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Noncardiac comorbidity clustering in heart failure: an overlooked aspect with potential therapeutic door

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Abstract

Heart failure is associated with a range of comorbidities that have the potential to impair both quality of life and clinical outcome. Unfortunately, noncardiac diseases are underrepresented in large randomized clinical trials, and their management remains poorly understood. In clinical practice, the prevalence of comorbidities in heart failure is high. Although the prognostic impact of comorbidities is well known, their prevalence and impact in specific heart failure settings have been overlooked. Many studies have described specific single noncardiac conditions, but few have examined their overall burden and grading in patients with multiple comorbidities. The risk of comorbidities in patients with heart failure rises with more advanced disease, older age, and increased frailty—three conditions that are poorly represented in clinical trials. The pathogenic links between comorbidities and heart failure involve many pathways and include neurohormonal overdrive, inflammatory activation, oxidative stress, and endothelial dysfunction. Such interactions may worsen prognoses, but details of these relationships are still under investigation. We propose a shift from cardiac-focused care to a more systemic approach that considers all noncardiac diseases and related medications. Some new drugs class such as ARNI or SGLT2 inhibitors could change prognosis by acting directly or indirectly on metabolic disorders and related vascular consequences.

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Authors and Affiliations

  1. Cardiovascular Diseases Unit, Department of Internal Medicine, Le Scotte Hospital, University of Siena, 53100, Siena, Italy

    Alberto Palazzuoli

  2. Cardiology Unit, Regina Montis Regalis Hospital, ASL-CN1, Mondovì, Cuneo, Italy

    Gaetano Ruocco

  3. Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico di Milano UOC di Nefrologia, Dialisi e Trapianto Renale dell’adulto Dipartimento Di Medicina e Specialità Mediche, Milan, Italy

    Edoardo Gronda

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  1. Alberto Palazzuoli
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Correspondence to Alberto Palazzuoli.

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Highlights

- Cardiac and extracardiac comorbidities are often associated with HF syndrome and could impair prognosis and clinical course

- The prevalence and severity of extracardiac condition is wide but in clinical practice is higher compared to the clinical registries

- Metabolic dysfunction such as obesity CKD and diabetes are directly involved in cardiovascular function deterioration and may negatively influence prognosis if not adequately treated

- Neprylisin inhibitor and SGLT-2 antagonist could improve both cardiovascular and kidney physiology respectively restoring endothelial function and intraglomerular feed back

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Palazzuoli, A., Ruocco, G. & Gronda, E. Noncardiac comorbidity clustering in heart failure: an overlooked aspect with potential therapeutic door. Heart Fail Rev 27, 767–778 (2022). https://doi.org/10.1007/s10741-020-09972-6

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  • DOI: https://doi.org/10.1007/s10741-020-09972-6

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