Purpose: To review the available information about cardiac disease in relation to the immunogenetic marker HLA-B27 and the inflammatory disorders associated with it (seronegative spondyloarthropathies). Data Sources: English-language clinical studies, case reports, and reviews published in 1995 or earlier were identified from a search of the MEDLINE database. These papers, textbooks, and other bibliographic sources were used to identify other relevant publications, enabling collection of references from 1936 through 1995 in a stepwise manner. Study Selection: Clinical studies, case reports, and topical reviews on the HLA-B27 histocompatibility locus, seronegative spondyloarthropathies, and cardiac disease were selected. Data Extraction: information from systematic or hypothesis-driven studies, including those showing clinically and statistically meaningful associations between disorders, and additional relevant information from case reports and reviews is presented. Data Synthesis: Immunogenetic, histopathologic, clinical and electrophysiologic evidence was examined to explore the concept of HLA-B27-associated cardiac disease. Results: Relative to the general population (in which the frequency is 6% to 8%), men (but not women) with pacemakers have a significantly increased frequency of HLA-B27. Furthermore, a cardiac syndrome that consists of severe conduction system abnormalities plus aortic regurgitation is associated with HLA-B27, which was present in 67% to 88% of the patients with both of these clinical findings. This proportion of HLA-B27 is similar to that found in patients with ankylosing spondylitis and Reiter disease. Cardiac and aortic tissue both show intimal proliferation of small arteries (obliterative endarteritis) and fibrosis, as seen in tissues adjacent to afflicted joints. Both cardiac conduction abnormalities and aortic regurgitation occur in patients with Various HLA-B27-related extracardiac disorders, regardless of the severity of the latter; in about 50% of patients with these cardiac findings, a diagnosis of an HLA-B27-related rheumatic disease has not previously been made. Third-degree (complete) atrioventricular block related to HLA-B27 is located within the atrioventricular node in 95% rather than the expected 20% of cases. Conclusions: The heart and the joints are both of major importance as targets for the HLA-B27-associated disease process. HLA-B27-related cardiac lesions may be found in the absence of other rheumatologic manifestations. Furthermore, a genetically linked cardiac syndrome has been defined: the combination of conduction system abnormalities and aortic regurgitation.
