Atrial fibrillation in hypertrophic cardiomyopathy A turning point towards increased morbidity and mortality Accepted Manuscript Atrial fibrillation in hypertrophic cardiomyopathy A turning point towa[.]
Accepted Manuscript Atrial fibrillation in hypertrophic cardiomyopathy: A turning point towards increased morbidity and mortality Thomas Zegkos, MD, Georgios K Efthimiadis, MD, Despoina G Parcharidou, MD, Thomas D Gossios, MD, Georgios Giannakoulas, MD, Dimitris Ntelios, MD, Antonis Ziakas, MD, Stelios Paraskevaidis, MD, Haralambos I Karvounis, MD PII: S1109-9666(16)30241-X DOI: 10.1016/j.hjc.2017.01.027 Reference: HJC 139 To appear in: Hellenic Journal of Cardiology Received Date: 18 October 2016 Revised Date: 12 January 2017 Accepted Date: 20 January 2017 Please cite this article as: Zegkos T, Efthimiadis GK, Parcharidou DG, Gossios TD, Giannakoulas G, Ntelios D, Ziakas A, Paraskevaidis S, Karvounis HI, Atrial fibrillation in hypertrophic cardiomyopathy: A turning point towards increased morbidity and mortality, Hellenic Journal of Cardiology (2017), doi: 10.1016/j.hjc.2017.01.027 This is a PDF file of an unedited manuscript that has been accepted for publication As a service to our customers we are providing this early version of the manuscript The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain ACCEPTED MANUSCRIPT Atrial fibrillation in hypertrophic cardiomyopathy: A turning point towards increased morbidity and mortality Authors: Thomas Zegkos MD, Georgios K Efthimiadis MD, Despoina G RI PT Parcharidou MD, Thomas D Gossios MD, Georgios Giannakoulas MD, Dimitris Ntelios MD, Antonis Ziakas MD, Stelios Paraskevaidis MD, Haralambos I Karvounis MD SC Affiliation: 1st Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece The authors take responsibility for discussed interpretation M AN U all aspects of the reliability and freedom from bias of the data presented and their TE D Running title: Atrial fibrillation in hypertrophic cardiomyopathy Address for correspondence: Thomas Zegkos EP AHEPA University Hospital, Aristotle University of Thessaloniki AC C Stilponos Kyriakidi Street 54636, Thessaloniki Greece Email: zegkosth@gmail.com Tel: +306944321060 Conflict of interest: None declared by all authors ACCEPTED MANUSCRIPT Abstract Background: Atrial fibrillation (AF) is the most common arrhythmic event in patients with hypertrophic cardiomyopathy (HCM) The aim of this study was to RI PT identify the clinical and the prognostic impact of the arrhythmia on a large cohort of patients with HCM Methods: The echocardiographic and clinical correlates, the predictors of AF and SC thromboembolic stroke and the prognostic significance of the arrhythmia were M AN U evaluated in 509 patients with an established diagnosis of HCM Results: A total of 119 (23.4%) were diagnosed with AF at index evaluation visit AF patients had higher prevalence of stroke and worse functional impairment Left atrial diameter (LA size) was a common independent predictor of the arrhythmia (OR: 2.2, 95% CI 1.6-3.3) and thromboembolic stroke (OR: 1.6, 95% CI 1.01-2.40) AF was an TE D important risk factor for overall (HR=3.4, 95% CI: 1.7-6.5), HCM-related (HR=3.9, 95% CI: 1.8-8.2) and heart failure-related mortality (HR=6.0, 95% CI: 2.0-17.9), even EP after adjusting for the significant clinical and demographic risk factors However, it did not affect the risk for sudden death AC C Conclusions: LA size was a common predictor of the arrhythmia and thromboembolic stroke AF patients, regardless of the type of the arrhythmia, displayed significantly higher mortality rates Keywords: hypertrophic cardiomyopathy; atrial fibrillation; left atrium; mortality; morbidity ACCEPTED MANUSCRIPT Abbreviations: AF: atrial fibrillation; CMR: cardiac magnetic resonance; CPEx: cardiopulmonary exercise testing; EF: ejection fraction; HCM: hypertrophic cardiomyopathy; LA size: left atrial diastolic diameter; LGE: late gadolinium AC C EP TE D M AN U SC NYHA: New York Heart Association; SR: sinus rhythm RI PT enhancement; LV: left ventricle; LVEDD: left ventricular end-diastolic diameter; ACCEPTED MANUSCRIPT Introduction Atrial fibrillation (AF) is the most common arrhythmic event in patients with hypertrophic cardiomyopathy (HCM) The prevalence of AF in HCM as well as its RI PT demographic, clinical and echocardiographic characteristics have been previously described [1-9] Predisposing factors include left atrial enlargement, left ventricular outflow tract (LVOT) obstruction and mitral regurgitation [10] Additionally, AF in SC HCM is generally related to increased mortality and morbidity and especially to an increased risk of cardiac death [9, 11, 12] However, this finding is not consistent M AN U across the literature, as a relatively benign prognosis has also been reported [13, 14] The aim of this study was to identify the prevalence, the echocardiographic and clinical correlates and the impact of AF on the survival of a large cohort of patients Methods EP Study Population TE D with HCM evaluated in a single tertiary, university affiliated medical center All the patients with an established diagnosis of HCM that were evaluated in the AC C Cardiomyopathy Center of AHEPA University Hospital from 1995 until 2014 were assessed retrospectively according to the presence of AF at index evaluation visit Clinical, imaging and functional parameters were examined The retrospective, purely observational type of this study did not necessarily require the acquisition of informed consents or ethics committee approval Definitions ACCEPTED MANUSCRIPT Hypertrophic cardiomyopathy HCM was diagnosed echocardiographically with the identification of a hypertrophied, non dilated left ventricle (LV) in the absence of any other cardiac or systemic disease RI PT that could explain the magnitude of the observed hypertrophy [15] Atrial Fibrillation AF was diagnosed on the basis of an electrocardiographic or Holter monitor recording SC as it was previously described [16] or by an established history of the arrhythmia AF M AN U was considered paroxysmal when it was self terminated or successfully converted to sinus rhythm (SR) within days Any other type of the arrhythmia was considered non paroxysmal Study Outcomes TE D Overall mortality was defined as death rate by any cause during the follow up period HCM-related mortality consisted of deaths directly attributed to the primary disease EP such as sudden, stroke-related and heart failure-related deaths Sudden cardiac death was defined as a sudden and unexpected collapse in patients, in the absence of AC C symptoms, who had previously experienced a relatively stable clinical course Heart failure related-mortality was defined as death rate in the context of refractory or progressive heart failure over one year before death [5] Echocardiography The echocardiographic measurements were obtained with a Sigma ratio (Kontron AG, Ausburg, Germany) instrument until 2003, and a GE Vivid ultrasound ACCEPTED MANUSCRIPT instrument afterwards Left atrial diastolic diameter (LA size) and LV end-diastolic diameter (LVEDD) were measured at the 2D long parasternal axis view.[17] The extent of LV hypertrophy was measure from the 2D parasternal axis view at the basal, mid LV and apical plane LV ejection fraction (EF) and mitral regurgitation were RI PT measured as previously described [17, 18] Maximal wall thickness was defined as the greatest measured at any LV segment Mitral inflow was analyzed for peak E and A velocities Pulse-Doppler was applied to allow for a spectral display of both septal and SC lateral mitral annular velocities and E/E’ was computed for both velocities [19] The obstructive phenotype was defined as LV outflow peak gradient >30mmHg at rest or M AN U provoked peak gradient >30mmHg (Valsalva maneuvre or standing) using continuous wave Doppler [17] Cardiac Magnetic Resonance TE D Cardiac magnetic resonance (CMR) was performed with a clinical 1.5-T imager (Magnetom Vision; Siemens, Erlangen, Germany) Late gadolinium enhancement (LGE) images were obtained 10-15 after intravenous administration of 0.2 EP mmol·kg-1 gadolinium-DTPA, using an inversion recovery turbo Fast Low Angle Shot AC C (FLASH) sequence with mm slice thickness at the same position as the long- and short-axis cines in end diastole [20] Cardiopulmonary Exercise Testing Exercise capacity was assessed by peak oxygen consumption that was measured by cardiopulmonary exercise testing (CPEx) as previously described [21] Exercise was performed in a Schiller Cardiovit CS 200 (Schiller America, Doral, FL, USA) Ergo6 ACCEPTED MANUSCRIPT Spiro treadmill ergometer, using the Bruce protocol Before each test the ergospirometer was calibrated using standard calibration The patients were stressed until exhaustion The respiratory exchange ratio was