Prognostic value of ventricular arrhythmia in early post-infarction left ventricular dysfunction: the French nationwide WICD-MI study.

BACKGROUND AND AIMS: Prophylactic implantable cardioverter-defibrillators (ICDs) are not recommended until left ventricular ejection fraction (LVEF) has been reassessed 40 to 90 days after an acute myocardial infarction. In the current therapeutic era, the prognosis of sustained ventricular arrhythmias (VAs) occurring during this early post-infarction phase (i.e. within 3 months of hospital discharge) has not yet been specifically evaluated in post-myocardial infarction patients with impaired LVEF. Such was the aim of this retrospective study. METHODS: Data analysis was based on a nationwide registry of 1032 consecutive patients with LVEF ≤ 35% after acute myocardial infarction who were implanted with an ICD after being prescribed a wearable cardioverter-defibrillator (WCD) for a period of 3 months upon discharge from hospital after the index infarction. RESULTS: ICDs were implanted either because a sustained VA occurred while on WCD (VA+/WCD, n = 72) or because LVEF remained ≤35% at the end of the early post-infarction phase (VA-/WCD, n = 960). The median follow-up was 30.9 months. Sustained VAs occurred within 1 year after ICD implantation in 22.2% and 3.5% of VA+/WCD and VA-/WCD patients, respectively (P < .0001). The adjusted multivariable analysis showed that sustained VAs while on WCD independently predicted recurrence of sustained VAs at 1 year (adjusted hazard ratio [HR] 6.91; 95% confidence interval [CI] 3.73-12.81; P < .0001) and at the end of follow-up (adjusted HR 3.86; 95% CI 2.37-6.30; P < .0001) as well as 1-year mortality (adjusted HR 2.86; 95% CI 1.28-6.39; P = .012). CONCLUSIONS: In patients with LVEF ≤ 35%, sustained VA during the early post-infarction phase is predictive of recurrent sustained VAs and 1-year mortality.

Prognostic significance of a low T/R ratio in Brugada syndrome.

OBJECTIVES: To determine the prognostic value of a low T/R ratio, defined as the amplitude ratio between the T waves and the R waves, in patients (pts) with a spontaneous type-1 Brugada pattern (SBT1). BACKGROUND: Abnormalities of myocardial repolarization may play a key role in the initiation of ventricular fibrillation (VF) in Brugada syndrome (BrS). Recent studies have shown that the height of the T waves and the T/R ratio are inversely proportional to sudden cardiac arrest (SCA) risk in early repolarization syndrome and hypertrophic cardiomyopathy. METHODS: In an international retrospective study, we reviewed 115 pts. (105 males, 91.3%). 45 had VF and/or SCA (38.7 ±â€¯11.5 years old, all males), while 70 (49.3 ±â€¯12.0 years, 10 women) remained free of ventricular arrhythmia. 6 ECG markers plus the T/R ratio in leads V5 & II were studied. RESULTS: The T/R ratio among leads II & V5 was significantly lower in the VF/SCA group (0.24 [0.14; 0.38]vs. 0.34 [0.24; 0.45]; p = 0.006). 44.4% of pts. in the VF/SCA group had a lowest T/R ratio among leads II & V5 ≤ 0.17 compared to 11.4% in the non-VF/SCA group (p < 0.001). In multivariate analysis, a lowest T/R ratio among leads II & V5 ≤ 0.17 was independently associated with VF/SCA (OR 6.10, 95% CI 1.92-19.40; p = 0.002). Type 1 Brugada pattern in the peripheral leads (OR 10.78) and early repolarization (OR 3.60) were other independent markers of VF/SCA. CONCLUSION: A low T/R ratio among leads II & V5 is an independent marker for VF/SCA risk in patients with type-1 Brugada pattern.

Prediction of ventricular arrhythmias in patients with a spontaneous Brugada type 1 pattern: the key is in the electrocardiogram.

AIMS: There is currently no reliable tool to quantify the risks of ventricular fibrillation or sudden cardiac arrest (VF/SCA) in patients with spontaneous Brugada type 1 pattern (BrT1). Previous studies showed that electrocardiographic (ECG) markers of depolarization or repolarization disorders might indicate elevated risk. We aimed to design a VF/SCA risk prediction model based on ECG analyses for adult patients with spontaneous BrT1. METHODS AND RESULTS: This retrospective multicentre international study analysed ECG data from 115 patients (mean age 45.1 ± 12.8 years, 105 males) with spontaneous BrT1. Of these, 45 patients had experienced VF/SCA and 70 patients did not experience VF/SCA. Among 10 ECG markers, a univariate analysis showed significant associations between VF/SCA and maximum corrected Tpeak-Tend intervals ≥100 ms in precordial leads (LMaxTpec) (P < 0.001), BrT1 in a peripheral lead (pT1) (P = 0.004), early repolarization in inferolateral leads (ER) (P < 0.001), and QRS duration ≥120 ms in lead V2 (P = 0.002). The Cox multivariate analysis revealed four predictors of VF/SCA: the LMaxTpec [hazard ratio (HR) 8.3, 95% confidence interval (CI) 2.4-28.5; P < 0.001], LMaxTpec + ER (HR 14.9, 95% CI 4.2-53.1; P < 0.001), LMaxTpec + pT1 (HR 17.2, 95% CI 4.1-72; P < 0.001), and LMaxTpec + pT1 + ER (HR 23.5, 95% CI 6-93; P < 0.001). Our multidimensional penalized spline model predicted the 1-year risk of VF/SCA, based on age and these markers. CONCLUSION: LMaxTpec and its association with pT1 and/or ER indicated elevated VF/SCA risk in adult patients with spontaneous BrT1. We successfully developed a simple risk prediction model based on age and these ECG markers.

Systematic analysis of SCN5A variants associated with inherited cardiac diseases.

BACKGROUND: SCN5A variants are associated with a spectrum of cardiac electrical disorders with clear phenotypes. However, they may also be associated with complex phenotypic traits like overlap syndromes or pleiotropy, which have not been systematically described. In addition, the involvement of SCN5A in dilated cardiomyopathies (DCMs) remains controversial. OBJECTIVE: We aimed to evaluate the different phenotypes associated with pathogenic (P)/likely pathogenic (LP) SCN5A variants and to determine the prevalence of pleiotropy in a large multicentric cohort of P/LP SCN5A variant carriers. METHODS: The DNA of 13,510 consecutive probands (9960 with cardiomyopathies) was sequenced with a custom panel of genes. Individuals carrying a heterozygous single P/LP SCN5A variant were selected and phenotyped. RESULTS: The study included 170 P/LP variants found in 495 patients. Of them, 119 (70%) were exclusively associated with a single well-established phenotype: 91 with Brugada syndrome, 15 with type 3 long QT syndrome, 6 with progressive cardiac conduction disease, 4 with multifocal ectopic Purkinje-related premature contractions, and 3 with sick sinus syndrome. Thirty-two variants (19%) were associated with overlap syndromes or pleiotropy. The 19 remaining variants (11%) were associated with atypical or unclear phenotypes. Of those, 8 were carried by 8 patients presenting with DCM with a debatable causative genotype/phenotype link. CONCLUSION: Most P/LP SCN5A variants were found in patients with primary electrical disorders, mainly Brugada syndrome. Nearly 20% were associated with overlap syndromes or pleiotropy, underscoring the need for comprehensive phenotypic evaluation. The concept of SCN5A variants causing DCM is extremely rare (8/9960) if not questionable.

ATE Score Diagnostic Accuracy for Predicting the Absence of Intra-Atrial Thrombi Before AF Ablation.

BACKGROUND: In a preliminary study in patients hospitalized for catheter ablation of atrial fibrillation (AF), the atrial thrombus exclusion (ATE) score (stroke, hypertension, heart failure, and D-dimers >270 ng/mL) was developed to rule out the diagnosis of intra-atrial thrombus, with a negative predictive value (NPV) of 100%, and to avoid performing transesophageal echocardiography (TEE). OBJECTIVES: The present study was designed to prospectively confirm the NPV of the ATE score in an independent population. METHODS: Consecutive patients hospitalized for catheter ablation of AF or left atrial tachycardia (LAT) were prospectively enrolled in a multicenter study. D-dimer levels were measured within 48 hours before ablation. An ATE score of 0 was considered predictive of no thrombus. TEE was routinely performed at the beginning or just before the ablation procedure. The primary endpoint was the presence of atrial thrombus diagnosed by TEE. RESULTS: The analysis included 3,072 patients (53.3% paroxysmal AF, 36.7% persistent AF, and 10% LAT). A thrombus was detected in 29 patients (0.94%; 95% CI: 0.63%-1.35%), all on appropriate anticoagulant therapy. An ATE score of 0 was observed in 818 patients (26.6%), and the sensitivity, specificity, positive predictive value, and NPV were 93.1%, 26.8%, 1.2%, and 99.8%, respectively. Follow-up of the 2 false negative patients revealed the persistence of chronic organized thrombi. CONCLUSIONS: In patients hospitalized for catheter ablation of AF or LAT, the ATE score identifies a population at very low risk for atrial thrombus. In consultation with the patient, the cardiologist may consider not performing a preoperative TEE in case of an ATE score of 0.

Impact of Neuroeffector Adrenergic Receptor Polymorphisms on Incident Ventricular Fibrillation During Acute Myocardial Ischemia.

Background Cardiac adrenergic receptor gene polymorphisms have the potential to influence risk of developing ventricular fibrillation (VF) during ST-segment-elevation myocardial infarction, but no previous study has comprehensively investigated those most likely to alter norepinephrine release, signal transduction, or biased signaling. Methods and Results In a case-control study, we recruited 953 patients with ST-segment-elevation myocardial infarction without previous cardiac history, 477 with primary VF, and 476 controls without VF, and genotyped them for ADRB1 Arg389Gly and Ser49Gly, ADRB2 Gln27Glu and Gly16Arg, and ADRA2C Ins322-325Del. Within each minor allele-containing genotype, haplotype, or 2-genotype combination, patients with incident VF were compared with non-VF controls by odds ratios (OR) of variant frequencies referenced against major allele homozygotes. Of 156 investigated genetic constructs, 19 (12.2%) exhibited significantly (P<0.05) reduced association with incident VF, and none was associated with increased VF risk except for ADRB1 Gly389 homozygotes in the subset of patients not receiving ß-blockers. ADRB1 Gly49 carriers (prevalence 23.0%) had an OR (95% CI) of 0.70 (0.49-0.98), and the ADRA2C 322-325 deletion (Del) carriers (prevalence 13.5%) had an OR of 0.61 (0.39-0.94). When present in genotype combinations (8 each), both ADRB1 Gly49 carriers (OR, 0.67 [0.56-0.80]) and ADRA2C Del carriers (OR, 0.57 [0.45- 0.71]) were associated with reduced VF risk. Conclusions In ST-segment-elevation myocardial infarction, the adrenergic receptor minor alleles ADRB1 Gly49, whose encoded receptor undergoes enhanced agonist-mediated internalization and ß-arrestin interactions leading to cardioprotective biased signaling, and ADRA2C Del322-325, whose receptor causes disinhibition of norepinephrine release, are associated with a lower incidence of VF. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT00859300.

A case of cardiomyopathy induced by inappropriate sinus tachycardia and cured by ivabradine.

We present the case of a 67-year-old woman with cardiomyopathy induced by inappropriate sinus tachycardia (IST) and a particularly high average heart rate. The patient was resistant and/or intolerant to treatment with conventional rate-slowing medications. We used ivabradine--a specific sinus node I(f) current inhibitor--and successfully lowered the heart rate (33 beats per minute mean heart rate decrease). Symptoms, systolic function, and heart rate variability parameters recovered dramatically. No side effect was noted. We suggest that ivabradine--evaluated in trials to treat stable angina--should be considered as a second-line treatment in patients with very symptomatic and refractory IST.

Exclusion of Intra-Atrial Thrombus Diagnosis Using D-Dimer Assay Before Catheter Ablation of Atrial Fibrillation.

OBJECTIVES: This study hypothesized that the association of D-dimer blood level and several clinical items in a new risk score could predict the absence of atrial thrombus. BACKGROUND: Symptomatic and drug resistant atrial fibrillation (AF) can be treated by catheter ablation. The procedure-related risk of thromboembolism is limited by the pre-operative use of transesophageal echocardiography (TEE) to detect atrial thrombi. METHODS: Patients admitted for catheter ablation of AF (n = 2,494) were prospectively included in a multicenter study. TEE was systematically performed before the procedure to search for atrial thrombus (primary endpoint). D-dimer level, CHADS2 score, left ventricular ejection fraction, pre-operative anticoagulation regimen, and medical history were collected. A logistic regression model was used to identify factors associated with the presence of atrial thrombus (hypertension, history of stroke, heart failure, D-dimer level >270 ng/ml). These factors were aggregated in a new score called atrial thrombus exclusion (ATE). RESULTS: The incidence of atrial thrombus was 1.92%. CHADS2 score and D-dimer level were significantly associated with atrial thrombus (p < 0.0001 and p < 0.0001, respectively). A zero CHADS2 score failed to exclude all atrial thrombi (5 false negatives; sensitivity: 89.58%, specificity: 52.2%). No false negative was found with a zero ATE score, which had a specificity of 37% and a higher sensitivity (100%) than the CHADS2 score (p < 0.031) to predict the absence of intra-atrial thrombi on TEE. Conversely, the positive predictive value was poor, and the ATE score should not be used to conclude a positive diagnosis of thrombus. CONCLUSIONS: An ATE score of zero was strongly associated with the absence of atrial thrombus. This new score could be useful to rule out a diagnosis of atrial thrombus before catheter ablation of AF.

Occurrence of Incomplete Endothelialization Causing Residual Permeability After Left Atrial Appendage Closure.

AIMS: Percutaneous left atrial appendage (LAA) occlusion is occasionally incomplete, with residual permeability of the LAA on cardiac computed tomography. The cause for this is unclear. Our objective was to determine if residual permeability was related to incomplete endothelialization. METHODS: A total of 35 consecutive patients contraindicated for anticoagulant therapy admitted for LAA occlusion were included; 12 patients received a Watchman device (Boston Scientific) and 23 patients received an Amplatzer Cardiac Plug (St. Jude Medical). Incomplete endothelialization was defined as residual permeability on cardiac computed tomography without peridevice leak on transesophageal echocardiography at follow-up. RESULTS: Five patients did not receive cardiac computed tomography. After 10 ± 6 months of follow-up, residual permeability of the LAA (at least partial) was recorded on cardiac computed tomography in 21 of 30 patients (70%). Seven of 30 patients presented with a peridevice leak on transesophageal echocardiography. Among the remaining 23 patients, 14 (61%) presented with incomplete endothelialization and 9 (39%) presented with complete endothelialization. There was no statistical difference between the patients presenting with complete vs incomplete endothelialization. CONCLUSION: We found that incomplete endothelialization, defined as residual permeability on cardiac computed tomography without peridevice leak on transesophageal echocardiography, occurred in 61% of the patients after 10 ± 6 months of percutaneous LAA closure. Predisposing factors and appropriate monitoring of LAA patients remain to be determined in larger cohorts.

Real-time atrial wall imaging during radiofrequency ablation in a porcine model.

BACKGROUND: Real-time monitoring of radiofrequency (RF) ablation remains challenging. OBJECTIVE: We used intravascular ultrasound (IVUS) to describe atrial wall changes during RF ablation and to assess the extent of RF-induced lesions. METHODS: In 9 piglets, RF and IVUS catheters were coupled and introduced into the right atrium. RF applications were performed along the intercaval line. Corresponding IVUS images were analyzed. Wall thickness was correlated with electrogram (EGM) changes (n = 9) and histology (n = 5). RESULTS: There were 66 RF applications performed in 57 sites. IVUS provided real-time imaging of the atrial wall during RF application in all but 2 sites. IVUS demonstrated significant (>20%) and immediate increase in atrial wall thickness in 71.4% of RF applications. It showed epicardial or intramyocardial effusion in 30% of cases, 2 steam pops, 1 intramural hematoma, and 1 thrombus. EGM amplitude decreased and thickness increased after RF application than at baseline (2.20 ± 1.11 to 0.99 ± 0.62 mV and 1.34 ± 0.53 to 1.93 ± 0.80 mm, respectively; P < .001 for each). However, EGM and thickness changes were poorly correlated (r = 0.43; P < .05). Histologically and echographically measured thicknesses were correlated (r = 0.71; P = .004), but echographic thickness change was not related to histological lesion transmurality. CONCLUSION: An IVUS probe coupled to an RF catheter can provide relevant real-time imaging of the atrial wall during ablation. Although thickness change does not appear as a good predictor of the transmural extent, direct visualization and monitoring of RF application may provide new information to guide and secure RF ablation.