BACKGROUND:Iron deficiency (ID) is common in patients with heart failure (HF). Current guidelines define ID based on serum ferritin and transferrin saturation (TSAT) rather than soluble transferrin receptor (STFR) or ratios such as iron/STFR or TSAT/STFR. We investigated the associations between these biomarkers and prognosis in patients with new-onset HF with reduced ejection fraction (HFrEF). METHODS:All patients hospitalised in 2016-2020 at Sahlgrenska University Hospital with new-onset HFrEF who had iron biomarkers measured within 6 months of discharge were included, with follow-up from the date of the iron biomarker test until 31 December 2021. The primary composite event of interest was first re-hospitalisation for HF (HHF) or all-cause mortality. The associations between ID biomarkers and endpoints were analysed using Cox regression adjusted for age, sex, previous HF, left ventricular ejection fraction, HF medications and comorbidity. Bonferroni-Holm correction was applied for multiple testing. RESULTS:Of 325 patients included (median age 68 (57-76) years, 70.2% men), 168 (52%) had ID using current guideline criteria and STFR was available for 224 (69%) patients. Median follow-up was 2.2 years. In the prespecified analysis plan, biomarkers of ID were not statistically significantly associated with the primary composite endpoint, although each SD increase in TSAT was associated with 56% lower risk of HHF (0.44 [0.27-0.71]) as were increased ratios of iron/STFR (0.58 [0.40-0.86]) and TSAT/STFR (0.55 [0.37-0.83]). However, in a post hoc sensitivity analysis in which patients with extreme values were excluded, each increase in SD of TSAT was associated with 47% lower risk of the primary composite endpoint (0.53 [0.35-0.79]). CONCLUSIONS:Lower TSAT is associated with a greater risk of clinical events in patients with new-onset HF, as were the ratios of iron/STFR and TSAT/STFR. However, neither ratio appeared to offer a substantial advantage compared with TSAT alone.

INTRODUCTION:To assess how national income level influences global variation in the diagnosis and management of heart failure with preserved ejection fraction (HFpEF). METHODS:A web-based survey on HFpEF diagnosis and treatment was distributed worldwide from May to July 2023 through email, scientific societies, and social networks. Respondents provided demographic information and details on diagnostic practices, resource availability, and treatment approaches. Countries were categorized according to the 2023 World Bank income classifications: high-income countries (HICs), upper-middle-income countries (UMICs), lower-middle-income countries (LMICs), and low-income countries (LICs). RESULTS:1459 physicians from 91 countries completed the survey (median age 42 years; 61% male). Income level influenced the type of clinician managing HFpEF, with cardiologists more frequently involved in UMICs and LMICs/LICs than HICs. Respondents in HICs reported a higher proportion of HFpEF among their HF patients (40% vs 30% elsewhere; P < .001). Use of natriuretic peptides varied significantly across settings, as did the availability of echocardiographic parameters required for HFpEF assessment, which was highest in HICs. Screening for coronary artery disease in new HFpEF cases ranged from 22% in LMICs/LICs to 40% in UMICs. Availability of ACE inhibitors, ARBs, MRAs, and loop diuretics showed clear income-related differences, while SGLT2 inhibitors were widely available across all groups (88%). Multi-disciplinary HF programmes were most common in HICs (62%) and least common in LMICs/LICs (24%; P < .001). CONCLUSION:National income level is associated with major differences in diagnostic testing, medication access, specialist involvement, and multi-disciplinary care for HFpEF. These disparities highlight the need for scalable, resource-adapted strategies to optimize HFpEF care globally.

AIMS:Hypertrophic cardiomyopathy (HCM), entailing increased risk of heart failure and death, affects approximately 200 per 100,000 population, with incidence rates of 4-12 per 100,000 person-years.We investigated the epidemiological changes and mortality trends in HCM, with and without left ventricular outflow tract obstruction, in Sweden between 2003 and 2022. METHODS:Using the Swedish National Patient Register, we analysed data for patients 17-85 years of age diagnosed with HCM in inpatient or specialised outpatient care, categorised by age and by ICD-10 codes for obstructive (oHCM) and non-obstructive (nHCM) disease. Annual age- and sex-adjusted incidence, prevalence and all-cause mortality were calculated. Temporal and group differences were assessed using negative binomial regression. RESULTS:In total, 11,299 patients were analysed (mean age 62.9 years; 58.8% male; 67% nHCM). During the study period, the overall prevalence increased from 14 to 73 per 100,000 population. The incidence increased from 5.1 to 9.3 per 100,000 person-years, largely due to nHCM, and with the steepest rise observed among middle-aged and older adults. Annual all-cause mortality declined from 9.8% to 4.3%, with similar rates for nHCM and oHCM at study end. Prognosis improved across all age groups, most notably among older age groups. DISCUSSION:Between 2003 and 2022, the prevalence of oHCM nearly quadrupled, while nHCM increased more than six-fold. Contributing factors include a nearly doubled incidence, primarily driven by a rise in nHCM, and halved all-cause mortality. These trends were most pronounced in older adults, consistent with increased detection of individuals with milder phenotypes.

Background Obesity in young women is increasing. To which extent elevated pre-pregnancy overweight and obesity with and without gestational diabetes increase long-term risk of type 2 diabetes later in life has not been quantified. Methods In a Swedish population-based cohort study we used data from the Swedish Medical Birth Registry in 1,153,074 primiparous women included in the registry between Jan 1, 1987 and Dec 31, 2019, with body mass index (BMI) at the first antenatal care visit as a proxy for pre-pregnancy weight to examine risk for gestational diabetes. We then compared women with gestational diabetes (n = 16,870) to age matched comparators (n = 81,862) and calculated hazards for developing type 2 diabetes identified from the National Diabetes registry over a median follow-up of 9 years. Findings Among 1,153,074 women, 21,438 (1.9%) were diagnosed with gestational diabetes. Women with pre-pregnancy BMI > 35 kg/m2 had an almost 10-fold risk of gestational diabetes compared to those with low-normal weight. Among women with gestational diabetes, the hazard of type 2 diabetes began to increase already at low- or normal weight, increasing nearly exponentially with rising BMI, while the increase in risk with increasing BMI among women without gestational diabetes was much less marked. No other social/pregnancy related factors improved the prediction of type 2 diabetes. Interpretation Gestational diabetes serves as a stress test for developing type 2 diabetes, markedly amplifying risk in even women with normal pre-pregnancy weight, and with very high absolute rates in women with pre-pregnancy obesity. Future work should ascertain to which extent women with gestational diabetes have a structured follow-up after their pregnancy, and their subsequent prognosis. Funding The Swedish Research Council; the Swedish governmental funding of clinical research (ALF); the Swedish Heart and Lung Foundation; and Diabetes Wellness.

BACKGROUND AND AIMS:The risk of heart failure progression or mortality in patients with peri-partum cardiomyopathy (PPCM) during subsequent pregnancies (SSPs) is a significant concern for patients, their families, and healthcare providers. However, there is limited contemporary, prospective data on SSP outcomes in PPCM patients from diverse ethnic and sociodemographic groups. This study aimed to assess maternal and neonatal outcomes in PPCM patients undergoing SSPs. METHODS:This is a sub-study on PPCM and SSPs of the global European Society of Cardiology PPCM Registry that recruited patients from 2012 to 2023. Maternal and neonatal outcomes were reported. RESULTS:From 332 patients with PPCM, there were 98 SSPs among 73 women. Of these, 25 (26%) SSPs ended prematurely due to therapeutic termination (20/25), miscarriage (4/25), and stillbirth (1/25). The median follow-up from the end of the SSP was 198 days (inter-quartile range 160-240). Left ventricular ejection fraction (LVEF) was persistently reduced to <50% prior to the SSP in 26% of patients, with only 6% having an LVEF <40%. Patient characteristics were similar, irrespective of SSP baseline LVEF. Clinical worsening [composite of all-cause death, cardiovascular rehospitalization, or decline in LVEF ≥10% (percentage points) and to <50%] occurred in 20% SSPs, with 2% all-cause maternal mortality. Signs/symptoms of heart failure and worsening of New York Heart Association class occurred in 26% and 22% of SSPs, respectively. At follow-up, the mean LVEF was 50% (±12%), and in 69% of SSPs, the LVEF was ≥50%. African women had similar outcome as the other ethnic groups. Pre-term delivery occurred in 24% of SSPs, 20% of babies were of low birth weight, and there was 3% all-cause neonatal mortality. Compared with women with SSP baseline LVEF <50%, fewer women with LVEF ≥50% were on heart failure pharmacotherapies prior to the SSP, and in this group of women, there was a significant decline in LVEF. CONCLUSIONS:Maternal morbidity and mortality rates were lower than anticipated. Baseline LVEF <50% was not associated with an increased frequency of adverse maternal outcomes, and no further decline in LVEF was observed in this group. In contrast, women with SSPs and a baseline LVEF ≥50% experienced a decline in LVEF, potentially attributable to reduced use of heart failure pharmacotherapy during pregnancy and the post-partum period. Therapeutic termination was performed in approximately a fifth of cases. The findings suggest that reclassification of a SSP with persisting mild left ventricular impairment from modified World Health Organization (mWHO) Class IV (contraindicated) to mWHO III may be considered, while remaining under the care of an experienced medical team and with appropriate pharmacological management.

Background: Although there is substantial evidence supporting the prevention of ischemic stroke (IS) in high-risk patients with atrial fibrillation (AF), knowledge regarding AF patients with a low cardiovascular risk profile remains limited. Furthermore, the necessity of anticoagulant therapy in this population has been widely debated. Methods: Data from Swedish health registers were utilized to identify all patients diagnosed with AF but without prior cardiovascular conditions between 1987 and 2018. The risk of IS was assessed using Cox regression models, with AF patients compared to age- and sex-matched controls without AF. Results: The study included a total of 229,075 patients with AF and 455,541 matched controls without AF. The overall risk of IS was 2.3 times higher (95% confidence interval [CI] 2.2?2.3) in patients with AF compared to controls over a mean follow-up period of 9 years (range 3?32 years). Women with AF had a 4.4-fold increased risk of developing IS within the first year following diagnosis (hazard ratio [HR] 4.4, CI 4.2?4.7) compared to matched women without AF. Additionally, younger patients with AF (aged 35?49 years) exhibited the highest risk of IS within the first year after diagnosis (HR 8.3, 95% CI 4.0?17.1). Conclusions: This large, nationwide, register-based cohort study found that even in the absence of cardiovascular conditions, patients with atrial fibrillation had more than double the risk of ischemic stroke compared to matched controls. The risk was especially elevated in women and younger individuals, particularly within the first year after AF diagnosis. These findings underscore the urgent need to refine risk stratification and explore preventive strategies beyond traditional clinical risk factors. ### Competing Interest Statement Per Ladenvall is an employee of AstraZeneca Biopharmaceuticals Research and Development, Gothenburg, Sweden. The other authors declare no disclosure. ### Funding Statement This work was supported by Trygg-Hansas Forksningsstiftelse, the Emelie Fond, and the Swedish Research Council (2019-00193 SIMSAM). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study complied with the Declaration of Helsinki, and the study protocol was approved by the Regional Ethical Review Board in Gothenburg, Sweden. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are available from the corresponding author upon reasonable request.

Background Turner syndrome (TS) is a complex genetic disorder with raised mortality. Our objective was to investigate mortality and causes of death in TS. Methods A matched retrospective observational study of women with TS recruited from the Turner centers in Sweden were conducted. A total of 472 women with TS, ≥ 16 years old with a cytogenetically verified diagnosis and 2357 controls, matched for birthyear and sex, were examined and followed since 1995 for up to 26 years. Survival analyses were performed with Cox proportional hazard models. Kaplan-Meier curves were generated. Cumulative incidence rates were evaluated by competing risks analysis, using cumulative incidence function. Results During a mean follow-up of 17 years, 35 (7.4%) women with TS and 70 (3.0%) controls died. All-cause mortality was elevated in TS, hazard ratio (HR) 2.90 (95% CI 1.92-4.37), mainly due to circulatory diseases and notably aortic dissection, with HR of 9.11 (95% CI 4.54-18.25) and 21.79 (95% CI 4.62-102.82), respectively. Aortic dissection was the single largest cause of death in TS, accounting for 23% (8/35) of total deaths. Death by cancer or external causes were not raised in TS. In individuals below 45 years of age death, aortic dissections were greatly increased compared to controls, HR 55.59 (95% CI 2.33-1325.69). From the ages 46 to 80 years a notably higher risk of dying by heart diseases, aortic dissection excluded, was shown in TS compared to controls HR, 7.7 (2.65-22.36). The median survival time was 8 years shorter in TS compared to controls. Conclusions The increased mortality in TS was mainly driven by aortic dissections in the young and by heart diseases in the older. Healthcare professionals should prioritize detection and monitoring, with emphasis on cardiovascular diseases.

Background and aims Pre-eclampsia complicates 3–5% of pregnancies worldwide and is associated with adverse outcomes for the mother and the offspring. Pre-eclampsia and heart failure have common risk factors, including hypertension, obesity and diabetes. It is not known whether heart failure increases the risk of pre-eclampsia. This study examines whether pregestational heart failure increases the risk of pre-eclampsia.Methods In a registry-based case–cohort study that included all pregnancies in Sweden (n=3 125 527) between 1990 and 2019, all pregnancies with pre-eclampsia (n=90 354) were identified and up to five control pregnancies (n=451 466) for each case were chosen, matched on the mother’s birth year. Multiple logistic regression analysis was used to evaluate the impact of heart failure on the risk of pre-eclampsia, with adjustment for established risk factors and other cardiovascular diseases.Results Women with heart failure had no increased risk for pre-eclampsia, OR 1.02 (95% CI 0.69 to 1.50). Women with valvular heart disease had an increased OR of preterm pre-eclampsia, with an adjusted OR of 1.78 (95% CI 1.04 to 3.06). Hypertension and diabetes were independent risk factors for pre-eclampsia. Obesity, multifetal pregnancies, in vitro fertilisation, older age, Nordic origin and nulliparity were more common among women who developed pre-eclampsia compared with controls.Conclusion Women with heart failure do not have an increased risk of pre-eclampsia. However, women with valvular heart disease prior to pregnancy have an increased risk of developing preterm pre-eclampsia independent of other known risk factors.

Journal Article Peripartum cardiomyopathy: the challenge of predicting cardiac function recovery Get access Carmen Basic, Carmen Basic Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Medicine Geriatrics and Emergency Medicine, Sahlgrenska University Hospital/Östra Hospital, Region Västra Götaland, Gothenburg, Sweden https://orcid.org/0000-0002-0493-0673 Search for other works by this author on: Oxford Academic PubMed Google Scholar Maria Schaufelberger Maria Schaufelberger Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Medicine Geriatrics and Emergency Medicine, Sahlgrenska University Hospital/Östra Hospital, Region Västra Götaland, Gothenburg, Sweden Corresponding author. Tel: +46 706 69 43 34, Fax: +46 31 258933, Email: maria.schaufelberger@gu.se https://orcid.org/0000-0002-0611-0863 Search for other works by this author on: Oxford Academic PubMed Google Scholar European Heart Journal, Volume 45, Issue 16, 21 April 2024, Pages 1440–1442, https://doi.org/10.1093/eurheartj/ehae111 Published: 05 March 2024

Abstract Background Heart failure remains a significant health burden, characterized by disabling symptoms and mortality rates comparable to cancer. Mineralocorticoid antagonists (MRAs), pivotal in treating heart failure with reduced ejection fraction (HFrEF), are underutilized due to concerns of hyperkalemia. Sodium Zirconium Cyclosilicate (SZC) enables optimized MRA therapy by reducing hyperkalemia. However, prospective studies on the efficacy and safety of SZC in patients with HFrEF and high hyperkalemia risk are lacking, particularly in the context of contemporary heart failure quadruple-therapy including angiotensin receptor neprilysin inhibitor (ARNI) and Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors. Purpose The OPRA-HF trial aims to assess the efficacy and safety of SZC in optimizing MRA treatment in symptomatic patients with HFrEF with risk for hyperkalemia on top of optimal guideline-directed medical therapy including ARNI and SGLT2 Inhibitors. Methods This investigator-initiated multicentred, randomized, placebo-controlled, and double-blinded trial include patients with HFrEF on suboptimal MRA treatment due to (1) history of hyperkalemia due to MRA, or (2) risk of hyperkalemia due to reduced renal function (eGFR 30-45 ml/min/m2) and current potassium 4.5-5-0 mmol/L. Patients undergo a Run-In phase with SZC, initiating or up-titrating MRA to target doses for 4-7 weeks and SZC was initiated in those patients that became hyperkalemic (K+>5 mEq/L. Those normokalemic and tolerating MRA ≥ 25 mg daily or at least 25 mg dose increase vs before run-in were randomized to SZC (5g or 10g) or placebo for 6 months. Study is powered to randomize 110 patients. Primary outcomes include maintaining daily MRA dose ≥ 25 mg or dose increase by 25 mg with normal potassium levels without rescue therapy. Secondary outcomes include evaluating the safety and tolerability of SZC as well as impact of SZC on quality of life. Results In this ongoing trial, so far 40 patients have been randomized. Of these, mean age was 74.3 years, 88.9% men. Most patients had ischemic etiology (54.2%), 36.1% had diabetes mellitus, 52.8% had hypertension.n. At screening 94.4% had beta-blockers, 35% ACEI/ARB, 60% ARNI and 72.2% had SGLT2 inhibitors, 33.3% had no MRAs and 35,6% of patients had less than 25 mg MRA daily,62,2% had 25 mg MRA daily, mean p-potassium was 4.7+0.4 mmol/L, and eGFR was 57.3 ml/min/1.73m². After run-in, 85.2% were on 50 mg MRA daily. A substantial number (51.2%) of eligible patients with previous hyperkalemia had Run-In failure as they now successfully tolerated target dose of MRA at 50 mg daily without recurrent hyperkalemia. SZC dosing was 5g once daily in 78.9% of patients. Conclusion This ongoing trial will provide evidence for the use of SZC to optimize MRA treatment in contemporary HFrEF patients. Preliminary findings suggest SZC effectively maintains normokalemia, enabling MRA optimization, potentially improving patients’ otcome.

Abstract Background Iron deficiency (ID) is the most common extracardiac comorbidity in heart failure (HF) and associated with worse outcomes. While a uniform definition of ID in HF remains lacking, several biomarkers for ID, including ferritin and transferrin saturation (TSAT), are used in both clinical trials and clinical practice. However, which biomarker is a superior prognostic predictor for ID in HF remains unsettled. In addition, real-world clinical data on ID screening and intravenous (IV) iron treatment is largely missing. Purpose To determine which biomarker is a superior prognostic predictor for the composite endpoint of HF rehospitalisation (HHF) and all-cause mortality in a real-world cohort of patients with HF and coexisting ID, and to investigate frequency and predictors of ID screening and IV iron treatment. Methods In this retrospective cohort study, all patients aged 18-85 years hospitalised at a tertiary university hospital with new onset HF with reduced ejection fraction (HFrEF) in 2016-2020 were consecutively included from medical records by ICD-10 code I50.0-I50.9 and followed until 31 December 2021. Patient characteristics, comorbidities, medications, laboratory results and data on follow-up, including if ID was tested for, IV iron administration, HHF and all-cause mortality was collected. First available iron status after admission for index hospitalisation was used. Predictors for ID screening and IV iron use were identified with univariate logistic regression. The association between ID markers and the composite endpoint was analysed with Cox regression adjusted for age, sex, baseline anemia, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and N-terminal pro-B type natriuretic peptide (NT-proBNP) below median value with median ferritin and TSAT values set as references respectively. Results In all, 753 patients were included (66.5 ± 12.7 years, 508 (67.5%) men, ejection fraction 29.5 ± 6.9% and mean NT-proBNP 6241 ± 7183 ng/L). Of these, 484 (64.3%) were screened for ID and 235 (48.6%) fulfilled criteria for ID. Of these, 94 (40.0%) received IV iron. Of screened patients, 28.6% had ID with anemia and 20.8% ID without anemia (Table 1). Factors associated with screening for ID were follow-up at hospital, anemia, eGFR <30 mL/min/1.73 m2 and ischemic heart disease, and for IV iron additionally chronic kidney disease and peripheral artery disease. Median ferritin was 140 µg/L and TSAT 0.2. Both ferritin and TSAT displayed an inversely linear association with outcomes, while TSAT <0.2 showed a stronger association with increased risk of HHF and all-cause mortality compared to median values (Figure 1-2). Conclusions In a real-world clinical setting, TSAT was a superior prognostic biomarker for worse outcomes compared to ferritin in patients hospitalised for acute HF. While both ID screening and IV iron use remained greatly underutilised in clinical practice, identification of a reliable biomarker for ID is critical.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

AIMS:Heart failure (HF) with preserved ejection fraction (HFpEF) is characterized by growing incidence and poor outcomes. A large majority of HFpEF patients are cared by non-cardiologists. The availability of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as recommended therapy raises the importance of prompt and accurate identification and treatment of HFpEF across diverse healthcare settings. We evaluated HFpEF management across specialties through a survey targeting cardiologists, HF specialists, and non-cardiologists. METHODS AND RESULTS:An independent web-based survey was distributed globally between May and July 2023. We performed a post-hoc analysis, comparing cardiologists, HF specialists, and non-cardiologists. A total of 1460 physicians (61% male, median age 41[34-49]) from 95 countries completed the survey; 20% were HF specialists, 65% cardiologists, and 15% non-cardiologists. Compared with HF specialists, non-cardiologists and cardiologists were less likely to use natriuretic peptides (p = 0.003) and HFpEF scores (p = 0.004) for diagnosis, and were also less likely to have access to or consider specific echocardiographic parameters (p < 0.001) for identifying HFpEF. Diastolic stress tests were used in less than 30% of the cases, regardless of the specialty (p = 1.12). Multidrug treatment strategies were similar across different specialties. While SGLT2i and diuretics were the preferred drugs, angiotensin receptor blockers and angiotensin receptor-neprilysin inhibitors were the least frequently prescribed in all three groups. However, when constrained to choose one drug, the proportion of physicians favoring SGLT2i varied significantly among specialties (66% HF specialists, 52% cardiologists, 51% non-cardiologists). Additionally, 10% of non-cardiologists and 8% of cardiologists considered beta blocker the drug of choice for HFpEF. CONCLUSION:Significant differences among specialty groups were observed in HFpEF management, particularly in the diagnostic work-up. Our results highlight a substantial risk of underdiagnosis and undertreatment of HFpEF patients, especially among non-HF specialists.

Abstract Background Heart failure (HF) among young patients may be from various causes, often triggered by heightened physical demands like pregnancy. Data regarding outcomes of women diagnosed with HF in conjunction to pregnancy and delivery are varied. There remains a notable gap in understanding the outcomes observed in women diagnosed with heart failure in conjunction with delivery. Also, long-term follow-up studies are crucial to elucidate the impact of pregnancy-associated HF on future cardiovascular. Purpose To study the interplay between pregnancy, HF, and subsequent cardiovascular risk. Method Using the personal identification numbers (PINs) that all individuals in Sweden have enables linkage of data between different registers. Data from the National Patient Register (NPR), Swedish Medical Birth Register (MBR) and the Cause of Death Register were also used. All women 18 to 50 years of age registered in the in MBR in the period 1st January 1997 to 31st December 2019 were included. Women with first-time HF in relation to delivery were identified using the international classification code for diseases (ICD-10) I50, I42, I43 and 090.3 together with co-morbidities. Every patient was compared with 5 controls without HF from the Total Population Register matched on age at delivery and calendar year of delivery. Outcomes: all-cause mortality, and any cardiovascular disease (CVD) diagnosed during the observation time. Results A total of 286 cases and 1,430 controls were included. The prevalence of comorbidities at baseline for both patients and controls was low; congenital heart disease (1.4%, vs. 0%), pulmonary hypertension (1.0% vs. 0%), valvular heart disease (5.9% vs. 0%), myocardial infarction 0.7% vs. 0%), arrhythmia (5.9% vs. 0%), hypertension (6.3 % vs. 0.1%), (all p<0.05). Preeclampsia prior to HF diagnosis had 31% of patients vs. 0.2% of controls (p<0.001). Patients exhibited higher mortality rates at 4.9% during median follow up 9.0 (IQR 5.6-13.0) years vs. 0.3%, median follow up 9.4 (6.2-13.5) years and hazard ratios (HR) for all-cause mortality HR (95% CI) of 18.20 (5.99 - 55.31) (p<0.001) compared to controls. During median follow up of 3.2 (0.0-9.2) years 60.1% of patients were diagnosed with CVD both at in-/out-patient settings compared with 4.1% in controls during 9.4 (5.8-13.5) years of follow up. Comparing patients with controls the HR (95% CI) was 22.24 (16.50 - 29.96) p<0.0001 for CVD diagnosis during follow-up, see Figure 1. Conclusion In conjunction with delivery, and in the years thereafter, women with heart failure diagnosis had more than eighteen times higher risk of mortality than women without heart failure. The risk of CVD event in the heart failure group is highest in conjunction with delivery. Figure 1. Cumulative incidence functions for all-cause mortality, CVD in- or out-patient visit adjusted for death as competing risk, comparing cases with controls.

AbstractAimsThis study aims to evaluate the worldwide variations in the diagnosis and treatment of heart failure with preserved ejection fraction (HFpEF), using an HF survey distributed internationally to physicians, including both cardiologists and non‐cardiologists.Methods and resultsA group of HF specialists designed an independent, academic web‐based survey focusing on HFpEF care and diagnosis, which was distributed via scientific societies and various social networks between 1 May 2023 and 1 July 2023. The survey included 1459 physicians (1242 cardiologists and 217 non‐cardiologists) from 91 countries, with a mean age of 42 (34–49) years and 61% male. Most physicians (89.2%) defined HFpEF as left ventricular ejection fraction ≥50%. Significant regional variations were observed in HFpEF management (P < 0.001 for all comparisons unless stated otherwise). Cardiologists managed 63.1% of HFpEF patients overall, with significant variability across regions (P < 0.001). The estimated HFpEF prevalence was highest in Eastern Asia and Western Europe and lowest in Africa and South America. Diagnostic practices varied: natriuretic peptide use ranged from 70%–74% in Africa to 95%–97% in Southern/Western Europe. Echocardiographic parameters showed regional differences, with diastolic stress testing used most in South‐Eastern Asia (47% vs. 13–36% elsewhere). HFpEF scoring systems were most common in South‐Eastern Asia (78%) and least in Africa (30.1%). Coronary artery disease screening approaches differed, with Eastern Asian physicians more likely to always perform routine angiograms (52%) compared with Northern Europeans (12%). Treatment preferences also varied regionally. Sodium glucose co‐transporter‐2 inhibitors (SGLT2i) was the preferred first‐line treatment (45%–70% across regions), followed by diuretics. In an ideal setting, 52% would primarily use SGLT2i, 33% loop diuretics, and 22% beta‐blockers. Drug availability differed significantly: SGLT2i was most available (88% overall), while ARNI was least available (61%). South America and Middle Eastern/Northern Africa reported lower availability of guideline‐directed therapies. Multidisciplinary HF programmes were most common in Asia (70%) and least in Africa (24%). The perceived benefit of atrial flow regulator devices also showed significant regional differences.ConclusionsThere are considerable global variations in the diagnosis and management of HFpEF. Most physicians favour SGLT2i despite regional disparities in health care resources and guideline adherence. Harmonized practices and improved access to comprehensive care can enhance outcomes of HFpEF patients worldwide.

Introduction: The high-risk population of patients with cardiovascular (CV) disease or risk factors (RF) suffering from COVID-19 is heterogeneous. Several predictors for impaired prognosis have been identified. However, with machine learning (ML) approaches, certain phenotypes may be confined to classify the affected population and to predict outcome. This study aimed to phenotype patients using unsupervised ML technique within the International Postgraduate Course Heart Failure Registry for patients hospitalized with COVID-19 and Cardiovascular disease and/or RF (PCHF-COVICAV). Methods: Patients from the eight centres with follow-up data available from the PCHF-COVICAV registry were included in this ML analysis (K-medoids algorithm). Results: Out of 617 patients included into the prospective part of the registry, 458 [median age: 76 (IQR: 65-84) years, 55% male] were analyzed and 46 baseline variables, including demographics, clinical status, comorbidities and biochemical characteristics were incorporated into the ML. Three clusters were extracted by this ML method. Cluster 1 (n = 181) represents mainly women with the least number of overall comorbidities and cardiovascular RF. Cluster 2 (n = 227) is characterized mainly by men with non-CV conditions and less severe symptoms of infection. Cluster 3 (n = 50) mainly rep- resents men with the highest prevalence of cardiac comorbidities and RF, more extensive inflammation and organ dysfunction with the highest 6-month all-cause mortality risk. Conclusions: The ML process has identified three important clinical clusters from hospitalized COVID-19 CV and/or RF patients. The cluster of males with severe CV disease, particularly HF, and multiple RF presenting with increased inflammation had a particularly poor outcome. (Cardiol J 2024; 31, 4: 512-521)

INTRODUCTION:The prevalence of cardiovascular disease during pregnancy (cardiovascular disease diagnosed before, during or up to 6 months after childbirth) and the risk of adverse outcomes associated with it have not been previously described in Sweden. This study examined trends in prevalence of cardiovascular disease and its association with maternal and perinatal outcomes, overall and by timing of diagnosis in relation to pregnancy. MATERIAL AND METHODS:This population-based observational retrospective cohort study consisted of women aged 15-49 years who were registered in the Swedish Medical Birth Register 2000-2019. Prevalence was defined as annual diagnosis of cardiovascular disease per pregnant woman as numerator and all pregnant women per year as denominator. Adverse maternal and perinatal outcomes were analyzed using time-dependent Cox regression and Poisson regression models. Outcomes were obtained during and after childbirth up to 1 year postpartum, depending on the outcome. RESULTS:There were 2 069 107 births to 1 186 137 women (911 101 primiparous). The prevalence of cardiovascular disease among pregnant women in Sweden during 2000-2019 increased from 0.31% to 1.34%, for non-congenital cardiovascular disease, this was primarily driven by arrythmia (0.11%-0.58%). Primiparous women with cardiovascular disease had a higher risk of eclampsia over-all (aHR 4.50, 95% CI 2.01-10.05) and when diagnosed during pregnancy (aHR 3.22, 95% CI 1.21-8.61); admission to psychiatric ward overall (aHR 2.51, 95% CI 1.30-4.83), and when diagnosed during pregnancy (aHR 2.54, 95% CI 1.21-5.34); and one-year mortality when diagnosed before pregnancy (aHR 1.67, 95% CI 1.16-2.42) and when diagnosed postpartum (aHR 6.59, 95% CI 3.38-12.84), compared to those without cardiovascular disease. Children born to women with cardiovascular disease diagnosed both overall and in relation to timing of diagnosis had an increased risk of being born preterm and small for gestational age. CONCLUSIONS:Cardiovascular disease prevalence among pregnant women in Sweden increased during 2000-2019, primarily driven by arrhythmias. In primiparous women, the timing of diagnosis of cardiovascular disease is important for maternal and perinatal outcomes, including when diagnosed postpartum. This calls for awareness among all staff when planning pregnancy and monitoring women with cardiovascular disease throughout pregnancy and in the postpartum period.

Background Overweight and obesity are increasing globally with aging, as are life expectancy and aging‐associated disorders, including calcific aortic stenosis (AS). Studies investigating the correlation between high body mass index (BMI) and AS are contradictory and inconclusive. This study examines a potential association between BMI and AS in women. Methods and Results By linking the Swedish Medical Birth Register and the Swedish National Patient Register, we included women aged 18 to 55 years with a first childbirth from 1981 to 2020. Diagnosis of AS and comorbidities were defined according to the International Classification of Diseases ( ICD ) codes. The women were divided into groups on the basis of BMI. Cox proportional hazards regression models were used to investigate the difference in the risk of being diagnosed with AS, with reference BMI 20 to <22.5 kg/m 2 . Among the 1 722 625 included women, the mean age was 28 years, and mean BMI was 24 kg/m 2 , with 21% being overweight (BMI 25 to <30 kg/m 2 ) and 8.5% obese (BMI ≥30 kg/m 2 ). During median follow‐up of 19.5 years, 2488 women (0.14%) were diagnosed with AS. The age‐adjusted risk of being diagnosed with AS increased with higher BMI to 2.82 (95% CI, 2.44–3.25) times higher in women with BMI 30 to <35 kg/m 2 , and to 3.72 (95% CI, 2.95–4.70) times higher in those with BMI ≥35 kg/m 2 . Similar results were found after excluding AS of rheumatic pathogenesis. Conclusions An increase in BMI from its upper normal range was consistently and independently associated with the risk of developing AS in women.

Both incidence in and prevalence of heart failure among young adults have been increasing over the last 35 years. Mortality is high and if a person gets heart failure at the age of 20, he/she is expected to live 36 years less than a person of the same age without heart failure. Therefore, everything must be done to stop the increase of heart failure in young adults. To do this, it is important to make both the profession and society aware of the ongoing heart failure epidemic, diagnose and treat known risk factors, and search for more, as yet unknown risk factors in young adults