Large Cohort Of Patients Research Articles

Prognostic value of additional midwall late gadolinium enhancement in patients with ischemic cardiomyopathy

Abstract Background Although several studies have reported the additional presence of midwall late gadolinium enhancement (LGE) using cardiac magnetic resonance (CMR) in patients with ischemic cardiomyopathy (ICM), its prognostic value is not well established. Purpose To assess the prognostic value of the additional presence of midwall-LGE in a large cohort of patients with ICM and reduced left ventricular ejection fraction (LVEF). Methods Between 2008 and 2022, all consecutive patients referred for myocardial viability assessment using CMR with an history of ICM (≥70% stenosis in ≥1 epicardial coronary vessel on angiography and/or history of myocardial infarction and/or coronary revascularization) and LVEF <50% were included. Midwall-LGE was defined by non-ischemic LGE corresponding to non-specific myocardial fibrosis. All patients with a history of acute myocarditis and/or sub-epicardial LGE were excluded. The primary outcome was all-cause death. Nested Cox proportional hazard models were used to assess the prognostic value of additional midwall-LGE including its location (lateral and/or septal and other location) and extent (1 or ≥2 segments), above the presence of ischemic-LGE and traditional prognostic factors. The incremental prognostic value of midwall-LGE extent and location was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), the integrative discrimination index (IDI) and the global Chi-2. Results Among the 6,082 included patients (65±12 years, 73% males), 702 (11.5%) had an additional midwall-LGE. During a median follow-up of 9 (IQR, 7-12) years, 652 (11%) patients died. The presence of midwall-LGE alone was strongly associated with the risk of death compared to patients without midwall-LGE (p<0.001, Figure 1A). Among these patients with midwall-LGE (N=702), survival curves showed an increased risk for midwall-LGE in lateral and/or septal location (p<0.001), for larger extent (p<0.001) and the presence of ischemic-LGE (p<0.001, Figure 1B). In this population with midwall-LGE (N=702), after adjustment for risk factors and extent of ischemic-LGE, midwall-LGE with septal and/or lateral location (adjusted HR: 2.6; 95%CI: 1.8-3.6) and extent ≥2 segments (adjusted HR: 2.6; 95%CI: 1.8-3.7, both p<0.001) were independently associated with all-cause death. A comprehensive LGE model combining all the characteristics of midwall-LGE showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.13; NRI=46%; IDI=19%, Chi-2 global=261, all p<0.05; LR-test p<0.001, Figure 2). Conclusion In a large cohort of ICM patients, the presence of an additional non-ischemic midwall-LGE is an independent prognosticator of all-cause death, particularly for larger extent or when present in the septal and/or lateral location.Prognostic value of midwall-LGEIncremental prognostic value

Pharmacologic treatment of hypertension guided by non-invasive haemodynamics in primary care improves blood pressure control

Abstract Background Current guidelines on hypertension (HTN) provide blood pressure (BP) targets and therapeutic algorithms but ignore the potential to treat individual patients according to their haemodynamic profile. We have shown that use of non-invasive haemodynamic information obtained by impedance cardiography (ICG) can improve BP control in the primary care setting. Purpose To investigate whether improved rates of BP control by matching patients’ non-invasive haemodynamics to specific pharmacologic treatments and increasing patient engagement translates into improved clinical outcome measures. Methods Electronic medical records (EMR) were obtained for 14,698 patients from two US primary care groups between 2014 and 2023. ICG was done when BP exceeded 140/90 mmHg. Haemodynamic measurements included mean arterial pressure (MAP), cardiac index (CI), cardiac power index (CPI), total peripheral resistance index (TPRI), stroke index (SI) and heart rate (HR) (Figure 1). Haemodynamic ICG profiles were classified as: Vasoconstriction, Hyperdynamic, or Mixed pattern. Printed clinical decision support (CDS) tools and later an EMR integrated CDS application were used to communicate recommendations to physicians. Printed reports were shared with patients to increase their engagement. Pharmacological therapy was tailored based on haemodynamic information. Rates of successful BP treatment and the occurrence of myocardial infarction (MI) or stroke were tracked through the EMR. Results Of 14,698 patients, 50% were women, 17% were Black and 17% were aged 18-49 years, 45% aged 50-69 years, and 38% age ≥ 70 years. A total of 21,246 ICGs were performed classifying patients as Vasoconstriction 47%, Hyperdynamic with high heart rate (HR) or high stroke index (SI) 24%, and Mixed Haemodynamic (combination of Vasoconstriction and Hyperdynamic) 29% (Figure 1). Demographic features were not strongly associated with haemodynamic classification. Within 2-3 years of inclusion, >85% of patient achieved BP control (<140/90 mmHg), which was sustained during follow-up. Over a median (IQR) follow-up of 8 (2016-2023) years, there were 14 (5) MI and 34 (16) strokes. These event rates appear to be lower than those reported in other large cohorts of patients with HTN. Conclusions Treating patients with HTN according to their individual haemodynamic profile is associated with high rates of BP control. Further analysis will determine whether the rates of MI, stroke and death are lower than expected based on the patients baseline risk profile.Haemodynamic Status (ICG Test Results)

Evolution over time of cardiac biomarkers, electrocardiographic and echocardiographic features in a large cohort of patients with wild-type transthyretin cardiac amyloidosis treated with tafamidis

Abstract Introduction Data on evolution of transthyretin wild-type cardiac amyloidosis (ATTRwt) during treatment with tafamidis is scarce. This hinders the quest for parameters of response and a priori treatment eligibility. Purpose To study the evolution of biomarkers, ECG, and echocardiographic features during early tafamidis treatment. Methods We prospectively collected data after 12-18 months of treatment in a single-centre database. Changes of NT-proBNP and high-sensitivity Troponin I (hs-cTnI) between baseline and follow-up evaluations (at 12 and 18 months) were tested for significance. For ECG and echocardiographic features, we considered baseline and the last available follow-up (median interval 11.1 months). Results We included 253 patients (median age 77[71-82]years; 90% males). Median (IQR) baseline NT-proBNP was 2472(1355-4749)ng/L, hs-cTnI 47(30-82)ng/L. Furosemide was administered in 58% of cases (median dose 25[25-50]mg/day). Compared to baseline, NT-proBNP was 2342(1316-4148)ng/L at 12 (p=0.886), and 2633(1393-6063)ng/L at 18 months (p=0.285), with 4% and 30% of patients showing ≥30% and ≥300ng/L increase at 12 and 18 months, respectively; hs-cTnI was 46(29-70)ng/L at 12 (p=0.947), and 44(25-68)ng/L at 18 months (p=0.866), with 35% and 7% showing a ≥20% increase at 12 and 18 months, respectively, and 21 (11.5% over 183 analyzable) with increase at 12 and reduction at 18 months. Patients on furosemide were 69% and 70% at 12 and 18 months, respectively; the dose increased to 37.5(25-75)mg/day at 18 months (p=0.009). At baseline, 117(47%) patients had history/permanent atrial fibrillation (AF). Forty-one(16%) had an implantable electronic device, 16(6%) underwent subsequent implantation. Median PR interval was 210(185-240)msec, trending toward prolongation (p=0.054). QRS duration increased (100[86-130]vs120[90-140]msec, p=0.004), together with conduction disturbances (left anterior fascicular block 30[21%]vs43[29%], p=0.036; right bundle branch block 14[10%]vs27[18%], p=0.002). AF prevalence raised from 19% to 25%. There were no significant changes in left ventricular (LV) geometry (septum thickness 18[16-20]vs18[16-20]mm, p=0.666; end-diastolic diameter 45±7vs45±8mm, p=0.434), systolic function (ejection fraction 51±10%vs49±11%, p=0.070), filling pressures (E/e’ 17[11-20]vs14.9[13-19], p=0.086) and left atrial size (mean volume 46±15vs48±13ml/m2, p=0.649). Tricuspid annular plane systolic excursion (18±4vs17±4mm) and pulmonary artery systolic pressure (40[33-45]vs36[30-45]mmHg) remained stable. Conclusions We did not observe neither improvement nor worsening of laboratory/instrumental variables within the first 12-18 months of tafamidis. There was a progression of electrical disorders. After initial progression hs-cTnI tended to improve. Extended follow-up and a matched case-control series will help identify possible later changes useful to monitor treatment response and effects of supporting heart failure treatments.

Visit-to-visit changes in heart rate in heart failure: a pooled participant-level analysis of the PARADIGM-HF and PARAGON-HF trials

Abstract Background Resting heart rate (HR) is a strong established marker of risk in patients with heart failure (HF), but the clinical implications of changes in HR over time are less well established. We aimed to explore the association between visit-to-visit changes in HR and cardiovascular (CV) outcomes in a pooled participant-level dataset of 2 large cohorts of patients with HF across the full range of left ventricular ejection fraction (LVEF). Methods PARADIGM-HF and PARAGON-HF were global, multicenter, randomized clinical trials testing sacubitril/valsartan against an active control (enalapril or valsartan, respectively) in patients with HF and LVEF ≤40% (in PARADIGM-HF) or LVEF ≥45% (in PARAGON-HF). Change in HR was defined as the difference in HR between a visit at any time and the preceding visit. The association between the change in HR and subsequent risk of first HF hospitalization (HFH) or CV death was assessed using Cox proportional hazards models, after adjusting for HR at the preceding visit and potential confounders. HR at any time was also assessed using repeated measures regression models with restricted cubic splines, and was plotted relative to time defined as the number of months prior to or immediately following a HFH event or end of follow-up. Patients who experienced HFH during the study period were compared to a control population who remained free of all-cause hospitalization and all-cause death during the follow-up period. Results A total of 13,194 patients (mean age 67±11 years, 67% men, mean LVEF 40±15%) were included. Heart rates were available in 16 visits in both PARADIGM-HF and PARAGON-HF. Over a median follow-up of 2.4 years, 3,114 patients underwent a first HFH or CV death (10.4 events per 100 patient-years). Any increase in HR from the preceding visit, compared with no change, was associated with a significantly higher risk of first HFH or CV death (Figure 1, adjusted hazard ratio 1.10, 95% confidence interval, CI: 1.08–1.13, P<0.001, per 5 bpm increase in HR). Conversely, a drop in HR was associated with significantly lower risk. This prognostic association between temporal changes of HR and risk of first HFH or CV death was consistent across the range of LVEF (Pinteraction=0.34) and seen irrespective of background use of β-blockers (Pinteraction=0.91). Relative increases in HR were especially prognostic in patients without a history of atrial fibrillation/flutter (Pinteraction=0.01). HR at any time appeared to increase during the 8 months prior to a HFH event, and remained elevated after hospitalization, in comparison to a relatively stable HR observed in the control group (Figure 2). Conclusions Across a broad spectrum of patients with chronic HF, relative increases in HR from a preceding visit strongly and independently predicted both CV and non-CV outcomes. Our findings suggest that detection of notable increases in HR between outpatient visits may help identify patients at heightened risk of adverse events.

Endomyocardial biopsy in the diagnosis of cardiac sarcoidosis

Abstract Background Definite diagnosis of cardiac sarcoidosis (CS) requires proof of sarcoid granulomas in the heart. Endomyocardial biopsy (EMB) is considered a risky procedure with poor sensitivity (<25%) in CS (1), although comprehensive studies on its diagnostic performance are not available. Purpose We investigated the sensitivity, complications, and prognostic significance of EMB in a large cohort of patients with CS to help to choose diagnostic strategy when the disease is suspected. Methods We analysed the data of 260 consecutive patients diagnosed with CS in 1988-2022 at our institution. All met the diagnostic criteria of the Heart Rhythm Society (1). The use, findings, and complications of EMB were retrospectively noted in addition to patients’ demographics, presenting phenotype, diagnostic examinations, and future serious cardiac events. The data were retrieved from hospital records and an ongoing CS registry (2). Advanced imaging studies (cardiac magnetic resonance, positron emission tomography) were re-analysed and the follow-up information was updated until June 2023. EMB’s performance was assessed also in 30 cardiac transplant recipients having CS at the histopathologic study of the explanted heart. Results Of the 260 patients (mean age 49, 60% females), 216 (83%) underwent diagnostic EMB, 48 with repeat procedures. The sensitivity of EMB was 38%, rising to 49% after repeats. The predictors of positive EMB (Table 1) included the presenting phenotype and characteristics of the activity, extent, and location of myocardial involvement. Presentation with ventricular tachyarrhythmia, left ventricular (LV) ejection fraction ≤45%, elevation of cardiac troponins, and presence of middle or apical LV septal late gadolinium enhancement on magnetic resonance imaging were independent predictors (p<0.05) of positive biopsy. The sensitivity of EMB was directly related to the count of the predictors present (Figure 1). The rate of procedural complications was 9.7% overall and 0.7% for major events. One pericardial effusion needed drainage, but no deaths or long-term sequels followed the biopsies. Minor complications included 10 paroxysms of ventricular tachycardia and 6 small pericardial effusions. The 10-year rate (95% CI) of the composite of cardiac death, end-stage heart failure, or ventricular tachyarrhythmia was 55% (44-67%) with positive EMB vs 29% (17-44%) with negative EMB (p<0.001). When adjusted for the presenting phenotype and LV ejection fraction, EMB did not predict outcome events. In the 30 patients with CS in explanted hearts, the sensitivity of EMB, including the repeats, was 60%. Conclusion The sensitivity of EMB is better than usually presented in CS and the higher the more extensive myocardial involvement is. Risk of serious complications is <1%. In patients with suspect CS, the pre-test likelihood and value of positive EMB should be weighed against the procedural risks in shared decision-making when choosing the diagnostic pathway.

Predictors of adverse cardiac events in a large cohort of patients with antiphospholipid syndrome

Abstract Background Non-valvular cardiac disease in antiphospholipid syndrome (APS) has been modestly evaluated. Aim We wanted to assess the prevalence and evolution of major adverse cardiovascular events(MACE) in a cohort of APS patients. Material and Methods From a large cohort of 181 APS patients included in a study from 2011-2012.year data for the occurrence of MACE in 10 years of follow-up were evaluated in 82 patients (86.6% females, 62.2% with primary (PAPS), and 37.8% patients with APS associated with systemic lupus erythematosus (SLE) (sAPS)). At the inclusion in all patients, a transthoracic echocardiography study for the assessment of dimensions and functionality of the left and right heart along with valvular functions and morphology. Standard atherosclerotic risk factors prevalence was analyzed. Antiphospholipid antibodies(aPL) analysis included the detection of aCL (IgG/IgM), ß2GPI (IgG/IgM), and LA, and all patients were treated according to the valid guidelines by the rheumatologist. Data regarding the occurrence of new myocardial infarction (MI), cerebrovascular events (CVI), arterial and/or venous thrombosis, heart failure (HF), and cardiovascular death (considered as MACE) have been collected 10 years after inclusion. Results The prevalence of standard atherosclerotic risk factors was less than 40% in both study groups. Left ventricle ejection fraction(LVEF) was over 45% in more than 90% of patients in both groups (p=0.246) with valvular dysfunction present in 49% of PAPS and 58.1% of sAPS patients (p=0.426). 9.8% PAPS and 12.9% sAPS had coronary artery disease(CAD) (p=0.724) and HF was present in 7.8% PAPS and 3.2% sAPS (p=0.645). MACE occurred in 17.6% of PAPS and 22.6% of sAPS (p=0.585). The new MI occurred in 9.8% of PAPS and 9.7% of sAPS (p=1.000), CVI in 5.9% of PAPS and 3.2% of sAPS (p=1.000), HF in 5.9% of PAPS and 3.2% of sAPS (p=1.000) and cardiovascular death in 9.8% of PAPS and 12.9% of sAPS (p=0.724). New thrombotic events (arterial and/or venous) occurred in 15.7% of PAPS and 17.2% of sAPS (p=1.000). During the follow-up period, 66.7% of PAPS and 55.2% of SAPS (p=0.313) were treated with aspirin, 25.5% of PAPS and 25.0% of sAPS with warfarin, and chloroquine was administered in 46.8% of PAPS and 53.6% of sAPS (p=0.571). Age (p=0.008), gender (p=0.034), thrombotic APS (p=0.033), hypertension (p=0.003), diabetes mellitus (p=0.043), and cardiovascular manifestations present at the time of APS diagnosis (p=0.035), namely CAD (p=0.001) and HF (p=0.005) were significantly associated with 10y MACE. aPL type and category were not associated with 10y MACE. In a multivariate logistic model, age. hypertension, and HF were independent predictors for 10y MACE. Conclusions APS patients develop new cardiovascular events despite optimal medical therapy. Cardiovascular evaluation at the time of diagnosis and proper cardiologist follow-up with the rigorous treatment of standard atherosclerotic risk factors is of utmost importance.

Plasma trimethylamine-n-oxide associates with reduced hippocampal volume and cognitive impairment in atrial fibrillation

Abstract Background/Introduction Atrial fibrillation (AF) is the most common cardiac arrhythmia in modern society and affected patients appear particularly vulnerable to cognitive dysfunction. Yet, the pathomechanism of this association other than thromboembolism (TE) is not fully understood. We have shown earlier an association of cognitive dysfunction with the gut microbiome derivate trimethylamine-N-oxide (TMAO), which predominantly results from the consumption of red meat. We therefore hypothesized that TMAO may affect hippocampal volume (HV) as a brain structure relevant for cognition. Purpose To demonstrate the structure-function correlation of high TMAO levels with reduced cognitive function and lower HV in a large cohort of patients with atrial fibrillation. Methods We included 1’736 patients with confirmed AF from the Swiss-AF-cohort with both, available blood samples for TMAO measurement and with brain magnetic resonance imaging (bMRI) for the determination of HV at baseline. TMAO levels were measured by liquid chromatography-mass spectrometry (LC-MS). bMRI were obtained by 1.5 or 3 Tesla scanners. HV was assessed by the FreeSurfer software (v 7.4.0) subregion segmentation module and normalized by using Sequence Adaptive Multimodal SEGmentation (SAMSEG) to determine the segmentation based intracranial volume. Patients were divided into TMAO quartiles (Q1: 0.6-3.8, Q2: 3.8-5.5, Q3: 5.5-8.5, Q4: 8.5-164.3μmol/l). Their TMAO levels were compared with their HV (unit = mm3) in linear mixed effect models adjusted for multiple covariates (model 1: age, sex, total intracranial volume (ICV), education level; model 2 = model 1 + smoking status, body mass index (BMI), alcohol consumption, physical activity; model 3 = model 2 + hypertension, coronary artery disease, previous stroke, geriatric depression scale). We assessed both unilateral HV (right = RHV, left = LHV) and bilateral HV standardized by the individual total ICV. Results Overall mean age was 72.5 years (+/-8.4 SD), 27.2% were female. Most of the patients were well educated (39.4% advanced, 48.8% middle education) and 44% never smoked. After multivariable adjustments, patients in the highest TMAO quartile showed a significant reduction of bilateral HV volume of 93.4mm3 (95% CI -179.0 to -7.8, p = 0.03). The RHV appeared more affected and was significantly reduced by 48.2mm3 (CI -93.4, -3.0, p=0.04), whereas LHV was decreased by 44.2mm3 (-89.4, 1.0, p=0.06) in the highest TMAO quartile. Conclusion(s) TMAO negatively associates with bilateral HV in patients with AF. Our results suggest a structure-function-correlation between high TMAO levels and cognitive dysfunction. The findings may be relevant for the high TMAO-exposed patients and advocates for the importance of (possible dietary) prevention in AF.

Sex differences in left ventricular dilatation in patients with significant aortic regurgitation: prognostic implications

Abstract Background Left ventricular (LV) dilatation is a strong indicator of adverse outcome in patients with aortic regurgitation (AR). Accordingly, current guidelines recommend the use of LV end-systolic diameter index (LVESDi) as one of the criteria to trigger aortic valve surgery (AVS) in patients with severe AR, but with the same threshold regardless of gender. Purpose To assess sex differences in LV remodeling using both volumetric and linear measurements in a large cohort of patients with significant AR (moderate or greater) and to investigate their prognostic implications. Methods A total of 1070 patients (56 ± 18 years, 691 men) were included. The primary outcome was all-cause mortality. Results Women presented with older age (58 ± 19 vs. 55 ± 17, p=0.023) and more advanced heart failure (HF) symptoms than men (NYHA class III-IV 12% vs. 9%, p=0.017). Men showed significantly larger LVESDi (21 ± 5 vs. 20 ± 5 mm/m2, p=0.013) and LV end-systolic volume index (LVESVi 37 ± 28 vs. 26 ± 17 ml/m2 p<0.001). During a median follow-up of 89 (IQR, 54-132) months, 168 patients died. Women had lower survival rates at 3, 5, and 10 years of follow-up compared to men (92% vs. 94.3%; 85% vs. 89.7% and 75.3% vs. 84.1%, p=0.005) (Figure 1). Spline curve analysis revealed that the threshold of LVESDi associated with an increased risk of mortality was 20 mm/m2 for both sexes. In turn, the threshold for LVESVi was 40 ml/m2 for women and 45 ml/m2 for men. Univariable Cox regression models were constructed separately for men and women. The variables associated with all-cause mortality were age, NYHA class III-IV, and AVS as time-dependent covariate in women, and age, diabetes, AVS as time-dependent covariate, and LAVI (left atrial volume index) in men. These parameters were used as a basal multivariable Cox regression model on top of which LVESDi >20 mm/m2 (Model 1), LVESVi >40 ml/m2 for women and 45 ml/m2 for men (Model 2) were added (Table 1A). LVESVi >40 ml/m2 was not a significant univariate predictor in men. In women, LVESDi >20 mm/m2 (HR: 2.046, 95%CI 1.244-3.419; p=0.006) and LVESVi >40 ml/m2 (HR 1.758, CI 1.095-2.825; p=0.020) showed an independent association with all-cause mortality among other factors (Table 1A). In men, death was independently associated with LVESDi >20 mm/m2 (HR 1.979, 95%CI 1.255-3.121; p=0.003) and LVESVi >45 ml/m2 (HR 2.388, 1.522-3.746; p<0.001), among other factors (Table 1A). Moreover, when added to a basal model that included clinical and echocardiographic variables associated with prognosis, LV dilatation based on volumetric LV enlargement resulted in a greater discriminatory power for both genders (Table 1B). Conclusion Men and women have a similar LVESDi threshold of 20 mm/m2, which is associated with an increased risk of death. However, their respective cut-off values for LVESVi differ, with the optimal threshold for women being 40 ml/m2 and for men 45 ml/m2.

Myocardial parametric mapping in patients with suspected acute myocarditis: a prognosis study

Abstract Background T1 mapping and T2 mapping have become essential components of the 2018 Lake Louise criteria and obtained excellent results in diagnosing myocarditis. However, their prognostic value in acute myocarditis has not yet been well recognized or established. Purpose Our study aims to investigate the prognostic value of T1 mapping, T2 mapping, and extracellular volume fraction (ECV) in a large cohort of patients with suspected acute myocarditis. Materials Patients meeting the recommended clinical criteria for suspected acute myocarditis were consecutively enrolled. The primary endpoint is the composite of cardiac death, heart failure hospitalization, heart transplantation, sustained ventricular arrhythmia, and recurrent myocarditis, defined as major adverse cardiovascular events (MACE). All patients underwent CMR at 3.0 T scanner using a standardized, routine imaging protocol, and the three short-axis view slices (basal, mid-ventricular, and apical) were divided into 16 segments according to the American Heart Association 17-segment model (apex excluded). We also averaged the native T1 values, ECV, and T2 values of all 16 segments to get global T1 and ECV fraction values, respectively. Statistically significant parameters from univariate Cox analyses were put into multivariate Cox analysis. Results A total of 235 patients (150 men; 32±13 years) were enrolled in this study. During a mean follow-up of 43.0±3.6 months, MACE occurred in 37 patients (15.7%) and was univariably associated with heart failure presentation, left ventricular ejection fraction, left ventricular end-systolic volume index, left ventricular end-diastolic volume index, native T1 and ECV. Patients with MACE showed higher global native T1, ECV, and T2 values (1348±59 vs 1266±51, p=<0.001; 40.0±8.7 vs 32.8±5.9, p<0.001; 63.4±12.1 vs. 55.5±9.1, p=0.011), and were more likely to have tissue changes in the interventricular septum and anterior wall (Figure 1). In a series of nesting multivariable Cox regression models, the addition of native T1 (per 10-ms increase: HR, 1.128; 95% CI: 1.043, 1.220; p = 0.003; Harrell’s C-index = 0.833) or ECV (per 5% increase: HR, 1.382; 95% CI: 1.060, 1.802; p = 0.017; Harrell’s C-index = 0.847) improved prognostication compared with the model based on clinical variables, left ventricular ejection fraction, and septal late gadolinium enhancement (Harrell’s C-index = 0.762) (Figure 2). T2 in multivariate Cox regression analysis didn’t show predictive value, but his inclusion increased the C-index of the model to 0.814. Conclusions Myocardial parametric mapping not only holds substantial diagnostic value but also plays a critical role in the prognostic assessment and risk prediction of myocarditis. Their utilization in these contexts enhances the accuracy and effectiveness of clinical evaluations and decision-making processes.

4-year follow-up results of percutaneous closure of atrial septal defect with the total biodegradable poly-L-lactic acid device: date from a prospective, single-center trial

Abstract Background The poly-L-lactic acid (PLLA) device is a novel, total biodegradable occluder dedicated to percutaneous closure of atrial septal defect (ASD) .Closure of ASD with the PLLA device has proven to be relatively safe and effective in our preclinical and first-in-human studies. Objective The aim of the study was to evaluate long-term safety and efficacy of the PLLA device in percutaneous closure of ASD in a large cohort of patients. Methods A prospective study enrolling patients who had a clinically significant ASD was conducted in our institution from May 2018 to August 2019. Percutaneous ASD closure was undertaken with the PLLA device. Evaluations were scheduled pre-hospital discharge and again at 1, 3, 6, 12, 24, 36 and 48 months post implantation. Primary endpoints were a composite of clinical success, including closure success and no major complications at the 48-month follow-up evaluation. Results A total of 52 patients (35 children, 55.8% females, median age 7.55 years, median weight 28.75Kg) underwent an attempt at percutaneous ASD closure with PLLA device. Successful device implantation was achieved in 50 (96.1%) of 52 patients with delivery attempts. All the 50 patients (100%) completed 4-year follow-up visit. Closure success at 4-year follow-up were 84% (42/50), with 8 patient (16%) reported to have clinically significant leaks, including 2 large residual leaks, 5 moderate residual leaks, and 1 small residual leak. 10 complications occurred, with 1 event of cardiac arrhythmia during procedure, and 9 follow-up events, consisting in cardiac arrhythmias (n=6), moderate or large mitral regurgitation (n=2), and headache (n=1). Conclusion Percutaneous ASD closure with PLLA device in human seems to be safe. However, increased occurrence of residual leaks overtime indicated that long-term efficacy of PLLA device in human was sub-optimal.TTE follow-up of a case with PLLA device

Remnant cholesterol and mortality in 37.559 patients from LIPIDOGRAM 2004, 2006 and 2015 studies

Abstract Introduction Remnant cholesterol (remnant-C) is produced by metabolism of triglyceride rich proteins and contributes to residual cardiovascular (CVD) risk. Purpose To asses association between remnant cholesterol and all-cause mortality in a large cohort of patients under the care primary care physicians. Methods The LIPIDOGRAM studies were carried out in the primary care in Poland in 2004, 2006 and 2015. Patients (n=47,398) recruited in all 16 administrative regions in Poland and physicians were proportionally distributed to the number of inhabitants in each administrative region. Each patient was asked to fill the questionnaire on risk factors, chronic diseases, treatment, and lifestyle. In the present analysis we included consecutive patients with body mass index (BMI) >18.5 kg/m2 aged 18-70 years. Median follow up was (5.3 years (interquartile range 5.7-17.3). For this analysis we approved the cut-off point of fasting remnant cholesterol >30 mg/dL (>0.77 mmol/L) that differentiated subjects at high risk of cardiovascular events. We used univariate and multivariate Cox regression modelling to assess the association between remnant-C and all-cause mortality. Results Finally, 37,559 patients were included meeting the inclusion criteria and for which the follow-up data was available. Mean remnant-C concentration was: 27 mg/dl / 0.7 mmol/l (standard deviation 15 mg/dl/ 0.38 mmol/l). Remnant-C was associated with 5-year mortality and overall mortality during the study period, with hazard ratios (HR) of 1.21 (95% CI: 1.04-1.41, p<0.001) and 1.42 (95% CI: 1.32-1.53, p<0.001) for each 1 mmol/l increase, respectively. After adjusting for age, sex, BMI, education level, place of residence, hypertension, diabetes mellitus, smoking, previous myocardial infarction, metabolic syndrome presence, and statin and fibrate treatments, remnant-C was associated with long-term mortality—HR (per 1 mmol/l) of 1.08 (95% CI: 1.00-1.17, p=0.049)—but not with 5-year mortality—HR (per 1 mmol/l) of 0.97 (95% CI: 0.83-1.13, p=0.7). Predefined level of remnant-C > 30 mg/dl (0.77 mmol/l) was associated with higher 5 year (HR- 1.15, 95%CI (1.02-1.31, p=0.021) (Figure 1A) and long-term all-cause mortality (HR- 1.26, 95%CI (1.19-1.33, p<0.001) (Figure 1B). Conclusions Higher remnant-C cholesterol levels are associated with long term all-cause mortality in patients aged 18-70 years.

One-year outcomes of patients with hypertrophic cardiomyopathy according to levels of inflammatory biomarkers

Abstract Background Hypertrophic cardiomyopathy (HCM) is a vastly heterogeneous sarcomere disorder unified by maximal left ventricular (LV) thickness increases. The lifetime relative risk of morbidity in HCM is four-fold higher than in the general population, primarily driven by arrhythmias and heart failure (HF). Numerous prognostic features have been identified, but our ability to identify high-risk patients of progression remains rudimentary. Small retrospective studies have shown that systemic inflammation is associated with adverse outcomes in patients with HF; others, small and single-center, have also shown associations between adverse outcomes and inflammation in HCM. Purpose We aimed to determine whether elevated levels of inflammatory biomarkers are associated with an increased risk of acute heart failure (AHF) and mortality at 1 year in a large cohort of patients with HCM across multiple centers in the United States (US). Methods In this retrospective study, using the US cohort of 60 healthcare organizations in the TriNetX database, we included more than 85,000 adult patients with HCM (ICD-10-CM codes I42.1 and I42.2) between 2004 and 2024. Patients were divided according to predetermined cut-offs of different inflammatory biomarkers (C-reactive protein [CRP], <2 mg/L vs. 2-100 mg/L; white blood cells [WBC], < vs. ≥ the median [8x10^3/µL]; neutrophils [Neu], < vs. ≥ the median [5x10^3/µL]). These cohorts were then 1:1 propensity score matched (PSM) for age, sex, and race. We used Kaplan-Meier survival curves to derive cumulative incidence curves (as 1 minus Kaplan-Meier survival estimates) for AHF (ICD-10-CM codes I50.21, I50.23, I50.31, I50.33, I50.41, I50.43) or death, and we compared them with the Log-rank (Mantel-Cox) test. We also derived Hazard Ratios (HR) with 95% Confidence Interval (CI) from Cox regression analysis to compare the outcomes within the groups at 1-year. Results After PSM, patients with HCM and CRP levels between 2-100 mg/L experienced higher rates of the composite outcome (19.6% vs. 12.2%, Log-rank p<0.001; HR 1.67, 95% CI [1.29-2.16]), as well as the separate outcomes of death (14.7% vs. 6.8%, Log-rank p<0.001; HR 2.23, 95% CI [1.68-2.98]) and AHF (10.9% vs. 7.5%, Log-rank p<0.001; HR 1.49, 95% CI [1.07-2.07]), compared to those with CRP <2 mg/L (Table 1)(Figure 1). Similarly, patients with Neu ≥5x10^3/µL reported higher incidences of the composite outcome (20.3% vs. 13.2%, Log-rank p<0.001; HR 1.62, 95% CI [1.55-1.68]) and the separates outcomes, compared to those with Neu <5x10^3/µL (Table 1) (Figure 1). Patients with WBC ≥8x10^3/µL also had increased rates of the composite outcome (19.4% vs. 14.1%, Log-rank p<0.001; HR 1.43, 95% CI [1.38-1.48]) and the separate outcomes, compared to those with WBC <8x10^3/µL (Table 1)(Figure 1). Conclusions In the first large 'real world' analysis of patients with HCM, elevated levels of inflammatory biomarkers were associated with worse outcomes of death and acute heart failure.

Race in heart failure: a pooled participant-level analysis of the global PARADIGM-HF and PARAGON-HF trials

Abstract Background Mechanisms of disease pathobiology, prognosis, and potentially treatment responses might vary by race in patients with heart failure (HF). Early experiences with neprilysin inhibition suggested possible increased risks of angioedema, especially among Black individuals. We aimed to examine the safety and efficacy profile of sacubitril/valsartan in a pooled participant-level dataset of 2 large cohorts of patients with HF by self-reported race. Methods PARADIGM-HF and PARAGON-HF were multicenter, randomized clinical trials testing sacubitril/valsartan against a renin-angiotensin system inhibitor (RASi, enalapril or valsartan, respectively) in patients with HF and LVEF ≤40% (PARADIGM-HF) or LVEF ≥45% (PARAGON-HF). We included all patients with available data on self-reported race and categorized patients as White, Asian, or Black. We assessed adjudicated outcomes including the composite of first HF hospitalization (HFH) or cardiovascular (CV) death, its components, and angioedema by racial group. Results Among 12,097 included participants, 9,451 (78.1%) were White, 2,116 (17.5%) were Asian, and 530 (4.4%) were Black. Asian participants were from 19 countries, with highest enrollment from India, China, and the Philippines. Black participants were from 18 countries, with highest enrollment from the US, South Africa, and Brazil. Black patients had the worst baseline health status (adjusted KCCQ-OSS mean 70.3), while White (71.4) and Asian patients (76.4) had better health status; P<0.001. Over 2.4-years of median follow-up, Black (adjusted HR 1.67; 95% CI 1.37-1.89; P<0.001) and Asian patients (adjusted HR 1.32; 95% CI 1.16-1.50; P<0.001) experienced higher risks of the primary outcome compared with White patients (Figure 1). The treatment effects of sacubitril/valsartan vs. RASi on the primary endpoint were consistent among White (HR 0.84; 95% CI: 0.77-0.91), Asian (HR 0.92; 95% CI: 0.78-1.10), and Black patients (HR 0.79; 95% CI: 0.58-1.07; Pinteraction = 0.39). In light of higher baseline risks, Black patients accrued the greatest absolute risk reduction with sacubitril/valsartan (Figure 2). Consistent treatment benefits by race were also observed for the individual components (CV death alone and first HFH alone). Rates of any adjudicated angioedema were numerically higher with sacubitril/valsartan vs. RASi across race groups (White 0.4% vs. 0.2%; Asian 0.6% vs. 0.2%; Black 2.3% vs. 0.8%), however no patient in either trial experienced airway compromise or required mechanical airway protection. Conclusions In a pooled experience of over 12,000 participants enrolled in 2 trials conducted across 56 countries, Black and Asian patients exhibited a higher risk of CV events than White patients. Rates of non-serious angioedema were numerically higher with sacubitril/valsartan across race groups. The relative CV benefits of sacubitril/valsartan were consistent across races, with greatest absolute benefits observed in Black patients.

Integrated care using the ABC-stroke pathway improves cardiovascular outcomes and survival in patients with recent ischaemic stroke: a population-based cohort study

Abstract Background A recent European Society of Cardiology (ESC) Council on Stroke position paper proposed the ABC-stroke pathway, a holistic and integrated care approach to optimise the post-stroke management for patients with recent stroke, and associated heart disease. The ABC-stroke pathway is based on 3 pillars: "A" Appropriate Antithrombotic therapy; "B" Better functional and psychological status; and "C" Cardiovascular risk factors and Comorbidity optimisation (including lifestyle changes). There are limited data on the impact of adherence to the ABC-stroke pathway on post-stroke patient outcomes. Purpose We aimed to investigate the potential impact of ABC-stroke pathway adherence in the Clinical Data Analysis and Reporting System (CDARS) database in Hong Kong. Methods The analysis included patients with new-onset ischaemic stroke recorded in CDARS between 1st June 2006 and 31st May 2022. Multivariable Cox proportional hazards regression analyses were performed to evaluate the association between adherence to the ABC-stroke pathway and the primary outcome. The primary endpoint was a composite outcome of recurrent ischaemic stroke, transient ischaemic attack, haemorrhagic stroke, myocardial infarction, heart failure and all-cause death. Secondary outcomes were the individual components of the composite outcome, and cardiovascular death. Results Of the 9,669 included patients with ischaemic stroke (mean age 69.6 ± 13.4 years; 42.5% female), 58.1% were adherent to all 3 main ABC-stroke pillars. After 1 year of follow-up, adherence to the ABC-stroke pathway was associated with a lower risk of the primary composite endpoint (HR: 0.80; 95% CI: 0.72–0.88). Risk reductions increased progressively with a higher number of ABC-stroke criteria obtained (Figure 1). On multivariate analyses of the secondary outcomes, ABC-stroke pathway-adherent care was associated with a reduced risk of all-cause mortality (HR: 0.72; 95% CI: 0.62–0.85), cardiovascular death (SHR: 0.64; 95% CI: 0.45–0.90), haemorrhagic stroke (SHR: 0.50; 95% CI: 0.38–0.67) and heart failure (SHR: 0.771; 95% CI: 0.596-0.998) (Table 1). Conclusion In a large cohort of patients with ischaemic stroke, adherence to the ABC-stroke pathway was associated with a reduction of the risk of adverse outcomes.

Chronic inflammation is associated with impaired cardiac structure and function in patients with inflammatory arthritis: the ARTCADIA Study

Abstract Background Inflammation as an underlying cause of cardiac dysfunction has been underscored in recent years. Patients with inflammatory arthritis (IA) are at risk of being exposed to a high degree of chronic and systemic inflammation. It is therefore important to investigate whether high inflammatory burden impacts cardiac structure and function in patients with IA. Purpose To examine the impact of long-term inflammation on measures of cardiac structure and function in individuals with rheumatoid arthritis (RA) and axial Spondyloarthritis (axSpA), collectively referred to as IA, in a large cohort. Methods In a prospective cohort study, outpatients with a diagnosis of IA were included over two years during their biannual rheumatological routine appointment. In total, 1,285 participants were included. Participants were evaluated at a cardiology research center where echocardiography was performed following a pre-defined protocol. To evaluate chronic inflammation, C-reactive protein (CRP) was averaged from clinical outpatient visits registered in a rheumatological database. Uni- and multivariable linear regressions were used to examine the relationship between echocardiographic measures and log-transformed CRP. Results Among the 1,285 participants, 903 (70%) were diagnosed with RA, 358 (28%) with axSpA, and 24 (2%) with other forms of IA. Mean age was 60 ± 13 years, 64% were female. The median number of outpatient visits was 30 (Interquartile range (IQR): 18 - 48), median disease duration was 12 (IQR: 6 - 20) years, and the median outpatient CRP was 5.7 (IQR: 3.7 – 9.8) mg/L. 519 (40%) patients had hypertension (HT), 113 (9%) diabetes mellitus (DM), 76 (5.9%) ischemic heart disease (IHD) and 35 (2.5%) heart failure (HF). Mean left ventricular (LV) ejection fraction was 54.6 ± 5.7%, mean numerical global longitudinal strain (GLS) was 17.8 ± 2.4%, mean LV mass index (LVMi) was 73 ± 18 g/m2 and mean tricuspid annular plane systolic excursion (TAPSE) was 2.5 ± 0.4 cm. In univariable analyses, higher levels of CRP were significantly associated with lower GLS, p < 0.001; higher E/e’, p = 0.001; higher LVMi, p < 0.001 and lower TAPSE, p = 0.005 (Figure). The associations remained significant after adjusting for clinical characteristics including disease duration, age, sex, blood pressure, body mass index, physical activity, pack-years of smoking, cholesterol, HT, DM, heart rate, atrial fibrillation, IHD and HF (p < 0.05 for all associations). We observed no significant interactions between the IA diagnosis and inflammation across the significant echocardiographic measures. Conclusion In a large cohort of patients with IA, increasing levels of chronic inflammation determined by outpatient CRP was associated with impaired measures of cardiac structure and function and remained significant after adjusting for clinical characteristics. The prognostic and clinical implication of these findings needs to be explored in future studies.Linear regression splines

Remnant cholesterol, clinical characteristics and mortality in 41.767 patients from LIPIDOGRAM 2004-2015 studies - the factor analysis for mixed data cluster analysis

Abstract Introduction Remnant cholesterol (remnant-C) contributes to residual cardiovascular risk and is produced by metabolism of triglyceride rich proteins. Aim To assess association between clinical characteristics of patients with elevated remnant-C in a large cohort of patients under the care of primary care physicians. Methods The LIPIDOGRAM studies were carried out in the primary care in Poland in 2004, 2006 and 2015. Patients (n=47,398) recruited in all 16 administrative regions in Poland and physicians were proportionally distributed to the number of inhabitants in each administrative region. Each patient was asked to fill the questionnaire on risk factors, chronic diseases, treatment and lifestyle. In the present analysis we included patients with body mass index (BMI )>18.5 kg/m2 aged 18-75 years. We set the cut-off point of fasting remnant cholesterol at >30 mg/dL (>0.77 mmol/L) that differentiated subjects at high risk of cardiovascular events. We carried out Factor Analysis for Mixed Data (FAMD) cluster analysis to discern groups of patients with similar clinical profiles. Results 41,767 patients, for which we had all relevant data, were included in the analysis. Follow-up rate was 97.8%. Three FAMD-derived clinical characteristics patterns accounted for 47.8% of the total variance and were retained for further analysis. The first pattern was associated with higher prevalence of metabolic syndrome (MetS), higher waist circumference, higher levels of non-HDL-C and remnant-C levels. The second pattern was distinguished by lipid parameters, particularly higher HDL-C levels, and was not significantly associated with comorbid conditions. The third pattern was linked to male sex, previous myocardial infarction, smoking, age, lower remnant-C levels, and reduced prevalence of obesity. All patterns were associated with 5-year mortality. The hazard ratio (HR) for mortality per 1 standard deviation (SD) increase in the first pattern score was 1.18 (95% CI: 1.16-1.22, p<0.001). Patients with clinical characteristics corresponding to second pattern had more favorable outcome HR (per 1SD score increase) – 0.75, 95%CI (0.73-0.78, p<0.001). Patients in third cluster, similarly to patients in cluster 1 had increased mortality HR (per 1SD score) – 1.10, (95%CI:1.06-1.15, p <0.001). Higher (>0.77 mmol/l / 30 mg/dl) remnant-C cholesterol significantly contributed to classification of patients into first and third clusters. It was positively associated with first pattern (r=0.64, p<0.001), but negatively with the third pattern (r=0.39, p<0.001). Conclusions Elevated Remnant-C was associated with clinical pattern typical for metabolic syndrome. Interestingly, lower remnant-C levels in patients with comorbidities and more advanced age may not automatically be indicative of a better prognosis – this requires further investigation.Figure 1.Figure 2.

Complete vs culprit-lesion-only myocardial revascularization in patients with out-of-hospital cardiac arrest: insights from the multicentric "Lombardia CARe" registry

Abstract Background Out-of-hospital Cardiac Arrest (OHCA) is a potentially devastating complication of patients with Myocardial Infarction (MI). Multivessel Disease (MVD) is a frequent occurrence in this setting, being present in nearly half patients undergoing Coronary Angiography (CAG). We previously reported that, in case of MI complicated by OHCA and evidence of MVD, a complete myocardial revascularization, as compared to culprit-lesion-only revascularization, was associated with an improved 1-year survival and favorable neurological outcomes. We aimed to validate and confirm these results on a multicentric scale with a larger patient cohort. Methods This is a multicentric, prospective, observational study. We considered all the consecutive patients with OHCA and MI enrolled in the Lombardia CARe Registry from January 1st 2015 to December 31st 2022 who underwent CAG in 6 centers in Northen Italy. Results A total of 623 patients were included; of these, 403 underwent CAG. Median age was 64 years, and about 80% had no previous history of ischemic heart disease. Median ejection fraction (EF) at presentation was 40%. MVD was present in 186 (46.1%) patients and was subsequently treated with either complete (32.3%) or incomplete (67.7%) coronary revascularization. Left anterior descendent (LAD) artery was the culprit lesion in almost 1/3 of patients. The 1-year survival rate was 78.3% in the complete revascularization group and 42.9% in the culprit-lesion-only revascularization group (p-value < 0.001). After correction for factors that were predictors on univariate analysis, complete revascularization strategy was independently associated with a reduced risk of death [HR: 0.27 (95% CI: 0.01 to 0.739; p = 0.01] and death or unfavorable neurological outcome [HR: 0.23 (95% CI: 0.08 to 0.67); p = 0.007]. Conclusions Complete revascularization strategy was confirmed to be associated with an improvement of 1-year survival and with a good neurological outcome in patients resuscitated from OHCA. These results highlight the independent impact on survival of a complete coronary intervention strategy in patients with OHCA plus MVD.

Machine learning methods for diagnostic disease prediction and treatment decisions in parvovirus B19 positive viral cardiomyopathy

Abstract Background Parvovirus B19 (B19V) is the most common type of virus found in endomyocardial biopsies (EMB) from patients with inflammatory heart disease. However, the detection of genomic B19V-DNA appears to have little clinical significance and is often considered an incidental finding. Recent analyses of a large cohort of B19V-positive patients revealed that the detection of RNA transcripts rather than DNA is of clinical importance, as B19V-RNA-positive patients have a significantly worse cardiovascular outcome. Here, we applied machine learning (ML) methods to assess the impact of B19V transcriptional activity on cardiac inflammation and patient clinical outcome. Methods and results A total of 305 patients with a known clinical course and a positive endomyocardial B19V-DNA test were included in this study. Follow-up measurements of the B19V-specific transcripts VP1/2 and NS1 revealed significantly worse clinical courses than in patients without B19V-RNA detection (P=0.019, hazard ratio (95% CI)=1.62 (1.10-2.57)). LVEF at follow-up was significantly lower in patients with detected B19V-RNA (P=0.007), and adverse events such as worsening LV function (P=0.003) or stable systolic dysfunction (P=0.013) were more frequent in this group. Importantly, analysis of inflammatory markers in EMB showed no difference in patients with and without RNA detection (P=0.432), suggesting that the deterioration in clinical outcome was related to B19V transcriptional activity rather than an increase in inflammation. The analysis of area under the receiver operating characteristic curve (AUROC) of B19V-RNA-negative patients revealed that the macrophage marker MAC-1 (AUROC=0.66, P=0.002) was the single most prognostically relevant parameter, while the T cell marker CD3 (AUROC=0.73, P<0.001) was identified as the most prognostically relevant marker in B19V-RNA-positive patients. The linear combination of several inflammatory markers increased the AUROC value to 0.67 in B19V-RNA-negative patients and to 0.74 in B19V-RNA-positive patients. To further increase prognostic accuracy, we trained ML models on features derived from EMB inflammatory markers. For the prediction of major adverse cardiac events within 60 months, the best ML-models achieved an AUROC of 0.87 in B19V-RNA-positive and of 0.86 in B19V-RNA-negative patients, while models that neglect the differentiation of patients with regard to the presence of B19V RNA transcripts only achieved an AUROC of up to 0.76. Conclusions These results show that B19V transcriptional activity is an independent risk marker for adverse cardiac events in patients with viral cardiomyopathy and thus confirm the clinical-therapeutic importance of myocardial biopsy. Furthermore, we present an ML-based algorithm that accurately indicates disease progression in B19V-positive cardiomyopathy patients and is thus helpful for appropriate therapy recommendation.

Premature ventricular contraction burden measured by an insertable cardiac monitor and the incidence of ventricular tachycardia and fibrillation

Abstract Background Insertable cardiac monitors (ICM) have the capability to continuously monitor premature ventricular contraction (PVC) burden over time [1] as well as detect ventricular tachycardia and fibrillation (VT/VF). Objective We investigated the association of PVC burden with incidence of VT/VF in a large real-world cohort of patients implanted with ICMs. Methods Patients implanted with an ICM for various reasons for monitoring and PVC detection turned on were included from the ICM manufacturer's de-identified data warehouse. Patients were included if they had at least 90 days of PVC burden follow-up. Tachycardia episodes that were detected by the ICM were first classified as VT/VF, SVT, or oversensing using an artificial intelligence (AI) model that was pre-trained using over 60,000 manually adjudicated ICM detected tachycardia episodes. If the AI model output probability for VT/VF was greater than 0.2, then those episodes were manually adjudicated for incidence of non-induced spontaneous VT/VF. The PVC burden trends recorded by the device were divided into 4 mutually exclusive patient groups: (1) 0% PVC burden on all days, (2) 1-4% PVC burden on ≥1 day, (3) 5-9% PVC burden on ≥1 day, and (4) >10% PVC on ≥1 day. The incidence rate of spontaneous VT/VF was compared between the PVC burden patient groups using a Generalized Estimating Equations model with negative binomial distribution. Time to first spontaneous VT/VF occurrence after the first day of occurrence of PVC burden for the respective PVC burden groups were estimated using Kaplan-Meier analysis and the groups were compared using the Cox proportional hazards model. Results A total of 5,521 patients were included in the analysis. Patients had an average age of 69±15 years and 49.8% being males. There was a total of 33,393 tachycardia episodes from 2,641 patients that were detected by the ICM. After AI model probability-based adjudications, 691 spontaneous VT/VF episodes were identified from 277 patients. Patients with ≥1 day of PVC burden of 1-4%, 5-9%, and ≥10% were associated with 2.9, 7.3, and 7.8 times increased incidence rate of VT/VF episodes during follow-up period relative to patients with 0% PVC burden on all days of follow-up (Figure A). Kaplan Meier curves for incidence of first spontaneous VT/VF episode for the four groups following occurrence of the first day of qualifying PVC burden for the respective groups are shown in figure B. Patients with a day of PVC burden ≥10% were 3.5 times more likely to develop VT/VF in the future compared to patients with 0% PVC burden on all days. Conclusion Days with high PVC burden, as detected by an ICM with continuous PVC detection capability, were associated with increased risk of VT/VF events in a group of real-world patients implanted with ICMs. PVC burden measured by ICMs may be a risk stratification tool for further investigation to prevent sudden cardiac arrest.

Prevalence of Brugada ECG pattern in psychiatric patients: a longitudinal prospective cohort of 550 patients

Abstract Background Brugada syndrome (BrS) is an inherited disorder with autosomal dominant transmission, which occurs predominantly in males in the third to fourth decade of life with resting syncope, nocturnal agonic breathing, major ventricular arrhythmias and sudden death. Arrhythmic complications can occur spontaneously or following exposure to triggers such as fever, or certain categories of medications, including psychiatric drugs. Aim of the study To evaluate the prevalence of Brugada ECG pattern in psychiatric patients. Methods from January 2023 to Decembre 2023, 550 consecutive patients who were admitted to the psychiatric department of our university hospital were enrolled. For each patient, electrocardiographic and anamnestic data including psychiatric diagnosis, current drug therapy and family history were collected. Results Twenty-one out of five-hundred and fifty patients (3.8%) presented with a Brugada ECG pattern. Mean age was 42±6 years and seventeen out of twenty-one patients (81%) were male. Two patients exhibited a Spontaneous type 1 Brugada ECG pattern meanwhile nineteen patients had a Brugada type 2 or 3 ECG pattern. When compared to the general population, those with Brugada ECG had longer P wave duration (110±7 vs 103±13 msec p<0.01) and longer QRS duration (97±14 vs 89±12 msec p=0.04). Evaluating psychiatric disorders, patients with Brugada ECG had high prevalence of mood disorders (10 out of 21, 47%). Other disorders were schizophrenia (3 out of 21, 14%), cognitive retardation (5 out of 21, 23%), and attention disorder (1 out of 21, 5%). Moreover 4 patients were drug addicted. Only 5 out of 21 (24%) patients had a family history of psychiatric and neurological disorders. Conclusions Brugada ECG pattern has a prevalence of 3.8% in a large cohort of psychiatric patients. Mood disorders was the most common diagnosis in this cohort. Large prospective registries are needed to evaluate the clinical feature and potential clinical implication of this findings.