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Background Despite well-established effectiveness of cardiac resynchronization therapy (CRT) in patients with heart failure (HF), it remained significantly under-utilized. The underlying causes are still not well described. Aim To investigate how many patients with HF were eligible for CRT and determine underlying causes why CRT was abstained for these patients in real life settings. Methods Retrospective review of medical data was carried out in all patients hospitalized for newly diagnosed HF from January 1, 2016 to December 31, 2019. Patients were identified from the local university hospital register with three afiliations by use of international classification of disease (ICD)-10 codes I50.0-I50.9. Medical journals, including electrocardiograms and echocardiograms, were reviewed. The indication for CRT was evaluated three months after mineralocorticoid receptor antagonists (MRA) were initiated as addition to angiotensin converting enzyme inhibitor /angiotensin-receptor blockers and beta-blocker treatment according to European guidelines for heart failure from 2016. Follow-up was minimum one year and up to two years after HF diagnosis. Results In 3456 patients with HF, 642 (18.6%) were patients hospitalized for new onset of HF with ejection fraction (EF) Conclusion In this real world HF cohort, 1/3 patients were eligible for CRT treatment. However only 1/3 received CRT and 58.6% had no contraindication but did not receive CRT, which emphasize urgent need for structured implementation methods for device treatment in patients with HF. Funding Acknowledgement Type of funding sources: None.

Background Heart failure (HF) is common in patients with atrial fibrillation (AF), and also associated with worse outcome. Consequently, it is commonly included in risk prediction models for AF, used in daily clinical praxis. However, knowledge about the association between solely AF and incidental HF is limited. Aim This study aims to evaluate the short and long-term risks for onset of HF in patients with AF and low cardiovascular risk profile. Methods All patients with first recorded hospitalization for AF in the Swedish National Patient Register, were included from the 1St January 1987 to 31st December 2018. Each patient with AF was matched by age, sex and county with two controls from the Swedish Total Population Register. Patients Results In total 227 811 patients and 452 712 controls met the inclusion and exclusion criteria and were included in the study. The incidence rate for incidental HF per 1000 person-year within one year after AF diagnosis was 6.2 (95% CI: 4.5–8.6) among patient 18–34, increased with increasing age and was 142.8 (95% CI: 139.4–146.3) among those >80 years. Within five years the incidence rate decreased in all age categories and was 2.4 (95% CI: 1.8–3.0) among the youngest and 94.0 (95% CI: 92.4–95.6) in the oldest age group. When compared to matched controls from the general population patients with AF had a hazard ratio (HR) and CI 95% to develop HF within one year at 103.9 (46.3–233.1), 34.9 (26.5–45.9), 17.5 (15.5–19.8), 10.3 (9.6–11.1) and 6.1 (5.8–6.4) among patients aged 18–34, 35–49, 50–59, 60–69, 70–79 and >80 years, respectively. Conclusion Despite low cardiovascular risk profile AF still carries high risk for developing incidental HF in particular during the first observation year with increasing tendency along with increasing age. Younger patients with AF and without other cardiovascular comorbidities had more than 100 times higher relative risk to develop HF within one year when compared to matched controls. Funding Acknowledgement Type of funding sources: None.

Background Despite beneficial effects on mortality and morbidity the use of mineralocorticoid receptor antagonists (MRA) in patients with reduced ejection fraction ( Aim To determine the incidence and magnitude of documented hyperkalemia and potential risk of hyperkalemia in patients with HFrEF in a real-world HF population. Methods Patients aged 18–85 years at the time of the baseline, hospitalized for newly onset of HFrEF between 2016–01–01 and 2019–12–31, were identified retrospectively and consecutively from hospital discharge records, by use of international classification of disease (ICD)-10 codes I50.0-I50.9 as principal diagnosis. Potential higher risk of hyperkalemia was based on an overall assessment of current potassium level, presence of diabetes mellitus and eGFR Results In total, 3456 patients with HF were identified, 642 (18.6%) were eligible, hospitalized for newly onset of HFrEF (66.8±12.7 years, 68.4% men and EF 29.4% ±6.8%). After six months 336 (52.3%) did not have MRA of which 279 (83%) never received MRAs and 57 (17%) had MRAs discontinued. Among patients on MRA treatment, 306 (14.4%) needed dose reduction. Occurrence of hypertension, ischemic heart disease, diabetes mellitus and renal dysfunction at baseline did not differ between groups with or without MRA. The incidence and magnitude of documented and potentially higher risk of hyperkalemia were assessed both at baseline and as highest potassium within six months after established diagnosis. Among patients without MRA after six months, at baseline only 3 (0.9%) patients had documented S/P-K ≥6 mmol/L, 7 (2.1%) patients had S/P-K 5.5–5.9 mmol/L and 26 (7.7%) patients had S/P-K 4.8–5.4 mmol/L. Moreover, 12.4% had potentially high risk of hyperkalemia at baseline. During the six-month follow up after initiation of HF therapy, 15 (4.5%) patients had documented hyperkalemia with S/P-K ≥6 mmol/L, 23 (6.8%) patients had S/P-K 5.4–5.9 mmol/L, and 123 (36.6%) patients had S/P-K 4.8–5.4 mmol/L during at least one occasion. Besides, 13.4% had potentially high risk of hyperkalemia. Hyperkalemia occurred frequently (40.4% vs 36.4%) in patients with discontinuation and dose reduction of MRA. Figure 1 presents the distribution of patients with risk of or documented hyperkalemia in the group without MRA. Conclusions Hyperkalemia was the most common cause for both discontinuation and dose reduction of MRA. Hyperkalemia was also increased significantly from baseline and during subsequent up-titration, with 4.6-fold increased risk for borderline hyperkalemia (S/P-K 4.8–5.4). This might explain why physicians refrain from prescribing MRAs to patients with HFrEF. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Vifor Pharma

Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the ‘HFA–PEFF diagnostic algorithm’. Step 1 (P=Pre-test assessment) is typically performed in the ambulatory setting and includes assessment for HF symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non-cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e′), left ventricular (LV) filling pressure estimated using E/e′, left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2–4 points) implies diagnostic uncertainty, in which case Step 3 (F1: Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F2: Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.

Background Acquired aortic stenosis (AS) is the most common valvular disorder that rises exponentially with age; it has high mortality after symptoms appear. Factors that predict the development of AS are still unknown. Some studies imply that the atherosclerotic factors are involved in the development of AS, but the findings have been heterogeneous. Purpose To estimate lifelong cumulative incidence of AS and analyse its predictors. Methods We included a random sample of men, born 1915–1925 in Gothenburg, Sweden, and examined them in 1970–1973 (participation rate 75%). They were between 47 and 55 years in the beginning and 57–65 years when the examination-period ended. Out of 7493 men 57 were excluded due to myocardial infarction prior to baseline; 7436 were thus followed from the inclusion date until a discharge diagnosis of AS or death, with a maximum follow up time of 42 years and mean follow-up time 26.8 years. Men with AS were identified from the Swedish National Patient Register and those who died from the Swedish Cause of Death Register. We used machine learning to identify the most important factors that predict AS. For these factors, we then estimated hazard ratios for the risk to acquire AS through Cox proportional hazards model. Results The lifelong cumulative incidence to acquire AS was 2.66% (198 out of 7436 individuals). For men with measurements approximately at the quartiles of the pulse pressure distribution, more specifically 44, 52, 62 mm Hg, the estimated cumulative risk were 1.97%, 2.74% and 3.07% respectively. For the body mass index (BMI) we had accordingly for measurements around 23, 25 and 27 kg/m2 estimated cumulative risk 2.52%, 2.80%, 2.79% respectively. For cholesterol values of 5, 6 and 7 mmol/l (approximately at quartile divisions) the estimated cumulative risk was 1.77%, 1.79% and 3.20% respectively. The estimated cumulative risks for the younger, with age around 47 and the older participants, with age around 55 were 1.76% and 2.68 respectively. Men with family history of infarction in a sibling had an estimated cumulative risk at 4.66% level whereas those with not at 2.51%. The factors that were significantly associated with the development of AS in the Cox proportional model are: cholesterol level (HR=1.24, CI 95% 1.11–1.39, p=0.0001), pulse pressure (HR=1.01, CI 95% 1.01–1.02, p=0.0037), BMI (HR=1.06, CI 95% 1.02–1.11, p=0.0089), age (HR=1.11, CI 95% 1.04–1.19, p=0.0010) and family history of myocardial infarction in a sibling (HR=2.38, CI 95% 1.50–3.79, p=0.0002). Conclusion Lifelong cumulative incidence of acquired AS is approximately 2.7%. Multiple factors known also to be associated with arteriosclerosis were identified to increase the life-long risk of developing AS. Funding Acknowledgement Type of funding source: None

Background It remains unclear whether the readmission of heart failure (HF) patients has decreased over time and how it differs among HF with preserved ejection fraction (EF) (HFpEF) versus reduced EF (HFrEF) and mid-range EF (HFmrEF). Methods We evaluated HF patients index hospitalized from January 2004 to December 2011 in the Swedish Heart Failure Registry with 1-year follow-up. Outcome measures were the first occurring all-cause, cardiovascular (CV) and HF readmissions. Results Totally 20,877 HF patients (11,064 HFrEF, 4,215 HFmrEF, 5,562 HFpEF) were included in the study. All-cause readmission was highest in patients with HFpEF, whereas CV and HF readmissions were highest in HFrEF. From 2004 to 2011, HF readmission rates within 6 months (from 22.3% to 17.3%, P=0.003) and 1 year (from 27.7% to 23.4%, P=0.019) in HFpEF declined, and the risk for 1-year HF readmission in HFpEF was reduced by 7% after adjusting for age and sex (P=0.022). Likewise, risk factors for HF readmission in HFpEF changed. However, no significant changes in cause-specific readmissions were observed in HFrEF. Time to the first readmission did not change significantly from 2004 to 2011, regardless of EF subgroup (all P-values>0.05). Conclusions Although the burden of all-cause readmission remained highest in HFpEF versus HFrEF and HFmrEF, a declining temporal trend in 6-month and 1-year HF readmission rates was found in patients with HFpEF, suggesting that non-HF-related readmission represents a big challenge for clinical practice. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The SwedeHF was funded by the Swedish National Board of Health and Welfare, the Swedish Association of Local Authorities and Regions.

Background Heart failure (HF) reduces survival and is one of the most common causes of hospitalizations in the elderly, imposing a major economic burden on the health care system, with frequency of rehospitalizations often used in interventional and observational studies in patients with HF. Home-time is a novel end-point measuring time spent alive and out of hospital and is easier for both clinicians and patients to relate to. Given the advances in treatment of HF over the last decades we postulated that an increase in home-time would follow. Purpose To investigate whether home-time for patients with HF has changed over the last decades in Sweden and if home-time differs between patients of working age and those retired, or between men and women. Methods Patients aged 18–84 years with a first hospitalization for HF in Sweden between 1992 and 2008 were identified using the National Inpatient Register which was linked to the Swedish Cause of Death Register. Information on rehospitalizations and mortality was collected and followed over a time period of 4 years. The patients were divided into two age groups: (i) 65 years. The cut off 65 years was chosen being the official age of retirement over the study period in Sweden. Results A total of 324,907 patients were included in this study, mean age 73.5 years (standard deviation 9.3). Only 15.6% were Conclusion Home-time for patients in Sweden increased over the study period and the increase was more marked for younger patients, where men spent more time at home than women. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Swedish state (ALF), The Swedish Heart and Lung Foundation, Västra Götaland Region, The Göteborg Medical Society

Background During the last decades we have witnessed gradually improved cardiovascular primary and secondary prevention, while life expectancy is increasing, with a growing population of elderly people. Heart failure is a disease of the elderly and end stage of other cardiac diseases. Accordingly, trends in incidence of heart failure are dynamic and may differ by age and gender Purpose To investigate overall trends in incidence for HF over the last decades in Western Sweden. Additionally we wanted to study incidence in relation to age and gender. Method The VEGA database is an administrative database of all patients managed in hospital care (through direct linkage to the Swedish nationwide patient registry) and/or in primary care facilities (private and public) living in Western Sweden. All patients with a main or contributory diagnosis of HF (I50) >18 years of age between 2008 and 2017 were included in our cohort. HF incidence was calculated based on the entire population of Vastra Gotaland (a region of Western Sweden). Results The adult population in Western Sweden increased by 8% from 2008 (n=1,234,609) to 2017 (n=1,338,906), with 69% In total, 62,229 incident cases of HF were identified during 2008–2017. In 2008 we identified 6464 cases with a mean age of 78.7 (11.5) and 49.8% (n=3222) male patients, while in 2017 5,727 cases were identified with a mean age of 78.3 (11.8) and 52.5% (n=3006) male cases. The yearly incidence rate of HF remained constant over the 10-year period but with large variations by age and gender. A constantly higher incidence of HF was seen for men compared to women in all age categories. Although overall incidence remained constant in the last decade, we did observe decreasing incidence among those >80 years of age with incidence rates dropping from 4.4% to 3.0% between 2008–2017 (80–90 years) and from 7.8 to 5.5% in the same period (>90 years of age). A similar pattern was seen in both men and women in these age groups with incidence decreasing over the last ten years. Conclusion The overall incidence of HF remained unchanged over the last decade. However a declining trend in incidence was observed in the oldest part of the population, who, however, constitutes only approximately 5% of the population. Our findings emphasize the need for implementation of effective preventive strategies for HF. Trends in HF incidence 2007-2018 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Swedish agreement between the government and the county councils concerning economic support for providing an infrastructure for research and education of doctors (ALF), and the Regional Development Fund, Västra Götaland County, Sweden (FOU-VGR)

Aims The EMPERIAL (Effect of EMPagliflozin on ExeRcise ability and HF symptoms In patients with chronic heArt faiLure) trials evaluated the effects of empagliflozin on exercise ability and patient-reported outcomes in heart failure (HF) with reduced and preserved ejection fraction (EF), with and without type 2 diabetes (T2D), reporting, for the first time, the effects of sodium-glucose co-transporter-2 inhibition in HF with preserved EF (HFpEF). Methods and results HF patients with reduced EF (HFrEF) (≤40%, N = 312, EMPERIAL-Reduced) or preserved EF (>40%, N = 315, EMPERIAL-Preserved), with and without T2D, were randomized to empagliflozin 10 mg or placebo for 12 weeks. The primary endpoint was 6-minute walk test distance (6MWTD) change to Week 12. Key secondary endpoints included Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and Chronic Heart Failure Questionnaire Self-Administered Standardized format (CHQ-SAS) dyspnoea score. 6MWTD median (95% confidence interval) differences, empagliflozin vs. placebo, at Week 12 were −4.0 m (−16.0, 6.0; P = 0.42) and 4.0 m (−5.0, 13.0; P = 0.37) in EMPERIAL-Reduced and EMPERIAL-Preserved, respectively. As the primary endpoint was non-significant, all secondary endpoints were considered exploratory. Changes in KCCQ-TSS and CHQ-SAS dyspnoea score were non-significant. Improvements with empagliflozin in exploratory pre-specified analyses of KCCQ-TSS responder rates, congestion score, and diuretic use in EMPERIAL-Reduced are hypothesis generating. Empagliflozin adverse events were consistent with those previously reported. Conclusion The primary outcome for both trials was neutral. Empagliflozin was well tolerated in HF patients, with and without T2D, with a safety profile consistent with that previously reported in T2D. Hypothesis-generating improvements in exploratory analyses of secondary endpoints with empagliflozin in HFrEF were observed.

Background Minor ECG abnormalities, such as T-wave inversions, are frequently seen in clinical practice in asymptomatic patients. Its prognostic role is incompletely studied. We have previously reported an association between T-wave inversion, and all-cause mortality during lifetime. Purpose To study the prognostic prediction of new-onset of T-wave inversion in ECG recorded at various ages, in a male random population-based cohort in lifetime follow up. Methods Subjects from a random longitudinal, prospective, population-based study: “The study of men born in 1913” (n=854) were examined at 50-years of age and re-examined at 60, 67, 75 and 80 years, including a 12-lead ECG recording, classified according to the Minnesota code. Participants were followed until death or year 2015 (48 years follow-up), and data were obtained through the Cause of Death Register. Unadjusted and adjusted Cox proportional hazards models, producing an overall hazard ratio (HR), and flexible parametric models for survival data by Royston and Parmar, producing continuous HR over studied time, were applied for prediction of time to all-cause death and cardiovascular disease (CVD) death by the incident negative T-wave. Results An increased risk of all-cause and CVD death associated with negative T-waves was evident at the majority of observational ages in unadjusted analyses. After adjustment for other conditions (smoking, physical activity level, BMI, systolic blood pressure (BP), hypertension, BP medication, s-cholesterol, hematocrit, Q/QS patterns, and ST-junction/segment depression), a negative T-wave at 50 years of age was significantly associated with all-cause and CVD death, [HR 1.46 (95% CI 1.06–2.01), p=0.021, and HR 1.58 (95% CI 1.06–2.36), p=0.025], respectively. However, the HR of 1.58 for CVD death interacted significantly with time (p=0.034), with greater risk in the years adjacent to observation than for later follow-up (Figure, right panel). The corresponding adjusted analyses of a newly diagnosed negative T-wave appearing at 60, 67 and 75 years were not statistically significant for either of the two outcomes. However, an incident negative T-wave at 80 years of age was shown to have numerically higher overall impact, but not statistically significant for all-cause death [HR 1.52 (95% CI 0.80–2.86), p=0.20], but for CVD death [HR 2.41 (95% CI 1.03–5.66), p=0.043], with no significant interaction with time. Conclusion In this population cohort, a first time registered negative T-wave at 50 years carried a considerably increased risk of mortality, specifically CVD mortality, which cannot be explained by other cardiovascular risk factors. The risk was greatest in middle age, and weakened with increasing age. Our findings warrant verification in other cohorts. If an independent risk indication of negative T-wave at middle age is confirmed it could be a valuable adjunct in screening and cardiovascular risk assessment. Acknowledgement/Funding Sweden Heart-Lung Foundation, ALF Västra Götalandsregionen-Göteborgs Universitet

Background Ischemic heart disease (IHD) often develops after decades of preceding subclinical coronary atherosclerosis. An early prediction of risk for IHD in a general population would be helpful for preventive decision-making. It is well known that biomarkers including troponine, natriuretic peptides and inflammatory biomarkers are useful prognostic predictors for IHD, their long-term predictive values in a general population for incident IHD have not been studied. Purpose The aim of the study was to investigate the predictive value of multi-modality biomarkers on the incident IHD in a random male sample from the general population followed from the age of 50 to 71 years. Method “The study of Men Born in 1943” is a longitudinal cohort study of men living in the city of Gothenburg in Sweden. All patients underwent a baseline examination in 1993, which included physical examination, questionnaires and blood samples. Because of multifactorial nature of atherosclerosis, a panel of biomarkers representing multiple mechanisms such as high-sensitivity troponine (hs-TNT), interleukin-6 (IL-6), cystatin C, high-sensitivity C-reactive protein (hs-CRP), urat, ferritin, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were analyzed from blood samples collected at 50 years of age. Incident IHD was defined as new-onset one of following (myocardial infarction, hospitalized unstable angina and intervention with either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) during 1993–2014. The impact of biomarkers on incident IHD was studied using univariable, followed by stepwise and multivariable Cox proportional hazards models. Results Among the, 753 patients in the study, 105 patients (13,9%) developed IHD during 21 years of follow up with an event rate per 1000 person years 7.49 and a 95% confidence interval (CI) of 6.19 - 9.07. In Cox proportional hazards model for time to first occurrence of IHD, univariable analyses showed that multi-modality biomarker (CRP >1 mg/ml, NT-proBNP >100 pg/mL, troponin >10 ng/L, IL-6 >8 ng/L) provide most powerful prediction, followed by total cholesterol and fasting plasma glucose. In multivariable Cox proportional hazards model for time to first of IHD, above four-biomarker combination modality remains a most powerful predictor with risk increased by one additional biomarker [Hazard Ratio (95% CI): 1.69 (1.26 - 2.26), p=0.0004], followed by total cholesterol (mmol/L) with risk increased by one [Hazard Ratio (95% CI: 1.31 (1.09 - 1.56), p=0.0031], and fasting plasma glucose (mmol/L) with risk increased by one unit [Hazard Ratio (95% CI): 1.11 (1.01 - 1.22), p=0.038]. Conclusion A multi-modality biomarker strategy can be used to predict increased risk of developing IHD during the following two decades after 50 years, enabling us to identify individuals who might benefit from early intensive risk modification to prevent the development of IHD.

Background Among patients with heart failure and reduced ejection fraction (HFrEF), angiotensin-converting enzyme inhibitors (ACEI/ARB), β-adrenergic receptor blockers (BB) and aldosterone antagonists (AA) are guideline-directed medical therapy (GDMT) to improve prognosis and well-being. However, low blood pressure (BP) and renal dysfunction are often challenges and barriersof the clinical implementation in real-world. Purpose To investigate whether it is beneficial to apply GDMT in real-world patients with HFrEF despite low blood pressure and renal dysfunction. Methods This study initially included 51060 HF patients from the Swedish Heart Failure Registry. After the exclusion of patients with ejection fraction ≥40% (53.4%), systolic BP>100mmHg (40.0%), eGFR>45ml/min/1.73m2 (3.3.%) and those died during hospitalization (0.3%), 1386 patients were ultimately enrolled in this study. Patients were grouped into five subgroups (ACEI/ARB+BB+AA, ACEI/ARB+BB, ACEI/ARB+AA, ACEI/ARB and BB). Outcome is all cause mortality. Results Among the study patients, 485 (35.0%) were treated with ACEI/ARB+BB+AA, 672 (48.5%) with ACEI/ARB+BB, 41 (3.0%) with ACEI/ARB+AA, 68 (4.9%) with ACEI/ARB and 120 (8.7%) with BB. Patients in ACEI/ARB+BB+AA group were younger (72.9±9.7 vs. 76.1±9.2 vs. 73.9±9.7 vs. 79.5±8.0 vs. 79.3±8.9), with higher BMI (25.4±4.5 vs. 25.5±4.7 vs. 23.7±4.2 vs. 23.4±3.8 vs. 24.7±6.3), more in NYHA I/II (30.8% vs. 33.3% vs. 1.7% vs. 18.9% vs. 24.3%). During the follow-up, all cause mortality was lowest in patients treated with ACEI/ARB+BB+AA (59% vs. 60.4% vs. 75.6% vs. 75% vs. 79.2%). After adjustement for age and gender, when compared with the ACEI/ARB+BB+AA group, the hazard ratio for ACEI/ARB+BB is 1.05 (0.91–1.23), ACEI/ARB+AA 1.16 (0.80–1.68), ACEI/ARB 1.51 (1.11–2.04), and BB 2.36 (1.86–2.98) respectively Conclusions In real-world HFrEF patients with low blood pressure and renal dysfunction, full medication of GDMT is associated with improved long-term survival.

Background Prediction of ischemic cerebral events in patients with heart failure (HF) in the absence of atrial fibrillation (AF) is challenging. Purpose To prospectively test a staged approach to identify patients with HF and sinus rhythm who are at high risk of developing TIA/ischemic stroke (TIA/IS) during the first two years after diagnosis. Methods The analysis is based on patient data reported in the Swedish Heart Failure Register from January 2003 until December 2013. Patients with AF and those treated with anticoagulants were excluded. The study population was categorized in two groups according to left ventricular ejection fraction: LVEF ≤40% and LVEF >40%. Factors associated with TIA/IS were determined by univariate proportional hazard regression. The risk score included: age (1p for 65–74y; 2p for 75–84y; 3p for ≥85y), previous ischemic heart disease (1p), hypertension (1p), diabetes mellitus (1p), TIA/IS (2p), and kidney dysfunction (1p). Two-year hazard ratios with death as competing risk were computed. The probability of observing the outcome was calculated using the cumulative incidence function. Results A total of 16,865 patients (mean age 72.1±13.2y) were included in the study, 39.9% women; 59.7% had LVEF ≤40%. The two-year crude rate of TIA/IS, hemorrhagic stroke, and all-cause mortality were 3.3%, 0.3%, and 26%, respectively. An incremental absolute risk for TIA/IS was observed for patients with LVEF ≤40% and score 1- ≥6: 1.6, 2.3, 3.6, 2.9, 6.3, and 7.1%, respectively. The corresponding HRs with 95% confidence interval (CI) and the patients with 0 points as reference group were: 2.8 (1.1–7.3), 4.0 (1.6–10.1), 6.6 (2.7–16.2), 5.5 (2.2–13.8), 14.4 (5.8–35.9) for score 1- ≥6, where all p-values were less than 0.05 and Wald χ2 for overall model fit In patients with LVEF >40% and score 1–≥6, the absolute TIA/IS risk was: 1.3, 3.1, 3.1, 3.3, 4.6, and 5.3%, respectively. The corresponding HRs with 95% CI and patients with 1 point as reference group was: 2.4 (1.1–5.2), 2.5 (1.2–5.3), 2.7 (1.3–5.7), 3.9 (1.8–8.2); and 4.6 (2.2–9.8), for score 1- ≥6 (all p Conclusion In the current study, a risk score compiling age and specific comorbidity was shown to predict increased risk of TIA/IS, regardless of LVEF, during the first two years after diagnosis in patients with incident HF in sinus rhythm.

Background In heart failure with left ventricular ejection fraction reduction Purpose To evaluate the difference in mortality between IHD and DCM in HFrEF, overall, in specific subgroups and over time. Methods By applying multivariable Cox regression analyses on Swedish Heart Failure Registry data from the years 2000 to 2012 (including 51,060 patients), the incidence of mortality in 8,982 patients with non-valvular clinical IHD-HFrEF was compared to 2,220 patients with DCM-HFrEF overall and for subgrouping variables of age category, sex and EF group ( Results The overall mortality was higher in IHD-HFrEF with the crude mortality of 42.1% and the event rate 15.4 (95% confidence interval [CI]: 14.9 - 15.9) per 100 person years compared with 19.4% and 5.5 (95% CI: 5.0–6.1) in DCM-HFrEF. The probability of survival in IHD-HFrEF was lower than in DCM-HFrEF (Figure). After multivariable adjustment the risk for mortality in IHD-HFrEF remained increased with a hazard ratio (HR) of 1.34 (95% CI: 1.18–1.50). The adjusted HR was higher in all groups of age Probability of survival Conclusions In patients with heart failure and reduced ejection fraction, ischaemic heart disease compared to dilated cardiomyopathy was associated with increased mortality in all age groups below 80 years of age, throughout the 13-year study period. Acknowledgement/Funding The Swedish Heart-Lung Foundation. The regional ALF agreement between Västra Götalandsregionen and University of Gothenburg (ALFGBG-72196, prof.Fu)

Aim To characterise the clinical significance of M2-muscarinic acetylcholine receptor autoantibodies (M2-AAB) in patients with dilated cardiomyopathy (DCM). Methods and results Sera from 104 patients with DCM, age-matched with 104 patients with idiopathic atrial fibrillation (Af) and 104 healthy control subjects, were screened for M2-AAB by enzyme-linked immunosorbent assay (ELISA). IgG purified by Protein-A column was also used as a primary antibody in ELISA. In DCM, M2-AAB were detected in 40% of patients using whole sera and in 36% of patients using purified IgG. M2-AAB were also found in several patients with idiopathic Af (23%, 23%), and these frequencies were significantly higher than those in healthy subjects (8%, 8%). Af was more common in AAB-positive than in AAB-negative patients with DCM. Multivariable analysis confirmed that M2-AAB were independent predictors of the presence of Af in such patients. We determined electrophysiological changes by adding patient purified M2-AAB to chick embryos. Purified IgG from both Af and DCM patients exhibited negative chronotropic effects and induced supraventricular arrhythmias. Conclusion M2-AAB may play a role in mediating the development of Af in patients with DCM.

Background: Inflammation has a crucial role in the development of coronary artery disease (CAD). Obstructive sleep apnea (OSA) is a common condition in CAD patients and associated with increased inflammation. The impact of OSA on inflammatory activity in CAD is unknown. Methods and results: Inflammatory markers, High-sensitive (Hs)-CRP, Interleukin (IL)-6, IL-8 and Tumor Necrosis Factor (TNF)-α, were studied in a non-obese cohort of revascularized CAD patients with OSA (Apnea Hypopnea-Index [AHI] ≥15 events/h; n=267) and non-OSA (AHI