Noncompaction

CHADS2- and CHA2DS2VASc Scores and Embolic Risk in Left Ventricular Hypertrabeculation/Noncompaction €llberger, MD,* Christian Wegner, MA,† and Josef Finsterer, MD, PhD*‡ Claudia Sto

Background: Left ventricular hypertrabeculation/noncompaction (LVHT) is associated with stroke or embolism (S/E). The aim of this study was to assess if the Congestive heart failure, Hypertension, Age .75 years, Diabetes, and Stroke (CHADS2) and CHA2DS2VASc scores are different between LVHT-patients with and without stroke/embolism. Methods: Records of LVHT patients were retrospectively screened. For stroke classification, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria were applied, for peripheral embolism angiographic findings. Baseline data were compared between patients with and without S/E. Results: In 26 of 169 patients (15%), stroke (n 5 24) or peripheric embolism (n 5 2) had occurred. S/E etiology was either cardioembolic (n 5 18), atherosclerotic (n 5 5), or undetermined (n 5 3). S/E occurred before (n 5 17) and after (n 5 9) diagnosis of LVHT/NC. The prevalence of hypertension (62 vs 35%; P , .05), CHADS2, and CHA2DS2-VASc scores were higher in patients with than without S/E (2.85 vs 1.26 and 3.69 vs 1.93, respectively; P ,.001). Conclusions: S/E in LVHT is not always cardioembolic, but may also have an atherosclerotic cause. The CHADS2 score may be useful for clinical decision-making about oral anticoagulation for the prevention of S/E in LVHT patients. Key Words: Cardiomyopathy—embolic risk—stroke. Ó 2013 by National Stroke Association

CHADS2 and CHA2DS2-VASc scores assess the risk for stroke or embolism (S/E) in patients with atrial fibrillation (AF). The CHADS2 (Congestive heart failure, Hypertension, Age .75 years, Diabetes, and Stroke) risk index is based on a system in which 2 points are assigned for a history of stroke or transient ischemic attack (TIA) and 1 point each is assigned for age .75 years, a history of hypertension, diabetes, or recent cardiac failure. The CHA2DS2-VASc (Congestive heart failure, Hypertension, Age .75, Diabetes, Stroke, VAScular disease, Age 65-74, female gender) risk index is based on a system in which 2 points are assigned for a history of stroke or TIA or

From the *Krankenanstalt Rudolfstiftung; †Vienna Institute of Demography of the Austrian Academy of Sciences, Wien; and ‡Danube University Krems, Krems, Austria. Received September 3, 2011; revision received October 21, 2011; accepted October 28, 2011. Address correspondence to Claudia St€ ollberger, MD, Krankenanstalt Rudolfstiftung, Steingasse 31/18, A-1030 Wien, Austria. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2013 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2011.10.014

age .75 years and 1 point each is assigned for age 6574 years, a history of hypertension, diabetes, recent cardiac failure, vascular disease, and female sex.1,2 Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology that is characterized by prominent trabeculations and intertrabecular recesses within the left ventricle. LVHT is frequently associated with neuromuscular disorders. Patients with LVHT present with heart failure, arrhythmias, and S/E that are reported to occur in 1% to 2% of patients per year.3,4 It is unknown if scores developed for AF patients may be useful to assess embolic risk in LVHT. Therefore, the aim of the study was to calculate CHADS2 and CHA2DS2VASc scores of LVHT patients with and without S/E.

Methods Consecutively included were patients in whom LVHT was diagnosed in the echocardiography laboratory of the Krankenanstalt Rudolfstiftung since June 1995. Echocardiographic criteria for the diagnosis of LVHT were .3 trabeculations protruding from the left ventricular wall, apically to the papillary muscles, visible in 1

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Table 1. Patients with stroke/embolism Birth/Sex

LVHT year

S/E year

CHADS2

CHA2DS2-VASc

Therapy before S/E

HTN

NMD

DM

AF

SYS DYS

CT

MR

CD

Stroke etiology

1930/F 1949/M 1958/F 1956/F 1930/F 1931/F 1965/M 1959/M 1922/F 1946/M 1977/F 1950/M 1930/M 1944/M 1951/M 1937/F 1930/F 1928/M 1942/M 1944/M 1934/M 1948/M 1948/M 1944/M 1952/M 1991/F

2009 1998 2002 2004 2008 1999 2003 2000 2002 2001 2009 2002 2006 1999 1998 2007 2005 2007 1999 2006 2008 1999 2010 2000 2008 2011

2009 1999 2002 2004* 2008 2009 2003 2000 1997 1994 2009 2002 2000 2002 2002 2007 2001 2007 1999 2000 1995 2004 2009 2010 2008 2011*

5 1 3 3 3 1 0 2 6 3 1 3 4 2 1 4 5 3 3 5 5 1 3 1 4 2

7 1 4 4 5 3 0 2 8 3 2 3 5 2 1 6 8 4 4 5 6 1 3 2 4 3

LMWH 0 ASS 0 ASS ASS 0 0 ASS ASS 0 0 OAC ASS ASS 0 ASS ASS ASS ASS ASS ASS 0 ASS 0 0

1 1 1 0 0 1 0 0 1 0 0 1 0 1 0 1 1 1 0 1 1 1 1 1 1 0

X U U U X N E X U U U X U E U U U U U U X U X X X N

1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 1 1 0 0 1 1 0 1 0 0 0

1 0 0 1 0 0 0 0 1 0 0 0 0 0 0 1 1 0 0 1 0 0 1 0 0 0

0 1 0 1 1 0 0 0 1 1 1 0 1 1 1 0 1 1 1 1 1 0 1 0 1 0

1 1 1 0 1 1 0 1 0 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0

1 1 1 1 1 1 1 1 0 0 0 1 0 1 0 1 0 0 1 1 1 0 1 0 0 1

0 1 1 0 1 1 0 1 0 0 1 1 1 0 0 1 0 0 0 0 1 0 1 1 1 0

CE AT Unknown CE AT Unknown Unknown CE CE CE CE AT CE CE CE CE CE CE CE CE AT AT CE CE CE CE € C. STOLLBERGER ET AL.

Abbreviations: AF, atrial fibrillation; ASS, acetyl salicylic acid; AT, atherosclerotic; CD, carotid duplex; CE, cardioembolic; CT, cerebral computed tomography; DM, diabetes mellitus; E, definite neuromuscular disorder; HTN, hypertension; LVHT, left ventricular hypertrabeculation/noncompaction (year of diagnosis); LMWH, low molecular weight–heparin; MR, cerebral magnetic resonance imaging; N, neurologically normal; NMD, neuromuscular disorder; OAC, oral anticoagulation with vitamin K antagonists; S/E, stroke/embolism; SYSDYS, left ventricular fractional shortening ,25%; U, neuromuscular disorder of unknown etiology; X, neurologically not investigated. *Peripheral embolism.

CHADS2 IN NONCOMPACTION

711

Table 2. Baseline characteristics of patients with and without stroke/embolism Characteristics

With S/E (n 5 26)

Without S/E (n 5 143)

Age (y), (6 SD) Female, n(%) Specific neuromuscular disorder, n (%) Neuromuscular disorder of unknown etiology, n (%) Diabetes mellitus, n (%) Arterial hypertension, n (%) Heart failure, n (%) NYHA I/II, n (%) NYHA III/IV, n (%) Left bundle branch block, n (%) Atrial fibrillation, n (%) Left ventricular end diastolic diameter, mm (6SD) Left ventricular fractional shortening, % (6SD) CHADS2 score (6SD) CHA2DS2VASc score (6SD)

58 (16) 10 (39) 2 (8) 14 (54) 7 (27) 16 (62) 14 (54) 5 (19) 9 (35) 5 (19) 7 (27) 61 (14) 25 (12) 2.85 (1.6) 3.69 (2.1)

52 (16) 40 (28) 23 (16) 63 (44) 24 (17) 50 (35)* 96 (67) 32 (22) 64 (45) 27 (19) 21 (15) 61 (12) 24 (10) 1.26 (0.9)y 1.93 (1.3)y

Abbreviations: NYHA, New York Heart Association; SD, standard deviation; S/E, stroke/embolism. *P , .05. yP , .001.

echocardiographic image plane; intertrabecular spaces perfused from the ventricular cavity, as seen on color Doppler imaging; and a double-layered structure of the myocardium, consisting of a trabeculated and a nontrabeculated layer. Systolic function was expressed as left ventricular fractional shortening. All patients underwent a baseline examination. Congestive heart failure was diagnosed if the patient had symptoms of heart failure. Hypertension was diagnosed if the patient had a history of arterial hypertension and received at least 1 antihypertensive drug. Diabetes was diagnosed if the patient received antidiabetic therapy. S/E was diagnosed if the patient reported symptoms and if the diagnosis was confirmed by instrumental findings. All patients were invited for a neurologic investigation comprising a medical history review and a clinical neurologic examination. If there were indications for polyneuropathy, an established screening program for polyneuropathy including blood tests, cerebrospinal fluid investigations, and eventually a nerve biopsy was carried out. If there were indications for a myopathy, a screening for myopathy was initiated, including muscle enzymes, electromyography and eventually a muscle biopsy. During May 2011, the records of LVHT patients were screened if S/E had ever occurred. For classification of stroke etiology, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria and for peripheral embolism angiographic findings were applied.5 CHADS2 and CHA2DS2-VASc scores were calculated using the baseline data. Group comparisons for noncategorical data were carried out with the t test. Categorical data were analyzed by the Chi square and the 2-sided Fisher exact test. Multivariate analysis was performed by applying standard logistic regression.

Results Between June 1995 and May 2011, LVHT was diagnosed in 169 patients. Indications for echocardiography were heart failure (n 5 94), chest pain (n 5 31), syncope (n 5 16), search for cardiac involvement in myopathy (n 5 11), search for a cardiac source of S/E (n 5 8), hypertension (n 5 6), and family screening (n 5 3). Data from a subgroup have been published.6 In 26 of 169 patients (15%), at least 1 stroke (n 5 24) or embolism to renal artery (n 5 1) or lower limb (n 5 1) occurred. The etiology of S/E was either cardioembolic (n 5 18), atherosclerotic (n 5 5), or undetermined (n 5 3). S/E occurred either before (n 5 17) or after (n 5 9) diagnosis of LVHT (Table 1). LVHT patients with S/E had a higher prevalence of hypertension and higher CHADS2 and CHA2DS2-VASc scores than patients without S/E (Table 2). Multivariate analysis revealed that the CHADS2 score (adjusted R2 5 0.36) better fits the model to predict S/E than CHA2DS2-VASc (adjusted R2 5 0.27) after correction for age and hypertension.

Discussion In LVHT, patients’ embolic risk scores, developed for AF patients, were useful, and the CHADS2 was superior to the CHA2DS2-VASc score. This may be explained by the relatively young age of LVHT patients and the male preponderance. Because of the lack of prospective randomized studies in LVHT, indications for oral anticoagulation can only be inferred from retrospective case series.4 LVHT patients with S/E, AF, or systolic dysfunction should receive oral anticoagulation. In the absence of these abnormalities, and based on the results of the present study, we recommend the use of the CHADS2 score

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for clinical decision-making about oral anticoagulation in LVHT patients. If the CHADS2 score is $2, oral anticoagulation should be strongly considered. Limitations include the fact that that S/E was only assessed retrospectively from records within the region covered by the computer information system, with the potential for ascertainment bias and missing events that occurred in another region. No 24-hour Holter monitoring was performed. It is unknown if patients had AF at the time of S/E. Neither peripheral vascular disease, hyperlipidemia, chronic renal failure, therapy with betablocking agents, angiotensin-converting enzyme inhibitors, angiotensin II–blocking agents and statins, nor all potential causes for S/E were assessed.

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