Pathophysiological and Prognostic Importance of an ExtraCardiac Comorbidity Burden in Patients with Heart Failure with Preserved Ejection Fraction

IF 2.5 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

CJC Open Pub Date : 2025-04-01 DOI:10.1016/j.cjco.2025.01.004

Yuki Saito MD, PhD , Tomonari Harada MD, PhD , Naoki Yuasa MD , Kazuki Kagami MD, PhD , Yuta Tani MSc , Ayami Naito MD , Fumitaka Murakami MD , Tomoaki Ishii RS , Toshimitsu Kato MD, PhD , Naoki Wada MD, PhD , Yasuo Okumura MD, PhD , Hideki Ishii MD, PhD , Masaru Obokata MD, PhD

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Abstract

Background

Extracardiac comorbidities are highly prevalent in patients with heart failure with preserved ejection fraction (HFpEF). We investigated the pathophysiological contribution of an extracardiac comorbidity burden to cardiac function, exercise capacity, and prognosis in patients with HFpEF.

Methods

A total of 775 patients (372 HFpEF patients and 403 control subjects) underwent exercise echocardiography, with simultaneous expired gas analysis. We separated the previously validated Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score into cardiac, extracardiac, and demographic categories. An Extracardiac burden was defined as an extracardiac domain score ≥ 5 (median value).

Results

Compared to control subjects (n = 403) and patients with HFpEF without an extracardiac burden (n = 185), patients with HFpEF with an extracardiac burden (n = 187) had higher natriuretic peptide levels and worse exercise capacity. They also had worse ventilatory efficiency and worse peripheral O₂ extraction during exercise. Kaplan–Meier analysis revealed that HFpEF patients with an extracardiac burden had a significantly higher risk of the composite outcome of all-cause mortality and worsening HF events than did those without this burden (log-rank P < 0.0001). Cox regression analysis showed that the extracardiac domain score was significantly associated with a higher risk of the composite events (P < 0.0001). In contrast, an extracardiac comorbidity burden was not associated with impaired exercise capacity, worse ventilatory efficiency, impaired peripheral O₂ extraction, or worse clinical outcomes in control subjects.

Conclusions

An extracardiac comorbidity burden in patients with HFpEF is associated with relevant pathophysiological features characterized by impaired exercise capacity, worse ventilatory efficiency, impaired O₂ extraction and utilization in the periphery, and poor clinical outcomes.

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