From ANCA-mediated vascular injury to coronary microvascular and myocardial involvement in granulomatosis with polyangiitis: an immunocardiology perspective

Abstract

Granulomatosis with polyangiitis (GPA) is a prototypical antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis characterized by necrotizing inflammation of small- and medium-sized vessels with granulomatous features. Although advances in immunosuppressive therapy have markedly improved short-term survival, long-term outcomes remain limited by cumulative organ damage, treatment-related toxicity, and an excess burden of cardiovascular morbidity and mortality. Cardiovascular risk in GPA appears to reflect a combination of conventional risk factors, treatment-related metabolic effects, renal dysfunction, systemic inflammation, and disease-associated vascular injury and may therefore extend beyond accelerated epicardial atherosclerosis alone. Cardiac magnetic resonance (CMR) studies in GPA and the broader AAV population have identified myocardial abnormalities, including late gadolinium enhancement, inflammatory changes, and fibrotic remodeling, sometimes in patients without overt cardiac symptoms. However, these observations do not establish the prevalence, mechanisms, or prognostic significance of coronary microvascular dysfunction (CMD) specifically in GPA. Neutrophil-mediated inflammation, complement amplification, endothelial dysfunction, oxidative stress, and thromboinflammatory pathways are established components of AAV pathophysiology. Their potential contribution to coronary microvascular dysfunction, impaired myocardial perfusion, and subsequent myocardial remodeling in GPA is biologically plausible but remains insufficiently demonstrated in dedicated human studies. Accordingly, the proposed links between AAV-related vascular inflammation, repetitive low-grade ischemia, fibrosis, and arrhythmogenesis should currently be considered hypothesis-generating and partly extrapolated from experimental AAV models and the broader cardiovascular literature. Unlike previous publications addressing cardiovascular manifestations across the wider AAV spectrum, the present review adopts a GPA-specific and coronary microcirculation-centered perspective. It integrates available immunopathological and imaging evidence with contemporary CMD and ischemia with non-obstructive coronary arteries frameworks while distinguishing established observations from proposed mechanistic relationships. This review also discusses the potential roles of advanced cardiovascular imaging, individualized risk assessment, and targeted cardiovascular evaluation within an emerging immunocardiology framework. Prospective GPA-specific studies are needed to determine the clinical significance of CMD and establish whether targeted cardiovascular monitoring and cardioprotective strategies improve patient outcomes.