Left Atrial Pressure as a Predictor of Success in Catheter Ablation of Atrial Fibrillation in a Real-Life Cohort

Aims: The clinical role of the left atrial (LA) hypertension in patients with atrial fibrillation (AF) and its role as predictor in those undergoing pulmonary vein (PV) isolation is still unknown. The aim of the present study was to analyze the role of LA pressure in patients with nonvalvular AF who underwent PV isolation and its implication for AF catheter ablation. Methods: Consecutive patients with drug resistant AF who underwent PV isolation at San Maurizio Regional Hospital of Bolzano (Italy) as index procedure were included in this analysis. Results: A total of 132 consecutive patients (97 males, 73%; mean age 58.0 ± 13.2 years) were included in the analysis. Eleven patients (8%) underwent radiofrequency ablation and 121 (92%) cryoballoon ablation. Higher LA pressures were found in 54 patients (40.9%). At a mean follow up of 14.3 ± 8.2 months (median 12 months), the success rate without antiarrhythmic therapy was 65.9% (87/132; considering the blanking period). Female gender and continuous mean LA pressure were significantly associated with AF recurrence and remained significant on multivariable Cox analysis (respectively, HR 1.845, 1.00–3.40, p = 0.05 and HR 1.066, 1.002–1.134, p = 0.04). We identified a LA mean pressure of >15 mmHg as ideal cutoff and constructed a model to predict AF recurrence which fitted with a concordance index (C-index) of 0.65 (95% CI 0.56–0.75), logrank score p = 0.003

Ten years differences in recently onset atrial fibrillation and flutter incidence and management

Objects and background: Atrial fibrillation (AF) and atrial flutter (AFl) are the most common arrhythmias in day-life clinical practice. Purpose of our study was to verify differences occurred in the last ten years in AF and AFl incidence and treatment in the emergency room (ER). Methods: from the 17th January to the 15th February 2000 and from the 18th January to the 16th February 2010 all the consecutive patients with AF or AFl referring to the ER of our hospital were included in the study. Epidemiological data were collected along with information about treatment, admission to hospital wards, days of hospital stay and therapy. Data from the year 2000 were compared to these collected ten years later. Results: incidence of AF and AFl has increased in the years (50%), patients are older (73.5 vs. 65.2 years; p 0.029) and refer late to the ER (45.6% in 2010 and 23.7% in 2000 with a delay of > 48 hours from arrhythmias onset; p 0.054). In 2010 only a minority of these patients is directly discharged from the ER (15.8% vs 14.4%) and there is an increased admission rate due to AF or AFl (67.5%; p 0.026), if compared to the whole admissions of the hospital. The median duration of hospital stay decreased from 6 days to 4.5 days in the year 2010 (NS). Conclusion: AF and AFl incidence is still increasing and account for a high admission rate from the ER to the hospital wards. Costs are consequently continuously increasing

Generation and characterization of three human induced pluripotent stem cell lines (EURACi007-A, EURACi008-A, EURACi009-A) from three different individuals of the same family with arrhythmogenic cardiomyopathy (ACM) carrying the plakophillin2 p.N346Lfs*12 mutation.

Abstract Arrhythmogenic Cardiomyopathy (ACM) is a genetically based cardiomyopathy associated with ventricular arrhythmias and fibro-fatty substitution of cardiac tissue. It is characterized by incomplete penetrance. We generated human iPSCs by episomal reprogramming of blood cells from three members of the same family: the proband, affected by ACM and carrying the heterozygous plakophillin2 p.N346Lfs*12 mutation, one asymptomatic carrier of the same mutation and one apparently healthy control. hiPSCs were characterized according to standard protocols including karyotyping, pluripotency marker expression and differentiation towards the three germ layers. These hiPSC lines can be used to study the mechanisms of ACM incomplete penetrance in vitro

Lipidomics, atrial conduction, and body mass index: evidence from association, mediation, and Mendelian randomization models

BACKGROUND: Lipids are increasingly involved in cardiovascular risk prediction as potential proarrhythmic influencers. However, knowledge is limited about the specific mechanisms connecting lipid alterations with atrial conduction. METHODS: To shed light on this issue, we conducted a broad assessment of 151 sphingo- and phospholipids, measured using mass spectrometry, for association with atrial conduction, measured by P wave duration (PWD) from standard electrocardiograms, in the MICROS study (Microisolates in South Tyrol) (n=839). Causal pathways involving lipidomics, body mass index (BMI), and PWD were assessed using 2-sample Mendelian randomization analyses based on published genome-wide association studies of lipidomics (n=4034) and BMI (n=734 481), and genetic association analysis of PWD in 5 population-based studies (n=24 236). RESULTS: We identified an association with relative phosphatidylcholine 38:3 (%PC 38:3) concentration, which was replicated in the ORCADES (Orkney Complex Disease Study; n=951), with a pooled association across studies of 2.59 (95% CI, 1.3-3.9; P=1.1×10-4) ms PWD per mol% increase. While being independent of cholesterol, triglycerides, and glucose levels, the %PC 38:3-PWD association was mediated by BMI. Results supported a causal effect of BMI on both PWD ( P=8.3×10-5) and %PC 38:3 ( P=0.014). CONCLUSIONS: Increased %PC 38:3 levels are consistently associated with longer PWD, partly because of the confounding effect of BMI. The causal effect of BMI on PWD reinforces evidence of BMI's involvement into atrial electrical activity

Left Atrial Pressure as a Predictor of Success in Catheter Ablation of Atrial Fibrillation in a Real-Life Cohort

Aims: The clinical role of the left atrial (LA) hypertension in patients with atrial fibrillation (AF) and its role as predictor in those undergoing pulmonary vein (PV) isolation is still unknown. The aim of the present study was to analyze the role of LA pressure in patients with nonvalvular AF who underwent PV isolation and its implication for AF catheter ablation. Methods: Consecutive patients with drug resistant AF who underwent PV isolation at San Maurizio Regional Hospital of Bolzano (Italy) as index procedure were included in this analysis. Results: A total of 132 consecutive patients (97 males, 73%; mean age 58.0 ± 13.2 years) were included in the analysis. Eleven patients (8%) underwent radiofrequency ablation and 121 (92%) cryoballoon ablation. Higher LA pressures were found in 54 patients (40.9%). At a mean follow up of 14.3 ± 8.2 months (median 12 months), the success rate without antiarrhythmic therapy was 65.9% (87/132; considering the blanking period). Female gender and continuous mean LA pressure were significantly associated with AF recurrence and remained significant on multivariable Cox analysis (respectively, HR 1.845, 1.00–3.40, p = 0.05 and HR 1.066, 1.002–1.134, p = 0.04). We identified a LA mean pressure of >15 mmHg as ideal cutoff and constructed a model to predict AF recurrence which fitted with a concordance index (C-index) of 0.65 (95% CI 0.56–0.75), logrank score p = 0.003

Left Atrial Pressure as a Predictor of Success in Catheter Ablation of Atrial Fibrillation in a Real-Life Cohort

Aims: The clinical role of the left atrial (LA) hypertension in patients with atrial fibrillation (AF) and its role as predictor in those undergoing pulmonary vein (PV) isolation is still unknown. The aim of the present study was to analyze the role of LA pressure in patients with nonvalvular AF who underwent PV isolation and its implication for AF catheter ablation. Methods: Consecutive patients with drug resistant AF who underwent PV isolation at San Maurizio Regional Hospital of Bolzano (Italy) as index procedure were included in this analysis. Results: A total of 132 consecutive patients (97 males, 73%; mean age 58.0 ± 13.2 years) were included in the analysis. Eleven patients (8%) underwent radiofrequency ablation and 121 (92%) cryoballoon ablation. Higher LA pressures were found in 54 patients (40.9%). At a mean follow up of 14.3 ± 8.2 months (median 12 months), the success rate without antiarrhythmic therapy was 65.9% (87/132; considering the blanking period). Female gender and continuous mean LA pressure were significantly associated with AF recurrence and remained significant on multivariable Cox analysis (respectively, HR 1.845, 1.00–3.40, p = 0.05 and HR 1.066, 1.002–1.134, p = 0.04). We identified a LA mean pressure of >15 mmHg as ideal cutoff and constructed a model to predict AF recurrence which fitted with a concordance index (C-index) of 0.65 (95% CI 0.56–0.75), logrank score p = 0.003

The usefulness of QRS Index for prediction of echocardiographic response in cardiac resynchronization therapy: a multicenter study

Background: The association between QRS narrowing and response to cardiac resynchronization therapy (CRT) has been investigated by several studies, but their findings remain inconclusive. Aim of our study was to explore the relationship between QRS Index and echocardiographic response to CRT. Methods: This multicenter, retrospective analysis included 326 consecutive patients (mean age was 70.0±10.1 years old; males 76.7%) who underwent CRT-D implantation in primary and secondary prevention between 2018 and 2020. The estimation of QRS shortening after CRT-D implantation was precisely assessed through the QRS Index, calculated as follows: [(QRS duration before implantation - paced QRS duration)/QRS duration before implantation]*100. Results: After a mean follow-up of 12.7±4.5 months, 55.2% (180/326) of the patients showed an echocardiographic response to CRT. The median [25-75th] QRS Index was 3.85% [-14.1% - +13.9%]. The best predictive cut-off value of QRS Index was 1.40% (sensitivity 70.4%, specificity 64.5%, AUC 0.70). In patients with left bundle branch block, the median [25-75th] QRS Index was 9.85% [+3.87% - +16.7%]. In this subgroup, the AUC was 0.737 and the best predictive cut-off of QRS Index was 2.20% (sensitivity 78.3%, specificity 67%). The multivariable model showed that only left ventricular ejection fraction and QRS Index were independently associated with CRT response (respectively OR 0.92, CI 95% 0.86-0.98, P=0.01 and OR 1.057, CI 95% 1.026-1.089, P<0.001). Conclusions: The QRS Index tightly correlated with CRT response. Only LVEF and QRS Index were independently associated with echocardiographic response to CRT

Modeling incomplete penetrance in arrhythmogenic cardiomyopathy by human induced pluripotent stem cell derived cardiomyocytes

Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are commonly used to model arrhythmogenic cardiomyopathy (ACM), a heritable cardiac disease characterized by severe ventricular arrhythmias, fibrofatty myocardial replacement and progressive ventricular dysfunction. Although ACM is inherited as an autosomal dominant disease, incomplete penetrance and variable expressivity are extremely common, resulting in different clinical manifestations. Here, we propose hiPSC-CMs as a powerful in vitro model to study incomplete penetrance in ACM. Six hiPSC lines were generated from blood samples of three ACM patients carrying a heterozygous deletion of exon 4 in the PKP2 gene, two asymptomatic (ASY) carriers of the same mutation and one healthy control (CTR), all belonging to the same family. Whole exome sequencing was performed in all family members and hiPSC-CMs were examined by ddPCR, western blot, Wes™ immunoassay system, patch clamp, immunofluorescence and RNASeq. Our results show molecular and functional differences between ACM and ASY hiPSC-CMs, including a higher amount of mutated PKP2 mRNA, a lower expression of the connexin-43 protein, a lower overall density of sodium current, a higher intracellular lipid accumulation and sarcomere disorganization in ACM compared to ASY hiPSC-CMs. Differentially expressed genes were also found, supporting a predisposition for a fatty phenotype in ACM hiPSC-CMs. These data indicate that hiPSC-CMs are a suitable model to study incomplete penetrance in ACM

Additional file 1: of Exploring digenic inheritance in arrhythmogenic cardiomyopathy

Includes Supplementary Methods; Tables S1, S2, and S3; Fig. S1. (DOCX 2344 kb

Influence of time between last myocardial infarction and prophylactic implantable defibrillator implant on device detections and therapies. <it>“Routine Practice” data from the SEARCH MI registry</it>

<p>Abstract</p> <p>Background</p> <p>A multicenter European Registry, SEARCH-MI, was instituted in the year 2002 in order to assess patients’ outcomes and ICD interventions in patients with a previous MI and depressed LV function, treated with an ICD according to MADIT II results. In this analysis, we evaluate the influence of the time elapsed between last myocardial infarction (MI) and prophylactic cardioverter defibrillator (ICD) implant on device activations.</p> <p>Methods</p> <p>643 patients with left ventricular dysfunction (mean LVEF 26 ± 5%) and NYHA class I-III were prospectively followed for 1.8 ± 1.2 years in a multicenter registry. The population was divided into 3 groups according to the time between last MI and ICD implant: [1] from 40 days to less than 1.5 years; [2] from 1.5 to less than 7 years and [3] at least 7 years.</p> <p>Results</p> <p>The cumulative incidence of ventricular tachyarrhymias and appropriate device therapy (ATP or shock) were higher in patients implanted longer time from last MI (Gray’s Test p = 0.002 and p = 0.013 respectively). No significant differences were seen in all cause mortality (Gray’s Test p = 0.618) or sudden cardiac death across the MI stratification groups (Gray’s Test p = 0.663).</p> <p>Conclusions</p> <p>Patients implanted with an ICD longer after the MI have a higher chance of presenting ventricular tachyarrhythmias and appropriate ICD therapy, while no differences were seen in overall mortality. These observations may be important for improving patient targeting in sudden death prevention.</p