Hypertrophic Cardiomyopathy Predicts Thromboembolism and Heart Failure in Patients With Nonvalvular Atrial Fibrillation　― A Prospective Analysis From the Hokuriku-Plus AF Registry ―

Abstract

Background: The prognostic effect of concomitant hypertrophic cardiomyopathy (HCM) on adverse events in patients with atrial fibrillation (AF) has not been evaluated in a multicenter prospective cohort study in Japan.

Methods and Results: Using the Hokuriku-Plus AF Registry, 1,396 patients with nonvalvular AF (1,018 men, 72.3±9.7 years old) were assessed prospectively; 72 (5.2%) had concomitant HCM. During a median follow-up of 5.0 years (interquartile range 3.5–5.3 years), 79 cases of thromboembolism (1.3 per 100 person-years) and 192 of heart failure (HF) (3.2 per 100 person-years) occurred. Kaplan-Meier analysis revealed that the HCM group had a significantly greater incidence of thromboembolism (P=0.002 by log-rank test) and HF (P<0.0001 by a log-rank test) than the non-HCM group. The Cox proportional hazards model demonstrated that persistent AF (adjusted hazard ratio 2.98, 95% confidence interval 1.56–6.21), the CHA₂DS₂-VASc score (1.35, 1.18–1.54), and concomitant HCM (2.48, 1.16–4.79) were significantly associated with thromboembolism. Conversely, concomitant HCM (2.81, 1.72–4.43), older age (1.07, 1.05–1.10), lower body mass index (0.95, 0.91–0.99), a history of HF (2.49, 1.77–3.52), and lower left ventricular ejection fraction (0.98, 0.97–0.99) were significantly associated with the development of HF.

Conclusions: Concomitant HCM predicts the incidence of thromboembolism and HF in AF patients.

Atrial fibrillation (AF) is a common arrhythmia associated with numerous adverse events, including cardiovascular death, heart failure (HF),¹ worsening renal function,² sudden cardiac death,³ and thromboembolism.⁴ AF is associated with a 5-fold relative risk of HF, a 2.3-fold risk of ischemic stroke, and a 1.5-fold risk of death.⁵ HF is a major cause of cardiovascular death in patients with AF.³ The prevention and management of thromboembolism in AF have been the primary focus of guidelines⁶ and clinical trials,^7,8 but limited data are available for predictors of HF onset in patients with AF.

Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease caused principally by sarcomere gene mutations,⁹ and can complicate existing AF.¹⁰ AF occurs in approximately 25% of patients with HCM, which is 4-fold more common than in the general population.^11–13 In addition, some degree of HF with preserved systolic function occurs in approximately 50% of patients with HCM.¹⁴ AF has been associated with an increased risk of death,¹¹ HF,^11,12 and thromboembolism^12,15 in several case–control and cohort studies of patients with HCM. HCM was reported as an independent predictor of thromboembolism in a retrospective cohort of patients with AF with a median follow-up of 2.4 years.¹⁵ In addition, a large retrospective cohort study from Western countries suggested that the presence of AF in patients with HCM was associated with worse outcomes.¹⁶ However, the prognostic effect of concomitant HCM on adverse events, including death, thromboembolism, bleeding, and HF, has not been evaluated using a prospective cohort design in Japan. Therefore, in this study we aimed to identify the predictors of thromboembolism and HF development and to evaluate the prognostic effect of HCM in a Japanese multicenter prospective cohort comprising patients with AF from the Hokuriku-Plus AF Registry.^2,15,17–19

Methods

Study Population

All the participants provided written informed consent. This study adhered to the principles outlined in the Declaration of Helsinki and was approved by the Ethics Committee for Medical Research of the Kanazawa University Graduate School of Medical Science (1394-4). The Hokuriku-Plus AF Registry is a multicenter population-based prospective cohort study that has been described previously.¹⁷ Briefly, 1,492 patients aged between 30 and 94 years were recruited from 19 institutions (3 cardiovascular centers, 15 affiliated/community hospitals, and 1 general practice) in Hokuriku and Yokohama. All patients with AF were treated by a cardiologist. Baseline enrollment was performed between January 2013 and May 2014, and follow-up examinations were conducted annually for 5 years. A total of 96 patients were excluded because of mitral stenosis and/or mechanical prosthetic valves. For evaluation, the remaining 1,396 patients with nonvalvular AF (NVAF) were divided into those with concomitant HCM (HCM group) and those without HCM (non-HCM group).

Risk Factor Definitions and Examination Data

The CHADS₂ and CHA₂DS₂-VASc stroke risk scores were recorded as the baseline stroke risk. The components of the CHADS₂ score were congestive HF (CHF), hypertension, age ≥75 years, diabetes mellitus, and stroke/transient ischemic attack (doubled); those of the CHA₂DS₂-VASc score were CHF, hypertension, age ≥75 years (doubled), diabetes mellitus, stroke/transient ischemic attack (doubled), vascular disease, age 65–74 years, and female. CHF was diagnosed if the patient had a history of hospitalization for HF, symptoms of HF (New York Heart Association functional class ≥2), or a left ventricular ejection fraction (LVEF) <40%. Diagnoses of hypertension, diabetes mellitus, and vascular disease were in accordance with the previous study.¹⁷ HCM was defined as a maximum left ventricular wall thickness ≥15 mm (≥13 mm in patients with a family history of HCM) measured using echocardiography or cardiac magnetic resonance imaging.²⁰ Persistent AF was defined as a sustained AF lasting >7 days. Anemia was defined as hemoglobin levels <13.0 g/dL in men and <12.0 g/dL in women. The prothrombin time (PT)-international normalized ratio (INR) and the time in therapeutic range (TTR) were measured to evaluate the intensity of anticoagulation by warfarin.²¹ The optimal intensity of anticoagulation for PT-INR was defined as 1.6–2.6 for older patients (≥70 years) and 2.0–3.0 for younger patients (<70 years).²² The estimated glomerular filtration rate was calculated using the modified diet renal disease study equation altered for the Japanese population: 194 × Cr^−1.094 × age^−0.287 (×0.739 for women).²³ Echocardiographic data were collected during entry into the registry.

Outcomes

The endpoint of this analysis was adverse events, including all-cause death, thromboembolism, major bleeding, and HF. Thromboembolism included ischemic or hemorrhagic strokes, transient ischemic attacks, and systemic embolism. Stroke was defined as the sudden onset of focal deficits lasting >24 h and was categorized as ischemic or hemorrhagic. Systemic embolism was defined as an acute vascular occlusion outside the brain. HF was defined as acute HF requiring additional medical therapy or hospitalization for treatment. Major bleeding events included intracranial hemorrhage, bleeding requiring transfusion, and bleeding with a >2 g/dL reduction in the hemoglobin level.

Statistical Analysis

Continuous variables are presented as the mean±standard deviation; categorical variables are presented as percentages. The continuous variables were compared using Student’s t-test for paired data, and the categorical variables were compared using Fisher’s exact test. The adjusted hazard ratios (HR) and corresponding 95% confidence intervals (CI) were calculated for each variable associated with adverse events by the Cox proportional hazards model. Differences in the cumulative ratio of adverse events were analyzed using Kaplan-Meier cumulative survival curves and compared using the log-rank test. Two-sided P values of <0.05 were considered statistically significant. All statistical analyses were performed using JMP Pro version 14 (SAS Institute; Cary, NC, USA) or EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface that adds biostatistical functions to the R software (The R Foundation for Statistical Computing; Vienna, Austria).²⁴

Results

Baseline Characteristics and Outcomes

The study prospectively evaluated the incidence of death, thromboembolism, major bleeding, and HF in 1,396 patients with NVAF (1,018 men, 72.3±9.7 years) for a median 5.0 years (interquartile range 3.5–5.3 years); 72 (5.2%) had concomitant HCM. Table 1 summarizes and compares the baseline characteristics between patients with and without HCM. In total, 63.0% of the patients had persistent AF with a CHA₂DS₂-VASc score of 3.24±1.74. The mean left atrial diameter and LVEF were 44.2 mm and 71.0%, respectively. In total, 86.0% of the patients were taking oral anticoagulants; 54.1% were taking warfarin, and 31.9% were taking a direct oral anticoagulant (DOAC: 14.3% dabigatran, 14.9% rivaroxaban, and 2.7% apixaban). Warfarin users demonstrated a TTR of 71.7%. In addition, 98 patients (7.0%) underwent catheter ablation for AF, and 58.7% were prescribed antiarrhythmia drugs. Compared with the non-HCM group, the HCM group had significantly more women, lower systolic blood pressure, more patients with a history of HF, and larger left atria. In addition, the HCM group received anticoagulant therapy frequently, particularly warfarin and antiarrhythmia drugs.

Table 1.

Baseline Characteristics of Entire Cohort, AF With HCM (HCM Group) and Without HCM (Non-HCM Group)

Variables	Entire cohort (n=1,396)	HCM group (n=72)	Non-HCM group (n=1,324)	P value
Age (years)	72.3±9.7	71.4±8.4	72.4±9.7	0.44
Male, n (%)	1,018 (72.9)	43 (59.7)	975 (73.6)	0.01
Heart rate (beats/min)	74.3±14.6	72.0±15.9	74.4±14.6	0.17
Systolic BP (mmHg)	125.5±17.4	121.2±16.9	125.7±17.4	0.03
Body mass index (kg/m2)	23.7±3.7	23.4±4.4	23.7±3.6	0.42
Persistent AF, n (%)	880 (63.0)	45 (62.5)	835 (63.1)	0.90
Prior heart failure, n (%)	443 (31.7)	31 (43.1)	412 (31.1)	0.04
Hypertension, n (%)	881 (63.1)	43 (59.7)	838 (63.3)	0.53
Diabetes mellitus, n (%)	382 (27.4)	23 (31.9)	359 (27.1)	0.42
Prior stroke or TIA, n (%)	186 (13.3)	9 (12.5)	177 (13.4)	1.00
Vascular disease, n (%)	300 (21.5)	9 (12.5)	291 (22.0)	0.06
CHADS2 score	1.93±1.30	1.99±1.33	1.93±1.30	0.72
CHA2DS2-VASc score	3.24±1.74	3.32±1.80	3.24±1.73	0.69
Anemia, n (%)	368 (26.4)	16 (22.2)	352 (26.6)	0.49
eGFR (mL/min/1.73 m2)	62.7±19.3	61.6±20.8	62.8±19.2	0.60
TTR (warfarin users; %)	71.7±19.9	76.3±15.5	71.3±20.1	0.09
Cancer	127 (9.1)	6 (8.3)	121 (9.1)	1.00
LA diameter (mm)	44.2±8.4	48.0±6.7	44.0±8.4	<0.0001
LVEF (%)	71.0±11.7	72.2±12.2	70.9±11.7	0.38
Any OAC, n (%)	1,200 (86.0)	69 (95.8)	1,131 (85.4)	0.009
Warfarin, n (%)	755 (54.1)	52 (72.2)	703 (53.1)	0.002
DOAC, n (%)	445 (31.9)	17 (23.6)	428 (32.3)	0.15
Catheter ablation, n (%)	98 (7.0)	5 (6.9)	93 (7.0)	1.00
Antiarrhythmia drugs, n (%)	819 (58.7)	53 (73.6)	766 (57.9)	0.01
Class I	301 (21.6)	16 (22.2)	285 (21.5)	0.88
Class II	431 (30.9)	29 (40.3)	402 (30.4)	0.09
Class III	33 (2.4)	7 (9.7)	26 (2.0)	0.001
Class IV	264 (18.9)	14 (19.4)	250 (18.9)	0.88

AF, atrial fibrillation; BNP, B-type natriuretic peptide; BP, blood pressure; DOAC, direct oral anticoagulant; eGFR, estimated glomerular filtration rate; HCM, hypertrophic cardiomyopathy; LA, left atrium; LVEF, left ventricular ejection fraction; OAC, oral anticoagulant; TIA, transient ischemic attack; TTR, time in therapeutic range.

During the median follow-up of 5.0 years, 165 patients died (2.7 per 100 person-years), 79 had a thromboembolism (1.3 per 100 person-years), 109 had major bleeding (1.8 per 100 person-years), and 192 had HF (3.2 per 100 person-years). Kaplan-Meier analysis of these adverse events found no significant difference between the HCM and non-HCM groups in the incidence of all-cause death and major bleeding (Figure 1A,C). However, the incidences of thromboembolism and HF (Figure 1B,D) were significantly greater in the HCM group than in the non-HCM group (adjusted HR 2.60, 95% CI 1.33–5.05, P=0.005 by Cox regression and P=0.004 by the log-rank test; HR 2.94, 95% CI 1.88–4.38, P<0.0001 by Cox regression and P<0.0001 by log-rank test, respectively). These results were similar in patients taking oral anticoagulants (Figure 2).

Figure 1.

Kaplan-Meier curves for the incidence of all-cause death (A), thromboembolism (B), major bleeding (C), and heart failure (D) in patients with atrial fibrillation with (red line) and without (black line) hypertrophic cardiomyopathy (HCM). CI, confidence interval.

Figure 2.

Kaplan-Meier curves for the incidence of all-cause death (A), thromboembolism (B), major bleeding (C), and heart failure (D) in patients with atrial fibrillation with (red line) and without (black line) hypertrophic cardiomyopathy (MCM) under anticoagulation therapy.

Predictors for Thromboembolism and HF

The Cox proportional hazards model was used to evaluate the predictors of the incidence of thromboembolism and HF. To predict thromboembolism, a multivariate Cox proportional hazards regression analysis was performed after adjusting for sex, persistent AF, vascular disease, HCM, left atrial diameter, CHADS₂ score (Model 1), and CHA₂DS₂-VASc score (Model 2). Model 1 suggested that persistent AF (HR 2.89, 95% CI 1.46–5.75), CHADS₂ score (HR 1.36, 95% CI 1.14–1.62), and concomitant HCM (HR 2.67, 95% CI 1.35–5.27) independently predicted the incidence of thromboembolism (Table 2). Model 2 suggested that persistent AF (HR 2.98, 95% CI 1.56–6.21), CHA₂DS₂-VASc score (HR 1.35, 95% CI 1.18–1.54), and concomitant HCM (HR 2.63, 95% CI 1.26–4.93) independently predicted the incidence of thromboembolism. Moreover, older age (HR 1.07, 95% CI 1.05–1.10), lower body mass index (BMI) (HR 0.95, 95% CI 0.91–0.99), prior HF (HR 2.49, 95% CI 1.77–3.52), concomitant HCM (HR 2.81, 95% CI 1.72–4.43), and lower LVEF (HR 0.98, 95% CI 0.97–0.99) independently predicted HF (Table 3). Thus, concomitant HCM was an independent predictor of the incidence of thromboembolism and HF in the AF cohort.

Table 2.

Cox Hazard Model Predictions of the Risk Factors for Thromboembolism in the Cohort

Variables	Univariate analysis		Multivariate analysis (Model 1)		Multivariate analysis (Model 2)
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
Age (years)	1.03 (1.01–1.06)	0.01
Male	0.83 (0.52–1.35)	0.44	0.75 (0.45–1.29)	0.31
Heart rate (beats/min)	1.00 (0.99–1.02)	0.65
Systolic BP (mmHg)	1.00 (0.99–1.02)	0.55
Body mass index (kg/m2)	1.01 (0.95–1.07)	0.88
Persistent AF	3.50 (1.99–6.83)	<0.0001	2.89 (1.46–5.75)	0.001	2.98 (1.56–6.21)	0.001
Prior heart failure	1.77 (1.12–2.76)	0.01
Hypertension	1.53 (0.95–2.56)	0.08
Diabetes mellitus	1.41 (0.87–2.22)	0.16
Prior stroke or TIA	1.80 (1.41–2.27)	<0.0001
Vascular disease	1.89 (1.15–3.00)	0.01	1.66 (0.98–2.81)	0.07
CHADS2 score	1.50 (1.28–1.75)	<0.0001	1.36 (1.14–1.62)	0.001
CHA2DS2-VASc score	1.40 (1.24–1.58)	<0.0001			1.35 (1.18–1.54)	<0.0001
Anemia	1.18 (0.69–1.91)	0.53
Serum creatinine level	1.17 (0.82–1.45)	0.32
HCM	2.60 (1.33–5.05)	0.005	2.67 (1.35–5.27)	0.01	2.63 (1.26–4.93)	0.01
LA diameter (mm)	1.05 (1.02–1.07)	0.0003	1.01 (0.99–1.04)	0.33	1.01 (0.98–1.04)	0.38
LVEF (%)	1.01 (0.99–1.03)	0.46
Catheter ablation	0.46 (0.14–1.46)	0.19
No OAC	0.88 (0.67–1.10)	0.29

CI, confidence interval; HR, hazard ratio. Other abbreviations as in Table 1.

Table 3.

Cox Hazard Model Predictions of the Risk Factors for Heart Failure in the Cohort

Variables	Univariate analysis		Multivariate analysis
	HR (95% CI)	P value	HR (95% CI)	P value
Age (years)	1.09 (1.07–1.11)	<0.0001	1.07 (1.05–1.10)	<0.0001
Male	0.70 (0.52–0.95)	0.02	0.98 (0.69–1.39)	0.94
Heart rate (beats/min)	1.01 (1.00–1.02)	0.21
Systolic BP (mmHg)	0.98 (0.98–0.99)	0.0003	1.00 (0.99–1.01)	0.17
Body mass index (kg/m2)	0.91 (0.88–0.95)	<0.0001	0.95 (0.91–0.99)	0.01
Persistent AF	1.44 (1.06–1.98)	0.02	0.83 (0.58–1.23)	0.36
Prior heart failure	3.72 (2.79–4.97)	<0.0001	2.49 (1.77–3.52)	<0.0001
Hypertension	1.09 (0.82–1.48)	0.55
Diabetes mellitus	1.08 (0.79–1.47)	0.62
Prior Stroke or TIA	1.14 (0.94–1.38)	0.19
Vascular disease	1.58 (1.14–2.15)	0.006	0.99 (0.68–1.42)	0.94
Anemia	2.67 (2.00–3.55)	<0.0001	1.27 (0.90–1.79)	0.17
Serum creatinine level	1.39 (1.21–1.56)	<0.0001	1.19 (0.98–1.38)	0.07
HCM	2.94 (1.88–4.38)	<0.0001	2.81 (1.72–4.43)	<0.0001
LA diameter (mm)	1.04 (1.03–1.06)	<0.0001	1.02 (0.99–1.04)	0.05
LVEF (%)	0.97 (0.97–0.99)	<0.0001	0.98 (0.97–0.99)	0.001
Catheter ablation	0.58 (0.28–1.07)	0.08
Antiarrhythmia drugs	0.91 (0.69–1.22)	0.54

CI, confidence interval; HR, hazard ratio. Other abbreviations as in Table 1.

Predictors for Thromboembolism and HF in NVAF With HCM

The baseline characteristics of AF with HCM with or without OAC are shown in Supplementary Table 1. Compared with the HCM with OAC group, the HCM without OAC group tended to be younger, and have more paroxysmal types, and lower CHADS₂ scores. Of the 72 patients with NVAF and HCM, 10 experienced thromboembolism (3.1 per 100 person-years) and 25 had HF (7.7 per 100 person-years) during the follow-up period. All patients with thromboembolism received anticoagulant therapy (8 patients were prescribed warfarin, and 2 were prescribed DOACs). No significant difference was found in the TTR level between warfarin users with NVAF and thromboembolism and those without thromboembolism (73±14% vs. 77±16%, P=0.49). Two DOAC users with thromboembolism received appropriate doses of DOACs. We also evaluated the maximal wall thickness in patients with HCM with thromboembolism or HF as events and those without these events; there was no significant difference between them (16.1±2.5 mm vs. 17.4±1.7 mm for thromboembolism, 16.3±2.3 mm vs. 16.3±2.9 mm for HF, respectively). In addition, the predictors of thromboembolism and HF were evaluated in patients with NVAF and HCM using the Cox hazard model (Supplementary Tables 2,3). The CHADS₂ and CHA₂DS₂-VASc scores were not useful for predicting thromboembolism in patients with HCM and AF. In patients with NVAF and HCM, persistent AF (HR 6.15, 95% CI 1.15–113.5) and prior HF (HR 3.97, 95% CI 0.09–18.5) independently predicted thromboembolism. Lower LVEF at baseline (HR 0.96, 95% CI 0.92–0.98) independently predicted HF in patients with AF and HCM. In contrast, the maximal wall thickness was not associated with the occurrence of thromboembolism or HF.

Discussion

Major Findings

In this Japanese multicenter prospective study of patients with AF the major findings were: (1) HCM occurred in 5.2% (72/1396) of the patients with NVAF, and thromboembolism and HF were more frequent in the HCM group than in the non-HCM group; (2) concomitant HCM was an independent predictor of thromboembolism and HF.

Prevalence of HCM in Patients With NVAF

AF is the most common sustained arrhythmia in HCM, and several studies of HCM have reported that approximately 25–34% of the patients had documented AF.^11–13,25 AF with HCM is associated with adverse events, including HCM-related death, HF, and thromboembolism.^11–13 However, prospective cohort studies of patients with NVAF have reported limited data on the prevalence of HCM and the risk factors for these adverse events. A study using the Korean National Health Insurance Service database demonstrated that the overall HCM prevalence was 1.1% in patients with NVAF, and the incidence of ischemic stroke was significantly greater in patients with NVAF and HCM than in those without HCM.²⁶ In the Hokuriku-Plus AF Registry, the overall HCM prevalence was 5.2%, which was relatively high compared with other AF registries. Actually, 53% of all HCM patients in this study were registered from 3 cardiovascular centers that examine many AF patients with structural heart disease. This selection bias may be one of the possible reasons for the high prevalence of HCM in our registry. In addition to the prevalence and associated stroke risk of HCM in patients with NVAF, we evaluated the association between HCM and the development of HF.

Risk of Thromboembolism in NVAF

In the Japanese Circulation Society guideline,⁶ “cardiomyopathy” is listed as 1 of the “other risks” for thromboembolism in patients with NVAF when considering anticoagulant therapy. A meta-analysis of HCM cohort studies found that the prevalence of AF in HCM was 22.5%, and the incidence of thromboembolism was 3.8 per 100 person-years.¹³ In a retrospective AF cohort, HCM was associated with thromboembolism.¹⁵ An increased relative wall thickness measured by echocardiography is a risk factor for thromboembolism,²⁷ suggesting that ventricular hypertrophy is associated with an increased risk of thromboembolism. In addition, the coagulation system is often activated in patients with cardiomyopathy.²⁸ Taken together, concomitant HCM is an independent predictor of thromboembolism in patients with NVAF. Western guidelines²⁹ recommend anticoagulant therapy regardless of the CHA₂DS₂-VASc score in patients with HCM and AF. In this study, all patients with thromboembolism in the HCM group received anticoagulation therapy, suggesting 71.3±14.3% TTR in warfarin users and no off-label DOAC users. Thus, preventing thromboembolism using appropriate anticoagulant therapy was difficult in these HCM patients with AF. Prevention of thromboembolism in patients with AF without anticoagulant therapy, including use of a left atrial appendage (LAA) closure device³⁰ or LAA surgical closure,³¹ may be a favorable strategy for this high-risk population. Further studies are required to investigate the effectiveness of the LAA closure strategy for thromboembolism prevention in patients with HCM and AF.

Risk of HF in NVAF

AF and HF are highly prevalent diseases that frequently occur together and lead to poor prognoses.¹ They also share a common risk profile with several coinciding cardiovascular risk factors, promoting the odds of developing both diseases separately.³² HF, not stroke or bleeding, is the most common non-fatal adverse event in patients with AF.³³ In addition, the onset of HF is a major cause of cardiovascular death in such patients.³

In the Framingham Heart Study,³⁴ the well-established risk factors associated with HF in the general population independently predicted HF in patients with AF. Consistent with those results, the present study confirmed that older age, lower BMI, a history of HF, and lower LVEF are independent predictors of HF among patients with AF.

Our findings add HCM to the list of known risk factors for HF in AF cohorts. AF is often poorly tolerated in patients with HCM because of severe diastolic dysfunction and shortened diastolic filling time during tachycardia, leading to elevated left atrial pressure and decreased cardiac output.²⁰ Miyamoto et al reported on the importance of AF for predicting the onset of HF in the Japanese HCM cohort.³⁵ Furthermore, less fractional shortening predicted HF, similar to our results. Regarding HF as a major cause of death in patients with AF,³ restoring sinus rhythm and preventing AF recurrence with antiarrhythmia drugs or catheter ablation may be a reasonable strategy to improve the clinical course of AF with HCM. Rowin et al reported that successfully treated AF was not a major contributor to HF morbidity or sudden arrhythmic death in patients with HCM and AF.³⁶ However, Zhao et al reported that a single ablation procedure is insufficient to achieve freedom from AF in patients with HCM because of the high recurrence rate of AF after catheter ablation.³⁷ Therefore, multiple ablation procedures and frequent additional antiarrhythmia drug therapy were required to maintain sinus rhythm. Further investigation is required to improve the success rate of rhythm control management in patients with HCM and AF.

Study Limitations

First, the study had a relatively small sample size compared with other AF studies. Second, our registry did not evaluate polypharmacy, frailty, or multimorbidity, possibly affecting the clinical course of patients with AF. Third, because our registry enrolled patients with AF from January 2013 to May 2014, edoxaban was not among the DOACs used at baseline. Fourth, catheter ablation was performed in only 7% of the patients with AF at baseline; therefore, the effect of catheter ablation performed during the follow-up could not be evaluated. Fifth, because the diagnosis of HCM was dependent on the degree of LV hypertrophy, it is possible that other cardiac diseases that exhibit LV hypertrophy, such as cardiac amyloidosis, Fabry disease, and hypertensive heart disease, were included in the HCM group. Finally, the study did not assess medical therapy for HF, which might have affected the incidence of cardiovascular events.

Conclusions

Concomitant HCM accurately predicted the incidence of thromboembolism and HF in a multicenter prospective cohort of Japanese patients with nonvalvular AF.

Acknowledgments

The authors thank the centers that participated in this study and the patients who provided consent for the use of their data. The participating institutions and physicians in the Hokuriku-Plus AF Registry are listed in the Supplementary Appendix. We also thank Editage (www.editage.com) for English language editing.

Funding

The Hokuriku-plus AF Registry was partially supported by the Japan Agency for Medical Research and Development (AMED) under grant number JP17ek0210082 (K.H.) and a Grant-in-Aid for Early-Career Scientists under grant number 21K16052 (T.T.).

Disclosures

The authors declare that there are no conflicts of interest.

IRB Information

The Hokuriku-Plus AF Registry was approved by the Ethics Committee for Medical Research of Kanazawa University Graduate School of Medical Science (1394-4) and by the participating hospitals.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circj.CJ-23-0418

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