Years Of Follow-up Research Articles

Revisiting the obesity paradox: lean body mass, fat mass, and mortality in patients with atrial fibrillation

Abstract Background Obesity has been associated with risk of atrial fibrillation (AF), but once AF is established, it seems to be favorable, which is termed the obesity paradox. However, body mass index (BMI), the commonly used anthropometric marker of obesity does not distinguish between fat and lean body mass, and could lead to the potential misclassification of risk categories. Understanding the role of fat and lean mass might provide new insights into the obesity paradox and promote targeted interventions in AF. Purpose To investigate the associations of BMI, lean body mass, and fat mass with all-cause mortality in patients with AF. Methods A total of 8,325 patients (mean age 62.1±6.07 years) with AF at baseline were included in the prospective cohort study using UK biobank data. Body composition data (fat mass and lean body mass) were estimated using an eight-contact electrode Tanita BC418MA segmental body composition analyser. Cox proportional hazards regression models were used to estimate the above associations. Results During a mean of 13.7 years of follow-up, 2,058 deaths were identified. A U-shaped association was observed between BMI and all-cause mortality. Multivariable adjusted Cox models including fat mass and lean body mass revealed U-shaped associations of fat and lean body mass with all-cause mortality. According to the restricted cubic spline models, the risk of all-cause mortality decreased until around 27 kg/m2 of BMI and increased afterward in both sexes. In women, the average fat mass and lean body mass with 27 kg/m2 of BMI were 27 and 42 kg, respectively. For fat mass, the risk of all-cause mortality decreased up to approximately 27 kg with a hazard ratio (HR) of 0.396 (95% confidence interval 0.383-0.410) per standard deviation (SD), and then increased with a HR of 1.323 (1.320-1.326) per SD. A larger reduction in risk was observed within the lower range until 42 kg of lean body mass with a HR per SD of 0.293 (0.275-0.312), which increased gradually thereafter with HR per SD of 1.174 (1.157-1.192). For men, the average fat mass and lean body mass with 27 kg/m2 of BMI were 22 and 60 kg, respectively. The risk of all-cause mortality decreased up to approximately 22 kg of fat mass with a HR of 0.427 (0.412-0.441) per SD, and then increased with a HR of 1.353 (1.348-1.359) per SD. A similar trend of risk reduction was observed until 60 kg of lean body mass [HR (0.443, 0.433-0.454) per SD], which increased gradually thereafter with HR per SD of 1.165 (1.162-1.167). Conclusion Our findings suggest that the associations between between fat and lean body mass, and mortality determined the shape of the association between BMI and mortality. The "obesity paradox" may be largely explained by both fat and lean body mass in AF. Maintaining healthy body composition is of critical importance to improve prognosis in AF. For patients with BMI ≥ 27 kg/m2, more emphasis should be placed on reducing fat mass than lean mass.Associations of BMI, WC, WHtR with deathAssociations of fat/lean mass with death

Long-term follow-up of single-chamber atrial pacing - system upgrade and wenckebach block point behavior: potential implications for leadless AAI pacing?

Abstract Introduction Until recently leadless pacemakers (PM) did not support atrial pacing. A novel dual chamber leadless PM system now provides treatment option for a wide range of indications. Single-chamber atrial stimulation (AAI) for the treatment of symptomatic sick sinus syndrome (SSS) is scarcely used due to concerns about the potential development of atrioventricular block (AVB) and development of paroxysmal atrial fibrillation (AF). Long-term follow-up data of AAI-PM is however scarce. Little is known about the role of serial Wenckebach block point (WBP) measurements in AAI-PM patients for risk stratification. Purpose To assess the incidence of dual chamber upgrade of patients treated with AAI-PM for SSS during long-term follow-up and to investigate the role of serial WBP measurements for risk stratification. Methods Prospectively enrolled patients undergoing implantation of an AAI-PM between October 2002 and December 2023. WBP was measured at implantation and serially during follow up. Results We included a total of 178 patients, of which 58% were female and the median age at implantation was 78 [IQR 71 – 83] years. The median follow-up duration was 6.5 [IQR 2.0 – 9.7] years. 24 patients (13.5%) received a system upgrade to DDD including 3 patients (1.7%) with a mode change to ventricular pacing only (VVI). Adjusted for years of follow-up the upgrade rate was 2.1% per year. Median time to system upgrade was 5.2 [IQR 1.6 – 8.7] years. Reasons for system upgrade were high-degree AVB (38%), low WBP (17%), atrial arrhythmias (33%), unclear syncope (8%) and infection (4%). Median WBP at implantation was 130 [120 – 140] bpm, showing a significant decline over time in the upgrade-group with 105 [95 – 130] bpm compared to the rest of the cohort with 130 [120-130] bpm (p = 0.009). A decline in WBP >20 bpm was found in 17.9% patients and a decline of 10-20 bpm in 33.7% of patients. New-onset atrial arrythmias were found in 36 patients (20%), 29% in the upgrade group and 19% in the rest of the cohort (p = 0.3). Neither age at implantation, sex, WBP at implantation, nor atrial arrhythmia prior to implantation were predictive for the need of a future system upgrade. Conclusion In this cohort of patients undergoing AAI-PM implantation for SSS, a system upgrade was required in 2% per year. The WBP remained stable in 48% of patients. Therefore, AAI-PM due to SSS emerges as a judicious and secure therapeutic modality, warranting increased consideration in the light of new treatment options for leadless pacing.

Real world data on SVT ablation in Denmark Higher risk of need for reablation in todays patient population a Nationwide registry based Danish study

Abstract Introduction Supraventricular tachycardias (SVTs) are a common reason for healthcare contacts and can have significant impact on patient’s quality of life. Today, ablation therapy is considered the treatment of choice for many cardiac tachyarrhythmias, and it is increasingly utilized to treat SVT-patients with chronic symptoms. Ablation therapy for SVTs is considered a safe procedure with high periprocedural success rates. However, recent studies on today’s patient population have shown a tendency towards higher age and more comorbidity, which might affect these success rates. Therefore, there is a need to explore more real-world data on long-term outcomes of catheter ablations in today’s population. Purpose To examine the long-term success rates of ablation therapy by investigating risk of reablation in patients treated for either an accessory pathway (AP), atrioventricular nodal re-entry tachycardia (AVNRT) or ectopic atrial tachycardia (EAT). Methods Using Danish nationwide registries, patients of 18 years or older who underwent RFA for AP, AVNRT or EAT between January 1st 2010 and January 1st 2019 were included. Comorbidities and use of antiarrhythmic drugs were analyzed. The cumulative incidences of reablation for either AP, AVNRT or EAT were estimated at 5-year follow-up. Results Figure 1 shows the baseline characteristics of the study population. A total of 5.905 patients were included in the study, with a median age of 52 [38, 65], and 47% were male. Among them, the AP group comprised 1.575 patients, with a mean age of 42 [29, 55], and 61% were male. The AVNRT group consisted of 3.598 patients, with a mean age of 56 [43, 67], and 42% were male. In the EAT group, there were 732 patients, with a mean age of 57 [42, 67], and 44% were male. The comorbidity burden was generelly higher in EAT patients, who also had the highest use of antiarrhythmic drugs. Figure 2 shows the 5-year cumulative incidence of reablation for AP, AVNRT or EAT-patients. Risk of reablation after 5 years was 12%, 5% and 12% for AP-, AVNRT- and EAT patients respectively. After 1 year the risk was 9%, 3% and 9% for AP-, AVNRT- and EAT patients respectively. Conclusion Despite the generally safe nature of ablation therapy with high periprocedural success rates, our findings highlight a notable risk of reablation, particularly for AP and EAT patients, after 5 years of follow-up.Baseline Characteristics5year cumulative incidence of reablation

Long-term changes in frailty and incident atrial fibrillation: multicenter prospective cohort study

Abstract Background Atrial fibrillation is the most common sustained cardiac arrhythmia and is prevalent among the elderly. Previous findings indicated a higher prevalence of AF in frail adults and frailty prevalent in AF patients. However, the association between dynamic changes of frailty and risk of new-onset AF is unclear. Purpose We aimed to investigate the associations of long-term changes in frailty with incident AF. Its associations with heart failure (HF), coronary heart disease (CHD), and stroke were also evaluated as a secondary aim. Methods Over 50,000 participants from UK Biobank cohort were included, with available frailty index (FI) data and free of AF, HF, CHD or stroke in both baseline and final follow-up assessments. Participants were categorized into nonfrailty, prefrailty and frailty based on their FI scores. Changes of frailty status from baseline to final follow-up assessment included alleviation, maintenance, and aggravation. Thus, transitions of frailty status included 7 categories: nonfrailty maintenance, nonfrailty aggravation (nonfrailty to prefrailty or frailty), prefrailty alleviation (prefrailty to nonfrailty), prefrailty maintenance, prefrailty aggravation (prefrailty to frailty), frailty alleviation (frailty to prefrailty or nonfrailty), and frailty maintenance. FI in baseline and follow-ups are used to calculate the trajectories of frailty (ΔFI). Cox proportional hazard models were used. Results Compared with nonfrailty at baseline, the HRs (95% CI) of AF for prefrailty and frailty were 1.32 (1.29, 1.36) and 1.89 (1.83, 1.96) in the multivariable-adjusted model. During a median of 5.1 years of follow-up from the final assessment, 1729 cases of AF were recorded. Frailty trajectory analysis showed that even a 0.01 point/year increase in ΔFI was associated with 14% (95% CI 1.08-1.20) higher risk of AF, independent of baseline FI and the risk rose to 1.89 (1.45, 2.46) with per 0.05 point/year increase in ΔFI. This association was strengthened in low genetic risk of AF, but sex, age, smoking status, alcohol intake, obesity, hypertension, diabetes and cancer did not materially modify the associations. Moreover, compared with nonfrailty maintenance, sustained frailty had the highest risk of AF (HR 1.95, 1.61-2.36). Alleviation from frailty reduced the risk of AF by 30% (95%CI 0.53-0.94), compared to sustained frailty. These associations were similar in HF and CHD, however, not significant in stroke. Conclusions Middle aged and elderly people, including those with diabetes, obesity and hypertension, may gain substantial benefits in risk of AF, HF and CHD by becoming less frail or maintaining nonfrailty, irrespective of past frailty status and established risk factors, delivering public health implications for the necessity of early identification and timely interventions of frailty in heart health management.

Impact of Phase III cardiac telerehabilitation on cardiorrespiratory fitness, safety and adherence in patients with ischemic heart disease

Abstract Background and Purpose Cardiac rehabilitation program (CRP) is an interdisciplinary intervention aimed to improve exercise tolerance, promote the reintegration of patients with heart disease into their normal lives, and reduce the rate of long-term complications and mortality. Of the three phases, Phase II is responsible for achieving sufficient and safe gains to guarantee adaptation, but it is in Phase III where the long-term beneficial effects and self-management will be achieved. Nevertheless, only 30% - 60% of patients report continuing regular exercise during this stage, adherence rates are heterogeneous, and the diversity of results sustained over time is wide. Therefore, cardiac telerehabilitation (CTR) emerged as an affordable tool to achieve closer and safer surveillance at Phase III. The aim of the study is to evaluate the impact of CTR on exercise tolerance, safety and phase III adherence in patients with ischemic heart disease (IHD) Methods Quasi-experimental study that follows Phase II, in which patients with IHD were assigned to virtual sessions at 1st, 3rd, 6th and 12th months, In each session, they were questioned about adherence to training, exercise tolerance, symptoms, outcomes and control of cardiovascular risk factors (CVRF). The percentage of moderate in relation to vigorous physical activity was also evaluated. After one year they underwent a cardiopulmonary exercise test to analyze comparisons in cardiorespiratory fitness (CRFit) and control of CRF between the end of Phase II and the annual follow-up of Phase III. Results At one year of Phase III follow-up, a significant gain in VO2p and maintenance of the other variables associated with fitness such as oxygen pulse (OP2) and VE/VCO2 slope were evident, with a reduction in weight and diastolic blood pressure. There was a significant gain in CRF measured by VO2p and METs-load in those patients who maintained adherence to CTR Phase III (p=0.0001, see figure), with more improvement in those with attendance>50% (2 or more virtual sessions; p=0.008 and p=0.004 , respectively). A directly proportional correlation was observed between the percentage of attendance and the percentage of vigorous physical activity (p<0.01, Pearson r=0.46, CI 0.16-0.68). A positive and significant correlation was observed between the percentage of attendance at CTR Phase III and the number of METs-load (p<0.05, Pearson r=0.36, CI 0.05-0.61), as well as positive and significant correlation with the amount of VO2p (p<0.01, Pearson r=0.50, CI 0.21-0.70) at the end of Phase III. No cardiovascular adverse events were reported. Conclusion CTR strategy in Phase III is safe, effective and has high adherence rates among patients in our population, achieving control of CVRF, maintaining levels of METs-load and obtaining even greater increases in VO2p at one year of follow-up compared to those obtained at the end of Phase II.

Serum circulating liver enzymes and human diseases

Abstract Background This study aimed to comprehensively investigate the observational and Mendelian randomization (MR) associations between liver enzymes (ALP, ALT, AST and GGT) with a wide spectrum of human diseases. Methods UK Biobank data was used for observational analysis. Cox proportional hazard models were used to quantify the observational associations between liver enzymes and risks of 1109 diseases, adjusted for covariates. A correction was applied to allow for multiple comparisons. Two-sample MR was performed to replicate the identified observational associations. We assessed the strength, consistency and pleiotropy of these MR associations. Results In 438571 participants with a median 12.4 years of follow-up, we found evidence linking liver enzymes and 654 diseases, 254 of which were further assessed in subsequent MR. In MR, 52 associations were replicated (10 for ALP, 14 for ALT, 10 for AST and 18 for GGT). Specifically, ALT was associated with liver conditions, diabetes, abnormal bleeding from the female genital tract, and prostate cancer. AST showed associations with prostate cancer, anxiety, diabetic neuropathy, and stroke. GGT was linked to hepatic and biliary conditions, coronary atherosclerosis, and pneumonia, while ALP displayed positive associations with vitamin D-calcium-parathyroid-bone conditions. Conclusions Elevated liver enzymes are risk factors for a wide range of hepatic and extrahepatic diseases, predominantly digestive, circulatory, metabolic/endocrine (including diabetes) diseases. Furthermore, the four liver enzymes demonstrated distinct patterns of disease associations. Key messages • Elevated liver enzymes are risk factors for a wide range of hepatic and extrahepatic diseases. • The four liver enzymes demonstrated distinct patterns of disease associations.

Prognostic implication of right ventricular - pulmonary arterial coupling in patients with non-valvular atrial fibrillation

Abstract Background The clinical importance of right ventricular (RV) - pulmonary arterial (PA) coupling has been reported in various cardiac diseases such as right heart failure, pulmonary hypertension, and valvular dysfunction. However, there is limited data on patients with non-valvular atrial fibrillation (AF). We aim to investigate whether RV-PA uncoupling affects the clinical outcome in patients with non-valvular AF. Methods A total of 807 consecutive patients with non-valvular AF who underwent echocardiography (mean age 70 ± 12 years, 39% female) were included. We excluded patients with significant (at least moderate degree) valvular diseases, left ventricular ejection fraction (LVEF) <50%, cardiac implantable electronic devices, previous cardiac surgery, and poor echocardiographic image for RV analysis. RV-PA coupling was assessed by the ratio of RV global longitudinal strain (GLS) to PA systolic pressure (PASP), and decreased RV-PA coupling was defined as less than 0.52 %/mmHg based on on the receiver operating characteristic analysis. The primary outcome was the composite of all-cause death and hospitalization for heart failure. Results Over a mean of 4.7 ± 3.5 years of follow-up, 178 (22%) patients had experienced primary outcomes. Among them, 107 (13%) patients were hospitalized for HF and 90 (11%) patients died. Patients with decreased RV-PA coupling were older (73 ± 11 vs. 68 ± 12 years, p<0.001), had a higher prevalence of females (51 vs. 33%, p<0.001) and diabetes (33 vs. 23%, p=0.003), lower left ventricular ejection fraction (60 ± 5 vs. 61 ± 5%, p=0.011), higher E/e’ (14 ± 5 vs. 11 ± 4, p<0.001), larger left atrial volume index (78 ± 37 vs. 62 ± 22 ml/m2, p<0.001) and larger RV end-systolic area (11 ± 4 vs. 10 ± 3 cm2/m2, p=0.001) compared to those with preserved RV-PA coupling. In multivariate Cox regression analysis, decreased RV-PA coupling was associated with worse clinical outcomes even after adjusting for age, diabetes, E/e’, and RV end-systolic area (Hazard ratio [HR] 1.50, 95% Confidence interval [CI] 1.09 – 2.07, p=0.014) (Figure 1). Conclusions In patients with non-valvular AF, RV-PA coupling was associated with clinical outcome, suggesting that it may provide additional information for predicting future cardiovascular risk in this population.

Electrocardiogram-based artificial intelligence to identify prevalent coronary artery disease

Abstract Background Coronary artery disease (CAD) often goes undetected for years before it manifests and results in substantial morbidity and mortality. Some patients have neither typical risk factors nor symptomatic angina despite progressive disease. Purpose Develop a deep-learning model to detect prevalent CAD and identify people at risk for adverse events using electrocardiograms (ECG) in a primary care setting. Methods We developed a convolutional neural network using 12-lead ECG waveforms to discriminate the presence of CAD defined using diagnostic codes ("ECG2CAD"). ECG2CAD was trained on 764,670 ECGs from 137,199 individuals at the Massachusetts General Hospital (MGH). Model performance for discrimination of prevalent CAD was measured using AUROC and AUPRC, and compared against a model comprising age and sex, as well as the Pooled Cohort Equations (PCE), in three test sets independent of model training: MGH, Brigham and Women’s Hospital (BWH) and UK Biobank. ECG2CAD was assessed across subgroups of age, sex and self-reported ethnicity and for incident CAD-related events in the BWH primary care subset. Results ECG2CAD was evaluated in MGH (N=18,706 [N=6,051 cases], age 57±16 years), BWH (N=88,270 [N=27,898 cases], age 57±16 years), and UK Biobank (N=42,147 [N=1,509 cases], age 65±8 years). ECG2CAD consistently discriminated prevalent CAD (MGH: AUROC 0.782, AUPRC 0.639; BWH: AUROC 0.747, AUPRC 0.588; UK Biobank: AUROC 0.760, AUPRC 0.155) and incrementally improved upon both a model based on age and sex (p<0.01) and the PCE (p<0.01) in MGH and BWH. In the BWH primary care subset (N=51,808), model performance was consistent in subgroups defined by age, sex and self-reported ethnicity/race. The incorporation of ECG2CAD in addition to age and sex consistently improved discrimination (AUROC delta of 0.011-0.086) in all subgroups. In the BWH primary care subset with over 10 years of follow-up, we observed that either the presence of ECG2CAD-predicted CAD (HR 2.18, 95% CI 2.00-2.38, P<0.001) and ICD-based known CAD (HR 2.13, 95% CI 1.86-2.45, P<0.001) were associated with increased risk for incident myocardial infarction. The presence of both definitions was associated with an almost five-fold increase in risk (HR 4.97, 95% CI 4.51-5.48, P<0.001). The risk of incident adverse events was highest among people in the top quintile of ECG-based predicted risk (high risk) compared with people from quintile 4-2 (intermediate risk) or the lowest quintile (low risk), even when excluding those with known prevalent CAD at baseline. Conclusions Artificial intelligence-enabled analysis of the 12-lead ECG may facilitate efficient identification of individuals with possible undiagnosed CAD and inform downstream testing and preventive measures.

Meal timing and risk of metabolic syndrome in the prospective French NutriNet-Santé biobank

Abstract Background Circadian rhythm disruption has been associated with higher risks of cardiometabolic diseases and several cancers. Mistimed eating patterns can desynchronize circadian rhythms, and could therefore influence metabolic health. However, long-term associations between meal timing and the metabolic syndrome remain unclear. The aim of this study was to evaluate the prospective associations between meal timing and the risk of developing metabolic syndrome. Methods We used measured biological and clinical data from 16 353 adults (51 years ± 13.72) in the NutriNet-Santé biobank (2011-2014), and examined the associations between meal timing, assessed with repeated 24-hour dietary records during the first two years of follow-up (starting 2009), and the risk of metabolic syndrome, using modified Poisson regression models, adjusted for main confounders. Results At the end of follow-up (mean 2.1 years (SD = 1.2)), a later timing of the first meal of the day was associated with a moderately higher risk of metabolic syndrome (1,788 cases; RR per 1-hour delay = 1.05; 95% CI: 1.00-1.10). However, after adjusting for overall diet quality, this association was attenuated (RR: 1.04; 95% CI: 0.99-1.09). Overall, we found no evidence of an association between the occurrence of metabolic syndrome and the time of the last meal (RR: 0.99; 95% CI: 0.95-1.05), the number of eating occasions (RR: 1.00; 95% CI: 0.98 - 1.03), or night-time fasting duration (RR: 1.03; 95% CI: 0.99 1.07). Conclusions In this large prospective study, timing of the first meal showed modest associations with metabolic syndrome. Further investigations using a longer follow-up are needed to elucidate how meal timing influences metabolic health. Key messages • Beyond the nutritional quality of meals, meal timing, particularly time of first meal, may be an accessible prevention strategy for metabolic health. • More largescale prospective and intervention studies are needed to better understand the links between meal timing and metabolic health.

Baseline shock index-creatinine clearance score and long-term mortality after ACS. Results from 24 years of follow-up of the ABC study on heart disease

Abstract Background Shock Index-Creatinine Clearance score (SI-C) is an updated version of the shock index that includes renal function. Recent studies reported its potential as a novel and simple risk stratification tool for predicting in-hospital mortality in acute coronary syndrome (ACS) patients. Purpose To assess the long-term predictive value of baseline SI-C score in patients after ACS. Methods This preliminary prospective analysis included 589 patients with ACS admitted to three Italian hospitals and discharged alive. Baseline clinical and laboratory data were collected within the first 7 hospitalization days and baseline SI-C score was calculated as [(SI×100)-estimated creatinine clearance]. Patients were prospectively followed for 24 years or until death. Results Virtually all patients completed the follow-up, representing 7066 person-years. Patients' mean age was 66±12 years, 70% were males, and 482(82%) had died during follow-up. Compared to those who survived, deceased patients were significantly different in many of the baseline clinical characteristics. They also showed a significantly higher SI-C values ( -11± 25 vs. -36±23, p<0.0001). The predictive value of SI-C for 24-year mortality was very good (area under the curve= 0.783, 95% CI: 0.738-0.827, p<0.001). The cumulative risk was significantly higher in the upper SI-C tertile (log-rank = 162.1, p < 0.001). Unadjusted Cox regression survival analysis showed that the SI-C score was significantly associated with long-term all-cause mortality (HR: 2.1, 95%CI 1.8-2.3, p<0.0001). Similar results were obtained with the fully adjusted model. Conclusion Baseline SI-C seems to be an effective and independent predictor of long-term all-cause mortality after ACS.

Prognostic value of synthetized right-side precordial leads in arrhythmogenic right ventricular cardiomyopathy: data from nordic, dutch, and canadian ARVC registers

Abstract Background T-wave inversion (TWI) in standard ECG leads is a proven risk marker for life-threatening ventricular arrhythmias (VA) in arrhythmogenic right ventricular cardiomyopathy (ARVC). Right-sided precordial leads (RSPL), which may be more sensitive for detection of the arrhythmogenic substrate, are rarely recorded and understudied in this context. Computerized ECG signal-processing allows synthesis of right-sided precordial ECG leads derived from standard 12-lead ECG. Objective We aimed to assess the value of TWI in RSPL, synthetized from the standard 12-lead ECG, for prediction of VA risk in ARVC patients with subtle ECG phenotypes. Methods Patients with definite ARVC by TFC2010 and no history of sustained VA prior to diagnosis from the Nordic, Canadian and Dutch ARVC registries were included. Patients with major repolarization criterion or complete right bundle branch block (RBBB) were excluded. RSPL (V3R-V6R) were derived from digitally recorded eight linearly independent leads (I, II and precordial V1 to V6) of the standard ECG using a linear ECG transformation matrix. The matrix was previously developed based on a library of body surface potential maps from a mixed group of healthy subjects and patients with cardiac diseases using multivariate linear regression and QRS-T data obtained from averaged beats of the right-sided-precordial leads and the basis leads. TWI exceeding 0.1 mV in any of the synthetized leads was tested for its ability to predict sustained VA, defined as either sustained ventricular tachycardia, appropriate ICD shock, aborted cardiac arrest, or sudden cardiac death. In a similar manner, the value of TWI in any of the inferior leads III, aVF or II was assessed. Hazard ratio was calculated using Cox regression analysis adjusted for age, sex, and proband status. Results In total, 144 patients without prior VA history were identified. After exclusion of patients with major repolarization criterion (n=37) and RBBB (n=11), 96 patients comprised the study group (mean age 40±16, 42% female, 41% probands, 48% ICD carriers). Fifty-nine patients (62%) had TWI in one or more synthetized RSPL and 33 patients (34%) had TWI in any of the inferior leads. During 10 years of follow-up, 11 patients (12%) developed VA. Kaplan-Meier curve analysis showed significant association between the presence of TWI in at least one of the RSPL and the risk of VA, which remained an independent predictor in the adjusted Cox regression analysis (HR 10.6, 95%CI 1.3-84.4, p=0.026). TWI in any of the inferior leads was not associated with the risk of VA in this cohort (HR 1.2 95%CI 0.26-5.42). Conclusions Synthetized right-sided precordial leads appear to contain information potentially useful for refining risk stratification of primary prevention ARVC patients with a subtle ECG phenotype, in whom traditional repolarization markers, such as major repolarization criterion or TWI in inferior leads, are not informative.

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.

Antiplatelet agents in patients with intermediate coronary artery stenosis and deferred revascularization

Abstract Background There is no specific recommendation regarding optimal antiplatelet therapy after deferral of revascularization in patients with established coronary artery disease. Objectives The current study investigated safety and efficacy of antiplatelet therapy in patients with intermediate coronary artery stenosis in whom revascularization was deferred based on fractional flow reserve (FFR). Methods In the Korean National Health Insurance Service database 2013-2020, we identified 4,657 patients who had intermediate coronary artery disease on angiography for which revascularization was deferred based on FFR. During this period, reimbursement criteria of FFR were patients with no previous evidence of myocardial ischemia and intermediate coronary artery stenosis (50-70%) by quantitative coronary angiography. Patients were then classified into two groups according to initiation of antiplatelet therapy after the index procedure. Primary efficacy outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, unplanned revascularization, and stroke, during 5 years of follow-up. Primary safety outcome was any gastrointestinal bleeding. Results After propensity score matching in a 1:1 ratio, there were 1,634 patients in antiplatelet therapy group and 1,634 in no therapy group (total N=3,268). The risk of MACCE was similar between the two groups (24.8% vs. 24.7%; adjusted hazard ratio [aHR], 0.97; 95% confidence interval [CI], 0.84-1.13; P=0.745). However, the risk of any gastrointestinal bleeding was higher in antiplatelet therapy group than no therapy group (2.2% vs. 1.2%; aHR, 2.07, 95% CI, 1.08-4.00). These results were consistently found in subgroup analyses. Conclusions In patients with intermediate coronary artery stenosis with deferred revascularization based on FFR, antiplatelet therapy was not associated with reduced risk of ischemic events but increased risk of gastrointestinal bleeding.

Ankle brachial index,a non invasive tool predicts cardiovascular events after acute myocardial infarction:a 3 year follow -up study

Abstract Background / Introduction The ankle-brachial index (ABI) is a non-invasive tool that was initially used for the diagnosis of lower-extremity peripheral artery disease (PAD). It has been proven that ABI is a marker of atherosclerosis in other vascular sites and can therefore be used to predict cardiovascular events regardless the presence or not of PAD symptoms. Purpose This study aims to examine the prognostic value of ABI in the setting of acute myocardial infarction (MI), as up till now there is not enough relevant evidence. Method We followed up 441 patients [79% male;mean age 62 years;67% hypertnesive; 30% with diabetes mellitus (DM); 52% current smokers] who were hospitalized because of MI for a period of three years. All patients underwent baseline estimation of clinical and laboratory parameters during theri hospitalization.The ABI was measured according to established methodology using a certified automated device and abnormal ABI defined as a value ≤ 0.9. The primary endpoint was a composite of all-cause and cardiovascular death, as well as major cardiovascular events including decompensated heart failure, new acute coronary syndrome, cerebrovascular event, malignant arrhythmia, PAD event and new onset renal dysfunction. All events were assessed both in-hospital and within 3 years of follow-up. Results Our study population had a mean ABI of 1.1 (IQR: 1.00 to 1.18). With the use of reduced multivariate regression models ABI was proven to be a prognostic indicator for the in-hospital composite endpoint. Patients with an abnormal ABI had a threefold risk of in-hospital events [HR 2.93, 95% CI: 1.48-5.81, p=0.002]. After conducting multivariate analysis ABI maintained its predictive power of all-cause mortality [HR 2.88, 95% CI: 1.53 – 5.42, p=0.001], regardless of hypertension DM, LDL levels and smoking status of the study population in 3 years follow-up. Conclusion An impaired ABI is associated with greater risk of in-hospital events in patients with acute MI. Moreover, ABI emerges as an independent predictor of long-term all-cause mortality in those patients.The findings of this study suggest that subclinical and clinical PAD are associated with poor outcomes among patients with acute MI; thus, routine ABI tests enhance risk stratification and might carry important prognostic significance in these patients regardless of PAD symptoms.

A study of intracoronary thrombolytic agents in high thrombotic burden lesions during primary PCI

Abstract Objectives High thrombus burden during Primary PCI begets worst possible outcomes, studies on adjunctive intracoronary thrombolytic agents show heterogeneous1,2 results & have limited long term follow-up. Although early studies support mechanical thrombectomy devices, larger randomized trial show that they are not able to reduce the MACE3, 4. There is no randomised clinical data for sustained mechanical thrombectomy devices till now. Purpose of the study The main purpose of this study is to analyse long term outcomes of low bleeding risk group patients undergoing Primary PCI with high thrombus burden, receiving intracoronary thrombolytic agents as an adjunctive therapy. Methods In this prospective observational single centre study, we analysed one year follow-up data of 108 consecutive primary PCI patients with high thrombus burden (G4, G5) and low bleeding risk, who were stratified into two groups basing on whether they receive intracoronary thrombolytic agent as an adjunctive agent before stent implantation. The primary outcome was NACE (Net Adverse Clinical Events, which include MACE, Death, ST/MI, major bleeding events), secondary outcomes include the individual components of the primary outcomes when analysed separately. Results The primary outcome events occurred in 21 patients (26%) in Primary stent group(PS, n=80), whereas it occurred in 2 patients(6%) in primary intra coronary thrombolysis group(PIT, n=28). Log-Rank (Mantel Cox) NACE curves show that PS group has high events when compared to PIT group(26% Vs 7%, p value – 0.042, Hazard ratio - 2.56; 95% CI - 0.76 – 8.57), there is no statistically significant difference in all other key secondary outcome event curves. Conclusion In patients presenting with STEMI, undergoing primary PCI, with high thrombus burden & low bleeding risk group, those receiving intracoronary thrombolytic agent as the adjunctive therapy before stent implantation, are able to reduce the NACE event rates during the one year of follow-up.Fig1:Log Rank (Mantel Cox) NACE curve

High discontinuation rate of statins among PCSK9i users: a nationwide study from 2015-2023

Abstract Background Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are recommended as additional lipid-lowering drug treatment for high-risk patients if the low-density lipoprotein cholesterol (LDL-C) targets are not achieved with statins and ezetimibe alone. Nationwide data from clinical practice on the use of PCSK9i are lacking. In 2015, PCSK9i became available in Norway with reimbursement restricted to patients with familial hypercholesterolemia (FH) and/or atherosclerotic cardiovascular disease (ASCVD) with LDL-C above certain levels. Purpose To investigate the use and adherence of lipid lowering drugs among a nationwide cohort of PCSK9i users, utlizing complete pharmacy dispensation data. Methods Information on all PCSK9i users ≤80 years with at least one year of follow-up after the first dispensation were extracted from the Norwegian Prescribed Drug Registry. We evaluated adherence to PCSK9i by calculating the proportion of days covered (PDC) during the initial year of PCSK9i therapy. Poor adherence was defined as PDC <80%, and discontinuation was defined as a gap in treatment ≥180 days during the follow-up period. We analyzed treatment patterns of statins and ezetimibe during the 1-year period before and after PCSK9i initiation by determining the proportion of patients with at least one dispensation of statin and/or ezetimibe treatment. Results A total of 2,997 PCSK9i users were identified. Median age at treatment initiation was 62 (IQR: 13) years and 43% were female. Non-adherence to PCSK9i was observed in 16% of the patients, and 18% discontinued treatment (Table). Non-adherence to PCSK9i was more prevalent in females, and in the lowest and highest age quartiles. No significant difference in non-adherence was found among patients with ASCVD compared to patients with FH. In the year preceding PCSK9i initiation, 74% of patients used statins (including combinations with ezetimibe), 11% used ezetimibe monotherapy, and 15% did not use any statin or ezetimibe treatment (Figure). During the year following PCSK9i initiation, 35% used statins (including combinations), 17% used ezetimibe monotherapy, and 48% did not use any statin or ezetimibe treatment. Among patients with ASCVD, 72% used statins prior to PCSK9i initiation, and 22% used statins after. Among patients with FH, 77% used statins prior to PCSK9i initiation, while 51% used statins after. Conclusion In this nationwide study of incident PCSK9i users, we observed a substantial decrease in usage of statins and ezetimibe following PCSK9i initiation. Further, almost 1 in 5 patients discontinued treatment with PCSK9i. There is a large potential for optimizing treatment and adherence to PCSK9i and conventional lipid-lowering drugs among Norwegian patients with ASCVD and familial hypercholesterolemia.Adherence and discontinuation to PCSK9iUse of statin and ezetimibe

Composition of non-HDL cholesterol and residual cardiovascular risk in secondary prevention

Abstract Background Non-high-density lipoprotein cholesterol (non-HDL-C) is associated with atherosclerotic cardiovascular disease (ASCVD) and is a recommended secondary prevention treatment target. However, the composition of non-HDL-C, that is, the relative contribution of remnant cholesterol (remnant-C) and low-density-lipoprotein cholesterol (LDL-C), is not considered for cardiovascular risk prediction. Purpose To examine ASCVD risk by composition of non-HDL-C. Methods Based on the Western Denmark Heart Registry, we established a cohort of patients with ischemic heart disease, including patients with acute coronary syndrome or stable angina pectoris, undergoing coronary angiography for evaluation of coronary artery disease between 2011 and 2020. A complete lipid panel within 1 year after coronary angiography on statin treatment was required. Patients with triglycerides >4.5 mmol/L were excluded. Exposures were remnant-C, LDL-C, non-HDL-C, and composition of non-HDL-C. The latter was defined as remnant-C of non-HDL-C, and LDL-C of non-HDL-C, in percentages. Cox regression analyses obtained adjusted hazard ratios (aHR) for myocardial infarction, ASCVD (myocardial infarction, ischemic stroke, and cardiovascular death), and all-cause death occurring from 1 year after coronary angiography to end of follow-up November 1, 2022. Results The secondary prevention cohort included 42,341 statin-treated patients (67.7% were men; median [IQR] age 66 [58-73] years). During median 4.1 years of follow-up, 3,846 patients developed ASCVD. Per 1 mmol/L increase in remnant-C, LDL-C, and non-HDL-C, the aHR for ASCVD was 1.41 (95% CI 1.28-1.55), 1.12 (95% CI 1.08-1.17), and 1.17 (95% CI 1.13-1.21), respectively (Figure 1). The relative contribution of remnant-C and LDL-C was median (IQR) 24.6% (18.5-33.1) and 75.4% (66.9-81.5) of non-HDL-C, respectively. When remnant-C constituted a larger percentage of non-HDL-C (and LDL-C a lower percentage), the aHR for ASCVD showed a linear increase in risk whereas the opposite trend was observed for LDL-C (Figure 2). Thus, per 10% increase in remnant-C of non-HDL-C, the aHR of ASCVD was 1.06 (95% CI 1.03-1.09) compared to 0.94 (95% CI 0.91-0.97) per 10% increase in LDL-C of non-HDL-C. Results were comparable for myocardial infarction and all-cause death, and by age, sex, and other clinically relevant subgroups. Conclusions The composition of non-HDL-C is strongly associated with ASCVD risk, with the risk escalating as remnant-C constitutes a larger percentage, and LDL-C a smaller percentage, of non-HDL-C. These findings challenge current guidelines and demonstrate the value of considering composition of non-HDL-C in clinical practice for more accurate risk assessment.Figure 1Figure 2

Persistence and predictors for non-persistence to edoxaban therapy in patients with atrial fibrillation: 4-year follow-up data from the ETNA-AF-Europe study

Abstract Background Non-persistence to non-vitamin K antagonist oral anticoagulants (NOACs) is associated with increased stroke risk in atrial fibrillation (AF) patients. To date, most NOAC persistence studies have been retrospective and often did not include patients receiving edoxaban. Identifying predictors for non-persistence may be useful when considering the design of future studies and help develop strategies to reduce non-persistence in clinical practice. Purpose To define and describe patients who did not reach the end of the study period and were non-persistent to edoxaban during the 4-year follow-up of ETNA-AF-Europe. Methods ETNA-AF-Europe was a prospective, observational study conducted in AF patients receiving edoxaban. In this subanalysis, patients not reaching the end of the study period and patients who were non-persistent (defined as permanent discontinuation of edoxaban) after 4 years of treatment were examined, including patients switching to other NOACs and reasons for discontinuation. Baseline predictors for not reaching the end of the study period and baseline predictors for non-persistence with edoxaban treatment during 4 years of follow-up were also examined. Persistent patients may have missed dose/interruption. Results Overall, 13,164 patients were included in the analysis. During the whole study period, 14.3% died. At the end of the study, 27.3% of patients prematurely terminated the study and 71.5% were classified as completing the study. Of patients who left the study (n=3598), 30.2% were lost-to-follow-up, 6.9% withdrew consent, and 5.9% transferred to another institution. Of patients who completed the study (n=9417), 87.4% were classified as persistent within the 4 years. Only 6.2% permanently discontinued edoxaban without switching to another NOAC (Table). Following backwards elimination, baseline characteristics associated with premature study termination (excluding death) were male sex, low body mass index, low renal function, chronic hepatic disease, long standing persistent/permanent AF, smoking, low compliance as judged by investigator, vitamin K antagonist-naïve, and no rate/rhythm control drug at baseline. Characteristics associated with non-persistence were increasing age, male sex, body weight extremes, low renal function, heart failure, vascular disease, chronic hepatic disease, alcohol use, perceived frailty, chronic obstructive pulmonary disease, smoking, current AF symptoms, and ablation (Figure). The criterion for backward elimination was p=0.05. Conclusions Most patients in ETNA-AF-Europe reached the end of the study. Less than a quarter were classified as non-persistent during the 4-year follow-up. The majority of patients who were non-persistent switched to another NOAC with a small number completely stopping anticoagulant therapy. Male sex, low renal function, chronic hepatic disease, and smoking were associated with both treatment discontinuation and non-persistence.Termination and persistence

Left atrial and left ventricular positive and negative remodeling after catheter ablation of atrial fibrillation

Abstract Introduction Atrial fibrillation (AF) is associated with negative remodeling of left atrium (LA) and in later stages of diseases with negative remodeling of left ventricle (LV). Can radiofrequency ablation (RFA) of pulmonary veins cure AF and retain progression of arrhythmia? Purpose This study evaluated positive and negative remodeling of LA and LV after RFA of pulmonary veins and a 7-year follow-up. The patients were divided into 4 groups on the basis of Pulmonary Vein Isolation Outcome Degree (PVIOD 1-4), a new measure for the efficacy of catheter ablation of AF. Methods One hundred seventeen patients with symptomatic drug-refractory paroxysmal and persistent AF were treated with RFA. At baseline and after a 7 years of follow-up, 2-dimensional echocardiography was performed to assess LA diameter, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and left ventricular ejection fraction (LVEF). Results After a 7-year follow-up 32.5% patients with successful single RFA of AF (PVIOD 1) showed significant positive LA and LV remodeling: LA diameter 39.3±0.6 vs 36.5±0.6 mm, p=0.0007; LVEDD 53.1±0.6 vs 50.9±0.7 mm, p=0.008; LVESD 34.7±0.8 vs 32.0±0.1 mm, p=0.005 and LVEF 56.8±0.8 vs 62.1±1.1 %, p=0.000008. In 29.1% of patients with success after multiple procedures (PVIOD 2) occurred significant reverse LA remodeling: LA diameter 41.9±0.7 vs 40.2±0.6 mm, p=0.04. Clinical success (PVIOD 3) after RFA was defined as a significant reduction in the number and duration of AF episodes with or without previously ineffective antiarrhythmic drugs (AAD) class I and III. In 14.5% of subjects with long-term clinical success (PVIOD 3 and baseline LA diameter 43.2±1.0 mm) remodeling of LA and LV was not occurred. In 23.9% of patients with procedural and clinical failure after RFA (PVIOD 4) long-term follow-up showed significant negative remodeling of LA and LV: LA diameter 44.7±0.7 vs 47.4±0.7 mm, p=0.006; LVEDD 52.8±0.9 vs 57.1±0.6 mm, p=0.0006; LVESD 36.5±1.1 vs 40.7±1.2 mm, p=0.006 and LVEF 50.7±1.7 vs 43.8±1.8 %, p=0.004. Conclusions Single successful RFA of pulmonary veins in early stage of AF with normal LA diameter cure arrhythmia, which was proved with LA and LV positive remodeling after a 7-year follow-up. With increase of LA diameter, the success of RFA decrease. The multiple procedures slow the progression of AF, but are less effective because of long periods of time between them. Clinical success and role of AAD therapy are also important in AF management. If AF is not treated with RFA properly on time it becomes progressive disease.

Real-life impact of complete revascularization of non-ST elevation myocardial infarction during index hospitalization

Abstract Introduction patients with non-ST elevation acute myocardial infarction (NSTEMI) frequently present multivessel disease (MVD) with significant stenosis in non-infarct-related arteries (non-IRA). Unlike for ST elevation acute myocardial infarction, there is a paucity of studies evaluating the prognostic impact of complete revascularization in these patients. In fact, recommendation for complete revascularization is based in observational and non-randomized studies suggesting a possible benefit regarding mortality and major cardiovascular events. Purpose to evaluate the prognostic impact of complete revascularization during the index hospitalization in the Portuguese patients with NSTEMI and MVD. Methods patients hospitalized for NSTEMI with MVD included in a national multicentre retrospective study between October 2010 and December 2022 were divided into two groups: group 1 was submitted to complete percutaneous revascularization during the index hospitalization (IRA and non-IRA with diameter stenosis ≥50% on angiography), and group 2 performed IRA-only revascularization. The impact of complete revascularization on the probability of cardiovascular re-hospitalization, as well as on in-hospital and one-year mortality rates was evaluated. Results a total of 3084 patients was included, 74.8% were males, with a mean age of 67.8±11.9 years. Most patients were submitted to IRA-only revascularization (72.9%). From the remaining, 81.4% performed complete revascularization during the index procedure and 18.6% staged during index hospitalization. Group 1 patients were younger (65.5±11.8 vs. 68.6±11.8 years, p<0.001), with fewer comorbidities and slightly higher left ventricular ejection fraction (55±11 vs. 51±11%, p<0.001). On the other hand, group 2 patients revealed a significantly higher percentage of previous, revascularization (14.8% vs. 1.6%), mostly surgical. Besides overall similar incidence of in-hospital complications, including recurrence of acute myocardial infarction, patients submitted to complete revascularization showed a non-significant trend to an inferior in-hospital mortality rate (0.7 vs. 1.6%, p=0.06). Also, 1-year mortality rate was similar between groups (4.2 vs. 5.0%, p=0.54). However, complete revascularization appeared to result in a long-term prognostic benefit, halving the incidence of unplanned cardiovascular re-hospitalizations at one year of follow-up (9.3 vs. 18.8%, p<0.001). Conclusion complete revascularization led to an overall long-term benefit, mainly due to a reduction in cardiovascular re-hospitalizations, without a significant impact on 1-year mortality rate.