Risk Difference Research Articles

Effectiveness of a check-up for rehabilitation and prevention needs in primary care

Abstract Background General practitioners play a central role in initiating rehabilitation and prevention services. However, systematic screening for rehabilitation and prevention needs has not been carried out in general practices so far. The legislation encourages the implementation and evaluation of so-called ‘check-up 45+’, which target individuals aged 45 and older. The study aims to evaluate the effectiveness of a check-up 45+ in primary care. Methods A pragmatic, randomized controlled trial was conducted in 26 general practices in the German states of Berlin and Brandenburg among patients aged 45 to 59 years (DRKS00028303). The control group (n = 695) received usual care plus a questionnaire on sociodemographic and health-related characteristics. The intervention group (n = 706) completed additionally the 2-page ‘screening 45+’, which captures rehabilitation and prevention needs in five dimensions. After algorithm-based ad hoc evaluation by practice staff, the general practice could modify the recommendation based on available information (e.g., diagnoses, social situation). Information and application documents were provided in case of identified needs. Applications (primary outcome) and approvals (secondary outcome) of rehabilitation and prevention services were recorded using routine data. Results In the intervention group, 64.2% were women, compared to 63.0% in the control group (mean age 52.1 (SD 4.3) and 52.5 (SD 4.4) years). In the intervention group, 85 applications (12.0%) for medical rehabilitation or prevention services were submitted within two months after the study participation, compared to 20 applications (2.9%) in the control group (p < 0.001). The number of approvals for these services was 59 vs. 17 (p < 0.001). Conclusions The application rate for rehabilitation and prevention services was significantly higher in the intervention group compared to the control group, with a relative risk difference by a factor of 4 and an absolute risk difference of 9.1%pt. Key messages • The implementation of a check-up 45+ in primary care leads to a higher rate of applications for rehabilitation and prevention services compared to usual care. • The check-up 45+ may assist general practitioners in systematically identifying rehabilitation and prevention needs of their patients and in applying for these services.

Bioadaptor implant versus contemporary drug-eluting stent in percutaneous coronary interventions in Sweden (INFINITY-SWEDEHEART): a single-blind, non-inferiority, registry-based, randomised controlled trial

Persistent non-plateauing adverse event rates in patients who underwent percutaneous coronary intervention (PCI) remain a challenge. A bioadaptor is a novel implant that addresses this issue by restoring the haemodynamic modulation of the artery, allowing cyclic pulsatility, vasomotion, and adaptative remodelling, by unlocking and providing dynamic support to the artery. We aimed to assess outcomes with the device versus a contemporary drug-eluting stent (DES) in a representative PCI population. INFINITY-SWEDEHEART is a single-blind, non-inferiority, registry-based, randomised controlled study conducted in 20 hospitals in Sweden. Patients aged 18-85 years, with chronic or acute coronary syndrome ischaemic heart disease, with an indication for PCI, with up to three de novo lesions suitable for implantation with one single device per lesion, and successful pre-dilatation were identified via the Swedish Coronary Angiography and Angioplasty Registry and eligible for enrolment. Participants were randomly assigned (1:1), using block randomisation with random variation in block size and stratified by site, to either the DynamX bioadaptor (Elixir Medical, Milpitas, CA, USA) or a zotarolimus-eluting DES (Resolute Onyx and Onyx Trustar, Medtronic, Minneapolis, MN, USA). The primary endpoint was the device-oriented clinical endpoint of target lesion failure at 12 months (a composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation), assessed in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment, regardless of treatment received) who had either experienced an event up to 12 months or completed the trial up to 12 months. Non-inferiority was established if the upper limit of the two-sided 95% CI for the absolute risk difference was less than 4·2%. Powered secondary endpoints were landmark analyses from 6 months onwards for target lesion failure, target vessel failure (composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target vessel revascularisation), and target lesion failure for patients with acute coronary syndrome assessed in the ITT population). This study is registered with ClinicalTrials.gov, NCT04562805, and follow-up to 5 years is ongoing. Between Sept 30, 2020, and July 11, 2023, 2399 patients were randomly assigned to receive the bioadaptor (n=1201) or DES (n=1198; ITT population). Median age was 69·5 years (IQR 61·2-75·6), 575 (24·0%) of 2399 patients were female, and 1824 (76·0%) were male (data on race and ethnicity were not collected), and 1838 (76·6%) patients presented with acute coronary syndrome. The primary endpoint of 12-month target lesion failure occurred in 28 (2·4%) of 1189 assessable patients in the bioadaptor group versus 33 (2·8%) of 1192 assessable patients in the DES group, with a risk difference of -0·41% (95% CI -1·94 to 1·11; pnon-inferiority<0·0001). In the prespecified landmark analysis from 6 months to 12 months, the Kaplan-Meier estimates of target lesion failure were 0·3% (with events in three of 1170 patients) in the bioadaptor group versus 1·7% (with events in 16 of 1176 patients) in the DES group (hazard ratio 0·19 [95% CI 0·06 to 0·65]; p=0·0079), of target vessel failure were 0·8% (events in eight of 1167) versus 2·5% (events in 23 of 1174; 0·35 [0·16 to 0·79]; p=0·011), and of target lesion failure in patients with acute coronary syndrome were 0·3% (events in two of 906) versus 1·8% (events in 12 of 895; 0·17 [0·04 to 0·74]; p=0·018). The rate of definite or probable device thrombosis, which was recorded as a safety outcome, was low and did not differ between groups (eight [0·7%] of 1201 in the bioadaptor group vs six [0·5%] of 1198 in the DES group; difference in event rates of 0·16% [95% CI -0·50 to 0·83]). Among patients with coronary artery disease, including those with acute coronary syndrome, treatment with the bioadaptor was non-inferior to contemporary DES, showing potential to mitigate non-plateauing device-related events and improving outcomes in patients undergoing PCI. The additional planned follow-up will help to reinforce the clinical significance of the 1-year findings. Elixir Medical.

Inhaled Reliever Therapies for Asthma

The optimal inhaled reliever therapy for asthma remains unclear. To compare short-acting β agonists (SABA) alone with SABA combined with inhaled corticosteroids (ICS) and with the fast-onset, long-acting β agonist formoterol combined with ICS for asthma. The MEDLINE, Embase, and CENTRAL databases were searched from January 1, 2020, to September 27, 2024, without language restrictions. Pairs of reviewers independently selected randomized clinical trials evaluating (1) SABA alone, (2) ICS with formoterol, and (3) ICS with SABA (combined or separate inhalers). Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses synthesized outcomes. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the certainty of evidence. Asthma symptom control (5-item Asthma Control Questionnaire; range, 0-6, lower scores indicate better asthma control; minimum important difference [MID], 0.5 points), asthma-related quality of life (Asthma Quality of Life Questionnaire; range, 1-7, higher scores indicate better quality of life; MID, 0.5 points), risk of severe exacerbations, and risk of serious adverse events. A total of 27 randomized clinical trials (N = 50 496 adult and pediatric patients; mean age, 41.0 years; 20 288 male [40%]) were included. Compared with SABA alone, both ICS-containing relievers were associated with fewer severe exacerbations (ICS-formoterol risk ratio [RR], 0.65 [95% CI, 0.60-0.72]; risk difference [RD], -10.3% [95% CI, -11.8% to -8.3%]; ICS-SABA RR, 0.84 [95% CI, 0.73-0.95]; RD, -4.7% [95% CI, -8.0% to -1.5%]) with high certainty. Compared with SABA alone, both ICS-containing relievers were associated with improved asthma control (ICS-formoterol RR improvement [MID] in total score, 1.07 [95% CI, 1.04-1.10]; RD, 4.1% [95% CI, 2.3%-5.9%]; ICS-SABA RR, 1.09 [95% CI, 1.03-1.15]; RD, 5.4% [95% CI, 1.8%-8.5%]) with high certainty. In an indirect comparison with ICS-SABA, ICS-formoterol was associated with fewer severe exacerbations (RR, 0.78 [95% CI, 0.66-0.92]; RD, -5.5% [95% CI, -8.4% to -2.0%]) with moderate certainty. Compared with SABA alone, ICS-formoterol (RD, -0.6% [95% CI, -1.3% to 0%]) was not associated with increased risk of serious adverse events (high certainty) and ICS-SABA (RD, 0% [95% CI, -1.1% to 1.2%]) was not associated with increased risk of serious adverse events (moderate certainty). In this network meta-analysis of patients with asthma, ICS combined with formoterol and ICS combined with SABA were each associated with reduced asthma exacerbations and improved asthma control compared with SABA alone.

Sex differences in clinical characteristics, phenotypes, management, and long-term outcomes of myocardial injury: an international cohort study

Abstract Background Several studies have demonstrated sex differences in patients presenting to the emergency department (ED) with myocardial infarction, heart failure or syncope. Whether sex-specific differences in chest pain patients with myocardial injury exist is unknown. Purpose To determine whether sex-specific differences in the clinical characteristics, phenotypes, management, and long-term outcomes of patients with myocardial injury exist. Methods Patients presenting to the ED with chest pain suggestive of MI were consecutively enrolled into a prospective multicenter international diagnostic study. Final diagnoses were centrally adjudicated by two independent cardiologists, applying the fourth universal definition of myocardial infarction, using all available medical records, including serial hs-cTn and cardiac imaging. Follow-ups were performed at 3 months, 1-, 2- and 5-years. The primary outcome was 5-year all-cause mortality. Secondary outcomes included 5-year cardiovascular mortality and non-cardiovascular mortality. Multivariable flexible parametric (Royston-Parmar) models assuming proportional hazards were fitted. Models were adjusted for age, history of coronary artery disease, history of malignancy, diabetes, hypertension, smoking status, history of liver disease, and renal function. Results Among 8046 chest pain patients presenting to the ED, 1158 (14.4%) had myocardial injury, of which 358 (31%) were females and 800 (69%) males. Women were older (79 years, vs. 73 years), had fewer cardiovascular risk factors and comparable non-cardiovascular comorbidities except for lung disease which was more commonly found in men. Myocardial injury phenotypes varied between sexes (Figure). The most common phenotype in both sexes was heart failure, yet it was more common in men (37.2%) than in women (22.3%). The second most common phenotype in women was hypertension (15.4%) and arrhythmia (15.4 %), while in men was myocarditis (17.8 %), followed by arrhythmia (15.8%). Women underwent less invasive coronary angiography (19.8% vs 26.9%) or stress testing (12% vs 21.5%). In the angiographic findings, women presented more often with normal findings (30.4% vs. 19.6%) or mild CAD (20.3% vs. 11.2%) whereas men displayed more frequently 3-vessel disease (14.5% vs. 36.4%), Table. After adjusting for known confounders, women were associated with a lower 5-years risk for all-cause mortality (HR 0.69; 95%CI: 0.56–0.83) and cardiovascular mortality (HR 0.61; 95%CI: 0.46–0.79). No statistically significant difference in non-cardiovascular mortality risk was found (HR 0.79; 95%CI: 0.59-1.04). Conclusions Women presenting with chest pain to the ED and having myocardial injury were less likely than men to undergo coronary angiography or non-invasive cardiac imaging. Long-term risk for all-cause or cardiovascular mortality was lower for women compared to men.Myocardial Injury phenotypesPatient management

The impact of peptide receptor radionucleotide therapy with Lutetium-177 DOTATATE on cardiac metastases in neuroendocrine tumors

Abstract Background Cardiac metastasis from neuroendocrine tumors (NET) is rare and has been thought to potentially result in life threatening sequalae. Peptide receptor radionucleotide therapy (PRRT), such as Lutetium-177 (Lu-177) DOTATATE, has been validated as effective treatment for patients with NET who have progressed on somatostatin analogue (SSA) therapy and more recently suggested for use in SAA-naïve higher risk grade 2 and grade 3 NETs. However, Lu-177 DOTATATE therapy has been found to have potentially serious adverse effects both locally and systemically. Overall, the clinical significance of cardiac metastasis of NET, as well as the safety and efficacy of Lu-177 DOTATATE in this cohort, has not been thoroughly evaluated. Purpose This study assessed the outcomes and clinical consequences of cardiac metastatic involvement in patients with NET. Furthermore, this study investigated the safety of Lu-177 DOTATATE therapy in patients with cardiac metastases from NET. Methods All patients who underwent 68Ga-DOTATATE positron emission tomography for evaluation of NET across three tertiary centers between 2016 and 2022 were retrospectively evaluated. Patients with evidence of cardiac metastasis were further evaluated. Baseline characteristics, treatment modality, and clinical outcomes including mortality, arrhythmia or conduction disease, carcinoid heart disease, and heart failure admissions were recorded. Patients with cardiac metastases were grouped and compared based on therapeutic modality (conservative therapy with surveillance or SSA, Lu-177 DOTATATE therapy, or surgical resection of metastases). Results From 3253 patients with NET, 51 patients were identified to have cardiac metastases (mean age 66.7 ± 12.2 years, 54% male). Three patients underwent surgical resection of cardiac metastases, and in two of whom this was concomitant while undergoing valve surgery for carcinoid heart disease. Patients with cardiac metastasis had significantly higher mortality than patients without cardiac metastasis (HR 2.12, 95%CI 1.00 – 4.52, p = 0.049, Figure 1A). Median follow-up from diagnosis of cardiac metastasis was 3.64 years [IQR 1.59 – 5.64]. There was no significant difference in clinical outcomes between patients that received Lu-177 DOTATATE therapy (n = 27) and conservative therapy (n = 21). Specifically, there was no significant difference in mortality risk at five years post the diagnosis of cardiac metastasis between these groups (p = 0.47, Figure 1B). Conclusion Patients with cardiac metastasis from NETs have worse clinical outcomes than NET patients without cardiac metastatic involvement. Lu-177 DOTATATE therapy appears to be safe in patients with cardiac metastasis from NET.Figure 1AFigure 1B

The severity of metabolic derangement predicts survival of out-of-hospital cardiac arrest and the benefit of extracorporeal life support

Abstract Aims This study aimed to develop Metabolic Derangement score and validate its prognostic performance in patients with out-of-Hospital Cardiac Arrest (OHCA) and also its discriminative performance in guiding the application of extracorporeal life support (ECLS). Methods and Results From 5,100 patients (average age 67 years, 69% male), Metabolic Derangement score was developed to predict primary outcome (death or poor neurologic outcome, cerebral performance category ≥ 3 at day 30) from initial blood laboratory test including pH, PaCO2, PaO2, potassium, haemoglobin, lactate, and creatinine. It was created using machine learning algorithms and a training set (60%), and validated with a test set (40%). The risk of primary outcome consistently increased from 34% to 100% as the Metabolic Derangement score ranged from 0 to 7. Patients with Metabolic Derangement score ≤ 2 showed no difference in the primary outcome risk between those with or without ECLS. Conversely, those with a Metabolic Derangement score ≥3 had a lower risk with ECLS (difference of restricted mean survival time=6.5 days, 95% CI=3.3-9.6 days, ratio of restricted mean time lost=0.76, 95%CI=0.65-0.88, all p&amp;lt;0.001). Clinical subgroup analyses showed generally consistent results. Metabolic Derangement score also outperformed OHCA-, CAHP-, and NULL-PLEASE-scores in prediction the primary outcome (p&amp;lt;0.05, all). Conclusions The severity of metabolic derangement predicted the clinical outcome of OHCA, and could also identify patients likely to benefit from ECLS.Metabolic Derangement score

Mini nutritional assessment is a predictor of mortality and morbidity in patients with pulmonary arterial hypertension

Abstract Background Malnutrition has been demonstrated as a predictor for unfavorable clinical outcomes in chronic heart failure, and may affect patients with pulmonary arterial hypertension (PAH). The Mini Nutritional Assessment (MNA) is a reliable indicator for nutritional status assessment, but its relationship with mortality risk and hospitalization in PAH patients has not yet been investigated. Purpose The study aimed to determine whether the MNA has prognostic value in stable patients with PAH. Methods A prospective multicenter study was performed. All patients completed the MNA at study entry in outpatient clinic or during planned hospitalization. The primary endpoint was all-cause mortality. Secondary end-point was the composite end-point of all cause death or PAH-related hospitalizations. Patients with malnutrition (MNA ≤17 points) or at risk of malnutrition (MNA 18-23,5 points) were considered as having abnormal nutritional status for statistical analysis. Results 182 PAH patients were included to the study (mean age 60 ± 17 years; 73% females; 57% idiopathic PAH). Abnormal nutritional status was identified in 68 (37%) patients. Median and the range of follow up period was 23 months and 0–32 months, respectively. 34 (18.7%) patients died, 53 (29.1%) were hospitalized due to PH, and 57 (31.3%) achieved the composite secondary end-point. Kaplan-Meier survival curves revealed significant differences in overall survival between patients with abnormal MNA and normal MNA, p &amp;lt;0.0001, and significant differences in composite risk of death and PAH-related hospitalization, p=0.02. In the multivariate Cox regression analysis including age, sex, and main risk factors (COMPERA 2.0 score, TAPSE/PASP, right atrial pressure, cardiac index, mix oxygen saturation), abnormal MNA remained significantly associated with all-cause mortality (HR 2.86 [95%CI: 1.29–6.38], p=0.01) and the composite end-point HR 2.39 [95% CI: 1.05–5.42], p=0.04) in PAH patients. Conclusions Using MNA as a routine screening tool allowed the detection of abnormal nutritional status in more than one third of PAH patients. Nutritional status assessed by the MNA was an independent predictor of all-cause death and the composite end-point of all-cause death and PAH-related hospitalization in patients with PAH.

Undiagnosed Diabetes Mellitus is an important risk factor in secondary prevention after an acute coronary syndrome and warrants active screening

Abstract Background/Introduction Previous studies have shown that patients with Diabetes Mellitus (DM) undergoing percutaneous coronary intervention (PCI) for an acute coronary syndrome (ACS) have an increased ischemic risk compared to non-diabetics. This has led to the recommendation to take DM into account when considering extended dual antiplatelet therapy (DAPT) to prevent ischemic events. Although screening for DM can simply be conducted by measuring HbA1c values, the ACS guidelines do not yet recommend to screen for DM de novo. This may lead to undertreatment. Purpose We aimed to determine the ischemic risk of previously diagnosed DM and of DM de novo compared to patients without DM in a real world ACS population. Methods We included patients from the South East (Zuid Oost) Netherlands Heart Registry (ZON-HR) undergoing PCI for ACS without using oral anticoagulants and compared outcomes between DM and non-DM patients. In a subgroup of patients without previously diagnosed DM with available HbA1c measurements at baseline, we compared outcomes between patients with or without DM de novo (HbA1c ≥48 mmol/mol). All analyses were performed using Cox regression analysis. We used multivariate analysis to adjust for known ischemic risk factors. Results Of the 2406 patients included, 426 were previously diagnosed with DM. Additional ischemic risk factors, such as a history of myocardial infarction (MI), multivessel disease and kidney disease, were significantly more often present in patients with DM. Patients with DM showed numerically more major adverse cardiac and cerebral events (MACCE). However, this was not significant (HR: 1.24, 95% CI: 0.92-1.66). All-cause mortality was higher in patients with DM at 30 days (HR: 1.51, 95% CI 1.00-2.29) and 1 year (HR: 1.55, 95% CI 1.10-2.18), which remained significant at 1 year when corrected for additional risk factors. The HbA1c values at baseline were available in 387 patients without previously diagnosed DM. In this subgroup, 69 (18%) patients showed an elevated HbA1c level of ≥48 mmol/mol. Outcomes within this subgroup are presented in table 1. Patients with de novo DM showed significant more ischemic events after one month and one year follow-up compared to patients without DM de novo. Figure 1 depicts the survival from MACCE over time in these subgroups. Conclusion In our real world population of ACS patients undergoing PCI, we found no significant difference in ischemic risk between patients with previously diagnosed DM compared to non-DM. However, all-cause mortality was significant higher in DM patients. Active screening for DM resulted in a large proportion of patients with DM de novo who showed a major increase in ischemic risk. These results demonstrate the importance of screening for DM in ACS patients undergoing PCI.

Differences in cardiovascular risk in the general population of low and high altitude residents in Peru. HIGH Altitude CArdiovascular REsearch Latin America Population Study (HIGHCARE-LAPS)

Abstract Introduction Living at high altitude (HA) is associated with profound changes in cardiovascular physiology, mostly caused by chronic hypoxia. Available data from high income countries (Switzerland, Austria) suggest beneficial effects of moderate altitude residence in terms of cardiovascular risk. Little is known, however, about cardiovascular risk profile in long-term residents of higher altitudes from low-income countries. Aim To compare cardiovascular risk estimated with validated score in population-based samples of permanent residents of low and high-altitude communities in Peru. Methods Study participants (adults permanently residing at either low or high altitude) were recruited by sex- and age-stratified random multistage cluster sampling from the general population of urban areas at different altitudes in Peru (lowlanders: &amp;lt;500 m above sea level, highlanders: cities at 3287 m, 3824 m and 4330 m). For all participants questionnaire-based information, conventional blood pressure (BP; 3 seated measurements with a validated oscillometric device) and laboratory variables were obtained. Based on the collected data atherosclerotic cardiovascular disease (ASCVD) risk was estimated according to Pooled Cohort Equations (PCE, previously calibrated in South American population). Participants below 40 years of age, with ASVCD history, with LDL-C≥190 mg/dL or on LDL-C lowering therapy were excluded from this analysis. Results The analysis included 146 lowlanders and 373 highlanders, most of whom had low 10-year ASVCD risk, with the median estimated risk being significantly higher among lowlanders. Comparisons between the groups in terms of principal variables of interest are reported in the Table. The highlanders were slightly younger, had lower BMI, conventional BP, HDL cholesterol, lower prevalence of antihypertensive medication and of diabetes, and higher heart rate. In a multivariable model the difference in ASCVD risk between lowlanders and highlanders was significant (p=0.0009) after adjusting for BMI and socio-economic variables but not after systolic BP was included in the model (p=0.800). Conclusions Residence at HA is associated with a lower estimated ASCVD risk in the general population of Peru, mainly because of lower BP levels. Considering that the prognostic value of cardiovascular risk estimates in highland populations is unknown, longitudinal cohort studies would be required to assess whether this finding is associated with a lower rate of cardiovascular events.

Cardiovascular risk factors and disease mortality among asian american subgroups

Abstract Background Asian Americans are the fastest growing racial group in the United States. Although Asian subgroups have distinct cardiovascular (CV) risk profiles, they are often aggregated together for public health surveillance. Purpose We provide the first comprehensive national estimates of CV and CV risk factor mortality in Asian American subgroups to assess differences in CV risk. Methods We used CDC WONDER, which captures all death certificates in the US (2018-2020), as well as the American Community Survey for demographic data. Adults aged ≥18 years were included. Estimates of age-adjusted overall CV mortality, as well as heart disease, hypertension, and stroke-related mortality, were determined by ICD-10 codes. To compare the contribution of each cause of mortality among subgroups with different baseline all-cause mortality rates, proportional mortality rates were determined by race. Proportional mortality was defined as the mortality rate of each condition divided by the all-cause mortality for that race group. Differences in proportional mortality by race and ethnicity, compared with White American adults, were assessed with age-sex adjusted linear regression. Results The US population consisted of 12,950,565 Asian Americans (53.7% female). Among the Asian American subgroups, 25.4% were Asian Indian, 28.5% Chinese, 19.7% Filipino, 5.3% Japanese, 9.6% Korean, and 11.8% Vietnamese. A total of 160,282,147 adults were White. Age-adjusted baseline mortality rates are shown in the Table. Compared with White adults, Asian Indian (34.5% vs 29.3%; adjusted difference 5.2%, [95% CI: 1.8%, 8.6%], P=0.009) and Filipino (32.8% vs 29.3%; adjusted difference 3.5%, [95% CI: 0.1%, 6.9%], P=0.04) adults had significantly higher proportional mortality from all CV causes. Asian Indian (26.0% vs 22.6%; adjusted difference 3.2%, [95% CI: 0.3%, 6.2%], P=0.04) adults had higher proportional mortality from heart disease than White adults, while Korean (17.3% vs 22.6%; adjusted difference -5.2%, [95% CI: -8.1%, -2.2%], P=0.01) and Vietnamese (17.5% vs 22.6%; adjusted difference -5.1%, [95% CI: -8.0%, -2.1%], P=0.01) adults had lower proportional mortality. Every Asian American subgroup had higher proportional mortality from hypertension causes compared with White adults, except for Asian Indians (Figure). In addition, every Asian American subpopulation had higher proportional mortality from stroke compared with White adults (Figure). Conclusions CV risk factor and disease-related mortality varies substantially among Asian American subgroups. Public health efforts targeted to address CV health disparities among the diverse group of Asian Americans are needed.

Posterior Fossa Arachnoid cysts (PFACs) in pediatric patients: a single-center retrospective study and proposal of a treatment flow-chart.

To investigate how different presentations of posterior fossa arachnoid cysts (PFACs) influence surgical indication and strategies and their impact on clinical and radiological outcome in children, proposing a treatment flow-chart. In this retrospective study, children < 14 years old with PFAC diagnosed at IRCCS Giannina Gaslini Hospital from 2008 to 2023 were identified Patients showing a mega cisterna magna (MCM), Dandy-Walker syndrome (DWS), Blake's pouch cyst (BPC), neuroenteric cysts or multiple cysts were excluded. Data regarding type of treatment, age at surgery, surgical complications were collected and analyzed. Clinical and radiological outcomes were considered at 1-, 3- and 5-years follow-up. A "wait and see" strategy in asymptomatic showed better clinical outcomes at 1-year follow-up (p = 0.047). No significant difference in clinical outcome or risk of re-surgery were observed between microsurgical fenestration, endoscopical fenestration or shunting were reported, while location of the cyst influenced surgical strategy (p = 0.015). Age < 12 months at surgery (p = 0.008), hydrocephalus (p = 0.001), especially when associated with macrocephaly (p = 0.004), and the placement of a shunt (p = 0.006) resulted as risk factors of re-surgery. An association between radiological and clinical outcomes was observed at 1-year follow-up. Treatment decision should be based on clinical presentation rather than radiological presentation. While a "wait and see" strategy is suggested in asymptomatic patients, when surgery is indicated, several factors should be considered, such as presence of hydrocephalus, location of the cyst and age of the patient, to improve clinical outcomes, reducing complications.

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

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

The effects of angiotensin receptor-neprilysin inhibitors on clinical outcomes in heart failure with mildly reduced or preserved ejection fraction: real-world evidence from the CCA Database-HF Center

Abstract Background Recent clinical trials have demonstrated the potential efficacy and safety of angiotensin receptor-neprilysin inhibitors (ARNI) in patients with heart failure (HF) with mildly reduced or preserved ejection fraction. Nevertheless, the generalizability of these findings in real-world clinical settings remains to be determined. We aimed to compare the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB)on clinical outcomes in HF patients with mildly reduced or preserved ejection fraction. Methods Patient-level data was derived from the China Cardiovascular Association Database-HF Center Registry. We included exclusively a subpopulation of HF patients with left ventricular ejection fraction (LVEF) &amp;gt;40% and comorbid with hypertension. Patients prescripted with ARNI at discharge and sustaining to ARNI therapy during follow-up were categorized as the ARNI group, while those maintaining the usage of ACEI/ARB after discharge were designated as the ACEI/ARB group. In complete cases, the primary endpoint of all-cause mortality at one year was assessed by the 1:1 propensity score matching (PSM) method. Results In all HF patients with LVEF &amp;gt;40% comorbid with hypertension, the usage of ARNI has increased from 0.9% in 2017 to 37.2% in 2021. A total of 3348 patients in the ARNI group and 7688 patients in the ACEI/ARB group were identified for comparative effectiveness. After 1:1 PSM, 5482 patients were included in the primary analysis, with 2741 patients in each treatment arm. The proportion of patients receiving higher dosages of ARNI (200mg/d and 400mg/d) was 20.9%, 26.6%, 29.2%, and 30.3% at discharge, 1-month, 3-month, and 1-year, respectively. Over the 1-year follow-up, ARNI was associated with a 20% relative reduction in all-cause death compared to the ACEI/ARB therapy (10.5% vs. 12.9%, adjusted hazard ratio [HR], 0.80 [95% CI, 0.69-0.94], P=0.005). The absolute risk difference in all-cause death between ARNI and ACEI/ARB arms was 2.88 per 100 patient-years (incidence rate difference, -2.88 [95% CI, -4.86 to -0.9]). Cardiovascular death also tended to decrease in the ARNI group but with missed statistical significance (4.5% vs. 4.9%, adjusted HR, 0.89 [95% CI, 0.70-1.14], P=0.373). Treatment benefits were more significant in those with LVEF between 40-50% (adjusted HR, 0.62 [95% CI, 0.48-0.79]), 50-60% (adjusted HR, 0.85 [95% CI, 0.68-1.06]), but not observed in HF patients with LVEF&amp;gt;60% (adjusted HR, 1.80 [95% CI, 1.08-2.98]; Pinteraction&amp;lt;0.001). Conclusion In real-world clinical settings, treatment with ARNI was associated with a significant relative risk reduction in all-cause mortality compared with ACEI/ARB in HF patients with mildly reduced or preserved LVEF. The cardiovascular benefit was concentrated in patients with LVEF ≤60%.

Impact of dapagliflozin on cardiometabolic outcomes after myocardial infarction according to baseline left ventricular ejection fraction: a DAPA-MI substudy

Abstract Background Dapagliflozin improved cardiometabolic outcomes compared with placebo following acute myocardial infarction (MI) in participants without prior diabetes mellitus (DM) or chronic heart failure (HF) in the DAPA-MI trial. Purpose Cardiometabolic outcomes were assessed in the DAPA-MI trial according to left ventricular ejection fraction (EF) at randomisation. Methods Participants were categorised according to whether baseline EF was ≥50 or &amp;lt;50%. Those without a baseline EF result and those who did not receive a dose of study drug were excluded. The primary objective was to determine the clinical effect of dapagliflozin 10 mg versus placebo assessed using a hierarchical composite outcome and analysed by the win ratio method. The primary outcome was the hierarchical composite, by order of perceived clinical importance, of death, hospitalization for HF (HHF), nonfatal MI, atrial fibrillation/flutter event, new diagnosis of type 2 DM, NYHA functional class at the last trial visit, and body weight decrease of ≥5% from baseline to the last trial visit. Time to first event of NYHA class II-IV or HHF and time to first event of NYHA class III-IV or HHF were assessed as endpoints of special interest. Hazard ratios (HR) with 95% confidence intervals (CI) were determined using Cox proportional hazards models. The main subgroup variable (baseline EF ≥50 or &amp;lt;50) and its interaction with treatment (P int) were included. Results 838 participants had EF≥50 and 2913 had EF&amp;lt;50 at baseline. The primary hierarchical composite outcome resulted in a win ratio for those with EF≥50 of 1.32 (CI 1.00-1.73) and 1.38 for those with EF&amp;lt;50 (CI 1.21-1.57; P int 0.8) (Figures). There were no significant interactions by EF for any of the secondary outcomes. In those with EF&amp;lt;50, a first event of NYHA class II-IV or HHF occurred in 435 (29.4%) participants in the dapagliflozin group and 485 (33.8%) in the placebo group (absolute risk difference [ARD] 4.4%; HR 0.83, CI 0.73-0.94, P&amp;lt;0.01). In those with EF≥50, this occurred in 81 (19.7%) and 93 (21.8%), respectively (ARD 2.1%; HR 0.96, CI 0.65-1.41, P=0.7; P int 0.47). In those with EF&amp;lt;50, a first event of NYHA class III-IV or HHF occurred in 77 (5.2%) in the dapagliflozin and 115 (8.0%) in the placebo groups (ARD 2.2%; HR 0.64, CI 0.48-0.85, P&amp;lt;0.01). In those with EF≥50, this occurred in 14 (3.4%) and 19 (4.4%), respectively (ARD 1.0%; HR 0.80, CI 0.40-1.60, P=0.5; P int 0.55). There was no significant effect of dapagliflozin on death/MI/stroke in either subgroup (EF&amp;lt;50: HR 0.96, CI 0.65-1.41; EF≥50: HR 0.83, CI 0.38-1.84; P int 0.75). Dapagliflozin increased the incidence of 5% weight loss in both of the EF subgroups with no significant interaction. Conclusions Dapagliflozin resulted in significant benefit in cardiometabolic outcomes compared with placebo regardless of baseline EF. The absolute reduction in HF symptoms or HHF with dapagliflozin, compared with placebo, was greatest in those with baseline EF&amp;lt;50.Figures

Proactive therapeutic drug monitoring of biologic drugs in patients with inflammatory bowel disease, inflammatory arthritis, and psoriasis: systematic review and meta-analysis

ObjectiveTo address the efficacy and safety of proactive therapeutic drug monitoring of biologic drugs for patients with inflammatory bowel disease, inflammatory arthritis, and psoriasis.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, Central,...

Progression of aortic stenosis in patients with diabetes mellitus type 2 compared with matched controls

Abstract Background Degenerative aortic stenosis (AS) and diabetes mellitus type 2 (DM) increase with age1,2 and their prevalence is expected to rise. Patients with DM have a higher risk to develop AS3 and the pathophysiological process leading from a normal aortic valve to AS involves factors associated with DM. AS develops over years, but it can evolve more rapidly. There is insufficient knowledge about risk factors for rapid progression in AS and monitoring strategies among patients at high risk for rapid progression. The aim of this project is to evaluate the AS progression towards combined outcome (incident heart failure, death, need for intervention) in patients with type 2 DM compared with matched controls. Methods From the Swedish National Diabetes Register (NDR) we identified all patients with type 2 DM between 01-01-2001- 31-12-2019 and for each patient 5 controls (matched for age, sex, region) from the Swedish Total Population Register. Afterwards we identified a cohort of individuals with AS from these two groups, by linking the NDR with the National Patient Register. The outcomes were: all- cause and cardiovascular mortality, and combined outcome (mortality, hospitalization for heart failure (HF) or aortic valve replacement (AVR)). We used Kaplan Meier survival curves to detect differences in all-cause mortality, cardiovascular mortality, time until AVR and combined outcome between cases and controls. Cox proportional hazards model adjusted for sex, age, obesity, renal failure, hyperparathyroidism, hypertension, hyperlipidemia was used to study the risk difference between the cases and controls for the combined outcome. Results We identified 16 144 individuals with type 2 DM and AS and 31 206 matched controls. The individuals with type 2 DM were predominately men (59% vs 53%), younger (mean age 70.6 vs 71.9), and had more comorbidities. In unadjusted analysis they were hospitalized for HF more often (8.2% vs 6.8%) and more often underwent AVR (surgically) (22.0% vs 19.0%) or transcatheter(6.6% vs 5.0%). Patients with AS and DM had higher all-cause and cardiovascular mortality and faster progression towards death, AVR or hospitalization for HF (see figure 1, A, B, C). The progression to AVR was significant, although the difference was small and not clinically relevant (plot D). In the adjusted model, the patients with AS and DM had 13% higher hazard to have the combined outcome compared with controls (see figure 2). Sex (female), hypertension and hyperlipidemia lowered the hazard for the combined event, while obesity, hyperparathyroidism and renal failure increased the hazard for the combined event. Conclusions Patients with concomitant AS and DM seem to have faster progression towards death (both all-cause and cardiovascular), and heart failure hospitalization or AVR compared with patients with AS without DM. Therefore, it might be appropriate to be more active regarding follow-up and intervention in these patients.Kaplan Meirer curvesForest plot for adjusted Cox model

Left ventricular dysfunction, pulmonary congestion, or both and cardiovascular risk after acute myocardial infarction

Abstract Background Patients with acute myocardial infarction (AMI) complicated by left ventricular systolic dysfunction (LVSD), pulmonary congestion, or both are at increased risk for adverse cardiovascular events, including long-term heart failure. The EMPACT-MI trial studied the efficacy and safety of early initiation of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) in this population. We set out to evaluate the contemporary real-world risk associated with AMI presenting with LVSD and/or congestion and the projected impact of implementing early SGLT2i post-MI across the spectrum of risk. Purpose To evaluate the independent risk of presenting with LVSD, congestion, or both in patients with AMI. We will further explore the potential impact of the implementation of early initiation of SGLT2i in real-world clinical practice. Methods We conducted a retrospective population-based cohort study in Ontario, Canada, analyzing AMI hospitalizations from April 2009 to March 2022, emulating the EMPACT-MI trial cohort. Patients that survived to hospital discharge were stratified by baseline presentation with LVSD (defined as LVEF&amp;lt;50%), signs or symptoms of congestion or both and compared with a referent group without either risk factor (none). Exclusion criteria were previously established heart failure, prior SGLT2i use, eGFR &amp;lt; 20 ml/min/1.73m2 or chronic dialysis. The primary outcome was a composite of HF hospitalization or all-cause mortality at 30 days and 1 year. We used a multivariable logistic regression model to report an odds ratio (OR) and 95% confidence intervals (CI) adjusted for clinical risk factors. Results Among 36,837 AMI patients, 3% presented with congestion, 55% with LVSD, 10% with both, and 32% with none. Age/sex-adjusted 30-day event rates for the primary endpoint were 30%, 22%, 57%, and 7%, respectively. The corresponding adjusted ORs were 3.34 (95% CI: 2.05-5.46) for congestion, 3.58 (95% CI: 2.72-4.71) for LVSD, and 7.01 (95% CI: 5.09-9.65) for both, versus the reference group (none) (Figure 1). At year 1, a similar pattern of risk was observed (Figure 2). Based on the results of the EMPACT-MI trial being reported at the ACC conference in April 2024, relative and absolute risk differences in outcomes with implementation of early initiation of SGLT2i post-MI in real-world clinical practice across the spectrum of presentation will be reported. Conclusion Patients presenting with pulmonary congestion and/or LVSD remain at high risk of adverse cardiovascular events following AMI. This high-risk group represents an unmet need with a potential impact for improvement with novel interventions such as SGLT2i.

Trends in major cardiac events after ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention from 2003 to 2017: the western Denmark heart registry

Abstract Background In Denmark, primary percutaneous coronary intervention (PCI) has been the national reperfusion strategy since 2003. We recently reported a gradual decline in 1-year mortality in patients treated with pPCI-treated STEMI from 2003 to 2017. To elucidate potential causes of this observation, we examined temporal trends in the 1-year risk of major adverse cardiovascular events (MACE). Purpose To examine trends in 1-year risks of MACE following STEMI treated with pPCI from 2003 to 2017. Methods Using the Western Denmark Heart Registry, we identified STEMI patients undergoing first-time pPCI from 2003 to 2017 and divided the patients into four time periods. The main outcome was 1-year risk of MACE, defined as recurrent myocardial infarction, ischaemic stroke, or cardiovascular death. Cause-specific adjusted hazard ratios (HR) were used to assess temporal trends using the first period (2003-2006) as reference. Further, temporal trends were compared to an age-, sex-, and calendar-year matched general population. Results From 2003 to 2017, 18,540 pPCI-treated STEMI patients were identified (median [Q1-Q3] age, 64 [55-74] years); 13,639 men [74%]). Trends in 1-year risk of MACE showed a gradual reduction over time from 13.0% in 2003-2006, 11.8% in 2007-2010, 9.7% in 2011-2014, to 8.7% in 2015-2017 (Figure). The adjusted relative risk reduction was 33% when comparing 2015-2017 with 2003-2006 (adjusted HR 0.67, 95% CI 0.58-0.76). Comparable relative risk reductions were observed for all three individual components of MACE of 33-35%. Compared to the matched general population, the 1-year risk difference in MACE decreased from 11% in 2003-2006 to 7% in 2015-2017. Conclusions In a high-income European country with a fully implemented pPCI strategy, 1-year risk of MACE declined by approximately one-third after first-time STEMI between 2003 to 2017. This MACE reduction was substantially larger than observed in the matched general population, i.e., confirming an important reduction in the excess risk associated with STEMI.

Mortality related to left ventricular ejection fraction and obstructive coronary artery disease in non-ST-segment elevation myocardial infarction

Abstract Background Extent of coronary artery disease (CAD) and the severity of reduced left ventricular ejection fraction (LVEF) have both been associated with the prognosis after non-ST-segment elevation myocardial infarction (NSTEMI). However, the contemporary mortality associated with the extent of obstructive CAD over a range of LVEF remains uncertain. Purpose The aim of this study was to assess the impact of CAD and LVEF on all-cause death following a first-time NSTEMI. Methods We included consecutive first-time NSTEMI patients undergoing coronary angiography from 2010 to 2021 in Western Denmark. Patients were stratified by extent of obstructive vessel disease (VD; 1, 2, or 3VD) and LVEF (≥51%, 41-50%, or 10-40%). Patients with previous myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting were excluded. The primary outcome was all-cause death. We calculated 5-year cumulative incidence proportions (CIP) as a measure of absolute risk and adjusted hazard ratios (HR). Results A total of 8,770 patients with first-time NSTEMI and obstructive CAD were examined with coronary angiography. Two-thirds were male and median age was 68 years (Q1-Q3: 58-78). The increase in mortality associated with decreasing LVEF was greater than observed by extent of CAD (Table). Thus, the 5-year mortality increased stepwise by extent of CAD from 14% for 1VD to 31% for 3VD (adjusted HR 1.35, 95% CI:1.19-1.54), but from 12% for LVEF ≥51% to 40% for LVEF 10-40% (adjusted HR 2.32, 95% CI: 2.04-2.65). When combining LVEF and extent of CAD, an increase in 5-year mortality was found from 9% for 1VD and LVEF ≥51% to 46% for 3VD and LVEF 10-40% (risk difference of 37.1%; Figure). Correspondingly, using 1VD and LVEF ≥51% as reference, the adjusted HRs increased gradually with extent of CAD and decline in LVEF to 3.05 (95% CI: 2.51-3.70) for patients with 3VD and LVEF 10-40% (Table). Conclusion In a contemporary all-comers cohort of first-time NSTEMI patients, increasing extent of CAD and declining LVEF are both associated with a gradual increase in 5-year mortality. Our data suggest that the level of LVEF reduction was more strongly associated with 5-year mortality than CAD extent.

Twenty-year trends in peripheral artery disease, lower extremity revascularization, and lower extremity amputation in newly diagnosed type 2 diabetes

Abstract Background Trends in risk of lower extremity complications in patients with newly diagnosed type 2 diabetes (T2DM) are largely unexplored. Purpose To examine the 5-year risk trends of peripheral artery disease (PAD), lower extremity revascularization (LER), and lower extremity amputation (LEA) in patients with newly diagnosed T2DM over a 25-year study period. Methods We conducted a cohort study that included all patients in Denmark diagnosed with T2DM from 1996 to 2015, who had no prior hospital diagnosis of atherosclerotic cardiovascular disease. These patients were age- and sex-matched with up to three comparisons from the general population. Individuals were assigned to 5-year calendar periods based on their year of inclusion and were followed for 5 years. The primary outcomes were the 5-year risks of PAD, LER, and LEA. Age- and sex-adjusted hazard ratios (aHR) were computed using Cox regression analysis. Results The study cohort consisted of 288,825 newly diagnosed T2DM patients (52% males; median age 61 years) and 782,232 comparisons from the general population. From 1996-2000 to 2015-2020, the 5-year risk of PAD decreased from 2.2% to 1.2% (aHR 0.56 [95% CI 0.52-0.61]), LER from 0.7% to 0.5% (aHR 0.73 [95% CI 0.63-0.84]), and LEA from 1.0% to 0.4% (aHR 0.44 [95% CI 0.38-0.50]) in T2DM patients (Figure). Compared with the general population, the 5-year risk differences decreased from 1.4% to 0.5% for PAD, from 0.4% to 0.2% for LER, and from 0.8% to 0.3% for LEA. The distribution of LEA types (hip/thigh, knee/lower leg, or ankle/foot/toe amputation) remained largely stable over time in T2DM patients. Use of prophylactic cardiovascular medications in T2DM patients increased notably during the study period, especially use of statins (5% to 50%) and multiple antihypertensive drugs (18% to 33%). Conclusions Over recent decades, the risks of PAD, LER, and LEA have decreased in patients with newly diagnosed T2DM, approaching the risk levels observed in the general population. This coincided with a great increase in use of prophylactic cardiovascular medications among T2DM patients.Trends in lower extremity complications.