Letters to the Editor [5] Maron BJ, Towbin JA, Thiene G, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006;113:1807–16. [6] Funabashi N, Asano M, Komuro I. Predictors of non-calcified plaques in the coronary arteries of 242 subjects using multislice computed tomography and logistic regression models. Int J Cardiol 2007;117:191–7. [7] Uehara M, Takaoka H, Kobayashi Y, Funabashi N. Diagnostic accuracy of 320-slice computed-tomography for detection of significant coronary artery stenosis in patients with various heart rates and heart rhythms compared with conventional coronary-angiography. Int J Cardiol 2013;167:809–15.

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[8] Takaoka H, Funabashi N, Uehara M, Fujimoto Y, Kobayashi Y. Diagnostic accuracy of coronary 320 slice CT angiography using retrospective electrocardiogram gated acquisition compared with virtual prospective electrocardiogram gated acquisition with and without padding. Int J Cardiol 2013;168:2811–5. [9] Uehara M, Funabashi N, Takaoka H, Fujimoto Y, Kuroda N, Kobayashi Y. Detection of luminal stenosis by 320-slice CT in coronary arteries with cross sectional area less than 4 mm2 confirmed by intravascular ultrasound compared with conventional coronary angiography. Int J Cardiol 2013;168:5457–60. [10] Uehara M, Funabashi N, Takaoka H, Fujimoto Y, Kobayashi Y. False-positive findings in 320-slice cardiac CT for detection of severe coronary stenosis in comparison with invasive coronary angiography indicate poor prognosis for occurrence of MACE. Int J Cardiol 2014;172:235–7. [11] Stevenson WG. Ventricular scars and ventricular tachycardia. Trans Am Clin Climatol Assoc 2009;120:403–12.

0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2014.06.070

Clinical characteristics and CHADS2 score in patients with heart failure and atrial fibrillation: Insights from the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) Sanae Hamaguchi a,b, Shintaro Kinugawa a, Shouji Matsushima a, Arata Fukushima a, Takashi Yokota a, Mamoru Sakakibara a, Hisashi Yokoshiki a, Miyuki Tsuchihashi-Makaya c, Hiroyuki Tsutsui a,⁎, for the JCARE-CARD Investigators a b c

Department of Cardiovascular Medicine, Hokkaido University, Graduate School of Medicine, Sapporo 060-8638, Japan Department of Cardiovascular Medicine, Social Welfare Corporation, Hokkaido Social Work Association Obihiro Hospital, Obihiro 080-0805, Japan School of Nursing, Kitasato University, Sagamihara 252-0373, Japan

a r t i c l e

i n f o

Article history: Received 28 April 2014 Accepted 28 June 2014 Available online 5 July 2014 Keywords: Heart failure Atrial fibrillation Stroke Anticoagulant Warfarin

CHADS2 score, which estimates thromboembolic risk in patients with nonvalvular atrial fibrillation (AF), is widely used in clinical practice to help the choice of anticoagulation [1]. However, the clinical characteristics and stroke risk in heart failure (HF) patients associated with AF are poorly defined. Several analyses using the data from the registry and contemporary clinical trials have described this information in AF patients associated with clinical HF and reduced left ventricular ejection fraction (LVEF) [2–6]. To examine the relationship between clinical HF and CHADS2 score, we analyzed the data from the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARECARD), a prospective database of the clinical characteristics and treatment in a broad sample of patients hospitalized with worsening HF in Japan [7–10]. The JCARE-CARD enrolled a total of 2675 patients hospitalized for HF. The diagnosis of AF was based on a 12-lead standard ECG performed at the time of inclusion in the study and a total of 937

⁎ Corresponding author at: Department of Cardiovascular Medicine, Hokkaido University, Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan. Tel.: + 81 11 706 6970; fax: +81 11 706 7874. E-mail address: [email protected] (H. Tsutsui).

patients (35.2%) had AF [8]. We excluded 397 patients with valvular heart disease as a cause of HF, 64 patients with missing LVEF data, and 4 patients with missing information regarding the valvular lesion from the analysis, resulting in 472 patients included in this analysis. CHADS2 score was calculated by adding 1 point for each of the following conditions: congestive HF, hypertension, age ≥75 years or diabetes mellitus, and 2 points for prior stroke [1]. CHADS2 scores in the studied patients from JCARE-CARD were compared with the reported values in HF subgroups from Euro Heart Survey on AF [2] and the clinical trials including the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) [3], the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) [5], the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) [4], and the Rivaroxaban Once daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) [6]. The characteristics of 472 HF patients with AF are shown in Table 1. The mean age was 70.9 years old and 29% were women. HF etiology was ischemic in 24.2%, hypertensive in 24.6%, and dilated cardiomyopathy in 28.0%. New York Heart Association (NYHA) functional class was I and II in almost all patients at discharge (35.9 and 56.1%, respectively). The mean LVEF was 42.0 ± 17.3%. These findings were largely similar to those from previous AF observational registries such as Euro Heart Survey and contemporary clinical trials including AFFIRM, RE-LY, ARISTOTLE, and ROCKET AF [2–6] (Table 1). Compared to previous data, the unique features in study patients in JCARE-CARD were lower body mass index (22 kg/m2 vs 28–29 kg/m2) and lower prevalence of ischemic heart disease as a cause of HF (24% vs 32–58%). As for other CHADS2 stroke risk factors, the prevalence of hypertension was lower in our study patients (50% vs 67–93%). In contrast, age (68–70 years old) and the prevalence of other factors such as diabetes mellitus (24–29%) and prior stroke (13– 19%) were similar to other studies such as Euro Heart Survey, AFFIRM, RE-LY, and ARISTOTLE [2–5]. As expected, patients enrolled in ROCKET

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Table 1 Characteristics of patients with HF and AF from JCARE-CARD, Euro Heart Survey on AF, RE-LY, ARISTOTLE, and ROCKET AF. Characteristics

Demographic Age, yrs (mean ± SD) Age, yrs (median, 25th–75th) Age ≥75 years, % Female, % Body mass index, kg/m2 Body mass index (median, 25th–75th) Causes of heart failure, % Ischemic Hypertensive Dilated cardiomyopathy Valvular heart disease Congenital heart disease Others Unknown Medical history, % Hypertension Diabetes mellitus Prior stroke COPD Smoking Prior myocardial infarction Sustained VT/VF Procedures, % PCI CABG PPM CRT ICD Vital signs NYHA functional class, % I II III IV Heart rate, bpm SBP, mm Hg SBP, mm Hg (median, 25th, 75th) DBP, mm Hg DBP, mm Hg (median, 25th, 75th) Echocardiographic parameters LVEF, % LVEF, % (median, 25th–75th) LVEF b 40%, % Medications, % ACE inhibitor ARB ACE inhibitor or ARB β blocker Diuretics Aldosterone antagonist Digitalis Ca channel blocker Aspirin Other antiplatelet Warfarin Statin CHADS 2 score 1, % 2, % ≥3, %

JCARE-CARD

Euro Heart Survey

AFFIRM

RE-LY

ARISTOTLE

ROCKET AF

n = 472

n = 1816

n = 722

n = 4904

n = 5943

n = 9033

LVEF ≤ 40%

LVEF N 40%

n = 2736

n = 3207

70.9 ± 12.3 72 (62–80) 43.4 29.0 22.8 ± 4.1 22.2 (20.0–25.0)

69 ± 12 NA NA 44 28 ± 6 NA

69.6 ± 9 NA NA 37 29.6 ± 6.6 NA

68.3 ± 10.2 NA NA 33.1 NA NA

NA 68 (60–74) 24.4 32.6 NA 28.1 (24.7–32.0)

24.2 24.6 28.0 0.0 2.5 15.3 23.7

45 NA NA 40 2

58 NA NA NA NA

31.8 NA NA 26.2 NA

45.6 NA NA NA NA

NA NA NA NA NA

50.2 25.7 18.7 6.5 42.0 18.9 7.8

67 24 13 20 NA 25 7

74 29 NA NA 17 32 NA

75.2 26.5 17.1 NA NA NA NA

82.6 26.0 16.7 NA 9.5 22.5 NA

93 42.4 42.6 12.4 NA 21.6 NA

11.1 7.2 0.4 2.9 2.9

7 8 8 NA 2

11 21 8 NA NA

NA NA NA NA NA

10.6 8.8 NA 1.5 4.2

NA 8.1 NA NA 3.6

21.2 56.3 21.5 0.9 NA NA 126 (114–138) NA 80 (70–85)

13.5 56.6 28.4 1.5 NA NA 130 (120–140) NA NA

35.9 56.1 5.4 2.6 69.7 ± 11.9 115.6 ± 16.7 112 (102–124) 66.5 ± 11.1 66 (60–74)

74 (II or III)

31.8

94 ± 29 NA NA NA NA

NA NA NA NA NA

0 74.4 23.2 2.4 76.1 ± 15.2 127.4 ± 17.3 NA 76.6 ± 10.7 NA

42.0 ± 17.3 40.0 (28.7–55.0) 49.4

47 ± 15 NA NA

NA NA NA

NA NA 43.5

NA 35 (30–39) NA

37.3 44.6 77.7 54.5 89.2 41.7 48.3 25.6 40.6 9.3 70.6 16.3 2.56 ± 1.27 23 31 46

64 12 75 50 82 NA 43 NA 33 (antiplatelets)

65 NA NA 40 81 NA 71 35 27 NA 90 NA 2.60 ± 1.06 NA NA NA

57.3 22.0 NA 68.5 72.8 NA NA NA NA NA – NA 2.6 ± 1.1 12 38 49

NA NA 78.7 71.4 71.1 1.8 43.0 21.5 33.0 2.1 – 40.2 2.22 ± 1.20 18 40 41

68 24 NA ~15 ~40 ~45

69 (61–75)

29.3 (25.8–33.5)

130 (120–140) 80 (71–88)

56 (50–62)

2.67 ± 1.08

NA 72 (65–78) NA 39.1 NA 28.7 (25.5-32.5)

NA NA 33.9 60.9 NA NA 69.6 70.9 NA 44.9 NA 31.0 NA – NA 3.7 ± 0.9 0 7 94

COPD = chronic obstructive pulmonary disease; VT/VF = ventricular tachycardia/fibrillation; PCI = percutaneous coronary intervention; CABG = coronary artery bypass grafting; PPM = permanent pacemaker; CRT = cardiac resynchronization therapy; ICD = implantable cardiac defibrillator; NYHA = New York Heart Association; SBP = systolic blood pressure; DBP = diastolic blood pressure; LVEF = left ventricular ejection fraction; ACE = angiotensin converting enzyme; ARB = angiotensin II receptor blocker; and NA = not available. Data are shown as percent, means ± SD or median.

AF had higher prevalence of hypertension (93%), diabetes mellitus (42%) and prior stroke (43%) [6]. Importantly, LVEF values measured by echocardiography were similar among the studies. Medication use including ACE inhibitor or angiotensin II receptor blocker, β-blocker,

diuretics, digitalis, and Ca channel blocker was almost similar among studies (Table 1). Warfarin was used in 70.6% of patients and aspirin in 40.6% in the JCARE-CARD and these values were also similar to those in Euro Heart Survey (68% and 33%).

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241

Table 2 Comparison of characteristics of patients with HF and AF from JCARE-CARD according to CHADS2 scores. Characteristics

Demographic Age, yrs (mean ± SD) Age, yrs (median, 25th–75th) Female, % Body mass index, kg/m2 Body mass index, kg/m2 (median, 25th–75th) Causes of heart failure, % Ischemic Hypertensive Dilated cardiomyopathy Congenital heart disease Others Unknown Medical history, % Hypertension Diabetes mellitus Hyperlipidemia Prior stroke COPD Smoking Prior myocardial infarction Sustained VT/VF Procedures, % PCI CABG PPM CRT ICD Vital signs NYHA functional class, % I II III IV Heart rate, bpm SBP, mm Hg SBP, mm Hg (median, 25th–75th) DBP, mm Hg DBP, mm Hg (median, 25th–75th) Laboratory data eGFR, mL/min/1.73 m2 Serum uric acid (mg/dL) Hemoglobin, g/dL Plasma BNP, pg/mL Echocardiographic parameters LV EDD, mm LV ESD, mm LVEF, % LVEF, % (median, 25th–75th) LVEF b 40%, % Medications, % ACE inhibitor ARB ACE inhibitor or ARB β blocker Diuretics Aldosterone antagonist Digitalis Ca channel blocker Nitrates Antiarrhythmic Aspirin Other antiplatelet Warfarin Statin

CHADS2 score

P value

1

2

≥3

n = 105

n = 145

n = 212

61.0 ± 10.8 63 (55–70) 18.1 22.8 ± 3.3 22.8 (20.3–25.0)

71.2 ± 11.7 72 (63–80) 21.4 22.8 ± 4.3 22.0 (19.7–25.2)

75.3 ± 10.4 77 (69–82) 39.2 22.9 ± 4.4 22.2 (19.7–25.3)

b 0.001

11.4 0.0 44.8 4.8 20.0 25.7

23.4 20.0 31.0 1.4 15.9 26.9

31.1 39.6 17.9 1.9 11.8 21.7

0.001 b 0.001 b 0.001 0.182 0.145 0.490

0.0 0.0 11.4 0.0 2.9 45.8 9.5 8.1

40.0 18.6 18.1 0.0 7.0 45.9 18.6 8.0

81.1 43.4 26.1 40.6 8.1 38.6 23.8 7.8

b 0.001 b 0.001 0.007 b 0.001 0.211 0.311 0.010 0.997

6.7 4.8 0.0 5.8 5.8

13.8 9.7 1.4 1.4 2.8

11.9 6.6 0.0 2.5 1.5

0.209 0.306 0.111 0.114 0.104

37.1 55.2 4.8 2.9 72.4 ± 14.5 107.6 ± 15.8 106 (98–120) 64.1 ± 13.4 64 (56–72)

33.3 58.3 6.9 1.4 69.5 ± 12.4 113.1 ± 15.4 110 (100–121) 66.4 ± 10.9 64 (60–74)

38.2 55.1 3.9 2.9 69.8 ± 11.5 118.1 ± 16.8 118 (106–130) 67.2 ± 10.9 68 (60–74)

0.773

57.6 ± 24.8 7.6 ± 2.3 13.5 ± 2.5 317 ± 286

53.8 ± 19.7 7.6 ± 2.0 13.2 ± 2.5 348 ± 334

51.6 ± 22.7 7.8 ± 4.9 12.4 ± 2.3 343 ± 296

59.1 ± 10.7 48.9 ± 12.5 35.7 ± 16.0 33.0 (24.0–45.5) 63.8

55.7 ± 9.5 43.7 ± 11.8 40.8 ± 16.7 37.0 (28.0–51.0) 54.5

53.2 ± 10.9 40.2 ± 12.3 46.1 ± 17.4 45.4 (31.0–59.0) 38.7

b 0.001 b 0.001 b 0.001

37.9 40.8 75.7 67 85.4 43.7 52.4 12.6 9.7 21.4 30.1 5.8 84.5 8.7

37.3 41.5 76.1 57.7 92.3 41.5 47.2 19 14.1 20.4 37.3 8.5 72.5 13.4

36.8 48.8 79.6 47.3 89.6 41.3 47.3 37.7 21.9 15.9 47.8 11.4 62.7 22.9

0.984 0.28 0.649 0.004 0.229 0.917 0.652 b 0.001 0.016 0.41 0.008 0.258 b 0.001 0.003

b 0.001 0.986

0.147 b 0.001 0.086

0.150 0.849 0.001 0.815

b 0.001

COPD = chronic obstructive pulmonary disease; VT/VF = ventricular tachycardia/fibrillation; PCI = percutaneous coronary intervention; CABG = coronary artery bypass grafting; PPM = permanent pacemaker; CRT = cardiac resynchronization therapy; ICD = implantable cardiac defibrillator; NYHA = New York Heart Association; eGFR = estimated glomerular filtration rate; BNP = B-type natriuretic peptide; LV = left ventricular; EDD = end-diastolic diameter; ESD = end-systolic diameter; EF = ejection fraction; ACE = angiotensin converting enzyme; and ARB = angiotensin II receptor blocker. Patient characteristics and treatment were compared using Pearson chi-square test for categorical variables and one-way ANOVA for continuous variables.

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Table 1 also shows the distribution of CHADS2 scores in study patients from JCARE-CARD and previous studies. The mean CHADS2 score was 2.56 ± 1.27 in the present study, which was also similar to that in HF subgroups from clinical trials of AF including AFFIRM (mean: 2.6; 2.46 ± 1.07 for HFrEF and 2.77 ± 1.05 for HFpEF), RE-LY (2.6 ± 1.1), and ARISTOTLE (mean: 2.46, 2.22 ± 1.20 in LV systolic dysfunction and 2.67 ± 1.08 in HFpEF) [3–5]. In contrast, CHADS2 score was higher in ROCKET AF (3.7 ± 0.9), which included patients exclusively with CHADS2 score greater than 2 [6]. A proportion of patients without an additional stroke risk factor (CHADS2 score = 1) in JCARE-CARD (23%) appears to be high compared to that in Euro Heart Survey on AF (approximately 15%), RE-LY (12%), and ARISTOTLE (18%). ROCKET AF did not include these patients due to the exclusion criteria. Table 2 provides a comparison of clinical characteristics of patients with HF and AF from JCARE-CARD classified into 3 groups according to CHADS2 score: 1, 2, and ≥3. Compared with patients with score ≥3, patients with score = 1 were younger (61 vs 75 years old, P b 0.001), more men (82% vs 61%, P b 0.001), and more often dilated cardiomyopathy as a cause (45% vs 18%, P b 0.001). Interestingly, these patients had even lower LVEF by echocardiography (35.7% vs 46.1%, P b 0.001). In contrast, as well expected, patients with higher CHADS2 score were older, had more comorbidities including hypertension, diabetes mellitus, dyslipidemia, and prior stroke. NYHA functional classes did not differ among groups. Patients with CHADS2 score = 1 were even more likely to receive β blockers (67.0% vs 47.3% for patients with score ≥3, P = 0.004) and warfarin (84.5% vs 62.7%, P b 0.001) (Table 2). In contrast, patients with higher CHADS2 score were prescribed more by Ca channel blocker, nitrates, aspirin, and statin at discharge. In conclusion, clinical characteristics and CHADS2 score in Japanese HF patients associated with AF were generally similar to those reported in observational registries and clinical trials on AF from western countries. They were diverse according to CHADS2

0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2014.06.068

score in a broad cohort of HF patients. Patients without an additional stroke risk factor (score = 1) were not rare and characterized by young, male, and dilated cardiomyopathy. Anticoagulation was highly used in these patients and considered to be reasonable, which, however, needs to be confirmed. We have no relationships to be construed as the conflict of interest.

References [1] Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001;285:2864–70. [2] Nieuwlaat R, Eurlings LW, Cleland JG, et al. Atrial fibrillation and heart failure in cardiology practice: reciprocal impact and combined management from the perspective of atrial fibrillation: results of the Euro Heart Survey on atrial fibrillation. J Am Coll Cardiol 2009;53:1690–8. [3] Badheka AO, Rathod A, Kizilbash MA, et al. Comparison of mortality and morbidity in patients with atrial fibrillation and heart failure with preserved versus decreased left ventricular ejection fraction. Am J Cardiol 2011;108:1283–8. [4] McMurray JJ, Ezekowitz JA, Lewis BS, et al. Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial. Circ Heart Fail 2013;6:451–60. [5] Ferreira J, Ezekowitz MD, Connolly SJ, et al. Dabigatran compared with warfarin in patients with atrial fibrillation and symptomatic heart failure: a subgroup analysis of the RE-LY trial. Eur J Heart Fail 2013;15:1053–61. [6] van Diepen S, Hellkamp AS, Patel MR, et al. Efficacy and safety of rivaroxaban in patients with heart failure and nonvalvular atrial fibrillation: insights from ROCKET AF. Circ Heart Fail 2013;6:740–7. [7] Tsutsui H, Tsuchihashi-Makaya M, Kinugawa S, Goto D, Takeshita A. Clinical characteristics and outcome of hospitalized patients with heart failure in Japan. Circ J 2006;70:1617–23. [8] Hamaguchi S, Yokoshiki H, Kinugawa S, et al. Effects of atrial fibrillation on longterm outcomes in patients hospitalized for heart failure in Japan: a report from the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD). Circ J 2009;73:2084–90. [9] Hamaguchi S, Furumoto T, Tsuchihashi-Makaya M, et al. Hyperuricemia predicts adverse outcomes in patients with heart failure. Int J Cardiol 2011;151:143–7. [10] Tsuchihashi-Makaya M, Hamaguchi S, Kinugawa S, et al. Sex differences with respect to clinical characteristics, treatment, and long-term outcomes in patients with heart failure. Int J Cardiol 2011;150:338–9.

Clinical characteristics and CHADS2 score in patients with heart failure and atrial fibrillation: insights from the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD).

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