Research Spotlight

Packer, M., F. Zannad and S. D. Anker (2021). “Heart Failure and a Preserved Ejection Fraction: A Side-by-Side Examination of the PARAGON-HF and EMPEROR-Preserved Trials.” Circulation 144(15): 1193-1195.

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Heart failure and a preserved ejection fraction (HFpEF) is characterized in many patients by the coexistence of a systemic metabolic or inflammatory disorder that causes coronary endothelial dysfunction, microvascular rarefaction, and cardiac fibrosis, leading to impaired left ventricular distensibility. Neurohormonal antagonists that are effective in patients with heart failure and a reduced ejection fraction have generally not been useful in patients with HFpEF. Until recently, large-scale trials of patients with HFpEF have reported no benefit or only a modest reduction in the risk of heart failure outcomes, with borderline levels of statistical significance. The trials have also noted meaningful subgroup interactions, which have further complicated interpretation of the results.[No abstract; excerpt from article].

Tromp, J., M. Packer and C. S. Lam (2021). “The diverging role of epicardial adipose tissue in heart failure with reduced and preserved ejection fraction: not all fat is created equal.” Eur J Heart Fail Oct 16. [Epub ahead of print].

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In this issue of the Journal, the study by Pugliese et al. significantly extends prior knowledge on the role of EAT in HF by studying the association of EAT with clinical biomarkers and outcomes in patients with HFrEF and HFpEF. The authors measured EAT thickness on echocardiography in a total of 393 patients with HF (48% HFpEF) and 44 controls. The HF diagnosis in participants was corroborated by objective signs and symptoms of HF, a reduced ejection fraction or increased natriuretic peptides. All participants underwent comprehensive exercise testing with measurement of peak oxygen consumption (VO2 max) and arterial–venous oxygen content difference (AVO2diff) and were followed up for 21 months. EAT thickness was significantly increased in patients with HFpEF relative to controls and decreased in patients with HFrEF. In HFrEF, EAT was inversely associated with the inflammatory biomarkers high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), N-terminal pro-B-type natriuretic peptide and troponin T. In HFpEF, thicker EAT was associated with higher concentrations of troponin T, hs-CRP, and IL-6. Notably, thinner EAT was associated with worse (lower) VO2 max and an increased risk for cardiovascular death or hospitalization for HF in HFrEF. In HFpEF, the converse was true: thicker EAT was associated with a decreased VO2 max and increased risk for cardiovascular death or hospitalization for HF.

Packer, M., J. Butler, F. Zannad, S. J. Pocock, G. Filippatos, J. P. Ferreira, M. Brueckmann, W. Jamal, C. Zeller, C. Wanner and S. D. Anker (2021). “Empagliflozin and Major Renal Outcomes in Heart Failure.” N Engl J Med 385(16): 1531-1533.

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Sodium–glucose cotransporter 2 inhibitors reduce the risk of serious adverse renal outcomes in type 2 diabetes, but the renal effects of these drugs in patients with heart failure remain uncertain. Although empagliflozin and dapagliflozin have been reported to slow the rate of decline in the estimated glomerular filtration rate (eGFR), changes in the eGFR slope may not predict the effects of these drugs on major renal outcomes. [No abstract, excerpt from article].

Brown, K. D., J. S. van Zyl, B. da Graca, J. Adams and D. M. Meyer (2021). “Keep Your Move in the Tube® Method and Self-Confidence After Coronary Artery Bypass Graft Surgery.” J Cardiopulm Rehabil Prev 41(6): 438-440.

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Keep Your Move in the Tube® (KMIT) methodology, described in detail elsewhere, allows patients to perform load-bearing tasks after median sternotomy (MS) previously contraindicated by sternal precautions (SP). Utilizing KMIT is associated with improved discharge disposition and reduced difficulty performing functional tasks following discharge without increased incidence of sternal complications or readmissions. However, the impact of KMIT on patient perceptions of their ability to perform essential activities during the acute post-operative period has yet to be investigated. Psychological recovery, specifically self-confidence, has been suggested to be a key factor in the successful return to function after MS. This study aimed to investigate self-rated confidence in performing upper-body functional activities prior to and after KMIT education in patients following coronary artery bypass graft (CABG) surgery via MS. Our secondary aim was to compare the force exerted by the upper body when performing KMIT activities with the load limit typically prescribed under SP (5 lb). [no abstract; excerpt from article].

Menter, A., A. S. Van Voorhees and S. Hsu (2021). “Pustular Psoriasis: A Narrative Review of Recent Developments in Pathophysiology and Therapeutic Options.” Dermatol Ther (Heidelb) Oct 9. [Epub ahead of print].

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Pustular psoriasis is an unusual form of psoriasis that frequently presents clinical challenges for dermatologists. The condition presents with pustules on an erythematous background and has two distinct subtypes: localized disease on the palms and soles, called palmoplantar pustulosis (PPP), and generalized pustular psoriasis (GPP). The involvement of the fingers, toes, and nails is defined as a separate localized variant, acrodermatitis continua of Hallopeau, and is now thought to be a subset of PPP. The rarity of pustular psoriasis frequently makes the correct diagnosis problematic. In addition, treatment is limited by a relative lack of evidence-based therapeutic options. Current management is often based on existing therapies for standard plaque psoriasis. However, there remains a need for treatments with high, sustained efficacy and a rapid onset of action in pustular psoriasis. Recent advances in understanding of the pathogenesis of pustular psoriasis have provided insights into potential therapies. Treatment of pustular psoriasis is generally determined by the extent and severity of disease, and recent years have seen an increasing use of newer agents, including biologic therapies. Current classes of biologic therapies with US Food and Drug Administration and European Medicines Agency approval for treatment of moderate-to-severe plaque psoriasis in the USA (and elsewhere) include tumor necrosis factor alpha inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab), interleukin (IL)-17 inhibitors (brodalumab, ixekizumab, secukinumab), an IL-12/23 inhibitor (ustekinumab), and IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab). Recently, specific inhibitors of the IL-36 pathway have been evaluated in GPP and PPP, including spesolimab, an IL-36 receptor inhibitor which has shown promising results in GPP. The emerging drugs for pustular psoriasis offer the possibility of rapid and effective treatment with lower toxicities than existing therapies. Further research into agents acting on the IL-36 pathway and other targeted therapies has the potential to transform the future treatment of patients with pustular psoriasis. This article reviews the clinical features of PPP and GPP, and current understanding of the genetics and immunopathology of these conditions; it also provides an update on emerging treatments.