| 1. |
- Erhardsson, Mikael, et al.
(författare)
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Acyl ghrelin increases cardiac output while preserving right ventricular-pulmonary arterial coupling in heart failure
- 2023
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Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822.
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Acyl ghrelin increases cardiac output (CO) in heart failure with reduced ejection fraction (HFrEF). This could impair the right ventricular-pulmonary arterial coupling (RVPAC), both through an increased venous return and right ventricular afterload. We aim to investigate if acyl ghrelin increases CO with or without worsening the right-sided haemodynamics in HFrEF assessed by RVPAC.METHODS AND RESULTS: The Karolinska Acyl ghrelin Trial was a randomized double-blind placebo-controlled trial of acyl ghrelin versus placebo (120-min intravenous infusion) in HFrEF. RVPAC was assessed echocardiographically at baseline and 120 min. ANOVA was used for difference in change between acyl ghrelin versus placebo, adjusted for baseline values. Of the 30 randomized patients, 22 had available RVPAC (acyl ghrelin n = 12, placebo n = 10). Despite a 15% increase in CO in the acyl ghrelin group (from 4.0 (3.5-4.6) to 4.6 (3.9-6.1) L/min, P = 0.003), RVPAC remained unchanged; 5.9 (5.3-7.6) to 6.3 (4.8-7.5) mm·(m/s)-1 , P = 0.372, while RVPAC was reduced in the placebo group, 5.2 (4.3-6.4) to 4.8 (4.2-5.8) mm·(m/s)-1 , P = 0.035. Comparing change between groups, CO increased in the acyl ghrelin group versus placebo (P = 0.036) while RVPAC and the right ventricular pressure gradient remained unchanged.CONCLUSION: Treatment with acyl ghrelin increases CO while preserving or even improving RVPAC in HFrEF, possibly due to increased contractility, reduced PVR and/or reduced left sided filling pressures. These potential effects strengthen the role of acyl ghrelin therapy in HFrEF with right ventricular failure.
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| 2. |
- Gatti, Paolo, et al.
(författare)
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What determines who gets cardiac resynchronization therapy in Europe? A comparison between ESC-HF-LT registry, SwedeHF registry, and ESC-CRT Survey II
- 2023
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Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : OXFORD UNIV PRESS. - 2058-5225 .- 2058-1742. ; 9:8, s. 741-748
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
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| 4. |
- Kapelios, Chris J., et al.
(författare)
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Non-cardiology vs. cardiology care of patients with heart failure and reduced ejection fraction is associated with lower use of guideline-based care and higher mortality : Observations from The Swedish Heart Failure Registry
- 2021
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Ingår i: International Journal of Cardiology. - : Elsevier Ireland Ltd. - 0167-5273 .- 1874-1754. ; 343
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with heart failure (HF) are often cared for by non-cardiologists. The implications are unknown. Methods: In a nationwide HF cohort with reduced ejection fraction (HFrEF), we compared demographics, clinical characteristics, guideline-based therapy use and outcomes in non-cardiology vs. cardiology in-patient and outpatient care. Results: Between 2000 and 2016, 36,076 patients with HFrEF were enrolled in the Swedish HF registry (19,337 [54%] in-patients overall), with 44% of in-patients and 45% of out-patients managed in non-cardiology settings. Predictors of treatment in non-cardiology were age > 75 years (adjusted odds ratio for non-cardiology 1.20; 95% confidence interval 1.14-1.27), lower education level (0.71; 0.66-0.76 for university vs. compulsory), valve disease (1.24; 1.18-1.31) and systolic blood pressure (SBP) >120 mmHg (1.05; 1.00-1.10). Non-cardiology care was significantly associated with lower use of beta-blockers (0.80; 0.74-0.86) and devices (intracardiac defibrillator [ICD] and/or cardiac resynchronization therapy [CRT]: 0.63; 0.56-0.71), and less frequent specialist follow-up (0.61; 0.57-0.65). Over 1-year follow-up the risk of all-cause mortality (adjusted hazard ratio 1.09; 1.03-1.15) was higher but the risk of first HF (re-) hospitalization was lower (0.93; 0.89-0.97) in non-cardiology vs. cardiology care. Conclusions: In HFrEF, non-cardiology care was independently associated with older ageand lower education. After covariate adjustment, non-cardiology care was associated with lower use of beta-blockers and devices, higher mortality, and lower risk of HF hospitalization. Access to cardiology care may not be equitable and this may have implications for use of guideline-based care and outcomes.
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| 5. |
- Lund, Lars H., et al.
(författare)
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Acyl ghrelin improves cardiac function in heart failure and increases fractional shortening in cardiomyocytes without calcium mobilization
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645.
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Tidskriftsartikel (refereegranskat)abstract
- Background and AimsGhrelin is an endogenous appetite-stimulating peptide hormone with potential cardiovascular benefits. Effects of acylated (activated) ghrelin were assessed in patients with heart failure and reduced ejection fraction (HFrEF) and in ex vivo mouse cardiomyocytes.Methods and resultsIn a randomized placebo-controlled double-blind trial, 31 patients with chronic HFrEF were randomized to synthetic human acyl ghrelin (0.1 µg/kg/min) or placebo intravenously over 120 min. The primary outcome was change in cardiac output (CO). Isolated mouse cardiomyocytes were treated with acyl ghrelin and fractional shortening and calcium transients were assessed. Acyl ghrelin but not placebo increased cardiac output (acyl ghrelin: 4.08 ± 1.15 to 5.23 ± 1.98 L/min; placebo: 4.26 ± 1.23 to 4.11 ± 1.99 L/min, P < 0.001). Acyl ghrelin caused a significant increase in stroke volume and nominal increases in left ventricular ejection fraction and segmental longitudinal strain and tricuspid annular plane systolic excursion. There were no effects on blood pressure, arrhythmias, or ischaemia. Heart rate decreased nominally (acyl ghrelin: 71 ± 11 to 67 ± 11 b.p.m.; placebo 69 ± 8 to 68 ± 10 b.p.m.). In cardiomyocytes, acyl ghrelin increased fractional shortening, did not affect cellular Ca2+ transients, and reduced troponin I phosphorylation. The increase in fractional shortening and reduction in troponin I phosphorylation was blocked by the acyl ghrelin antagonist D-Lys 3.ConclusionIn patients with HFrEF, acyl ghrelin increased cardiac output without causing hypotension, tachycardia, arrhythmia, or ischaemia. In isolated cardiomyocytes, acyl ghrelin increased contractility independently of preload and afterload and without Ca2+ mobilization, which may explain the lack of clinical side effects. Ghrelin treatment should be explored in additional randomized trials.
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| 6. |
- Savarese, Gianluigi, et al.
(författare)
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Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum : A blueprint for clinical trial design
- 2020
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 313, s. 76-82
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundComorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes.Methods and resultsOf 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF.ConclusionHFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk.
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| 7. |
- Settergren, Camilla, et al.
(författare)
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Cause-specific death in heart failure across the ejection fraction spectrum: A comprehensive assessment of over 100 000 patients in the Swedish Heart Failure Registry
- 2024
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844.
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Tidskriftsartikel (refereegranskat)abstract
- AimTo assess cause-specific death in patients with heart failure with preserved, mildly reduced, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF). Methods and resultsData were analysed from the Swedish Heart Failure Registry (SwedeHF) and the National Patient Register of patients enrolled in SwedeHF 2000-2021. Cox proportional hazards regression models were performed and adjusted for age, sex and time period. Among 100 584 patients (23% HFpEF, 23% HFmrEF, 53% HFrEF), median age (interquartile range) was 75 (66-82) and 36% were female. Of those who died within 5 years, most deaths were ascribed to cardiovascular (CV) causes across all ejection fraction (EF) categories. Within 5 years, HFpEF had higher adjusted risk of non-CV death (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.28-1.38, p < 0.001) and lower adjusted risk of CV death (HR 0.85, 95% CI 0.82-0.88, p < 0.001) compared to HFrEF. Ischaemic heart disease (IHD) and cancer were the most common causes of CV and non-CV death regardless of EF category. The incidence rate of CV death due to IHD was highest in HFrEF while incidence rates of CV death due to pulmonary vascular disease, stroke, valvular heart disease and atrial fibrillation increased with increasing EF. The incidence rates of non-CV deaths due to cancer, respiratory disease, and infections increased with increasing EF. ConclusionCardiovascular death was more common than non-CV death across all EF categories although the risk of non-CV death within 5 years was higher with increasing EF. IHD and cancer were the most common causes of CV and non-CV deaths, respectively, regardless of EF category.
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| 8. |
- Stolfo, Davide, et al.
(författare)
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Use of evidence-based therapy in heart failure with reduced ejection fraction across age strata
- 2022
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:6, s. 1047-1062
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Tidskriftsartikel (refereegranskat)abstract
- Aims In older patients, guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (<40%; HFrEF) is not contraindicated, but adherence to guidelines is limited. We investigated the implementation of GDMT in HFrEF across different age strata in a large nationwide cohort. Methods and results Patients with HFrEF and HF duration >= 3 months registered in the Swedish HF Registry between 2000-2018 were analysed according to age. Multivariable logistic and multinomial regressions were fitted to investigate factors associated with underuse/underdosing. Of 27 430 patients, 31% were <70 years old, 34% 70-79 years old, and 35% >= 80 years old. Use of treatments progressively decreased with increasing age. Use of renin-angiotensin system/angiotensin receptor-neprilysin inhibitors, beta-blockers and mineralocorticoid receptor antagonists was 80%, 88% and 35% in age >= 80 years; 90%, 93% and 47% in age 70-79 years; and 95%, 95% and 54% in age <70 years, respectively. Among patients with an indication, use of implantable cardioverter defibrillator and cardiac resynchronization therapy (CRT) was 7% and 23% in age >= 80 years; 22% and 42% in age 70-79 years; and 29% and 50% in age <70 years, respectively. Older patients were less likely treated with target doses or combinations of HF medications. Except for CRT, after extensive adjustments, age was inversely associated with the likelihood of GDMT use and target dose achievement. Conclusion In HFrEF, gaps persist in the use of medications and devices. In disagreement with current recommendations, older patients remain undertreated. Improving strategies and a more individualized approach for implementing use of GDMT in HFrEF are required, particularly in older patients.
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| 9. |
- Thorvaldsen, Tonje, et al.
(författare)
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Eligibility for Dapagliflozin and Empagliflozin in a Real-world Heart Failure Population
- 2022
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Ingår i: Journal of Cardiac Failure. - : Churchill Livingstone. - 1071-9164 .- 1532-8414. ; 28:7, s. 1050-1062
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Tidskriftsartikel (refereegranskat)abstract
- Background: We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), and EMPEROR (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction and Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with APreserved Ejection Methods and Results: Selection criteria were applied to the Swedish HF registry outpatient population according to 3 scenarios: (i) a "trial scenario" applying all selection criteria; (ii) a "pragmatic scenario" applying the most clinically relevant criteria; and (iii) a "label scenario" following the regulatory agencies labels. Of the 49,317 patients, 55% had an ejection fraction of less than 40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had ejection fraction of 40% or greater and were assessed based on EMPEROR-Preserved and DELIVER. Eligibility using trial, pragmatic, and label scenarios was 35%, 61%, and 80% for DAPA-HF; 31%, 55%, and 81% for EMPEROR-Reduced; 30%, 61%, and 74% for DELIVER; and 32%, 59%, and 75% for EMPEROR-Preserved, respectively. The main selection criteria limiting eligibility were HF duration and N-terminal pro-B type natriuretic peptide levels. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality and morbidity. Clinical Highlights: Large clinical trials for the approval of new drugs in heart failure often apply numerous selection criteria, limiting the generalizability of trial findings to real-world populations. We assessed eligibility for dapagliflozin and empagliflozin according to trial criteria, the more practical criteria usually applied in daily practice for treatment selection, and the criteria mandated by regulatory agencies, in a real-word heart failure population. Our results from the Swedish Heart Failure Registry show that a great number of patients with heart failure might be candidates for these therapies, which have been shown to significantly decrease morbidity and mortality; therefore, their use should be implemented in clinical practice. Lay summary: When strictly applying selection criteria used in clinical trials, only one-third of a real-world heart failure population is eligible for treatment with empagliflozin and dapagliflozin. Adopting approaches that consider the most meaningful criteria, that is, those most clinically relevant or those mandated by regulatory agencies, significantly broadened eligibility. These results might contribute to future trial design taking into consideration the characteristics of real-world populations, feasibility, and potential cost benefits. Conclusions: In a real-world HF setting, eligibility for sodium glucose co-transporter-2 inhibi-tors was similar whether selection criteria from DAPA-HF or EMPEROR-Reduced were applied in HFrEF, or EMPEROR-Preserved or DELIVER in HFpEF. These data might help stakeholders assessing the consequences of future trial eligibility. (J Cardiac Fail 2022;28:1050-1062)
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| 10. |
- Thorvaldsen, Tonje
(författare)
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Heart failure : studies of prognosis and advanced therapy
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Heart failure (HF) is a major health problem affecting 2-3% of the Western population. The clinical syndrome of HF is associated with reduced (HFrEF) or preserved (HFpEF) ejection fraction. Around 50% of the patients have HFrEF and despite advances in treatment, prognosis remains poor and treatments are underutilized. In HFpEF the prognosis is comparable to in HFrEF, but there is no evidence-based therapy. Aims - to investigate: 1) The use of evidence-based therapy and survival over time in patients with HFrEF; 2) The use of the inotropic drug levosimendan in HF in Sweden; 3 a) Contemporary prognosis in patients with severe HFrEF; 3 b) If simple predictors of prognosis can be identifid and used as criteria for referral to a HF center; and 4) Predictors of mortality in patients hospitalized with acute decompensated HFpEF. Evidence-based therapy and survival: We studied 5,908 HFrEF patients with New York Heart Association (NYHA) class II-IV registered in the Swedish Heart Failure registry (SwedeHF) between 2003 and 2012. The use of beta-blockers and renin angiotensin system (RAS) blockers was >85% and stable over time. There was a decrease in the use of mineralocorticoid receptor antagonists (MRA) from 53 to 42%. The use of cardiac resynchronization therapy (CRT) and implantable cardioverter defirillators (ICD) increased over time, but absolute numbers were low, less than 11% for both. In 2003 vs. 2012, the 30-day, oneyear, and 3-year survival was 92 vs. 94%, 81 vs. 77% and 58 vs. 54% respectively. The changes in survival were not statistically signifiant. Reported numbers are risk-adjusted. The use of levosimendan in Sweden: In SwedeHF, 655 registrations were confimed with use of inotropes. Levosimendan alone was the inotropic drug of choice in 91% of the registrations. Of all levosimendan registrations, 38% were planned repetitive treatment. The proportion of planned repetitive to all levosimendan registrations ranged from 0 to 65% between hospitals. Who should be referred to a heart failure center? We studied 10,062 HFrEF patients with NYHA class III-IV from SwedeHF. One-year survival in the age groups ≤65 years, 66-80 years, and >80 years was 90, 79, and 61% respectively. Five prespecifid risk factors were assessed as potential triggers for referral to a HF center: systolic blood pressure ≤90 mmHg; creatinine ≤160 mmol/L; hemoglobin ≤120 g/L; no use of RAS antagonist; and no use of beta-blocker. In patients <80 years of age, the presence of 1, 2, or 3-5 of these risk factors were associated with a one-year survival of 79, 60, and 39% respectively. Risk prediction in HFpEF: HF Surveillance data from four different communities in the United States were used to study 2,304 hospitalizations of HFpEF. Mortality at 28 days and one year was 11 and 34% respectively. The most powerful predictors of mortality were higher age, hypoxia, higher blood urea nitrogen and lower hemoglobin. Conclusions: Patients with HF face a high risk of death. In HFpEF novel interventions are urgently called for, whereas improving implementation of existing evidence-based treatments should be emphasized in HFrEF. Specifially, the poor use of ICD and CRT needs to be recognized. Levosimendan was the dominant choice of inotrope in Sweden. Effects of the frequent use of planned repetitive levosimendan treatment in a non-acute setting need to be further evaluated. Few and simple risk factors used as referral criteria to a HF center, may increase the number of patients who can benefi from further therapy. In HFpEF, risk predictors may be used for discrimination of high risk patients and contribute to further characterization of this population.
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