| 1. |
- Ahmed, Abdulla, et al.
(author)
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Elevated plasma sRAGE and IGFBP7 in heart failure decrease after heart transplantation in association with haemodynamics
- 2020
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In: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:5, s. 2340-2353
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Journal article (peer-reviewed)abstract
- AIMS: Metabolic derangement is implicated in the pathophysiology of heart failure (HF) and pulmonary hypertension (PH). We aimed to identify the dynamics of metabolic plasma proteins linked to end-stage HF and associated PH in relation to haemodynamics, before and after heart transplantation (HT).METHODS AND RESULTS: Twenty-one metabolic plasma proteins were analysed with proximity extension assay in 20 controls and 26 patients before and 1 year after HT. Right heart catheterizations were performed in the HF patients pre-operatively and 1 year after HT. Plasma levels of soluble receptor for advanced glycation end products (sRAGE) and insulin-like growth factor-binding protein 7 (IGFBP7) were higher in HF patients compared with controls (P < 0.0001) and decreased after HT (P < 0.0001), matching controls' levels. The decrease in sRAGE after HT correlated with improved mean pulmonary arterial pressure (rs = 0.7; P < 0.0001), pulmonary arterial wedge pressure (rs = 0.73; P < 0.0001), pulmonary vascular resistance (rs = 0.65; P = 0.00062), and pulmonary arterial compliance (rs = -0.52; P = 0.0074). The change in plasma IGFBP7 after HT correlated with improved mean right atrial pressure (rs = 0.71; P = 0.00011) and N-terminal pro-brain natriuretic peptide (rs = 0.71; P < 0.0001).CONCLUSIONS: Our results indicate that plasma sRAGE may reflect passive pulmonary vascular congestion and the 'mechanical' state of the pulmonary vasculature in HF patients with or without related PH. Furthermore, sRAGE and IGFBP7 may provide additional insight into the pathophysiological mechanisms in HF and associated PH. Their potential clinical and therapeutic relevance in HF and associated PH need further investigation.
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| 2. |
- Ahmed, Abdulla, et al.
(author)
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Prolargin and matrix metalloproteinase-2 in heart failure after heart transplantation and their association with haemodynamics
- 2020
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In: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:1, s. 224-235
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Journal article (peer-reviewed)abstract
- AIMS: Remodelling of the extracellular matrix (ECM) is a key mechanism involved in the development and progression of heart failure (HF) but also functional in associated pulmonary hypertension (PH). Our aim was to identify plasma ECM proteins associated to end-stage HF and secondary PH in relation to haemodynamics, before and after heart transplantation (HT).METHODS AND RESULTS: Twenty ECM plasma proteins were analysed with proximity extension assay in 20 controls and 26 HF patients pre-HT and 1 year post-HT. Right heart catherization haemodynamics were assessed in the patients during the preoperative evaluation and at the 1 year follow-up post-HT. Plasma levels of prolargin and matrix metalloproteinase-2 (MMP-2) were elevated (P < 0.0001) in HF patients compared with controls and decreased (P < 0.0001) post-HT towards controls' levels. The decrease in prolargin post-HT correlated with improved mean right atrial pressure (rs = 0.63; P = 0.00091), stroke volume index (rs = -0.73; P < 0.0001), cardiac index (rs = -0.64; P = 0.00057), left ventricular stroke work index (rs = -0.49; P = 0.015), and N-terminal pro brain natriuretic peptide (rs = 0.7; P < 0.0001). The decrease in MMP-2 post-HT correlated with improved mean pulmonary artery pressure (rs = 0.58; P = 0.0025), mean right atrial pressure (rs = 0.56; P = 0.0046), pulmonary artery wedge pressure (rs = 0.48; P = 0.016), and N-terminal pro brain natriuretic peptide (rs = 0.56; P = 0.0029).CONCLUSIONS: The normalization pattern in HF patients of plasma prolargin and MMP-2 post-HT towards controls' levels and their associations with improved haemodynamics indicate that prolargin and MMP-2 may reflect, in part, the aberrant ECM remodelling involved in the pathophysiology of HF and associated PH. Their potential clinical use as biomarkers or targets for future therapy in HF and related PH remains to be investigated.
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| 3. |
- Bergh, Niklas, 1979, et al.
(author)
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Invasive haemodynamics in de novo everolimus vs. calcineurin inhibitor heart transplant recipients
- 2020
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In: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:2, s. 567-576
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Journal article (peer-reviewed)abstract
- Aims: Invasive haemodynamic profiles at rest and during exercise after heart transplantation (HTx) have never been described in a randomized trial where de novo everolimus (EVR)-based therapy with early calcineurin inhibitor (CNI) withdrawal has been compared with conventional CNI treatment. We report central invasive haemodynamic parameters at rest and exercise during a 3 year follow-up after HTx in a sub-study of the SCandiavian Heart transplant Everolimus De novo stUdy with earLy calcineurin inhibitor avoidancE trial. We hypothesized that the nephroprotective properties, the less development of cardiac allograft vasculopathy (CAV), and the antifibrotic properties of EVR, in comparison with CNI-based immunosuppression, would demonstrate favourable invasive haemodynamic profiles in patients at rest and during exercise. Methods and results: Ninety of 115 HTx recipients randomized to EVR or CNI treatment performed right heart catheterization at rest and 68 performed right heart catheterization at exercise up to 3 years after HTx. Haemodynamic profiles were compared between EVR and CNI treatment groups. Resting haemodynamics improved in both groups from pre-HTx to the first follow-up at 7–11 weeks post-HTx and thereafter remained unchanged up to 3 years of follow-up. During follow-up, cardiac reserve during exercise increased with higher levels of maximum heart rate (118 to 148 b.p.m., P < 0.001), mean arterial pressure (103 to 128 mmHg, P < 0.001), and cardiac output (10.3 to 12.2 l/min, P < 0.001). No significant differences in haemodynamic parameters were observed between the EVR and CNI groups at rest or exercise. Isolated post-capillary pulmonary hypertension (mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure ≥ 15 mmHg, and pulmonary vascular resistance <3) were measured in 11% of the patients at 7–11 weeks, 5% at 12 months, and 6% at 36 months after HTx. The EVR group had significantly better kidney function (76 mL/min/1 vs. 60 mL/min/1, P < 0.001) and reduced CAV (P < 0.01) but an increased rate of early biopsy-proven treated rejections (21.2% vs 5.7%, P < 0.01) compared with the CNI group at any time point. The differences in renal function, CAV, or early biopsy-proven treated acute rejections were not associated with altered haemodynamics. Conclusions: De novo EVR treatment with early CNI withdrawal compared with conventional CNI therapy did not result in differences in haemodynamics at rest or during exercise up to 3 years after HTx despite significant differences in renal function, reduced CAV, and number of early biopsy-proven treated rejections.
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| 4. |
- Blomqvist, Andreas, et al.
(author)
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Utility of single-item questions to assess physical inactivity in patients with chronic heart failure
- 2020
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In: ESC Heart Failure. - : WILEY PERIODICALS, INC. - 2055-5822. ; 7:4, s. 1467-1476
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Journal article (peer-reviewed)abstract
- Aim The purpose of this study was to explore the utility of two single-item self-report (SR) questions to assess physical inactivity in patients with heart failure (HF). Methods and results This is a cross-sectional study using data from 106 patients with HF equipped with accelerometers for 1 week each. Two SR items relating to physical activity were also collected. Correlations between accelerometer activity counts and the SR items were analysed. Patients were classified as physically active or inactive on the basis of accelerometer counts, and the SR items were used to try to predict that classification. Finally, patients were classified as having high self-reported physical activity or low self-reported physical activity, on the basis of the SR items, and the resulting groups were analysed for differences in actual physical activity. There were significant but weak correlations between the SR items and accelerometer counts: rho = 0.24, P = 0.016 for SR1 and rho = 0.21, P = 0.033 for SR2. Using SR items to predict whether a patient was physically active or inactive produced an area under the curve of 0.62 for SR1, with a specificity of 92% and a sensitivity of 30%. When dividing patients into groups on the basis of SR1, there was a significant difference of 1583 steps per day, or 49% more steps in the high self-reported physical activity group (P < 0.001). Conclusions There might be utility in the single SR question for high-specificity screening of large populations to identify physically inactive patients in order to assign therapeutic interventions efficiently where resources are limited.
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| 5. |
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| 6. |
- Ciu, Xiaotong, et al.
(author)
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Trends in cause-specific readmissions in heart failure with preserved vs. reduced and mid-range ejection fraction
- 2020
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In: Esc Heart Failure. - : Wiley. - 2055-5822. ; 7:5, s. 2894-2903
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Journal article (peer-reviewed)abstract
- Aims The aim of this study was to investigate whether the readmission of heart failure (HF) patients has decreased over time and how it differs among HF with preserved ejection fraction (EF) (HFpEF) vs. reduced EF (HFrEF) and mid-range EF (HFmrEF). Methods and results We evaluated HF patients index hospitalized from January 2004 to December 2011 in the Swedish Heart Failure Registry with 1 year follow-up. Outcome measures were the first occurring all-cause, cardiovascular (CV), and HF readmissions. A total of 20 877 HF patients (11 064 HFrEF, 4215 HFmrEF, and 5562 HFpEF) were included in the study. All-cause readmission was the highest in patients with HFpEF, whereas CV and HF readmissions were the highest in HFrEF. From 2004 to 2011, HF readmission rates within 6 months (from 22.3% to 17.3%,P = 0.003) and 1 year (from 27.7% to 23.4%,P = 0.019) in HFpEF declined, and the risk for 1 year HF readmission in HFpEF was reduced by 7% after adjusting for age and sex (P = 0.022). Likewise, risk factors for HF readmission in HFpEF changed. However, no significant changes were observed in all-cause or CV readmission rates in HFpEF, and no significant changes in cause-specific readmissions were observed in HFrEF. Time to the first readmission did not change significantly from 2004 to 2011, regardless of EF subgroup (all P-values > 0.05). Conclusions Declining temporal trend in HF readmission rates was found in HFpEF, but all-cause readmission still remained the highest in HFpEF vs. HFrEF and HFmrEF. More efforts are needed to reduce the non-HF-related readmission in patients with HFpEF.
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| 7. |
- Diebold, Matthias, et al.
(author)
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Mortality and pathophysiology of acute kidney injury according to time of occurrence in acute heart failure
- 2020
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In: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:5, s. 3219-3224
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Journal article (peer-reviewed)abstract
- AimsAcute kidney injury (AKI) during acute heart failure (AHF) is common and associated with increased morbidity and mortality. The underlying pathophysiological mechanism appears to have prognostic relevance; however, the differentiation of true, structural AKI from hemodynamic pseudo‐AKI remains a clinical challenge.Methods and resultsThe Basics in Acute Shortness of Breath Evaluation Study (NCT01831115) prospectively enrolled adult patients presenting with AHF to the emergency department. Mortality of patients was prospectively assessed. Haemoconcentration, transglomerular pressure gradient (n = 231) and tubular injury patterns (n = 253) were evaluated to investigate pathophysiological mechanisms underlying AKI timing (existing at presentation vs. developing during in‐hospital period). Of 1643 AHF patients, 755 patients (46%) experienced an episode of AKI; 310 patients (19%; 41% of AKI patients) presented with community‐acquired AKI (CA‐AKI), 445 patients (27%; 59% of AKI patients) developed in‐hospital AKI. CA‐AKI but not in‐hospital AKI was associated with higher mortality compared with no‐AKI (adjusted hazard ratio 1.32 [95%‐CI 1.01–1.74]; P = 0.04). Independent of AKI timing, haemoconcentration was associated with a lower two‐year mortality. Transglomerular pressure gradient at presentation was significantly lower in CA‐AKI compared to in‐hospital AKI and no‐AKI (P < 0.01). Urinary NGAL ratio concentrations were significantly higher in CA‐AKI compared to in‐hospital AKI (P < 0.01) or no‐AKI (P < 0.01).ConclusionsCA‐AKI but not in‐hospital AKI is associated with increased long‐term mortality and marked by decreased transglomerular pressure gradient and tubular injury, probably reflecting prolonged tubular ischemia due to reno‐venous congestion. Adequate decongestion, as assessed by haemoconcentration, is associated with lower long‐term mortality independent of AKI timing.
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| 8. |
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| 9. |
- Fernandez, Celine, et al.
(author)
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Circulating protein biomarkers predict incident hypertensive heart failure independently of N-terminal pro-B-type natriuretic peptide levels
- 2020
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In: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:4, s. 1891-1899
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Journal article (peer-reviewed)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.
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| 10. |
- Fu, Michael, 1963, et al.
(author)
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Implementation of sacubitril/valsartan in Sweden: clinical characteristics, titration patterns, and determinants
- 2020
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In: Esc Heart Failure. - : Wiley. - 2055-5822.
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Journal article (peer-reviewed)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.
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| 11. |
- Gasim Elsied, Anwar Ali, et al.
(author)
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The importance of heart rate in isoprenaline-induced takotsubo-like cardiac dysfunction in rats
- 2020
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In: Esc Heart Failure. - : Wiley. - 2055-5822. ; 7:5, s. 2690-2699
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Journal article (peer-reviewed)abstract
- Aims Takotsubo syndrome (TS) is an acute cardiac syndrome characterized by regional myocardial akinesia that cannot be attributed to a culprit lesion in coronary arteries. Cardiac overstimulation by catecholamines in the setting of stress is implicated in the pathogenesis of TS. While catecholamine-induced alterations in cardiac contractility have been studied as part of the causal pathway in TS, the importance of catecholamine-mediated tachycardia has not been studied. Our aim was to explore whether the reduction in heart rate, either by pharmacological suppression of the sinoatrial node with ivabradine or by surgical induction of third-degree atrioventricular block, prevents isoprenaline-induced TS-like akinesia in an experimental animal model. Methods and results We used 142 female Sprague-Dawley rats in two separate protocols. The TS-like phenotype was induced by an intraperitoneal bolus dose of isoprenaline (ISO) 50 mg/kg. In the first protocol, we randomized 54 rats to ivabradine 10 min before ISO (IVAB1), ivabradine 10 min after ISO (IVAB2), or saline 10 min before ISO (CONTROL). In the second protocol, we randomized 88 rats to surgically induced complete heart block (CHB) or sham operation (CTRL) 10 min before the administration of ISO. All drugs were administered intraperitoneally. We recorded heart rate and blood pressure invasively in the right carotid artery. Cardiac morphology and function were evaluated by high-resolution echocardiography (VisualSonics 770 VEVO, Toronto, Ontario, Canada) 90 min after ISO injection. IVAB1 and IVAB2 rats had significantly lower heart rate and less pronounced TS-like cardiac dysfunction than CONTROL. CHB rats had a lower (54%) heart rate, and no animal developed left ventricular akinesia. In the first protocol, the CONTROL group had a median degree of akinesia of 10.2 [inter-quartile range (IQR) 0.0-18.6]. The IVAB1 group showed a median of akinesia of 0% (IQR 0.0-0.0, P < 0.001 vs. CONTROL). In the IVAB2 group, 5% had TS-like dysfunction (P = 0.001). Ejection fraction was higher in both the IVAB1 (92%, IQR 89-95) and IVAB2 groups (93%, IQR 87-96) than in the CONTROL group (78%, IQR 63-87, P < 0.05). In the second protocol, the median degree of akinesia in the CTRL group was 21.9% (IQR 8.9-24.6). In the CHB group, no rat developed akinesia (median 0%; IQR 0.0-0.0, P < 0.001 vs. CONTROL). Ejection fraction was higher in the CHB group (90%, IQR 87-92) than in the CTRL group (51%, IQR 8792, P < 0.05). Conclusions Isoprenaline-induced TS-like cardiac dysfunction can be prevented by lowering heart rate. Tachycardia may be an important part of the causal pathway in TS.
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| 12. |
- Giallauria, F., et al.
(author)
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Individual patient data meta-analysis of the effects of the CARILLON (R) mitral contour system
- 2020
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In: Esc Heart Failure. - : Wiley. - 2055-5822. ; 7:6, s. 3383-3391
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Journal article (peer-reviewed)abstract
- Aims Functional mitral regurgitation (MR) (FMR) is common in heart failure with reduced ejection fraction and worsens morbidity and mortality, even when mild. The CARILLON (R) mitral contour system (Cardiac Dimensions, Kirkland, WA, USA), a mitral annuloplasty device delivered percutaneously to the coronary sinus, is designed to reduce the mitral annular dimension by virtue of the close anatomic relationship between the coronary sinus and the posterior mitral annulus. We performed a comprehensive individual patient data meta-analysis of all studies that used CARILLON (R) device vs. control that have measured mitral regurgitation severity, left ventricular (LV) remodelling, functional status, and heart failure-related outcomes in heart failure with reduced ejection fraction patients. Methods and results The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched in July 2020. Primary outcomes of interest were measures of MR severity, LV remodelling, New York Heart Association functional class and heart failure-related outcomes [mortality and heart failure hospitalization (HFH) during follow up]. All data were received as individual patient and individual time point data-points. Mean differences and 95% confidence intervals (CIs) were calculated for continuous data using a fixed-effects model. Three studies (REDUCE FMR, TITAN and TITAN II) enrolling 209 participants were identified and included. Pooled analysis showed that, compared with control, CARILLON (R) device significantly improved both MR volume (mean difference MD -9.20, 95% C.I. -16.11 to -2.29 mL, P = 0.009) and MR grade (MD -1.12, 95% CI -1.36 to -0.88, P < 0.00001) and this was associated with a significant reduction in LA volume, MD -7.54 mL, 95% CI -14.90 to - 0.18, P = 0.04. Significant LV reverse remodelling was also seen in terms of EDV (MD -16.53, 95% CI -28.61 to -44.4 mL, P = 0.007), and a trend in ESV (MD -8.68, 95% CI -18.69 to -1.34 mL, P = 0.09) but no significant effect on LVEF (MD 0.88, 95% CI -1.52% to 2.38%, P = 0.47), due presumably to the greater residual MR in the control patients falsely elevating the LVEF. In addition, the CARILLON (R) device significantly improved New York Heart Association functional Class (MD -0.22, 95% CI -0.24 to -0.16, P < 0.00001), associated with a lower rate of HFH compared with controls (45.3% vs. 64%, respectively, P = 0.04). As a sensitivity analysis we also restricted the analyses to those patients with Class 3+/4+ MR at baseline. In this cohort, the echocardiographic results were similar, and the reduction in HFH rates was even more marked (43.9% vs. 82.9%, respectively, P = 0.04). Conclusions This comprehensive meta-analysis of individual patient data has shown that CARILLON (R) device provides statistically significant and clinically meaningful benefits on MR severity, LA and LV volumes, and remodelling and rates of subsequent heart failure hospitalization
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| 13. |
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| 14. |
- Hage, C., et al.
(author)
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Myeloperoxidase and related biomarkers are suggestive footprints of endothelial microvascular inflammation in HFpEF patients
- 2020
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In: Esc Heart Failure. - : Wiley. - 2055-5822. ; 7:4, s. 1534-1546
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Journal article (peer-reviewed)abstract
- Aims In heart failure (HF) with preserved ejection fraction (HFpEF), microvascular inflammation is proposed as an underlying mechanism. Myeloperoxidase (MPO) is associated with vascular dysfunction and prognosis in congestive HF. Methods and results MPO, MPO-related biomarkers, and echocardiography were assessed in 86 patients, 4-8 weeks after presentation with acute HF (EF >= 45%), and in 46 healthy controls. Patients were followed up for median 579 days (Q1;Q3 276;1178) regarding the composite endpoint all-cause mortality or HF hospitalization. Patients were 73 years old, 51% were female, EF was 64% (Q1;Q3 58;68), E/e ' was ratio 10.8 (8.3;14.0), and left atrial volume index (LAVI) was 43 mL/m(2) (38;52). Controls were 60 (57;62) years old (vs. patients; P < 0.001), 24% were female (P = 0.005), and left ventricular EF was 63% (59;66; P = 0.790). MPO was increased in HFpEF compared with controls, 101 (81;132) vs. 86 (74;101 ng/mL, P = 0.015), as was uric acid 369 (314;439) vs. 289 (252;328 mu mol/L, P < 0.001), calprotectin, asymmetric dimethyl arginine (ADMA), and symmetric dimethyl arginine (SDMA), while arginine was decreased. MPO correlated with uric acid (r = 0.26; P = 0.016). In patients with E/e ' > 14, uric acid and SDMA were elevated (421 vs. 344 mu M, P = 0.012; 0.54 vs. 0.47 mu M, P = 0.039, respectively), and MPO was 121 vs. 98 ng/mL (P = 0.090). The ratios of arginine/ADMA (112 vs. 162; P < 0.001) and ADMA/SDMA (1.36 vs. 1.17; P = 0.002) were decreased in HFpEF patients, suggesting reduced NO availability and increased enzymatic clearance of ADMA, respectively. Uric acid independently predicted the endpoint [hazard ratio (HR) 3.76 (95% CI 1.19-11.85; P = 0.024)] but not MPO [HR 1.48 (95% CI 0.70-3.14; P = 0.304)] or the other biomarkers. Conclusions In HFpEF, MPO-dependent oxidative stress reflected by uric acid and calprotectin is increased, and SDMA is associated with diastolic dysfunction and uric acid with outcome. This suggests microvascular neutrophil involvement mirroring endothelial dysfunction, a central component of the HFpEF syndrome and a potential treatment target.
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| 15. |
- Hedström, Erik, et al.
(author)
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Risk assessment in PAH using quantitative CMR tricuspid regurgitation : relation to heart catheterization
- 2020
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In: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:4, s. 1653-1663
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Journal article (peer-reviewed)abstract
- AIMS: Improved risk stratification is of value for decision making in pulmonary arterial hypertension (PAH). Right heart catheterization combined with quantitative tricuspid regurgitation (TR) by cardiovascular magnetic resonance (CMR) may provide this. The aims were to study: (i) to what extent quantitative TR is associated with event-free survival; (ii) how quantitative TR is related to known prognostic markers in PAH; and (iii) to what extent quantitative TR and right atrial pressure determine right atrial dilation.METHODS AND RESULTS: Fifty patients (63 ± 17 years) with PAH referred for CMR were included. Volumes and pulmonary artery flow by CMR and pressure and vascular resistance by right heart catheterization were obtained. Composite outcome was lung transplantation or death. Four transplantations and 27 deaths occurred over a median of 2.7 years. A trend towards higher hazard ratio was shown for TR volume (TRV; 2.1, 95% CI 1.0-4.4) and TR fraction (TR%; 1.6, 95% CI 0.8-3.3) above median. TRV and TR% correlated with right ventricular (RV) end-diastolic (TRV r = 0.50; TR% r = 0.39) and end-systolic (TRV r = 0.35; TR% r = 0.30) volumes, pulmonary vascular resistance (TRV r = 0.28; TR% r = 0.43), N terminal pro brain natriuretic peptide (TRV r = 0.65; TR% r = 0.68), cardiac index (TRV r = -0.32; TR% r = -0.54), pulmonary artery stroke volume (TRV r = -0.32; TR% r = -0.58) and effective RV ejection fraction by pulmonary artery quantitative flow (TRV r = -0.56; TR% r = -0.69), but not RVEF. Both TR% and right atrial pressure determined right atrial volumes (r2 = 0.38; r2 = 0.48).CONCLUSIONS: A clear trend towards worse outcome with larger TRV or TR% was shown; however, the number of events was insufficient for significant outcome differences. Prognostic value of quantitative TR should be investigated in a larger multicentre cohort. Effective RV ejection fraction may be considered an improved measure of RV function in PAH.
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| 16. |
- Holm, Hannes, et al.
(author)
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Cognitive test results are associated with mortality and rehospitalization in heart failure: Swedish prospective cohort study
- 2020
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In: ESC Heart Failure. - : WILEY PERIODICALS, INC. - 2055-5822. ; 7:5, s. 2948-2955
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Journal article (peer-reviewed)abstract
- Aims We aimed to search for associations between cognitive test results with mortality and rehospitalization in a Swedish prospective heart failure (HF) patient cohort. Methods and results Two hundred and eighty-one patients hospitalized for HF (mean age, 74 years; 32% women) were assessed using cognitive tests: Montreal Cognitive Assessment (MoCA), A Quick Test of Cognitive speed, Trail Making Test A, and Symbol Digit Modalities Test. The mean follow-up time censored at rehospitalization or death was 13 months (interquartile range, 14) and 28 months (interquartile range, 29), respectively. Relations between cognitive test results, mortality, and rehospitalization risk were analysed using multivariable Cox regression model adjusted for age, sex, body mass index, systolic blood pressure, atrial fibrillation, diabetes, smoking, educational level, New York Heart Association class, and prior cardiovascular disease. A total of 80 patients (29%) had signs of cognitive impairment (MoCA score < 23 points). In the fully adjusted Cox regression model using standardized values per 1 SD change of each cognitive test, lower score on MoCA [hazard ratio (HR), 0.75; confidence interval (CI), 0.60-0.95;P = 0.016] and Symbol Digit Modalities Test (HR, 0.66; CI, 0.48-0.90;P = 0.008) yielded significant associations with increased mortality. Rehospitalization risk (n = 173; 62%) was significantly associated with lower MoCA score (HR, 0.84; CI, 0.71-0.99;P = 0.033). Conclusions Two included cognitive tests were associated with mortality in hospitalized HF patients, independently of traditional risk factors. In addition, worse cognitive test scores on MoCA heralded increased risk of rehospitalization.
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| 17. |
- Jonsson, Anna, et al.
(author)
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Comparison of creatinine-based methods for estimating glomerular filtration rate in patients with heart failure
- 2020
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In: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 7:3, s. 1150-1160
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Journal article (peer-reviewed)abstract
- Aims: Glomerular filtration rate is an important factor in management of heart failure (HF). Our objective was to validate eight creatinine-based equations for estimating glomerular filtration rate (eGFR) in an HF population against measured glomerular filtration rate.Methods and results: One hundred forty-six HF patients (mean age 68 +/- 13 years, mean left ventricular ejection fraction 45% +/- 15) within a single-centre hospital that underwent Cr-51-EDTA clearance between 2010 and 2018 were included in this retrospective study. eGFR was estimated by means of Cockcroft-Gault ideal and actual weight, the Modification of Diet in Renal Disease Study (MDRD), simplified MDRD with isotope dilution mass spectroscopy traceable calibration, the Chronic Kidney Disease Epidemiology Collaboration, revised Lund-Malmo, full age spectrum, and the Berlin Initiative Study 1. Mean measured glomerular filtration rate was 42 mL/min/1.73 m(2). Pearson's correlation coefficient (r) had the highest precision for MDRD (r = 0.9), followed by revised Lund-Malmo (r = 0.88). All equations except MDRD (mean difference -4.8%) resulted in an overestimation of the renal function. The accuracy was below 75% for all equations except MDRD.Conclusions: None of the exclusively creatinine-based methods was accurate in predicting eGFR in HF patients. Our findings suggest that more accurate methods are needed for determining eGFR in patients with HF.
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| 18. |
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| 19. |
- Karaye, Kamilu M., et al.
(author)
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Incidence, clinical characteristics, and risk factors of peripartum cardiomyopathy in Nigeria : results from the PEACE Registry
- 2020
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In: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 7:1, s. 236-244
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Journal article (peer-reviewed)abstract
- Aims: The aim of this study was to describe the incidence, clinical characteristics and risk factors of peripartum cardiomyopathy (PPCM) in Nigeria.Methods and Results: The study was conducted in 22 hospitals in Nigeria, and PPCM patients were consecutively recruited between June 2017 and March 2018. To determine factors associated with PPCM, the patients were compared with apparently healthy women who recently delivered, as controls. Four hundred six patients were compared with 99 controls. The incidence and disease burden (based on the rate of consecutive recruitment of subjects) varied widely between the six geographical zones of Nigeria. From the North-West zone, 72.3% of the patients was recruited, where an incidence as high as 1 per 96 live births was obtained in a centre, while the disease was uncommon (7.6% of all recruited patients) in the South. Majority of the patients (76.6%) and controls (74.8%) (p = 0.694) were of Hausa-Fulani ethnic group. Atrial fibrillation, intracardiac thrombus, stroke, and right ventricular systolic dysfunction were found in 1.7%, 6.4%, 2.2%, and 54.9% of the patients, respectively. Lack of formal education (odds ratio [OR] 3.08, 95% confidence interval [1.71, 5.53]; P < 0.001), unemployment (OR: 3.28 [2.05, 5.24]; P < 0.001), underweight (OR: 13.43 [4.17, 43.21]; P < 0.001) and history of pre-eclampsia (OR: 9.01 [2.18, 37.75]; P = 0.002) emerged as independent PPCM risk factors using regression models. Customary hot baths (OR: 1.24 [0.80, 1.93]; P = 0.344), pap enriched with dried lake salt (OR: 1.20 [0.74, 1.94]; P = 0.451), and Hausa-Fulani ethnicity (OR: 1.11 [0.67, 1.84]; P = 0.698) did not achieve significance as PPCM risk factors.Conclusions: In Nigeria, the burden of PPCM was greatest in the North-West zone, which has the highest known incidence. PPCM was predicted by sociodemographic factors and pre-eclampsia, which should be considered in its control at population level. Postpartum customary birth practices and Hausa-Fulani ethnicity were not associated with PPCM in Nigeria.
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| 20. |
- Kashioulis, Pavlos, 1980, et al.
(author)
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Patients with moderate chronic kidney disease without heart disease have reduced coronary flow velocity reserve
- 2020
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In: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:5, s. 2797-2805
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Journal article (peer-reviewed)abstract
- Aims The overall aim was to identify sub-clinical cardiac abnormalities by echocardiography in patients with chronic kidney disease (CKD) stages 3 and 4 and to investigate underlying mechanisms. Methods and results Ninety-one patients with CKD stages 3 and 4, without a diagnosis of heart disease, and 41 healthy matched controls were included in this cross-sectional study. Cardiac morphology and function were analysed with Doppler echocardiography and coronary flow velocity reserve (CFVR) in response to adenosine was measured in the left anterior descendent artery to detect coronary microvascular dysfunction (CMD). All study subjects had a left ventricular (LV) ejection fraction > 50%. Patients with CKD showed statistically significant increases in left atrial volume index and transmitral and pulmonary vein flow velocities during atrial contraction and prolonged LV isovolumetric relaxation time. Patients with CKD had significantly reduced CFVR vs. controls (2.74 +/- 0.86 vs. 3.40 +/- 0.89, P < 0.001), and 43% of patients were classified as having CMD compared with 9% of controls (P = 0.001). Conclusions Patients with CKD stages 3 and 4, without a diagnosis of heart disease, showed early abnormalities in LV diastolic function that did not fulfil the criteria for LV dysfunction according to current guidelines. A large proportion of CKD patients had CMD, suggesting that microvascular abnormalities may have a pathogenic role in the development of heart failure in this patient group.
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| 21. |
- Keramida, Kalliopi, et al.
(author)
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Takotsubo syndrome in Heart Failure and World Congress on Acute Heart Failure 2019: highlights from the experts.
- 2020
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In: ESC heart failure. - : Wiley. - 2055-5822. ; 7:2, s. 400-406
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Journal article (peer-reviewed)abstract
- Takotsubo syndrome was featured in various sessions and posters at the recent Heart Failure Congress and World Congress on Acute Heart Failure 2019 held in Athens. The importance and increasing recognition of this acute heart failure syndrome is reflected by the growing activity at Heart Failure Association congresses over the last 8 years. Two dedicated sessions to Takotsubo syndrome with comprehensive lectures from experts in the field and several posters highlighted new scientific progress, important aspects of epidemiology, pathophysiology, risk stratification, and management of the syndrome and discussed gaps in knowledge of this intriguing entity. This paper will summarize the topics discussed in these sessions including the most recent data from large registries, clinical, and pre‐clinical studies presented at the meeting.
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| 22. |
- Kissopoulou, Antheia, et al.
(author)
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Monozygotic twins with myocarditis and a novel likely pathogenic desmoplakin gene variant
- 2020
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In: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:3, s. 1210-1216
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Journal article (peer-reviewed)abstract
- Myocarditis most often affects otherwise healthy athletes and is one of the leading causes of sudden death in children and young adults. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disorder with increased risk for paroxysmal ventricular arrhythmias and sudden cardiac death. The clinical picture of myocarditis and ARVC may overlap during the early stages of cardiomyopathy, which may lead to misdiagnosis. In the literature, we found several cases that presented with episodes of myocarditis and ended up with a diagnosis of arrhythmogenic cardiomyopathy, mostly of the left predominant type. The aim of this case presentation is to shed light upon a possible link between myocarditis, a desmoplakin (DSP) gene variant, and ARVC by describing a case of male monozygotic twins who presented with symptoms and signs of myocarditis at 17 and 18 years of age, respectively. One of them also had a recurrent episode of myocarditis. The twins and their family were extensively examined including electrocardiograms (ECG), biochemistry, multimodal cardiac imaging, myocardial biopsy, genetic analysis, repeated cardiac magnetic resonance (CMR) and echocardiography over time. Both twins presented with chest pain, ECG with slight ST-T elevation, and increased troponin T levels. CMR demonstrated an affected left ventricle with comprehensive inflammatory, subepicardial changes consistent with myocarditis. The right ventricle did not appear to have any abnormalities. Genotype analysis revealed a nonsense heterozygous variant in the desmoplakin (DSP) gene [NM_004415.2:c.2521_2522del (p.Gln841Aspfs*9)] that is considered likely pathogenic and presumably ARVC related. There was no previous family history of heart disease. There might be a common pathophysiology of ARVC, associated with desmosomal dysfunction, and myocarditis. In our case, both twins have an affected left ventricle without any right ventricular involvement, and they are carriers of a novel DSP variant that is likely associated with ARVC. The extensive inflammation of the LV that was apparent in the CMR may or may not be the primary event of ARVC. Nevertheless, our data suggest that irrespective of a possible link here to ARVC, genetic testing for arrhythmogenic cardiomyopathy might be advisable for patients with recurrent myocarditis associated with a family history of myocarditis.
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| 23. |
- Lindgren, Martin, et al.
(author)
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Elevated resting heart rate in adolescent men and risk of heart failure and cardiomyopathy.
- 2020
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In: ESC heart failure. - : Wiley. - 2055-5822. ; 7:3, s. 1178-1185
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Journal article (peer-reviewed)abstract
- This study aims to investigate the association of resting heart rate (RHR) measured in late adolescence with long-term risk of cause-specific heart failure (HF) and subtypes of cardiomyopathy (CM), with special attention to cardiorespiratory fitness.We performed a nation-wide, register-based cohort study of all Swedish men enrolled for conscription in 1968-2005 (n=1008363; mean age=18.3years). RHR and arterial blood pressure were measured together with anthropometrics as part of the enlistment protocol. HF and its concomitant diagnoses, as well as all CM diagnoses, were collected from the national inpatient, outpatient, and cause of death registries. Risk estimates were calculated by Cox-proportional hazards models while adjusting for potential confounders. During follow-up, there were 8400 cases of first hospitalization for HF and 3377 for CM. Comparing the first and fifth quintiles of the RHR distribution, the hazard ratio (HR) for HF associated with coronary heart disease, diabetes, or hypertension was 1.25 [95% confidence interval (CI)=1.13-1.38] after adjustment for body mass index, blood pressure, and cardiorespiratory fitness. The corresponding HR was 1.43 (CI=1.08-1.90) for HF associated with CM and 1.34 (CI=1.16-1.54) for HF without concomitant diagnosis. There was an association between RHR and dilated CM [HR=1.47 (CI=1.27-1.71)] but not hypertrophic, alcohol/drug-induced, or other cardiomyopathies.Adolescent RHR is associated with future risk of HF, regardless of associated aetiological condition. The association was strongest for HF associated with CM, driven by the association with dilated CM. These findings indicate a causal pathway between elevated RHR and myocardial dysfunction that warrants further investigation.
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| 24. |
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| 25. |
- Molvin, John, et al.
(author)
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A diabetes-associated genetic variant is associated with diastolic dysfunction and cardiovascular disease.
- 2020
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In: ESC heart failure. - : Wiley. - 2055-5822. ; 7:1, s. 345-353
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Journal article (peer-reviewed)abstract
- Although the epidemiological association between Type 2 diabetes and congestive heart failure (CHF) as well as cardiovascular disease (CVD) is well established, associations between diabetes-related single-nucleotide polymorphisms (SNPs), CHF, and CVD have been surprisingly inconclusive. Our aim is to examine if 43 diabetes-related SNPs were associated with prevalent diastolic dysfunction assessed by echocardiography and incident CVD and/or CHF.We genotyped 43 SNPs that previously reported genome-wide significant associations with Type 2 diabetes, in 1444 subjects from the population-based Malmö Preventive Project-Re-examination Study (MPP-RES) (mean age 68 years; 29% women, 36% prevalent diabetes) (discovery cohort) and in 996 subjects from the VARA cohort (mean age 51 years, 52% women, 7% prevalent diabetes) (replication cohort). Multivariable logistic regression was assessed. Genetic variants that reached significant association with diastolic dysfunction in both cohorts were then analysed for association with incident CVD/CHF in a larger sample of the MPP-RES cohort (3,407 cases and 11,776 controls, median follow up >30 years) using Cox regression analysis. A common variant at the HNF1B [major allele (T) coded, also the risk allele for diabetes] was the only SNP associated with increased risk of prevalent diastolic dysfunction in both the discovery [MPP-RES; odds ratio (OR) 1.21, P = 0.024), and the replication cohort (VARA; OR 1.38, P = 0.042]. Cox regression analysis showed that carriers of the T-allele of rs757210 had an increased risk of future CVD (HR 1.05, P = 0.042). No significant association was seen for incident CHF.The diabetes susceptibility locus HNF1B is associated with prevalent diastolic dysfunction in two independent Swedish cohorts as well as incident cardiovascular disease.
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