Incidence Rate Research Articles

The very long-term risk of stroke after acute coronary syndrome and geographic differences. The ABC-10* study on heart disease

Abstract Background Little is known about the very long-term risk of stroke among acute coronary syndrome (ACS) survivors. Methods In this prospective study, we enrolled 535 ACS patients admitted to hospitals in three Italian provinces, discharged alive and followed for 24 years or death. The patient's residency was classified into three urban and three nearby rural areas. Results All patients completed the follow-up (6142 Perso-years). 85 (16%) patients suffered an acute stroke. Patients median age was 67 years, 70% were male, and 318 patients were residing in rural areas. Patients who had a stroke and those who had not shared most of the demographic and clinical characteristics. The incidence rate of overall stroke was 14/1000 person-year. Cox analyses showed older age (HR 3.13;95%CI 2.31-4.26), male gender (HR 1.88;95%CI 1.20-2.95), baseline diabetes (HR 2.25 95%CI 1.37-3.69), heart failure (HR 2.69;95%CI 1.71-4.24), and higher albumin/creatinine ratio (HR 1.75;95%CI 1.33-2.30) were all associated with an increased risk of stroke. while higher baseline eGFR, reperfusion, statin and beta-blockers treatment during follow-up were associated with a decreased risk; HR (0.55 (95%CI 0.42-0.72), 0.45(95%CI 0.29-0.71), 0.21(95%CI 0.13-0.34), and 0.37(95%CI 0.23-0.57), respectively). In the multivariate analysis, only older age (HR1.55;95%CI 1.08-2.21; p=0.02) was an independent predictor of stroke while statin treatment was independently associated with a lower risk (HR 0.35;95% CI 0.21-0.58; p<0.0001). However, all these variables did not predict the risk of stroke in competing risk regression analysis where death was treated as the competing event. A sub-analysis of the 43 patients who had a fatal stroke (FS) revealed 7/1000 person-year FS IR. The Cox regression and competing risk analyses of predictors of FS showed similar results. Interestingly, we observed an association between geographic areas of residence and the long-term FS risk as the risk increased going from rural to urban (HR 2.08;95%CI 1.14-3.80; p=0.02) areas and from north to middle and south provinces (HR 1.47;95%CI 1.00-2.15; p=0.04) in the univariate Cox regression analysis. Results kept true using multivariate Cox and Competing risk regression models. Conclusion This analysis reveals the significant urban-rural difference in the very long–term risk of fatal stroke among unselected ACS patients which highlights the importance of implementing a preventive policy based on area-specific knowledge.

The Relationship Between Social Isolation, Psychological Resilience, and Psychological Well-Being Among Older People in the Community

Objective: To explore the relationship between social isolation, psychological resilience, and psychological well-being in community-dwelling older adults. Methods: A questionnaire survey was conducted with 265 community-dwelling older adults using the Social Isolation Scale for the Elderly (C-SIS), the 10-item Brief Psychological Resilience Scale, and the Comprehensive Happiness Questionnaire (MHQ). The results were statistically analyzed using SPSS 27.0. Results: The highest score on the Social Isolation Scale for Community Elderly was 23, with a mean entry score of 2.36 ± 0.62. A score of 14 was the cut-off point, with scores of ≤ 14 classified as social isolation. There were 136 cases with scores below 14, resulting in a social isolation incidence rate of 51.3%. The median (P50) psychological resilience score was 27, indicating a higher level of resilience. The total score on the Psychological Well-being Scale was 161, suggesting a moderate to slightly higher level of well-being. Social isolation had a direct negative effect on psychological well-being, while psychological resilience had a positive effect. Conclusion: Older adults should be supported in reducing the incidence of social isolation and increasing psychological resilience to enhance psychological well-being and promote successful aging.

Cardiological monitoring during BTK inhibitor, ICI, and RAF/MEK inhibitor therapy: the single-center prospective registry for cardiovascular events under new cancer therapies (RECENT)

Abstract Background The advent of novel targeted cancer therapies have revolutionized cancer treatment. However, concerns about their impact on cardiovascular health persist and current guidelines recommend cardiac monitoring. Yet, prospective data on incidence rates of cardiovascular events are lacking. The Registry for Cardiovascular Events under new cancer Therapies (RECENT) aims to systematically assess clinical as well as subclinical cardiovascular incidents in patients undergoing these novel therapies to identify baseline risk factors and derive individualized monitoring strategies. Methods This ongoing single-center prospective registry enrolls cancer patients receiving BTK inhibitors, ICI, or RAF/MEK inhibitors. Baseline cardiovascular assessment, risk stratification according to HFA-ICOS risk score, and follow up visits for 12 months at three-monthly intervals (including ECG, biomarkers and echocardiography) during treatment are conducted. Treatment-related events, in particular hypertension, arrhythmias, cancer therapy-related cardiac dysfunction (CTRCD), and (peri-) myocarditis, as defined according to current guideline recommendations, are recorded. Results We report data of the first 85 patients (60.9 ± 14.7 years, 52.9% male) included in this ongoing registry. Of those, 17/85 patients received treatment with BTK inhibitors (20%), 45/85 with ICI (53%) and 23/85 with RAF/MEK inhibitors (27%). Most common treatment indication were dermatological (39/85, 45.9%), hematologic (17/85, 20%), urological (13/85, 15.3%) and head and neck (11/85, 12.9%) cancers. Before treatment, the majority of patients were stratified as low-risk (31/85) or moderate-risk (32/85), and 22/85 (25.9%) as high-risk. 7/85 (8.2%) patients were newly diagnosed with cardiovascular disease at baseline visit, resulting in a change in risk category and subsequent initiation of cardiovascular treatment. This includes 3 patients who had been initially categorized as low-risk and would not have been referred for further cardiac workup due to current guideline recommendations. The six months follow up visit has been completed in 44/85 patients. Among these, 1/20 patients (5%) with ICI developed a perimyocarditis and 2/11 patients (18.2%) with BTK inhibitors developed atrial fibrillation. 1/13 patients (7.7%) with RAF/MEK inhibitor therapy, classified as low-risk at baseline, developed asymptomatic CTRCD, which resolved after initiation of cardioprotective drug therapy. Conclusion This interim analysis of the RECENT registry indicates benefit of a structured baseline cardiac assessment prior to cancer treatment in all patients, irrespective of the initial risk stratification. Contrary to current guidelines, which recommend routine echocardiographic monitoring in patients receiving RAF/MEK inhibitors only in high-risk patients, the current data advocate for extending this also to low-risk patients to detect subclinical deterioration of the cardiovascular status.

Sex differences at different ages in 30-day survival of COVID-19 hospitalized patients in Israel

Abstract Background Sex differences in mortality from COVID-19 have been described. It is not clear to what extent sex is an independent risk factor for mortality or is confounded by co-morbidities and whether it varies by age. It is also not clear whether it is constant over time since diagnosis. We studied sex differences in 30-day mortality rates in patients hospitalized with COVID-19, after controlling for co-morbidities. Methods Data on patients hospitalized with COVID-19 were extracted from the majority of general hospitals in Israel during 2020 to 2022. The outcome variables were death during 30 days from onset of hospitalization. Sex differences in survival rates were assessed using Cox proportional hazards models controlling for age, heart disease, cancer, respiratory disease, diabetes and hypertension. Results Mortality rates in women were significantly lower than in men in all age groups. There was an approximate 5-6 year lag in the mortality rates between men and women. Conclusions Sex was an independent predictor of 30 day mortality from COVID-19 with women experiencing better survival. This advantage was not explained by differences in co-morbidities or the magnitude of the differences in survival by age. The sex differences in the 30-day mortality of hospitalized patients are compatible with the male dominance in the incidence rates of many infectious diseases. Poorer survival of men hospitalized for COVID-19 is likely to be part of the disease mechanism and should be explored further. Key messages • Poorer survival of male COVID-19 patients seems to be part of the disease mechanism and should be explored further. • Sex differences in disease should be included in personalized management of disease.

From crisis to chronic: a comparative analysis of Long COVID impact in Italy and the United States

Abstract Background The aftermath of COVID-19 is bringing about socio-economic consequences, such as diminished quality of life (QoL), decreased productivity, and considerable healthcare expenditures. Despite the emerging acknowledgment of a clinical syndrome following COVID-19 disease, known as Long COVID (LC), notable research gaps persist. This study aims to assess the epidemiological and economic impact of LC in both Italy and the United States (US). Methods This ecological analysis comprises epidemiologic and economic data from 2020 to January 2023, regarding working-age individuals (18-64 years). An Italy/US incidence rate ratio (eIRR) was estimated to compute LC cases in each country. The product between the value of a year spent in good health, individual Quality-Adjusted Life Year (QALY) loss, and LC cases yielded total lost QoL. Temporary productivity loss (TPL) was calculated through the Human Capital Approach. All estimates were deemed significant at a p-value less than 0.05. Results Up to date, the eIRR was 0.78 [0.43 - 0.91] implying 22% fewer LC cases in Italy with respect to the US. Total LC cases were 11 [8.7 - 13.5] and 1.8 [0.9 - 2.1] million in the US and Italy, respectively. The relative QALYs loss was 1.5 [0.8 - 3.1] and 0.2 [0.1 - 0.9] million. Reduced QoL cost roughly $189 [164 - 214] billion in the US and €6 [1 - 11] billion in Italy. TPL amounted to $37 [21 - 57] billion in the US and €2.8 [1.2 - 7.4] billion in Italy. Americans aged 30-39 years showed the largest income loss (26.6%), while in Italy it occurred in the age group 50-64 years (38%). Conclusions LC places a substantial burden in Italy and the US, impacting both the productivity of the working-age population and influencing the younger generation, who constitute the future workforce. Our study underpins the necessity for comprehensive health policies, programs, and interventions alongside effective tertiary prevention strategies to tackle the challenges posed by LC. Key messages • According to this analysis, both countries show significant productivity and quality-adjusted life years loss due to LC among working age individuals. • Steering the formulation of evidence-based sounding health policies to address LC burden, among working age individuals, both in Italy and in the US.

Inetetamab combined with S-1 and oxaliplatin as first-line treatment for human epidermal growth factor receptor 2-positive gastric cancer

BACKGROUND Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer have poor outcomes. Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer. Inetetamab is a novel anti-HER2 drug, and its efficacy and safety in gastric cancer have not yet been reported. AIM To evaluate the efficacy and safety of the S-1 plus oxaliplatin (SOX) regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer. METHODS Thirty-eight patients with HER2-positive advanced gastric cancer or gastroesophageal junction adenocarcinoma were randomly divided into two groups: One group received inetetamab combined with the SOX regimen, and the other group received trastuzumab combined with the SOX regimen. After 4-6 cycles, patients with stable disease received maintenance therapy. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were the objective response rate, disease control rate, and adverse events (AEs). RESULTS Thirty-seven patients completed the trial, with 18 patients in the inetetamab group and 19 patients in the trastuzumab group. In the inetetamab group, the median PFS was 8.5 months, whereas it was 7.3 months in the trastuzumab group (P = 0.046); this difference was significant. The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months (P = 0. 33), and the objective response rate was 50% vs 42% (P = 0.63), respectively; these differences were not significant. Common AEs included leukopenia, thrombocytopenia, nausea, and vomiting. The incidence rates of grade ≥ 3 AEs were 56% in the inetetamab group and 47% in the trastuzumab group (P = 0.63), with no significant difference. CONCLUSION In the first-line treatment of HER2-positive advanced gastric cancer, inetetamab and trastuzumab showed comparable efficacy. The inetetamab group showed superior PFS, and both groups had good safety.

Periprocedural changes in systolic pulmonary artery pressure in transcatheter aortic valve implantation

Abstract Background Pulmonary hypertension (PH) is common in patients with aortic stenosis and associated with increased mortality following transcatheter aortic valve replacement (TAVR). PH often improves after TAVR and systolic pulmonary artery pressure (sPAP) can change, but to what extent these changes in sPAP following TAVR affect long-term prognosis is unclear. Purpose To investigate the association between periprocedural changes in sPAP and long-term prognosis after TAVR. Methods Patients undergoing TAVR between 2012-2021 from the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY) were included. sPAP was estimated from echocardiography before and after TAVR and categorized as: (1) No PH before and unchanged (≤5 mmHg change) after, (2) No PH before and worsened (>5 mmHg increase) after, (3) PH before and improved (>5 mmHg decrease) after, (4) PH before and unchanged after and (5) PH before and worsened after. An sPAP cutoff at >50 mmHg was applied for PH. Patients were followed for a median of 3.1 years for the primary endpoint heart failure hospitalizations (HFH) and the secondary endpoint all-cause mortality. Cox regression analyses were performed and adjusted for age, sex, body mass index, atrial fibrillation, eGFR class, diabetes, frailty, left ventricular ejection fraction and chronic obstructive pulmonary disease. Results In total, 4926 patients were included (mean age 82 years, 50% female) among whom 2596 (53%) patients had no PH and unchanged, 864 (18%) had no PH and worsened after, 912 (19%) had PH and improved after, 401 (8%) had PH and unchanged after and 153 (3%) had PH and worsened after. The mean sPAP levels preoperatively in each group were 36, 31, 60, 58, 57 mmHg respectively. Mean change in patients with no PH and worsened was +16 mmHg, in patients with PH and improved -20 mmHg and in patients with PH and worsened +14 mmHg. Cumulative incidence rates of HFH at 5 years among the five groups were 18%, 25%, 32%, 41%, and 52%, respectively (p<0.001). In adjusted analyses, there was a stepwise increase in the risk of HFH (Figure 1A) and all-cause mortality (Figure 1B) for no PH and worsened, PH and improved, PH and unchanged and PH and worsened as compared with no PH and unchanged. Conclusion Increase of periprocedural sPAP in patients with and without known PH before TAVR was associated with worse prognosis whereas reduction of sPAP was associated with improved outcomes.

CKD incidence, predictors & progression: African migrants vs. Non-Migrants (RODAM cohort study)

Abstract Background Limited longitudinal data exist on chronic kidney disease (CKD) in African populations undergoing epidemiological transitions. We investigated incidence, long-term predictors, and progression of CKD among Ghanaians residing in rural- and urban-Ghana, and Ghanaian migrants in the Netherlands (Amsterdam). Methods We analysed data from 2183 participants in the transcontinental population-based prospective RODAM-cohort, followed for approximately seven years. CKD incidence and its progression to end-stage renal disease (ESRD) were defined using KDIGO criteria. CKD incidence was calculated using age-and sex-standardization for those without CKD at baseline. Long-term predictors of CKD incidence were identified using one-step robust Poisson regression. CKD progression to ESRD from baseline was also assessed using robust Poisson regressions. Results Overall age-and-sex standardized CKD incidence was 11.0% (95%CI; 9.3%-12.3%). Rural and urban-Ghanaians had higher CKD incidence (12.5%;8.5%-15.5%; 12.3%;8.2%-15.8%; respectively) than Amsterdam-Ghanaians (7.6%; 5.4%-10.6%). Residence in Amsterdam was associated with lower CKD incidence compared to rural Ghana after adjustments (Incidence Rate Ratio=0.34; 0.13-0.89), but not with urban-Ghana (IRR=1.07; 0.69-1.67). CKD incidence predictors were advanced age, female sex, alcohol consumption, uric acid levels, and hypertension. CKD progression to ESRD was 2.5% (1.4%-3.6%) in rural- Ghana, 2.3% (1.3%-3.2%) in urban-Ghana and 0.0% in Amsterdam. Conclusions One-tenth of Ghanaians developed CKD over seven-years, with higher incidence in Ghana compared to Europe. Age, female sex, alcohol use, uric acid levels, and hypertension were predictive factors. CKD progression to ESRD was minimal. High CKD incidence among Ghanaians, especially among non-migrants, calls for in-depth assessment of contributing factors and targeted interventions. Key messages • We observed higher CKD Rates in Rural/Urban Ghana vs. Amsterdam:Indicating geographic Disparities. • CKD Predictors: Age, Sex, Alcohol, Uric Acid, Hypertension (Minimal ESRD Progression). Interventions target: Non-Migrant Ghanaians.

Similar incidence of ICD-shocks in diabetic compared to non-diabetic patients receiving implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D)

Abstract Background and aims Recent studies have suggested that diabetes patients with implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) may experience a reduced incidence of appropriate ICD-shocks and an increased mortality rate. This study aims to assess whether there is parity in ATP-treatment and ICD-shocks between patients with and without type 2 diabetes mellitus (T2DM), and to analyze associated mortality rates. Methods Using the Danish pacemaker and ICD registry we included patients who received a first-time ICD or CRT-D implantation with a primary or secondary prophylactic indication, between January 1st 2000 to December 31st 2018. Outcomes were analyzed individually for each outcome. Cause specific Cox was used for i) appropriate ATP therapy or ICD-shock, ii) inappropriate ATP therapy or ICD-shock, and a standard Cox regression model was used for iii) all-cause mortality, iv) mortality rate following an ATP-therapy or ICD-shock. Cumulative incidence curves, generated using the Aalen Johansen estimator, were utilized to compare the incidence rates for ATP therapy and ICD-shock while accounting for competing risk of death, while Kaplan-Meier methodology was utilized for survival curves. Analyses were conducted in the total population and in subgroups divided on indication and device type. Results Out of 14 747 patients who received an ICD or CRT-D, 4377 (30%) had T2DM, 4593 (31%) patients received first-time appropriate ATP therapy or ICD-shock, and 1244 (8,4%) experienced first-time inappropriate treatments, 5 112 (35%) experienced death during the follow-up time (mean 3.9 years (SD 2.7)). T2DM patients were more likely to be male (85% vs 80%), slightly older (66 vs 65 years) and burdened with more comorbidities. No significant differences were seen between T2DM and non-T2DM patients for appropriate ATP therapy (HR 0.96[0.88:1.04] p=0.31), appropriate ICD-shock (HR 0.95[0.86:1.05] p=0.32), inappropriate ATP therapy (HR 0.92 [0.77;1.09] p=0.32) and inappropriate ICD-shock (HR 0.96 [0.78;1.18] p=0.71). In the subgroup analyses, no difference was seen in the primary prophylactic subgroups (Figure 1.), only significant difference was observed in the secondary prophylactic ICD group who received less ATP-therapy at 5-year follow-up (HR0.83[0.70;0.99] p=0.04), and in the secondary prophylactic CRT-D group, were T2DM patients seemed to experience more appropriate ICD-shock treatments (HR 2.07[1.23;3.48] p=0.006). Further, we found a higher mortality rate in T2DM with primary prophylactic ICD (HR 1.46[1.31;1.62] p<0.001) and secondary prophylactic ICD (HR 1.30[1.13;1.51] p<0.001), (Figure 2.) this mortality rate remained largely unchanged post appropriate ATP or ICD-shock in the ICD subgroups. Conclusions Despite similar incidence of ATP-therapy and ICD-shocks, T2DM patients with ICD-device experienced a significantly higher post-treatment mortality and all-cause mortality rate.

Metabolically healthy obesity and cardiovascular outcomes

Abstract Obesity increases cardiovascular risk through a deterioration of the metabolic profile. However, obesity is not always accompanied by a worsening metabolic profile. This longitudinal study aimed to determine whether obesity with a normal metabolic profile, i.e. metabolically healthy obesity, increases the risk of cardiovascular disease. We analyzed a health insurance data of Shizuoka prefecture resident. This data includes data from annual health check-ups performed for insured persons. This study analyzed data from 168,699 individuals aged <65 years. Obesity was defined as ≥ 25 kg/m2 body mass index. Metabolically healthy was defined as ≤ 1 metabolic risk factors (high blood pressure, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol, or high hemoglobin A1c). Incidence rate of cardiovascular diseases (stroke and myocardial infarction), and all-cause mortality identified from the insurance data were compared between clinical profile-matched metabolically healthy obesity and non-obesity groups (n = 8,644 each). Clinical parameters, namely systolic blood pressure (standard mean difference = 0.03), HDL cholesterol (0.01), LDL cholesterol (0.01), and hemoglobin A1c (0.01) did not differ among the metabolically healthy obesity and non-obesity groups. The incident rate of stroke (obesity: 9.2 per 10,000 person-years; non-obesity: 10.5; log-rank test P = 0.595), myocardial infarction (obesity: 3.7; non-obesity: 3.1; P = 0.613), and all-cause mortality (obesity: 26.6; nonobesity: 23.2; P = 0.304) also did not differ significantly among the groups even when abdominal obesity was considered in the analysis, though the population with metabolically healthy obesity reported negligibly worse metabolic profiles than the population with nonobese at the 5.6-year follow-up. Obesity, when accompanied by a healthy metabolic profile, did not increase the risk of cardiovascular outcomes and all-cause mortality. Key messages • Metabolically healthy obesity did not increase cardiovascular disease risks. • Metabolically healthy obesity was associated with worse metabolic profiles after a few years later.

Clinical prediction model of main adverse cardiovascular and cerebrovascular events for elderly patients with acute coronary syndrome

Abstract Background Age is an independent factor for adverse outcomes in acute coronary syndrome (ACS). With the accelerated aging process, there is an increasing incidence of ACS in the elderly; however, research on this population is underrepresented. Due to the unique presence of multiple diseases and organ changes in the elderly, specialized risk assessment tools are required. Purpose To explore the risk factors for poor prognosis of elderly patients with ACS and establishing a risk stratification tool. Methods The derivation cohort consisted of 1674 elderly ACS patients consecutively enrolled in a single center from January 2013 to December 2013. The validation cohort included 2333 elderly ACS patients consecutively enrolled in nine medical centers from January 2015 to May 2019. All patients were followed up for 2 years, and the study endpoint was defined as major adverse cardiovascular and cerebrovascular events (MACCE). Model selection was performed using Cox regression and the Akaike Information Criterion (AIC) to construct the final risk assessment model. The performance of the predictive model was evaluated in the derivation and validation cohorts using the c-index, receiver operating characteristic (ROC) curves, and calibration curves. Results A total of 1,674 elderly ACS patients (70.97±4.68 years, 23.24% female) were included in the derivation cohort, and 210 cases (12.54%) of MACCE were recorded during the 2-year follow-up period. In the validation cohort, there were 2,333 elderly ACS patients (72.13±5.82 years, 35.83% female), with 364 cases (15.60%) of MACCE documented during the 2-year follow-up. Initially, 25 variables were preliminarily selected based on the results of univariate Cox regression and the clinical importance of these variables. Subsequently, these variables were included in a multivariable Cox model, and model selection was performed based on the AIC, resulting in the final selection of 10 variables (including age, cardiac insufficiency, current smoker, DAPT use, history of PCI or CABG, IABP use, number of lesions, residual SYNTAX score, preoperative HGB, and preoperative PLT). Then we developed and validated a nomogram to predict the 2-year MACCE in elderly ACS patients based on the assessment of 10 clinically easily obtainable variables during hospitalization. In both the derivation and validation cohorts, the nomogram demonstrated good discriminative ability (AUC of 0.723 and 0.699, c-index of 0.727 and 0.661, respectively) and calibration (calibration curves closely approximating the 45-degree diagonal line). The Kaplan-Meier analysis reveals significant differences in MACCE incidence rates between groups stratified by the median predicted probability (p<0.001). Conclusion Our study developed and validated a practical nomogram for predicting the 2-year risk of MACCE in elderly patients with ACS.

Sex differences in outcomes among patients undergoing transcatheter atrial septal defect closure: Do they benefit equally?

Abstract Background Although sex differences in congenital heart disease are prevalent and relevant, there is limited research on their role in atrial septal defect (ASD) closure. We aimed to investigate sex differences in baseline characteristics, procedural and long-term outcomes of patients with transcatheter ASD closure. Methods Data from adult patients undergoing ASD closure between 2005-2016 were retrospectively analyzed. Results Of the 853 patients included, 281 (32.9%) were male and 572 (67.1%) were female. Females were more symptomatic at presentation than males (p < 0.001). Males had a higher frequency of cardiovascular comorbidities than females (p < 0.001). Although echocardiographic right ventricular (RV) diameter relative to body surface area was equal in males and females (2.49 cm/m2 versus 2.57 cm/m2; p = 0.072), males had more RV dysfunction (12.1% versus 7.6%; p = 0.028). In contrast, females had higher RV systolic pressures (39.71 mmHg versus 37.23 mmHg; p = 0.025), and were more likely to have moderate to severe tricuspid regurgitation (15.4% versus 8.9%; p = 0.007). Males had larger defects with use of larger implants (p < 0.05). Procedure-related complications were rare and did not differ by sex. At 12-month follow-up, both male and females showed comparable decreases in RV diameter (-0.57 cm versus -0.59 cm; p = 0.751), RV systolic pressure (-4.57 mmHg versus -6.31 mmHg; p = 0.094), and severity of tricuspid regurgitation (p = 0.173; Figure). After a mean follow-up of 3 years (SD = 5), no significant differences were observed in the incidence of death (incidence rate ratio (IRR) = 0.49 [95% CI 0.27-0.83]; p = 0.402), new onset atrial fibrillation (IRR = 3.22 [95% CI 2.57-3.99]; 0.063), cardioversion or ablation (IRR = 0.40 [95% CI 0.20-0.71], p = 0.335), stroke/TIA (IRR = 0.29 [95% CI 0.12-0.56]; p = 0.745), and pacemaker implantation (IRR = 0.29 [95% CI 0.12-0.57], p = 0.728). Conclusions Although patient profiles differed by sex, procedural and long-term outcomes were comparable, suggesting that transcatheter ASD closure can be safely performed in both males and females.Figure.Sankey Plot

Arrhythmia burden in patients with congenital heart disease

Abstract Background The prevalence of congenital heart defects (CHD) is rising. Many patients experience arrhythmias either due to the defect itself or necessary intervention. Sudden onset of arrhythmia poses grave risks such as heart failure, stroke, or cardiac death. Research gaps exist regarding high-risk defects, age susceptibility, and prognostic implications of arrhythmia. Purpose Delineate the burden of arrhythmias in patients with CHD. Methods Patients born in the period 1970-2017 and diagnosed with CHD were identified in Swedish nationwide medical registries. Each patient was matched by birthyear and sex with ten controls from the general population. Cox proportional hazard regression model and Fine-Gray regression model with death as competing risk were used to compute risk (hazard ratio [HR]) and cumulative incidence of arrhythmias (supraventricular and ventricular arrhythmias). Estimates were compared with the matched controls. Follow-up started at time of birth. Results We included 63,559 patients and 583,205 matched controls with median follow-up of 12.8 years. Almost two-thirds of the total CHD population were born after year 2000 and 89% (n=56,564) had a simple lesion (defined as atrial or ventricular septal defect, coarctation of the aorta or malformation of the heart valves). During follow-up, 1,632 events of arrhythmia (90% of supraventricular origin) were registered in the population of patients with CHD, yielding an incidence rate of 16.4 per 10,000 person-years (versus 1.6 in the control population). The cumulative incidence of arrhythmias in the total CHD population was slightly increased during childhood compared with the control population, but rose significantly hereafter, illustrated in Figure 1, yielding an overall risk of 10.5 (CI 95%: 9.8-11.2). Stratified by lesion severity, the risk for arrhythmias was 8.7 (CI 95%: 7.6-8.7) and 30.4 (CI 95%: 26.2-35.2) in patients with simple and complex lesions, respectively. Patients with simple CHD lesions displayed a risk of 7.7 (95% CI: 7.1-8.4) for supraventricular arrhythmias and 11.5 (95% CI: 9.2-14.5) for ventricular arrhythmias. Correspondingly, patients with complex CHD lesions displayed risks of 66.7 (95% CI: 42.7-104.2) and 28.9 (95% CI: 24.8-33.6). Conclusion Arrhythmias, irrespective of origin, are common in patients with CHD and correlate with lesion severity. The overall burden of arrhythmias increased significantly after childhood. Meticulous follow-up is vital in order to prevent, detect and treat arrhythmias as it might trigger clinical deterioration and even sudden cardiac death in patients with CHD.

The risk factors for in-stent restenosis following drug-eluting stent implantation in end-stage renal disease patients receiving renal replacement therapy

Abstract Background Chronic renal disease is a recognized risk factor for in-stent restenosis (ISR) following percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). However, the specific risk of ISR among individuals with end-stage renal disease (ESRD) remains unclear or insufficiently studied. Purpose It is imperative to identify the risk factors associated with ISR among patients with ESRD and coronary artery disease following the implantation of DES. This identification is crucial for generating evidence-based strategies aimed at preventing ISR. Methods ESRD patients undergoing renal replacement therapy with concomitant coronary artery disease who underwent PCI with their initial DES implantation at our hospital between January 2013 and December 2022 were included in the study cohort. Clinical data, laboratory test results, and PCI specifics were compared between patients with and without ISR. Univariate and multivariate analyses utilizing Cox proportional hazard regression were employed to identify independent risk factors for DES-ISR. Results Among the 321 patients with ESRD who underwent PCI with DES implantation, totaling 874.5 patient-years of follow-up, 53 cases of ISR occurred during this period, yielding an incidence rate of 6.1 per 100 patient-years. Several baseline characteristics, angiographic findings, and procedural details were found to elevate the risk of ISR significantly. These included underlying diabetes mellitus, peripheral artery disease (PAD), high serum parathyroid hormone levels, LDL-C levels, acute coronary syndrome as the clinical presentation, the presence of triple vessel disease, duration of dual antiplatelet therapy less than 1 year, target lesion involving the left main (LM) or left anterior descending (LAD) artery, target vessel size less than 3 mm, ostial lesion, bifurcation lesion, number of stents implanted equal to or more than 3, and stent size less than 3 mm. In the multivariate Cox proportional hazard model, bifurcation lesion (HR 14.70, 95% CI 4.66-46.38), PCI of LM or LAD (HR 5.29, 95% CI 1.14-24.60), target vessel size less than 3 mm (HR 4.10, 95% CI 1.77-9.50), PAD (HR 3.92, 95% CI 1.52-10.08), and ostial lesion (HR 2.92, 95% CI 1.16-7.38) were identified as independent risk factors for ISR (all p-values < 0.05). Conclusions Among ESRD patients with coronary artery disease, bifurcation lesion, PCI involving the LM or LAD, target vessel size less than 3 mm, PAD, and ostial lesion are identified as independent risk factors for ISR. These findings hold significance in enhancing risk stratification and decision-making concerning treatment planning for this population.Univariate analysis risk factors for ISR

Diagnosis of chronic thromboembolic pulmonary disease from an intensive pulmonary embolism treatment center

Abstract Background The diagnosis of Chronic Thromboembolic Pulmonary Disease (CTEPD) following an episode of acute pulmonary embolism (PE) has exhibited inconsistencies across different healthcare institutions, and the issue of underdiagnosis remains unresolved. Purpose The aim of this study is to ascertain the incidence of CTEPD following an episode of acute PE through a follow-up conducted at a specialized PE outpatient clinic located within a PE expert center. Methods and Results In this retrospective study, a cohort of 106 consecutive patients (mean age: 63.7±17.5 years, female: 51.9%) diagnosed with acute PE between March 2015 and August 2020 at our hospital were included. Patients who were capable of visiting the hospital received follow-up care at an outpatient clinic specializing in PE. The diagnosis of CTEPD was established in cases where patients, regardless of the presence of pulmonary hypertension, exhibited chronic-phase dyspnea and demonstrated perfusion defects on lung perfusion scintigraphy. Furthermore, individuals with a mean pulmonary arterial pressure ≥25 mmHg and a pulmonary capillary wedge pressure ≤15 mmHg, as determined by right heart catheterization, were diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH). During the follow-up period (median duration: 27.5 months), 23 patients were diagnosed with CTEPD, and 10 patients were diagnosed with CTEPH. The cumulative incidence rates of CTEPD and CTEPH were as follows: 20.8% and 10.8% at 1 year, 26.9% and 12.7% at 2 years, respectively; and 28.9% at 3 years for CTEPD. Signs of RV dysfunction on CT or Echocardiography may have contributed to the detection of CTEPH and were discussed with respect to parameters indicating RVdisfunction. Conclusions In present study, the cumulative incidence of CTEPD and CTEPH is notably elevated. This results suggest that active surveillance after acute PE follow-up practices may have contributed to an enhanced rate of diagnosis or that chronic PE or CTEPH may have been included at the time of PE diagnosis.Cumulative Incidence of CTEPDCumulative Incidence of CTEPH

Effect of catheter ablation vs medical therapy on cardiovascular outcomes in hypertrophic cardiomyopathy with atrial fibrillation

Abstract Background Atrial fibrillation (AF) increases the risks of stroke and mortality. AF ablation in patients with heart failure (HF) was associated with a lower risk of death and hospitalisation for worsening HF. Whether AF ablation is beneficial to improve cardiovascular outcomes in patients with concomitant hypertrophic cardiomyopathy (HCM) and AF remains unclear. Objective To investigate whether AF ablation is more effective than conventional medical therapy for improving outcomes in HCM. Methods 2,281 patients with HCM and AF undergoing catheter ablation or medical therapy (antiarrhythmic drugs or rate control drugs) in 2005–2015 were identified from the Korean National Health Insurance Service database. The primary composite outcome of death from cardiovascular causes, ischaemic stroke, hospitalization for worsening HF, or acute myocardial infarction was compared between catheter ablation and medical therapy using propensity score overlap weighting. The time-at-risk was counted from the first medical therapy, and catheter ablation was analysed as a time-varying exposure. Results Of the included (41.1% female; median age: 66 years), 145 (6.1%) underwent catheter ablation for AF during the study period. During a mean follow-up of 3.1 (IQR 1.3–5.8) years, a total of 831 composite outcomes occurred including 292 cardiovascular deaths and 401 strokes. Catheter ablation, compared with medical therapy, was associated with lower risks of the primary composite outcome (weighted incidence rate: 3.84 vs. 6.43 per 100 person-years; weighted HR 0.61, 95% CI 0.38–0.96) and ischaemic stroke (weighted HR 0.43, 95% CI 0.19–0.97). The association between ablation and a lower risk of composite outcome was more pronounced in cases of ablation success whereas no significant difference was observed in cases of ablation failure. Conclusions In patients with AF and HCM, catheter ablation was associated with a lower risk of adverse cardiovascular outcomes than medical therapy.

Healthcare utilization in general practice and hospitals preceding a diagnosis of systemic sclerosis: a nationwide registry study.

Irreversible tissue damage is frequently present at the time of diagnosis in systemic sclerosis (SSc), which calls for earlier diagnosis. This study estimated healthcare utilization three years before the diagnosis of SSc. We conducted a population-based cohort study using data from Danish national registries. Incident patients diagnosed with SSc between January 1, 2005, and December 31, 2018, were matched by age and gender with 10 references without SSc. The date of diagnosis was the index date. We estimated quarterly rates and adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CI) of healthcare utilization in the three years preceding the diagnosis for patients with SSc and their references. A total of 1,650 SSc patients (1,255 women and 395 men) and 16 500 non-SSc references were included. The mean age was 58 years (interquartile range 48-68). Three years before diagnosis, patients with SSc had more contacts with general practice (IRRwomen= 1.43 [95% CI: 1.33; 1.53], IRRmen= 1.47 [95% CI: 1.26; 1.71]) and hospitals (IRRwomen= 1.86 [95% CI: 1.62; 2.14], IRRmen= 2.70 [95% CI: 2.04; 3.58]) compared with their references. In the last three months before diagnosis, patients with SSc had significantly more contacts with general practice (IRRwomen= 2.30 [95% CI: 2.16; 2.44], IRRmen= 2.98 [95% CI: 2.64; 3.35]) and hospitals (IRRwomen= 5.62 [95% CI: 5.08; 6.20], IRRmen= 9.53 [95% CI: 7.81; 11.63]). The higher use of healthcare services in general practice and hospitals in the three years before diagnosis suggests an opportunity to facilitate earlier diagnosis and treatment of SSc.

Age-dependent associations with the risk of mental disorders in patients with myocardial infarction: a UK Biobank cohort study

Abstract Background Despite an overall decrease in cardiovascular mortality in recent decades due to effective preventive strategies, a concerning trend is emerging among young adults, with a rising incidence of myocardial infarction (MI) and its poor prognosis. Previous studies report that a significant association between mental disorders and the incidence and prognosis of MI. However, a detailed age-specific information is still lacking. Purpose We aimed to determine whether the risk of developing mental disorders after MI differs based on age and to stratify individuals at a higher risk. Methods From the UK Biobank prospective database (n=502,386), we collected data on patients with a prior MI (n=10,840) and compared them to age- and sex-matched controls (n=54,197) in a 1:5 ratio. Diagnoses of mental disorders were ascertained through linked hospital admission and mortality data, using the appropriate ICD-10-CM codes. Mental disorders were defined by at least two inpatient or outpatient claims within 1 year. The primary outcome was a composite of incident mental disorders, including depression, anxiety, stress-related, and somatoform disorders. Follow-up was done until the first diagnosis of mental disorders or the end of 2022. Results During a median follow-up of 13.7 years (interquartile range 12.8-14.5 years), the incidence rate of the primary outcome was 9.28 vs. 5.37/1,000 person-years among patients with MI and controls, respectively (p<0.001). A prior MI history demonstrated an independent association with the risk of incident mental disorders, yielding an adjusted hazard ratio (aHR) of 1.41 (95% confidence interval [CI], 1.29–1.54; p<0.001) after adjusting for confounders. This was comparable to heavy drinking and family history of depression. Notably, the risk of mental disorders attributed to previous MI was more prominent in younger individuals aged <55 years than their older counterpart (aHR 1.61 vs. 1.33) (p-for-interaction 0.020). Similar results were observed in the analysis of two important components: depression and anxiety disorder. Furthermore, in younger patients with MI (<55 years), mental disorders significantly increased the risk of mortality, while not in older patients. Conclusion MI was associated with a higher risk of incident mental disorders, resulting in poor prognosis, particularly in young individuals. Active surveillance and prevention for incident mental disorders after young MI may be beneficial.Cumulative Incidence of Mental Disorders

Does the presence of severe pulmonary hypertension affect survival at 5 years follow-up in patients who underwent TAVI for severe aortic stenosis?

Abstract Background Pulmonary hypertension (PH) is common in patients with severe aortic stenosis (AS) and is associated with increased mortality after transcatheter aortic valve implantation (TAVI) as well as surgical aortic valve replacement (SAVR). Preprocedural systolic pulmonary artery pressure (sPAP) often improves after TAVI because the most common type of PH is postcapillary PH secondary to left-sided heart disease, which potentially improves after treatment for AS. However, there are limited data regarding the prognostic impact on outcomes after TAVI and their predictors. Purpose The aim of this study is to compare survival at 5 years between patients with severe PH against those who did not have severe PH who underwent TAVI. Methods Between January 2012 until December 2022, we carried out a retrospective study of all patients who underwent TAVI at our hospital. Severe PH was defined as the presence of sPAP >40mmHg on echocardiography. Patients with aortic regurgitation and mixed aortic valve disease were excluded. Co-morbid pulmonary disease was defined as the presence of any significant pulmonary disease including COPD and Asthma. Co-morbid neurological disease was defined as the presence of any significant neurological disease including CVA/ TIA. Diabetes mellitus was defined as per WHO and included patients who were diet, medication and insulin controlled. Survival status and date of death were ascertained from our electronic health records. Counts and incidence rates of clinical outcomes at 5-year follow-up were computed from Kaplan-Meier analysis (See Figure 1). A Cox proportional hazards model was used to compute HRs and 95% CIs for the study outcomes. Results Of the 274 patients available for analysis, 115 (14%) patients had severe PH. The mean age was 84 years in both cohorts whilst patients in the severe PH cohort were frailer by Katz Index Score. Death occurred in 67 patients out of 115 patients who had severe PH and in 87 out of 158 patients who did not have severe PH after a median follow-up time of 4.1 years (58% vs 55%; adjusted HR: 1.04; 95% CI: 0.71-1.51; P = 0.86). Conclusion Our data shows that presence of severe pulmonary hypertension in severe aortic disease patients who had undergone TAVI did not affect survival at 5 years follow up compared to patients without severe pulmonary hypertension undergoing TAVI. Determining predictors of mortality in this high-risk cohort is likely to be complex and multifactorial, owing to the severe multi-comorbidity precluding them from SAVR.

Evaluation of bleeding events in a cohort of patients with transthyretin cardiac amyloidosis

Abstract Introduction and purpose transthyretin amyloidosis is an infiltrative disease with several comorbidities, including bleeding. The aim of this study was to evaluate the incidence of bleeding in patients with transthyretin amyloidosis and the underlying risk factors that promote bleeding. Methods a retrospective observational study was conducted on a cohort of patients with transthyretin amyloidosis diagnosed between 2016 and 2023 according to the diagnostic criteria of the Working Group on Myocardial and Pericardial Diseases of the European Society of Cardiology. Bleeding risk was calculated according to HAS-BLED score and bleeding events at follow-up were analysed. Results 184 patients were diagnosed with a median age of 84 years [IQR 79-8], 154 (8%) males. 123 patients (67%) were on anticoagulant therapy. 91 patients (50%) had a bleeding event, with a total of 189 events recorded and a median time from transthyretin amyloidosis diagnosis to bleeding of 10 months [IQR 6-14]. The most frequent bleeding sites were gastrointestinal (32%) and cutaneous (22%). 35 patients (39%) had a haemorrhage which fulfilled severe bleeding criteria and 4 patients died of haemorrhagic causes. As a consequence of bleeding, 6 atrial appendage closure were indicated and anticoagulation therapy was modified in 15 individuals. The incidence rate of haemorrhage was 50 bleeds per 100 patient-years and 58 per 100 patient-years in patients on anticoagulant treatment. Anticoagulant therapy resulted in a 3,5-fold raise in bleeding (95% CI 2-7) and a punctuation ≥2 in HAS-BLED score increased haemorrhages 4,6 times (95% CI 2-9), with higher rates of bleeding the higher the score on the scale. Conclusions bleeding is a frequent complication in transthyretin amyloidosis, with a higher risk in those individuals with anticoagulant therapy or with a HAS-BLED score ≥2. Subsequently, it should be considered in the follow-up both haemorrhagic risk and anticoagulant treatment, with the aim of implementing strategies to reduce the bleeding risk.