Heart failure and chronic obstructive pulmonary disease. A combination not to be underestimated

Authors, Journal, Affiliations, Type, DOI

• Damiano Magrì, Emiliano Fiori, Piergiuseppe Agostoni, Michele Correale, Massimo Piepoli, Savina Nodari, Matteo Beltrami, Stefania Paolillo, Pasquale Perrone Filardi, Alberto Palazzuoli; on behalf of the Working Group on Heart Failure of the Italian Society of Cardiology
• Heart Failure Reviews 2025; 30:1525–1538 (Published online 7 October 2025)
• Affiliations: Sapienza University of Rome; Centro Cardiologico Monzino Milan; University Federico II Naples; University of Siena; and others (multi-center Italian)
• Type: Narrative review
• DOI: https://doi.org/10.1007/s10741-025-10566-3

Overview

This 2025 narrative review from the Italian Society of Cardiology Working Group on Heart Failure comprehensively examines the bidirectional pathophysiological interaction between COPD and heart failure across the full ejection fraction spectrum. Key messages include: ~20% of COPD patients have HF with 70% being HFpEF; COPD in HF is an independent prognostic driver (particularly in HFpEF where comorbidities dominate disease expression); CPET-derived VE intercept (≥2.6 L/min) is the best non-invasive tool to identify COPD in HF; β1-selective blockers (bisoprolol, nebivolol) are safe and beneficial in HFrEF+COPD, reducing both HF and COPD exacerbations, while β-blockers should be avoided in HFpEF+COPD; and evidence-based bronchodilator therapy should continue in HF, though LAMA+ICS may be preferred over LABA in new diagnoses.

Keywords

Heart failure · Lung disease · Cardiopulmonary exercise test · Cardiopulmonary interaction

Key Takeaways

Epidemiology of COPD Along the HF Spectrum

COPD → HF Perspective

• Among COPD patients, HF incidence is ~1.2 per 100 person-years; prevalence of HF in COPD ranges from 11.1–21.1% (~1 in 5).
• Of COPD patients with HF, 70% present with HFpEF phenotype — making HFpEF the dominant HF expression in COPD.
• COPD+HFrEF: higher risk of HF-specific hospitalisation and mortality than COPD+HFpEF.
• COPD+HFpEF: outcomes largely driven by COPD (AECOPD dominates), with a worsening respiratory trajectory over time.
• Over 10 years, no decrease in cardiovascular mortality was seen in COPD+HF — in contrast to the trend of decreasing CV deaths in the wider COPD population, underscoring a persistent unmet need.

HF → COPD Perspective (Registry and RCT Data)

• COPD prevalence in HF patients: 13% (most recent European HF registry) — highest in HFpEF (16%), then HFmrEF (12%), then HFrEF (11%).
• Patients with HF+COPD were older, more often female, had higher comorbidity burden, and more severe HF.
• COPD independently associated with higher risks of CV death, first and recurrent HF hospitalisation, and all-cause death across the EF spectrum.
• Statistically significant interaction between EF phenotype and COPD for HF hospitalisation outcomes — highest risk in HFmrEF and HFpEF.
• In RCTs (prevalence 11.1–14.2%): GDMT benefit is preserved irrespective of COPD presence — post-hoc analyses consistently demonstrate this.

Pathophysiological Interactions

How HF Aggravates COPD

• Pulmonary congestion (HF) → volume overload → reduced lung volumes and airway calibre; elevated LAP during exercise → bronchial mucosa vascular engorgement → increased bronchial reactivity.
• In HFpEF, LAP may be near-normal at rest but double during mild exercise or when supine — clinically silent congestion that worsens airway function.
• Volume shifts during exercise → interstitial oedema → during recovery, fluid moves to alveolar-capillary membrane → impaired gas diffusion → V/Q mismatch → hypoxemia → pulmonary vasoconstriction → worsened dead-space ventilation in COPD.
• HF-associated basal ventilatory restriction (particularly in dilated CM/HFrEF) + exaggerated ventilatory response (sympathetic chemoreceptor activation, metaboreflex from skeletal/respiratory muscles) further burdens COPD.
• Muscle wasting and cachexia (both HFrEF and HFpEF) exacerbate respiratory muscle fatigue in COPD.

How COPD Aggravates HF

• Among COPD patients without established CVD: >50% have Grade II diastolic dysfunction — suggesting high prevalence of elevated LV filling pressures and possible HFpEF.
• Landmark study (n=2,816 severe COPD): linear relationship between emphysema percentage and reductions in LVEDV, stroke volume, and cardiac output — upstream circulatory impairment via ventricular underfilling.
• Airflow obstruction → air trapping → dynamic hyperinflation during exercise → positive intrathoracic pressures → reduced venous return → reduced biventricular preload.
• Diaphragm flattening (from chronic air trapping) impairs its normal modulation of venous return and biventricular filling.
• COPD → increased RV afterload (precapillary PH rises with severity; mPAP/CO slope >3 even without resting PH) → RV-PA uncoupling → blunted CO reserve during exercise.
• Unifying hypothesis: COPD → reduced biventricular preload + increased RV afterload → reduced CO with exercise (preload failure) — particularly severe in HFpEF with coexisting chronotropic incompetence.

Differential Diagnosis

Natriuretic Peptides

• HFpEF+COPD: NP reliability significantly reduced. Elevated NP levels in stable COPD without HF reduce rule-in accuracy; a significant subset of HFpEF has congestion only on exercise with normal resting NP → further reduces NP utility. Both PPV and NPV are impaired when COPD and HFpEF coexist.
• HFrEF+COPD: NP maintain reliable NPV for ruling out LV systolic dysfunction — even in stable COPD and during COPD exacerbations. NP levels are typically higher in HFrEF even with COPD.
• Overall: COPD is an important confounding factor for NP interpretation, especially in HFpEF workup. No validated COPD-specific NP cut-offs exist.

Pulmonary Function Tests

• Spirometry performed in only ~30% of HF patients with suspected COPD.
• Consequence of underutilisation: ~30% of chronic HF patients are misdiagnosed with COPD without confirmed airflow obstruction; another ~30% have undetected airflow limitation.
• Acute HF → dynamic airway obstruction (volume-dependent); spirometry normalises in 50% of patients when repeated under stable conditions — landmark finding.
• Chronic HF → restrictive pattern (cardiomegaly + interstitial fibrosis); proportional FEV1/FVC reduction (10–20%) can pseudo-normalise obstruction → underdiagnosis/underestimation of COPD.
• Recommendation: Spirometry should be performed under euvolemic, stable conditions to avoid both over- and under-diagnosis.
• Body plethysmography (measuring TLC and RV) as second-line when spirometry inconclusive or dynamic component suspected — pulmonary congestion does not influence air trapping, improving differentiation.

Cardiopulmonary Exercise Testing (CPET)

• VE/VCO2 slope does not significantly differ among HF, COPD, or HF+COPD — limiting its discriminatory value for identifying COPD in HF.
• VE intercept (VEint ≥2.6–4.07 L/min): A positive VE intercept reflects higher dead-space load — primary in COPD but secondary in HF. Identified as a promising CPET tool to identify COPD as an HF comorbidity across the full EF spectrum.
• CPET recommended as an additional diagnostic step in stable dyspnoeic HF patients to confirm or exclude coexisting COPD.

Treatment Interactions

Beta-Blockers

• Non-selective β-blockers (carvedilol) impact respiratory function at multiple levels: reduces DLCO (via β2 blockade of alveolar cell membrane transport), reduces FEV1 and FEV1/FVC ratio vs bisoprolol/nebivolol/metoprolol, attenuates hyperventilation (VE/VCO2 slope) possibly via chemoreceptor modulation.
• β1-selective blockers (bisoprolol, nebivolol, metoprolol): neutral effect on airway function; do not change FEV1 response to β-agonists; no deleterious airway effects.
• BLOCK COPD trial (metoprolol): Interrupted early — hospitalisations for exacerbation more common in metoprolol arm. Cautionary against using β-blockers purely for COPD without HF indication.

HFrEF+COPD (Class I, Level A):

• β-blockers remain strongly recommended. Bisoprolol preferred — reduces mortality and incidence of HF and COPD exacerbations in a dose-dependent manner (superior to carvedilol and metoprolol).
• Swedish HF Registry (HFrEF+COPD): beta-blocker use → lower CV death/total HFH without evidence of COPD exacerbation harm.
• Agent selection algorithm:
  • Hypoxia or reduced DLCO → nebivolol or bisoprolol
  • Exaggerated VE/VCO2 → carvedilol (low dose; repeat PFTs after titration)
  • Frequent AECOPD → bisoprolol (preferred); metoprolol second choice

HFpEF+COPD:

• β-blockers not recommended in HFpEF (detrimental evidence, including chronotropic incompetence); even more so in the presence of COPD.
• Existing β-blockers should be discontinued (unless required for non-HF indication: angina, AF) to improve functional capacity and avoid side effects.

HFimpEF+COPD:

• Evidence for continuing β-blockers once LVEF normalises (>50%) is limited — decision to maintain should be individualised, weighing airflow obstruction severity and respiratory symptoms.

Bronchodilators

• LABAs → stimulate β2-adrenergic receptors → increased sympathetic tone → vasoconstriction, ↑HR; failing myocytes have β1 downregulation with shift toward β2 → more vulnerable to β2 agonists.
• LAMAs → inhibit M3 cholinergic receptors → indirect sympathetic increase (vagal inhibition).
• Bronchodilators may break the vicious cycle of dynamic hyperinflation → cardiac underfilling — a potential cardiorespiratory benefit.
• In COPD without known HF: Clinical trials on LABA/LAMA have not demonstrated significant CV outcome impact; patients with symptomatic HF were excluded from these trials.
• In COPD+known HF: LABA associated with HF exacerbations in retrospective data (dose-response), but the association disappears after adjusting for smoking and other confounders; one well-characterised prospective cohort showed no LABA-long-term-outcome relationship when adjusted for BNP. Misdiagnosis between HFH and AECOPD confounds all retrospective studies.
• Practical recommendation: Evidence-based COPD treatment (LABA/LAMA) should be offered regardless of HF status. LAMA+ICS may be preferred over LABA alone for HF patients newly diagnosed with COPD. Concurrent β1-selective blockers may mitigate LABA side effects (by promoting β1-receptor re-exposure and reducing β2 dependence) — but this remains theoretical.

Limitations of the Document

• Narrative review without systematic search — inherits selective literature coverage
• Retrospective evidence base for bronchodilator safety (confounders including smoking, AECOPD/HFH misdiagnosis, lack of disease-severity stratification)
• β-blocker trials in COPD+HF are mostly retrospective observational cohorts or subgroup analyses from HFrEF trials — no RCT designed specifically for COPD+HF β-blocker comparison
• No RCT of LABA vs LAMA specifically in HF patients focused on HF safety outcomes — a major evidence gap
• CPET VE intercept data based on small studies; external validation across EF spectrum needed

Key Concepts Mentioned

• concepts/HF-COPD-Comorbidity — bidirectional pathophysiological interaction; epidemiology across EF spectrum; treatment interactions
• concepts/Cardiopulmonary-Exercise-Testing — CPET in HF differential diagnosis; VE intercept; VE/VCO2 slope
• concepts/Pulmonary-Hypertension — precapillary PH in COPD; mPAP/CO slope >3; RV-PA uncoupling

Key Entities Mentioned

• entities/COPD — epidemiology, pathophysiology, diagnostic challenges, treatment in HF context
• entities/HFpEF — dominant HF phenotype in COPD patients; β-blockers contraindicated; NP unreliable
• entities/HFrEF — β-blockers Class I in HFrEF+COPD; bisoprolol preferred

Wiki Pages Updated

• Created wiki/sources/hf-copd-hfreview-2025.md
• Created wiki/concepts/HF-COPD-Comorbidity.md
• Created wiki/concepts/Cardiopulmonary-Exercise-Testing.md
• Updated wiki/entities/COPD.md — added beta-blocker algorithm, CPET findings, NP insights, spirometry detail, epidemiology numbers
• Updated wiki/entities/HFpEF.md — added beta-blocker avoidance in HFpEF+COPD
• Updated wiki/entities/HFrEF.md — added COPD+HFrEF beta-blocker section
• Updated wiki/wikiindex.md
• Updated wiki/sourceindex.md
• Appended log.md