Prediction of Thromboembolism in Patients With Hypertrophic Cardiomyopathy
論文ID: CJ-20-0250
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論文ID: CJ-20-0250
Hypertrophic cardiomyopathy (HCM) is associated with a high incidence of cerebrovascular disease, transient cerebral ischemic attacks, and peripheral embolism, and therefore, high rates of morbidity and mortality.1 In a community-based Japanese patient cohort, the 5-year embolic event rate was 5.5% and thromboembolic events were not rare in patients with HCM.2 Atrial fibrillation (AF) is one of the most common arrhythmias in HCM. A recent meta-analysis reported that the prevalence of AF in HCM was 22.5% and the incidence of thromboembolism in HCM patients with AF was 27.1%.3 Furthermore, the incidence of thromboembolism in HCM patients with AF is 3.8%, and age and left atrial enlargement are considered as risk factors for its incidence.
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According to the American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines, as well as Japanese Circulation Society guidelines,4,5 anticoagulation with vitamin K antagonists is recommended for HCM patients with AF, regardless of the CHADS2 or CHA2DS2-VASc score (recommended as Class I). On the other hand, in HCM patients without AF, it is unclear whether anticoagulant therapy should be initiated. In fact, 9% (39/431 cases) of HCM patients without AF can experience cerebrovascular disease.6 Moreover, age and left atrial enlargement (≥48 mm) are reported as significant risk factors for cerebrovascular events in patients without AF.6 Therefore, the decision on anticoagulation in HCM patients without AF is a tough but extremely important challenge in the clinical setting.
In this issue of the Journal, Hohneck et al7 report that the extent of late gadolinium enhancement (LGE) on contrast-enhanced cardiac magnetic resonance (CMR) imaging was a predictor of thromboembolic events, independently of AF, in HCM patients. Moreover, they propose a cutoff level of LGE >14.4% for predicting thrombotic events. These results grab our attention about LGE on CMR imaging as a novel predictor for thromboembolism in HCM patients. According to the Kaplan-Meier survival curves in this study,7 the group with absence of AF and LGE >14% and the group with presence of AF and LGE ≤14% appeared to have approximately similar risks of thromboembolism. This finding suggests that antithrombotic therapy should be initiated in HCM patients with LGE >14%, as followed for AF patients, even if the patients do not have AF.
However, in this study, the thromboembolic event group had significantly higher New York Heart Association (NYHA) functional class, lower left ventricular ejection fraction (LVEF), higher prevalence of AF before CMR imaging, and a higher usage rate of amiodarone.7 Furthermore, reduced LVEF or increased pressure gradient in the left ventricular outflow tract are associated with the prevalence of AF, and with HCM-related deaths including stroke.8,9 Morphological abnormalities of the left ventricle such as apical ballooning might also be associated with a high prevalence of thrombus formation.10 On the other hand, the risk of systemic embolism in HCM patients is associated with AF, not with the severity of symptoms.11 Because the effects of such confounding factors have not been completely ruled out, further investigations based on improved methodologies are needed.
The mechanisms underlying the association between the development of thromboembolism and left ventricular LGE, which may reflect myocardial fibrosis, are also noteworthy (Figure). Besides the possibility that transient AF may not be accurately identified, a hypothetical mechanism is that HCM is a cardiomyopathy (atrial myopathy) that affects not only the ventricles but also the atria.12 Atrial cardiomyopathy is considered to beget thrombus formation even in the absence of atrial rhythm disorders such as AF. The extent of LGE may be a potential predictor of thromboembolism by reflecting HCM stage progression. Another hypothetical mechanism of embolism is thrombus formation in an impaired ventricle. The comprehensive mechanism by which blood clots form in the left ventricle in cardiomyopathy has not been established. Causes of intracardiac thrombus formation include stagnation of blood flow because of reduced intraventricular blood flow velocity and enhancement of the coagulation system by blood viscosity, blood cell morphology, and inflammation.13,14 Hamada reported that reduced active blood aspiration from the left atrium in the region of impaired left ventricular myocardium may cause the formation of left ventricular thrombus.15
Hypothetical mechanism by which thromboembolic events occur in hypertrophic cardiomyopathy. AF, atrial fibrillation; LA, left atrial; LGE, late gadolinium enhancement; LV, left ventricular; LVEF, LV ejection fraction; LVOT, LV outflow tract.
Optimal management of HCM includes risk assessment and appropriate prevention of thromboembolic events. In patients with HCM, we should assess potential thromboembolic risk factors such as age, left atrial enlargement, reduced LVEF, pressure gradient in the left ventricular outflow tract, and extent of LGE, even in the absence of AF. Furthermore, we need to consider the risk of bleeding and carefully make a clinical decision on anticoagulant therapy.
T.M. is a member of Circulation Journal ’ Editorial Team. T.O. received research grants from Ono Yakuhin, Bayer, Daiichi-Sankyo, Amgen, and Astellas (outside the submitted work) and lecture fees from Ono Yakuhin, Novartis, Otsuka, and Medtronic. T.M. received unrestricted research grants for the Department of Cardiology, Nagoya University Graduate School of Medicine from Astellas, Daiichi-Sankyo, Dainippon Sumitomo, Kowa, MSD, Mitsubishi Tanabe, Boehringer Ingelheim, Novartis, Otsuka, Pfizer, Sanofi-Aventis, Takeda, and Teijin, as well as lecture fees from Bayer, Daiichi-Sankyo, Dainippon Sumitomo, Kowa, MSD, Mitsubishi Tanabe, Boehringer Ingelheim, Novartis, Pfizer, Sanofi-Aventis, Takeda, Astellas, Otsuka, and Teijin.
