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IntroductionAdverse left ventricular remodelling (AR) develops over time in approximately 30% of patients with a history of coronary artery disease. AR manifests as a structural change in the left ventricle (LV) in terms of increased volumes and reduced left ventricular ejection fraction (LVEF). Manganese dipyridoxyl diphosphate (mangafodipir) has demonstrated interesting cardioprotective features in acute myocardial ischaemia. Pharmacological postconditioning (PP) with mangafodipir as an adjunct to primary percutaneous coronary intervention may possibly reduce the development of AR over time in ST-elevation myocardial infarction (STEMI). The aim of this 4-7-year follow-up study is to investigate the potential benefits of PP with mangafodipir in STEMI patients. MethodThirteen out of the initial 20 patients that were included in the primary study of Karlsson et al. were followed up between April and June 2017. The study group underwent review of the hospital records, a clinical examination with ECG and blood sample analysis before cardiac magnetic resonance examination of the patient. LVEF, left ventricular diastolic volume, left ventricular end systolic volume, LV mass and myocardial strain in all directions were computed. ResultsThe PP group showed a decrease in LV volume, mass and higher LVEF at follow-up (p < 0.05) while the individual response of the placebo group showed features that are seen in AR. Although there was no difference in myocardial strain, measurement for the PP-group was higher in absolute terms. ConclusionPharmacological postconditioning with mangafodipir in STEMI demonstrated cardioprotective features compared to the placebo group at follow-up. This article is protected by copyright. All rights reserved., Funding Agencies|Futurum-Academy for Health and Care, Region Jonkoeping County [414891, 598791, 635951, 851331]

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF).Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m(2) and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus =60 ml/min/1.73 m(2), from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus =6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively.Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient, Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Atrial fibrillation (AF) is the most common arrhythmia seen in clinical practice. In cardiac surgery, the negative influence of AF on short- and long-term outcomes has made concomitant ablation procedures more common. The indications, clinical aspects, results, risks, and benefits of the additional surgical ablation are still valuable topics for discussion. This compilation thesis consists of four papers aiming to investigate some of the clinical, biochemical, and echocardiographic aspects of surgical ablation for AF (Cox-Maze IV) when performed concomitant to mitral valve surgery (MVS). Through a retrospective, case-control, single-center study, we described the impact of the Cox-Maze IV procedure added to MVS with focus on postoperative heart failure (paper I). Cryoenergy (cryo) and radiofrequency (RF) are the two different energy sources mainly used in Cox-Maze IV for AF ablation. To achieve linear scars in the atrial wall, the RF procedure uses heat damage, whereas the cryo method freezes down to -150°C. Through a prospective, randomized, longitudinal, controlled study, we compared the biochemical responses of the two ablative methods in concomitant MVS and the release of enzymes expressing myocardial injury, as well as inflammatory, cell stress, and apoptosis-specific proteins. We could show that cryo results in a larger release of markers for myocardial damage but has no impact on the early inflammatory response (paper II). Extended scar lesions resulting after maze may influence atrial function. As the left atrium plays a key role in the altered cardiac hemodynamics in AF, an echocardiographic analysis of the effects of the Cox-Maze IV procedure concomitant to MVS on the left atrium was carried out. The impacts of the two energy sources (cryo and RF) on left atrial remodeling and function had not been compared previously. Their direct effect on left atrial remodeling and mechanical function were assessed 1 year after surgery in patients with restored sinus rh, Förmaksflimmer (FF) är den vanligaste arytmin som ses i klinisk praxis. Inom hjärtkirurgi har den negativa inverkan på kort- och långtidsutfall för patienter med FF gjort samtidiga ablationsprocedurer vanligare. Indikationerna, de kliniska aspekterna, resultaten, riskerna och fördelarna med den extra kirurgiska ablationen är fortfarande under diskussion. Den aktuella avhandligen består av fyra artiklar som syftar till att undersöka några av de kliniska, biokemiska och ekokardiografiska aspekterna av kirurgisk ablation vid förmaksflimmer (Cox-Maze IV) när det utförs samtidigt med mitralisklaffkirurgi. I en retrospektiv fallkontrollstudie beskrev vi effekten av Cox-Maze IVproceduren som tillägg till mitralisklaffkirurgin med fokus på postoperativ hjärtsvikt (första artikeln). Kryo och Radiofrekvens är de två olika energikällorna som huvudsakligen används vid Cox-Maze IV för FF-ablation. För att uppnå ärrlinjer i förmaksväggen använder Radiofrekvens-proceduren värmeskada, medan Kryo-metoden fryser ner vävnader till minus 150º C grader Celsius. En jämförelse av de biokemiska svaren presenteras mellan de två ablativa metoderna vid samtidig mitralisklaffkirurgi. Frisättningen av biokemiska markörer som uttrycker myokardskada samt inflammatoriska, cellstress- och apoptosspecifika (celldödsspecifika) proteiner rapporteras. Genom en prospektiv randomiserad longitudinell kontrollerad studie kunde vi visa att Kryo hade en större frisättning av hjärtskademarkörer, men ingen inverkan på tidig inflammatorisk respons (andra artikeln). Ärrskador som uppstår efter Cox-Maze IV kan påverka förmaksfunktionen. Eftersom det vänstra förmaket spelar en nyckelroll vid förmaksflimmer förändrade hemodynamiken, genomfördes en ekokardiografisk analys av effekterna av Cox-Maze IV-proceduren samtidigt med mitralisklaffkirurgi på vänster förmak. Effekten av de två energikällorna (Kryo och Radiofrekvens) på vänster förmaks remodeling och funktion har inte jämförts tidigare på ett prospektivt sätt.

Aims The Heart Failure Association of the European Society of Cardiology has recently proposed to optimize guideline-directed medical treatments according to patient s profiles. The aim of this analysis was to investigate prevalence/characteristics/treatments/outcomes for individual profiles Methods and results Patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Swedish Heart Failure Registry (SwedeHF) between 2013 and 2021 were considered. Among 108 profiles generated by combining different strata of renal function (by estimated glomerular filtration rate [eGFR]), systolic blood pressure (sBP), heart rate, atrial fibrillation (AF) status and presence of hyperkalaemia, 93 were identified in our cohort. Event rates for a composite of cardiovascular (CV) mortality or first HF hospitalization were calculated for each profile. The nine most frequent profiles accounting for 70.5% of the population had eGFR 30- 60 or =60 ml/min/1.73m(2), sBP 90-140mmHg and no hyperkalaemia. Heart rate and AF were evenly distributed. The highest risk of CV mortality/first HF hospitalization was observed in those with concomitant eGFR 30- 60ml/min/1.73m(2) and AF. We also identified nine profiles with the highest event rates, representing only 5% of the study population, characterized by no hyperkalaemia, even distribution among the sBP strata, predominance of eGFR < 30 ml/min/1.73m(2) and AF. The three profiles with eGFR 30- 60ml/min/1.73m(2) also showed sBP < 90 mmHg Conclusions In a real-world cohort, most patients fit in a few easily identifiable profiles; the nine profiles at highest risk of mortality/morbidity accounted for only 5% of the population. Our data might contribute to identifying profile-tailored approaches to guide drug implementation and follow-up., Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Background Guideline recommendations for the treatment of heart failure with mildly reduced ejection fraction (HFmrEF) derive from small subgroups in post-hoc analyses of randomized trials. Objectives We investigated predictors of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) and beta-blockers use, and the associations between these medications and mortality/morbidity in a large real-world cohort with HFmrEF. Methods and results Patients with HFmrEF (EF 40-49%) from the Swedish HF Registry were included. The associations between medications and cardiovascular (CV) mortality/HF hospitalization (HFH), and all-cause mortality were assessed through Cox regressions in a 1:1 propensity score-matched cohort. A positive control analysis was performed in patients with EF < 40%, while a negative control outcome analysis had cancer-related hospitalization as endpoint. Of 12 421 patients with HFmrEF, 84% received RASI/ARNI and 88% beta-blockers. Shared-independent predictors of RASI/ARNI and beta-blockers use were younger age, being an outpatient, follow-up in specialty care, and hypertension. In the matched cohorts, use of both RASI/ARNI and beta-blocker use was separately associated with lower risk of CV mortality/HFH [hazard ratio (HR) = 0.90, 95% confidence interval (CI): 0.83-0.98 and HR = 0.82, 95% CI: 0.74-0.90, respectively] and of all-cause mortality (HR = 0.75, 95% CI: 0.69-0.81 and HR = 0.79, 95% CI: 0.72-0.87, respectively). Results were consistent at the positive control analysis, and there were no associations between treatment use and the negative control outcome. Conclusions RASI/ARNI and beta-blockers were extensively used in this large real-world cohort with HFmrEF. Their use was safe since associated with lower mortality and morbidity. Our findings confirm the real-world evidence from previous post-hoc analyses of trials, and represent a further call for implementing guideline recommendations.

Background: Women with Turner syndrome (TS) have an increased risk of aortic dissection. The current recommended cutoff to prevent aortic dissection in TS is an aortic size index (ASI) of >= 2.5 cm/m2. This study estimated which aortic size had the best predictive value for the risk of aortic dissection, and whether adjusting for body size improved risk prediction.Methods: A prospective, observational study in Sweden, of women with TS, n = 400, all evaluated with echocardiography of the aorta and data on medical history for up to 25 years. Receiver operating characteristic (ROC) curves, sensitivity and specificity were calculated for the absolute ascending aortic diameter (AAD), ascending ASI and TS specific z-score.Results: There were 12 patients (3%) with aortic dissection. ROC curves demonstrated that absolute AAD and TS specific z-score were superior to ascending ASI in predicting aortic dissection. The best cutoff for absolute AAD was 3.3 cm and 2.12 for the TS specific z-score, respectively, with a sensitivity of 92% for both. The ascending ASI cutoff of 2.5 cm/m2 had a sensitivity of 17% only. Subgroup analyses in women with an aortic diameter >= 3.3 cm could not demonstrate any association between karyotype, aortic coarctation, bicuspid aortic valve, BMI, antihypertensive medication, previous growth hormone therapy or ongoing estrogen replacement treatment and aortic dissection. All models failed to predict a dissection in a pregnant woman.Conclusions: In Turner syndrome, absolute AAD and TS-specific z-score were more reliable predictors for aortic dissection than ASI. Care should be taken before and during pregnancy.

Aims Hypertrophic cardiomyopathy (HCM) is characterized by hypercontractility and diastolic dysfunction, which alter blood flow haemodynamics and are linked with increased risk of adverse clinical events. Four-dimensional flow cardiac magnetic resonance (4D-flow CMR) enables comprehensive characterization of ventricular blood flow patterns. We characterized flow component changes in non-obstructive HCM and assessed their relationship with phenotypic severity and sudden cardiac death (SCD) risk. Methods and results Fifty-one participants (37 non-obstructive HCM and 14 matched controls) underwent 4D-flow CMR. Left-ventricular (LV) end-diastolic volume was separated into four components: direct flow (blood transiting the ventricle within one cycle), retained inflow (blood entering the ventricle and retained for one cycle), delayed ejection flow (retained ventricular blood ejected during systole), and residual volume (ventricular blood retained for >two cycles). Flow component distribution and component end-diastolic kinetic energy/mL were estimated. HCM patients demonstrated greater direct flow proportions compared with controls (47.9 +/- 9% vs. 39.4 +/- 6%, P = 0.002), with reduction in other components. Direct flow proportions correlated with LV mass index (r = 0.40, P = 0.004), end-diastolic volume index (r = -0.40, P = 0.017), and SCD risk (r = 0.34, P = 0.039). In contrast to controls, in HCM, stroke volume decreased with increasing direct flow proportions, indicating diminished volumetric reserve. There was no difference in component end-diastolic kinetic energy/mL. Conclusion Non-obstructive HCM possesses a distinctive flow component distribution pattern characterised by greater direct flow proportions, and direct flow-stroke volume uncoupling indicative of diminished cardiac reserve. The correlation of direct flow proportion with phenotypic severity and SCD risk highlight its potential as a novel and sensitive haemodynamic measure of cardiovascular risk, Funding Agencies|British Heart Foundation [FS/CRTF/21/24144]; National Institute of Health and Care Research Oxford Biomedical Research Centre; British Heart Foundation, Oxford Centre of Research Excellence [RE/18/3/34214]; Swedish Research Council; Swedish Heart and Lung Foundation; ALF Grant Region Ostergotland; Oxford British Heart Foundation Centre of Research Excellence

BACKGROUND Prognostic assessment of ventricular tachycardia (VT) or ventricular fibrillation (VF) in ST-segment elevation myocardial infarction (STEMI) is based mainly on distinguishing between early (,48 hours) and late arrhythmias, and does not take into account its time distribution with regard to reperfusion, or type of arrhythmia.OBJECTIVE We analyzed the prognostic value of early ventricular arrhythmias (VAs) in STEMI with regard to their type and timing. METHODS The prespecified analysis of the multicenter prospective Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Eleva-tion Myocardial Infarctionin Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Ev-idence-based Care in Heart Disease evaluated according to Recom-mended Therapies Registry Trial included 2886 STEMI patients undergoing primary percutaneous coronary intervention (PCI). VA episodes were characterized regarding their type and timing. Survival status at 180 days was assessed through the population registry.RESULTS Nonmonomorphic VT or VF was observed in 97 (3.4%) and monomorphic VT in 16 (0.5%) patients. Only 3 (2.7%) early VA epi-sodes occurred after 24 hours from symptom onset. VA was associated with higher risk of death (hazard ratio 3.59; 95% confidence interval [CI] 2.01-6.42) after adjustment for age, sex, and STEMI localization. VA after PCI was associated with an increased mortality compared with VA before PCI (hazard ratio 6.68; 95% CI 2.90-15.41). Early VA was associated with in-hospital mortality (odds ratio 7.39; 95% CI 3.68-14.83) but not with long-term prognosis in patients dis-charged alive. The type of VA was not associated with mortality.CONCLUSION VA after PCI was associated with an increased mortal-ity compared with VA before PCI. Long-term prognosis did not differ between patients with monomorphic VT and nonmonomorphic VT or VF, but events were few. VA incidence during 24 to 48 hours of STEMI is negligibly low, thus, Funding Agencies|Swedish Heart Lung Foundation [20180222, 20200674]; Swedish government

Aims Cardiac resynchronization therapy (CRT) is effective in heart failure with reduced ejection fraction (HFrEF) and dyssynchrony but is underutilized. In a cohort study, we identified clinical, organizational, and level of care factors linked to CRT implantation. Methods and results We included HFrEF patients fulfilling study criteria in the ESC-HF-Long Term Registry (ESC-HF-LT, n = 1031), the Swedish Heart Failure Registry (SwedeHF) (n = 5008), and the ESC-CRT Survey II (n = 11 088). In ESC-HF-LT, 36% had a CRT indication of which 47% had CRT, 53% had indication but no CRT, and the remaining 54% had no indication and no CRT. In SwedeHF, these percentages were 30, 25, 75, and 70%. Median age of patients with CRT indication and CRT present vs. absent was 68 vs. 65 years with 24% vs. 22% women in ESC-HF-LT, 76 vs. 74 years with 26% vs. 26% women in SwedeHF, and 70 years with 24% women in CRT Survey II (all had CRT). For ESC-HF-LT, independent predictors of having CRT were guideline-directed medical therapy (GDMT), atrial fibrillation (AF), prior HF hospitalization, and NYHA class. For SwedeHF, they were GDMT, age, AF, previous myocardial infarction, lower NYHA class, enrolment at university hospital, and follow-up at HF centre/Hospital. In SwedeHF, above median income and higher education level were also independently associated with having CRT. In the ESC-CRT Survey II (n = 11 088), all patients received CRT but with differences in the clinical characteristics between countries. Conclusion CRT was used in a minority of eligible patients and more used in ESC-HF-LT than in SwedeHF.

Atrial fibrillation (AF) is the most common arrhythmia seen in clinical practice. In cardiac surgery, the negative influence of AF on short- and long-term outcomes has made concomitant ablation procedures more common. The indications, clinical aspects, results, risks, and benefits of the additional surgical ablation are still valuable topics for discussion. This compilation thesis consists of four papers aiming to investigate some of the clinical, biochemical, and echocardiographic aspects of surgical ablation for AF (Cox-Maze IV) when performed concomitant to mitral valve surgery (MVS). Through a retrospective, case-control, single-center study, we described the impact of the Cox-Maze IV procedure added to MVS with focus on postoperative heart failure (paper I). Cryoenergy (cryo) and radiofrequency (RF) are the two different energy sources mainly used in Cox-Maze IV for AF ablation. To achieve linear scars in the atrial wall, the RF procedure uses heat damage, whereas the cryo method freezes down to -150°C. Through a prospective, randomized, longitudinal, controlled study, we compared the biochemical responses of the two ablative methods in concomitant MVS and the release of enzymes expressing myocardial injury, as well as inflammatory, cell stress, and apoptosis-specific proteins. We could show that cryo results in a larger release of markers for myocardial damage but has no impact on the early inflammatory response (paper II). Extended scar lesions resulting after maze may influence atrial function. As the left atrium plays a key role in the altered cardiac hemodynamics in AF, an echocardiographic analysis of the effects of the Cox-Maze IV procedure concomitant to MVS on the left atrium was carried out. The impacts of the two energy sources (cryo and RF) on left atrial remodeling and function had not been compared previously. Their direct effect on left atrial remodeling and mechanical function were assessed 1 year after surgery in patients with restored sinus rh, Förmaksflimmer (FF) är den vanligaste arytmin som ses i klinisk praxis. Inom hjärtkirurgi har den negativa inverkan på kort- och långtidsutfall för patienter med FF gjort samtidiga ablationsprocedurer vanligare. Indikationerna, de kliniska aspekterna, resultaten, riskerna och fördelarna med den extra kirurgiska ablationen är fortfarande under diskussion. Den aktuella avhandligen består av fyra artiklar som syftar till att undersöka några av de kliniska, biokemiska och ekokardiografiska aspekterna av kirurgisk ablation vid förmaksflimmer (Cox-Maze IV) när det utförs samtidigt med mitralisklaffkirurgi. I en retrospektiv fallkontrollstudie beskrev vi effekten av Cox-Maze IVproceduren som tillägg till mitralisklaffkirurgin med fokus på postoperativ hjärtsvikt (första artikeln). Kryo och Radiofrekvens är de två olika energikällorna som huvudsakligen används vid Cox-Maze IV för FF-ablation. För att uppnå ärrlinjer i förmaksväggen använder Radiofrekvens-proceduren värmeskada, medan Kryo-metoden fryser ner vävnader till minus 150º C grader Celsius. En jämförelse av de biokemiska svaren presenteras mellan de två ablativa metoderna vid samtidig mitralisklaffkirurgi. Frisättningen av biokemiska markörer som uttrycker myokardskada samt inflammatoriska, cellstress- och apoptosspecifika (celldödsspecifika) proteiner rapporteras. Genom en prospektiv randomiserad longitudinell kontrollerad studie kunde vi visa att Kryo hade en större frisättning av hjärtskademarkörer, men ingen inverkan på tidig inflammatorisk respons (andra artikeln). Ärrskador som uppstår efter Cox-Maze IV kan påverka förmaksfunktionen. Eftersom det vänstra förmaket spelar en nyckelroll vid förmaksflimmer förändrade hemodynamiken, genomfördes en ekokardiografisk analys av effekterna av Cox-Maze IV-proceduren samtidigt med mitralisklaffkirurgi på vänster förmak. Effekten av de två energikällorna (Kryo och Radiofrekvens) på vänster förmaks remodeling och funktion har inte jämförts tidigare på ett prospektivt sätt.

Aims Patients with bicuspid aortic valve (BAV) and aortic regurgitation have higher rate of aortic complications compared with patients with BAV and stenosis, as well as BAV without valvular disease. Aortic regurgitation alters blood haemodynamics not only in systole but also during diastole. We therefore sought to investigate wall shear stress (WSS) during the whole cardiac cycle in BAV with aortic regurgitation.Methods and results Fifty-seven subjects that underwent 4D flow cardiovascular magnetic resonance imaging were included: 13 patients with BAVs without valve disease, 14 BAVs with aortic regurgitation, 15 BAVs with aortic stenosis, and 22 normal controls with tricuspid aortic valve. Peak and time averaged WSS in systole and diastole and the oscillatory shear index (OSI) in the ascending aorta were computed. Students t-tests were used to compare values between the four groups where the data were normally distributed, and the non-parametric Wilcoxon rank sum tests were used otherwise. BAVs with regurgitation had similar peak and time averaged WSS compared with the patients with BAV without valve disease and with stenosis, and no regions of elevated WSS were found. BAV with aortic regurgitation had twice as high OSI as the other groups (P <= 0.001), and mainly in the outer mid-to-distal ascending aorta.Conclusion OSI uniquely characterizes altered WSS patterns in BAVs with aortic regurgitation, and thus could be a haemodynamic marker specific for this specific group that is at higher risk of aortic complications. Future longitudinal studies are needed to verify this hypothesis. Graphical Abstract Patients with bicuspid aortic valve and aortic regurgitation present with regions of elevated oscillatory shear index in the ascending aorta, namely in the outer mid-to-distal segments. The 2D map represents segments with higher oscillatory shear index for a group of patients with bicuspid aortic valve and aortic regurgitation compared with patients with bicuspi, Funding Agencies|Swedish Research Council [2021-03716]; Medical Faculty at Linkoeping University; ALF; Region Ostergoetland; University of Calgary [1054341]; Libin Cardiovascular Institute; Siemens Healthineers; Natural Science and Engineering Research Council of Canada [DGECR-2020-00204, RGPIN- 2020-04549]

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF).Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m(2) and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus =60 ml/min/1.73 m(2), from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus =6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively.Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient, Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Background Guideline recommendations for the treatment of heart failure with mildly reduced ejection fraction (HFmrEF) derive from small subgroups in post-hoc analyses of randomized trials. Objectives We investigated predictors of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) and beta-blockers use, and the associations between these medications and mortality/morbidity in a large real-world cohort with HFmrEF. Methods and results Patients with HFmrEF (EF 40-49%) from the Swedish HF Registry were included. The associations between medications and cardiovascular (CV) mortality/HF hospitalization (HFH), and all-cause mortality were assessed through Cox regressions in a 1:1 propensity score-matched cohort. A positive control analysis was performed in patients with EF < 40%, while a negative control outcome analysis had cancer-related hospitalization as endpoint. Of 12 421 patients with HFmrEF, 84% received RASI/ARNI and 88% beta-blockers. Shared-independent predictors of RASI/ARNI and beta-blockers use were younger age, being an outpatient, follow-up in specialty care, and hypertension. In the matched cohorts, use of both RASI/ARNI and beta-blocker use was separately associated with lower risk of CV mortality/HFH [hazard ratio (HR) = 0.90, 95% confidence interval (CI): 0.83-0.98 and HR = 0.82, 95% CI: 0.74-0.90, respectively] and of all-cause mortality (HR = 0.75, 95% CI: 0.69-0.81 and HR = 0.79, 95% CI: 0.72-0.87, respectively). Results were consistent at the positive control analysis, and there were no associations between treatment use and the negative control outcome. Conclusions RASI/ARNI and beta-blockers were extensively used in this large real-world cohort with HFmrEF. Their use was safe since associated with lower mortality and morbidity. Our findings confirm the real-world evidence from previous post-hoc analyses of trials, and represent a further call for implementing guideline recommendations.

Aims Compelling evidence from randomized trials has shown that sodium-glucose cotransporter 2 inhibitors (SGLT2is) are effective in heart failure (HF) across the spectrum of left ventricular ejection fractions. However, there are very few studies with real-world data.Methods and results A retrospective cohort analysis was performed based on patient-level data from the Swedish Heart Failure Registry (SwedeHF) linked with three other national registers. Patients included had an index registration between 3 September 2013 and 31 December 2020 in SwedeHF and were on treatment with guideline-recommended therapy without or with SGLT2i 3 months before or 6 months after their index registration. Endpoints were mortality or readmissions. Association between the use of SGLT2i and endpoints was studied using adjusted Cox models. In the overall cohort, 796/22 405 patients were included with/without SGLT2i. In patients with SGLT2i, 93.5% had diabetes mellitus. In the overall cohort, SGLT2i was statistically significantly associated with all-cause mortality {hazard ratio [HR]: 0.61 [95% confidence interval (CI) 0.48-0.79], P < 0.0001}, cardiovascular mortality [HR: 0.29 (95% CI 0.17-0.50), P < 0.0001], cardiovascular mortality or HF readmission [HR: 0.89 (95% CI 0.80-1.00), P = 0.046], and all-cause readmissions [HR: 0.90 (95% CI 0.81-0.99), P = 0.038]. Similar results were obtained for the diabetes cohort. However, no association with cause-specific readmissions was observed.Conclusions This nationwide real-world study indicates that patients with HF, in which majority coexisted with diabetes mellitus, who received SGLT2i were statistically significantly associated with lower risk for all-cause mortality, cardiovascular mortality, cardiovascular mortality or HF readmissions, and all-cause readmissions, in line with the randomized trials assessing SGLT2i.

Background: The prevalence of aortic valve stenosis (AS) is increasing due to an ageing population. Despite that right ventricular function has prognostic value for postoperative outcome, the right ventricle (RV) is not extensively studied and often not routinely assessed in AS. Our aim was to explore the relation between severe AS and RV function in a surgical aortic valve replacement (SAVR) cohort, comparing two imaging modalities for RV evaluation.Methods: Patients with severe AS, underwent cardiovascular magnetic resonance imaging (CMR) and transthoracic echocardiography (TTE) before SAVR. RV dysfunction was defined as one or more of the following: tricuspid annular plane systolic excursion (TAPSE) < 17 mm, RV free wall strain (RVFWS) > -20% by TTE and RV ejection fraction (RVEF) <50% by CMR.Results: Sixteen (33%) patients were found to have RV dysfunction. Patients with RV dysfunction showed significantly lower indexed aortic valve area, left ventricular (LV) ejection fraction as well as RV and LV stroke volumes compared to patients with maintained RV function. All patients with reduced RVEF also had changes in TAPSE or RVFWS and a larger number of patients had a reduced longitudinal RV function despite a normal RVEF.Conclusion: In a SAVR cohort one-third of the patients had RV dysfunction, defined by RVEF, TAPSE or RVFW strain. Echocardiography detected subtle changes in RV function before RVEF was reduced. It is likely that the more pronounced the AS, the more frequent the occurrence of RV dysfunction., Funding Agencies|ALF grant; Region Ostergotland and Linkoping University [RO-935260]; From student to docent, Region Ostergotland [RO-965090]

Aims The Heart Failure Association of the European Society of Cardiology has recently proposed to optimize guideline-directed medical treatments according to patient s profiles. The aim of this analysis was to investigate prevalence/characteristics/treatments/outcomes for individual profiles Methods and results Patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Swedish Heart Failure Registry (SwedeHF) between 2013 and 2021 were considered. Among 108 profiles generated by combining different strata of renal function (by estimated glomerular filtration rate [eGFR]), systolic blood pressure (sBP), heart rate, atrial fibrillation (AF) status and presence of hyperkalaemia, 93 were identified in our cohort. Event rates for a composite of cardiovascular (CV) mortality or first HF hospitalization were calculated for each profile. The nine most frequent profiles accounting for 70.5% of the population had eGFR 30- 60 or =60 ml/min/1.73m(2), sBP 90-140mmHg and no hyperkalaemia. Heart rate and AF were evenly distributed. The highest risk of CV mortality/first HF hospitalization was observed in those with concomitant eGFR 30- 60ml/min/1.73m(2) and AF. We also identified nine profiles with the highest event rates, representing only 5% of the study population, characterized by no hyperkalaemia, even distribution among the sBP strata, predominance of eGFR < 30 ml/min/1.73m(2) and AF. The three profiles with eGFR 30- 60ml/min/1.73m(2) also showed sBP < 90 mmHg Conclusions In a real-world cohort, most patients fit in a few easily identifiable profiles; the nine profiles at highest risk of mortality/morbidity accounted for only 5% of the population. Our data might contribute to identifying profile-tailored approaches to guide drug implementation and follow-up., Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Despite abundant knowledge about the relationship between inflammation and coronary atherosclerosis, it is still unknown whether systemic inflammation measured as high-sensitivity C-reactive protein (hsCRP) is associated with coronary atherosclerosis in a general population. This study aimed to examine the association between hsCRP and coronary computed tomography angiography (CCTA)-detected coronary atherosclerosis in a population-based cohort. Out of 30,154 randomly invited men and women aged 50 to 64 years in the Swedish Cardiopulmonary Bioimage Study (SCAPIS), 25,408 had a technically acceptable CCTA and analysed hsCRP. Coronary atherosclerosis was defined as presence of plaque of any degree in any of 18 coronary segments. HsCRP values were categorised in four groups. Compared with hsCRP below the detection limit, elevated hsCRP (& GE; 2.3 mg/L) was weakly associated with any coronary atherosclerosis (OR 1.15, 95% CI 1.07-1.24), coronary diameter stenosis & GE; 50% (OR 1.27, 95% CI 1.09-1.47), & GE; 4 segments involved (OR 1.13, 95% CI 1.01-1.26 ) and severe atherosclerosis (OR 1.33, 95% CI 1.05-1.69) after adjustment for age, sex and traditional risk factors. The associations were attenuated after further adjustment for body mass index (BMI), although elevated hsCRP still associated with noncalcified plaques (OR 1.16, 95% CI 1.02-1.32), proposed to be more vulnerable. In conclusion, the additional value of hsCRP to traditional risk factors in detection of coronary atherosclerosis is low. The association to high-risk noncalcified plaques, although unlikely through a causal pathway, could explain the relationship between hsCRP and clinical coronary events in numerous studies., Funding Agencies|Karolinska Institute

IntroductionAdverse left ventricular remodelling (AR) develops over time in approximately 30% of patients with a history of coronary artery disease. AR manifests as a structural change in the left ventricle (LV) in terms of increased volumes and reduced left ventricular ejection fraction (LVEF). Manganese dipyridoxyl diphosphate (mangafodipir) has demonstrated interesting cardioprotective features in acute myocardial ischaemia. Pharmacological postconditioning (PP) with mangafodipir as an adjunct to primary percutaneous coronary intervention may possibly reduce the development of AR over time in ST-elevation myocardial infarction (STEMI). The aim of this 4-7-year follow-up study is to investigate the potential benefits of PP with mangafodipir in STEMI patients. MethodThirteen out of the initial 20 patients that were included in the primary study of Karlsson et al. were followed up between April and June 2017. The study group underwent review of the hospital records, a clinical examination with ECG and blood sample analysis before cardiac magnetic resonance examination of the patient. LVEF, left ventricular diastolic volume, left ventricular end systolic volume, LV mass and myocardial strain in all directions were computed. ResultsThe PP group showed a decrease in LV volume, mass and higher LVEF at follow-up (p < 0.05) while the individual response of the placebo group showed features that are seen in AR. Although there was no difference in myocardial strain, measurement for the PP-group was higher in absolute terms. ConclusionPharmacological postconditioning with mangafodipir in STEMI demonstrated cardioprotective features compared to the placebo group at follow-up. This article is protected by copyright. All rights reserved., Funding Agencies|Futurum-Academy for Health and Care, Region Jonkoeping County [414891, 598791, 635951, 851331]

Aims Hospital admission during nighttime and off hours may affect the outcome of patients with various cardiovascular conditions due to suboptimal resources and personnel availability, but data for acute heart failure remain controversial. Therefore, we studied outcomes of acute heart failure patients according to their time of admission from the global International Registry to assess medical practice with lOngitudinal obseRvation for Treatment of Heart Failure.Methods and results Overall, 18 553 acute heart failure patients were divided according to time of admission into morning (7:00-14:59), evening (15:00-22:59), and night (23:00-06:59) shift groups. Patients were also dichotomized to admission during working hours (9:00-16:59 during standard working days) and non-working hours (any other time). Clinical characteristics, treatments, and outcomes were compared across groups. The hospital length of stay was longer for morning (odds ratio: 1.08; 95% confidence interval: 1.06-1.10, P < 0.001) and evening shift (odds ratio: 1.10; 95% confidence interval: 1.07-1.12, P < 0.001) as compared with night shift. The length of stay was also longer for working vs. non-working hours (odds ratio: 1.03; 95% confidence interval: 1.02-1.05, P < 0.001). There were no significant differences in in-hospital mortality among the groups. Admission during working hours, compared with non-working hours, was associated with significantly lower mortality at 1 year (hazard ratio: 0.88; 95% confidence interval: 0.80-0.96, P = 0.003).Conclusions Acute heart failure patients admitted during the night shift and non-working hours had shorter length of stay but similar in-hospital mortality. However, patients admitted during non-working hours were at a higher risk for 1 year mortality. These findings may have implications for the health policies and heart failure trials., Funding Agencies|Novartis

Atrial fibrillation (AF) is the most common arrhythmia seen in clinical practice. In cardiac surgery, the negative influence of AF on short- and long-term outcomes has made concomitant ablation procedures more common. The indications, clinical aspects, results, risks, and benefits of the additional surgical ablation are still valuable topics for discussion. This compilation thesis consists of four papers aiming to investigate some of the clinical, biochemical, and echocardiographic aspects of surgical ablation for AF (Cox-Maze IV) when performed concomitant to mitral valve surgery (MVS). Through a retrospective, case-control, single-center study, we described the impact of the Cox-Maze IV procedure added to MVS with focus on postoperative heart failure (paper I). Cryoenergy (cryo) and radiofrequency (RF) are the two different energy sources mainly used in Cox-Maze IV for AF ablation. To achieve linear scars in the atrial wall, the RF procedure uses heat damage, whereas the cryo method freezes down to -150°C. Through a prospective, randomized, longitudinal, controlled study, we compared the biochemical responses of the two ablative methods in concomitant MVS and the release of enzymes expressing myocardial injury, as well as inflammatory, cell stress, and apoptosis-specific proteins. We could show that cryo results in a larger release of markers for myocardial damage but has no impact on the early inflammatory response (paper II). Extended scar lesions resulting after maze may influence atrial function. As the left atrium plays a key role in the altered cardiac hemodynamics in AF, an echocardiographic analysis of the effects of the Cox-Maze IV procedure concomitant to MVS on the left atrium was carried out. The impacts of the two energy sources (cryo and RF) on left atrial remodeling and function had not been compared previously. Their direct effect on left atrial remodeling and mechanical function were assessed 1 year after surgery in patients with restored sinus rh, Förmaksflimmer (FF) är den vanligaste arytmin som ses i klinisk praxis. Inom hjärtkirurgi har den negativa inverkan på kort- och långtidsutfall för patienter med FF gjort samtidiga ablationsprocedurer vanligare. Indikationerna, de kliniska aspekterna, resultaten, riskerna och fördelarna med den extra kirurgiska ablationen är fortfarande under diskussion. Den aktuella avhandligen består av fyra artiklar som syftar till att undersöka några av de kliniska, biokemiska och ekokardiografiska aspekterna av kirurgisk ablation vid förmaksflimmer (Cox-Maze IV) när det utförs samtidigt med mitralisklaffkirurgi. I en retrospektiv fallkontrollstudie beskrev vi effekten av Cox-Maze IVproceduren som tillägg till mitralisklaffkirurgin med fokus på postoperativ hjärtsvikt (första artikeln). Kryo och Radiofrekvens är de två olika energikällorna som huvudsakligen används vid Cox-Maze IV för FF-ablation. För att uppnå ärrlinjer i förmaksväggen använder Radiofrekvens-proceduren värmeskada, medan Kryo-metoden fryser ner vävnader till minus 150º C grader Celsius. En jämförelse av de biokemiska svaren presenteras mellan de två ablativa metoderna vid samtidig mitralisklaffkirurgi. Frisättningen av biokemiska markörer som uttrycker myokardskada samt inflammatoriska, cellstress- och apoptosspecifika (celldödsspecifika) proteiner rapporteras. Genom en prospektiv randomiserad longitudinell kontrollerad studie kunde vi visa att Kryo hade en större frisättning av hjärtskademarkörer, men ingen inverkan på tidig inflammatorisk respons (andra artikeln). Ärrskador som uppstår efter Cox-Maze IV kan påverka förmaksfunktionen. Eftersom det vänstra förmaket spelar en nyckelroll vid förmaksflimmer förändrade hemodynamiken, genomfördes en ekokardiografisk analys av effekterna av Cox-Maze IV-proceduren samtidigt med mitralisklaffkirurgi på vänster förmak. Effekten av de två energikällorna (Kryo och Radiofrekvens) på vänster förmaks remodeling och funktion har inte jämförts tidigare på ett prospektivt sätt.

BackgroundAtrial linear scars in Cox-Maze IV procedures are achieved using Cryothermy (Cryo) or radiofrequency (RF) techniques. The subsequent postoperative left atrial (LA) reverse remodelling is unclear. We used 2- and 3-dimensional echocardiography (2-3DE) to compare the impact of Cryo and RF procedures on LA size and function 1 year after Cox-maze IV ablation concomitant with Mitral valve (MV) surgery. MethodsSeventy-two patients with MV disease and AF were randomized to Cryo (n = 35) or RF (n = 37) ablation. Another 33 patients were enroled without ablation (NoMaze). All patients underwent an echocardiogram the day before and 1 year after surgery. The LA function was assessed on 2D strain by speckle tracking and 3DE. ResultsForty-two ablated patients recovered sinus rhythm (SR) 1 year after surgery. They had comparable left and right systolic ventricular function, LA volume index (LAVI), and 2D reservoir strain before surgery. At follow-up, the 3DE extracted reservoir and booster function were higher after RF (37 & PLUSMN; 10% vs. 26 & PLUSMN; 6%; p < 0.001) than Cryo ablation (18 & PLUSMN; 9 vs. 7 & PLUSMN; 4%; p < 0.001), while passive conduit function was comparable between groups (24 & PLUSMN; 11 vs. 20 & PLUSMN; 8%; p = 0.17). The extent of LAVI reduction depended on the duration of AF preoperatively. ConclusionsSR restoration after MV surgery and maze results in LA size reduction irrespective of the energy source used. Compared to RF, the extension of ablation area produced by Cryo implies a structural LA remodelling affecting LA systolic function., Funding Agencies|ALF Grant Region Ostergotland

Assessment of left atrial (LA) fibrosis from late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) adds to the management of patients with atrial fibrillation (AF). However, accurate assessment of fibrosis in the LA wall remains challenging. Excluding anatomical structures in the LA proximity using clipping techniques can reduce misclassification of LA fibrosis. A novel FK-means approach for combined automatic clipping and automatic fibrosis segmentation was developed. This approach combines a feature-based Voronoi diagram with a hierarchical 3D K-means fractal-based method. The proposed automatic Voronoi clipping method was applied on LGE MRI data and achieved a Dice score of 0.75, similar as the score obtained by a deep learning method (3D UNet) for clipping (0.74). The automatic fibrosis segmentation method, which utilizes the Voronoi clipping method, achieved a Dice score of 0.76. This outperformed a 3D U-Net method for clipping and fibrosis classification, which had a Dice score of 0.69. Moreover, the proposed automatic fibrosis segmentation method achieved a Dice score of 0.90, using manual clipping of anatomical structures. The findings suggest that the automatic FK-means analysis approach enables reliable LA fibrosis segmentation and that clipping of anatomical structures in the atrial proximity can add to the assessment of atrial fibrosis., For access to data and code please contact datamanagement@liu.se for further information.

Aims Heart failure (HF) medication may reduce blood pressure (BP). Low BP is associated with worse outcomes but how this association is modified by HF medication has not been studied. We evaluated the association between BP and outcomes according to HF medication dose in HF with reduced ejection fraction (HFrEF). Methods and results We studied HFrEF patients from the Swedish HF registry (2000-2018). Associations between systolic BP (SBP) and cardiovascular death (CVD) and/or HF hospitalization (HFH) were analysed according to doses of renin-angiotensin system (RAS) inhibitors, beta-blockers and mineralocorticoid receptor antagonists (MRA). Among 42 040 patients (median age 74.0), lower baseline SBP was associated with higher risk of CVD/HFH (adjusted hazard ratio [HR] per 10 mmHg higher SBP: 0.92, 95% confidence interval [CI] 0.92-0.93), which was less high risk under optimized RAS inhibitor and beta-blocker doses (10% decrease in event rates per 10 mmHg SBP increase in untreated patients vs. 7% decrease in patients at maximum dose, both adjusted p < 0.02). Among the 13 761 patients with repeated measurements, 9.9% reported a SBP decrease >10 mmHg when HF medication doses were increased, whereas 24.6% reported a SBP decrease >10 mmHg with stable/decreasing doses. Decreasing SBP was associated with higher risk of CVD/HFH in patients with stable (HR 1.10, 95% CI 1.04-1.17) or decreasing (HR 1.29, 95% CI 1.18-1.42) HF medication dose but not in patients with an increase in doses (HR 0.94, 95% CI 0.86-1.02). Conclusions The association of lower SBP with higher risk of CVD/HFH is attenuated in patients with optimized HF medication. These results suggest that low or declining SBP should not limit HF medication optimization., Funding Agencies|French National Research Agency Fighting Heart Failure [ANR-15-RHU-0004]; French PIA project Lorraine Universite dExcellence GEENAGE [ANR-15-IDEX-04-LUE]; Contrat de Plan Etat Region Lorraine; FEDER

Aims How different degrees of adherence to guideline-directed medical therapy (GDMT) affect mortality risk in patients with heart failure (HF) in a real-world clinical setting is poorly understood. This study sought to investigate how different levels of adherence to GDMT were associated with the risk of all-cause mortality in patients with HF across a spectrum of left ventricular ejection fractions (LVEFs) in a real-world clinical setting.Methods and results A total of 64 610 HF patients with no missing value of LVEF from the Swedish Heart Failure Registry were included in the study. Patients were divided according to different LVEFs (<30%, 30-39%, 40-49%, and >= 50%) and stratified by an adherence score (good, moderate, or poor) according to the triple, double, and single one usage of GDMT: angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists. The outcome is time to all-cause mortality. The mean age of the whole cohort was 73.9 +/- 12.1 years, and the proportion of patients in LVEF < 30%, 30-39%, 40-49%, and >= 50% groups was 27.6%, 26.9%, 22.1%, and 23.3%, respectively. Patients with LVEF < 30% had the highest mortality rate, almost 20% higher than those with LVEF >= 50% {hazard ratio [HR] [95% confidence interval (CI)]: 0.80 [0.71-0.90], P < 0.001}. After treatment of GDMT with good adherence, patients with LVEF < 30% had similar mortality to those with LVEF >= 50% [HR (95% CI): 0.97 (0.86-1.10), P = 0.664]. However, the percentage of moderate or poor GDMT was alarmingly high, with good adherence only in 20% of the patients.Conclusions Good adherence to GDMT works best in patients with LVEF < 50%, whereas moderate adherence to GDMT varies in efficacy depending on the components of the drug combinations., Funding Agencies|Swedish Heart Lung Foundation (Hjart-Lungfonden) [20210247]; Swedish Federal Government through the Swedish Association of Local Authorities and Regions

Aims Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD.Methods and results We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR <30, 30-44, 45-59 or >= 60 ml/min/1.73 m(2), respectively. An eGFR >= 60 ml/min/1.73 m(2) and patient characteristics linked with more severe HF were independently associated with more likely MRA use. In multivariable analyses, MRA use was consistently not associated with a higher risk of renal events (i.e. composite of dialysis/renal death/hospitalization for renal failure or hyperkalaemia) (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.98-1.10), all-cause death (HR 1.02, 95% CI 0.97-1.08) as well as of all-cause hospitalization (HR 0.99, 95% CI 0.95-1.02) across the eGFR spectrum including also severe CKD.Conclusions The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum., Funding Agencies|We thank all staff members at all care units in Sweden for their contribution to the SwedeHF.

Purpose: To evaluate the diagnostic performance of three different cardiac stress protocols for myo-cardial perfusion imaging (MPI) using a cadmium-zinc-telluride (CZT) camera with invasive coronary angiography (ICA) correlation for the diagnosis of coronary artery disease in a high risk population. Methods: Retrospective study of 263 patients (96 women and 167 males, mean age 68 years) from which 119 patients performed a bicycle stress test (BST), 113 pharmacological stress test (PST) and 31 a com-bination of the two (CST) between September 2014 and December 2018. The patients then underwent myocardial perfusion imaging (MPI), followed by ICA and evaluated by means of quantitative angio-graphy software, within six months after the MPI. The mean pre-test probability score for coronary disease according to the European Society of Cardiology criteria was 36% for the whole population. The MPI was performed in a dedicated CZT cardio camera (D-SPECT Spectrum Dynamics) with a two-day protocol, according to the European Association of Nuclear Medicine guidelines.Results: No significant difference was observed between the three stress protocols in terms of diagnostic accuracy (BST 85%, PST 88% and CST 84%). The overall diagnostic accuracy of MPI to identify patients with any obstructive CAD at ICA was 86%, Sensitivity 93%, Specificity 54%, PPV 90% and NPV 63%.Conclusion: The CZT D-SPECT camera achieves overall satisfactory results in the diagnosis of CAD, obser-ving no significant differences in the diagnostic performance when the stress test was performed as a BST, PST or CST.& COPY; 2023 Sociedad Espanola de Medicina Nuclear e Imagen Molecular. Published by Elsevier Espana, S.L.U. All rights reserved., ObjetivoEvaluar el rendimiento diagnóstico de tres protocolos diferentes de estrés cardiaco utilizados en imagen de perfusión miocárdica (IPM), usando una cámara de cadmio-zinc-telurio (CZT) en correlación con angiografía coronaria (AC) para el diagnóstico de enfermedad arterial coronaria (EAC) en una población de alto riesgo.MétodosEstudio retrospectivo realizado en 263 pacientes (96 mujeres y 167 varones, edad media 68 años), de los cuales 119 realizaron una prueba de estrés con bicicleta (PEB), 113 una prueba de estrés farmacológica (PEF) y 31 una combinación de ambas (PEC), entre septiembre de 2014 y diciembre de 2018. Posteriormente realizaron una IPM, seguida de AC dentro de los seis meses posteriores a la IPM. La probabilidad preprueba media para EAC según los criterios de la Sociedad Europea de Cardiología fue de 36%. La IPM se realizó en una cámara CZT cardio dedicada (D-SPECT Spectrum Dynamics) con un protocolo de dos días, de acuerdo con las guías de la Asociación Europea de Medicina Nuclear (EANM).ResultadosNo se observaron diferencias significativas entre los diferentes protocolos de estrés en términos de precisión diagnóstica (PEB 85%, PEF 88%, PEC 84%). La exactitud diagnóstica general de IPM para identificar pacientes con cualquier EAC obstructiva en AC fue de 86%, sensibilidad de 93%, especificidad de 54%, VPP de 90% y VPN de 63%.ConclusiónLa cámara CZT D-SPECT logra resultados generales satisfactorios en el diagnóstico de la EAC, sin encontrar diferencias significativas en el rendimiento diagnóstico cuando la prueba de esfuerzo se realizó como PEB, PEF o PEC.

Background: Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased atherosclerotic burden in the coronary and carotid arteries. This study will estimate the cross-sectional prevalence of atherosclerosis in the coronary and carotid arteries in individuals with prediabetes and diabetes, compared with normoglycaemic individuals in a large population-based cohort.Methods: The 30,154 study participants, 50-64 years, were categorized according to their fasting glycaemic status or self-reported data as normoglycaemic, prediabetes, and previously undetected or known diabetes. Prevalence of affected coronary artery segments, severity of stenosis and coronary artery calcium score (CACS) were determined by coronary computed tomography angiography. Total atherosclerotic burden was assessed in the 11 clinically most relevant segments using the Segment Involvement Score and as the presence of any coronary atherosclerosis. The presence of atherosclerotic plaque in the carotid arteries was determined by ultrasound examination.Results: Study participants with prediabetes (n = 4804, 16.0%) or diabetes (n = 2282, 7.6%) had greater coronary artery plaque burden, more coronary stenosis and higher CACS than normoglycaemic participants (all, p < 0.01). Among male participants with diabetes 35.3% had CACS >= 100 compared to 16.1% among normoglycaemic participants. For women, the corresponding figures were 8.9% vs 6.1%. The prevalence of atherosclerosis in the coronary arteries was higher in participants with previously undetected diabetes than prediabetes, but lower than in patients with known diabetes. The prevalence of any plaque in the carotid arteries was higher in participants with prediabetes or diabetes than in normoglycaemic participants.Conclusions: In this large population-based cohort of currently asymptomatic people, the atherosclerotic burden in the coronary, Funding Agencies|Not applicable.

BACKGROUND Previous reports suggest that risk factors, management, and outcomes of acute heart failure (AHF) may differ by sex, but they rarely extended analysis to low-and middle-income countries.OBJECTIVES In this study, the authors sought to analyze sex differences in treatment and outcomes in patients hospitalized for AHF in 44 countries.METHODS The authors investigated differences between men and women in treatment and outcomes in 18,553 patients hospitalized for AHF in 44 countries in the REPORT-HF (Registry to Assess Medical Practice With Longitudinal Observation for the Treatment of Heart Failure) registry stratified by country income level, income disparity, and world region. The primary outcome was 1-year all-cause mortality.RESULTS Women (n = 7,181) were older than men (n = 11,372), were more likely to have heart failure with preserved left ventricular ejection fraction, had more comorbid conditions except for coronary artery disease, and had more severe signs and symptoms at admission. Coronary angiography, cardiac stress tests, and coronary revascularization were less frequently performed in women than in men. Women with AHF and reduced left ventricular ejection fraction were less likely to receive an implanted device, regardless of region or country income level. Women were more likely to receive treatments that could worsen HF than men (18% vs 13%; P < 0.0001). In countries with low-income disparity, women had better 1-year survival than men. This advantage was lost in countries with greater income disparity (P-interaction < 0.001).CONCLUSIONS Women were less likely to have diagnostic testing or receive guideline-directed care than men. A survival advantage for women was observed only in countries with low income disparity, suggesting that equity of HF care between sexes remains an unmet goal worldwide. (J Am Coll Cardiol HF 2023;11:1262-1271) (c) 2023 by the American College of Cardiology Foundation.

Background: Ventilator-associated lower respiratory tract infections (VA-LRTI) increase morbidity and mortality in intensive care unit (ICU) patients. Higher incidences of VA-LRTI have been reported among COVID-19 patients requiring invasive mechanical ventilation (IMV). The primary objectives of this study were to describe clinical characteristics, incidence, and risk factors comparing patients who developed VA-LRTI to patients who did not, in a cohort of Swedish ICU patients with acute hypoxemic respiratory failure due to COVID-19. Secondary objectives were to decipher changes over the three initial pandemic waves, common microbiology and the effect of VA-LTRI on morbidity and mortality.Methods: We conducted a multicenter, retrospective cohort study of all patients admitted to 10 ICUs in southeast Sweden between March 1, 2020 and May 31, 2021 because of acute hypoxemic respiratory failure due to COVID-19 and were mechanically ventilated for at least 48 h. The primary outcome was culture verified VA-LRTI. Patient characteristics, ICU management, clinical course, treatments, microbiological findings, and mortality were registered. Logistic regression analysis was conducted to determine risk factors for first VA-LRTI.Results: Of a total of 536 included patients, 153 (28.5%) developed VA-LRTI. Incidence rate of first VA-LRTI was 20.8 per 1000 days of IMV. Comparing patients with VA-LRTI to those without, no differences in mortality, age, sex, or number of comorbidities were found. Patients with VA-LRTI had fewer ventilator-free days, longer ICU stay, were more frequently ventilated in prone position, received corticosteroids more often and were more frequently on antibiotics at intubation. Regression analysis revealed increased adjusted odds-ratio (aOR) for first VA-LRTI in patients treated with corticosteroids (aOR 2.64 [95% confidence interval [CI]] [1.31-5.74]), antibiotics at intubation (aOR 2.01 95% CI [1.14-3.66]), and days of IMV (aOR 1.05 per day of IMV, 95% C, Funding Agencies|Thanks to Michelle S Chew for contributing to the construction of our database as well as manuscript revisions. Thanks to Anzal Abdirashid, Henrik Brofeldt, and Robert Staroscinski, for contributing greatly to data collection. The authors declare no confli

Objective Catheter ablation of atrial fibrillation effectively reduces symptomatic burden. However, its long-term effect on mortality and stroke is unclear. We investigated if patients with atrial fibrillation who undergo catheter ablation have lower risk for all-cause mortality or stroke than patients who are managed medically. Methods We retrospectively included 5628 consecutive patients who underwent first-time catheter ablation for atrial fibrillation between 2008 and 2018 at three major Swedish electrophysiology units. Control individuals with an atrial fibrillation diagnosis but without previous stroke were selected from the Swedish National Patient Register, resulting in a control group of 48 676 patients. Propensity score matching was performed to produce two cohorts of equal size (n=3955) with similar baseline characteristics. The primary endpoint was a composite of all-cause mortality or stroke. Results Patients who underwent catheter ablation were healthier (mean CHA(2)DS(2)-VASc score 1.4 +/- 1.4 vs 1.6 +/- 1.5, p<0.001), had a higher median income (288 vs 212 1000 Swedish krona [KSEK]/year, p<0.001) and had more frequently received university education (45.1% vs 28.9%, p<0.001). Mean follow-up was 4.5 +/- 2.8 years. After propensity score matching, catheter ablation was associated with lower risk for the combined primary endpoint (HR 0.58, 95% CI 0.48 to 0.69). The result was mainly driven by a decrease in all-cause mortality (HR 0.51, 95% CI 0.41 to 0.63), with stroke reduction showing a trend in favour of catheter ablation (HR 0.75, 95% CI 0.53 to 1.07). Conclusions Catheter ablation of atrial fibrillation was associated with a reduction in the primary endpoint of all-cause mortality or stroke. This result was driven by a marked reduction in all-cause mortality., Funding Agencies|Swedish Research Council; Swedish Heart- Lung Foundation [20190301, 20200537, 202110302]; Center for Innovative Medicine [FoUI- 954510, FoUI- 954075]

Background: Plaque analysis with coronary computed tomography angiography (CCTA) is a promising tool to identify high risk of future coronary events. The analysis process is time-consuming, and requires highly trained readers. Deep learning models have proved to excel at similar tasks, however, training these models requires large sets of expert-annotated training data. The aims of this study were to generate a large, high-quality annotated CCTA dataset derived from Swedish CArdioPulmonary BioImage Study (SCAPIS), report the reproducibility of the annotation core lab and describe the plaque characteristics and their association with established risk factors.Methods and results: The coronary artery tree was manually segmented using semi-automatic software by four primary and one senior secondary reader. A randomly selected sample of 469 subjects, all with coronary plaques and stratified for cardiovascular risk using the Systematic Coronary Risk Evaluation (SCORE), were analyzed. The reproducibility study (n = 78) showed an agreement for plaque detection of 0.91 (0.84-0.97). The mean percentage difference for plaque volumes was-0.6% the mean absolute percentage difference 19.4% (CV 13.7%, ICC 0.94). There was a positive correlation between SCORE and total plaque volume (rho = 0.30, p < 0.001) and total low attenuation plaque volume (rho = 0.29, p < 0.001).Conclusions: We have generated a CCTA dataset with high-quality plaque annotations showing good reproducibility and an expected correlation between plaque features and cardiovascular risk. The stratified data sampling has enriched high-risk plaques making the data well suited as training, validation and test data for a fully automatic analysis tool based on deep learning., Funding Agencies|VINNOVA to the "SCAPIS AI platform"; Swedish Heart and Lung Foundation; Knut and Alice Wallenberg Foundation; Swedish Research Council and VINNOVA; Heart and Lung foundation [20180324]; Swedish Research Council [2019-01140]; LUA/ALF [ALFGBG-718851]

Introduction: Atrial fibrillation (AF) is associated with an increased risk of stroke, often caused by thrombi that form in the left atrium (LA), and especially in the left atrial appendage (LAA). The underlying mechanism is not fully understood but is thought to be related to stagnant blood flow, which might be present despite sinus rhythm. However, measuring blood flow and stasis in the LAA is challenging due to its small size and low velocities. We aimed to compare the blood flow and stasis in the left atrium of paroxysmal AF patients with controls using computational fluid dynamics (CFD) simulations.Methods : The CFD simulations were based on time-resolved computed tomography including the patient-specific cardiac motion. The pipeline allowed for analysis of 21 patients with paroxysmal AF and 8 controls. Stasis was estimated by computing the blood residence time.Results and Discussion: Residence time was elevated in the AF group (p < 0.001). Linear regression analysis revealed that stasis was strongest associated with LA ejection ratio (p < 0.001, R-2 = 0.68) and the ratio of LA volume and left ventricular stroke volume (p < 0.001, R-2 = 0.81). Stroke risk due to LA thrombi could already be elevated in AF patients during sinus rhythm. In the future, patient specific CFD simulations may add to the assessment of this risk and support diagnosis and treatment., Funding Agencies|This project was funded by the Swedish Medical Research Council (2018-02779); the Swedish research council (2018-04454), ALF Grants, Region Ouml;stergouml;tland (974839 and 969563); Swedish Heart and Lung Foundation (20200220 and 20210441), VINNOVA (2019 [2018-04454]; Swedish Medical Research Council [974839]; Swedish research council [969563, 20200220]; ALF Grants [20210441, 2019-02261]; Swedish Heart and Lung Foundation [2021/3-35]; VINNOVA; Henry och Ella Sthls foundation; Swedish National Infrastructure for Computing (SNIC) - Swedish Research Council; [2018-02779]

Introduction: In this article, we explore to what extent it is possible to leverage on very small data to build machine learning (ML) models that predict acute exacerbations of chronic obstructive pulmonary disease (AECOPD).Methods: We build ML models using the small data collected during the eHealth Diary telemonitoring study between 2013 and 2017 in Sweden. This data refers to a group of multimorbid patients, namely 18 patients with chronic obstructive pulmonary disease (COPD) as the major reason behind previous hospitalisations. The telemonitoring was supervised by a specialised hospital-based home care (HBHC) unit, which also was responsible for the medical actions needed.Results: We implement two different ML approaches, one based on time-dependent covariates and the other one based on time-independent covariates. We compare the first approach with standard COX Proportional Hazards (CPH). For the second one, we use different proportions of synthetic data to build models and then evaluate the best model against authentic data.Discussion: To the best of our knowledge, the present ML study shows for the first time that the most important variable for an increased risk of future AECOPDs is "maintenance medication changes by HBHC". This finding is clinically relevant since a sub-optimal maintenance treatment, requiring medication changes, puts the patient in risk for future AECOPDs.Conclusion: The experiments return useful insights about the use of small data for ML., Funding Agencies|Medical Research Council of Southeast Sweden (FORSS) [FORSS-969385, FORSS-980999]; Swedens innovation agency Vinnova [2019-05402]

Aims Ticagrelor is associated with a lower risk of ischemic events than clopidogrel. However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in patients who have a high bleeding risk (HBR). Therefore, this study compared ticagrelor and clopidogrel in myocardial infarction (MI) patients with HBR. Methods and results This study included all patients enrolled in the SWEDEHEART registry who were discharged with dual antiplatelet therapy using ticagrelor or clopidogrel following MI between 2010 and 2017. High bleeding risk was defined as a PRECISE-DAPT score & GE;25. Information on ischemic events, major bleeding, and mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and bleeding. This study included 25 042 HBR patients, of whom 11 848 were treated with ticagrelor. Ticagrelor was associated with a lower risk of MI, stroke, and MACE, but a higher risk of bleeding compared to clopidogrel. There were no significant differences in mortality and NACE. Additionally, when examining the relationship between antiplatelet therapy and bleeding risk in 69 040 MI patients, we found no statistically significant interactions between the PRECISE-DAPT score and treatment effect. Conclusions We observed no difference in NACE when comparing ticagrelor and clopidogrel in HBR patients. Moreover, we found no statistically significant interactions between bleeding risk and the comparative effectiveness of clopidogrel and ticagrelor in a larger population of MI patients., Funding Agencies|Stockholm County council

Left ventricular diameter (LVEDD) increases with systematic endurance training but also in various cardiac diseases. High exercise capacity associates with favorable outcomes. We hypothesized that peak work rate (W-peak) indexed to LVEDD would carry prognostic information and aimed to evaluate the association between W-peak/LVEDDrest and cardiovascular mortality. W-peak/LVEDDrest (W/mm) was calculated in patients with an echocardiographic examination within 3 months of a maximal cycle ergometer exercise test. Low W-peak/LVEDDrest was defined as a value below the sex- and age-specific 5th percentile among lower-risk subjects. The association with cardiovascular mortality was evaluated using Cox regression. In total, 3083 patients were included (8.0 [5.4-11.1] years of follow-up, 249 (8%) cardiovascular deaths). W-peak/LVEDDrest (W/mm) was associated with cardiovascular mortality (adjusted hazard ratio (HR) 0.28 [0.22-0.36]), similar to W-peak in % of predicted, with identical prognostic strength when adjusted for age and sex (C-statistics 0.87 for both). A combination of low W-peak/LVEDDrest and low W-peak was associated with a particularly poor prognosis (adjusted HR 6.4 [4.0-10.3]). W-peak/LVEDDrest was associated with cardiovascular mortality but did not provide incremental prognostic value to W-peak alone. The combination of a low W-peak/LVEDDrest and low W-peak was associated with a particularly poor prognosis., Funding Agencies|Lund University; Department of Research and Development, Region Kronoberg, Sweden; Swedish Research Council [2019-02081]

Introduction: Heart failure (HF) is a heterogeneous syndrome, and the specific sub-category HF with mildly reduced ejection fraction (EF) range (HFmrEF; 41-49% EF) is only recently recognised as a distinct entity. Cluster analysis can characterise heterogeneous patient populations and could serve as a stratification tool in clinical trials and for prognostication. The aim of this study was to identify clusters in HFmrEF and compare cluster prognosis.Methods and results: Latent class analysis to cluster HFmrEF patients based on their characteristics was performed in the Swedish HF registry (n = 7316). Identified clusters were validated in a Dutch cross-sectional HF registrybased dataset CHECK-HF (n =1536). In Sweden, mortality and hospitalisation across the clusters were compared using a Cox proportional hazard model, with a Fine-Gray sub-distribution for competing risks and adjustment for age and sex. Six clusters were discovered with the following prevalence and hazard ratio with 95% confidence intervals (HR [95%CI]) vs. cluster 1: 1) low-comorbidity (17%, reference), 2) ischaemic-male (13%, HR 0.9 [95% CI 0.7-1.1]), 3) atrial fibrillation (20%, HR 1.5 [95% CI 1.2-1.9]), 4) device/wide QRS (9%, HR 2.7 [95% CI 2.2-3.4]), 5) metabolic (19%, HR 3.1 [95% CI 2.5-3.7]) and 6) cardio-renal phenotype (22%, HR 2.8 [95% CI 2.2-3.6]). The cluster model was robust between both datasets.Conclusion: We found robust clusters with potential clinical meaning and differences in mortality and hospitalisation. Our clustering model could be valuable as a clinical differentiation support and prognostic tool in clinical trial design., Funding Agencies|Swedish National Board of Health and Welfare; Swedish Association of Local Authorities and Regions; Swedish Society of Cardiology; Swedish Heart-Lung Foundation; Servier, the Netherlands; EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart; Swedish Research Council; Swedish Heart Lung Foundation [116074]; Stockholm County Council [2013-23897-104604-23, 523-2014-2336]; UCL Hospitals NIHR Biomedical Research Centre [20150557, 20170841]; Dutch Heart Foundation [20140220, 20170112]

Aim We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria. Methods and results From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration >= 6months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios. Conclusion In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality. [GRAPHICS] ., Funding Agencies|Bayer; Horizon Europe programme [101095479]; Swedish Heart and Lung Foundation [20220680]

BackgroundInterpretation of cardiopulmonary exercise testing (CPET) results requires thorough understanding of test confounders such as anthropometrics, comorbidities and medication. Here, we comprehensively assessed the clinical determinants of cardiorespiratory fitness and its components in a heterogeneous patient sample. MethodsWe retrospectively collected medical and CPET data from 2320 patients (48.2% females) referred for cycle ergometry at the University Hospital Leuven, Belgium. We assessed clinical determinants of peak CPET indexes of cardiorespiratory fitness (CRF) and its hemodynamic and ventilatory components using stepwise regression and quantified multivariable-adjusted differences in indexes between cases and references. ResultsLower peak load and peak O-2 uptake were related to: higher age, female sex, lower body height and weight, and higher heart rate; to the intake of beta blockers, analgesics, thyroid hormone replacement and benzodiazepines; and to diabetes mellitus, chronic kidney disease, non-ST elevation myocardial infarction and atrial fibrillation (p < 0.05 for all). Lower peak load also correlated with obstructive pulmonary diseases. Stepwise regression revealed associations of hemodynamic and ventilatory indexes (including heart rate, O-2 pulse, systolic blood pressure and ventilation at peak exercise and ventilatory efficiency) with age, sex, body composition and aforementioned diseases and medications. Multivariable-adjusted differences in CPET metrics between cases and controls confirmed the associations observed. ConclusionWe described known and novel associations of CRF components with demographics, anthropometrics, cardiometabolic and pulmonary diseases and medication intake in a large patient sample. The clinical implications of long-term noncardiovascular drug intake for CPET results require further investigation., Funding Agencies|Fonds Wetenschappelijk Onderzoek [1225021N, 1S07421N, G0C5319N]; KU Leuven [C24M/21/025, DB/22/010/BM]; Onderzoeksraad

Background: Glutamate plays a key role for post-ischaemic recovery of myocardial metabolism. According to post hoc analyses of the two GLUTAMICS trials, patients without diabetes benefit from glutamate with less myocardial dysfunction after coronary artery bypass surgery (CABG). Copeptin reflects activation of the Arginine Vasopressin system and is a reliable marker of heart failure but available studies in cardiac surgery are limited. We investigated whether glutamate infusion is associated with reduced postoperative rises of plasma Copeptin (p-Copeptin) after CABG. Methods: A prespecified randomised double-blind substudy of GLUTAMICS II. Patients had left ventricular ejection fraction <= 0.30 or EuroSCORE II >= 3.0 and underwent CABG +/- valve procedure. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h was commenced 10-20 min before the release of the aortic cross-clamp and then continued for another 150 min P-Copeptin was measured preoperatively and postoperatively on day one (POD1) and day three. The primary endpoint was an increase in p-Copeptin from the preoperative level to POD1. Postoperative stroke <= 24 h and mortality <= 30 days were safety outcomes. Results: We included 181 patients of whom 48% had diabetes. The incidence of postoperative mortality <= 30 days (0% vs. 2.1%; p =.50) and stroke <= 24 h (0% vs. 3.2%; p =.25) did not differ between the glutamate group and controls. P-Copeptin increased postoperatively with the highest values recorded on POD1 without significant inter-group differences. Among patients without diabetes, p-Copeptin did not differ preoperatively but postoperative rise from preoperative level to POD1 was significantly reduced in the glutamate group (73 +/- 66 vs. 115 +/- 102 pmol/L; p =.02). P-Copeptin was significantly lower in the Glutamate group on POD1 (p =.02) and POD 3 (p =.02). Conclusions: Glutamate did not reduce rises of p-Copeptin significantly after mod, Funding Agencies|Region Ostergotland [RO~796412, RO~693091, RO~610951]; Swedish Heart-Lung Foundation [20140633, 20180607]

Aims To investigate whether a heart failure (HF) hospitalization is associated with initiation/discontinuation of guideline-directed medical HF therapy (GDMT) and consequent outcomes.Methods and results Among patients in the Swedish HF registry with an ejection fraction <50% enrolled in 2009-2018, initiation/discontinuation of GDMT was investigated by assessing dispensations of GDMT in those with versus without a HF hospitalization. Of 14 737 patients, 6893 (47%) were enrolled when hospitalized for HF. Initiation of GDMT was more likely than discontinuation following a HF hospitalization compared to a control group of patients without a HF hospitalization (odds ratio range 2.1-4.0 vs. 1.4-1.6 for the individual medications), although the proportion of patients not on GDMT was still high (8.1-44.0%). Key patient characteristics triggering less use of GDMT (i.e. less initiation or more discontinuation) were older age and worse renal function. Following a HF hospitalization, initiation of renin-angiotensin system inhibitors/angiotensin receptor-neprilysin inhibitors or beta-blockers was associated with lower and their discontinuation with higher mortality risk, but no association with mortality was observed for initiation/discontinuation of mineralocorticoid receptor antagonists.Conclusions Following a HF hospitalization, initiation of GDMT was more likely than discontinuation, although still limited. Perceived or actual low tolerance were barriers to GDMT implementation. Early re-/initiation of GDMT was associated with better survival. Our findings represent a call for further implementing the current guideline recommendation for an early re-/initiation of GDMT following a HF hospitalization., Funding Agencies|Abbott; Swedish Heart and Lung Foundation; Abbott Vascular; Bayer; Pharmacosmos; [20220680]

The adenosine-requiring physiological index fractional flow reserve (FFR) is the gold-standard method for determining the significance of intermediate lesions, while the resting full-cycle ratio (RFR) is a novel nonhyperaemic index without the need for adenosine administration. The aim of this study was to investigate the degree of concordance between RFR and FFR in indicating the need for revascularisation in patients with intermediate coronary lesions. This was a retrospective, registry-based study utilising data from the SWEDEHEART registry. Patients treated at Ryhov County Hospital in Jonkoping, Sweden, between the 1(st) of January 2020 and the 30(th) of September 2021, were included. The degree of correlation and concordance between RFR and FFR was determined, both when used with a single cut-off (significant stenosis if RFR = 0.89) and with a hybrid approach (significant stenosis if RFR = 0.85, not significant if RFR & GE;0.94, and FFR measurement when RFR was in the grey zone 0.86-0.93). The study population consisted of 143 patients with 200 lesions. The overall correlation between FFR and RFR was significant (r = 0.715, R-2 = 0.511, p = 0.01). A strong correlation was seen for lesions in the left anterior descending artery (LAD) and the left circumflex artery (LCX) (r = 0.748 and 0.742, respectively, both p = 0.01), while the correlation in the right coronary artery (RCA) was moderate (r = 0.524, p = 0.01). The overall concordance between FFR and RFR using a single cut-off was 79.0%. With a hybrid cut-off approach, the degree of concordance was 91%, with no need of adenosine in 50.5% of the lesions. In conclusion, there was a strong correlation and a high degree of concordance between FFR and RFR in determining the significance of a stenosis. The use of a hybrid approach could improve the identification of physiologically significant stenoses while minimising the use of adenosine., Funding Agencies|Academy for Healthcare; Futurum-The Academy for Healthcare, Region Joenkoeping County [967142]

Aims Cardiac resynchronization therapy (CRT) is effective in heart failure with reduced ejection fraction (HFrEF) and dyssynchrony but is underutilized. In a cohort study, we identified clinical, organizational, and level of care factors linked to CRT implantation. Methods and results We included HFrEF patients fulfilling study criteria in the ESC-HF-Long Term Registry (ESC-HF-LT, n = 1031), the Swedish Heart Failure Registry (SwedeHF) (n = 5008), and the ESC-CRT Survey II (n = 11 088). In ESC-HF-LT, 36% had a CRT indication of which 47% had CRT, 53% had indication but no CRT, and the remaining 54% had no indication and no CRT. In SwedeHF, these percentages were 30, 25, 75, and 70%. Median age of patients with CRT indication and CRT present vs. absent was 68 vs. 65 years with 24% vs. 22% women in ESC-HF-LT, 76 vs. 74 years with 26% vs. 26% women in SwedeHF, and 70 years with 24% women in CRT Survey II (all had CRT). For ESC-HF-LT, independent predictors of having CRT were guideline-directed medical therapy (GDMT), atrial fibrillation (AF), prior HF hospitalization, and NYHA class. For SwedeHF, they were GDMT, age, AF, previous myocardial infarction, lower NYHA class, enrolment at university hospital, and follow-up at HF centre/Hospital. In SwedeHF, above median income and higher education level were also independently associated with having CRT. In the ESC-CRT Survey II (n = 11 088), all patients received CRT but with differences in the clinical characteristics between countries. Conclusion CRT was used in a minority of eligible patients and more used in ESC-HF-LT than in SwedeHF.

Aims The Heart Failure Association of the European Society of Cardiology has recently proposed to optimize guideline-directed medical treatments according to patient s profiles. The aim of this analysis was to investigate prevalence/characteristics/treatments/outcomes for individual profiles Methods and results Patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Swedish Heart Failure Registry (SwedeHF) between 2013 and 2021 were considered. Among 108 profiles generated by combining different strata of renal function (by estimated glomerular filtration rate [eGFR]), systolic blood pressure (sBP), heart rate, atrial fibrillation (AF) status and presence of hyperkalaemia, 93 were identified in our cohort. Event rates for a composite of cardiovascular (CV) mortality or first HF hospitalization were calculated for each profile. The nine most frequent profiles accounting for 70.5% of the population had eGFR 30- 60 or =60 ml/min/1.73m(2), sBP 90-140mmHg and no hyperkalaemia. Heart rate and AF were evenly distributed. The highest risk of CV mortality/first HF hospitalization was observed in those with concomitant eGFR 30- 60ml/min/1.73m(2) and AF. We also identified nine profiles with the highest event rates, representing only 5% of the study population, characterized by no hyperkalaemia, even distribution among the sBP strata, predominance of eGFR < 30 ml/min/1.73m(2) and AF. The three profiles with eGFR 30- 60ml/min/1.73m(2) also showed sBP < 90 mmHg Conclusions In a real-world cohort, most patients fit in a few easily identifiable profiles; the nine profiles at highest risk of mortality/morbidity accounted for only 5% of the population. Our data might contribute to identifying profile-tailored approaches to guide drug implementation and follow-up., Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Background: Women with Turner syndrome (TS) have an increased risk of aortic dissection. The current recommended cutoff to prevent aortic dissection in TS is an aortic size index (ASI) of >= 2.5 cm/m2. This study estimated which aortic size had the best predictive value for the risk of aortic dissection, and whether adjusting for body size improved risk prediction.Methods: A prospective, observational study in Sweden, of women with TS, n = 400, all evaluated with echocardiography of the aorta and data on medical history for up to 25 years. Receiver operating characteristic (ROC) curves, sensitivity and specificity were calculated for the absolute ascending aortic diameter (AAD), ascending ASI and TS specific z-score.Results: There were 12 patients (3%) with aortic dissection. ROC curves demonstrated that absolute AAD and TS specific z-score were superior to ascending ASI in predicting aortic dissection. The best cutoff for absolute AAD was 3.3 cm and 2.12 for the TS specific z-score, respectively, with a sensitivity of 92% for both. The ascending ASI cutoff of 2.5 cm/m2 had a sensitivity of 17% only. Subgroup analyses in women with an aortic diameter >= 3.3 cm could not demonstrate any association between karyotype, aortic coarctation, bicuspid aortic valve, BMI, antihypertensive medication, previous growth hormone therapy or ongoing estrogen replacement treatment and aortic dissection. All models failed to predict a dissection in a pregnant woman.Conclusions: In Turner syndrome, absolute AAD and TS-specific z-score were more reliable predictors for aortic dissection than ASI. Care should be taken before and during pregnancy.

IntroductionAdverse left ventricular remodelling (AR) develops over time in approximately 30% of patients with a history of coronary artery disease. AR manifests as a structural change in the left ventricle (LV) in terms of increased volumes and reduced left ventricular ejection fraction (LVEF). Manganese dipyridoxyl diphosphate (mangafodipir) has demonstrated interesting cardioprotective features in acute myocardial ischaemia. Pharmacological postconditioning (PP) with mangafodipir as an adjunct to primary percutaneous coronary intervention may possibly reduce the development of AR over time in ST-elevation myocardial infarction (STEMI). The aim of this 4-7-year follow-up study is to investigate the potential benefits of PP with mangafodipir in STEMI patients. MethodThirteen out of the initial 20 patients that were included in the primary study of Karlsson et al. were followed up between April and June 2017. The study group underwent review of the hospital records, a clinical examination with ECG and blood sample analysis before cardiac magnetic resonance examination of the patient. LVEF, left ventricular diastolic volume, left ventricular end systolic volume, LV mass and myocardial strain in all directions were computed. ResultsThe PP group showed a decrease in LV volume, mass and higher LVEF at follow-up (p < 0.05) while the individual response of the placebo group showed features that are seen in AR. Although there was no difference in myocardial strain, measurement for the PP-group was higher in absolute terms. ConclusionPharmacological postconditioning with mangafodipir in STEMI demonstrated cardioprotective features compared to the placebo group at follow-up. This article is protected by copyright. All rights reserved., Funding Agencies|Futurum-Academy for Health and Care, Region Jonkoeping County [414891, 598791, 635951, 851331]

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF).Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m(2) and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus =60 ml/min/1.73 m(2), from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus =6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively.Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient, Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Aims Hypertrophic cardiomyopathy (HCM) is characterized by hypercontractility and diastolic dysfunction, which alter blood flow haemodynamics and are linked with increased risk of adverse clinical events. Four-dimensional flow cardiac magnetic resonance (4D-flow CMR) enables comprehensive characterization of ventricular blood flow patterns. We characterized flow component changes in non-obstructive HCM and assessed their relationship with phenotypic severity and sudden cardiac death (SCD) risk. Methods and results Fifty-one participants (37 non-obstructive HCM and 14 matched controls) underwent 4D-flow CMR. Left-ventricular (LV) end-diastolic volume was separated into four components: direct flow (blood transiting the ventricle within one cycle), retained inflow (blood entering the ventricle and retained for one cycle), delayed ejection flow (retained ventricular blood ejected during systole), and residual volume (ventricular blood retained for >two cycles). Flow component distribution and component end-diastolic kinetic energy/mL were estimated. HCM patients demonstrated greater direct flow proportions compared with controls (47.9 +/- 9% vs. 39.4 +/- 6%, P = 0.002), with reduction in other components. Direct flow proportions correlated with LV mass index (r = 0.40, P = 0.004), end-diastolic volume index (r = -0.40, P = 0.017), and SCD risk (r = 0.34, P = 0.039). In contrast to controls, in HCM, stroke volume decreased with increasing direct flow proportions, indicating diminished volumetric reserve. There was no difference in component end-diastolic kinetic energy/mL. Conclusion Non-obstructive HCM possesses a distinctive flow component distribution pattern characterised by greater direct flow proportions, and direct flow-stroke volume uncoupling indicative of diminished cardiac reserve. The correlation of direct flow proportion with phenotypic severity and SCD risk highlight its potential as a novel and sensitive haemodynamic measure of cardiovascular risk, Funding Agencies|British Heart Foundation [FS/CRTF/21/24144]; National Institute of Health and Care Research Oxford Biomedical Research Centre; British Heart Foundation, Oxford Centre of Research Excellence [RE/18/3/34214]; Swedish Research Council; Swedish Heart and Lung Foundation; ALF Grant Region Ostergotland; Oxford British Heart Foundation Centre of Research Excellence

Atrial fibrillation (AF) is the most common arrhythmia seen in clinical practice. In cardiac surgery, the negative influence of AF on short- and long-term outcomes has made concomitant ablation procedures more common. The indications, clinical aspects, results, risks, and benefits of the additional surgical ablation are still valuable topics for discussion. This compilation thesis consists of four papers aiming to investigate some of the clinical, biochemical, and echocardiographic aspects of surgical ablation for AF (Cox-Maze IV) when performed concomitant to mitral valve surgery (MVS). Through a retrospective, case-control, single-center study, we described the impact of the Cox-Maze IV procedure added to MVS with focus on postoperative heart failure (paper I). Cryoenergy (cryo) and radiofrequency (RF) are the two different energy sources mainly used in Cox-Maze IV for AF ablation. To achieve linear scars in the atrial wall, the RF procedure uses heat damage, whereas the cryo method freezes down to -150°C. Through a prospective, randomized, longitudinal, controlled study, we compared the biochemical responses of the two ablative methods in concomitant MVS and the release of enzymes expressing myocardial injury, as well as inflammatory, cell stress, and apoptosis-specific proteins. We could show that cryo results in a larger release of markers for myocardial damage but has no impact on the early inflammatory response (paper II). Extended scar lesions resulting after maze may influence atrial function. As the left atrium plays a key role in the altered cardiac hemodynamics in AF, an echocardiographic analysis of the effects of the Cox-Maze IV procedure concomitant to MVS on the left atrium was carried out. The impacts of the two energy sources (cryo and RF) on left atrial remodeling and function had not been compared previously. Their direct effect on left atrial remodeling and mechanical function were assessed 1 year after surgery in patients with restored sinus rh, Förmaksflimmer (FF) är den vanligaste arytmin som ses i klinisk praxis. Inom hjärtkirurgi har den negativa inverkan på kort- och långtidsutfall för patienter med FF gjort samtidiga ablationsprocedurer vanligare. Indikationerna, de kliniska aspekterna, resultaten, riskerna och fördelarna med den extra kirurgiska ablationen är fortfarande under diskussion. Den aktuella avhandligen består av fyra artiklar som syftar till att undersöka några av de kliniska, biokemiska och ekokardiografiska aspekterna av kirurgisk ablation vid förmaksflimmer (Cox-Maze IV) när det utförs samtidigt med mitralisklaffkirurgi. I en retrospektiv fallkontrollstudie beskrev vi effekten av Cox-Maze IVproceduren som tillägg till mitralisklaffkirurgin med fokus på postoperativ hjärtsvikt (första artikeln). Kryo och Radiofrekvens är de två olika energikällorna som huvudsakligen används vid Cox-Maze IV för FF-ablation. För att uppnå ärrlinjer i förmaksväggen använder Radiofrekvens-proceduren värmeskada, medan Kryo-metoden fryser ner vävnader till minus 150º C grader Celsius. En jämförelse av de biokemiska svaren presenteras mellan de två ablativa metoderna vid samtidig mitralisklaffkirurgi. Frisättningen av biokemiska markörer som uttrycker myokardskada samt inflammatoriska, cellstress- och apoptosspecifika (celldödsspecifika) proteiner rapporteras. Genom en prospektiv randomiserad longitudinell kontrollerad studie kunde vi visa att Kryo hade en större frisättning av hjärtskademarkörer, men ingen inverkan på tidig inflammatorisk respons (andra artikeln). Ärrskador som uppstår efter Cox-Maze IV kan påverka förmaksfunktionen. Eftersom det vänstra förmaket spelar en nyckelroll vid förmaksflimmer förändrade hemodynamiken, genomfördes en ekokardiografisk analys av effekterna av Cox-Maze IV-proceduren samtidigt med mitralisklaffkirurgi på vänster förmak. Effekten av de två energikällorna (Kryo och Radiofrekvens) på vänster förmaks remodeling och funktion har inte jämförts tidigare på ett prospektivt sätt.

BACKGROUND Prognostic assessment of ventricular tachycardia (VT) or ventricular fibrillation (VF) in ST-segment elevation myocardial infarction (STEMI) is based mainly on distinguishing between early (,48 hours) and late arrhythmias, and does not take into account its time distribution with regard to reperfusion, or type of arrhythmia.OBJECTIVE We analyzed the prognostic value of early ventricular arrhythmias (VAs) in STEMI with regard to their type and timing. METHODS The prespecified analysis of the multicenter prospective Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Eleva-tion Myocardial Infarctionin Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Ev-idence-based Care in Heart Disease evaluated according to Recom-mended Therapies Registry Trial included 2886 STEMI patients undergoing primary percutaneous coronary intervention (PCI). VA episodes were characterized regarding their type and timing. Survival status at 180 days was assessed through the population registry.RESULTS Nonmonomorphic VT or VF was observed in 97 (3.4%) and monomorphic VT in 16 (0.5%) patients. Only 3 (2.7%) early VA epi-sodes occurred after 24 hours from symptom onset. VA was associated with higher risk of death (hazard ratio 3.59; 95% confidence interval [CI] 2.01-6.42) after adjustment for age, sex, and STEMI localization. VA after PCI was associated with an increased mortality compared with VA before PCI (hazard ratio 6.68; 95% CI 2.90-15.41). Early VA was associated with in-hospital mortality (odds ratio 7.39; 95% CI 3.68-14.83) but not with long-term prognosis in patients dis-charged alive. The type of VA was not associated with mortality.CONCLUSION VA after PCI was associated with an increased mortal-ity compared with VA before PCI. Long-term prognosis did not differ between patients with monomorphic VT and nonmonomorphic VT or VF, but events were few. VA incidence during 24 to 48 hours of STEMI is negligibly low, thus, Funding Agencies|Swedish Heart Lung Foundation [20180222, 20200674]; Swedish government

Background Guideline recommendations for the treatment of heart failure with mildly reduced ejection fraction (HFmrEF) derive from small subgroups in post-hoc analyses of randomized trials. Objectives We investigated predictors of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) and beta-blockers use, and the associations between these medications and mortality/morbidity in a large real-world cohort with HFmrEF. Methods and results Patients with HFmrEF (EF 40-49%) from the Swedish HF Registry were included. The associations between medications and cardiovascular (CV) mortality/HF hospitalization (HFH), and all-cause mortality were assessed through Cox regressions in a 1:1 propensity score-matched cohort. A positive control analysis was performed in patients with EF < 40%, while a negative control outcome analysis had cancer-related hospitalization as endpoint. Of 12 421 patients with HFmrEF, 84% received RASI/ARNI and 88% beta-blockers. Shared-independent predictors of RASI/ARNI and beta-blockers use were younger age, being an outpatient, follow-up in specialty care, and hypertension. In the matched cohorts, use of both RASI/ARNI and beta-blocker use was separately associated with lower risk of CV mortality/HFH [hazard ratio (HR) = 0.90, 95% confidence interval (CI): 0.83-0.98 and HR = 0.82, 95% CI: 0.74-0.90, respectively] and of all-cause mortality (HR = 0.75, 95% CI: 0.69-0.81 and HR = 0.79, 95% CI: 0.72-0.87, respectively). Results were consistent at the positive control analysis, and there were no associations between treatment use and the negative control outcome. Conclusions RASI/ARNI and beta-blockers were extensively used in this large real-world cohort with HFmrEF. Their use was safe since associated with lower mortality and morbidity. Our findings confirm the real-world evidence from previous post-hoc analyses of trials, and represent a further call for implementing guideline recommendations.