| 1. |
- Shen, L., et al.
(författare)
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Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction
- 2019
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 21:8, s. 974-984
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Tidskriftsartikel (refereegranskat)abstract
- Aims Insulin causes sodium retention and hypoglycaemia and its use is associated with worse outcomes in heart failure (HF) with reduced ejection fraction. We have investigated whether this is also the case in HF with preserved ejection fraction (HFpEF). Methods and results We examined the association between diabetes/diabetes treatments and the risk of the primary composite of cardiovascular death or HF hospitalization, as well as other outcomes in adjusted analyses in CHARM-Preserved (left ventricular ejection fraction >= 45%), I-Preserve and TOPCAT (Americas) pooled. Of 8466 patients, 2653 (31%) had diabetes, including 979 (37%) receiving insulin. Patients receiving insulin were younger, had a higher body mass index, prevalence of ischaemic aetiology, N-terminal pro-B-type natriuretic peptide and use of diuretics, worse New York Heart Association class and signs and symptoms, and worse quality of life and renal function, compared to patients with diabetes not on insulin. Among the 1398 patients with echocardiographic data, insulin use was associated with higher left ventricular end-diastolic pressure and more diastolic dysfunction than in other participants. The primary outcome occurred at a rate of 6.3 per 100 patient-years in patients without diabetes, and 10.2 and 17.1 per 100 patient-years in diabetes patients without and with insulin use, respectively [fully adjusted hazard ratio (aHR) insulin-treated diabetes vs. other diabetes: 1.41, 95% confidence interval (CI) 1.23-1.63, P < 0.001]. The adjusted HR is 1.67 (95% CI 1.20-2.32, p = 0.002) for sudden death (insulin-treated diabetes vs. other diabetes). Conclusions Insulin use is associated with poor outcomes in HFpEF. Although we cannot conclude a causal association, the safety of insulin and alternative glucose-lowering treatments in HF needs to be evaluated in clinical trials.
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| 2. |
- Dewan, P., et al.
(författare)
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Differential Impact of Heart Failure With Reduced Ejection Fraction on Men and Women
- 2019
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 73:1, s. 29-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Heart failure (HF) trials initiated in the last century highlighted many differences between men and women. Of particular concern was undertreatment of women compared with men, but much has changed during the past 20 years. OBJECTIVES This study sought to identify these changes, which may give a new perspective on the management of, and outcomes in, women with HF. METHODS The study analyzed 12,058 men and 3,357 women enrolled in 2 large HF with reduced ejection fraction (HFrEF) trials with near identical inclusion and exclusion criteria and the same principal outcomes. Outcomes were adjusted for other prognostic variables including N-terminal pro-B-type natriuretic peptide. RESULTS Women were older and more often obese than men were, had slightly higher systolic blood pressure and heart rate, and were less likely to have most comorbidities, except hypertension. Women had more symptoms and signs (e.g., pedal edema 23.4% vs 19.9%; p < 0.0001) and worse quality of life-median Kansas City Cardiomyopathy Questionnaire Clinical Summary Score 71.3 (interquartile range: 53.4 to 86.5) versus 81.3 (interquartile range: 65.1 to 92.7; p < 0.0001)-despite similar left ventricular ejection fraction and N-terminal pro-B-type natriuretic peptide. However, women had lower mortality (adjusted hazard ratio: 0.68; 95% confidence interval: 0.62 to 0.74; p < 0.001) and risk of HF hospitalization (hazard ratio: 0.80; 95% confidence interval: 0.72 to 0.89; p < 0.001). Diuretics and anticoagulants were underutilized in women. Device therapy was underused in both men and women, but more so in women (e.g., defibrillator 8.6% vs. 16.6%; p < 0.0001). CONCLUSIONS Although women with HFrEF live longer than men, their additional years of life are of poorer quality, with greater self-reported psychological and physical disability. The explanation for this different sex-related experience of HFrEF is unknown as is whether physicians recognize it. Women continue to receive suboptimal treatment, compared with men, with no obvious explanation for this shortfall.
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| 3. |
- Dewan, P., et al.
(författare)
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Income Inequality and Outcomes in Heart Failure A Global Between-Country Analysis
- 2019
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Ingår i: Jacc-Heart Failure. - : Elsevier BV. - 2213-1779. ; 7:4, s. 336-346
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES This study examined the relationship between income inequality and heart failure outcomes. BACKGROUND The income inequality hypothesis postulates that population health is influenced by income distribution within a society, with greater inequality associated with worse outcomes. METHODS This study analyzed heart failure outcomes in 2 large trials conducted in 54 countries. Countries were divided by tertiles of Gini coefficients (where 0% represented absolute income equality and 100% represented absolute income inequality), and heart failure outcomes were adjusted for standard prognostic variables, country per capita income, education index, hospital bed density, and health worker density. RESULTS Of the 15,126 patients studied, 5,320 patients lived in Gini coefficient tertile 1 countries (coefficient: <33%), 6,124 patients lived in tertile 2 countries (33% to 41%), and 3,772 patients lived in tertile 3 countries (>41%). Patients in tertile 3 were younger than tertile 1 patients, were more often women, and had less comorbidity and several indicators of less severe heart failure, yet the tertile 3-to-1 hazard ratios (HRs) for the primary composite outcome of cardiovascular death or heart failure hospitalization were 1.57 (95% confidence interval [CI]: 1.38 to 1.79) and 1.48 for all-cause death (95% CI: 1.29 to 1.71) after adjustment for recognized prognostic variables. After additional adjustments were made for per capita income, education index, hospital bed density, and health worker density, these HRs were 1.46 (95% CI: 1.25 to 1.70) and 1.30 (95% CI: 1.10 to 1.53), respectively. CONCLUSIONS Greater income inequality was associated with worse heart failure outcomes, with an impact similar to those of major comorbidities. Better understanding of the societal and personal bases of these findings may suggest approaches to improve heart failure outcomes. (C) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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| 4. |
- Kristensen, S. L., et al.
(författare)
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Prevalence and incidence of intraventricular conduction delays and outcomes in patients with heart failure and reduced ejection fraction: Insights from PARADIGM-HF and ATMOSPHERE
- 2020
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 22:12, s. 2370-9
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The importance of intraventricular conduction delay (IVCD), incidence of new IVCD and its relationship to outcomes in heart failure and reduced ejection fraction (HFrEF) is not well studied. We addressed these questions in the PARADIGM-HF and ATMOSPHERE trials. METHODS AND RESULTS: Risk of the primary composite outcome of cardiovascular death or HF hospitalization and all-cause mortality were estimated by use of Cox regression according to baseline QRS duration and morphology in 11,861 patients without an intracardiac device. At baseline, 1,789 (15.1%) patients had left bundle branch block (LBBB), 524 (4.4%) RBBB, 454 (3.8%) non-specific IVCD, 2588 (21.8%) "mildly abnormal" QRS (110-129 milliseconds [ms]) and 6506 (54.9%) QRS <110 ms. During a median follow-up of 2.5 years, the risk of the primary composite endpoint was higher among those with a wide QRS, irrespective of morphology: hazard ratios (95% CI) LBBB 1.36 (1.23, 1.50), RBBB 1.54 (1.31, 1.79), nonspecific IVCD 1.65 (1.40, 1.94) and QRS 110-129 ms 1.35 (95% CI 1.23, 1.47), compared with QRS duration <110 ms. A total of 1,234 (15.6%) patients developed new-onset QRS-widening >/=130 ms (6.1 per 100 py). Incident LBBB occurred in 495 (6.3%) patients (2.4 per 100 py) and was associated with a higher risk of the primary composite outcome; HR 1.42 (1.12, 1.82). CONCLUSION: In patients with HFrEF, a wide QRS was associated with worse clinical outcomes irrespective of morphology. The annual incidence of new-onset LBBB was around 2.5%, and associated with a higher risk of adverse outcomes, highlighting the importance of repeat ECG review.
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| 5. |
- Kristensen, S. L., et al.
(författare)
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Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart Failure Patients With and Without Atrial Fibrillation
- 2017
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Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with heart failure (HF) and atrial fibrillation (AF) have higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) than HF patients without AF. There is uncertainty about the prognostic importance of a given concentration of NT-proBNP in HF patients with and without AF. We investigated this question in a large cohort of patients with HF and reduced ejection fraction. METHODS AND RESULTS: We studied 14 737 patients with HF and reduced ejection fraction and a measurement of NT-proBNP at time of screening, enrolled in either the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) or the ATMOSPHERE trial (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure), of whom 3575 (24%) had AF on their baseline ECG. Median (Q1, Q3) levels of NT-proBNP were 1817 pg/mL (1095-3266 pg/mL) in those with AF and 1271 pg/mL (703-2569 pg/mL) in those without (P<0.0001). Patients with AF were older (67 versus 62 years), had worse New York Heart Association class (III/IV; 36% versus 24%), and experienced fewer previous HF hospitalizations (52% versus 61%) or myocardial infarction (30% versus 46%); all P<0.001. We categorized patients with and without AF into 5 NT-proBNP bands: <400, 400 to 999 (reference), 1000 to 1999, 2000 to 2999, and >/=3000 pg/mL. For the primary composite outcome of cardiovascular death or HF hospitalization, event rates differed for patients with and without AF in the lowest band (<400 pg/mL; 8.2 versus 5.0 per 100 patient-years), but not for the higher bands (400-999 pg/mL, 7.4 versus 7.7 per 100 patient-years; 1000-1999 pg/mL, 9.8 versus 11.4 per 100 patient-year; 2000-2999 pg/mL, 13.5 versus 13.4 per 100 patient-years; >/=3000 pg/mL, 22.7 versus 23.0 per 100 patient-years). These findings were consistent whether NT-proBNP was examined as a categorical or continuous variable and before and after adjustment for other prognostic variables. We found similar results for the components of the composite outcome and all-cause mortality. CONCLUSIONS: HF and reduced ejection fraction patients with AF had higher NT-proBNP than those without AF. However, above a concentration of 400 pg/mL (representing most patients in each group), NT-proBNP had similar predictive value for adverse cardiovascular outcomes, irrespective of AF status. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier NCT00853658 (ATMOSPHERE) and NCT01035255 (PARADIGM-HF).
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| 6. |
- Rorth, R., et al.
(författare)
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The prognostic value of troponin T and N-terminal pro B-type natriuretic peptide, alone and in combination, in heart failure patients with and without diabetes
- 2019
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 21:1, s. 40-49
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Tidskriftsartikel (refereegranskat)abstract
- Aims We examined the prognostic importance of N-terminal pro B-type natriuretic peptide (NT-proBNP) and troponin T (TnT) in heart failure patients with and without diabetes. Methods and results We measured NT-proBNP and TnT in the biomarker substudy of the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF). Of 1907 patients, 759 (40%) had diabetes. Median TnT in patients with diabetes was 18 (interquartile range 11-27) ng/L and 13 (9-21) ng/L in those without (P < 0.001). The TnT frequency-distribution curve was shifted to the right in patients with diabetes, compared to those without diabetes. By contrast, NT-proBNP did not differ between patients with and without diabetes. Diabetes and each biomarker were predictive of worse outcomes. Thus, patients with diabetes, an elevated TnT and a NT-proBNP level in the highest tertile (9% of all patients) had an absolute risk of cardiovascular death or heart failure hospitalization of 265 per 1000 person-years, compared to a rate of 42 per 1000 person-years in those without diabetes, a TnT < 18 ng/L and a NT-proBNP in the lowest tertile (16% of all patients). TnT remained an independent predictor of adverse outcomes in multivariable analyses including NT-proBNP. Conclusion TnT is elevated to a greater extent in heart failure patients with diabetes compared to those without (whereas NT-proBNP is not). TnT and NT-proBNP are additive in predicting risk and when combined help identify diabetes patients at extremely high absolute risk.
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| 7. |
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| 8. |
- Wijkman, Magnus, et al.
(författare)
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Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials
- 2022
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) and diabetes, and across the spectrum of left ventricular ejection fraction (LVEF) in heart failure and diabetes. Methods We compared the effect of sacubitril/valsartan, relative to valsartan, on HbA1c, new insulin therapy and hypoglycemia in the randomized controlled trial PARAGON-HF, and performed pooled analyses of PARAGON-HF and PARADIGM-HF. Results Among 2395 patients with HFpEF and diabetes in PARAGON-HF, sacubitril/valsartan compared with valsartan reduced HbA1c (baseline-adjusted between-group difference in HbA1c change at 48 weeks: - 0.24%, 95% CI - 0.33 to - 0.16%, P < 0.001). Numerically, new insulin treatment was initiated less often in the sacubitril/valsartan group than in the valsartan group, but the difference was not statistically significant (12.8% vs. 16.1%; HR: 0.80, 95% CI 0.62-1.02, P = 0.07). Hypoglycemia adverse event reports were low, but more frequent in those receiving sacubitril/valsartan than in the valsartan group (4.2% vs. 2.6%; HR: 1.64, 95% CI 1.05-2.56, P = 0.030). In a pooled analysis of PARAGON-HF and PARADIGM-HF, the effect of sacubitril/valsartan on change in HbA1c was not significantly modified by LVEF (P-interaction = 0.56). Across the spectrum of LVEF, sacubitril/valsartan reduced new insulin therapy (HR: 0.75, 95% CI 0.63-0.89, P = 0.001), compared with enalapril or valsartan. Conclusions Sacubitril/valsartan reduced HbA1c and new insulin therapy in patients with heart failure and diabetes across the spectrum of LVEF but may be associated with a slightly higher risk for hypoglycemia. Trial registration ClinicalTrials.gov NCT01920711
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