Years Of Follow-up Research Articles

Leadless pacemaker - lead parameters stability and battery longevity in the mid-term follow-up

Abstract Background A leadless pacemaker (L-PM) has been designed to avoid the need for a pacemaker pocket and transvenous lead. Long-term safety will largely depend on the need for replacements, mainly due to battery depletion (end-of-life). While the mean L-PM battery longevity predicted by the manufacturer is 12 years, real-world longevity data are still scarce. We aimed to describe L-PM parameters’ stability and battery longevity during the mid-term follow-up. Methods Single-center registry of consecutive patients undergoing L-PM implantation from May 2015 to November 2023. Procedural characteristics, lead parameters and battery longevity were collected immediately after implantation and during the most recent follow-up visit. Results Overall, 261 consecutive patients had a transcatheter L-PM implanted through a femoral vein (mean age 78±10 years; 66% male). Mean procedural duration was 44±28min and fluoroscopy time was 4,4±3,9min. The device was successfully implanted in all but one patient. The main indications for permanent pacing were high-degree atrioventricular block [N=130 (50%)], atrial fibrillation with pauses [N=78 (30%)], and sinus node disease [N=28 (11%)]. Immediately after implantation, three cases (1,2%) of pericardial effusion (one with tamponade) were reported. In one case (0,4%), a conventional pacemaker was implanted due to L-PM acute dysfunction. No other procedure-related complications, including dislodgment, were reported at discharge. After a mean follow-up of 2,8±1,7years, the pacing threshold and R-wave amplitude remained stable [0,67mV vs. 0,62mV (p=0,9); and 10,3mV vs. 16,1mV (p<0,001), respectively] and mean ventricular pacing was 54±38%. Expected battery longevity was >8 years (maximum value) in 84% of the patients. In the subgroup of patients with >5 years of follow-up (N=20; mean follow up of 6,3±1,8years), the expected battery longevity was >8 years in 85% (N=17) of the patients. In three cases, the L-PM was upgraded to cardiac resynchronization therapy or left bundle branch area pacing due to pacing-induced left ventricular dysfunction. There was one case of L-PM end-of-life 6 years after implant (pacing threshold 0,5mV; ventricular pacing 100%), in which a second L-PM was successfully implanted. Overall, 78 (31%) patients died, a mean of 2,2±1,9 years after L-PM implantation, none related to the device. Conclusion In this real-world cohort, L-PM maintained stable pacing parameters and, in the mid-term follow-up, only one battery depletion was observed while expected longevity remained above 8 years in the large majority of patients. Longer follow up will allow better understanding of both technical and clinical aspects relevant to manage end-of-life devices.Table 1Figure 1

Is there an association of anthracyclines with HFrEF and/or HFpEF in patients treated for breast cancer or lymphoma after 30 years of follow-up? Insights from the Rochester epidemiology project

Abstract Introduction Anthracyclines (ACs) have been identified as cardiotoxic drugs. They are associated with contractile dysfunction of the heart, which can manifest as heart failure. However, differentiating between HFrEF (left ventricular ejection fractions [LVEF] ≤40%) or HFpEF (LVEF >40%) has been overlooked. Purpose Using a retrospective cohort of patients with breast cancer (BC), Hodgkin (HL) or non-Hodgkin lymphoma (NHL) and controls from the Rochester Epidemiology Project, we evaluated the association of ACs use with risk of HFrEF and/or HFpEF. Methods 797 subjects with BC, HL or NHL diagnosed from 1988 to 2010 were identified, 658 treated with ACs (ACs group) and 139 not treated with ACs (no-ACs group). Controls (n=1526) were subjects without cancer. The median (Q1, Q3) follow up was 11.5 years (7.4, 16.7). Cox proportional hazards regression was used to compare the risk of HFpEF and HFrEF in the three cohorts, adjustment for sex, CV comorbidities (type 2 diabetes [T2D], hypertension [HTN] and dyslipidemia), radiotherapy (RT), and ACs cumulative dose was performed. Results Baseline characteristics are shown in table 1. HFpEF occurred in 29/1526 subjects in the control group, 3/139 in the no-ACs group and in 14/658 in the ACs group. Compared to the control group, there was not an increased risk of developing HFpEF in the no-ACs group (HR 1.67, CI 95%: 0.5 – 5.53, p = 0.39) or in the ACs group (HR 1.83, CI 95%: 0.95 – 3.52, p = 0.06) (Figure 1). Compared with no-ACs group, the ACs group had a similar risk of developing HFpEF (HR 1.09, CI 95%: 0.3 – 3.87, p = 0.88). RT was associated with a lower risk of HFpEF (HR 0.21, CI 95%: 0.06 – 0.75, p = 0.01). In the multivariable analysis, T2D (HR 6.91, CI 95%: 3.07-15.56, p = <0.0001) was associated with higher risk of HFpEF. A cumulative dose of ACs > 250 mg/m2 was not associated with increased risk of HFpEF. HFrEF occurred in 25/1526 subjects in the control group, in 4/139 in the no-ACs group and in 31/658 in the ACs group. Compared to the control group, the ACs group had a significant increase in the risk of HFrEF (HR 4.77, CI 95%: 2.76 – 8.22, p < 0.0001), the no-ACs group did not (HR 2.81, CI 95%: 0.97 – 8.12, p = 0.055) (figure 2). RT was associated with lower risk of HFrEF (HR 0.29, CI 95%: 0.13 – 0.65, p = 0.002). In the multivariable analysis, ACs (HR 4.23, CI 95%: 2.4-7.47, p = < 0.0001) being male (HR 2.45, CI 95%: 1.43 – 4.15, p < 0.0001), smoking history (HR 2, CI 95%: 1.16 – 3.44, p < 0.01), and HTN (HR 3.23, CI 95%: 1.9 – 5.61, p < 0.0001), were associated with higher risk of HFrEF. A cumulative dose of ACs > 250 mg/m2 was not associated with increased risk of HFrEF. Conclusion To our knowledge this is the first study to differentiate between HFpEF and HFrEF in this cohort. ACs were not associated with increased risk of HFpEF. However, ACs were associated with increased risk of HFrEF, but not with a specific dose. These results should be validated in other population cohorts.

The incidence of death and risk factors for mortality following major bleeding in patients anticoagulated with factor Xa inhibitors: an observational study in the UK clinical setting (AXIOM UK)

Abstract Background Major bleeding (MB) in association with anticoagulant use results in significant mortality. Mortality can be directly attributed to bleeding, or may follow bleeding complications such acute kidney injury, myocardial infarction, stroke and other cardiovascular events. Most real-world data relating to bleeding mortality is derived from cohorts receiving vitamin-K antagonists. We investigated all-cause mortality (ACM) after MB in a large cohort anticoagulated with Factor Xa inhibitors (FXai), e.g. direct oral anticoagulants (DOAC) rivaroxaban, apixaban and low-molecular-weight heparins (LMWH). Purpose To describe incidence rates of and risk factors for ACM following MB in patients receiving FXai. To investigate MB related ACM by bleeding site, treatment indication, treatment subgroups and individual and cumulative time periods. Methods Retrospective cohort analysis of new users of FXai, between 2012-2020, for therapeutic indications including atrial fibrillation (AF), venous thromboembolism, bioprosthetic cardiac valves or adult congenital heart disease was conducted. MB was defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria. Incidence rates were reported per 100 person-years. Sub-distribution hazard ratios with 95% confidence intervals (95% CI) were estimated from Fine and Gray regression models accounting for competing risks. Results In 240,357 new users of FXai, 88% used an oral FXai. The most common FXai indication was AF (72%). There were 10,163 patients (4.2%) hospitalised for bleeding events during FXai use. Of these, 3,873 MB events (38%) fulfilled the ISTH definition of MB and 1312 died during 3,542 person years of follow-up (Table 1). ACM incidence rates varied by time, indication, bleeding subtype, and drug type. ACM occurred in 926 patients (23.9%) in the first month. Mortality rates were highest in the first month 607 (95% CI 568-647) per 100 person years, the rates then decreased over the year but remained elevated throughout the first year compared with subsequent years. Those receiving LMWH had higher ACM than those receiving a DOAC, but this was not significant in the adjusted risk factor analysis. Risk factors for ACM following bleeding included age ≥80, and a history of current smoking, myocardial infarction, congestive heart failure, peripheral artery disease, Stage 4 or 5 kidney disease, metastatic cancer, and intracranial haemorrhage. Age<60, bleeding following major trauma, and a history of anaemia were associated with lower risk of ACM (Table 2). Conclusions There is a significant incidence of ACM following MB among FXai users. The incidence rate of ACM in patients treated with FXai was highest in the first month after FXai initiation, declined during the first year and then plateaued. Multiple risk factors associated with ACM have been recognised and these could guide urgent therapies such as antidotes.

The triglyceride-glucose index is a marker of thromboembolic events in atrial fibrillation patient under oral anticoagulation therapy

Abstract Background Atrial fibrillation (AF) increases the risk of stroke and thromboembolism; and appropriate risk stratification is central for better targeted patient management. The triglyceride-glucose (TyG) index indirectly assesses insulin resistance, and has been associated with cardiovascular risk. Purpose To investigate whether the TyG index could be a biomarker for assessing the risk of thromboembolic events in patients with AF. Methods We performed an observational prospective cohort study including outpatients diagnosed with AF starting vitamin K antagonist (VKA) or direct-acting oral anticoagulants (DOAC) therapy from January, 2016 to November, 2021. The primary endpoint was a combination of thromboembolic events, considered as the composite of myocardial infarction, and/or venous thromboembolism, and/or ischemic stroke/transient ischemic attack, over 2 years of follow-up. The TyG index was calculated as the natural logarithm (Ln) of the product of baseline plasma glucose and triglyceride using the following formula: Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. Patients were stratified into tertiles according to their TyG index (ie. first tertile: TyG index <4.59; second tertile: TyG index 4.59-4.83; third tertile: TyG index >4.83). Results We included 2907 patients (median age 77 [70-83] years; 52.5% female). The median TyG index was 4.71 (4.53-4.91), and 34% (989) where in the third tertile of TyG index. During a follow-up of 2 years, 209 (7.2%) patients suffered a thromboembolic event. Compared to patients in the first or second tertiles of TyG index, patients in the third tertile had an increased annual event rate of thromboembolic events (3.40 per 100 patient-years vs. 4.76 per 100 patient-years, p=0.043; and 3.41 per 100 patient-years vs. 4.76 per 100 patient-years, p=0.044), and higher incidence rate ratio (1.41 [95% CI 1.01-1.98], p=0.044 vs. first tertile; 1.40 [95% CI 1.01-1.97], p=0.044 vs. second tertile). Cox regression analyses adjusted for several risk factors demonstrated that the TyG index was an independent predictor for thromboembolic events (aHR 1.82; 95% CI 1.15-2.89; p=0.011). Patients in the third tertile of TyG index presented a 64% higher risk of thromboembolic events (aHR 1.64; 95% CI 1.17-2.29; p=0.004) (Table), with significantly lower event free survival (log-rank test p-value = 0.016) (Figure). Conclusions In this real-world cohort of AF patients under oral anticoagulation therapy, elevated TyG index was an independent risk factor for thromboembolic events. The TyG index is a simple, low-cost indicator, that could be used as a screening tool in everyday clinical practice.

Prevalence and outcomes of American Heart Association stages of heart failure in an adult brazilian population of the ELSA-Brasil study

Abstract Aims Heart failure (HF) has a major impact on public health, affecting up to 2% of adult population. HF staging is helpful in capturing pre-clinical disease and its progression to advanced stages. We aimed to determine the prevalence and mortality of HF stages in the participants of a Brazilian adult cohort. Methods The ELSA-Brasil cohort comprises 15,105 adult public servants from 6 Brazilian capitals. In the initial evaluation of the study (2008-2010), ELSA carried out interviews and clinical, laboratory, and cardiovascular ancillary tests. In this analysis, we included participants who had electrocardiogram and echocardiogram performed at baseline visit, and additional information regarding risk factors and functional capacity. The HF stages were defined based on AHA guidelines criteria as follow: Stage 0 was defined as a healthy individual with no risk factors for heart failure. Stage A (at risk for HF) included those without cardiac structural or functional abnormality but with any of the following conditions: systemic hypertension; diabetes mellitus, obesity, history of myocardial revascularization, history of rheumatic fever, and seropositivity for Chagas’ disease. Stage B (pre-HF) was defined as asymptomatic participants with history of myocardial infarction or any major abnormalities on ECG or echocardiogram. Stage C (symptomatic HF) included participants with a clinical history of HF, or HF symptoms in the presence of structural heart disease (defined as in Pre-HF stage). Considering the community-dwelling profile of the sample, we did not expect to have advanced heart failure patients in our sample. Results We included the 3,267 participants (61±9 years; 53% women) with baseline data. Prevalences of HF stages were stage 0: 938 (29%) A: 1,385 (42%), B: 651 (28%) and C: 293 (9%), with different distribution between sexes (p<0.001). Older participants had higher prevalences of stages B and C (p<0.001), with the prevalence of stage C increasing from 1.8% at 35-44 years to 12.2% at 65-74 years. After 12 years of follow-up, total mortality rates of HF stages were Stage 0: 4%; A:10%. B: 16%, and C: 26%, and respective Cox proportional hazard ratios [95% CI] adjusted for age and sex were A: 1.94 [1.3-2.8], B:2.78 [1.9-4.1], and C: 5.39 [3.6-8.1] compared to stage 0. Conclusions The prevalence of HF in Brazilians reflects what is described in international literature, with a large proportion of individuals in pre-symptomatic stages. A notable shift in the sample toward pre-symptomatic and symptomatic HF occurred gradually and persistently across the age span studied. Mortality rates increase incrementally across the HF stages. This information is important for understanding and planning health policies for this syndrome.

Rates of therapeutic interventions in a large real-world cohort with insertable cardiac monitors

Abstract Background Insertable cardiac monitors (ICMs) provide up to several years of continuous monitoring and have demonstrated high diagnostic yields for arrhythmia detection. However, the rates of arrhythmia-related therapeutic interventions following ICM implant have not been comprehensively characterized across indicated patient populations. Purpose To quantify rates of arrhythmia therapies in a large, real-world U.S. cohort of ICM patients. Methods De-identified patients receiving a Reveal LINQ ICM between Oct 1, 2016 – Sept 30, 2020 with no prior cardiac implantable electronic devices (CIEDs) and ≥1 year of follow-up in the Optum Clinformatics® Data Mart claims database were identified (N=17,037). Patients were stratified by indication for ICM placement: N=431 (2.5%) of patients were indicated for AF ablation monitoring, 2,193 (12.9%) for AF management, N=4,852 (28.5%) Cryptogenic stroke, N=1,252 (7.3%) Palpitations, 1,346 (7.9%) Suspected AF, 6,716 (39.4%) Unexplained syncope, and 247 (1.4%) Ventricular tachycardia (VT). Each patient was followed in the claims database after ICM insertion until end of continuous claims enrollment, end of database, or death. Therapeutic interventions for arrhythmias were characterized during follow-up, including procedures (CIED implants, cardioversion, and ablation) and arrhythmia medication initiation (antiarrhythmics, rate-control medications, and oral anticoagulants). Results Mean(SD) follow-up in the claims database post ICM placement was 3.4(1.3) years; 52.4% of patients were female, and mean age was 70.8(11.9) years. Overall, 54.5% of patients received a therapeutic intervention during follow-up, with 25.0% of patients receiving a therapeutic procedure and 44.0% initiating an arrhythmia-related medication (table). The highest procedure rates included implantable pulse generator (IPG) implants in the Unexplained syncope population (21.4% of patients) and cardiac ablations in the populations receiving ICM for known AF (27.8% of AF ablation monitoring patients and 23.5% of AF management patients). Medication initiation rates were highest for oral anticoagulants in the Cryptogenic stroke population (31.0% of patients). The mean time from ICM insertion to therapeutic action was 13(13) months for procedures and 7(11) months for medication initiation. Conclusions In a large sample of real-world ICM patients, more than half received a therapeutic intervention after ICM placement. Time to intervention was lengthy and showed substantial variability amongst patients, underscoring the importance of long-term continuous monitoring to uncover clinically-relevant arrhythmia findings.

Edoxaban for stroke prevention in routine practice patients with atrial fibrillation with and without atherosclerotic disease: a post-hoc sub-study of ETNA-AF-Europe

Abstract Background Patients with atrial fibrillation (AF) and concomitant coronary and peripheral artery disease (CAD and/or PAD) have an increased risk of adverse health events compared to those without such atherosclerotic disease. The annual risks of major adverse cardiovascular outcomes for these patients treated with edoxaban in routine clinical practice remain uncertain. Purpose To determine the clinical characteristics and rates of key adverse events over multiple years of follow-up in patients with and without atherosclerotic disease (defined as CAD and/or PAD). Methods This is a post-hoc sub-study of ETNA-AF-Europe, a multinational, prospective cohort study on unselected patients with AF treated with edoxaban. In total, 13,164 (97%) of the 13,632 patients who provided informed consent were included in this substudy. The included patients were followed for a total of 48 months. Data were collected at baseline and yearly thereafter (±2 months). The present analysis compared baseline clinical characteristics (n [%] or mean [SD]) and clinical outcomes (events per 100 patient-years [%/year] with 95% confidence intervals [95% CI]) by CAD/PAD status at baseline. Results Of the 13,164 patients included in the analysis, 2973 had CAD and/or PAD (n=2762 CAD only). Patients with atherosclerotic disease were older (75.3 years vs 73.2 years), had higher CHA2DS2-VASc scores (3.8 vs 3.0) and HAS-BLED scores (2.8 vs 2.4), and more frequently received the reduced dose of 30 mg edoxaban than those without CAD/PAD (30.2% vs 21.0%) (Table). Cardiovascular comorbidities were in general more prevalent in those with atherosclerotic disease vs those without. Rates of stroke or systemic embolism (0.89%/year, 95%-CI 0.72–1.09 vs 0.59%/year, 95%-CI 0.52–0.68), myocardial infarction (0.73%/year, 95%-CI 0.58–0.92 vs 0.25%/year, 95%-CI 0.20–0.30), and cardiovascular (1.56%/year, 95%-CI 1.33–1.83 vs 0.85%/year, 95%-CI 0.76–0.95) as well as all-cause death (5.96%/year, 95%-CI 5.50–6.46 vs 3.56%/year, 95%-CI 3.37–3.77) were higher for patients with CAD/PAD vs those without such atherosclerotic disease (Figure). Conclusion Annual rates of thromboembolic and bleeding events were low for AF patients treated with edoxaban in routine practice. The higher rates of thrombotic and bleeding events in patients with CAD/PAD are most likely caused by differences in baseline intrinsic risks. Nonetheless, these differences, particularly the threefold higher rate of myocardial infarction, warrants further investigation.Baseline Characteristics

Quality of life in patients with heart failure and improved ejection fraction: one-year follow-up with ARNI and SGLT2i

Abstract Introduction A baseline Heart Failure (HF) with reduced Ejection fraction (HFrEF) <=40% that improved for >=10 points and a second measured left ventricle ejection fraction (LVEF) >40%, can be considered as HF with improved ejection fraction (HFimpEF). The novel therapy for HFrEF and HFimpEF are sacubitril/valsartan (ARNI- angiotensin receptor/neprilysin inhibitor) and Sodium-glucose cotransporter-2 inhibitors (SGLT2i). Purpose Our study aimed to evaluate ARNI and SGLT2i therapy on the health status of HFrEF patients, as well as the prognostic impact of HFimpEF in terms of quality of life and outcomes (mortality and rehospitalization due to HF) during a one-year follow-up. Methods In this prospective study, we included 376 hospitalized HFrEF patients, in whom ARNI and SGLT2i were initiated into regular therapy. A 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) was performed at discharge and after one year. The primary prognostic endpoints were all-cause mortality and HF rehospitalization. Results Initially, about two-thirds of the study population were men (71%), mean age of 61.0±11.5 years, mean LVEF 27.5±5.2 % and mean KCCQ overall summary (KCCQ-OS) score of 48.5±12.5, while quality of life KCCQ-QoL 37.4±10.2. After one year LVEF was increased by 35.6±7.1 %. The total number of 143 patients (38%) met the criteria for HFimpEF, with the improvement of mean LVEF (45.2±8.6 %., p<0.001). Overall, HFimpEF patients experienced an average 5.3 ± 18.6-point improvement in the KCCQ-OS compared with 2.5 ± 17.4 points for non-HFimpEF group (differences in mean changes of 2.9 [95% CI: 1.4 to 4.7). This is largely due to improvements in the domain of KCCQ-QoL (5.8 ± 29.7 points vs. 2.9 ± 22.2 points, respectively). During one year of follow-up, combined SGLT2i + ARNI therapy was represented statistically significantly more in HFimpEF compared to the non-HFimpEF group (86% vs. 34%, p<0.0005), where 45% took only one medicine and 21% none. The HFimpEF group had a significantly better outcome in terms of all-cause mortality (2.8% vs. 18.9%, p<0.005) and HF rehospitalization (3.5% vs. 40%, p<0.0001). The one-year KCCQ-12 was independently associated with outcomes; the hazard ratio for the integrated endpoints (mortality and HF rehospitalization) was 1.08 (95% CI: 1.05–1.11, p = 0.005). Conclusions In routine clinical practice, initiation of the ARNI and SGLT2i therapy was associated with significant improvements in the health status of HFrEF patients, but also change to HFimpEF. The one-year quality of life in patients with heart failure and improved ejection fraction was superior to baseline and compared to the non-HFimpEF group. HFimpEF was associated with a better outcome. All HF patients should undergo KCCQ-12 because it is an independent predictor of outcome.

Incidence and risk factors for development of left ventricular hypertrophy in Fabry disease

Abstract Background Left ventricular hypertrophy (LVH) is the principal cardiac manifestation of Fabry disease (FD). This study aimed to determine the incidence and predictors of LVH development in a contemporary cohort of patients with FD and no LVH at baseline evaluation. Methods Consecutively referred adult (age ≥16 years) patients with FD were enrolled into an observational cohort study. Patients were prospectively followed in a specialist cardiomyopathy centre and the primary endpoint was the first detection of LVH (left ventricular mass index (LVMi) ≥115 g/m2 in men and ≥95 g/m2 in women). Results From a cohort of 393 patients, 214 (age 35.8 ±13.8 years; 61 [29%] males) had no LVH at first evaluation. During a median follow-up of 9.4 years (interquartile range [IQR] 4.7-12.7), 55 patients (24.6%) developed LVH. The estimated incidence of LVH was 11.3% (95% confidence interval [CI] 6.5-16.1) at 5 years, 29.1% (95%CI 21.5-36.7) at 10 years, and 45.0% (95%CI 33.8-62.4) at 15 years of follow-up. On multivariable analysis, independent predictors for LVH development were age (hazard ratio [HR] 1.04 [95%CI 1.02-1.06] per 1 year increase, p-value <0.001), male sex (HR 2.90 [95%CI 1.66-5.09], p-value <0.001), and an abnormal ECG (HR 3.10 [95%CI 1.72-5.57], p-value <0.001). The annual rate of change in LVMi was +2.77 (IQR 1.45-4.62) g/m2/year in males and +1.38 (IQR 0.09-2.85) g/m2/year in females (p-value <0.001). Conclusions Approximately one quarter of FD patients developed LVH during follow-up. Age, male sex, and ECG abnormalities were associated with a higher risk of developing LVH in patients with FD.Central Illustration

Mean body mass index during 20 years of follow-up and cardiovascular disease incidence: results from the ATTICA cohort study (2002-2022)

Abstract Background/Introduction The Global Burden of Disease study has estimated that the burden of increased body mass index (BMI) (i.e., approximately >2.000.000 deaths and >70.000.000 disability-adjusted life years) was predominantly dominated by cardiovascular disease (CVD) during 1990–2017. However, the lifelong body weight (BW) status and its relation to CVD risk remains poorly elucidated. Purpose The purpose of this study was to evaluate the relationship between mean BMI during a 20-year period and CVD incidence. Methods Participants initially free-of-CVD from the ATTICA cohort study were used (n=1,348). At baseline and the 10- and 20-year follow-up, CVD events were assessed, according to WHO-ICD-10. Based on three measurements of weight and height, BMI for each measurement was calculated, and, afterwards, the mean BMI during the whole 20-year period was computed. Results During the whole 20-year period, 41% (n=552) of participants consistently had a normal BW, 48% (n=651) had overweight and 11% (n=145) had obesity. The 20-year CVD incidence was: 8.0% (n=44), 14.9% (n=97) and 19.3% (n=28) in those who consistently had a normal BW, overweight and obesity, respectively (p-value<0.001). In multi-adjusted Cox proportional hazards models, adjusted for age, sex, clinical and lifestyle characteristics, compared to participants who consistently had a normal BW, those who had overweight as well as those who had obesity had almost 2 times higher risk to develop CVD during the 20-year period [Hazard Ratio-HR: 1.73, 95%Confidence Interval-CI: 1.13-2.66 and HR: 2.04, 95%CI: 1.11-3.76, for participants with overweight and obesity, respectively]. Conclusion The study findings highlight that, despite the observations of the J-shaped relationship between BMI and all-cause mortality observed in some studies, both overweight and obesity can be significant risk factors for CVD, when lifelong BW status is assessed. Therefore, currently, new lifelong measures are needed to prevent and manage the pervasive overweight and obesity.

Prevalence and incidence of heart failure in patients with type 2 diabetes mellitus. Results of the prospective DIABET-IC study

Abstract Introduction Heart failure (HF) is one of the major health problems in our environment today. Type 2 diabetes mellitus (DM2) is an important cardiovascular risk factor and can increase the burden of HF through various mechanisms. The incidence of HF in DM2 has not been well studied. Purpose The aim of our study was to evaluate the prevalence and incidence of HF in patients with DM2 followed in hospital cardiology and endocrinology departments. Methods The DIABET-IC study is a longitudinal cohort, prospective, multicenter follow-up study that included 1,249 consecutive patients with DM2 in 2018-2019 in 30 Spanish centers in cardiology and endocrinology outpatient clinics. HF was diagnosed according to the clinical records and following the criteria of the European Society of Cardiology. The prevalence of HF at the inclusion visit was analyzed, as well as the incidence of HF (new diagnoses) during a 3-year follow-up. Results Mean age was 67.3±+9.9 years, with 31.7% of the patients being women. Cardiology clinics included 61.9% of patients and endocrinology clinics the remaining 38.1%. There was a previous history of coronary artery disease in 38.6%, hypertensive heart disease in 21% and atrial fibrillation in 31.9%. Cardiovascular and antidiabetic drugs prescribed at the baseline and 3-year visits are shown in figure 1. Figure 2 summarizes the results of the study. The prevalence of HF at the baseline visit was 39.2%, 490 cases (with reduced LVEF 17.3%, mildly reduced 8.1% and preserved 13.8%). After a follow-up of 1,935/100 persons-year of cases without baseline HF, 58 incident cases of HF were diagnosed, 7.6% (32 in the first year, 13 in the second and 13 in the third year of follow-up). The incidence rate was 3.01/100 person-years (95%CI: 2.30-3.92). Of these 58 cases, 23.7% were with reduced LVEF, 28.9% with slightly reduced LVEF and 47.4% preserved. The incidence was higher in patients followed by endocrinology (3.90 vs 2.90/100 persons-year; p=0.042). At the end of the 3-year follow-up, including baseline prevalence, 46.8% of all patients had HF. Conclusions The prevalence and incidence of HF in patients with DM2 are very high. The incidence of HF is around 3% per year, which is almost 8 times higher than the rate found in large studies in the general population. Approximately half of the new cases were HF with preserved LVEF, and the other half with LVEF < 50%. The use of new antidiabetic drugs, such as iSGLT2, which have been shown to reduce the incidence of HF, should be encouraged.

Outcomes of percutaneous coronary interventions after transcatheter aortic valve replacement

Abstract Background The number of percutaneous coronary interventions (PCI) after transcatheter aortic valve replacement (TAVR) is expected to increase with the extension of this treatment toward younger and lower-risk patients. However, little is known about the prognosis of this evolving subset of patients. Purpose This study aims to assess the clinical outcomes of patients undergoing PCI after TAVR. Methods Patients undergoing PCI after TAVR were retrospectively included from 20 centers across 7 European Countries from July 2008 to November 2023. The patients and procedural characteristics at the time of PCI, post-discharge antithrombotic regimen, and clinical outcomes were collected by each center. The primary endpoint was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, or stroke. Results A total of 464 patients underwent PCI at a median interval of 106 days (interquartile range: 40-502) after TAVR (45.4% balloon-expandable, 49.6% self-expandable, and 5.0% mechanically-expandable valve). The cohort had a mean age of 80.9±6.2 years, a mean Euroscore II of 5.5±6.2, and 48% had undergone prior PCI or coronary artery bypass graft. Indications for PCI included chronic coronary syndrome (64.6%), non-ST elevation myocardial infarction (20.5%), unstable angina (7.9%), ST elevation myocardial infarction (5.7%), and other acute reasons (1.2%). PCI was complex in approximately 20% of the cases and radial access was utilized only in about 47.4% of them. Still, PCI success rate was 96.7%, achieving complete revascularization in 70.5% of cases. There were 19 periprocedural myocardial infarctions (4.3%). The predominant antithrombotic regimen was 12-month dual antiplatelet therapy (49.1% of patients). MACE incidence over one year of follow-up was 11.8% (95% CI: 9.0%-15.4%), with no differences among TAVR valve types (p-value=0.260). The incidences of the individual component of MACE were 8.7% for cardiovascular deaths, 5.3% for myocardial infarctions, and 2.3% for strokes. Conclusion At present, patients undergoing PCI after TAVR represents a high-risk subgroup. Nonetheless, elucidating actionable factors could potentially improve their outcomes. This preliminary analysis did not reveal any association with the type of implanted valve.

Telomere shortening and cardiac alterations in asymptomatic type 2 diabetes patients: impact of sex

Abstract Background Telomere shortening is associated with the occurrence of deleterious events in the context of cardiometabolic disorders, including type 2 diabetes mellitus (T2DM). However, no evidence is available on the link between leukocyte telomere length (LTL) and subclinical cardiac alterations in T2DM patients. Purpose Our aim is to evaluate the relation between LTL and cardiovascular function in asymptomatic T2DM patients, taking into consideration the impact of the sex. Methods We analyzed a cohort of asymptomatic T2DM patients free from any overt cardiovascular disease (including coronary artery disease) and other T2DM comorbidities. A detailed metabolic and echocardiographic evaluation was performed together with LTL measurements at inclusion and after 2 years of follow-up. Univariate analyses in regard of the comparison of three graded LTL tertiles and different gender were used to test individual relationships betweenbioclinical and echocardiographic parameters and LTL measures. Subsequently, an unsupervised clustering method (self-organizing maps [SOM]) was used to identify cluster at risk of cardiomyopathy. Results We studied 89 T2DM patients aged 50±4 years (43% female) with a mean T2DM duration of 10±5.8 years and an average follow-up of 2.1±0.2 years. Leukocyte TL analysis demonstrated a slight but significant attrition after 2 years. The analysis of echocardiographic variables (transmitral flow velocities, velocity of mitral annular motion, left ventricular ejection fraction) did not show any evidence for ouvert cardiomyopathy. However, in the lower LTL tertile a higher proportion of patients with global longitudinal strain [GLS]<18% was found [41.6% vs. 22.8% vs. 21.6%]. Interestingly, leukocyte TL was associated with T2DM duration, FIB-4, a noninvasive indice used to assess fibrosis associated with non-alcoholic fatty liver disease (NAFLD), and usage of GLP-1 agonists. Comparison of men and women by univariate analysis did not show any differences in both LTL and echocardiographic parameters. However, unsupervised cluster method (SOM) unmasked a subgroup of female T2DM patients with diastolic alterations (e’ mean) and systolic alteration (GLS) both linked with lower LTL, whereas no specific subgroup in male T2DM patients could be distinguished. Conclusion Our study identifies subclinical diastolic and systolic dysfunction together with shorter LTL in a subgroup of female T2DM patients. These findings raise the importance of considering sex effect in the understanding of diabetic cardiomyopathy.

Sex-differences in the clinical features, managements and outcomes of early-onset atherosclerotic coronary artery disease in China

Abstract Background/Introduction There is an alarming rise in the incidence of atherosclerotic coronary artery disease (CAD) among young adults, particularly in young women. Sex disparities of early-onset CAD in the context of contemporary cardiovascular practice are not well understood. Purpose We aimed to delineate the differences in clinical profiles and prognosis between young men and women with established early-onset CAD. Methods This is a nationwide, hospital-based, longitudinal prospective cohort study. Young patients (aged ≥18 years and ≤ 45 years) with angiographically confirmed severe atherosclerotic obstructive coronary arteries (luminal narrowing ≥ 70%) were included from 38 hospitals across China between May 2017 and May 2020. Coronary risk factors, clinical features and treatments were compared between men and women at baseline. Participants were followed for 3 years. The outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, non-fatal myocardial infarction (MI), unplanned revascularization, and ischemic stroke. The Cox regression analyses were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs) for outcome. Results There were 1524 patients (female: 4.4%) included in this study. The female patients were older than the male patients (41.1±4.0 years for females vs. 39.6±4.4 years for males, p=0.006). They showed a lower prevalence of hypertension, lipid disorders, and smoking or drinking (all p<0.01). The female patients were less likely to have at least 1 modifiable risk factors (female: n=45 (67.2%) vs. male: n=1382 [94.6 %], p<0.001); they showed more favorable laboratory results at baseline, including lipids, serum creatinine and uric acid (all p<0.05) as compared to male patients. Besides, young females presented more often with stable angina on admission, whereas young males tended to present with acute MI (p<0.001). There was no significant sex difference in Gensini Score (p=0.15). Female patients were less likely to undergo revascularization procedures than male patients (73.1% vs. 85.3%, p=0.01). During the 3 years of follow-up, female patients were at a significantly higher risk of MACE compared to their male counterparts (13.4% vs. 5.8%, adjusted HR: 3.07, 95% CI:1.36–6.94, p=0.007) after adjusting for age, smoking, drinking, body mass index, hypertension, diabetes, dyslipidemia, diagnosis and revascularization. Conclusions Distinct sex disparities, unfavorable to young females, were documented among patients with early-onset CAD, with the largest gaps noted in the treatment and prognosis. Despite more favorable baseline profiles, young female patients had insufficient care and 3-fold greater risk for MACE compared to young males. These results highlight the need for strengthening the treatment strategies for this vulnerable disease entity.Figure 1

Synthetic assessment of cardiac autonomic modulation and Baevsky stress index in patients with synucleinopathies

Abstract Background The Baevsky Stress Index (BSTRi), calculated from Heart Rate Variability (HRV) data, has been proposed for quantitative assessment of physiological stress, with higher scores indicating higher levels of physical and/or psychological stress [1]. Cardiac autonomic modulation can be synthetically quantified by calculating the parasympathetic (PNSi) and the sympathetic (SNSi) indexes. The values of the BSTRi, SNSi, and PNSi in patients with synucleinopathies of different prognoses have not been reported yet. Purpose To quantify, in patients with Parkinson's disease (PD) and Multisystem Atrophy (MSA), the BSTRi, its correlation with the PNSi and the SNSi indexes, and their potential value for a synthetic assessment of cardiac autonomic modulation and early differential diagnosis between PD and MSA. Methods Holter ECG data of 66 patients with Parkinsonian syndromes were retrospectively analyzed after 10 years of follow-up. Out of them, 34 patients with a certain diagnosis of PD (17) and MSA (17) were selected for this study. HRV was analyzed with the Kubios software (version 4.0), providing automatic calculation of the BSTRi, PNSi, and SNSi [2], as well as of time domain (TD), frequency domain (FD), nonlinear (NL), and time-varying (TV) HRV parameters. HRV was calculated from selected short-term intervals (of 5 minutes), during daily activity (ACT5’), and non-REM sleep (NREM5’), and from 24-hours Holter recordings. Patients’ HRV findings were compared with those of 51 age-matched healthy subjects (HS). Results An example of individual automatic graphic summary is shown in Figure 1. Both short-term and 24-hour BSTRi and SNSi values were significantly (p < 0.05) higher in PD and MSA compared to those of HS, in all investigated conditions. Short-term PNSi was significantly higher in HS than in PD in all conditions, but only during NREM5’ in MSA patients (Table 1). No significant difference was found between the indexes of PD and MSA patients. As in HS (R=92), BSTRi was positively correlated with the SNSi in MSA (average R= 0.83 and 0.89 during ACT5’ and NREM5’, respectively), but less evident in PD (R=0.67). The inverse correlation between PNSi and SNSi (R=0.75 in HS) was lost in both MSA and PD. Conclusions Higher values of BSTRi in PD and MSA compared to HS suggest that patients with synucleinopathies do experience higher levels of psychophysiological stress, which may affect their quality of life negatively. However, since no significant difference was found in this study between BSTRi values of PD and MSA patients, BSTRi seems at present unreliable for early differentiation between the two diseases. Telematic assessment of BSTRi, SNSi, and PNSi could be useful for remote monitoring of PD and MSA patients’ psychophysiological stress, to provide timely intervention and adaptive treatment.Fig.1 Example of graphic summary (ACT5')

Albumin creatinine index added to the grace score increases its discriminative capacity for mortality at 12 years of follow-up in patients with acute coronary syndrome

Abstract introduction There is currently no information on the prognostic value of the GRACE score with the additional addition of the albumin-creatinine index (ABI) for the prediction of very long-term mortality in unselected populations of acute coronary syndromes (ACS). Objectives To evaluate the additive value of the albumin-creatinine index in spontaneous urine sample to the GRACE score for the prediction of 12-year mortality from all causes in an unselected cohort of patients with acute coronary syndrome. Material and methods A prospective cohort study was carried out, which included patients admitted to a Community Hospital with a diagnosis of ACS. These patients had their IAC measured in a single spontaneous urine sample based on the principle of immunoturbidimetry in the first 24 hours of admission. The end point of the analysis was all-cause mortality at follow-up. The GRACE 2.0 score was calculated for all patients in the study. The scores were compared according to the following metrics: their power to discriminate between events and non-events (ROC Areas), calibration or goodness of fit, evaluating the agreement between the proportion of events and non-events expected by both scores observed by Hosmer Lemeshow Test. The comparison between the areas under the ROC Curves was carried out using De Long's test with the MEDCALC program version 19.1.7. The net reclassification index and its 95% CI (GRACE score + IAC/GRACE score) were evaluated. Results 600 patients with ACS were analyzed, with an average age of 64 years. The GRACE score risk subgroups were divided by the established cut-off values: low risk (0 to 108), intermediate (109 to 139) and high risk (greater than 139). The area under the curve of the Grace score for mortality during follow-up was 0.79 (95% CI 0.69-0.89), while the area under the ROC curve of the GRACE + IAC score was 0.81 (95% CI 0.74-0.87). ). Comparing the two areas by the De Long test, the difference was statistically significant (P < 0.0001; 95% CI 0.07- 0.015). On the other hand, contingency tables were developed and the Hosmer Lemeshow Test (goodness of fit) was performed on the GRACE score and the GRACE + IAC score, observing agreement between expected events and non-events, throughout all subgroups of risk. In addition, reclassifications were made into deceased and survivors by applying the GRACE + IAC score on the GRACE score. The net reclassification rate was 28% (95% CI 21-35). The chi square of its Mc Nemar Test was 3.69 p < 0.0002. The absolute comprehensive discriminatory improvement was 0.01 (95% CI 0.009-0.02) and the corresponding relative value was 8.2% (95% CI 7.9-8.5). Conclusions In this unselected ACS cohort, the albumin-creatinine index added to the GRACE score significantly increases its ability to discriminate mortality from all causes in a 12-year follow-up.Comparison between ROC curvesHosmer Lemeshow test

Unequal effects of adolescent health behaviors on adult cardiometabolic conditions: a cohort study

Abstract Background Health behaviors in adolescence could have a life-long effect on cardiometabolic health and differ by parental socioeconomic conditions. Adopting a life course perspective and a causal inference framework, we aimed to quantify the differential effect of adolescent unhealthy behaviors on adult cardiometabolic conditions by parental financial situation. Methods Using the National Longitudinal Study of Adolescent to Adult Health in the United States (n = 3,772), we estimated conditional causal effect by parental financial situation through inverse probability-weighted marginal structural models. Exposures were adolescent health behaviors (dietary habits, cigarette smoking, alcohol consumption and physical activity) and the effect modifier was parental financial situation (difficulty paying bills vs. no difficulty), both measured at ages 12-19 (1994-1995). Outcomes were cardiometabolic conditions (hypertension, stroke, cardiac failure, diabetes, chronic kidney disease), measured at ages 33 - 43 (2016-2018) using biomarkers and self-reports. Results There were 1,206 participants with cardiometabolic conditions after 20 years of follow-up. Alcohol consumption among adolescents with parental financial difficulty led to 325 more cardiometabolic cases (95% confidence interval: 2 - 647) compared to alcohol consumption by their peers without financial difficulty. This differential effect is driven more by cardiovascular conditions (hypertension, stroke, or cardiac failure) than by metabolic conditions (diabetes or chronic kidney disease). There were no differential effects of dietary habits, cigarette smoking and physical inactivity on the occurrence of adult cardiometabolic conditions. Conclusions Public health initiatives targeting alcohol consumption during adolescence could mitigate socioeconomic inequalities in adult cardiometabolic conditions. Key messages • Socioeconomically disadvantaged adolescents are more susceptible to the long-term detrimental health effects of alcohol consumption. • These susceptible groups may need targeted interventions to mitigate the cardiometabolic effect of alcohol consumption.

Onset of cognitive impairment, diet quality and adherence to dietary guidelines over 12 years: the Personality and Total Health Cohort Study.

Around 55 million people worldwide live with dementia, and more are expected due to population ageing. We aimed to investigate associations between healthy diet and mild cognitive impairment and dementia in 1753 older adults aged 60-64 from the PATH (Personality and Total Health Through Life Cohort) study. Healthy diet was defined by the Mediterranean-DASH diet Intervention for Neurological Delay (MIND) and two dietary guideline quality scores (Dietary Guideline Index (DGI) and Index Diet Quality (IDQ)), which were calculated from baseline FFQ. Higher dietary scores indicated higher diet quality. Incidence of Alzheimer's disease/vascular dementia (National Institute of Neurological Disorders criteria) and mild cognitive impairment (Winbald criteria) was assessed after 12 years of follow-up using validated questionnaires with nominated proxies. Logistic regression explored associations between dietary scores and cognitive function, adjusting for demographics, lifestyle factors and medical preconditions. Adjusted logistic regression comparing the per unit linear increase in diet scores showed MIND (OR = 0·82, 95 % CI = 0·68, 0·99), but not DGI (0·99 (0·97, 1·00)) or IDQ (1·12 (0·95, 1·32)), was significantly associated with lower odds of developing cognitive impairment. In conclusion, a healthier neuroprotective dietary pattern is associated with better cognitive function over time, whereas dietary patterns generated from general dietary guidelines did not show a significant association. Further research and well-designed clinical studies are needed to determine the effects of the MIND diet on cognitive impairment in older adults without a family history of dementia.

The role of fibrosis and inflammation for response and outcome prediction in candidates to cardiac resynchronization therapy: is response the right answer?

Abstract Background Cardiac resynchronization therapy (CRT) is an established treatment in selected patients suffering from heart failure with reduced ejection fraction (HFrEF). It has been proposed that myocardial fibrosis and inflammation could influence CRT "response" and outcome. Purpose Our study investigated the long-term prognostic significance of cardiac biomarkers in HFrEF patients with an indication for CRT. Methods 86 consecutive patients referred for CRT implantation were retrospectively evaluated. The soluble suppression of tumorigenicity 2 (sST2), galectin-3 (Gal-3), N-terminal portion of the B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR) were measured at baseline and after 1 year of follow-up. An echocardiographic reduction of LV end-systolic volume ≥15% was used to define a patient as responder to CRT. Multivariate analyses were performed to evaluate their correlation with the primary composite outcome of cardiovascular mortality and heart failure hospitalizations at a mean follow-up of 9 ± 2 years. Results 44% of patients experienced the primary outcome. the mean baseline values of NT-proBNP, Gal-3, and sST2 were significantly higher compared with the patients without cardiovascular events. At the multivariate analyses, baseline Gal-3 [cut-off: 38.5 ng/ml, AUC: 0.63, p=0.03, (OR 7.13 [1.12;45.41], p=0.03), together with TAPSE>17.5 mm (OR 10.86 [3.15;37.44], p<0.001) significantly correlated with the structural response to CRT in several prediction models. Baseline Gal-3 [cut-off: 16.6 ng/ml, AUC: 0.91, p<0.001, HR 8.33 (1.88–33.33), p = 0.005] and sST2 [cut-off: 35.6 ng/ml AUC: 0.91, p<0.001, HR 333 (250–1,000), p = 0.003] significantly correlated with the composite outcome in the prediction models with high likelihood (Table). At Kaplan-Meyer curve patients with both high baseline sST2 and Gal-3 had the lowest survival probability (Figure). Among the parameters evaluated at 1-year follow-up, sST2, eGFR, and the variation from baseline to 1-year of Gal-3 levels showed a strong association with the primary outcome [HR 1.15 (1.08–1.22), p < 0.001; HR: 0.84 (0.74–0.91), p = 0.04; HR: 1.26 (1.10–1.43), p ≤ 0.001, respectively]. Conversely, the echocardiographic definition of CRT response did not correlate with any outcome. Conclusion In HFrEF patients with CRT, sST2, Gal-3, and renal function were associated with the combined endpoint of cardiovascular death and HF hospitalizations at long term follow-up, while the echocardiographic CRT response did not seem to influence the outcome of the patients.

Socioeconomic deprivation and atrial fibrillation risk: an observational and gene-environment interaction analysis

Abstract Background The association between socioeconomic deprivation and incident atrial fibrillation (AF) is debated, along with limited evidence on how genetic predisposition to AF interacts with socioeconomic deprivation and AF risk. Purpose To evaluate the association and gene-environmental interaction between socioeconomic deprivation and the risk of incident AF. Methods From the UK Biobank prospective cohort, we selected participants who were free from previous AF. Participants with missing values and those who did not pass the genetic quality control were excluded. As an indicator of socioeconomic deprivation, we utilised the indices of multiple deprivation (IMD), which is calculated from scores of multiple socioeconomic factors, including crime, education, employment, health, housing, income, and living environment. Participants were divided into 3 groups by IMD; the top 20% as high IMD (most deprived), the bottom 20% as low IMD, and 20-80% as mid IMD. Using a polygenic risk score (PRS) for AF generated using a Bayesian approach applied to external genome-wide association study data, the interaction between genetic risk and socioeconomic deprivation was assessed. The primary endpoint was incident AF during a median of 13.7 years of follow-up. Results A total of 377,386 (aged 56.5±8.1 years, 45.2% male) were analysed. The high IMD group (n=85,108) was younger and had a higher proportion of comorbidities than the mid or low-IMD groups. An increase in IMD as a continuous variable was significantly associated with an increased risk of incident AF. The high IMD group showed a significantly increased risk of AF (multivariable-adjusted hazard ratio [aHR]=1.12, 95% confidence interval=1.07-1.17, P<0.001) compared with the low IMD group (incidence rate 7.7 vs. 4.8/1,000 person-year). All components of IMD except housing score significantly increased the risk of incident AF (aHR ranged from 1.07 to 1.15). Within each IMD group, higher AF PRS groups were significantly associated with an increased risk of incident AF with the low AF PRS group as a reference, showing aHRs of 1.50 for mid-PRS and 2.57 for high-PRS in the low IMD group, 1.60 and 2.65 in the mid-IMD group, and 1.55 and 2.33 in the high IMD group, respectively (all P<0.001). The impact of socioeconomic deprivation was attenuated in participants with high AF PRS (P for interaction=0.042), mainly driven by the interaction effect of crime (P for interaction [Pi]=0.005), employment deprivation (Pi=0.005), and health deprivation scores (Pi=0.043). Conclusion Socioeconomically deprived individuals had a significantly higher risk of AF, and the effect was partially modified by genetic predisposition to AF. A personalised approach to applying AF screening for high-risk individuals may be more efficacious. Legal measures and policies to enhance public health by alleviating socioeconomic inequalities are needed to mitigate AF risk and improve cardiovascular health outcomes.