Pre-existing maternal cardiovascular disease and the risk of offspring cardiovascular disease from infancy to early adulthood.

BACKGROUND AND AIMS: A variety of maternal heart conditions are associated with abnormal placentation and reduced foetal growth. However, their impact on offspring's long-term cardiovascular health is poorly studied. This study aims to investigate the association between intrauterine exposure to pre-existing maternal cardiovascular disease (CVD) and offspring CVD occurring from infancy to early adulthood, using paternal CVD as a negative control. METHODS: This nationwide cohort study used register data of live singletons without major malformations or congenital heart disease born between 1992 and 2019 in Sweden. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for essential maternal characteristics. Paternal CVD served as a negative control for assessment of unmeasured genetic and environmental confounding. RESULTS: Of the 2 597 786 offspring analysed (49.1% female), 26 471 (1.0%) were born to mothers with pre-existing CVD. During a median follow-up of 14 years (range 1-29 years), 17 382 offspring were diagnosed with CVD. Offspring of mothers with CVD had 2.09 times higher adjusted HR of CVD (95% CI 1.83, 2.39) compared with offspring of mothers without CVD. Compared with maternal CVD, paternal CVD showed an association of smaller magnitude (HR 1.49, 95% CI 1.32, 1.68). Increased hazards of offspring CVD were also found when stratifying maternal CVD into maternal arrhythmia (HR 2.94, 95% CI 2.41, 3.58), vascular (HR 1.59, 95% CI 1.21, 2.10), and structural heart diseases (HR 1.48, 95% CI 1.08, 2.02). CONCLUSIONS: Maternal CVD was associated with an increased risk of CVD in offspring during childhood and young adulthood. Paternal comparison suggests that genetic or shared familial factors may not fully explain this association.

Sudden cardiac death after myocardial infarction: individual participant data from pooled cohorts.

BACKGROUND AND AIMS: Risk stratification of sudden cardiac death after myocardial infarction and prevention by defibrillator rely on left ventricular ejection fraction (LVEF). Improved risk stratification across the whole LVEF range is required for decision-making on defibrillator implantation. METHODS: The analysis pooled 20 data sets with 140 204 post-myocardial infarction patients containing information on demographics, medical history, clinical characteristics, biomarkers, electrocardiography, echocardiography, and cardiac magnetic resonance imaging. Separate analyses were performed in patients (i) carrying a primary prevention cardioverter-defibrillator with LVEF ≤ 35% [implantable cardioverter-defibrillator (ICD) patients], (ii) without cardioverter-defibrillator with LVEF ≤ 35% (non-ICD patients ≤ 35%), and (iii) without cardioverter-defibrillator with LVEF > 35% (non-ICD patients >35%). Primary outcome was sudden cardiac death or, in defibrillator carriers, appropriate defibrillator therapy. Using a competing risk framework and systematic internal-external cross-validation, a model using LVEF only, a multivariable flexible parametric survival model, and a multivariable random forest survival model were developed and externally validated. Predictive performance was assessed by random effect meta-analysis. RESULTS: There were 1326 primary outcomes in 7543 ICD patients, 1193 in 25 058 non-ICD patients ≤35%, and 1567 in 107 603 non-ICD patients >35% during mean follow-up of 30.0, 46.5, and 57.6 months, respectively. In these three subgroups, LVEF poorly predicted sudden cardiac death (c-statistics between 0.50 and 0.56). Considering additional parameters did not improve calibration and discrimination, and model generalizability was poor. CONCLUSIONS: More accurate risk stratification for sudden cardiac death and identification of low-risk individuals with severely reduced LVEF or of high-risk individuals with preserved LVEF was not feasible, neither using LVEF nor using other predictors.

Associations between rheumatoid arthritis, incident heart failure, and left ventricular ejection fraction.

BACKGROUND: Rheumatoid arthritis (RA) is an independent risk factor for heart failure (HF). Yet, the association between RA and left ventricular ejection fraction (LVEF) in incident HF is not well studied, nor are outcomes of HF in RA by LVEF. METHODS: We identified incident HF patients between 2003 and 2018 through the Swedish Heart Failure Registry, enriched with data from national health registers. Using logistic regression, associations between a prior diagnosis of RA and LVEF among HF patients and vs age, sex, and geographical area matched general population controls without HF were assessed. Additionally, associations between HF with vs without a prior diagnosis of RA, by LVEF, and outcomes up to 5 years after HF diagnosis were investigated using Cox regression. LVEF was primarily dichotomized at 40% and secondarily categorized as <40%, 40% to 49%, and ≥50%. Covariates included demographics and cardiovascular comorbidities. RESULTS: Among 20,916 incident HF patients, 331 (1.6%) had RA vs 1,047/103,501 (1.0%) of HF-free controls. The odds ratio (OR) for RA was 1.4 (95% CI: 1.1-1.8) in LVEF<40% vs HF-free controls and 1.6 (95% CI: 1.3-2.0) in LVEF≥40% vs HF-free controls. Among HF patients, RA was more common in HF with LVEF ≥40% (1.9%) vs LVEF<40% (1.3%), corresponding to OR 1.4 (95% CI: 1.1-1.7). No associations between RA and cardiovascular outcomes were observed across LVEF. An association between RA and all-cause mortality was observed only for patients with LVEF<40% (hazard ratio: 1.4; 95% CI: 1.1-1.8). CONCLUSIONS: RA was independently associated with incident HF, particularly HF with LVEF≥40%. RA did not associate with cardiovascular outcomes following HF diagnosis but was associated with increased risk of all-cause mortality in HF with LVEF<40%.

Dyskalemias and adverse events associated with discharge potassium in acute myocardial infarction.

BACKGROUND: The incidence of dyskalemias and associated outcomes in acute myocardial infarction (AMI) are unknown in real-world settings and likely differ from the controlled environment of randomized controlled trials. METHODS: We examined consecutive survivors of an AMI during 2006-2011 in SWEDEHEART registry and with plasma potassium at discharge (exposure). Study outcomes were 1-year risk of hyperkalemia (potassium >5.0 mmol/L), hypokalemia (potassium <3.5 mmol/L), and others (1-year risk of death, new myocardial infarction, heart failure, and de novo atrial fibrillation). Covariates included demographics, comorbidities, hospital procedures, and medications. RESULTS: We included 4,861 patients (65% male, age 71.4 ±â€¯12.6 years) with mean discharge potassium of 4.0 ±â€¯0.4 mmol/L. Within 1 year, 784 (16.1%) new hyperkalemic and 991 (20.4%) new hypokalemic events occurred. Discharge potassium and kidney dysfunction were independent predictors of their occurrence. Compared with discharge potassium of 4.0 to <4.5 mmol/L, the adjusted risk of incident hyperkalemia was 1.71 (95% confidence interval 1.41-2.06) for potassium of 4.5-5.0 mmol/L and 2.38 (1.69-3.35) for potassium of >5.0 mmol/L; the adjusted risk of incident hypokalemia was 1.43 for potassium of 3.5 to <4.0 mmol/L (1.23-1.66) and 3.12 (2.58-3.77) for potassium of <3.5 mmol/L. A U-shaped association was observed between discharge potassium and the risk of death (n = 718), with increased hazards for potassium <3.5 and >4.5 mmol/L. No association was found between discharge potassium and the risk of new myocardial infarction, heart failure, or de novo atrial fibrillation. CONCLUSIONS: Among real-world AMI survivors, both hyperkalemia and hypokalemia are frequent. Discharge potassium and kidney function strongly predicted their occurrence, as well as the 1-year risk of death.

Chest compression alone cardiopulmonary resuscitation is associated with better long-term survival compared with standard cardiopulmonary resuscitation.

BACKGROUND: Little is known about the long-term survival effects of type-specific bystander cardiopulmonary resuscitation (CPR) in the community. We hypothesized that dispatcher instruction consisting of chest compression alone would be associated with better overall long-term prognosis in comparison with chest compression plus rescue breathing. METHODS AND RESULTS: The investigation was a retrospective cohort study that combined 2 randomized trials comparing the short-term survival effects of dispatcher CPR instruction consisting either of chest compression alone or chest compression plus rescue breathing. Long-term vital status was ascertained by using the respective National and State death records through July 31, 2011. We performed Kaplan-Meier method and Cox regression to evaluate survival according to the type of CPR instruction. Of the 2496 subjects included in the current investigation, 1243 (50%) were randomly assigned to chest compression alone and 1253 (50%) were randomly assigned to chest compression plus rescue breathing. Baseline characteristics were similar between the 2 CPR groups. During the 1153.2 person-years of follow-up, there were 2260 deaths and 236 long-term survivors. Randomization to chest compression alone in comparison with chest compression plus rescue breathing was associated with a lower risk of death after adjustment for potential confounders (adjusted hazard ratio, 0.91; 95% confidence interval, 0.83-0.99; P=0.02). CONCLUSIONS: The findings provide strong support for long-term mortality benefit of dispatcher CPR instruction strategy consisting of chest compression alone rather than chest compression plus rescue breathing among adult patients with cardiac arrest requiring dispatcher assistance.

Pregnancy-Induced Hypertensive Disorder and Risks of Future Ischemic and Nonischemic Heart Failure.

BACKGROUND: Although adverse pregnancy outcomes are associated with an increased risk of cardiovascular disease, studies on timing and subtypes of heart failure after a hypertensive pregnancy are lacking. OBJECTIVES: The goal of this study was to assess the association between pregnancy-induced hypertensive disorder and risk of heart failure, according to ischemic and nonischemic subtypes, and the impact of disease characteristics and the timing of heart failure risks. METHODS: This was a population-based matched cohort study, comprising all primiparous women without a history of cardiovascular disease included in the Swedish Medical Birth Register between 1988 and 2019. Women with pregnancy-induced hypertensive disorder were matched with women with normotensive pregnancies. Through linkage with health care registers, all women were followed up for incident heart failure, classified as ischemic or nonischemic. RESULTS: In total, 79,334 women with pregnancy-induced hypertensive disorder were matched with 396,531 women with normotensive pregnancies. During a median follow-up of 13 years, rates of all heart failure subtypes were more common among women with pregnancy-induced hypertensive disorder. Compared with women with normotensive pregnancies, adjusted HRs (aHRs) with 95% CIs were as follows: heart failure overall, aHR: 1.70 (95% CI: 1.51-1.91); ischemic heart failure, aHR: 2.28 (95% CI: 1.74-2.98); and nonischemic heart failure, aHR: 1.60 (95% CI: 1.40-1.83). Disease characteristics indicating severe hypertensive disorder were associated with higher heart failure rates, and rates were highest within the first years after the hypertensive pregnancy but remained significantly increased thereafter. CONCLUSIONS: Pregnancy-induced hypertensive disorder is associated with an increased short-term and long-term risk of incident ischemic and nonischemic heart failure. Disease characteristics indicating more severe forms of pregnancy-induced hypertensive disorder amplify the heart failure risks.

Sex-related differences in the management and outcomes of patients hospitalized with ST-elevation myocardial infarction: a comparison within four European myocardial infarction registries.

Aims: Data on how differences in risk factors, treatments, and outcomes differ between sexes in European countries are scarce. We aimed to study sex-related differences regarding baseline characteristics, in-hospital managements, and mortality of ST-elevation myocardial infarction (STEMI) patients in different European countries. Methods and results: Patients over the age of 18 with STEMI who were treated in hospitals in 2014-17 and registered in one of the national myocardial infarction registers in Estonia (n = 5817), Hungary (n = 30 787), Norway (n = 33 054), and Sweden (n = 49 533) were included. Cardiovascular risk factors, hospital treatment, and recommendation of discharge medications were obtained from the infarction registries. The primary outcome was mortality, in-hospital, after 30 days and after 1 year. Logistic and cox regression models were used to study the associations of sex and outcomes in the respective countries. Women were older than men (70-78 and 62-68 years, respectively) and received coronary angiography, percutaneous coronary intervention, left ventricular ejection fraction assessment, and evidence-based drugs to a lesser extent than men, in all countries. The crude mortality in-hospital rates (10.9-15.9 and 6.5-8.9%, respectively) at 30 days (13.0-19.9 and 8.2-10.9%, respectively) and at 1 year (20.3-28.1 and 12.4-17.2%, respectively) after hospitalization were higher in women than in men. In all countries, the sex-specific differences in mortality were attenuated in the adjusted analysis for 1-year mortality. Conclusion: Despite improved awareness of the sex-specific inequalities on managing patients with acute myocardial infarction in Europe, country-level data from this study show that women still receive less guideline-recommended management.

Incidence and Predictors of Out-of-Hospital Cardiac Arrest Within 90 Days After Myocardial Infarction.

BACKGROUND: The risk of sudden cardiac death (SCD) is high early after myocardial infarction (MI). Current knowledge and guidelines mainly rely on results from older clinical trials and registry studies. Left ventricular ejection fraction (LVEF) alone has not been proven a reliable predictor of SCD. OBJECTIVES: This study sought to identify the incidence and additional predictors of SCD early after MI in a contemporary nationwide setting. METHODS: The authors used data from SWEDEHEART, the Swedish Cardiopulmonary Resuscitation Registry, and the Swedish Pacemaker and Implantable Cardioverter-Defibrillator (ICD) Registry. Cases of MI, which had undergone coronary angiography and were discharged alive between 2009 to 2017 without a prior ICD, were followed up to 90 days. Cox regression models were used to assess associations between clinical parameters and out-of-hospital cardiac arrest (OHCA). RESULTS: Among 121,379 cases, OHCA occurred in 349 (0.29%) and non-OHCA death in 2,194 (1.8%). A total of 6 variables (male sex, diabetes, estimated glomerular filtration rate <30 ml/min/1.73 m2, Killip class ≥II, new-onset atrial fibrillation/flutter, and impaired LVEF [reference ≥50%] categorized as 40% to 49%, 30% to 39%, and <30%) were identified as independent predictors, were assigned points, and were grouped into 3 categories, where the incidence of OHCA ranged from 0.12% to 2.0% and non-OHCA death from 0.76% to 11.7%. Stratified by LVEF <40% alone, the incidence of OHCA was 0.20% and 0.76% and for non-OHCA death 1.1% and 4.9%. CONCLUSIONS: In this nationwide study, the incidence of OHCA within 90 days after MI was <0.3%. A total of 5 clinical parameters in addition to LVEF predicted OHCA and non-OHCA death better than LVEF alone.

SWEDEHEART-1-year data show no benefit of newer generation drug-eluting stents over bare-metal stents in patients with severe kidney dysfunction following percutaneous coronary intervention.

BACKGROUND: We hypothesized that the transition from bare-metal stents (BMS) to newer generation drug-eluting stents (n-DES) in clinical practice may have reduced the risk also in patients with kidney dysfunction. METHODS: Observational study in the national SWEDEHEART registry, that compared the 1-year risk of in-stent restenosis (RS) and stent thrombosis (ST) in all percutaneous coronary intervention treated patients(n = 92 994) during 2007-2013. RESULTS: N-DES patients were younger than BMS, but had more often diabetes, previous myocardial infarction, previous revascularization and were more often treated with potent platelet inhibition. N-DES versus BMS, was associated with lower 1-year risk of RS in patients with estimated glomerular filtration rate (eGFR) >60 with a cumulative probability of 2.1% versus 5.3%, adjusted hazard ratio 0.30, 95% CI (0.27-0.34) and with eGFR 30-60: 3.0% versus 4.9%; hazard ratio 0.46 (0.36-0.60) but not in patients with eGFR <30: 8.1% versus 6.0%; hazard ratio 1.32 (0.71-2.45) (pinteraction = 0.009) as well as lower risk of ST for eGFR >60 and eGFR 30-60: 0.5% versus 0.9%; hazard ratio 0.52 (0.40-0.68) and 0.6% versus 1.3%; hazard ratio 0.54 (0.54-0.72) but not for eGFR <30; 2.1% versus 1.1%; hazard ratio 1.49 (0.56-3.98) (pinteraction = 0.027). CONCLUSION: N-DES is associated with lower 1-year risk of in-stent restenosis and stent thrombosis in patients with normal or moderately reduced kidney function but not in patients with severe kidney dysfunction, where stenting is associated with worse outcomes regardless of stent type.

Potassium levels and risk of in-hospital arrhythmias and mortality in patients admitted with suspected acute coronary syndrome.

BACKGROUND: In acute coronary syndrome (ACS), potassium imbalance at admission has been associated with in-hospital arrhythmias, cardiac arrest, and mortality. However, several important presentation characteristics and subtype of ACS have not been considered. METHODS: Consecutive patients (n = 32,955) admitted with suspected ACS between 2006 and 2011, registered in the Swedish Web-System for Enhancement and Development of Evidence-Based care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) and the Stockholm CREAtinine Measurements (SCREAM) project were included. Associations between admission plasma potassium categories (reference 3.5-<4.0 mmol/L) and in-hospital outcomes including mortality, cardiac arrest, new-onset atrial fibrillation, and second- or third-degree atrioventricular block were assessed with logistic regression models. Covariates included demographics, presentation characteristics, comorbidities, estimated glomerular filtration rate (eGFR), main diagnosis, and medication on admission. RESULTS: U-shaped associations between admission potassium, mortality and cardiac arrest were observed. However, in fully adjusted models, only hyperkalemia (5.0-<5.5 [OR 1.83; 95% CI, 1.34-2.49] and ≥5.5 mmol/L [OR 2.27; 95% CI, 1.57-3.27]) was associated with mortality, while only hypokalemia (3.0-<3.5 [OR 1.63; 95% CI, 1.21-2.19] and <3.0 mmol/L [OR 2.72; 95% CI, 1.56-4.74]) was associated with cardiac arrest. Potassium <3.0 mmol/L (OR 1.93; 95% CI, 1.00-3.76) was associated with new-onset atrial fibrillation. After multivariable adjustment, no association was observed between potassium and second- or third-degree atrioventricular block. Results were not modified by main diagnosis (ACS subtype or non-ACS diagnosis) or eGFR. CONCLUSIONS: Hyperkalemia at admission is associated with in-hospital mortality and hypokalemia with cardiac arrest and new-onset atrial fibrillation in patients admitted with suspected ACS.

Development and external validation of a post-discharge bleeding risk score in patients with acute coronary syndrome: The BleeMACS score.

BACKGROUND: Accurate 1-year bleeding risk estimation after hospital discharge for acute coronary syndrome (ACS) may help clinicians guide the type and duration of antithrombotic therapy. Currently there are no predictive models for this purpose. The aim of this study was to derive and validate a simple clinical tool for bedside risk estimation of 1-year post-discharge serious bleeding in ACS patients. METHODS: The risk score was derived and internally validated in the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry, an observational international registry involving 15,401 patients surviving admission for ACS and undergoing percutaneous coronary intervention (PCI) from 2003 to 2014, engaging 15 hospitals from 10 countries located in America, Europe and Asia. External validation was conducted in the SWEDEHEART population, with 96,239 ACS patients underwent PCI and 93,150 without PCI. RESULTS: Seven independent predictors of bleeding were identified and included in the BleeMACS score: age, hypertension, vascular disease, history of bleeding, malignancy, creatinine and hemoglobin. The BleeMACS risk score exhibited a C-statistic value of 0.71 (95% CI 0.68-0.74) in the derivation cohort and 0.72 (95% CI 0.67-0.76) in the internal validation sample. In the SWEDEHEART external validation cohort, the C-statistic was 0.65 (95% CI 0.64-0.66) for PCI patients and 0.63 (95% CI 0.62-0.64) for non-PCI patients. The calibration was excellent in the derivation and validation cohorts. CONCLUSIONS: The BleeMACS bleeding risk score is a simple tool useful for identifying those ACS patients at higher risk of serious 1-year post-discharge bleeding. ClinicalTrials.govIdentifier: NCT02466854.

A user-friendly risk-score for predicting in-hospital cardiac arrest among patients admitted with suspected non ST-elevation acute coronary syndrome - The SAFER-score.

AIM: To develop a simple risk-score model for predicting in-hospital cardiac arrest (CA) among patients hospitalized with suspected non-ST elevation acute coronary syndrome (NSTE-ACS). METHODS: Using the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART), we identified patients (n=242 303) admitted with suspected NSTE-ACS between 2008 and 2014. Logistic regression was used to assess the association between 26 candidate variables and in-hospital CA. A risk-score model was developed and validated using a temporal cohort (n=126 073) comprising patients from SWEDEHEART between 2005 and 2007 and an external cohort (n=276 109) comprising patients from the Myocardial Ischaemia National Audit Project (MINAP) between 2008 and 2013. RESULTS: The incidence of in-hospital CA for NSTE-ACS and non-ACS was lower in the SWEDEHEART-derivation cohort than in MINAP (1.3% and 0.5% vs. 2.3% and 2.3%). A seven point, five variable risk score (age ≥60 years (1 point), ST-T abnormalities (2 points), Killip Class >1 (1 point), heart rate <50 or ≥100bpm (1 point), and systolic blood pressure <100mmHg (2 points) was developed. Model discrimination was good in the derivation cohort (c-statistic 0.72) and temporal validation cohort (c-statistic 0.74), and calibration was reasonable with a tendency towards overestimation of risk with a higher sum of score points. External validation showed moderate discrimination (c-statistic 0.65) and calibration showed a general underestimation of predicted risk. CONCLUSIONS: A simple points score containing five variables readily available on admission predicts in-hospital CA for patients with suspected NSTE-ACS.