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Background Several studies have reported excess female mortality in patients with hypertrophic cardiomyopathy, but the cause is unknown. Aims To compare risk-factors for disease-related death in both sexes in a geographical cohort of patients with obstructive hypertrophic cardiomyopathy (oHCM). Methods and results Data-bases in all ten hospitals within West Götaland Region yielded 250 oHCM-patients (123 females, 127 males). Mean follow-up was 18.1 y. Risk-factors for disease-related death were evaluated by Cox-hazard regression and Kaplan-Meier survival-curves, with sex-comparisons of distribution of risk-factors and therapy in total and age-matched (n = 166) groups. At diagnosis females were older, median 62 y vs. 51 y, (P Conclusion Addressing sex-disparities in the timing of diagnosis and pharmacological therapy has the potential to improve the care of females with oHCM.

Aims To compare trends in short‐term and long‐term survival of patients with heart failure (HF) compared with controls from the general population. Methods and results We used data from the Swedish National Inpatient Registry to identify all patients aged ≥18 years with a first recorded diagnosis of HF between 1 January 1987 and 31 December 2014 and compared them with controls matched on age and sex from the Total Population Register. We included 702 485 patients with HF and 1 306 183 controls. In patients with HF aged 18–64 years, short‐term (29 days to 6 months) and long‐term mortality (>11 years) decreased from 166 and 76.6 per 1000 person‐years in 1987 to 2000 to 99.6 and 49.4 per 1000 person‐years, respectively, in 2001 to 2014. During the same period, mortality improved marginally, in those aged ≥65 years: short‐time mortality from 368.8 to 326.2 per 1000 person‐years and long‐term mortality from 219.6 to 193.9 per 1000 person‐years. In 1987–2000, patients aged 11 years) increased moderately from 2.49 (95% CI 2.41–2.57) and 3.16 (95% CI 3.07–3.24) in 1987–2000 to 4.35 (95% CI 4.09–4.63) and 4.11 (95% CI 3.49–4.85) in 2001–2014, largely because survival among controls improved more than that among patients with HF (P

Background As opposed to the decreasing overall rates of coronary heart disease (CHD) incidence and overall cardiovascular disease (CVD) mortality, heart failure (HF) and stroke incidence are increasing in young people, potentially due to rising rates of obesity and reduced cardiorespiratory fitness (CRF). Objectives We investigated trends in early major CVD outcomes in a large cohort of young men. Methods Successive cohorts of Swedish military conscripts from 1971 to 1995 (N = 1,258,432; mean age, 18.3 years) were followed, using data from the National Inpatient and Cause of Death registries. Cox proportional hazard models were used to analyse changes in 21-year CVD event rates. Results 21-year CVD and all-cause mortality and incidence of acute myocardial infarction (AMI) decreased progressively. Compared with the cohort conscripted in 1971-1975 (reference), the hazard ratios (HRs) for the last 1991-1995 cohort were 0.50 [95% confidence interval (CI) 0.42-0.59] for CVD mortality; 0.57 (95% CI 0.54-0.60) for all-cause mortality; and 0.63 (95% CI 0.53-0.75) for AMI. In contrast, the incidence of ischaemic stroke, intracerebral haemorrhage and HF increased with HRs of 1.43 (95% CI 1.17-1.75), 1.30 (95% CI 1.01-1.68) and 1.84 (95% CI 1.47-2.30), respectively. During the period, rates of obesity increased from 1.04% to 2.61%, whilst CRF scores decreased slightly. Adjustment for these factors influenced these secular trends only moderately. Conclusion Secular trends of young-onset CVD events demonstrated a marked shift from AMI and CVD mortality to HF and stroke incidence. Trends were significantly, though moderately, influenced by changing baseline BMI and CRF.

Aims This study aims to investigate hospital readmissions and timing, as well as risk factors in a real world heart failure (HF) population. Methods and results All patients discharged alive in 2016 from Sahlgrenska University Hospital/Östra, Gothenburg, Sweden, with a primary diagnosis of HF were consecutively included. Patient characteristics, type of HF, treatment, and follow‐up were registered. Time to first all‐cause or HF readmission, as well as number of 1 year readmissions from discharge were recorded. In total, 448 patients were included: 273 patients (mean age 78 ± 11.8 years) were readmitted for any cause within 1 year (readmission rate of 60.9%), and 175 patients (mean age 76.6 ± 13.7) were never readmitted. Among readmissions, 60.1% occurred during the first quarter after index hospitalization, giving a 3 month all‐cause readmission rate of 36.6%. HF‐related 1 year readmission rate was 38.4%. Patients who were readmitted had significantly more renal dysfunction (52.4% vs. 36.6%, P = 0.001), pulmonary disease (25.6% vs. 15.4%, P = 0.010), and psychiatric illness (24.9% vs. 12.0%, P = 0.001). Number of co‐morbidities and readmissions were significantly associated (P

Aims We investigated the 2 year rate of ischaemic stroke/transient ischaemic attack (IS) in patients with heart failure (HF) who were in sinus rhythm (HF-SR) and aimed to develop a score for stratifying risk of IS in this population. Methods and results A total of 15 425 patients (mean age 71.5 years, 39% women) with HF-SR enrolled in the Swedish Heart Failure Register were included; 28 815 age-matched and sex-matched controls, without a registered diagnosis of HF, were selected from the Swedish Population Register. The 2 year rate of IS was 3.0% in patients and 1.4% in controls. In the patient group, a risk score including age (1p for 65-74 years; 2p for 75-84 years; 3p for >= 85 years), previous IS (2p), ischaemic heart disease, diabetes, hypertension, kidney dysfunction, and New York Heart Association III/IV class (1p each) was generated. Over a mean follow-up of 20.1 (SD 7.5) months, the cumulative incidences (per 1000 person-years) of IS in patients with score 0 to >= 7 were 2.2, 5.3, 8.9, 13.2, 15.7, 20.4, 26.4, and 33.0, with hazard ratios for score 1 to >= 7 (with 0 as reference): 2.4, 4.1, 6.1, 7.2, 9.4, 12.2, and 15.3. The risk score performed modestly (area under the curve 63.7%; P = 0.4711 for lack of fit with a logistic model; P = 0.7062 with Poisson, scaled by deviance). Conclusions In terms of absolute risk, only 27.6% of patients had an annual IS incidence of Funding Agencies|Swedish government [ALFGBG-717211]; County Councils Concerning Economic Support of Research and Education of Doctors [ALFGBG-717211]; Swedish Heart and Lung Foundation (Hjart-Lungfonden) [2015-0438, 2018-0366]; Swedish Research Council (Vetenskapsradet)Swedish Research Council [2013-05187, 2018-02527]

The PARADIGM-HF trial showed that sacubitril-valsartan - an angiotensin receptor-neprilysin inhibitor (ARNI) - is more effective than enalapril for some patients with heart failure. However, the eligibility of the PARADIGM-HF study to a real-world heart failure population was not well established.We made secondary analysis of patients (n = 4872) with heart failure prospectively enrolled in the Swedish Heart Failure Registry from Sahlgrenska University Hospital/Östra Hospital, Sweden during 2005-2016. The eligibility of the PARADIGM-HF trial in the real world was studied based on patients whether they were either fully or partially compatible with the PARADIGM-HF population. Patients were judged to be fully eligible for the PARADIGM-HF trial if they completely met the inclusion and exclusion criteria, and partially eligible if they did not stay on target dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), despite their having been treated with ACEI/ARB for at least 6 months.Among patients who had heart failure with reduced left ventricular ejection fraction (≤40%) (HFrEF) (n = 2165), 653 (30%) and 958 (44%) patients were fully and partially compatible with PARADIGM-HF criteria, respectively. In both fully and partially eligible groups, patients were more male. Despite those fully eligible patients being younger (77.6 ± 12.7 vs. 84.0 ± 13.7 years) than noneligible patients, they were much older than in the PARADIGM-HF trial. Moreover, those fully eligible patients had lower all-cause mortality compared with both partially and noneligible patients. However, both fully and partially eligible patients had higher all-cause mortality than that in the PARADIGM-HF trial.In a real-world outpatient clinical setting, around 1/3-1/2 of HFrEF were eligible for treatment of Sac/Val except that they are older, sicker, and carry higher risk for all-cause mortality than the PARADIGM-HF trial population.

Aims The aim of this study is to validate a diagnosis of heart failure (HF) according to the European Society of Cardiology (ESC) guidelines among patients hospitalized at Sahlgrenska University Hospital, Gothenburg, Sweden, between 2000 and 2012. Methods and results In Sweden, it is mandatory to report all hospital discharge diagnoses to the Swedish national inpatient register. In total, 27 517 patients were diagnosed with HF at the Sahlgrenska University hospital between 2000 and 2012. Altogether, 1100 records with a primary (n = 550) or contributory (n = 550) diagnosis of HF were randomly selected. The diagnosis was validated according to the ESC guidelines from 1995, 2001, 2005, and 2008, and cases were divided into three groups: definite, probable, and miscoded. In total, 965 cases were validated, while 135 records were excluded for various reasons. Of the 965 records, the diagnosis was validated as definite in 601 (62.3%) and as probable in 310 (32.1%); only 54 (5.6%) of cases had been miscoded. Echocardiography, as an objective evidence of cardiac dysfunction, had been performed in 581 (96.7%) of the definite, 106 (34.2%) of the probable, and 31 (57.4%) of the miscoded cases. Among the probable cases, the main reason they had not been classified as a definitive diagnosis of HF was lack of examination by echocardiography (63.8%). Conclusions The overall validity of HF diagnosis at Sahlgrenska University Hospital is high. This may reflect a high diagnostic validity at the time of diagnosis in the national Swedish patient register, supporting the continued use of this register in epidemiological research.

Aims This study was performed to compare trends in home‐time for patients with heart failure (HF) between those of working age and those of retirement age in Sweden from 1992 to 2012. Methods and results The National Inpatient Register (IPR) was used to identify all patients aged 18 to 84 years with a first hospitalization for HF in Sweden from 1992 to 2012. Information on date of death, comorbidities, and sociodemographic factors were collected from the Swedish National Register on Cause of Death, the IPR, and the longitudinal integration database for health insurance and labour market studies, respectively. The patients were divided into two groups according to their age: working age (

Background Heart failure (HF) is increasing in people of working age in Sweden (1). Given high morbidity and reduced quality of life among HF patients (2, 3), working capacity could be greatly affected, however, studies are scarce. Purpose To determine trends in sick leave rates following a first hospitalization for HF in Sweden 1995–2015 compared to controls matched by age and sex. Methods In Sweden, people who cannot work receive sickness benefit. Sickness benefit pay days are registered by Statistics Sweden. We identified all patients aged 18–60 years with a first hospitalization for HF in Sweden 1995–2012 in the National Patient Register (NPR). For each case we selected 2 controls matched for age and sex. Cases and controls were split into age groups, Results A total of 24,677 cases and 65,923 controls were included, mean age for the younger and older age group 36.6 and 54.5 years, and proportion of women 35.3% and 23.8%, respectively. In 1995, the proportion of time on sickness benefit in patients Conclusion Patients had a longer time on sick leave than controls over the study period. Time on sickness benefit initially declined over the course of the study period for both patients and controls, but the last years of the study period this decline stalled for both patients and controls. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Swedish state under an agreement between the Swedish government and the County Councils Concerning Economic Support of Research and Education of Doctors [ALFGBG-717211, ALFGBG-433211, ALFGBG-725081]; the Swedish Heart and Lung Foundation [2013-0307, 2018-0419, 2018-0589]. Figure 1Figure 2

Objectives: Investigate trends in incidence and prognosis of myocarditis in Sweden during 2000-2014.Background: Myocarditis is an inflammatory heart disease, with scarce data concerning incidence and prognosis.Methods: Linking Swedish National Patient and Cause of Death Register, we identified individuals ≥16 years with first-time diagnosis of myocarditis during 2000-2014. Reference population, matched for age and birth year (n=16 622) was selected from the Swedish Total Population Register. Results: Among the 8 679 cases, (75% men, 64% Conclusion: The incidence of myocarditis during 2000-2014 increased, predominantly in younger men. One-year mortality in the young was low, but fourfold higher compared with reference population.

Investigate trends in myocarditis incidence and prognosis in Sweden during 2000–2014. Little data exist concerning population-trends in incidence of hospitalizations for myocarditis and subsequent prognosis. Linking Swedish National Patient and Cause of Death Registers, we identified individuals ≥ 16 years with first-time diagnosis of myocarditis during 2000–2014. Reference population, matched for age and birth year (n = 16,622) was selected from Swedish Total Population Register. Among the 8 679 cases (75% men, 64%

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 Heart failure in the young is increasing. Increasing prevalence of overweight and obesity may be of importance. While alcohol and drugs are known to have cardiotoxic effects, few studies have investigated the prevalence of alcohol- or substance abuse among young patients with HF. Aim To investigate the prevalence of alcohol- and substance abuse in a cohort of young patients with heart failure. Methods All patients that received a diagnosis of heart failure at Sahlgrenska University Hosital (Sweden) between 1997 and 2016, ages 18–54, with a previously documented transthoracic echocardiogram were included. A systematic evaluation of participants electronic health records was performed, where predefined details about the use of alcohol, narcotic drugs and anabolic steroids, as well as echocardiographic findings were recorded. Result A total of 1363 patients were included (1001 men and 366 women, mean age 45 years), 190 (14%) of which were Conclusion There was a high prevalence of alcohol- and/or drug-abuse among young adults with heart failure, especially in male patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Swedish state under the agreement concerning research and education of doctors [grant number ALFGBG-427301]; The Swedish Society for Physicians, the Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, Sweden, and the Swedish Heart and Lung Foundation [grant number 2015-0438]

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)

Background Peripartum cardiomyopathy (PPCM) is idiopathic pregnancy‐associated heart failure (HF) with reduced left ventricular ejection fraction (LVEF). We aimed to assess arterial stiffness and left ventricular (LV) function in women recovered from PPCM compared with controls. Methods Twenty‐two PPCM patients were compared with 15 age‐matched controls with previous uncomplicated pregnancies. Eleven of the patients were at inclusion in the study recovered and off medication since at least 6 months and still free from cardiovascular symptoms with normal LVEF and normal NT‐proBNP. All underwent echocardiography, including LV strain, left atrial (LA) reservoir strain and tissue Doppler early diastolic velocity (e´) and non‐invasive assessment for arterial stiffness and central aortic systolic blood pressure (AoBP) at rest and immediately postexercise. Results The patients off medication showed alterations compared with controls. AoBP was higher (120 ± 9 mm Hg vs. 104 ± 13 mm Hg; p = .001), a difference which persisted postexercise. The arterial elastance was higher (1.9 ± 0.4 mm Hg/ml vs. 1.3 ± 0.2 mm Hg/ml; p

Aims The prevalence and hospitalizations of patients with heart failure (HF) aged = 18 years in the Swedish Heart Failure Register from 2003 to 2014 were included. Data were merged with National Patient and Cause of Death Registers. Among 60 962 patients, 3752 (6.2%) were = 55 years, patients = 55 years, patients = 55 years. The highest mortality risk relative to that of controls was among the youngest patients. Funding Agencies|Swedish Research CouncilSwedish Research Council [2013-5187 SIMSAM]; Swedish state [ALFGBG-433211, ALFGBG-725081, ALFGBG-717211]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [2013-0307, 2018-0419, 2015-0438]; Vastra Gotaland Region; Gothenburg Society of Medicine [GLS-328971]; Swedish Council for Health, Working Life and Welfare (FORTE) [2013-0325]; Cardiology Research Foundation at the Medical Clinic at Sahlgrenska University Hospital/Ostra; Swedish National Board of Health and Welfare; Swedish Association of Local Authorities and Regions; Swedish Society of Cardiology and Cardiology Research Foundation

Supplemental Digital Content is available in the text., Background: Incidence rates of cardiomyopathies, which are a common cause of heart failure in young people, have increased during the last decades. An association between body weight in adolescence and future cardiomyopathy among men was recently identified. Whether or not this holds true also for women is unknown. The aim was therefore to determine whether for young women being overweight or obese is associated with a higher risk of developing cardiomyopathy. Methods: This was a registry-based national prospective cohort study with data collected from the Swedish Medical Birth Register, 1982 to 2014, with up to 33 years of follow-up. Included women were of childbearing age (18–45 years) during the initial antenatal visit in their first or second pregnancy (n=1 393 346). We obtained baseline data on body mass index (BMI), smoking, education, and previous disorders. After exclusions, mainly because of previous disorders, the final sample was composed of 1 388 571 women. Cardiomyopathy cases were identified by linking the Medical Birth Register to the National Patient and Cause of Death registers. Results: In total, we identified 1699 cases of cardiomyopathy (mean age at diagnosis, 46.2 [SD 9.1] years) during the follow-up with an incidence rate of 5.9 per 100 000 observation years. Of these, 481 were diagnosed with dilated cardiomyopathy, 246 had hypertrophic cardiomyopathy, 61 had alcohol/drug-induced cardiomyopathy, and 509 had other forms. The lowest risk for being diagnosed with a cardiomyopathy was detected at a BMI of 21 kg/m2, with a gradual increase in risk with higher BMI, particularly for dilated cardiomyopathy, where a hazard ratio of 4.71 (95% CI, 2.81–7.89) was found for severely obese subjects (BMI ≥35 kg/m2), as compared with BMI 20 to

Purpose Loop diuretics are recommended to treat congestive symptoms in patients with heart failure. However, observational studies have indicated that loop diuretic treatment in heart failure is associated with increased mortality. Therefore, loop diuretic discontinuation or dose reduction, when clinically possible, is recommended. Our aim was to study nationwide temporal trends in loop diuretic treatment from 2005 to 2014 in real-life patients with chronic heart failure. Methods Data from the nationwide Swedish National Patient, Prescribed Drug and Cause of Death Registers were linked. The annual proportions of patients with chronic heart failure treated with loop diuretics from 2005 to 2014 were calculated. In addition, the annual median loop diuretic doses (DDD) in patients with chronic heart failure treated with loop diuretics from 2005 to 2014 were calculated. Results The proportion of real-life patients with chronic heart failure treated with loop diuretics decreased from 73.2% in 2005 to 65.7% in 2014 (p for trend

Background Peripartum cardiomyopathy (PPCM), a potentially life-threatening condition in women, can have a profound impact on the family. Although structured support systems are developed, these systems tend to be based on the healthcare providers’ perceptions and focus mainly on mothers’ care. Fathers’ vital role in supporting their partners has been advocated in previous research. However, the impact of PPCM on the male partners of women is less understood. The aim of this study was to explore the experiences of healthcare in fathers whose partner was suffering from peripartum cardiomyopathy. Methods The data from interviews with fourteen fathers were analysed using inductive content analysis. Results An overarching category “The professionals could have made a difference” was identified from the data, characterised by the sub-categories: ‘To be informed/not informed,’ ‘To feel secure/insecure,’ ‘To feel visible/invisible’ and ‘Wish that it had been different’. Lack of timely information did not allow fathers to understand their partner´s distress, and plan for the future. The birth of the child was an exciting experience, but a feeling of helplessness was central, related to seeing their partner suffering. A desire for follow-up regarding the effect of PPCM on themselves was expressed. Conclusions When men, as partners of women with PPCM, get adequate information of their partner´s condition, they gain a sense of security and control that gives them strength to handle their personal and emotional life-situation during the transition of becoming a father, along with taking care of an ill partner with PPCM. Hence, maternity professionals should also focus on fathers’ particular needs to help them fulfil their roles. Further research is urgently required in this area.

Background The incidence of heart failure (HF) is decreasing in older ages, but increasing rates have been observed among younger persons in Sweden. Therefore, we investigated the relationship between risk of hospitalization for HF and body mass index (BMI). Methods This was a prospective registry-based cohort study. We included 1,374,031 women aged 18–45 years (mean age 27.9 years) who gave birth during 1982–2014, and were registered in the Medical Birth Register. Information on hospitalization because of HF was collected through linkage to the National Inpatient Register. Results Compared to women with a BMI of 20–2, women with a BMI of 22.5–2, respectively. The multiple-adjusted HRs (95% CI) associated with risk of HF per one-unit increase in BMI in women with a BMI ≥ 22.5 kg/m2 ranged from 1.01 (0.97–1.06) for HF related to valvular disease to 1.14 (1.12–1.15) for coronary heart disease, diabetes, or hypertension. Conclusion Increasing body weight was strongly associated with the risk of early HF in women. Compared with lean women, the risk for HF started to increase at high-normal BMI levels, and was nearly five-fold in women with a BMI ≥ 35 kg/m2.

Aims Examination of long-term results following different treatments in hypertrophic obstructive cardiomyopathy (HOCM) in a complete geographical cohort. Methods and results HOCM patients attending during 2002–13 in all 10 hospitals in the West Götaland Region, Sweden, were identified (n = 251), follow-up 14.4 (±8.9) years (mean ± SD), 121 managed medically, 42 treated with myectomy and 88 with short atrioventricular (AV) delay pacing as first interventional procedure. Post-intervention follow-up was 12.9 ± 8.7 years and 12.2 ± 5.0 years, respectively. Both intervention treatments improved New York Heart Association (NYHA) class and outflow gradients significantly. Patients treated with pacing were older (median age 64 vs. 43 years, P

Aim Hospital discharges with a diagnosis of cardiomyopathy have more than doubled in Sweden since 1987. We validated the cardiomyopathy diagnoses over this time period to investigate that the increase was real and not a result of improved recognition of the diagnosis and better diagnostic methods. Methods and results Every fifth year from 1989 to 2009, records for all patients with a cardiomyopathy diagnosis were identified by searching the local registers in three hospitals in Vastra Gotaland, Sweden. The diagnoses were validated according to criteria defined by the European Society of Cardiology from 2008. The population comprised 611 cases with cardiomyopathy diagnoses [mean age 58.9 (SD 15.5) years, 68.2% male], divided into three major groups: dilated, hypertrophic, and other cardiomyopathies. Hypertrophic cardiomyopathy and hypertrophic obstructive cardiomyopathy were analysed as a group. Cardiomyopathies for which there were few cases, such as restrictive, arrhythmogenic right ventricular, left ventricular non-compaction, takotsubo, and peripartum cardiomyopathies, were analysed together and defined as 'other cardiomyopathies'. Relevant co-morbidities were registered. The use of echocardiography was 99.7%, of which 94.6% was complete echocardiography reports. The accuracy rates of the diagnoses dilated cardiomyopathy, hypertrophic cardiomyopathy, and other cardiomyopathies were 85.5%, 87.5%, and 100%, respectively, with no differences between the three hospitals or years studied; nor did the prevalence of co-morbidities differ. Conclusions The accuracy rate of the cardiomyopathy diagnoses from in-hospital records from >600 patients in western Sweden during a 20 year period was 86.6%, with no significant trend over time, strengthening epidemiological findings that this is likely due to an actual increase in cardiomyopathy diagnoses rather than changes in coding practices. The use of echocardiography was high, and there was no significant difference in co-morbidities during the study period. The accuracy rate of the cardiomyopathy diagnoses during the 20 year period was high. The use of diagnostic tools did not increase under the study period, and once cardiomyopathy diagnoses were suspected, echocardiography was performed in almost all cases. In this study, the occurrence of cardiomyopathy was increasing over time without significant increase of co-morbidity, supporting that an actual increase of cardiomyopathy has occurred.

Objective Obesity has been shown to be a risk factor for heart failure (HF), but whether the association varies by age is not understood. The aim was to examine the impact of obesity/overweight on the risk of developing heart failure in women of different ages by analysing prospective data from 2 population studies. Methods Data were obtained from the Population Study of Women in Gothenburg and the Gerontologic and Geriatric Population Studies concerning body mass index (BMI) collected in 1980 or later. Follow-up ended in 2006. Cox proportional hazard methods were used to determine associations between developing HF and BMI in 2574 women, 1243 aged 26–65 years and 1331 aged 66–76 years, at baseline. Results Women aged 26–65 years at baseline with BMI ≥30 kg/m 2 had an increased risk of developing HF (hazard ratio [HR] 2.61, 95% confidence interval [CI] 1.56–4.35) even when controlling for age, glucose, smoking, alcohol consumption, serum triglycerides, and systolic blood pressure (reference group: women with BMI 18.5–22.4 kg/m 2 ). Obese women aged 66–76 years at baseline did not show increased risk of developing HF (HR 0.55, 95% CI 0.23–1.29). Conclusions Obesity in middle-age women increases their risk of developing HF later in life. In contrast, obesity later in life shows no association with HF.

Germline genetic variants are an important cause of dilated cardiomyopathy (DCM). However, recent sequencing studies have revealed rare variants in DCM-associated genes also in individuals without known heart disease. In this study, we investigate variant prevalence and genotype-phenotype correlations in Swedish DCM patients, and compare their genetic variants to those detected in reference cohorts.We sequenced the coding regions of 41 DCM-associated genes in 176 unrelated patients with idiopathic DCM and found 102 protein-altering variants with an allele frequency of0.04% in reference cohorts; the majority were missense variants not previously described in DCM. Fifty-five (31%) patients had one variant, and 24 (14%) patients had two or more variants in the analysed genes. Detection of genetic variants in any gene, and in LMNA, MYH7 or TTN alone, was associated with early onset disease and reduced transplant-free survival. As expected, nonsense and frameshift variants were more common in DCM patients than in healthy individuals of the reference cohort 1000 Genomes Europeans. Surprisingly however, the prevalence, conservation and pathogenicity scores, and localization of missense variants were similar in DCM patients and healthy reference individuals.To our knowledge, this is the first study to identify correlations between genotype and prognosis when sequencing a large number of genes in unselected DCM patients. The similar distribution of missense variants in DCM patients and healthy reference individuals questions the pathogenic role of many variants, and suggests that results from genetic testing of DCM patients should be interpreted with caution.

Background The last two decades incidence and prevalence of heart failure (HF) among young patients have increased in Sweden. Up to the beginning of the 21st century mortality in patients with HF has decreased but causes of death and the effects of co-morbidity on mortality in young patients with HF are not well studied. Purpose To address causes of death and the effect of co-morbidity at baseline on mortality during the last decade in young patients with HF. Methods The Swedish Heart Failure Register (SwedeHF,) a nationwide quality register, was introduced in Sweden in 2003. All hospital discharge diagnoses are recorded in the National Patient Register (NPR) and deaths are registered in the Cause of Death Register. All patients ≥18 and Results We identified 3752 (6.2%) patients Effect of co-morbidity on mortality Conclusion Compared to matched controls young patients with HF had worse survival. Almost one quarter of women with HF had cancer as a principal cause of death. Men with AF, obesity and depression at baseline had higher risk to die than women. Women with HF and hypertension, PAH or kidney disease at baseline had higher risk to die than men with HF and the same co-morbidities. Acknowledgement/Funding Swedish state under the agreement concerning research and education of doctors, The Swedish Heart and Lung Foundation, Västra Götaland Region grants

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 Increasing numbers of stroke cases in the young are reported in many countries, potentially at least partly due to rising rates of overweight and obesity. Most data on the effect of obesity on stroke is derived from middle aged populations; there is a comparative lack of information on the effect of excessive body weight in young people. Purpose We aimed to determine whether body mass index (BMI) at age 18 predicted early stroke events among men in Sweden. Methods Population-based Swedish cohort study of conscripts (n=1,668,921; mean age at baseline, 18.3 years) who enlisted during 1968–2005. Follow-up was done through linkage to the nationwide Swedish patient and death registries. Risk of a first hospitalization for stroke (any type) during follow-up (5–46 years) was calculated with Cox proportional hazards models. Objective baseline measures of fitness and cognition were included in the models in a second set of analyses. Results During follow-up there were 12,512 first hospitalizations for stroke (mean age at diagnosis, 48.5 (SD 9.4) years, maximum 64 years). Compared with men with BMI of 18.5 to 20.0 kg/m2, men with BMI 20 to Conclusion We found a rise in risk of early hospitalisation for stroke detectable already at normal levels of body weight at age 18, and rising to more than 3-fold in the highest weight category. Given increasing levels of body weight, and prevalence of overweight, obesity, and severe obesity in young adults, the increased incidence of stroke in the young may potentially partly be explained by rising body weight, with an obvious potential for prevention.

Background Cardiovascular disease (CVD) mortality is decreasing in Western countries, including Sweden. However, there are reports of increases in incidence in young people with respect to heart failure (HF) and atrial fibrillation (AF). The magnitude and causes of these changes are only partly known. Aims We investigated secular trends in incidence in CVD outcomes and their attenuation by changes in body mass index (BMI). The outcomes were risk of acute myocardial infarction (AMI), heart failure (HF) and atrial fibrillation (AF) as well as cardiovascular and all-cause death in a population of Swedish adolescents. Methods We followed a cohort of Swedish men enrolled for military service conscription in 1969–1996 (n=1,326,082; mean age=18.3) until December 2016, collected from the national inpatient (IPR) and outpatient registries (OPR). Cox-proportional hazard models were used to analyse the longitudinal change in incidence by with respect to early (0–21 years) of follow-up for subgroups with conscription 1968–1971, 1971–1976, 1976–1981, 1981–1986, 1986–1991, 1991–1996 (with the group born 1971–1976 as reference). Adjustments for potential confounders including BMI were performed. Results We found that CVD and all-cause mortality and MI decreased progressively during the follow-up with hazard ratios (HR) of 0.51, 95% confidence interval (CI) 0.43–0.62, HR 0.51 CI 0.57–0.62, and 0.60 CI 0.50–0.72, respectively. In contrast, we found increases in the incidence of HF (HR 1.86, CI 1.48–2.33], and AF (HR 8.26, CI 6.87–9.92). Adjustments for changes in BMI partly attenuated the changes in secular trends. Cubic spline models showed where the changes in secular trends were most prominent. Conclusion The incidences of cardiovascular outcomes show diverging secular changes. While MI and cardiovascular mortality are continually decreasing, there is an increase in HF and AF. The associations appear to be partly explained by changes in index BMI over time. Acknowledgement/Funding grants from the Swedish Government and the county councils, the ALF–GBG-719761, ALFGBG-751111, Swedish Stroke Association, Göteborg Medical Society

Background Cardiorespiratory fitness and physical activity have well–known cardio–protective effects. Along with reports on declining levels of physical activity globally, heart failure caused by cardiomyopathy is increasing among young people. Still, it is unknown whether poor fitness in adolescence can be associated with cardiomyopathy in adulthood. Purpose To study a possible link between cardiorespiratory fitness in adolescence and being diagnosed with cardiomyopathy in adulthood. Methods A nationwide register-based prospective cohort study of 1,668,893 young men (mean age 18.3 years, SD 0.7), enlisting for compulsory military service 1969–2005. Body mass index (BMI) and blood pressure were registered at baseline, along with test results for fitness. Values were trichotomized and about 13.5% were classified as having poor cardiorespiratory fitness. Cardiomyopathy diagnoses were identified from the National Hospital Register and Cause of Death Register, during an up to 46-year follow-up, and divided into categories: 1) dilated, 2) hypertrophic, 3) alcohol/drug-induced, and 4) other. Hazard ratios (HR) were calculated with Cox proportional hazards models. Results During follow-up (median 27 years; interquartile interval 19–35 years), 4,477 cases of cardiomyopathy were registered, of which 2,631 (59%) were dilated, 673 (15%) were hypertrophic, and 480 (11%) were alcohol/drug-induced. Poor cardiorespiratory fitness was strongly associated with elevated risk of both dilated (HR 1.59, 95% confidence interval (CI) 1.38–1.83) and alcohol/drug–induced cardiomyopathy (HR 2.32, 95% CI 1.68–3.20), adjusted for BMI, age at conscription, conscription year, test center, and baseline comorbidities (diabetes, hypertension, congenital heart disease). Conclusion The present study shows that poor cardiorespiratory fitness in adolescence may be associated with both dilated and alcohol/drug–induced cardiomyopathy in adulthood. This strengthens the evidence of fitness as a cardio–protective factor, and brings further support to the importance of interventions promoting physical activity already in childhood. Acknowledgement/Funding The Swedish Research Council, The Swedish Heart and Lung Foundation

Background In the PARADIGM-HF trial sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), was more effective than enalapril for some patients with heart failure (HF). However, the eligibility of the PARADIGM-HF study to a real-world heart failure population was not well established. Purpose To investigate the eligibility of PARADIGM-HF Trial in a real-world clinical setting and its cardiovascular risk. Methods We made secondary analysis of patients (n=4872) with heart failure prospectively enrolled in the Swedish Heart Failure Registry from the Outpatient Clinic, during 2005–2016. The eligibility for PARADIGM-HF in real world was studied based on patients whether they were either fully or partially compatible with the PARADIGM-HF study population. Mortality data during follow-up were obtained from the Death Registry of the National Board of Health and Welfare in Sweden. Results Heart failure with reduced LVEF (≤40%) (HFrEF) were found in 2165 patients, 653 patients (30%) were fully and 958 (44%) were partially compatible with PARADIGM-HF criteria respectively (figure). In both the fully and partially eligible groups there were more male. Despite that the fully eligible patients were younger than non-eligible patients (77.6±12.7 vs. 84.0±13.7 years), they were clearly older than in PARADIGM-HF trial. Moreover, those fully-eligible patients had lower all-cause mortality compared with both partially-and non-eligible patients (45.6% vs. 68.5, HR 1.43 (1.18–1.75) p figure Conclusion In a real world outpatient clinical setting, around 35% to 50% of HFrEF were eligible for treatment with ARNI except that they are older, sicker and carried higher risk for all-cause mortality than the PARADIGM-HF trial population.

Background To improve cardiovascular disease (CVD) prevention, knowledge of early key risk factors, especially those that are modifiable such as overweight and obesity, is essential. Purpose We aimed to determine whether body mass index (BMI) at age 18 predicted early acute coronary events among men in Sweden. Methods Population-based Swedish cohort study of conscripts (n=1,668,921; mean age at baseline, 18.3 years) who enlisted during 1968–2005. Follow-up was done through linkage to the nationwide Swedish patient- and death registries. Risk of an acute coronary event (hospitalization for acute myocardial infarction or coronary death) during follow-up (5–46 years) was calculated with Cox proportional hazards models. Objective baseline measures of fitness and cognition were included in the models in a second set of analyses. Results During follow-up there were 22,412 acute coronary events (mean age at diagnosis, 50.2 (SD 7.4) years, maximum 64 years). Compared with men with BMI of 18.5 to 20.0 kg/m2, men with BMI 20 to Conclusion We found a rise in risk of an early acute coronary event detectable already at normal levels of body weight at age 18, and rising to more than 3-fold in the highest weight category. Given increasing levels of body weight, and prevalence of overweight and obesity in young adults, the current decrease in coronary heart disease incidence in Sweden may flatten or even reverse in the near future. Acknowledgement/Funding The Swedish Heart and Lung Foundation [2015-0438]; the Swedish Research Council [2013-5187,2013-4236]

Objectives This study was designed to analyze the prevalence and potential genetic basis of cancer and heart failure in peripartum cardiomyopathy (PPCM). Background PPCM manifests as heart failure late in pregnancy or postpartum in women without previous heart disease. Methods Clinical history and cancer prevalence were evaluated in a cohort of 236 PPCM patients from Germany and Sweden. Exome sequencing assessed variants in 133 genes associated with cancer predisposition syndromes (CPS) and in 115 genes associated with dilated/hypertrophic cardiomyopathy (DCM/HCM) in 14 PPCM patients with a history of cancer, and in 6 PPCM patients without a history of cancer. Results The prevalence of cancer was 16-fold higher (8.9%, 21 of 236 patients) in PPCM patients compared to age-matched women (German cancer registry, Robert-Koch-Institute: 0.59%; p < 0.001). Cancer before PPCM occurred in 12 of 21 patients of whom 11 obtained cardiotoxic cancer therapies. Of those, 17% fully recovered cardiac function by 7 ± 2 months of follow-up compared to 55% of PPCM patients without cancer (p = 0.015). Cancer occurred after PPCM in 10 of 21 patients; 80% had left ventricular ejection fraction of ≥50% after cancer therapy. Whole-exome sequencing in 14 PPCM patients with cancer revealed that 43% (6 of 14 patients) carried likely pathogenic (Class IV) or pathogenic (Class V) gene variants associated with DCM/HCM in CPT2, DSP, MYH7, TTN, and/or with CPS in ATM, ERCC5, NBN, RECQL4, and SLX4. All CPS variants affected DNA damage response genes. Conclusions Cardiotoxic cancer therapy before PPCM is associated with delayed full recovery. The high cancer prevalence in PPCM is linked to likely pathogenic/pathogenic gene variants associated with DCM/HCM and/or CPS/DNA damage response–related cancer risk. This may warrant genetic testing and screening for heart failure in pregnant women with a cancer history and screening for cancer in PPCM patients., Central Illustration

Supplemental Digital Content is available in the text., Background: Modifiable lifestyle factors in relation to risk for cardiomyopathy, a common and increasing cause of heart failure in the young, have not been widely studied. We sought to investigate a potential link between obesity, a recognized predictor of early heart failure, in adolescence and being diagnosed with cardiomyopathy in adulthood. Methods: This was a nationwide register-based prospective cohort study of 1 668 893 adolescent men (mean age, 18.3 years; SD, 0.7 years) who enlisted for compulsory military service from 1969 to 2005. At baseline, body mass index (BMI), blood pressure, and medical disorders were registered, along with test results for fitness and muscle strength. Cardiomyopathy diagnoses were identified from the National Hospital Register and Cause of Death Register during an up to 46-year follow-up and divided into categories: dilated, hypertrophic, alcohol/drug-induced, and other. Hazard ratios were calculated with Cox proportional hazards models. Results: During follow-up (median, 27 years; Q1–Q3, 19–35 years), 4477 cases of cardiomyopathy were identified, of which 2631 (59%) were dilated, 673 (15%) were hypertrophic, and 480 (11%) were alcohol/drug-induced. Increasing BMI was strongly associated with elevated risk of cardiomyopathy, especially dilated, starting at levels considered normal (BMI, 22.5–8-fold increased risk at BMI ≥35 kg/m2 compared with BMI of 18.5 to

Background Heart failure (HF) and non-cardiac comorbidities often coexist and are known to have an adverse effect on outcome. However, the prevalence and prognostic impact of non-cardiac comorbidities in patients with HF with reduced ejection fraction (HFrEF) vs. those with preserved (HFpEF) remain inadequately studied. Methods and results We used data from the Swedish Heart Failure Registry from 2000 to 2012. HFrEF was defined as EF amp;lt; 50% and HFpEF as EF amp;gt;= 50%. Of 31 344 patients available for analysis, 79.3% (n = 24 856) had HFrEF and 20.7% (n = 6 488) HFpEF. The outcome was all-cause mortality. We examined the association between ten non-cardiac comorbidities and mortality and its interaction with EF using adjusted hazard ratio (HR). Stroke, anemia, gout and cancer had a similar impact on mortality in both phenotypes, whereas diabetes (HR 1.57, 95% confidence interval [CI] [1.50-1.65] vs. HR 1.39 95% CI [1.27-1.51], p = 0.0002), renal failure (HR 1.65, 95% CI [1.57-1.73] vs. HR 1.44, 95% CI [1.32-1.57], p = 0.003) and liver disease (HR 2.13, 95% CI [1.83-2.47] vs. HR 1.42, 95% CI [1.09-1.85] p = 0.02) had a higher impact in the HFrEF patients. Moreover, pulmonary disease (HR 1.46, 95% CI [1.40-1.53] vs. HR 1.66 95% CI [1.54-1.80], p = 0.007) was more prominent in the HFpEF patients. Sleep apnea was not associated with worse prognosis in either group. No significant variation was found in the impact over the 12-year study period. Conclusions Non-cardiac comorbidities contribute significantly but differently to mortality, both in HFrEF and HFpEF. No significant variation was found in the impact over the 12-year study period. These results emphasize the importance of including the management of comorbidities as a part of a standardized heart failure care in both HF phenotypes. Funding Agencies|Swedish Heart-Lung Foundation [20170453]; Vastra Gotalands region [ALFGBG-721961]; University of Gothenburg [ALFGBG-721961]