Nationwide Cohort Research Articles

Characterizing disease burden and health care resource utilization in patients with hypertrophic cardiomyopathy: a nationwide real-world study in Finland

Abstract Background Hypertrophic cardiomyopathy (HCM) is an often hereditary myocardial disease with an estimated prevalence of 1:500 in the general population. Purpose This study aimed to investigate healthcare resource utilization (HCRU) and associated costs in patients diagnosed with HCM (and the associated subtypes: obstructive or non-obstructive) in a nationwide cohort in Finland. Methods This retrospective, registry-based cohort study included all Finnish patients diagnosed with HCM between 2000 and 2021, who were 12+ years old at the time of diagnosis, as identified from the national care registers for healthcare. HCRU data were collected between 2014 and 2021 from the Finnish national care registers for health care and the social insurance institution. Data pertaining to New York Heart Association (NYHA) classification were collected from three Finnish university hospitals. Results The study cohort comprised 5,834 patients with an HCM diagnosis; obstructive HCM accounted for 34% of cases. Mean per patient-year costs were €6638, 95% confidence interval (CI) €6472-€7415, and €6112, 95% CI €5957-€6560 for those with obstructive and non-obstructive HCM respectively. All-cause hospitalizations at specialized care were the most prominent cost associated with patients with obstructive and non-obstructive HCM equating to 46.3% and 46.1% of the total cost respectively (Fig 1.). Comorbidity burden, as measured by Charlson comorbidity index (CCI) score, was greater in patients with the obstructive than non-obstructive phenotype of the disease (CCI ≥4: 2.2 and 1.8, p<0.01, respectively). The highest utilization of invasive procedures was found for patients with NYHA class III-IV. Conclusion This population-based study, utilizing real-world data, provides novel insights into HCRU and related costs among Finnish patients with HCM (and associated subtypes). HCRU appears to be primarily driven by hospitalizations at specialized care. Furthermore, the data indicate that patients with obstructive HCM are likely to have a more severe disease, with higher comorbidity burden and requiring more invasive procedures than patients with the non-obstructive form of the disease. However, there were no statistically significant differences in health care costs between those with obstructive and non-obstructive HCM.

Epidemiology and prognosis of obstructive and non-obstructive hypertrophic cardiomyopathy in Finland: a nationwide cohort study

Abstract Background Hypertrophic cardiomyopathy (HCM) is an often hereditary myocardial disease. The Finnish population has a specific genetic background, which may influence and even predispose people to various hereditary diseases. Whilst advances in genetic testing and imaging techniques may have influenced the detection of HCM and associated subtypes, contemporary data on incidence and prevalence remain limited. Purpose This study aimed to evaluate the current trends in the incidence, prevalence, and prognosis of obstructive and non-obstructive HCM in a nationwide cohort in Finland. Methods A population-based registry study was conducted using data from Finnish nationwide healthcare registries (HILMO/avoHILMO) including individuals aged at least 12 years with recorded HCM diagnosis between 2000 and 2021. The incidence was calculated by dividing the number of newly diagnosed HCM patients by the Finnish background population. Furthermore, the mean incidence per age-group was calculated by dividing the sum of age-group specific incidences by the number of age groups. The date and cause of death were obtained from national registries (Statistics Finland). Mortality was computed by dividing the number of deaths by follow-up length. Patients were followed from 2014 to 2021, and incident cases were defined as new diagnoses after 2014. HCM cases were stratified into obstructive HCM and non-obstructive HCM based on ICD-10 codes I42.1 and I42.2, respectively. Results Among 5,834 documented patients with HCM, the overall mean incidence by age-group was 2.64/100,000, with incidence increasing with age, peaking in those aged ≥85 years (6.22/100,000 patient-years [PY]). Annual incidence of obstructive HCM decreased from 2.2 to 1.4/100,000 PY, while non-obstructive HCM increased from 4.6 to 5.4/100,000 PY between 2014 and 2021 (Fig 1). Prevalence of non-obstructive HCM rose from 40 to 56/100,000 PY, while obstructive HCM prevalence remained stable (23-24/100,000 PY). All-cause mortality was 5.5/100 PY, with obstructive and non-obstructive HCM mortality at 5.7 and 4.6/100 PY, respectively. HCM-specific deaths accounted for 16% and 12% of all deaths in patients with non-obstructive and obstructive HCM, respectively. Conclusions This nationwide study in Finland revealed an increasing incidence and prevalence of non-obstructive HCM over time, contrasting with stable rates among patients with obstructive HCM. Incidence and prevalence were strongly age dependent. Non-HCM-related deaths were predominant in both HCM subtypes.

Predictors of acute ischemic strokes and subsequent mortality in patients hospitalized for percutaneous coronary interventions

Abstract Background Acute ischemic strokes (AIS) occurring post percutaneous coronary intervention (PCI) are an infrequent but severe complication, resulting in increased mortality rates and morbidity in survivors. Purpose We aimed to investigate independent predictors of AIS and subsequent mortality in patients hospitalized for PCI in a nationwide cohort. Methods A retrospective analysis using on ICD-10-GM and OPS-codes obtained from 2006-2021 from the German Federal Statistical Office was performed. Patients with a peri-interventional AIS aged ≥18 years which were admitted for PCI were included in this analysis. A stepwise regression analysis was employed to identify factors independently associated with AIS and to determine variables linked to in-hospital mortality. Results From 4,910,430 PCI cases registered from 2006-2021, AIS occurred in 4,098 (0.08%) patients. Patients with an AIS were 70.9±11.3 years of age, predominantly male (65.3%) and displayed a high burden of comorbidities such as diabetes (36.1%), a prior medical history of atrial fibrillation (34.6%) and chronic kidney disease (19.4%). In patients with AIS, 27.4% presented with a ST-elevation myocardial infarction (STEMI), whilst 38.9% were admitted with a Non-STEMI. Concerning procedural characteristics, 84.2% underwent a coronary stent implantation, and in 5.5% cases a coronary thrombectomy was carried out. Important predictors of peri-interventional AIS after a PCI were: carotid artery disease, history of stroke, presentation with myocardial infraction, atrial fibrillation, and coronary thrombectomy. For variables like hyperlipoproteinemia, obesity and stent implantation an inverse association was noted (also see Figure 1A). With regard to mortality, during a mean in-hospital stay of 18 ± 15.1 days, a total of 18.1% (n=742) patients died. We identified several independent predictors of mortality including clinical presentation with cardiogenic shock, dialysis and STEMI as indication for PCI. A negative correlation with in-hospital mortality was seen for variables such as arterial hypertension and coronary stent implantation (see Figure 1B for full set of independently associated variables). Conclusion In a nationwide cohort of patients hospitalized for PCI over 16 years, we identified important predictors of AIS including carotid artery disease and coronary thrombectomy. Moreover, a substantial rate of in-hospital mortality as well as several predictors of death were recognized. Our findings might help clinicians identify patients undergoing PCI who are at highest risk for ischemic cerebral complications and subsequent mortality.

The impact of body mass index for atrial fibrillation ablation; real-world data on outcomes and quality of life

Abstract Background Pulmonary vein isolation (PVI) is a cornerstone in the management of atrial fibrillation (AF). Increasing numbers of overweight and obese patients undergo PVI, despite the association between a higher body mass index (BMI) and adverse ablation outcomes. The risks of perioperative complications and quality of life have hardly been studied for the different bodyweight groups. Purpose The purpose of this study is to clarify the impact of BMI on PVI outcomes, including both perioperative complications and change in quality of life after PVI. Methods This is an observational, multicentre cohort study of prospectively collected data, covering all 15 ablation centres in the Netherlands. The study included all patients who underwent their first catheter-PVI between January 2015 and December 2021. Patients with a BMI below 18.5 kg/m2, missing BMI data, or prior ablations were excluded. Patients were categorized by BMI; normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2) and obesity (BMI ≥30 kg/m2). The primary outcome was repeat ablation within one year. A logistic regression model was used to adjust for patient characteristics. A generalized additive model was fitted to visualize the correlation between BMI and the risk of repeat ablation. Secondary outcomes were repeat ablation within 3 years, a composite of the periprocedural complications, and change in quality of life, assessed using the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire before and at one year after PVI. Results A total of 20,725 patients (33% female) were included; 72% had a paroxysmal AF pattern. Of all patients, 30% were normal weight, 47% overweight and 23% obese. Within the first year post-index PVI, obese patients had a higher incidence of repeat ablation than normal-weighing and overweight patients (17.8% versus 15.6% and 16.1%, P <0.05). Obesity independently predicted an increased risk of repeat ablation within 1 year (odds ratio 1.15; 95%-confidence interval 1.01-1.31, P =0.03). This increased risk was also apparent for repeat ablations within 3 years (hazards ratio 1.15; 95%-confidence interval 1.06-1.25; P <0.01). The composite complication rate was 3.8% in normal weighing, 3.0% in overweight, and 4.6% in obese patients, with weight class not being an independent predictor. All weight groups had a substantial improvement in quality of life one year after ablation. Post PVI, summarized AFEQT score was still lower in obese patients (81), than in normal weight (88; P <0.01) and overweight patients (88; P <0.01). Conclusions In a nation-wide contemporary cohort, obesity is an independent predictor for undergoing a repeat ablation within both 1 and 3 years. This relation is not apparent for overweight individuals. Catheter ablation can safely be performed in all weight classes. Despite an overall lower quality of life among obese individuals, substantial improvements in quality of life occur in all weight groups.Visual abstract

Predicting atrial fibrillation from ECG characteristics

Abstract Background/Introduction Atrial fibrillation (AF) is the most common cardiac arrythmia, and demographic shifts in age continues to increase the prevalence of atrial fibrillation on a global scale. With manifestations of short and intermittent duration, identifying and diagnosing AF often proves to be a challenge. As a consequence, patients who develop AF are at risk of experiencing stroke and other cardiac diseases such as heart failure (HF) before appropriate treatment is initialized. Despite the potential benefits of early AF detection, risk profiling based on electrocardiographic (ECG) findings is currently lacking. Several smaller studies have identified ECG characteristics associated with increased risk of AF, but these characteristics have not been individually evaluated in large-scale nationwide cohorts, and no evidence exists on the additive effect of these ECG characteristics. Purpose We aimed to evaluate the risk of new-onset AF, HF, and stroke according to five ECG characteristics previously linked to AF, in order to identify potential predictors of AF. Methods We used national registers and the Danish Nationwide ECG Cohort to include patients with ECG measurements taken between 2010 and 2022. Patients were grouped according to how many of the following ECG characteristics were present in their baseline ECG: Elevated heart rate (>80), prolonged PR-interval (≥196 ms for women and ≥204 ms for men), biphasic P-waves (positive and negative amplitude within same p-wave), abnormal P terminal force (≥ 6000 mV×ms), and prolonged P-wave duration(≥120 ms). Patients were followed for 2 years to evaluate the risk of atrial fibrillation, heart failure (HF), and stroke, according to baseline ECG characteristics. Results We included 1,505,474 patients of whom 594,702 had exactly one ECG characteristic, 197,367 had two characteristics, 44,983 had three characteristics, 6,390 had four characteristics, and 451 had all five characteristics on their baseline ECG. The risk of developing AF or HF increased with the number of ECG characteristics present on the baseline ECG. Patients with two ECG characteristics had a 2-fold increased risk of AF or HF compared to patients with no ECG characteristics (HR: 2.11 95%CI: 2.05-2.16). Patients with two or more ECG characteristics present on their baseline ECG exceeded a 5% 2-year absolute risk of developing either AF or HF. Among patients with only one ECG characteristic on their baseline ECG, elevated heart rate and prolonged PR interval were the factors most associated with an increased risk of AF compared to patients with none of the ECG characteristics on their baseline ECG. Conclusions The absolute and relative risk of atrial fibrillation, heart failure, and stroke increased with the number of ECG characteristics present on the baseline ECG. We suggest that the ECG characteristics evaluated in this study could be used in screening scenarios for atrial fibrillation to identify high risk patients.Absolute and relative 2-year risksRisk acc. to specific ECG characteristic

Assessing one-year risk of heart failure following first time myocardial infarction and subsequent five-year mortality risk: a nationwide study of 34,401 patients

Abstract Introduction A comprehensive understanding of the post-myocardial infarction (MI) trajectory leading to heart failure (HF) and its profound impact on long-term mortality is imperative for effective secondary prevention and risk assessment. Methods We conducted a registry-based nationwide cohort study of all Danish patients with a first MI during 2014 to 2020. Excluding patients with prior HF, individuals were followed for one year post-MI, assessing HF incidence through hospital admissions and visits to elective HF ambulatory clinics. Among those who survived one year, long-term mortality 1-6 years post-index MI was assessed using landmark analysis and Cox proportional hazards models adjusting for age, gender and comorbidities and hazard. Patients were categorized into three groups: not HF, referred for elective HF outpatient follow-up, and acute admission for HF. Results Among 34,301 individuals with a first MI and surviving the first year (median age 67.5, and 66.9 % male), 3.3 % were admitted acute for HF while 11.2 % had an elective HF outpatient follow-up within one year of the MI event (see Figure 1a). We observed a significant association between acute HF admissions post-MI and increased five-year mortality risk (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.40-1.90, p-value <0.001, see Figure 1b) (absolute 5-year risk: 18.4 %). In contrast, the five-year mortality risk for patients with elective outpatient HF follow-up was comparable to that of individuals without HF (HR 1.06 [0.94-1.19], p-value 0.34) (absolute 5-year risk: 9.6 vs 8.5 %). Conclusion Our findings suggest that acute admission for HF after a first time MI occur in 3.3 % of the patients with a subsequent significantly increased mortality risk compared to patients that do not develop clinical HF. Admission for HF in patients with a first time MI should be considered as a relatively rare but fatal complication.

Infective endocarditis - characteristics and long-term outcomes in patients with congenital heart disease are distinct from those without congenital heart disease

Abstract Background Patients with congenital heart disease (CHD) form a high-risk niche among patients considered at high-risk of infective endocarditis (IE). Their life-long exposure to the risk of IE, starting from birth, necessitates a nuanced approach to both prevention and treatment strategies. However, comprehensive data from an unselected nationwide cohort, including children, are lacking. Purpose This study sets out to compare characteristics and associated outcomes among patients with IE with and without CHD. Methods Using nationwide registries, all Danish patients diagnosed with IE from 1977-2021 were identified and stratified on whether they had a diagnosis of CHD, regardless of its complexity. Characteristics prior to and during admission as well as associated outcomes (i.e., in-hospital mortality, 1-year mortality, and 10-year mortality, and IE recurrence) were compared between groups. Results In total, 14,040 patients were diagnosed with IE from 1977-2021 including 895 (6.4%) with a diagnosis of CHD. Patients with versus without CHD were significantly younger at time of IE diagnosis (median age 38.8 years [IQR 21.2-56.4 years] versus 70.7 years [IQR 58.8-78.9 years], Figure 1) and less comorbid. Patients with versus without CHD were hospitalized due to IE for a similar period of time but more often underwent cardiac surgery during admission (44.9% versus 21.3%). The IE-related bacteremia was significantly different between groups: the most common bacteriemia in relation to IE was Streptococci (29.9%) in patients with CHD and Staphylococcus Aureus (29.9%) in patients without CHD. Patients with CHD were associated with a significantly lower risk of in-hospital mortality (6.4% versus 19.8%), 1-year mortality (10.5% versus 32.4%) and 10-year mortality (21.3% versus 58.7%) compared with those without CHD. The 10-year incidence of IE recurrence was similar among groups (p-value 0.5). Conclusions Patients with CHD who develop IE are distinctive from patients with IE without CHD in terms of characteristics as well as long-term outcomes. Notably, our findings stress a key point: the majority of children and adolescents with IE have a CHD. These unselected findings should help guide future preventive strategies, diagnosis, and management.

The association of steatotic liver disease with recurrent ischemic events in patients with chronic coronary syndrome: a multicenter cohort study

Abstract Background/introduction A panel of multi-society experts has proposed new subcategories under the term steatotic liver disease (SLD), replacing the exclusive term non-alcoholic fatty liver disease with the new nomenclature metabolic dysfunction-associated steatotic liver disease (MASLD). However, the prognostic impact of SLD subtypes in patients with chronic coronary syndrome (CCS) remains unknown. Purpose We aimed to investigate the associations between SLD subtypes and recurrent event risks in CCS patients. Methods Our analysis included a total of 9,448 patients with CCS from a large multicenter nationwide cohort. Hepatic steatosis was defined as hepatic steatosis index ≥36 and ultrasound evidence. Patients were categorized into four groups based on the evidence of steatosis, cardiometabolic risk factors and alcohol intake: 1) no SLD; 2) MASLD; 3) MASLD with increased alcohol intake (MetALD) and 4) SLD with other causes. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality, myocardial infarction, stroke and unplanned revascularization. Results The prevalence of no SLD, MASLD, MetALD and SLD with other causes in our population was 37.3%, 47.7%, 14.7% and 0.3%, respectively. During a median follow-up of 2.0 years, 759 (8.0%) MACCE events occurred. After multivariable adjustment, MASLD (HR 1.25, 95%CI 1.06-1.48), MetALD (HR 1.31, 95%CI 1.04-1.65) and SLD with other causes (HR 2.81, 95%CI 1.04-7.57) were all significantly associated with higher MACCE risks compared to no SLD. Conclusions A significant proportion of SLD was observed in CCS patients. Patients with various SLD subcategories all had higher risks of recurrent events.

The long-term clinical impact of high-intensity statin therapy in older patients with acute myocardial infarction

Abstract Introduction Despite substantial clinical evidence supporting the benefits of high-intensity statins for acute myocardial infarction, the clinical implications of their use in elderly populations have yet to be fully elucidated. Purpose This study aims to clarify the importance of high-intensity statin therapy at discharge for patients aged over 65 with acute myocardial infarction (AMI). Methods In this retrospective cohort analysis conducted with data from the Korean Acute Myocardial Infarction Registry (KAMIR), we evaluated 4,147 patients aged 65 and above who experienced acute myocardial infarction (AMI), underwent coronary interventions utilizing second-generation drug-eluting stents, and were prescribed statins at the time of discharge. The primary outcome was major adverse cardiovascular events (MACE) at 3 years, defined as the composite of all-cause deaths, any myocardial infarction, and any coronary revascularization. The secondary outcome was target-lesion failure (TLF), defined as the composite endpoint of all cardiac deaths, target vessel myocardial infarction, and ischemia-driven target lesion revascularization at 3 years. Results In this study, 1,268 patients (30.5%) were treated with high-intensity statins at discharge. The patients were stratified into two groups using an age threshold of 78 years. In the propensity-matched cohort aged 65 to 78, the use of high-intensity statins was associated with a significant reduction in MACE (19.1% versus 14.5%, p=0.011). In the propensity score-matched cohort aged over 78, however, treatment with high-intensity statins did not lead to a reduction in MACE (24.8% versus 24.5%, p>0.99). Additionally, multivariate analysis revealed that high-intensity statin therapy was associated with a reduced risk of MACE (HR 0.69, 95% CI [0.57-0.85], p<0.001) in patients aged 65 to 78. However, the effects of high-intensity statins on TLF were not significant in matched patients aged 65 to 78 (7.9% versus 6.5%, p=0.269) and in those aged over 78 (13.7% versus 12.1%, p=0.638). Conclusion This extensive, nationwide cohort study suggests that treatment with high-intensity statins upon discharge may not offer clinical benefits in reducing MACE and TLF in patients with AMI aged over 78, compared to those aged 65 to 78.

Socioeconomic inequalities in avoidable mortality: results from the Italian nationwide cohort

Abstract Background Inequalities in avoidable mortality have been well evaluated in many European countries. We aimed to assess the association between socioeconomic status and avoidable mortality in Italy. Methods The nationwide closed cohort of the 2011 Census of Population and Housing was followed up for 2012- 2019 mortality. Outcomes of preventable and of treatable mortality were evaluated among people aged 30-74. Exposures were education level and residence macro area (North-West, North-East, Center, South-Islands). Adjusted mortality rate ratios (MRRs) were estimated through multivariate quasi-Poisson regression models, by sex and group of causes, taking into account age at death and macro area of residence. Relative index of inequalities (RII) was estimated for preventable, treatable, and non-avoidable mortality and for some specific causes. Results The cohort consisted of 35,708,459 residents (48.8% men, 17.5% aged 65-74), 34% with a high school diploma, 33.5% living in the South-Islands; 1,127,760 deaths were observed, of which 65.2% for avoidable causes (40.4% preventable and 24.9% treatable). Inverse trends between education level and mortality were observed for all causes; comparing the least with the most educated groups, a strong association was observed for preventable (males MRR = 2.39; females MRR = 1.65) and for treatable causes of death (males MRR = 1.93; females MRR = 1.45). Highest RII were observed for HIV/AIDS and alcohol-related diseases (both sexes), drug-related diseases and tuberculosis (males), and diabetes mellitus, cardiovascular diseases, and renal failure (females). Higher risks of preventable and of treatable mortality were found for those living in the South-Islands. Conclusions We documented relevant socioeconomic inequalities in avoidable mortality in Italy, especially in the Southern regions. They represent a possible missed gain in health and suggest a reassessment of priorities and definition of health targets with the lens of equity. Key messages • An inverse socioeconomic gradient in avoidable mortality was observed in Italy, both for preventable and for treatable mortality, with geographical heterogeneity. • Greatest social disparities were found in mortality for causes strongly associated with risk behavior and for which it is possible to identify risk factors on which to intervene.

Postoperative heart valve infection, when and which bacteria: a nationwide cohort study

Abstract Background In patients undergoing heart valve surgery, subsequent bacteremia and infective endocarditis are feared events due to the associated high mortality. Knowledge on the incidence and specification of bacteremia following left-sided valve surgery are sparse and may have implications for prophylactic strategies and follow-up. Purpose To examine the six months incidence of bacteremia and infective endocarditis following left-sided heart valve surgery. Methods In the period from January 2010 to December 2021 all patients undergoing left-sided valve surgery were identified using Danish nationwide registries. Patients were followed until a maximum of six months, end of study, emigration, death, or outcome of interest (i.e., bacteremia or infective endocarditis). Cumulative incidence curves were computed with death as a competing risk stratified on bacterial species and for subgroups of interest: type of valve surgery, age, and sex. Results A total of 14,305 patients were included in the study. The majority of the study population were male (68.6%), and the median age was 70.2 years (25th-75th percentile 62.0-76.0 years). In total, 10,469 (73.2%) of the study population underwent aortic valve surgery, 3,497 (24.5%) underwent mitral valve surgery, while 339 (2.4%) underwent surgery on both valves. The cumulative incidence of bacteremia at six months of follow-up was 2.4% (95% CI 2.2-2.7%), Figure 1. For the overall study population, the most frequently occurring bacteremia was with Coagulase-negative Staphylococci (28%) and Staphylococcus aureus (14%). Within 30 days 0.35% of the patients had bacteremia with coagulase-negative staphylococci while this was 0.68% at six months of follow-up. For Staphylococcus aureus this was 0.19% and 0.34%, respectively. The cumulative incidence of infective endocarditis at six months of follow up was 1.0% (95% CI 0.8-1.2%). The majority of the infective endocarditis incidents were blood culture negative (27%) or caused by Enterococci (19%), Streptococci (17%) or Coagulase-negative Staphylococci (17%) while Staphylococcus aureus accounted for 14%. In crude analysis, simultaneous surgery on the mitral and aortic valve was associated with a statistically significant higher rate of bacteremia (P=0.004). Similarly, higher age was associated with a statistically significant higher rate of bacteremia (P<0.001). On the contrary, in crude analysis, no difference in the risk of bacteremia was found between sexes (P=0.9). Conclusions Bacteremia following left-sided heart valve surgery occurred in little over 2%. The majority was with Staphylococci, and half of these occurred within 30 days of the surgery. There is a continued need to optimize prophylactic strategies.

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.

Risk of long COVID and associated symptoms after acute SARS-COV-2 infection in ethnic minorities: a Danish nationwide cohort study

Abstract Background and aim Ethnic minorities living in high-income countries have been disproportionately affected by COVID-19 in terms of infection rates, hospitalisations, and deaths; however, less is known about long COVID in these populations. Our aim was to examine the risk of long COVID and associated symptoms among ethnic minorities. Methods We used Danish nationwide register-based cohort data on individuals diagnosed with COVID-19 aged ≥18 years (n = 2 334 271) between January 2020 and August 2022. We calculated the risk of long COVID diagnosis and long COVID symptoms among ethnic minorities compared with native Danes using multivariable Cox proportional hazard regression and logistic regression, respectively. Results Of the diagnosed COVID-19 cases, 1 973 998 (84.6%) were native Danes and 360 273 (15.4%) were ethnic minorities. After adjustment for age, sex, civil status, education, family income, and Charlson comorbidity index, ethnic minorities from North Africa (adjusted hazard ratio [aHR] 1.41, 95% CI [1.12,1.79]), Middle East (aHR 1.38, 95% CI [1.24,1.55]), Eastern Europe (aHR 1.35, 95% CI [1.22,1.49]), and Asia (aHR 1.23, 95% CI [1.09,1.40]), had significantly greater risk of long COVID diagnosis than native Danes. In the analysis by largest countries of origin, the greater risks of long COVID diagnosis were found in Iraqis (aHR 1.56, 95% CI [1.30,1.88]), Turks (aHR 1.42, 95% CI [1.24,1.63]), and Somalis (aHR 1.42, 95% CI [1.07,1.91]). A significant factor associated with an increased risk of long COVID diagnosis was COVID-19 hospitalisation. Conclusions Migrants and ethnic minorities had higher risk of long-COVID compared to native Danes.

The obesity paradox in patients with hypertrophic cardiomyopathy: A Korean nationwide cohort study

Abstract Background In cardiomyopathies, obesity is known to affect the cardiac remodeling and is associated with a poor prognosis. However, in hypertrophic cardiomyopathy, which is included in the category of heart failure with preserved ejection fraction, the risk of underweight has been suggested, and its impact in practice is controversial. Purpose The aim of this study was to investigate the potential relationship between obesity and cardiovascular outcomes in patients diagnosed with hypertrophic cardiomyopathy. Methods We conducted a retrospective national cohort study from 2013 to 2020 utilizing administrative claims data and health check-up database from the Korean National Health Insurance Service. Patients newly diagnosed with hypertrophic cardiomyopathy from January 2015 to December 2019 were included. Body mass index was stratified into five groups based on the World Health Organization's recommended criteria for Asian populations, and patients were followed until the date of each outcome or the end of the study period. Predefined clinical outcomes included heart failure hospitalization events, fatal arrest events, all-cause death, and composite clinical outcomes. Results A total of 6,361 patients were included in the study, with a mean age was 60 ± 13 years and 32.6% female. During a median follow-up of 3.0 years (interquartile range, 1.8 to 4.3), 921 heart failure hospitalization, 185 fatal arrest, and 340 deaths occurred. The underweight group had higher adjusted hazard ratios for heart failure hospitalization, fatal arrest, all-cause death, and the composite outcome compared to the normal range body mass index group (HR 1.69, 95% CI 1.16-2.47; HR 2.29, 95% CI 1.06-4.93; HR 2.74, 95% CI 1.77-4.24; HR 1.77, 95% CI 1.28-2.45). In addition, the adjusted hazard ratios for the composite outcome were lower in the overweight and obese I group compared to the normal range (HR 0.80, 95% CI 0.68-0.95; HR 0.84, 95% CI 0.72-0.98). Conclusions Among patients with hypertrophic cardiomyopathy, those classified as underweight had an increased risk of heart failure hospitalization, fatal arrest, all-cause death, and composite outcomes compared with normal weight patients, while those classified as overweight and obese had a decreased risk of composite outcomes.

Incidence and factors associated with mitral valve reoperation in patients undergoing intervention for mitral regurgitation: a nationwide cohort study

Abstract Background When intervention is needed for the treatment of mitral regurgitation, the risk of reoperation is of concern for both patients and physicians. As such, contemporary and nationwide data on the incidence and factors associated with mitral reoperation can provide crucial information to support patient education and clinical follow-up after intervention. Purpose To examine the incidence of mitral reoperation in patients operated for mitral regurgitation. Second, to assess whether reoperation rates differed according to time since surgery and identify potential factors associated with reoperation. Methods Using Danish nationwide registries, patients undergoing first-time surgery for mitral regurgitation 1996–2021 were identified. Exclusion included first-time surgery due to endocarditis. According to index surgery, the population was categorized into 1) mitral repair; 2) mechanical prosthesis; 3) bioprosthesis. Patients were followed from date of discharge. Cumulative incidence of reoperation was examined using competing risk analysis during a maximum of 20-years follow-up. Crude incidence rates of reoperation were reported from 0-6 months and for overall study period. Multivariate Cox analysis was used to examine factors associated with reoperation. Results We identified 7,063 patients: 4,680 (66.3%) with repair (72% male, median age 66), 1,273 (18.0%) with mechanical prosthesis (52% male, median age 59), and 1,110 (15.7%) with bioprosthesis (57% male, median age 74). Median follow-up was 7.2 years, 10.7 years, and 4.5 years, respectively. At end of follow-up, cumulative incidences were 7.7% for repair, 6.8% for mechanical prostheses, and 7.5% for bioprostheses. Of these, reoperation was preceded by endocarditis in 8.0%, 21.5%, and 30.4% of the respective patient groups. The cumulative incidence function demonstrates that the highest proportion of reoperations occurred within first six months, Figure 1. From 0-6 months following surgery, incidence rates per 100 person-years were 9.1 for repair, 11.7 for mechanical prostheses, and 18.4 for bioprostheses, while this was 8.6, 9.4, and 17.0, respectively for the overall study period. Factors associated with increased rate of reoperation were heart failure (HR=1.80, 95% CI 1.40-2.32), chronic renal failure (HR=1.48, 95% CI 1.11-1.98) and chronic obstructive pulmonary disorder (COPD) (HR=1.34, 95% CI 1.01-1.77), Figure 2. Compared to mitral repair, mechanical prostheses were associated with lower rate of reoperation (HR=0.57, 95% CI 0.42-0.78), while there was no statistically significant difference between repair and bioprostheses (HR=1.10, 95% CI 0.81-1.50). Conclusion In patients operated for mitral regurgitation, cumulative incidences of reoperation with a maximum of 20-year follow-up were 7.7% for repair, 6.8% for mechanical prostheses, and 7.5% for bioprostheses. Comorbidities such as heart failure, renal failure and COPD were associated with increased risk of reoperation.Figure 1Figure 2

Bacteremia after transcatheter aortic valve implantation: a nationwide cohort study

Abstract Background Bacteremia and infective endocarditis (IE) are rare but severe complications to transcatheter aortic valve implantation (TAVI). However, data on early bacteremia and microbiological etiological profile are scarce. Purpose The study aimed to investigate the incidence of bacteremia and IE within six months after TAVI. Methods Using Danish nationwide registries, we identified all patients who underwent TAVI from 2012 to 2021. These patients were matched 1:1 by age, sex, and index-year with individuals who underwent elective coronary angiography (CAG). The primary outcomes were bacteremia and IE within six months. Outcomes were compared with cumulative incidence functions and adjusted hazard ratios (HR). All patients were followed six months from the index date until the outcome of interest, death, emigration, or end of study (December 31st, 2021), whichever came first. Results We identified 5,990 patients undergoing first-time TAVI, of whom 56 % were men, and the median age was 81 years [IQR 77–85]. All patients were matched with controls undergoing CAG (56% men, median age 81 [IQR 77-85]). Patients undergoing TAVI had more comorbidities than controls. The six-month cumulative incidence of bacteremia was 4.2% [95% CI 3.7-4.7] and 2.6% [95% CI 2.2-3.0] after TAVI and CAG, respectively, corresponding to an adjusted HR of 1.57 (95% CI 1.27-1.96) (Figure 1). The common bacterial etiologies for bacteremia after TAVI were Streptococci (20%), Coagulase-negative staphylococci (CoNS) (19%), and Enterococci (18%). After CAG, CoNS (22%) and Staphylococcus aureus (16%) were the most frequent. By six months, 1.1% [95% CI 0.9-1.4] and 0.2% [95% CI 0.1-0.3] developed IE after TAVI and CAG, respectively, with an adjusted HR of 20.01 (95% CI 5.97-67.48). Conclusion In this nationwide cohort study, the risks of bacteremia and infective endocarditis within six months post-TAVI were significantly higher than in the matched coronary angiography population. Bacteremia post-TAVI was characterized by significantly more Enterococci spp. These results could have implications in the selection of peri-procedural antibiotics, as commonly used antibiotic regimens do not cover Enterococci spp.Cumulative incidence of bacteremia

Temporal trends of prescription rates, dosing of non-vitamin K antagonist oral anticoagulants and clinical outcomes in patients with atrial fibrillation

Abstract Background The launch of non-vitamin K antagonist oral anticoagulant (NOAC) has revolutionized the landscape of stroke prevention in atrial fibrillation (AF). We aimed to analyze the temporal trends of prescription rates of oral anticoagulants (OACs), NOAC dosing, clinical outcomes and in patients with AF. Methods This was a retrospective study using the Taiwan National Health Insurance Research Database. During 2011 to 2020, A total of 249,107 patients aged ≥30 years with newly diagnosed AF were identified. We analyzed the 1-year risks of ischemic stroke, intracranial hemorrhage (ICH), and all-cause mortality for overall population and specifically for NOAC users. Results The prescription rate of OAC increased from 22.1% in year 2011 to 57.7% in 2020 (P<0.001) with NOAC accounting for 91.0% of overall OAC prescriptions. Compared to patients with incident AF diagnosed in 2011, there were increasing trends for a greater decrease in the risks of ischemic stroke (adjusted hazard ratios [aHRs] 0.914 in 2012, 0.879 in 2013, 0.925 in 2014, 0.822 in 2015, 0.754 in 2016, 0.763 in 2017, 0.769 in 2018, 0.713 in 2019 and 0.707 in 2020; all P<0.05) and mortality (aHRs 0.903 in 2014, 0.899 in 2015, 0.830 in 2016, 0.808 in 2017, 0.788 in 2018, 0.810 in 2019, 0.788 in 2020; all P<0.05), while the risk of ICH did not change significantly (Figure 1). For NOAC users, the percentages of high-dose NOACs increased from 11.04% in year 2012 to 44.29% in year 2019 to 2020. The increasing trend in the use of high-dose NOACs was temporally associated with a lower risk of ischemic stroke observed for patients receiving NOACs in year 2015 to 2017 (aHR 0.794) and year 2018 to 2020 (aHR 0.688) compared to those in year 2012 to 2014 (Figure 2). Conclusion In this nationwide cohort study, there was an increasing trend of OAC prescription, temporally associated with a decline of the risk of ischemic stroke and mortality. Even among NOACs users, the risk of ischemic stroke declined gradually, partly explained by the increasing prescriptions of high-dose NOACs.

Long-term clinical outcomes of acute myocardial infarction based on a center's experience with IVUS in the contemporary drug-eluting stent era

Abstract Introduction Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) is recognized for improving patient prognosis. However, how a center's experience with IVUS affects clinical outcomes remains unclear. Purpose This study aims to elucidate the impact of a center's expertise in IVUS on clinical outcomes, emphasizing the value of institutional experience. Methods In this retrospective cohort study from the Korean AMI Registry (KAMIR), we analyzed 9,752 patients diagnosed with acute myocardial infarction (AMI) who underwent intervention with second-generation drug-eluting stents. The primary outcome was major adverse cardiovascular events (MACE) at 3 years, defined as the composite of all-cause deaths, any myocardial infarction, and any coronary revascularization. The secondary outcome was target-lesion failure (TLF), defined as the composite endpoint of all cardiac deaths, target vessel myocardial infarction, and ischemia-driven target lesion revascularization at 3 years. Results In this study, the median frequency of IVUS usage across 20 institutions was 10.3%. Hospitals were categorized as centers with extensive experience in IVUS or those with limited experience, based on the median frequency of IVUS usage. In centers with extensive experience in IVUS, IVUS-guided PCI consistently showed a reduction in MACE (18.5% vs. 15.3%, p=0.016) and TLF (8.3% vs. 6.3%, p=0.039) within propensity-score matched populations. Furthermore, multivariate Cox regression analysis revealed that IVUS-guided PCI was associated with decreased risks of MACE (HR 0.80, 95% CI [0.69-0.93], p=0.003) and TLF (HR 0.75, 95% CI [0.59-0.95], p=0.01). However, from propensity matched population in centers with limited experience in IVUS, there were no significant reductions in the incidences of MACE (18.6% versus 15.7%, p=0.422) and TLF (10.4% versus 8.9%, p=0.644). Conclusion This comprehensive, nationwide cohort study shows that outcomes of IVUS-guided PCI are more favorable in centers with extensive IVUS experience compared to those with limited experience. These results indicate that the clinical advantages of IVUS-guided PCI are more pronounced in centers with extensive experience than in those with limited experience.

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

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

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.