| 61. |
|
|
| 62. |
- Engel Sällberg, Adam, et al.
(författare)
-
Plasma tumour necrosis factor-alpha-related proteins in prognosis of heart failure with pulmonary hypertension
- 2023
-
Ingår i: ESC Heart Failure. - 2055-5822. ; 10:6, s. 3582-3591
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Patients with heart failure (HF) exhibit poor prognosis, which is further deteriorated by pulmonary hypertension (PH), with negative impact on morbidity and mortality. As PH due to left HF (LHF-PH) is among the most common causes of PH, there is an urge according to the 2021 European Society of Cardiology HF guidelines to find new biomarkers that aid in prognostication of this patient cohort. Given the role of tumour necrosis factor-alpha (TNF-α) in HF progression, we aimed to investigate the prognostic value of plasma proteins related to TNF-α in patients with LHF-PH, in relation to haemodynamic changes following heart transplantation (HT). Methods and results: Twenty TNF-α-related plasma proteins were analysed using proximity extension assay in healthy controls (n = 20) and patients with LHF-PH (n = 67), before and 1 year after HT (n = 19). Plasma levels were compared between the groups, and the prognostic values were determined using Kaplan–Meier and Cox regression analyses. Plasma levels of lymphotoxin-beta receptor (LTBR), TNF receptor superfamily member 6B (TNFRSF6B), and TNF-related apoptosis-inducing ligand receptors 1 and 2 (TRAIL-R1 and TRAIL-R2, respectively) were higher in LHF-PH pre-HT vs. controls (P < 0.0001), as well as higher in pre-HT vs. post-HT (P < 0.001). The elevated pre-HT levels of LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 decreased towards the levels of healthy controls after HT. Higher preoperative levels of LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 in LHF-PH were associated with worse survival rates (P < 0.002). In multivariate Cox regression models, each adjusted for age and sex, LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 predicted mortality (P < 0.002) [hazard ratio (95% confidence interval): 1.12 (1.04–1.19), 1.01 (1.004–1.02), 1.28 (1.14–1.42), and 1.03 (1.02–1.04), respectively]. Conclusions: Elevated pre-HT plasma levels of the TNF-α-related proteins LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 in LHF-PH decreased 1 year after HT, displaying a normalization pattern towards the levels of the healthy controls. These proteins were also prognostic, where higher levels were associated with worse survival rates in LHF-PH, providing new insight in their potential role as prognostic biomarkers. Larger studies are warranted to validate our findings and to investigate their possible pathobiological mechanisms in LHF-PH.
|
|
| 63. |
- Erhardsson, Mikael, et al.
(författare)
-
Acyl ghrelin increases cardiac output while preserving right ventricular-pulmonary arterial coupling in heart failure
- 2023
-
Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822.
-
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.
|
|
| 64. |
- Erhardsson, M., et al.
(författare)
-
Regional differences and coronary microvascular dysfunction in heart failure with preserved ejection fraction
- 2023
-
Ingår i: ESC Heart Failure. - 2055-5822. ; 10:6, s. 3729-3734
-
Tidskriftsartikel (refereegranskat)abstract
- Aims In heart failure with preserved ejection fraction (HFpEF), regional heterogeneity of clinical phenotypes is increasingly recognized, with coronary microvascular dysfunction (CMD) potentially being a common shared feature. We sought to determine the regional differences in clinical characteristics and prevalence of CMD in HFpEF.Methods and results We analysed clinical characteristics and CMD in 202 patients with stable HFpEF (left ventricular ejection fraction >= 40%) in Finland, Singapore, Sweden, and United States in the multicentre PROMIS-HFpEF study. Patients with unrevascularized macrovascular coronary artery disease were excluded. CMD was assessed using Doppler echocardiography and defined as coronary flow reserve (adenosine-induced vs. resting flow) < 2.5. Patients from Singapore had the lowest body mass index yet highest prevalence of hypertension, dyslipidaemia, and diabetes; patients from Finland and Sweden were oldest, with the most atrial fibrillation, chronic kidney disease, and high smoking rates; and those from United States were youngest and most obese. The prevalence of CMD was 88% in Finland, 80% in Singapore, 77% in Sweden, and 59% in the United States; however, non-significant after adjustment for age, sex, N-terminal pro-brain natriuretic peptide, smoking, left atrial reservoir strain, and atrial fibrillation. Associations between CMD and clinical characteristics did not differ based on region (interaction analysis).Conclusions Despite regional differences in clinical characteristics, CMD was present in the majority of patients with HFpEF across different regions of the world with the lowest prevalence in the United States. This difference was explained by differences in patient characteristics. CMD could be a common therapeutic target across regions.
|
|
| 65. |
|
|
| 66. |
- Fernandez, Celine, et al.
(författare)
-
Circulating protein biomarkers predict incident hypertensive heart failure independently of N-terminal pro-B-type natriuretic peptide levels
- 2020
-
Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:4, s. 1891-1899
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Hypertension is the leading cause for the development of heart failure (HF). Here, we aimed to identify cardiomyocyte stretch-induced circulating biomarkers for predicting hypertension-associated HF. Methods and results: Circulating levels of 149 proteins were measured by proximity extension assay at baseline examination in 4742 individuals from the Malmö Diet and Cancer study. Protein levels were compared with stretch-activated gene expression changes in cultured neonatal rat ventricular myocytes (NRVMs) in response to 1–48 h of mechanical stretch. We also studied the association between protein levels and hypertension and HF incidence using respectively binary logistic and Cox regressions. Levels of 35 proteins were differentially expressed after Bonferroni correction in incident HF vs. control (P < 3.4E−4). Growth differentiation factor-15 (GDF-15), interleukin-6 (IL-6), IL-1 receptor type 1, and urokinase plasminogen activator surface receptor had corresponding mRNA levels up-regulated by stretch in NRVMs at all time points (P < 0.05). These four proteins were individually associated with increased risk of HF after age and sex adjustment [hazard ratio (HR) per standard deviation: 1.19 ≤ HR ≤ 1.49, P ≤ 4.90E−3]. GDF-15 and IL-6 were associated with HF independently of each other (1.22 ≤ HR ≤ 1.33, P ≤ 0.001). In subjects with hypertension, these associations remained significant after further adjustment for N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (1.23 ≤ HR ≤ 1.45, P ≤ 0.001). A higher fasting value of a GDF-15, IL-6 score aggregate was associated with increased risk of hypertensive HF after adjustment for all traditional risk factors for HF and NT-proBNP (HR = 1.31, P = 2.19E−4). Conclusions: Cardiomyocyte mRNA levels of GDF-15 and IL-6 are consistently up-regulated by stretch, and their circulating protein levels predict HF in hypertensive subjects independently of NT-proBNP during long-term follow-up. Our results encourage further studies on lower blood pressure goals in hypertensive subjects with high GDF-15 and IL-6, and interventions targeted at stretch-induced cardiomyocyte expressed biomarkers.
|
|
| 67. |
- Ferrannini, Giulia, et al.
(författare)
-
N-terminal pro-B-type natriuretic peptide concentrations, testing and associations with worsening heart failure events
- 2023
-
Ingår i: ESC Heart Failure. - : WILEY PERIODICALS, INC. - 2055-5822.
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: In patients with heart failure (HF), we aimed to assess (i) the time trends in N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing; (ii) patient characteristics associated with NT-proBNP testing; (iii) distribution of NT-proBNP levels, focusing on the subgroups with (WHFE) vs. without (NWHFE) a worsening HF event, defined as an HF hospitalization; and (iv) changes of NT-proBNP levels over time.Methods and results: NT-proBNP testing and levels were investigated in HF patients enrolled in the Swedish Heart Failure Registry (SwedeHF) linked with the Stockholm CREAtinine Measurements project from January 2011 to December 2018. Index date was the first registration in SwedeHF. Patterns of change in NT-proBNP levels before (in the previous 6 +/- 3 months) and after (in the following 6 +/- 3 months) the index date were categorized as follows: (i) <3000 ng/L at both measurements = stable low; (ii) <3000 ng/L at the first measurement and >= 3000 ng/L at the second measurement = increased; (iii) >= 3000 ng/L at the first measurement and <3000 ng/L at the second measurement = decreased; and (iv) >= 3000 ng/L at both measurements = stable high. Univariable and multivariable logistic regression models, expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs), were performed to assess the associations between (i) clinical characteristics and NT-proBNP testing and (ii) changes in NT-proBNP from 6 months prior to the index date and the index date and a WHFE. Consistency analyses were performed in HF with reduced ejection fraction (HFrEF) alone. A total of 4424 HF patients were included (median age 74 years, women 34%, HFrEF 53%), 33% with a WHFE. NT-proBNP testing increased over time, up to 55% in 2018, and was almost two-fold as frequent, and time to testing was less than half, in patients with WHFE vs. NWHFE. Independent predictors of testing were WHFE, higher heart rate, diuretic use, and preserved ejection fraction. Median NT-proBNP was 3070 ng/L (Q1-Q3: 1220-7395), approximately three-fold higher in WHFE vs. NWHFE. Compared with stable low NT-proBNP levels, increased (OR 4.27, 95% CI 2.47-7.37) and stable high levels (OR 2.48, 95% CI 1.58-3.88) were independently associated with a higher risk of WHFE. Results were consistent in the HFrEF population.Conclusions: NT-proBNP testing increased over time but still was only performed in half of the patients. Testing was associated with a WHFE, with features of more severe HF and for differential diagnosis purposes. Increased and stable high levels were associated with a WHFE. Overall, our data highlight the potential benefits of carrying further implementation of NT-proBNP testing in clinical practice.
|
|
| 68. |
- Forsgard, Niklas, et al.
(författare)
-
Cardiac arrest in Wilson's disease after curative liver transplantation: a life-threatening complication of myocardial copper excess?
- 2019
-
Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 6:1, s. 228-231
-
Tidskriftsartikel (refereegranskat)abstract
- We report the case of a 38-year-old man who presented with cardiac arrest 1 year after curative liver transplantation for Wilson's disease. Clinical work-up proofed myocardial copper and iron accumulation using mass spectrometry, which led most likely to myocardial fibrosis as visualized by cardiovascular magnetic resonance (unprecedented delayed enhancement pattern) and endomyocardial biopsy. Consequently, cardiac arrest due to ventricular fibrillation and subsequent episodes of sustained ventricular tachycardia were considered as primary cardiac manifestation of Wilson's disease. This can, as illustrated by our case, occur even late after curative liver transplantation, which is an important fact that treating physicians should be aware of during clinical follow-up of these patients.
|
|
| 69. |
|
|
| 70. |
- Fu, Michael, 1963, et al.
(författare)
-
Implementation of sacubitril/valsartan in Sweden: clinical characteristics, titration patterns, and determinants
- 2020
-
Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822.
-
Tidskriftsartikel (refereegranskat)abstract
- Aims The aim of this study is to study the introduction of sacubitril/valsartan (sac/val) in Sweden with regards to regional differences, clinical characteristics, titration patterns, and determinants of use and discontinuation. Methods and results A national cohort of heart failure was defined from the Swedish Prescribed Drug Register and National Patient Register. A subcohort with additional data from the Swedish Heart Failure Registry (SwedeHF) was also studied. Cohorts were subdivided as per sac/val prescription and registration in SwedeHF. Median sac/val prescription rate was 20 per 100 000 inhabitants. Between April 2016 and December 2017, we identified 2037 patients with >= 1 sac/val prescription, of which 1144 (56%) were registered in SwedeHF. Overall, patients prescribed with sac/val were younger, more frequently male, and had less prior cardiovascular disease than non-sac/val patients. In SwedeHF subcohort, patients prescribed with sac/val had lower ejection fraction. Overall, younger age [hazard ratio 2.81 (95% confidence interval 2.45-3.22)], registration in SwedeHF [1.97 (1.83-2.12)], male gender [1.50 (1.37-1.64)], ischaemic heart disease [1.50 (1.39-1.62)], lower left ventricular ejection fraction [3.06 (2.18-4.31)], and New York Heart Association IV [1.50 (1.22-1.84)] were predictors for sac/val use. As initiation dose in the sac/val cohort, 38% received 24/26 mg, 54% 49/51 mg, and 9% 97/103 mg. Up-titration to the target dose was achieved in 57% of the overall cohort over a median follow-up of 6 months. The estimated treatment persistence for any dose at 360 days was 82%. Conclusions Implementation of sac/val in Sweden was slow and varied five-fold across different regions; younger age, male, SwedeHF registration, and ischaemic heart disease were among the independent predictors of receiving sac/val. Overall, treatment persistence and tolerability was high.
|
|
