Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design

Savarese, Gianluigi; Settergren, Camilla; Schrage, Benedikt; Thorvaldsen, Tonje; Löfman, Ida; Sartipy, Ulrik; Mellbin, Linda; Meyers, Alan; Farsani, Soulmaz Fazeli; Brueckmann, Martina; Brodovicz, Kimberly G.; Vedin, Ola; Asselbergs, Folkert W.; Dahlström, Ulf; Cosentino, Francesco; Lund, Lars H.

doi:10.1016/j.ijcard.2020.04.068

Cited by 39 publications

(41 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, chronic kidney disease and anaemia in HF have been shown to be associated with all-cause mortality with HRs ranging 1.2-1.5. 21,22 In a previous study assessing patient characteristics independently associated with COVID-19, the most important predictor was the highest chronic disease score category (i.e. severe multimorbidity status), with an OR of 1.6.…”

Section: Discussionmentioning

confidence: 99%

Association between renin–angiotensin–aldosterone system inhibitor use and COVID‐19 hospitalization and death: a 1.4 million patient nationwide registry analysis

Savarese

Benson

Sundström³

et al. 2020

European J of Heart Fail

Self Cite

View full text Add to dashboard Cite

Aims Renin–angiotensin–aldosterone system inhibitors (RAASi) improve outcomes in cardiorenal disease but concerns have been raised over increased risk of incident hospitalization and death from coronavirus disease 2019 (COVID‐19). We investigated the association between use of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) and COVID‐19 hospitalization/death in a large nationwide population. Methods and results Patients with hypertension, heart failure, diabetes, kidney disease, or ischaemic heart disease registered in the Swedish National Patient Registry until 1 February 2020 were included and followed until 31 May 2020. COVID‐19 cases were defined based on hospitalization/death for COVID‐19. Multivariable logistic and Cox regressions were fitted to investigate the association between ACEi/ARB and MRA and risk of hospitalization/death for COVID‐19 in the overall population, and of all‐cause mortality in COVID‐19 cases. We performed consistency analysis to quantify the impact of potential unmeasured confounding. Of 1 387 746 patients (60% receiving ACEi/ARB and 5.8% MRA), 7146 (0.51%) had incident hospitalization/death from COVID‐19. After adjustment for 45 variables, ACEi/ARB use was associated with a reduced risk of hospitalization/death for COVID‐19 (odds ratio 0.86, 95% confidence interval 0.81–0.91) in the overall population, and with reduced mortality in COVID‐19 cases (hazard ratio 0.89, 95% confidence interval 0.82–0.96). MRA use was not associated with risk of any outcome. Consistency analysis showed that unmeasured confounding would need to be large for there to be harmful signals associated with RAASi use. Conclusions In a 1.4 million nationwide cohort, use of RAASi was not associated with increased risk of hospitalization for or death from COVID‐19.

show abstract

Section: Discussionmentioning

confidence: 99%

Association between renin–angiotensin–aldosterone system inhibitor use and COVID‐19 hospitalization and death: a 1.4 million patient nationwide registry analysis

Savarese

Benson

Sundström³

et al. 2020

European J of Heart Fail

Self Cite

View full text Add to dashboard Cite

show abstract

“…With the known limitations of observational studies, large, registry-based studies suggest that angiotensin-converting enzyme inhibitors, angiotensin-receptor antagonists and β-blockers might potentially provide benefit in patients with HFmrEF 10 , 151 . The rate of HFrEF medication use in registries is high in the population of patients with HFmrEF, which might be explained by the role of these therapies in treating risk factors and comorbidities that are frequent in HF regardless of EF, such as hypertension, diabetes, chronic kidney disease, IHD and atrial fibrillation 48 , 152 . Diuretic use is also high in patients with HFmrEF, presumably for symptom relief, which is indicated regardless of EF 6 , 48 .…”

Section: Treatment Of Hfmrefmentioning

confidence: 99%

Heart failure with mid-range or mildly reduced ejection fraction

et al. 2021

Self Cite

View full text Add to dashboard Cite

Left ventricular ejection fraction (EF) remains the major parameter for diagnosis, phenotyping, prognosis and treatment decisions in heart failure. The 2016 ESC heart failure guidelines introduced a third EF category for an EF of 40–49%, defined as heart failure with mid-range EF (HFmrEF). This category has been largely unexplored compared with heart failure with reduced EF (HFrEF; defined as EF <40% in this Review) and heart failure with preserved EF (HFpEF; defined as EF ≥50%). The prevalence of HFmrEF within the overall population of patients with HF is 10–25%. HFmrEF seems to be an intermediate clinical entity between HFrEF and HFpEF in some respects, but more similar to HFrEF in others, in particular with regard to the high prevalence of ischaemic heart disease in these patients. HFmrEF is milder than HFrEF, and the risk of cardiovascular events is lower in patients with HFmrEF or HFpEF than in those with HFrEF. By contrast, the risk of non-cardiovascular adverse events is similar or greater in patients with HFmrEF or HFpEF than in those with HFrEF. Evidence from post hoc and subgroup analyses of randomized clinical trials and a trial of an SGLT1–SGLT2 inhibitor suggests that drugs that are effective in patients with HFrEF might also be effective in patients with HFmrEF. Although the EF is a continuous measure with considerable variability, in this comprehensive Review we suggest that HFmrEF is a useful categorization of patients with HF and shares the most important clinical features with HFrEF, which supports the renaming of HFmrEF to HF with mildly reduced EF.

show abstract

“…Accordingly, a Japanese registry confirmed an intermediate profile of HFmrEF patients supposing that the current condition may be a transitional status between HFpEF and HFrEF (17). In a recent Swedish registry analysis comparing three common comorbidities such as AF diabetes and CKD, HFmrEF revealed an intermediate prevalence of CKD and AF, whereas diabetes was similarly expressed in all HF groups (18). Finally, the combined analysis of PARADIGM and PARAGON confirmed an intermediate range regarding age, female sex, body mass, natriuretic peptides, and hypertension, whereas history of myocardial infarction resembled HFrEF (19).…”

Section: Clinical Characteristics Of Hfmrefmentioning

confidence: 95%

Are HFpEF and HFmrEF So Different? The Need to Understand Distinct Phenotypes

Palazzuoli

Beltrami

2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Traditionally, patients with heart failure (HF) are divided according to ejection fraction (EF) threshold more or <50%. In 2016, the ESC guidelines introduced a new subgroup of HF patients including those subjects with EF ranging between 40 and 49% called heart failure with midrange EF (HFmrEF). This group is poorly represented in clinical trials, and it includes both patients with previous HFrEF having a good response to therapy and subjects with initial preserved EF appearance in which systolic function has been impaired. The categorization according to EF has recently been questioned because this variable is not really a representative of the myocardial contractile function and it could vary in relation to different hemodynamic conditions. Therefore, EF could significantly change over a short-term period and its measurement depends on the scan time course. Finally, although EF is widely recognized and measured worldwide, it has significant interobserver variability even in the most accredited echo laboratories. These assumptions imply that the same patient evaluated in different periods or by different physicians could be classified as HFmrEF or HFpEF. Thus, the two HF subtypes probably subtend different responses to the underlying pathophysiological mechanisms. Similarly, the adaptation to hemodynamic stimuli and to metabolic alterations could be different for different HF stages and periods. In this review, we analyze similarities and dissimilarities and we hypothesize that clinical and morphological characteristics of the two syndromes are not so discordant.

show abstract

Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design

Cited by 39 publications

References 22 publications

Association between renin–angiotensin–aldosterone system inhibitor use and COVID‐19 hospitalization and death: a 1.4 million patient nationwide registry analysis

Association between renin–angiotensin–aldosterone system inhibitor use and COVID‐19 hospitalization and death: a 1.4 million patient nationwide registry analysis

Heart failure with mid-range or mildly reduced ejection fraction

Are HFpEF and HFmrEF So Different? The Need to Understand Distinct Phenotypes

Contact Info

Product

Resources

About