VTI. In 11 patients (Group 1) the maximal VTI was achieved at the AV delay suggested by the algorithm, in 6 patients (Group 2) after a 25% reduction, and in 6 patients (Group 3) after a 50% reduction. While EIAD was similar among the three groups, MIAD was significantly different (P< 0.001). MIAD was longer than EIAD in Group 1 (P= 0.028) and shorter than EIAD in Groups 2 (P= 0.028) and 3. (P< 0.001). Mechanical inter-atrial delay was the only independent predictor of the AV interval associated with the best VTI (R(2) = 0.77; P< 0.001). CONCLUSION: Our results show that MIAD plays the main role in determining the optimal AV delay, thus caution should be taken when optimizing AV by IEGM-based methods.