Death Registry Research Articles

Addressing disparities in the long-term mortality of non-ST segment myocardial infarction (NSTEMI) patients according to the presence of diabetes mellitus: a nationwide cohort study

Abstract Background Diabetes mellitus (DM) is an important risk factor for non−ST segment elevation myocardial infarction (NSTEMI). How DM is related to management and longer-term clinical outcomes in contemporary NSTEMI cohorts is not well described. Methods and Results We analysed data on 456,376 adults hospitalised with NSTEMI from the United Kingdom Myocardial Ischaemia National Audit Project (MINAP) registry, linked with Office for National Statistics (ONS) death registry. We compared outcomes and quality of care by DM status. People with DM were older (median age 74 vs. 73 years, p<0.001) and more commonly of Asian ethnicity (13% vs. 4%, p< 0.001). Those with DM underwent invasive coronary angiography (59% vs. 63%, p <0.001) or revascularization (PCI or CABG) (38% vs. 40%, p <0.001) less frequently. Mortality risks for people with DM were significantly higher at 30-days (HR: 1.06, CI; 1.04-1.09, p <0.001), 1-year, (HR: 1.17, CI; 1.15-1.18, p <0.001) and 5-years, (HR: 1.25, CI; 1.24-1.26, p <0.001), when compared to people without DM. In people with DM, higher-quality inpatient care, assessed by opportunity-based quality-indicator score category (OBQI; poor, fair, good or excellent), was associated with lower mortality rates (good: HR 0.70, CI 0.67-0.73, P<0.001; excellent: HR 0.59, CI 0.57- 0.62, P<0.001), when compared to people receiving poor quality care. In people with DM, "excellent-care", compared to those receiving poor quality care, was associated with the lowest mortality in diet-treated or insulin-treated subgroups (diet-treated: HR 0.55, CI 0.50-0.61, P<0.001)(insulin-treated: 0.60 CI 0.56-0.64, P<0.001). Conclusion People with DM experience wide disparities in inpatient care following NSTEMI. They have a higher risk of long-term mortality compared to people without DM, with some evidence that better quality inpatient care is linked to better survival.

Genetic and lifestyle risks for coronary artery disease and risk of incident dementia

Abstract Background Lifestyle risk factors for coronary artery disease (CAD) have been associated with neurodegeneration and dementia. Whether an underlying genetic risk for the development of CAD further increases this risk, however, remains unclear. Purpose To examine whether an increased genetic risk for CAD is associated with an increased risk of dementia, and to investigate whether lifestyle factors modify these associations. Methods A prospective cohort study of 457,353 participants of European ancestry without dementia at baseline (mean [SD], age 57 [8] years; 55% were female) was conducted within the UK Biobank study. Exposures were a genome-wide polygenic risk score (PRS) for CAD and a modified version of the American Heart Association’s Life’s Essential 8 (LE8) cardiovascular health score comprising four biological (BMI, BP, lipids, glucose) and four lifestyle (smoking status, diet, physical activity, and sleep duration) risk factors previously linked to both CAD and dementia. Dementia diagnoses were obtained from death register and inpatient records. Results 9,337 cases of all-cause dementia were observed over a median 13.9-year follow-up. There were no significant interactions between genetic risk for CAD and lifestyle factors for all-cause dementia, or any other dementia subtype. After adjusting for potential demographic confounders, a higher genetic risk for CAD was associated with elevated risk of developing all-cause dementia (hazard ratio (HR) per 1-SD increase in PRS = 1.08 [95% CI, 1.05-1.10]), Alzheimer’s disease (HR 1.08 [1.03-1.12]), and vascular dementia (HR 1.13 [1.06-1.19]). An unfavourable LE8 cardiovascular health score was also associated with an increased risk of developing all-cause dementia (HR 1.05 [1.02-1.08]), predominantly through its association with vascular dementia (HR 1.14 [1.06-1.22]), as we found no evidence for any associations between LE8 and Alzheimer’s disease (HR 1.00 [0.97-1.02]). Conclusion These findings indicate that a high genetic risk for CAD is associated with an increased risk of developing major dementia subtypes. Regardless of this underlying genetic risk, however, our results suggest that lifestyle interventions designed to reduce the risk of CAD may also reduce one’s risk of developing dementia, particularly in those with underlying vascular pathology.

Propensity score-matched analysis in isolated left ventricular dilation and non-ischaemic dilated cardiomyopathy

Abstract Background The presence and extent of late gadolinium enhancement (LGE) assessed by cardiac magnetic resonance imaging (CMR) are strong prognosticators of death in patients with non-ischaemic dilated cardiomyopathy (DCM), defined by the current guidelines as left ventricular (LV) dilation and left ventricular ejection fraction (LVEF)<50%. Although the current guidelines defined the concept of "isolated LV dilation" as LV dilation with preserved LVEF≥50%, the prognostic value of the LGE granularity including its extent, location and pattern is not established in this population. Purpose To assess the prognostic value of the concept of "LGE granularity" including its extent, location, and pattern for predicting all-cause death above traditional prognosticators in patients with LV dilation and reduced LVEF (i.e. DCM) or preserved LVEF (i.e. isolated LV dilation), separately. Methods Between 2008 and 2021, all consecutive patients with DCM and isolated LV dilation without ICD or history of sustained ventricular arrhythmia referred for CMR were included in two centres. All patients with history of coronary artery disease or myocarditis were excluded. The primary outcome was all-cause death using the French National Registry of Death. A 1:1 propensity score matching was performed to balance baseline characteristics in patients with DCM vs. those with isolated LV dilation. Cox regressions were performed to determine the prognostic value of each LGE findings. Results Of 2,752 patients analysed (age 52±8 years, 56% male), 408 (15%) patients died after a median (interquartile range) follow-up of 9 (7-12) years. A total of 737 (27%) patients had LGE. Patients with DCM had a higher rate of death than patients with isolated LV dilation (16% versus 13%, p=0.02). In the propensity-score matched population (N=1,084 in DCM subgroup and N=1,084 in isolated LV dilation), the LGE presence was associated with death (HR=2.98, 95%CI: 1.97-4.50, p<0.001). In isolated LV dilation patients with LGE (N=265), the LGE extent (HR=1.41, 95%CI:1.09-1.83, p=0.009), the presence of LGE in multiple areas (HR=3.86, 95%CI: 1.73-8.61, p<0.001) and the septal location (HR=2.97, 95%CI:1.37-6.46, p=0.006) were strong prognosticators of death after adjustment for traditional prognosticators. Similarly, in DCM patients with LGE (N=268), the LGE extent (HR=1.42, 95% CI:1.07-1.89, p=0.014), the presence of LGE in multiple areas (HR=8.41, 95%CI: 3.32-21.3, p<0.001) and the septal location (HR=6.65, 95% CI: 3.02-14.6, p<0.001) were strongly associated with death after adjustment. Conclusion In a large cohort of DCM and isolated LV dilation patients, the concept of "LGE granularity" was independently associated with all-cause death after adjustment for all traditional prognosticators in both DCM and isolated LV dilation. These results suggest the existence of a continuum between isolated LV dilation and DCM, and that CMR assessment could improve the risk stratification in this population.

Improving prognostic accuracy in ischemic cardiomyopathy: the CMR-LGE score

Abstract Background There is a need for accurate prognostic stratification tools in patients with ischemic cardiomyopathy (ICM). Several studies have shown the considerable impact of cardiac magnetic resonance (CMR) imaging findings notably late gadolinium enhancement (LGE) but an easy interpretable score to guide clinical practice is lacking. Purpose To determine the CMR parameters most predictive of mortality in a cohort of ICM patients with left ventricular ejection fraction (LVEF) less than 50%, and then to develop a readily interpretable score based on these parameters. Methods Between 2008 and 2022, all consecutive patients with a history of ICM with LVEF<50% and presence of ischemic LGE on viability CMR examination, were recruited by two independent centers. The primary outcome was all-cause death using French National Registry of Death. The first center (N=2,900) was designated as the derivation cohort for variable selection and score development, and the second center (N=691) was used as the validation cohort to evaluate the performance of the final score. Thirty-two variables (17 clinical and 15 CMR) were initially assessed. Automatic feature selection was performed using a machine-learning approach with a Random Survival Forest (RSF) algorithm. Using the selected variables, our proposed score, the CMR-LGE score, was derived from coefficients of the Cox regression. Performance evaluation on the validation cohort was conducted using Harrel’s C index compared with traditional prognostic factors associated with poor outcomes in ICM. Categories for the prognostic score were identified using a survival conditional inference tree analysis on the derivation cohort, aiming to maximize the log-rank score. Results Among the 3,591 patients included (mean age 65±12 years; 75% male; mean LVEF 44±6%), 549 (15.3%) died over a median follow-up of 9 (interquartile range: 7–12) years. Feature selection with RSF highlighted that the most important variables to predict death were LGE variables: the extent, the location (septal and anterior) and the transmurality of ischemic LGE as well as the extent of additional midwall LGE (Figure 1). Following these findings, we developed the CMR-LGE score by rounding the coefficient of a Cox regression (Figure 2A). Harrel’s C index of CMR-LGE score outperformed traditional prognostic factors, including LVEF (0.88 vs 0.69). Finally, based on our CMR-LGE score, we identified a low-risk population (CMR-LGE score below 6) and a high-risk population (CMR-LGE above 8), validated using survival curves in the validation cohort (Figure 2B). Conclusion Using RSF, we identified that the 5 most important CMR variables to predict mortality in ICM were all LGE features. Our CMR-LGE score showed excellent performance to stratify patient risk compared to traditional prognostic factors including LVEF.Variable selectionModel building and evaluation

Incremental prognostic value of late gadolinium enhancement granularity in patients with hypertrophic cardiomyopathy

Abstract Background The prognostic stratification of hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance (CMR) is based on the extent of late gadolinium enhancement (LGE). To enhance risk stratification for sudden cardiac death (SCD), the ESC has recently added LGE extent in the guidelines, at ≥15% of LV mass. However, SCD has become an uncommon event in this population, and mortality is now mostly related to other phenotypes, such as atrial fibrillation, stroke, and heart failure. While previous studies have showed the prognostic value of LGE to predict all-cause mortality, the prognostic impact of additional LGE features is not well established. Therefore, we aimed to assess the incremental prognostic value of the granularity of LGE including extent, location, and pattern in patients with HCM to predict all-cause death. Methods Between 2008 and 2021, all patients referred for HCM assessment using CMR, without history of coronary artery disease (CAD) or clinical history of myocarditis were prospectively recruited in two French centers. The outcome was all-cause death using the French National Registry of Death. The concept of "LGE granularity" was defined as a comprehensive model combining all the following LGE features with extent (by segment), location (septal or others), and pattern (midwall and/or subepicardial). Using nested Cox proportional hazard models, the additional predictive value of LGE features was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), the integrative discrimination index (IDI) and the global Chi-2. Results Among the 2,672 included patients (52±7 years, 56% males), 862 (32%) had LGE. After a median (IQR) follow-up of 9 (7–11) years, 447 (17%) patients died. Survival curves show an increased risk for LGE presence (log-rank p<0.001, Figure 1A). After adjustment for traditional prognosticators in the overall population (N=2,672), the presence of LGE was strongly associated with all-cause death (adjusted hazard ratio (HR) 3.96, 95% CI: 3.26-4.80, p<0.001). In the subgroup of patients with LGE (n=862), survival curves showed that all parameters defining the LGE granularity were associated with a higher risk of all-cause death (all p<0.001, Figure 1B). A nested Cox model adjusted on traditional prognosticators showed that the LGE extent, location and pattern were all independently associated with all-cause death (all p<0.001, Figure 2). The model of "LGE granularity" combining all independently significative LGE features showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.90; NRI=41.9%; IDI=13.2%, Chi-2 global=450, all p<0.001; LR-test p<0.001, Figure 2). Conclusion In a large cohort of HCM patients, the "LGE granularity" model combining the extent, location, and pattern of LGE had an incremental prognostic value over and above traditional prognosticators to predict all-cause death.Prognostic value of LGE granularityIncremental prognostic value LGE granula

Prognostic impact of the concept of late gadolinium enhancement granularity in non-ischaemic dilated cardiomyopathy

Abstract Background The prognostic stratification of non-ischaemic dilated cardiomyopathy (DCM) to predict the risk of death is mainly driven by the left ventricular ejection fraction (LVEF). Indeed, LVEF<35% is currently the only indication for primary prevention with implantable cardioverter-defibrillator (ICD) in these patients. Beyond LVEF, several cardiac magnetic resonance imaging (MRI) studies have suggested the strong prgnostic impact of late gadolinium enhancement (LGE), and particularly its extent and location. Therefore, we assumed that a more granular approach combining detailed LGE findings including extent, location and pattern could improve risk stratification in this population. Purpose To assess the additional prognostic value of the concept of "Late Gadolinium Enhancement (LGE) Granularity" that includes extent, location, and pattern in non-ischaemic dilated cardiomyopathy (DCM) patients to predict all-cause death. Methods Between 2008-2021, all consecutive patients with DCM without ICD or history of sustained ventricular arrythmia referred for cardiac MRI were included in two French centres. In line with the current ESC and AHA guidelines, DCM was defined by the LV dilation and LVEF< 50% using cardiac MRI. All patients with history of coronary artery disease or clinical history of myocarditis were excluded. The primary outcome was all-cause death using the French National Registry of Death. Cox regressions were performed to determine the prognostic value of each LGE findings. The additional prognostic value of the LGE granularity was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), and the integrative discrimination index (IDI). Results Of 1,668 DCM patients (age 52±8 years, 54% males), 268 (16%) died after a median (interquartile range) follow-up of 9 (7-12) years. With a median LVEF value of 39% (30-46), 472 (28%) patients had non-ischemic LGE. Using survival curves, patients with LVEF>35% but the LGE septal location showed a higher risk of death compared to all patients with LVEF≤35% with or without LGE (except for the septal location, all p<0.001). In DCM patients with LGE (N=472), LGE extent (adjusted HR: 4.27, 95% CI: 2.22-8.22), septal location (HR: 5.74, 95% CI: 3.35-9.85) and multiple areas of LGE (HR: 4.38, 95% CI: 2.08-9.22; all p<0.001) were all independently associated with death after adjustment for prognosticators. The concept of "LGE granularity" combining all these LGE features showed the best improvement in model discrimination and reclassification over traditional prognosticators including LVEF (C-statistic improvement: 0.14; net reclassification improvement=64.3%; integrative discrimination index=29.0%; all p<0.05). Conclusion In a large cohort of DCM patients, the concept of "LGE granularity" combining LGE extent, location and the presence of multiple areas had an additional prognostic value above traditional prognosticators including LVEF to predict all-cause death.

Time trends in mortality, incidence and case-fatality of acute myocardial infarction in Norway - do we see the end of the coronary heart disease epidemic?

Abstract Background In Norway and most industrialized countries the mortality rates from acute myocardial infarction (AMI) increased after World War II, peaked in the 1960s – 1970s, and have since that time declined (Figure). Recent studies have suggested that the decline may have leveled off, and that the favourable trends do not include younger age groups, possibly due obesity and diabetes. Also, the relative contribution of a reduction in incidence and improved case-fatality rates (CFR) to the AMI mortality trends are not known with certainty. We examined mortality trends of AMI in Norway during 1951 – 2021, and the incidence and CFR of hospitalized and non-hospitalized AMI during 2013-2021. Methods Fatal AMI cases were identified in the National Causes of Death Registry. Norwegian hospitals are required by law to register all patients hospitalized for AMI in the Norwegian AMI Registry. Hospitalized cases not registered in the AMI registry were retrieved from the Norwegian Patient Registry which contains discharge diagnoses for hospitalized patients. The national unique 11-digit identification number allowed linkage of the registries and identification of transfers between hospitals and re-hospitalizations. An AMI (either hospitalization or death) was classified as incident if no hospitalization was found for that individual during the previous 5 years. We calculated age-adjusted rates with the Norwegian population in 2017 as standard. Results Norwegian AMI mortality rates increased from 1951, peaked in the late 1960s, and have since that time declined steadily, although steeper after around 1990 (Figure). Present AMI mortality rates are lower than in the 1950s, and are still declining. Incidence of AMI (hospitalized and non-hospitalized) fell from 391/100 000 in 2013 to 271/100 000 in 2021, corresponding to a mean reduction of 3.6 % per year (p<0.001). Incidence of out-of-hospital fatal AMI fell by 6.5 % per year, incidence of hospitalized ST-segment elevation AMI (STEMI) fell by 2.3 % per year, and incidence of non-ST-segment elevation AMI (NSTEMI) fell by 3.1 % per year (all p<0.001). 30-days CFR of hospitalized and non-hospitalized AMI fell from 21.3 % in 2013 to 17.5 % (3.6 % per year; p<0.001). CFR after NSTEMI fell from 8.2 % in 2013 to 6.4 % in 2021 (4.4 % per year; p<0.001), whereas there was no significant change in CFR after STEMI (13.3 % in 2013 and 12.0 % in 2021). The incidence and CFR trends were similar in men and women aged 20-49, 50-79 and 80+ years. Comments Declining incidence of out-of-hospital fatal AMI and declining incidence of hospitalized STEMI and NSTEMI were major contributors to the declining AMI mortality rates in Norway. Improved case-fatality rates among hospitalized patients have contributed to the declining mortality rates, but there was no improvement in case-fatality in STEMI during 2013-2021.

External validation of the Systematic COronary Risk Evaluation 2 (SCORE2) model in cancer patients

Abstract Background Guidelines recommend cardiovascular disease (CVD) risk stratification before cancer treatment to better identify patients for intensified follow-up or cardioprotective treatment. Only a limited number of CVD risk stratification tools exists for cancer patients which at present is not widely used nor extensively validated. The ESC Guidelines on Cardio-oncology 2022 suggest using traditional CVD models like the SCORE2 (Systematic Coronary Risk Estimation 2). However, external validation in cancer populations is lacking. Purpose Our aim was to study the prevalence of CVD risk factors and incidence of cardiovascular events in a cancer cohort and externally validate the Systematic COronary Risk Evaluation 2 (SCORE2) model in this context. Methods We included 1058 patients from a large-scale populational study without diabetes or established CVD aged 40 to 69 years and diagnosed with cancer between 2006 and 2012. Participants were assessed for cardiovascular risk factors at baseline and followed until Sept 2023. The Norwegian Cancer Registry provided patient specific information about cancer characteristics and therapy. The primary outcome was the combination of myocardial infarction (MI), stroke or CVD mortality, which was retrieved from the local hospitals’ registries and the national causes of death registry. Performance was assessed using smooth calibration curves of predicted and observed risk and Harrel’s C-statistic for discrimination, both corrected for competing risks. SCORE2 was recalibrated by adapting the model with a single multiplicative constant based on the expected-to-observed ratio (E/O-ratio). Results The most common cancer types were gastrointestinal cancer (19%), male genital including prostate cancer (19%) and breast cancer (18%). Mean (SD) age was 58.6 (7.6) years, 54% were female. Prevalence of cardiovascular risk factors are shown in Table 1. In total, 121 (11%) individuals had a CVD event (MIs 53 (44%), strokes 46 (38%) and CVD deaths 22 (18%)) during a median (interquartile range) follow-up of 11.1 (3.4 to 13.1) years, and 360 (34%) died due to non-CVD causes. Calibration plots showed adequate agreement between estimated and observed 10-year prognosis after recalibration (C-statistics 0.685, 95% CI 0.643 to 0.728), Figure 1. E/O-ratio for men was 0.65 and for women 0.63, indicating underestimation of the observed CVD incidence. After recalibration, the median estimated 10-year risk was 8.1% (IQR 5 to 11), 36% had >10% 10-year risk and 9% had >15% 10-year risk. Conclusion SCORE2 underestimated CVD risk in a general cancer population but showed adequate agreement after recalibration and C-statistics aligned with the original external validation cohorts. SCORE2 is useful also in cardio-oncology setting (after recalibration) to identify individuals at higher risk of developing CVD.

Comorbidities and risk of death in atrial fibrillation: a nationwide cohort study

Abstract Background Atrial fibrillation (AF) is associated with increased mortality, cardiovascular morbidity, and risk of stroke. With aging population, the number of AF patients is increasing, and they present with more comorbidities representing a major public health challenge. Purpose The influence of concomitant diseases on survival of patients with AF is not well established. Using data from a comprehensive nationwide cohort study, we studied the influence of several comorbidities on one-year mortality after the diagnosis of new-onset AF. Methods All patients with newly diagnosed AF in Finland 2007-17 were identified from nationwide registries. Individualized data on concomitant diseases were gathered from ICD-10 diagnoses during hospitalizations and outpatient visits in primary and specialist care and from drug reimbursements registries. Patients were followed until the end of 2018 from the causes of death registry, which records every death in the country. All-cause mortality associated with several comorbidities per 1000 person-years was determined, and relative risk (RR) of death was calculated. Results A total of 229,321 patients (mean age 73 ± 13.2 years, 50.0% male) with new-onset AF were identified. Mean age of men and women with new-onset AF was 69.4 ± 13.4 and 77.1 ± 11.8 years, respectively. During the one-year follow-up, 11.6% of men and 13.7% of women died. Heart failure, kidney disease and dementia were the strongest predictors of mortality and were associated with an over threefold risk of death within one year. Cancer, history of bleeding and vascular disease carried over twofold risk of death. In addition, hypertension, diabetes, alcohol abuse and history of stroke predicted mortality. The risk of death associated with these comorbidities is presented in Table. Conclusions Several comorbidities were associated with significantly increased risk of death within one year of the AF diagnosis. Heart failure, kidney disease and dementia were strongest predictors of subsequent mortality with over threefold risk. These data will inform the treatment decisions regarding AF patients with comorbidities.

The annual trend of suicide rates from 2010 to 2021 in patients with cannabis use disorder – a national registry study

Abstract Purpose The temporal trend of suicide in patients with cannabis use disorder (CUD) is important to investigate, considering the recent increases in THC concentration in cannabis products. This study describes the annual suicide rates in patients with CUD from 2010 to 2021. To investigate if any change in suicide rate was specific to CUD, we compared these suicide rates with corresponding data for patients with alcohol use disorders (AUD) and other substance use disorders (SUDs). Method The study used a time series design. We used a national registry linkage between the Norwegian Cause of Death Registry and the Norwegian Patient Registry from 2010 to 2021, including patients with CUD (ICD-10 code F12), AUD (F10), or other SUDs (F11; F13-F16; F18-F19) who died by suicide, supplemented with the total number of patients treated with specific disorders to estimate the suicide rates. The trend was analyzed by comparing the annual suicide rate to 2010 and using Poisson regression, adjusting for gender, age, and mental disorders. Results We found increased annual incidence rate ratios for patients with CUD in 2018 (IRR = 2.14 (95% CI 1.14–3.99)) and onwards and an increasing time trend over the study period (IRR = 1.08 (1.05–1.12)). No increases in trends were found for AUD or other SUDs. The time trend for CUD was attenuated when adjusting for depressive or anxiety disorders (aIRR = 1.00 (0.92–1.08)) or other SUDs (aIRR = 0.96 (0.87–1.06)). Conclusions Increasing suicide rates were found in patients with CUD. Comorbid anxiety and depression or other SUDs, but not other mental disorders, could partly explain these results.

Clinical characteristics and long-term outcomes of patients with heart failure with supra-normal ejection fraction: data from LECRA-HF registry

Abstract Background Heart failure with preserved ejection fraction (HFpEF) remains insufficiently characterized subgroup of HF with increasing prevalence and limited treatment options. Relationship between clinically assessed left ventricular ejection fraction (LVEF) and survival showed that LVEF ≥65% is associated with higher mortality. Therefore, a novel category of heart failure with supra-normal left ventricular ejection fraction (HFsnEF) was introduced in 2019. However, clinical characteristics and long-term outcomes of HFsnEF patients remain insufficiently elucidated. Purpose We sought to characterize Polish HFsnEF patients and to provide their long-term mortality in comparison to HFpEF. Methods Of 1186 patients enrolled in the single-center Lesser Poland Cracovian Heart Failure (LECRA-HF) Registry between 2009 and 2019 and hospitalized due to HF decompensation 261 (22%) of them were those with LVEF ≥50%. 40 (15.3%) of them were classified as HFsnEF (LVEF ≥65%) and the remaining 221 (84.7%) as HFpEF. The data including patients’ demography, anthropometric measurements, cardiovascular risk factors, prior cardiological treatment and other comorbidities were collected. The long-term follow-up of all-cause mortality was obtained from the Polish National Death Registry. Results HFsnEF patients were less frequently hypertensive (75 vs 88.2%, P=0.026) and had higher baseline LVEF (65 [65-70] vs 55 [50-60] %, P<0.001) than HFpEF subjects. Furthermore, HFsnEF patients presented lower INR (1.1 [1-1.6] vs 1.3 [1.1-1.9], P=0.027) and total protein level (57 [25-63] vs (65.2 [60.2-69.9] g/L, P=0.008) on admission. HFsnEF patients were less frequently treated on discharge with mineralocorticoid receptor antagonists (25 vs 46.2%, P=0.013) as well as loop diuretics (60 vs 76%, P=0.017). The Kaplan-Meier analysis showed that all-cause mortality is higher in HFsnEF than in HFpEF (65.0 vs 55.2%, P=0.044, Figure 1). The independent predictors of long-term mortality were age and diagnosis of HFsnEF (HR 1.037, 95% CI 1.018-1.056 and HR 1.665, 95% CI 1.063-2.608, respectively). Conclusions Our findings indicate that every seventh Polish patient admitted with HFpEF could be classified as HFsnEF. Baseline characteristics of HFsnEF patients are different than HFpEF. Simultaneously, the HFsnEF diagnosis is associated with lower long-term survival.

The association between left ventricular mass index and all-cause mortality

Abstract Background Left ventricular hypertrophy (LVH) has been associated with a higher risk of all-cause mortality. However, there is a lack of optimal cut-off values for grading the severity of LVH in the general population. Purpose We aim to investigate the association between the left ventricular mass index (LVMi) estimated by echocardiography and all-cause mortality and determine the optimal cut-off values of LVMi for the general population to predict outcomes. Methods Consecutive participants undergoing echocardiography in a tertiary medical center in Taiwan during 2005-2021 were enrolled. LVMi was calculated using the cube formula from the linear method. The primary outcome was all-cause mortality by linking to the National Death Registry. The association between LVMi and all-cause mortality was assessed using the joinpoint linear regression analysis to derive the optimal cut-off values for LVMi. Using the Kaplan-Meier methods, we validated our results with a community-based cohort with a long-term follow-up period. Results 85,503 participants (age 64.3 ± 16.9 years, 53.7% men) were enrolled. During a mean follow-up of 67.6 ± 48.5 months, there were 14,565 deaths (17%). A U-shaped relationship between LVMi and the risk of all-cause mortality could be observed. The joinpoint linear regression analysis revealed that LVMi could be categorized into the following groups (less than 66 gm/m2, 66-87 gm/m2, 88-132 gm/m2, 133-170 gm/m2, and more than 171 gm/m2), with each group representing a different risk for all-cause mortality. (Figure 1) In the validated cohort categorized by the cut-off values of LVMi, the Kaplan-Meier analysis showed divergent risks for all-cause mortality between different groups in the community-indwelled populations (Figure 2, log-rank P-value< 0.001). Conclusion There was a U-shaped relationship between LVMi and the risk of all-cause mortality. Grading for the severity of LVH using the LVMi is warranted for the risk assessment in the general population.Figure 1Figure 2

External validation of the HFA-ICOS risk stratification tool for prediction of cardiovascular complications after cancer treatment

Abstract Background The 2022 ESC Guidelines on Cardio-oncology recommends using the HFA-ICOS (Heart Failure Association and the International Cardio-Oncology Society) four-category risk stratification tool to predict risk of heart failure (HF) and other cardiovascular disease (CVD) complications during and after cancer therapy. However, the actual risk associated with assignment to these categories is unknown. Purpose We aimed to assess the prognostic performance the HFA-ICOS risk stratification tool in a large cancer subpopulation of a general health survey linked to Norwegian health registries. Methods Participants in a large-scale population study diagnosed with cancer between 2006 and 2012 were included (n=2290) and followed for CVD endpoints until Sept 2023. CVD risk factors were measured at baseline between 2006 and 2008. The Norwegian Cancer Registry provided detailed information about cancer characteristics and therapy. We retrieved CVD endpoints from the local hospitals’ registries and the national causes of death registry. Kaplan Meier survival curves were used to estimate the risk of the combined endpoint of HF hospitalization, myocardial infarction (MI), stroke and CVD death, as well as HF hospitalization alone and non-CVD death. Harrel’s C-statistic was used to validate the discriminative abilities. Results Mean (SD) age was 65.8 (12.4) years, 48% were female, cancer types and cardiovascular risk factors are shown in Table 1. During a median (interquartile range) follow-up of 6.9 (1.4 to 12.2) years, there were 460 first CVD events (HF hospitalizations 87 (19%), MIs 161 (35%), strokes 130 (28%), CVD deaths 82 (18%)) and 1003 (44%) non-CVD deaths. When applying the HFA-ICOS tool, 649 (28%) were assigned to the low-risk category, 912 (40%) to medium, 661 (29%) to high-risk and 68 (3%) to the very high-risk category. Between the HFA-ICOS risk categories, there were clear differences in the observed risk of CVD events, HF hospitalizations and non-CVD mortality (Figure 1). CVD incidence was highest in the highest HFA-ICOS risk categories (7% in the low risk group, 21% in the medium risk group, 31% in the high risk group and 37% in the very high-risk group (p-value <0.001)). C-statistics for predicting CVD events was 0.696 (95% CI, 0.674 to 0.718). When only assessing patients with HF hospitalizations as (first) outcome (n=116), the risk of HF was higher in the high and very high-risk groups (0% in the low risk group, 4% in the medium, 9% in high and 21% in the very high risk group (C-statistics 0.794 (95% CI, 0.762 to 0.827)). Conclusion The HFA-ICOS baseline risk assessment was useful to identify patients at risk of both clinical overt heart failure and other major CV complications and non-CV death in a population with a variety of cancers. These results can help communicate absolute risks to cancer patients, which may be helpful in the shared decision-making for cardioprotective treatment and intensified follow-up.

Weekend compensatory sleep is associated with reduced risk of heart disease: a prospective UK Biobank-based cohort study

Abstract Background and Aims Influenced by the demands of school or work, people often fall out of sync with their circadian rhythms, which leads to sleeping in on days off. Despite this phenomenon, there is a lack of research examining whether compensatory weekend sleep has positive effects on heart health. Methods and results Our prospective cohort study utilized data from the UK Biobank (UKB) and encompassed 90,903 participants. To evaluate the relationship between compensated weekend sleep and heart disease. The sleep data was recorded by Axivity AX3 accelerometer from UKB and grouped by quartiles. Hospitalization records and cause of death registry information were used to diagnose various cardiac diseases including IHD, HF, AF, and stroke. Then multivariate Cox proportional hazard modeling was used to examine the potential impact of compensated sleep on the risk of heart disease. At a median follow-up time of up to 13.8 years, we found that participants in the compensatory sleep group(Q4) had a lower risk of having heart disease in the fully adjusted model (HR: 0.809, 95%CI: 0.766,0.854), which was not influenced by the effect of genetic risk for IHD, HF, or AF. These relationships were even more pronounced in the subgroup with daily sleep deprivation (HR:0.801, 95%CI: 0.718,0.894). Conclusion Sufficient compensatory sleep on weekends is linked to a low risk of heart disease, including IHD, AF, HF, and stroke, which is independent of genetic risk. And the association becomes even more pronounced among individuals who regularly experience inadequate sleep on weekdays.Visual abstract

Left ventricular ejection fraction and clinical outcomes after transcatheter aortic valve implantation

Abstract Background Reduced left ventricular ejection fraction (LVEF ≤50%) has been associated with poor prognosis in patients with severe aortic stenosis treated medically or with aortic valve replacement. However, less is known regarding the impact of different degrees of LVEF including moderately to severely reduced LVEF after transcatheter aortic valve replacement (TAVR). Purpose To examine the association between baseline LVEF and clinical outcomes after TAVR. Methods Patients undergoing TAVR between 2008-2021 from the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY) were included. LVEF was estimated from echocardiography before TAVR and categorized as ≥50%, 40-49%, 30-39% and <30%. SWENTRY was linked to the National Patient Registry and Cause of Death Registry for outcome variables. Patients were followed for a median of 3.2 years for the primary outcome heart failure hospitalizations and the secondary outcome all-cause mortality. Cox regression analyses adjusted for age, sex, BMI, atrial fibrillation, eGFR class, diabetes, hypertension, frailty, chronic pulmonary disease and coronary artery disease were performed for the association between LVEF groups and outcome. Results In total, 8686 patients were included (mean age 81 years, 47% female) of whom 5904 (68%) patients had LVEF ≥50%, 1342 (15%) had LVEF 40-49%, 906 (10%) had LVEF 30-39% and 534 (6%) had LVEF <30%. Significant differences were observed across the LVEF groups in the cumulative incidence rates of heart failure hospitalizations (19, 30, 37 and 43%; p<0.001) and all-cause mortality (41, 54, 55, 57%; p<0.001) at five years. In adjusted analyses there was a stepwise increase in the risks of heart failure hospitalizations (Figure 1A) and all-cause mortality (Figure 1B) for each respective LVEF category. Conclusion Reduced LVEF, especially LVEF <30%, was associated with a dramatically increased long-term risk of heart failure hospitalizations and all-cause mortality in patients undergoing TAVR. LVEF should be considered in risk stratification and patient selection for TAVR.

Impact of body mass index on aortic valve stenosis and its clinical outcomes in early adulthood: a long-term study of young men

Abstract Aims Studies investigating associations between body mass index (BMI), incidence of aortic valve stenosis (AVS), and clinical outcomes in AVS patients are scarce. Purpose To investigate the relationship between BMI in youth and subsequent diagnosis of AVS. A secondary aim was to determine the role of obesity in clinical outcomes in individuals diagnosed with AVS. Methods This was a nationwide, register-based cohort study of 1 701 390 men (mean age, 18.3 ±0.8 years) enrolled in compulsory conscription for military service in Sweden from 1969 through 2005. Anthropometrics, blood pressure, fitness, muscle strength and IQ were recorded at baseline. AVS cases and cardiovascular outcomes were identified according to the International Classification of Diseases (ICD)-10 registered in the National patient register and Cause of Death Register through the Swedish 12-digit personal identification number. BMI (kg/m2) was categorized as <18.5, 18.5–<20, 20–<22.5, 22.5–<25, 25–<27.5, 27.5 <30, 30–<35, and 35–<50 kg/m2. Cox proportional hazard models were used to estimate the association between adolescent BMI and future hospitalization for AVS while adjusting for potential confounders. The BMI reference was set as 20–<22.5. Those who developed AVS formed a subcohort that was followed until a first clinical cardiovascular outcome of death, cardiovascular mortality, Heart failure, Atrial fibrillation, myocardial infarction, or ischaemic stroke. Results During a median follow-up of 32 years (IQR, 24-41 years), 5766 cases (mean age 54.7±9.4 years) of AVS were diagnosed. After adjustment, underweight subjects with a BMI of <18.5 kg/m2, compared to those with a low-normal BMI (20.0–<22.5 kg/m2) showed lower risk (HR 0.70; 95% CI 0.61–0.80) of AVS. The multivariable-adjusted HR for AVS increased from HR 1.28; 95% CI 1.17–1.39 for BMI 22.5–<25 kg/m2 to HR 1.91; 95% CI 1.12–3.25 for those with BMI 35–50 kg/m2. Further on, individuals diagnosed with AVS were followed for a median of ~5.5 years. The multivariable-adjusted HR for all-cause mortality, cardiovascular mortality, and heart failure for obese (BMI 30–50 kg/m2), compared to BMI <20.0 kg/m2 in men diagnosed with AVS, were 4.69 (95% CI 2.61–8.44), 4.09 (95% CI 1.72–9.73), and 2.76 (95% CI, 1.36–5.60), respectively. Conclusions Elevated BMI in youth, even within the normal range, is associated with increased risk of developing AVS, while subnormal BMI was protective. Excess weight in youth diagnosed with AVS is associated with higher risk of subsequent clinical outcomes. These findings are novel, generating new questions as to potential mechanisms and implying more vigilant monitoring of patients with AVS and a history of obesity in youth.Figure 1Figure 2

Antithrombotic treatment in univentricular heart

Abstract Background Univentricular heart (UVH) corrected with Fontan surgery may be associated with an increased risk of thrombosis. Data regarding optimal thrombotic prevention strategy after Fontan surgery in patients with UVH is scarce, and guidelines for antithrombotic treatment are not yet available. Purpose The aim was to evaluate the prevalence of antithrombotic treatments and their relation to mortality in patients with Fontan circulation. Methods A total of 5,075 patients with UVH were identified using data from the Swedish National Patient Register, the Cause of Death Register, and the National Prescribed Drug Register. Patients with UVH born in Sweden between 1970 and 2017 who underwent Fontan surgery were included. The study population was divided into three groups based on medication: anticoagulation therapy, antiplatelet therapy, and no therapy. Incidence rate (IR) was reported per 1000 person-years and calculated as the total number of deaths divided by total follow-up time. Confidence interval (CIs) for IR was estimated with Poisson regression. Kaplain-Meier was used to estimate the survival probability of 95% for UVH. The Stratified Cox proportional hazards model was used to estimate hazard ratios (HR) with 95% CI. Results The total cohort consisted of 864 patients of which 280 individuals (32%) had hypoplastic left heart syndrome (HLHS). The median follow-up time was 14.4 (IQR 3.9;24.9) years, maximum follow-up time was 47 years. Out of all the patients, 36% received no anticoagulation or antiplatelet therapy. Among those who did receive therapy, 75% were treated with antiplatelets. The patients who had no therapy had a higher mortality rate. During long-term follow-up, patients with UVH had higher survival rates when treated with antiplatelets. Conclusion Antithrombotic therapy, in particular antiplatelet therapy, was associated with the highest survival in patients with UVH as compared to no treatment. Our data suggest that antithrombotic treatment, and in particular antiplatelet treatment, could be considered in patients with UVH.Survival with Antithrombotic treatment

Pregnancy complications and long-term risk of cardiovascular events in women with heart disease

Abstract Background/Introduction Women with congenital heart or acquired heart disease are at increased risk of atherosclerotic cardiovascular disease. Pregnancy complications are established risk factors for cardiovascular disease in the general population, but their prognostic value for cardiovascular outcomes in the population with congenital or acquired heart disease is unknown. Purpose To determine the frequency and prognostic value of pregnancy complications for the risk of cardiovascular outcomes in women with congenital or acquired heart disease. Methods This nationwide registry-based cohort study included women in Sweden with heart disease (pulmonary arterial hypertension, congenital heart disease or acquired valvular heart disease) with singleton births registered in the national Medical Birth Register between 1973 and 2014. Exposures of pregnancy complications (preeclampsia/gestational hypertension, preterm birth or birth of an infant small for gestational age) were collected from the Medical Birth Register, and cardiovascular outcomes (mortality and hospitalizations) from the Cause of Death Register and the National Inpatient Register. Cox regression models were performed with time-dependent covariates, to determine the possible prognostic value of the studied pregnancy complications for cardiovascular outcomes including atherosclerotic cardiovascular disease, heart failure and arrythmias after adjustment for major confounding including smoking and body mass index. Results Among the total of 2,134,239 women included from the Medical Birth Register, 2,554 women with 5,568 singleton births were affected by heart disease. Preeclampsia/gestational hypertension affected 5.8% of pregnancies, preterm birth 9.7%, and birth of an infant small for gestational age 2.8%. Preterm birth (adjusted HR 1.91 (95% CI 1.38-2.64)) was associated with an increased risk of maternal all-cause mortality. Preeclampsia/gestational hypertension (adjusted HR 1.64 (95% CI 1.18-2.29)) and preterm birth (adjusted HR 1.56 (95% CI 1.19-2.04)) were associated with an increased risk of hospitalizations for atherosclerotic cardiovascular disease. Conclusions Pregnancy complications were frequent in women with congenital or acquired heart disease. With a median follow-up time of 22 years, preterm birth was associated with a higher risk of cardiovascular mortality, and preeclampsia/gestational hypertension and preterm birth were associated with cardiovascular morbidity. In women with heart disease, pregnancy complications may provide additional information for the risk assessment of future cardiovascular outcomes.Overview of study designPrevalence and risk estimation

Trends in heart failure mortality in Sweden between 1997 and 2022.

Data from US have shown a reversal in the improvement of heart failure (HF)-related mortality over the last ~10 years. It is unknown whether these trends generalize to European universal healthcare systems. We assessed temporal trends in (i) HF-related mortality in the overall national population; and (ii) all-cause mortality following an incident HF diagnosis, overall and stratified by ejection fraction (EF), in Sweden between 1997 and 2022. Annual mortality rates with a HF diagnosis as underlying cause were extracted from the Cause of Death Register. All-cause mortality following incident HF was assessed in two HF cohorts derived from the National Patient Register (NPR) and the Swedish HF Registry (SwedeHF). Temporal trends were presented as average annual percentage change (AAPC). Between 1997 and 2022, age-adjusted HF-related mortality in the general population declined from 33.4 to 23.8 per 100 000 individuals (AAPC -2.15%, p < 0.001). In the HF cohort from NPR (n = 423 092), all-cause mortality at 1, 3, and 5 years following a first diagnosis of HF was 25%, 46%, and 58%, respectively, in 2022; 1-year mortality declined (AAPC -1.10%, p < 0.001) over time regardless of age or sex. In SwedeHF (n = 63 753), the decline in 1-year mortality was less steep with increasing EF (AAPC -2.64%, p < 0.001; -2.30%, p = 0.062; and -2.16%, p = 0.032 in EF <40%, 40-49%, and ≥50%, respectively). Heart failure-related mortality has declined over the last ~25 years in Sweden. All-cause mortality in patients with HF has also declined, more in HF with reduced than preserved EF, mirroring the different availability of life-saving treatments across the EF spectrum.

Comorbidities and use of proarrhythmic drugs in patients with torsade de pointes arrhythmia

Abstract Introduction Drug-induced long QT interval syndrome (LQTS) is a risk factor for torsade de pointes (TdP) ventricular arrhythmia. Combining several QT-prolonging drugs can also increase risk. Clinical decision support systems (CDSS) can help prescribers assess the risk for TdP associated with drugs. Use of combination of drugs and prevalence of other risk factors is not fully known in TdP . Purpose To describe 1) comorbidities (risk-diagnoses) 2) dispensed prescription drugs and their risk for TdP (risk-drugs) using two different CDSS. The hypothesis was that individuals with TdP had risk-diagnoses and used risk-drugs. Personalized decision regarding risk stratification and medication is important to prevent TdP. Methods Patients with first episode of TdP (ICD-10 I472.C) in the National Patient Register (NPR) between 2006 and 2018 were included in this retrospective register-based cohort study. Comorbidities within 5 years prior to the hospital care episode and at the time of TdP diagnosis were retrieved. Mortality was analyzed (National Cause of Death Register). Medications dispensed within 90 days prior to TdP were retrieved (Swedish Prescribed Drug Register). Drugs were classified using 2 different CDSS (Credible Meds and Janusmed Risk Profile). Individual medication data linked with Janusmed Risk Profile gave a risk score of combination of drugs according to an algorithm. Results 762 patients with TdP were identified, most were elderly (72% ≥65 years old), 50% females. After TdP, 31 patients (4.1%) died within 7 days, 61 (8.0%) within 30 days, 87 (11%) within 90 days. Five years prior to TdP 338 patients (44%) had ≥1 risk-diagnosis (heart failure, cardiomyopathies, acute/ chronic coronary syndromes, renal failure,liver disease, LQTS, ventricular arrhythmia and/or cardiac arrest). More males vs. females had risk-diagnoses (28% vs. 22%, p&amp;lt;0.0015). A median of 6 drugs (IQR 2-9) were dispensed. Anti-depressants and antiarrhythmics were the most common risk-drugs. According to Credible Meds, 192 (25%) patients used ≥1 drug with known risk, 51 patients (6.7%) ≥1 drug with possible risk and 208 patients (27%) ≥1 drug with conditional risk only. 470 patients (62%) had ≥1 risk-diagnosis and/or ≥ 1 risk-drug (known or possible risk). Another 88 patients had ≥1 risk-diagnosis and/or ≥1 risk-drug (conditional risk). Thus, 558 patients (73%) had ≥1 risk-diagnosis and/or ≥ 1 risk-drug (Credible Meds). Analysis of combination of drugs showed that 290 patients (38 %) had drugs with increased risk, 547 patients (72%) had ≥1 risk-diagnosis and/or a combined drugs associated with increased risk (Janusmed Risk Profile). Conclusion Prior to TdP approximately a third of patients were dispensed prescription drugs with proarrhythmic risk according to two different CDSS. Almost 75% of patients were dispensed drugs associated with proarrhythmic risk and/or had other proarrhythmic risk factors. Vigilance should be undertaken to modify risk factors to prevent TdP.Baseline characteristicsRisk-drugs dispensed prior to TdP