A novel stepwise approach incorporating ethanol infusion in the vein of Marshall for the ablation of persistent atrial fibrillation.

Introduction: Apart from pulmonary vein isolation (PVI), several step-by-step procedures that aim to modify left atrial substrate have been proposed for the ablation of persistent atrial fibrillation (AF), yet the optimal strategy remains elusive. There are cumulative data suggesting an incremental benefit of adding vein of Marshall (VOM) ethanol infusion to PVI in patients with persistent AF. We sought to evaluate the feasibility and efficacy of a novel stepwise ablation approach, incorporating a VOM alcoholization step, for persistent AF. Methods: In this single-center study, we prospectively enrolled 66 consecutive patients with symptomatic persistent AF and failure of at least one antiarrhythmic drug (ADD). The ablation procedure consisted of (i) PVI, (ii) left atrial segmentation with VOM ethanol infusion and the deployment of linear radiofrequency lesions across the roof and the mitral isthmus and (iii) electrogram-based ablation of dispersion zones. The first two steps were performed in all patients, whereas the third step was carried out only in those still in AF at the end of the second step. Atrial tachycardias during the procedure were mapped and ablated. At the end of the procedure, cavotricuspid isthmus ablation was additionally performed in all patients. The primary endpoint was 12-month freedom from AF and atrial tachycardia after a single procedure and an initial three-month blanking period. Results: Total procedure time was 153 ± 38.5 min. Fluoroscopy time was 16 ± 6.5 min and the radiofrequency ablation time was 26.14 ± 0.26 min. The primary endpoint occurred in 54 patients (82%). At 12 months, 65% of patients were off any AAD. In the univariate Cox regression analysis, left ventricular ejection fraction < 40% was the only predictor of arrhythmia recurrence (HR 3.56; 95% CI, 1.04-12.19; p = 0.04). One patient developed a pericardial tamponade and another a minor groin hematoma. Conclusion: A novel stepwise approach, including a step of ethanol infusion in the VOM, is feasible, safe and provides a high rate of sinus rhythm maintenance at 12 months in patients with persistent AF.

Pulsed-Field Ablation on Mitral Isthmus in Persistent Atrial Fibrillation: Preliminary Data on Efficacy and Safety.

BACKGROUND: Pulsed-field ablation (PFA) is a new and promising modality of ablation that has been shown to specifically ablate cardiac tissue while sparing other anatomic structures, thus avoiding thermal ablation-related complications. Recent studies have certified safety and efficacy of PFA for pulmonary vein isolation (PVI) in the setting of paroxysmal atrial fibrillation (AF). However, there are very limited data assessing the feasibility and safety of PFA ablation of different substrates within the left atrium in the setting of persistent AF. OBJECTIVES: The purpose of this study was to evaluate the feasibility and safety of mitral isthmus (MI) ablation in addition to PVI and posterior wall (PW) ablation with PFA in patients with persistent AF. METHODS: We prospectively included all consecutive patients with persistent AF who underwent a first ablation procedure with PFA. We performed in all these patients a substrate ablation strategy comprising PVI, PW, and MI ablation with the use of PFA only. The primary feasibility endpoint was obtaining a persistent MI block at the end of the procedure. The safety endpoint was a composite of major safety events. RESULTS: From November 2021 to September 2022, we included 45 patients. Complete MI block was achieved in all 45 (100%). Three patients presented with complications, among them 2 cases (4.4%) of reversible and nonfatal coronary spasm. During a mean follow-up time of 107.8 ± 59.5 days, a 20% recurrence rate was observed. CONCLUSIONS: PFA is a feasible and safe ablation approach for mitral isthmus ablation in addition to PVI in patients with persistent AF.

Phenotypic characteristics and prognosis of newly diagnosed diabetes in hospitalized patients with COVID-19: Results from the CORONADO study.

In patients with diabetes hospitalized for COVID-19 in CORONADO study, 2.8% had a newly discovered. 2.8% had a newly discovered diabetes (NDD): mean age 60.2 ± 12.5 years and HbA1C 9.0 ± 2.5%. When compared with center, age and sex-matched patients with established type 2 diabetes, NDD was not significantly associated with a more severe COVID-19 prognosis.

Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19.

AIMS: Metformin exerts anti-inflammatory and immunosuppressive effects. We addressed the impact of prior metformin use on prognosis in patients with type 2 diabetes hospitalised for COVID-19. METHODS: CORONADO is a nationwide observational study that included patients with diabetes hospitalised for COVID-19 between March 10 and April 10, 2020 in 68 French centres. The primary outcome combined tracheal intubation and/or death within 7 days of admission. A Kaplan-Meier survival curve was reported for death up to day 28. The association between metformin use and outcomes was then estimated in a logistic regression analysis after applying a propensity score inverse probability of treatment weighting approach. RESULTS: Among the 2449 patients included, 1496 were metformin users and 953 were not. Compared with non-users, metformin users were younger with a lower prevalence of diabetic complications, but had more severe features of COVID-19 on admission. The primary endpoint occurred in 28.0% of metformin users (vs 29.0% in non-users, P = 0.6134) on day 7 and in 32.6% (vs 38.7%, P = 0.0023) on day 28. The mortality rate was lower in metformin users on day 7 (8.2 vs 16.1%, P < 0.0001) and on day 28 (16.0 vs 28.6%, P < 0.0001). After propensity score weighting was applied, the odds ratios for primary outcome and death (OR [95%CI], metformin users vs non-users) were 0.838 [0.649-1.082] and 0.688 [0.470-1.007] on day 7, then 0.783 [0.615-0.996] and 0.710 [0.537-0.938] on day 28, respectively. CONCLUSION: Metformin use appeared to be associated with a lower risk of death in patients with diabetes hospitalised for COVID-19.

An African loss-of-function CACNA1C variant p.T1787M associated with a risk of ventricular fibrillation.

Calcium regulation plays a central role in cardiac function. Several variants in the calcium channel Cav1.2 have been implicated in arrhythmic syndromes. We screened patients with Brugada syndrome, short QT syndrome, early repolarisation syndrome, and idiopathic ventricular fibrillation to determine the frequency and pathogenicity of Cav1.2 variants. Cav1.2 related genes, CACNA1C, CACNB2 and CACNA2D1, were screened in 65 probands. Missense variants were introduced in the Cav1.2 alpha subunit plasmid by mutagenesis to assess their pathogenicity using patch clamp approaches. Six missense variants were identified in CACNA1C in five individuals. Five of them, A1648T, A1689T, G1795R, R1973Q, C1992F, showed no major alterations of the channel function. The sixth C-terminal variant, Cavα1c-T1787M, present mostly in the African population, was identified in two patients with resuscitated cardiac arrest. The first patient originated from Cameroon and the second was an inhabitant of La Reunion Island with idiopathic ventricular fibrillation originating from Purkinje tissues. Patch-clamp analysis revealed that Cavα1c-T1787M reduces the calcium and barium currents by increasing the auto-inhibition mediated by the C-terminal part and increases the voltage-dependent inhibition. We identified a loss-of-function variant, Cavα1c-T1787M, present in 0.8% of the African population, as a new risk factor for ventricular arrhythmia.

Duration of hospital admission, need of on-demand analgesia and other peri-procedural and short-term outcomes in sub-cutaneous vs. transvenous implantable cardioverter-defibrillators.

BACKGROUND: Post-procedural recovery following sub-cutaneous ICD (S-ICD) implantation is feared to be more painful and to require more prolonged hospital admission. The purpose of this study was to compare peri-procedural and short clinical outcomes of the S-ICD vs. the Transvenous ICD (TV-ICD). METHODS: We conducted a single-center cross-sectional study including all consecutive patients who underwent S-ICD implantation by the same operator since January 2016 and a gender and age-matched control group with all single chamber TV-ICD implanted patients over a contemporary time period. RESULTS: Thirty-one patients (sex ratio 1/5; mean age 58.7±13.2years) with S-ICD were compared to 31 matched TV-ICD patients. Duration of the implant procedure was significantly longer for the S-ICD (58.0±24.4min vs 41.7±20.8min TV-ICD, p<0.01). Mean fluoroscopy time for the TV-ICD was 3.5±3.6min vs 0.1±0.01min for all S-ICD patients (p<0.01). Requirement of on-demand analgesia administration, and duration of hospitalization (1.5days for both groups; p=NS) were similar in the two groups. No peri-procedural events were reported, and after a mean follow-up of 6months, the only complication was a pocket infection requiring reintervention in the TV-ICD group. CONCLUSIONS: The S-ICD appears to be as effective and safe as the conventional single chamber TV-ICD. Duration of hospital admission and need of on-demand analgesia are also comparable for S-ICD patients.

Prevalence and long-term prognosis of patients with 'narrower than normal' QRS complexes.

Aims: Very narrow QRS have been reported in sudden death survivors but prevalence and prognosis role of narrow QRS is unknown. Methods and results: 546 healthy men between 50 and 60 years (group 1) and 373 similar patients with coronary artery disease (368 men, group 2) underwent signal averaged ECG (SA-ECG) allowing precise measurement of QRS duration. All cause-mortality was determined after 18 ± 3 years follow-up. Mean QRS duration was 97 ± 13 ms in group 1 and 103 ± 16 ms in group 2. Tenth percentile was 84 ms in group 1 and 85 ms in group 2. All cause-mortality in group 1 was 10.4% (57/546): 6/85 in case of QRS <85 ms (7%) and 2/23 (9%) in case of QRS >120 ms (ns). HR for all-cause mortality was 0.75 (95% CI 0.32-1.76, P = 0.52) for QRS <85 ms and 0.86 (95% CI 0.21-3.53, P = 0.84) for QRS >120 ms. All cause mortality in group 2 was 29% (109/373): 7/44 in case of QRS <85 ms (16%) and 22/44 (50%) in case of QRS >120 ms (P = 0.002). HR for all-cause mortality was 0.65 (95% CI 0.29-1.45, P = 0.29) for QRS <85 ms and 1.73 (95% CI 1.02-2.94, P = 0.05) for QRS >120 ms. Conclusion: QRS duration <80-85 ms can be observed in a significant proportion of middle-aged healthy males and in similar patients with ischemic heart disease. Narrow QRS were not linked to prognosis in any group.

Shortening of the Short Refractory Periods in Short QT Syndrome.

BACKGROUND: Diagnosis of short QT syndrome (SQTS) remains difficult in case of borderline QT values as often found in normal populations. Whether some shortening of refractory periods (RP) may help in differentiating SQTS from normal subjects is unknown. METHODS AND RESULTS: Atrial and right ventricular RP at the apex and right ventricular outflow tract as determined during standard electrophysiological study were compared between 16 SQTS patients (QTc 324±24 ms) and 15 controls with similar clinical characteristics (QTc 417±32 ms). Atrial RP were significantly shorter in SQTS compared with controls at 600- and 500-ms basic cycle lengths. Baseline ventricular RP were significantly shorter in SQTS patients than in controls, both at the apex and right ventricular outflow tract and for any cycle length. Differences remained significant for RP of any subsequent extrastimulus at any cycle length and any pacing site. A cut-off value of baseline RP <200 ms at the right ventricular outflow tract either at 600- or 500-ms cycle length had a sensitivity of 86% and a specificity of 100% for the diagnosis of SQTS. CONCLUSIONS: Patients with SQTS have shorter ventricular RP than controls, both at baseline during various cycle lengths and after premature extrastimuli. A cut-off value of 200 ms at the right ventricular outflow tract during 600- and 500-ms basic cycle length may help in detecting true SQTS from normal subjects with borderline QT values.

Prevalence of early repolarisation pattern in children.

BACKGROUND: Prevalence of early repolarisation ECG pattern (ER) has been repetitively determined in adults, but has not been reported in large unselected children populations so far. METHODS: ECG from 1000 successive healthy children from birth to 17years old were prospectively recorded and analyzed. ER was defined by ≥0.1mV J point elevation in at least two contiguous inferior or lateral ECG leads. Correlations with age, gender, ethnic origin, physical activity, Sokolow index and heart rate were performed. RESULTS: Prevalence of ER pattern was 23,6% (95% CI 21-26.2%) and increased after 8years of age. ER was independently correlated to a non Caucasian origin and a higher Sokolow index, but not to gender or level of physical activity. ER was independently correlated to an older age in children with heart rate <100bpm, and to a slower heart rate in children ≥8yo. CONCLUSION: ER is present in a quarter of children of various age and is related to ethnic origin, an older age, a slower heart rate and a higher Sokolow index.

Sudden QRS morphology change during ventricular pacing in a scar-related isthmus What is the mechanism?

We present an example of sudden modification in QRS morphology during ventricular pacing inside a scar-related isthmus. This is explained by a "concealed" sudden block in both the orthodromic and antidromic wavefront directions, allowing then the activation to proceed through a now overt antidromic conduction.

Reversal of left ventricular dysfunction after ablation of premature ventricular contractions related parameters, paradoxes and exceptions to the rule.

BACKGROUND: Suppression of frequent premature ventricular contractions (PVCs) does not systematically lead to an expected reversal of PVC-induced cardiomyopathy and determinants of left ventricular ejection fraction (LVEF) recovery (reverse remodeling) after ablation remain largely unknown. METHODS: Ninety-six consecutive patients with a suspicion of PVC induced-cardiomyopathy were retrospectively included. Parameters potentially related to reverse remodeling (>10% increase in LVEF) were analyzed in patients w/wo long-term success (decrease in PVC burden >80%). RESULTS: Over a mean follow-up of 24±21months, long-term ablation success was obtained in 76 patients (79%). In these, reverse remodeling was observed in 63 (83%) (LVEF 39±8 to 56±8%, p<0.0001). In multivariate analysis, only an older age (and marginally a lower PVC QRS amplitude) was independently associated with the lack of reverse remodeling. Only 10 of the 35 patients who initially should have received an ICD for primary prevention remained candidates for implantation after ablation. Lack of reverse remodeling was significantly linked to a higher mortality. CONCLUSION: Reverse remodeling was observed in 83% of patients with frequent PVC and unexplained cardiomyopathy undergoing long-term successful ablation of the PVC. A younger age was independently correlated with the occurrence of reverse remodeling.

Use of a subcutaneous ICD in a patient with short QT syndrome.

Short QT syndrome carries the risk for inappropriate therapies using transvenous ICD because of overdetection of the ample T wave. SQT syndrome may also benefit from subcutaneous ICD, although additional cases are needed to affirm the safety of such device in this setting.

Premature ventricular contraction-induced cardiomyopathy: Related clinical and electrophysiologic parameters.

BACKGROUND: Factors associated with premature ventricular contraction-induced cardiomyopathy (PVCi-CMP) remain debated. OBJECTIVE: The purpose of this study was to test the correlation of various factors to the presence PVCi-CMP in a large multicenter population. METHODS: One hundred sixty-eight consecutive patients referred for ablation of frequent premature ventricular contractions (PVCs) were included. Patients were divided into 2 groups: group 1 with suspected PVCi-CMP (96 patients, ejection fraction 38% ± 10%, left ventricular end-diastolic diameter 62 ± 8 mm, with or without additional structural heart disease); and group 2 (control group, 72 patients with normal ejection fraction and left ventricular dimensions). Various clinical and electrophysiologic parameters were compared between groups. RESULTS: In univariate analysis, left ventricular origin of PVC, lack of palpitations, long PVC coupling interval, epicardial origin of the focus, long sinus beat QRS duration, male gender, high PVC burden, presence of polymorphic PVCs, high PVC QRS duration, and older age were significantly related to the presence of PVCi-CMP. In multivariate analysis, only lack of palpitations, PVC burden, and epicardial origin remained significantly and independently correlated with the presence of cardiomyopathy. Even if sinus QRS duration or PVC left ventricular origin were also found independently linked to PVCi-CMP in the whole population, they were no longer correlated when patients with additional heart disease were excluded. CONCLUSION: Lack of palpitations, PVC burden, and epicardial origin are independent factors that identify patients prone to developing PVCi-CMP.

Increased Tpeak-Tend interval is highly and independently related to arrhythmic events in Brugada syndrome.

BACKGROUND: Risk stratification in Brugada syndrome (BS) remains controversial. The time interval between the peak and the end of the T wave (Tpe interval), a marker of transmural dispersion of repolarization, has been linked to malignant ventricular arrhythmias in various settings but leads to discordant results in BS. OBJECTIVE: We study the correlation of the Tpe interval with arrhythmic events in a large cohort of patients with BS. METHODS: A total of 325 consecutive patients with BS (mean age 47±13 years, 259 men-80%) with spontaneous (n=143, 44%) or drug-induced (n=182, 56%) type 1 electrocardiogram were retrospectively included. 235 were asymptomatic (70%), 80 presented with unexplained syncope (22%), and 10 presented with sudden death (SD) or appropriate implantable cardioverter-defibrillator therapy (AT) (8%) at diagnosis or over a mean follow-up of 48 ± 34 months. The Tpe interval was calculated as the difference between the QT interval and the QT peak interval as measured in each of the precordial leads. RESULTS: The Tpe interval from lead V1 to lead V4, maximum value of the Tpe interval (max Tpe), and Tpe dispersion in all precordial leads were significantly higher in patients with SD/AT or in patients with syncope than in asymptomatic patients (P < .001). A max Tpe of ≥100 ms was present in 47 of 226 asymptomatic patients (21%), in 48 of 73 patients with syncope (66%), and in 22 of 26 patients with SD/AT (85%) (P < .0001). In multivariate analysis, a max Tpe of ≥100 ms was independently related to arrhythmic events (odds ratio 9.61; 95% confidence interval 3.13-29.41; P < .0001). CONCLUSION: The Tpe interval in the precordial leads is highly related to malignant ventricular arrhythmias in this large cohort of patients with BS. This simple electrocardiographic parameter could be used to refine risk stratification.

Lack of Correlations between Electrophysiological and Anatomical-Mechanical Atrial Remodeling in Patients with Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) progressively leads to electrical remodeling (ER) and anatomical-mechanical remodeling (AR), whose relationships in humans remain poorly known. METHODS: ER and AR were compared in patients undergoing percutaneous radiofrequency (RF) ablation for AF. ER was defined by right and left appendage activation rates as a surrogate for atrial refractory periods. AR was approached by left atrial (LA) diameters and area and left atrial appendage (LAA) area and contractile function (mean emptying flow velocity) (LAAFV) before RF ablation. Mean duration between successive LAA contractions was considered as LAA mechanical rate. RESULTS: Forty-one patients (31 men, age: 64 ± 9 years) with paroxysmal (27%), persistent (61%), or long-persistent AF (12%) were prospectively included (ejection fraction: 44 ± 16%). Parameters exploring AR were highly correlated to each other: LA area (28 ± 7 cm(2) ), LAA area (5.7 ± 2.25 cm(2) ), LA transverse (49 ± 7 mm), and anteroposterior diameter (59 ± 13 mm) or LAAFV (29 ± 13 cm/s; P < 0.05 for each comparison). Parameters exploring ER were also highly correlated: right atrial appendage (RAA; 181 ± 39 ms) and LAA (176 ± 33 ms) activation rates (P < 0.0001). There was no significant correlation between any ER and AR parameter. Only LAA mechanical rate (174 ± 36 ms) was correlated to LAA or RAA activations rates (P ≤ 0.01). CONCLUSION: ER and AR are not mutually related, atrial activation rate being not correlated to LA or LAA size or function. Thus, the mechanisms leading to AF-induced atrial remodeling may differ for anatomical and electrophysiological aspects.

Higher contact-force values associated with better mid-term outcome of paroxysmal atrial fibrillation ablation using the SmartTouch™ catheter.

AIMS: Real-time measurement of contact force (CF) during catheter ablation of atrial fibrillation (AF) has been recently suggested to potentially impact procedural outcome. However, the role of CF intensity on mid-term results using the SmartTouch™ catheter has not been investigated so far. METHODS AND RESULTS: Pulmonary vein isolation (PVI) using the SmartTouch™ catheter was performed in 100 eligible patients (age 62 ± 8; 79% men) undergoing a first procedure of paroxysmal AF catheter ablation. Continuous CF monitoring during catheter ablation allowed calculation of mean CF per patient. Patients were dichotomized into high CF (≥22 g, upper quartile) and low CF (<22 g, remaining) and enroled in a standardized follow-up programme (after a 3-month blanking period), free from antiarrhythmic therapy, with regular evaluations including 24 h Holter recordings at 1, 3, 6, 9, 12, 18, and 24 months. Atrial fibrillation relapse was defined as any symptomatic or asymptomatic atrial arrhythmia lasting >30 s. The average CF among all procedures was 19.6 ± 3.7 g. Though complete PVI was eventually achieved in all cases in both groups, success using an exclusively anatomical approach was higher in the high CF group (92.0 vs. 72.0%; P = 0.04). During a mean follow-up of 19 ± 5 months, a lower incidence of AF relapse was observed in higher CF patients (4.0 vs. 20.0%; log rank P = 0.04). Pericardial tamponade occurred in one patient in the higher CF group. No thromboembolism or procedure-associated deaths were observed. CONCLUSION: Higher values of CF overall during antral PVI appear to be associated with a higher likelihood of sinus rhythm maintenance without significantly increasing the complication rate.

Contact-force guided radiofrequency vs. second-generation balloon cryotherapy for pulmonary vein isolation in patients with paroxysmal atrial fibrillation-a prospective evaluation.

AIMS: In the setting of paroxysmal atrial fibrillation (AF), there are no available data comparing the mid-term outcome of patients undergoing pulmonary vein isolation (PVI) catheter ablation using contact-force (CF)-guided radiofrequency (RF) vs. second-generation balloon cryotherapy. METHODS AND RESULTS: Prospective single-centre evaluation, carried out from March 2011 to February 2013, comparing CF radiofrequency (Thermocool(®) SmartTouch™, Biosense Webster, Inc.) (CF group) with cryoballoon ablation (Arctic Front Advance™ 28 mm cryoballoon, Medtronic, Inc.) (CB group), in regards to procedural safety and efficacy, as well as recurrence at 12 months. Overall, 150 consecutive patients were enrolled (75 in each group). The characteristics of patients of both the groups were similar (61.2 ± 9.9 years, women 25.3%, mean AF duration 4.1 ± 4.0 years, mean CHA2DS2-VASc score 1.4 ± 1.3, mean HAS-BLED 1.4 ± 0.6). Duration of the procedure was significantly lower in the CF group (110.7 ± 32.5 vs. 134.5 ± 48.3 min, P = 0.001), with a lower duration of fluoroscopy (21.5 ± 8.5 vs. 25.3 ± 9.9 min, P = 0.017) and X-ray exposure (4748 ± 2411 cGy cm² vs. 7734 ± 5361 cGy cm², P = 0.001). In contrast, no significant difference was found regarding significant procedural complication (2.7 vs. 1.3% in CF and CB groups, respectively; P = 0.56), and PVI was eventually achieved in all cases. At 12 months, AF recurrence occurred in 11 patients (14.7%) in the CB group and in 9 patients (12.0%) in the CF group (HR = 1.20 95% CI 0.50-2.90; log rank P = 0.682). CONCLUSIONS: Our preliminary findings suggest that CF-guided radiofrequency and cryotherapy present very similar performances in the setting of paroxysmal AF catheter ablation.