[Sportschosun Reporter Jang Jong-ho] The left atrial pathophysiology of patients with hypertrophic cardiomyopathy (HCM), a genetic heart disease affecting approximately one in every 200 to 500 adults, has been elucidated.
The patients were classified into stages 1 through 4 by combining two echocardiographic measures: left atrial pressure and contractile function. Patients in stage 4, who had the highest risk of atrial fibrillation, faced up to 7.4 times the risk of developing new-onset atrial fibrillation compared with those in stage 1, which had the lowest risk. The findings are expected to help establish atrial fibrillation surveillance strategies for patients with HCM.
A research team led by Jae-Hyun Lim and Hyeong-Kwan Kim, professors of cardiology at Seoul National University Hospital, conducted a joint study with In-Chang Hwang of Seoul National University Bundang Hospital and Sang-Chol Lee of Samsung Medical Center. The team followed 705 patients with HCM treated at Seoul National University Hospital and Samsung Medical Center from 2007 to 2024 for approximately 7.5 years, presenting a four-stage system based on left atrial pressure and contractile function and analyzing the risk of new-onset atrial fibrillation. The findings were announced on the 28th.
HCM is a disease in which the heart muscle becomes thickened and cannot relax properly. As diastolic dysfunction progresses, pressure in the left atrium rises, and the left atrium may become enlarged or fibrotic, potentially leading to atrial fibrillation. Atrial fibrillation is the most common sustained arrhythmia in patients with HCM and is an independent risk factor for stroke and death. In this study cohort, atrial fibrillation developed in 14.3% of patients, or 101 people, during the follow-up period.
Current clinical guidelines recommend monitoring high-risk patients for atrial fibrillation with electrocardiography and Holter monitoring every year or every two years. However, evidence for identifying which patients belong to the high-risk group has been limited. Left atrial size, the conventional measure, is a relatively late marker that reflects the cumulative effects of prolonged pressure overload. It does not adequately explain how the left atrium adapts to rising pressure or how its function deteriorates.
The research team therefore analyzed left atrial contractile function, measured by strain, together with left atrial pressure using echocardiography. Based on these measures, the team classified the functional and hemodynamic status of the left atrium into stages.
The staging system proposed by the research team classifies patients as follows: stage 1 (normal), when both left atrial pressure and contractile function are normal; stage 2 (hypercompensation), when left atrial contractile function is relatively enhanced to cope with rising left atrial pressure; stage 3 (functional impairment), when pressure is elevated, the compensatory increase in contraction has disappeared, and the left atrium begins to enlarge; and stage 4 (exhaustion), when pressure remains elevated and contractile function falls below the lower limit of normal. Separately, the team identified a group with isolated left atrial contractile dysfunction, in which pressure was normal but contractile function was impaired.
Among all patients, 18.6% were in stage 1, 40.6% in stage 2, 25.7% in stage 3, and 10.9% in stage 4. Each one-stage increase in left atrial stage was associated with a significant 1.83-fold increase in the risk of new-onset atrial fibrillation (adjusted hazard ratio, 1.83; 95% confidence interval, 1.42–2.37).
The 10-year cumulative incidence of new-onset atrial fibrillation rose with advancing stage, from 4.8% in stage 1 to 16.7% in stage 2, 23.9% in stage 3, and 49.1% in stage 4. Adding left atrial stage to the existing atrial fibrillation risk prediction models CHARGE-AF and the HCM-AF score also significantly improved their ability to predict the risk of atrial fibrillation over the following 10 years.
The findings were reproduced in an external validation analysis. Among 425 patients at Seoul National University Bundang Hospital, with a mean age of 59.7 years, each one-stage increase in left atrial stage was associated with a 1.82-fold increase in the risk of new-onset atrial fibrillation, consistent with the results from the Seoul National University Hospital and Samsung Medical Center cohort.
The risk of ischemic stroke, which may occur when atrial fibrillation develops in patients with HCM, also increased significantly by 1.81 times for each one-stage increase in left atrial stage (adjusted hazard ratio per stage, 1.81). In particular, the annual incidence of stroke among patients in stages 3 and 4 was approximately 1%.
In an additional analysis of 217 patients who underwent follow-up examinations four to six years after their first echocardiogram, the research team found that most patients either remained at their current stage or progressed to a higher stage. While 39.6% remained in the same stage, 43.8% progressed to a higher stage or developed atrial fibrillation, supporting the sequential progression of left atrial stages proposed by the team.
The research team explained that because the risk of atrial fibrillation differs clearly by stage, the system is expected to help develop personalized surveillance strategies based on risk. For example, surveillance intensity could be reduced somewhat for low-risk patients in stage 1, while high-risk patients in stage 4 could be monitored more closely.
Jae-Hyun Lim, a professor of cardiology at Seoul National University Hospital, said, "This study shows in four stages how the left atrium adapts to increased pressure and eventually reaches its limit. We plan to identify treatment windows that can slow disease progression at each stage and develop treatment strategies to prevent atrial fibrillation and stroke early in high-risk patients."
Hyeong-Kwan Kim, a professor of cardiology at Seoul National University Hospital, stated, "The left atrium has long been regarded only as a passive measure reflecting left ventricular function. Through this study, however, we confirmed that it is an active organ capable of adapting and eventually becoming exhausted on its own. Because staging based on this measure showed consistent value in predicting atrial fibrillation in two independent patient groups, we are considering ways to naturally incorporate left atrial staging into the echocardiographic interpretation process."
Meanwhile, the findings were published in the latest online edition of the Journal of the American College of Cardiology (JACC; impact factor, 22.3), the flagship journal of the American College of Cardiology.
Jang Jong-ho, Reporter
bellho@sportschosun.com
This article has been translated by GripLabs Mingo AI.
