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Frequency of Left Ventricular Hypertrophy in Non-Valvular Atrial Fibrillation

      Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the “Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study” (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 ± 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index ≤0.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc ≥2 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention.
      Atrial fibrillation (AF) is the most prevalent supraventricular tachyarrhythmia
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      European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery
      Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC).
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      Absolute and attributable risks of atrial fibrillation in relation to optimal and borderline risk factors: the Atherosclerosis Risk in Communities (ARIC) study.
      One of the hypertension-related target organ damage is left ventricular hypertrophy (LVH).
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      Determinants of left ventricular hypertrophy in patients with recent diagnosis of essential hypertension.
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      Left ventricular hypertrophy and clinical outcomes in hypertensive patients.
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      • Massie B.
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      • Savage D.
      • Shub C.
      The heart in hypertension.
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      • Negri F.
      • Mancia G.
      • Morganti A.
      Italian Society of Hypertension
      Prevalence of left-ventricular hypertrophy in hypertension: an updated review of echocardiographic studies.
      Data on gender differences in development of LVH have been reported in hypertensive patients with
      • Gori M.
      • Lam C.S.
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      PARAMOUNT Investigators. Sex-specific cardiovascular structure and function in heart failure with preserved ejection fraction.
      or without concomitant heart failure.
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      • Mancia G.
      • Morganti A.
      Italian Society of Hypertension
      Prevalence of left-ventricular hypertrophy in hypertension: an updated review of echocardiographic studies.
      Notwithstanding different definitions and threshold criteria, LVH prevalence ranges widely in the general population.
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      • Sala C.
      • Negri F.
      • Mancia G.
      • Morganti A.
      Italian Society of Hypertension
      Prevalence of left-ventricular hypertrophy in hypertension: an updated review of echocardiographic studies.
      Nonetheless, LVH is an independent risk factor for major cardiovascular events and all cause death.
      • Levy D.
      • Garrison R.J.
      • Savage D.D.
      • Kannel W.B.
      • Castelli W.P.
      Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study.
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      • Circo A.
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      • Lombardo M.
      • Solinas P.
      • Gorini M.
      • Maggioni A.P.
      MAVI (MAssa Ventricolare sinistra nell'Ipertensione) Study Group
      Left ventricular mass and cardiovascular morbidity in essential hypertension: the MAVI study.
      • Devereux R.B.
      • Roman M.J.
      Left ventricular hypertrophy in hypertension: stimuli, patterns, and consequences.
      • Apostolakis S.
      • Sullivan R.M.
      • Olshansky B.
      • Lip G.Y.
      Left ventricular geometry and outcomes in patients with atrial fibrillation: the AFFIRM Trial.
      Also, left ventricular remodeling has been identified as an independent risk factor for stroke and mortality in patients with AF.
      • Verdecchia P.
      • Reboldi G.
      • Di Pasquale G.
      • Mazzotta G.
      • Ambrosio G.
      • Yang S.
      • Pogue J.
      • Wallentin L.
      • Ezekowitz M.D.
      • Connolly S.J.
      • Yusuf S.
      RE-LY Study Investigators
      Prognostic usefulness of left ventricular hypertrophy by electrocardiography in patients with atrial fibrillation (from the Randomized Evaluation of Long-Term Anticoagulant Therapy Study).
      The aim of our study was to determine LVH prevalence, using well-defined echocardiographic criteria based on left ventricular mass (LVM) indexed by body surface area (BSA) in a cohort of patients with non-valvular (NV) AF. Second, we aimed to identify the clinical factors independently associated with LVH in our patients with NVAF. Third, we conducted a gender-stratified analysis to investigate relevant gender differences in LVH in patients with NVAF.

      Methods

      We performed a cross-sectional analysis on the “Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study” (ARAPACIS), a multicenter, observational, prospective on-going study designed to estimate prevalence of ankle-brachial index (ABI) ≤0.90 in patients with NVAF and its influence on cardiovascular and cerebrovascular events incidence over a 3-year follow-up.
      • Lang R.M.
      • Bierig M.
      • Devereux R.B.
      • Flachskampf F.A.
      • Foster E.
      • Pellikka P.A.
      • Picard M.H.
      • Roman M.J.
      • Seward J.
      • Shanewise J.S.
      • Solomon S.D.
      • Spencer K.T.
      • Sutton M.S.
      • Stewart W.J.
      Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography
      Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.
      • Violi F.
      • Daví G.
      • Hiatt W.
      • Lip G.Y.
      • Corazza G.R.
      • Perticone F.
      • Proietti M.
      • Pignatelli P.
      • Vestri A.R.
      • Basili S.
      ARAPACIS Study Investigators
      Prevalence of peripheral artery disease by abnormal ankle-brachial index in atrial fibrillation: implications for risk and therapy.
      Details on standard study procedures have been previously reported.
      • Violi F.
      • Daví G.
      • Hiatt W.
      • Lip G.Y.
      • Corazza G.R.
      • Perticone F.
      • Proietti M.
      • Pignatelli P.
      • Vestri A.R.
      • Basili S.
      ARAPACIS Study Investigators
      Prevalence of peripheral artery disease by abnormal ankle-brachial index in atrial fibrillation: implications for risk and therapy.
      In addition, a standard transthoracic echocardiography
      • Raparelli V.
      • Proietti M.
      • Buttà C.
      • Di Giosia P.
      • Sirico D.
      • Gobbi P.
      • Corrao S.
      • Davì G.
      • Vestri A.R.
      • Perticone F.
      • Corazza G.R.
      • Violi F.
      • Basili S.
      Medication prescription and adherence disparities in non valvular atrial fibrillation patients: an Italian portrait from the ARAPACIS study.
      was performed where feasible. Even if a central analysis of echocardiographic images was not performed, an experienced cardiologist in echocardiography performed a blinded evaluation of measurements for consistency and reliability.
      Patients were consecutively recruited, both as inpatients or outpatients, if they were aged ≥18 years and had NVAF diagnosis recorded in the preceding 12 months. Enrollment was performed in 136 facilities belonging to the Italian Internal Medicine Society network from October 2010 and continued until 30 October 2012. All patients signed a written informed consent. The study was conducted in accordance with the EU Note for Guidance on Good Clinical Practice CPMP/ECH/135/95 and the Declaration of Helsinki.
      LVM estimation was calculated according to American Society of Echocardiography (ASE) and European Association of Echocardiography (EAE) joint recommendations.
      • Raparelli V.
      • Proietti M.
      • Buttà C.
      • Di Giosia P.
      • Sirico D.
      • Gobbi P.
      • Corrao S.
      • Davì G.
      • Vestri A.R.
      • Perticone F.
      • Corazza G.R.
      • Violi F.
      • Basili S.
      Medication prescription and adherence disparities in non valvular atrial fibrillation patients: an Italian portrait from the ARAPACIS study.
      LVM values have been indexed by BSA, calculated with the Dubois and Dubois formula (BSA = 0.007184 × weight [Kg]0.425 × height [cm]0.725). Thus, we defined the presence of LVH for an LVM indexed by BSA (LVMI-BSA) >95 g/m2 for women and an LVMI-BSA >115 g/m2 for men.
      • Raparelli V.
      • Proietti M.
      • Buttà C.
      • Di Giosia P.
      • Sirico D.
      • Gobbi P.
      • Corrao S.
      • Davì G.
      • Vestri A.R.
      • Perticone F.
      • Corazza G.R.
      • Violi F.
      • Basili S.
      Medication prescription and adherence disparities in non valvular atrial fibrillation patients: an Italian portrait from the ARAPACIS study.
      The definition of LV remodeling was assessed calculating the relative wall thickness (RWT). In accordance to ASE/EAE recommendations,
      • Raparelli V.
      • Proietti M.
      • Buttà C.
      • Di Giosia P.
      • Sirico D.
      • Gobbi P.
      • Corrao S.
      • Davì G.
      • Vestri A.R.
      • Perticone F.
      • Corazza G.R.
      • Violi F.
      • Basili S.
      Medication prescription and adherence disparities in non valvular atrial fibrillation patients: an Italian portrait from the ARAPACIS study.
      RWT ≥0.42 defined a concentric remodeling, otherwise an RWT <0.42 defined an eccentric remodeling. All patients were then categorized into 4 categories of cardiac remodeling: (1) no remodeling, that is, patients without LVH and with an RWT <0.42; (2) concentric remodeling, that is, patients without LVH and with an RWT ≥0.42; (3) eccentric hypertrophy, that is, patients with LVH and an RWT <0.42; and (4) concentric hypertrophy, that is, patients with LVH and an RWT ≥0.42.
      According to Shapiro–Wilk normality test, variables with a normal distribution were tested for differences by the Student t test and reported as mean ± standard deviation. Variables with nonhomogeneous variances were tested by the Mann–Whitney U test and reported as median and interquartile range. Categorical variables, expressed as counts and percentages, were analyzed by a chi-square test. A gender-stratified analysis was also conducted. Finally, a multivariate regression analysis was performed to establish LVH determinants in patients with NVAF. To reduce interobserver variability, the regression analysis was corrected for enrolling centers. The probability values were 2 sided; a p value <0.05 was considered statistically significant. All analyses were carried out with SPSS version 20 (IBM, NY, USA).

      Results

      Among a total of 2,027 patients enrolled in ARAPACIS, echocardiographic data were available for 1,184 subjects (59%). After data revision, 1,087 patients (72 ± 11 years; 56% men) were eligible for analysis (Figure 1). Clinical and demographic variables in nonincluded patients were similar to those analyzed (Table 1).
      Figure thumbnail gr1
      Figure 1Flow diagram of NVAF patient selection.
      Table 1Clinical and demographic characteristics according to the presence of left ventricular hypertrophy
      VariableExcluded Patients

      N= 940
      Left Ventricular HypertrophyP value

      Yes vs. No
      Yes

      N=576
      No

      N=511
      Age (years.), mean±SD74±975±970±12<0.0001
      Student t test.
      Age Classes<0.0001
      Chi-square test.
      <65 years263 (28%)123 (21%)191 (37%)
      65-74 years209 (22%)141 (25%)142 (28%)
      ≥75 years468 (50%)312 (54%)178 (35%)
      Women439 (47%)353 (56%)158 (31%)<0.0001
      Chi-square test.
      Body Mass Index (Kg/m2), mean±SD28±528±528±50.4876
      Student t test.
      Type of Atrial Fibrillation0.0866
      Chi-square test.
      Paroxysmal425 (45%)233 (41%)221 (43%)
      Persistent120 (13%)82 (14%)90 (18%)
      Permanent395 (42%)261 (45%)200 (39%)
      Hypertension
      Blood Pressure>140/90 mm Hg or treated with anti-hypertensive drugs.
      785 (84%)515 (89%)374 (73%)<0.0001
      Chi-square test.
      Diabetes Mellitus237 (25%)152 (26%)77 (15%)<0.0001
      Chi-square test.
      Smoker138 (15%)77 (13%)100 (20%)0.0057
      Chi-square test.
      Hypercholesterolemia
      Total Cholesterol≥ 240 mg/dl or treated with lipid lowering drugs.
      353 (38%)231 (40%)205 (40%)0.9964
      Chi-square test.
      Metabolic Syndrome282 (31%)164 (30%)141 (29%)0.6767
      Chi-square test.
      Previous Transient Ischemic Attack/Stroke116 (12%)67 (12%)52 (10%)0.4429
      Chi-square test.
      Previous Myocardial Infarction159 (17%)105 (18%)49 (9.6%)<0.0001
      Chi-square test.
      Previous Peripheral Artery Disease13 (1.4%)9 (1.4%)10 (1.9%)0.5624
      Chi-square test.
      Heart Failure189 (20%)102 (18%)87 (17%)0.7668
      Chi-square test.
      Ankle-Brachial Index ≤0.90
      Data referred to 1,084 patients.
      212 (23%)128 (22%)88 (17%)0.0391
      Chi-square test.
      CHA2DS2-VASc, median [IQR]3 [2-4]4 [3-5]2 [1-4]<0.0001
      Mann Whitney U test.
      CHA2DS2-VASc Classes<0.0001
      Chi-square test.
      Score 025 (2.7%)8 (1.4%)46 (9.0%)
      Score 1108 (11.5%)35 (6.1%)94 (18.4%)
      Score≥2807 (85.8%)533 (92.5%)371 (72.6%)
      IQR = Interquartile Range; SD = Standard Deviation.
      Student t test.
      Chi-square test.
      Blood Pressure>140/90 mm Hg or treated with anti-hypertensive drugs.
      § Total Cholesterol≥ 240 mg/dl or treated with lipid lowering drugs.
      Data referred to 1,084 patients.
      Mann Whitney U test.
      Previous cardiovascular disease was recorded for about 1/4 of patients. Among classic cardiovascular risk factors, hypertension was the most prevalent (82%). The mean LVMI-BSA was 112 ± 31 g/m2. Values of LVMI-BSA were greater in permanent NVAF compared to those with persistent AF (p = 0.0107) or paroxysmal AF (p = 0.0023). LVMI-BSA progressively increased with higher CHA2DS2-VASc risk classes (p <0.0001; Figure 2).
      Figure thumbnail gr2
      Figure 2LVMI-BSA values distribution according to CHA2DS2-VASc score.
      LVH was recorded in 52% of patients. Clinical and demographic characteristics in the groups are reported in Table 1. Patients with LVH were older, had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI) compared to those without. ABI ≤0.90 was prevalent in patients with LVH. CHA2DS2-VASc ≥2 class was recorded more frequently in patients with LVH.
      Table 2 summarizes echocardiographic characteristics of the 2 groups. Patients with LVH had poorer ventricular function compared to those without LVH. In 59% of patients with LVH, there was a concentric hypertrophy pattern.
      Table 2Echocardiographic characteristics according to the presence of left ventricular hypertrophy
      VariableLeft Ventricular HypertrophyP
      Yes

      N=576
      No

      N=511
      Left Ventricular Ejection Fraction (%), mean±SD54±1057±8<0.0001
      Student t test.
      Left Ventricular Ejection Fraction <50%133 (23%)62 (12%)<0.0001
      Chi-square test.
      Left Ventricular Mass Indexed by Body Surface Area (g/m2), mean±SD132±2789±15<0.0001
      Student t test.
      Relative Wall Thickness (>0.42)338 (59%)215 (42%)<0.0001
      Chi-square test.
      Left Ventricular Internal End-Diastolic Dimension (mm), mean±SD53±648±5<0.0001
      Student t test.
      Interventricular Septum Thickness (mm), mean±SD12±210±2<0.0001
      Student t test.
      Posterior Wall Thickness (mm), mean±SD11±29±1<0.0001
      Student t test.
      Left Atrial Diameter (mm), mean±SD
      Data referred to 912 patients.
      45±844±90.2488
      Student t test.
      Cardiac Remodeling<0.0001
      Chi-square test.
      None Remodeling0 (0)296 (58%)
      Concentric Remodeling0 (0)215 (42%)
      Eccentric Hypertrophy238 (41%)0 (0)
      Concentric Hypertrophy338 (59%)0 (0)
      SD = Standard Deviation.
      Student t test.
      Chi-square test.
      Data referred to 912 patients.
      Pharmacologic treatments distribution in the 2 groups are reported in Table 3. Patients with LVH were more likely treated with oral anticoagulants (OAC) and angiotensin-converting enzyme inhibitors than those without LVH.
      Table 3Pharmacologic treatments distribution according to the presence of left ventricular hypertrophy
      VariableLeft Ventricular HypertrophyP
      Chi-square test.
      Yes

      N=576
      No

      N=511
      Anti-Thrombotic0.0134
      None48 (8.3%)62 (12%)
      Oral Anticoagulant381 (66%)309 (61%)
      Antiplatelets117 (20%)125 (25%)
      Oral Anticoagulant+Antiplatelets30 (5.1%)15 (2.9%)
      Statins218 (38%)189 (37%)0.7697
      Beta-Blockers260 (45%)213 (42%)0.2513
      Angiotensin-Converting-Enzyme Inhibitors222 (39%)155 (30%)0.0045
      Angiotensin II Receptor Blockers212 (37%)169 (33%)0.1979
      Calcium Channel Blockers165 (29%)127 (25%)0.1591
      Nitrates83 (14%)38 (7.4%)0.0002
      Antiarrhythmics159 (28%)156 (31%)0.2888
      Digoxin117 (20%)64 (13%)0.0005
      Diuretics
      Data referred to 859 patients.
      293 (60%)193 (45%)<0.0001
      Oral Hypoglycemic Agents92 (16%)52 (10%)0.0049
      Subcutaneous Insulin44 (7.6%)11 (2.1%)<0.0001
      Chi-square test.
      Data referred to 859 patients.
      Final forward logistic model showed that female gender (odds ratio [OR] 2.808, 95% confidence interval [CI] 2.152 to 3.664, p <0.001), age (OR per year 1.035, 95% CI 1.021 to 1.048, p <0.001), hypertension (OR 2.302, 95% CI 1.606 to 3.299, p <0.001), diabetes (OR 1.623, 95% CI 1.169 to 2.253, p = 0.004), and previous MI (OR 1.964, 95% CI 1.328 to 2.903, p = 0.001) were independently associated with LVH. No influence of enrolling centers was evident.
      LVH was detected in 67% of NVAF women compared to 42% in men. Number of atherosclerotic risk factors was greater in male patients with LVH compared to those without (2.04 ± 1.20 vs 1.76 ± 1.02, p = 0.0041). Similar data were recorded in female patients with LVH compared to those without (1.92 ± 1.12 vs 1.70 ± 1.10, p = 0.0434). Concentric hypertrophy was more common in female patients (F = 46% vs M = 29%, p = 0.0003). Women with LVH, compared with men, were less treated with OAC (65% vs 69%, p = 0.0318).

      Discussion

      The present analysis of a selected cohort from the ARAPACIS study provides, for the first time, data on the high prevalence of LVH, defined as LVM indexed by BSA. Second, we identified female gender, age, hypertension, diabetes, and previous MI as clinical factors associated with the presence of LVH in patients with NVAF. Third, we observed that concentric hypertrophy was the most common remodeling pattern in female patients with NVAF.
      These findings could contribute to a better understanding of ventricular remodeling in patients with NVAF. In fact, previous clinical studies reported a huge range (from 23% to 68%) of LVH prevalence in AF,
      • Apostolakis S.
      • Sullivan R.M.
      • Olshansky B.
      • Lip G.Y.
      Left ventricular geometry and outcomes in patients with atrial fibrillation: the AFFIRM Trial.
      • Verdecchia P.
      • Reboldi G.
      • Di Pasquale G.
      • Mazzotta G.
      • Ambrosio G.
      • Yang S.
      • Pogue J.
      • Wallentin L.
      • Ezekowitz M.D.
      • Connolly S.J.
      • Yusuf S.
      RE-LY Study Investigators
      Prognostic usefulness of left ventricular hypertrophy by electrocardiography in patients with atrial fibrillation (from the Randomized Evaluation of Long-Term Anticoagulant Therapy Study).
      probably because of heterogeneity of patients enrolled or to different LVH evaluations.
      • Apostolakis S.
      • Sullivan R.M.
      • Olshansky B.
      • Lip G.Y.
      Left ventricular geometry and outcomes in patients with atrial fibrillation: the AFFIRM Trial.
      • Verdecchia P.
      • Reboldi G.
      • Di Pasquale G.
      • Mazzotta G.
      • Ambrosio G.
      • Yang S.
      • Pogue J.
      • Wallentin L.
      • Ezekowitz M.D.
      • Connolly S.J.
      • Yusuf S.
      RE-LY Study Investigators
      Prognostic usefulness of left ventricular hypertrophy by electrocardiography in patients with atrial fibrillation (from the Randomized Evaluation of Long-Term Anticoagulant Therapy Study).
      Using a standard recommended method for LVH definition, we have now provided more reliable data on LVH prevalence in patients with NVAF. Second, taking in account that LVMI-BSA seems to be one of the most reliable method to determine the cardiovascular risk associated with left ventricular remodeling,
      • Cuspidi C.
      • Facchetti R.
      • Bombelli M.
      • Sala C.
      • Grassi G.
      • Mancia G.
      Differential value of left ventricular mass Index and Wall thickness in predicting cardiovascular prognosis: data from the PAMELA population.
      our work could represent a premise for evaluating clinical usefulness of LVH detection in cardiovascular risk assessment also in patients with NVAF. Indeed, higher prevalence of ABI ≤0.90 could suggest an association between atherosclerosis and LVH,
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      Endothelial dysfunction predicts regression of hypertensive cardiac mass.
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      Pulse pressure and endothelial dysfunction in never-treated hypertensive patients.
      which requires further investigations. Moreover, the recognition of LVH may play a pivotal role to correctly stratify cerebrovascular risk of patients with NVAF as reported in hypertensive patients.
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      • Devereux R.B.
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      • Savage D.D.
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      Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension.
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      • Wang H.
      • Hui R.
      Left ventricular hypertrophy, abnormal ventricular geometry and relative wall thickness are associated with increased risk of stroke in hypertensive patients among the Han Chinese.
      In fact, previous data demonstrated that increased LVM, and abnormal RWT, are associated with increased risk of stroke in hypertensive patients, even higher in patients with a concentric pattern.
      • Wang S.
      • Xue H.
      • Zou Y.
      • Sun K.
      • Fu C.
      • Wang H.
      • Hui R.
      Left ventricular hypertrophy, abnormal ventricular geometry and relative wall thickness are associated with increased risk of stroke in hypertensive patients among the Han Chinese.
      A post hoc analysis from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial
      • Verdecchia P.
      • Reboldi G.
      • Di Pasquale G.
      • Mazzotta G.
      • Ambrosio G.
      • Yang S.
      • Pogue J.
      • Wallentin L.
      • Ezekowitz M.D.
      • Connolly S.J.
      • Yusuf S.
      RE-LY Study Investigators
      Prognostic usefulness of left ventricular hypertrophy by electrocardiography in patients with atrial fibrillation (from the Randomized Evaluation of Long-Term Anticoagulant Therapy Study).
      reported that LVH assessed by LVM was an independent predictor of both all-cause mortality and stroke in patients with AF.
      • Verdecchia P.
      • Reboldi G.
      • Di Pasquale G.
      • Mazzotta G.
      • Ambrosio G.
      • Yang S.
      • Pogue J.
      • Wallentin L.
      • Ezekowitz M.D.
      • Connolly S.J.
      • Yusuf S.
      RE-LY Study Investigators
      Prognostic usefulness of left ventricular hypertrophy by electrocardiography in patients with atrial fibrillation (from the Randomized Evaluation of Long-Term Anticoagulant Therapy Study).
      Further evaluations of follow-up data of ARAPACIS study will provide a relevant evidence to clarify this poorly explored issue.
      Although patients with LVH are at greater thromboembolic risk, we found suboptimal OAC use, as previously reported for the overall ARAPACIS study population.
      • Lang R.M.
      • Bierig M.
      • Devereux R.B.
      • Flachskampf F.A.
      • Foster E.
      • Pellikka P.A.
      • Picard M.H.
      • Roman M.J.
      • Seward J.
      • Shanewise J.S.
      • Solomon S.D.
      • Spencer K.T.
      • Sutton M.S.
      • Stewart W.J.
      Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography
      Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.
      Moreover, female patients with LVH seem to be significantly less treated with OAC. Considering the higher stroke risk in women with LVH compared to men with or without LVH,
      • Regitz-Zagrosek V.
      Therapeutic implications of the gender-specific aspects of cardiovascular disease.
      • Vaccarino V.
      • Badimon L.
      • Corti R.
      • de Wit C.
      • Dorobantu M.
      • Hall A.
      • Koller A.
      • Marzilli M.
      • Pries A.
      • Bugiardini R.
      Working Group on Coronary Pathophysiology and Microcirculation
      Ischaemic heart disease in women: are there sex differences in pathophysiology and risk factors? Position paper from the working group on coronary pathophysiology and microcirculation of the European Society of Cardiology.
      the underuse of OAC could contribute to the higher stroke risk of female patients. The standard evaluation of LVH presence in patients with NVAF could be useful to better define thromboembolic risk, independently by other thromboembolism risk factors. When available, prospective data coming from ARAPACIS study might clarify this aspect.
      Our data suggest that different LVH development among sex might be relevant in stratifying thromboembolic risks of patients with NVAF. The prevalence of concentric hypertrophy in our female patients with NVAF was significantly higher compared with men. Indeed, experimental data suggest that cardiac hypertrophy development in response to a pathologic stimulus may be blunted in women compared with men,
      • Liao Y.
      • Cooper R.S.
      • MensHypertension G.A.
      • McGee D.L.
      Left ventricular hypertrophy has a greater impact on survival in women than in men.
      yet the relative mortality risk, when hypertrophy does occur, is greater in women and is more commonly concentric.
      • Lip G.Y.
      • Nieuwlaat R.
      • Pisters R.
      • Lane D.A.
      • Crijns H.J.
      Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation.
      • Pancholy S.B.
      • Sharma P.S.
      • Pancholy D.S.
      • Patel T.M.
      • Callans D.J.
      • Marchlinski F.E.
      Meta-analysis of gender differences in residual stroke risk and major bleeding in patients with nonvalvular atrial fibrillation treated with oral anticoagulants.
      As stated previously, concentric hypertrophy in hypertensive patients carries the greatest stroke risk.
      • Wang S.
      • Xue H.
      • Zou Y.
      • Sun K.
      • Fu C.
      • Wang H.
      • Hui R.
      Left ventricular hypertrophy, abnormal ventricular geometry and relative wall thickness are associated with increased risk of stroke in hypertensive patients among the Han Chinese.
      Furthermore, gender differences in LVH distribution and worse cardiac remodeling in patients with NVAF may partly explain why female gender confers additional risk of thromboembolic stroke. Accordingly, the presence of LVH, as defined by electrocardiography, confers a greater stroke risk of in patients with LVH AF.
      • Apostolakis S.
      • Sullivan R.M.
      • Olshansky B.
      • Lip G.Y.
      Left ventricular geometry and outcomes in patients with atrial fibrillation: the AFFIRM Trial.
      As with any observational analysis, residual unmeasured confounders may exist and impact the validity of our results. Given the cross-sectional nature of the study, data presented cannot establish a pathophysiological link between NVAF and LVH but provide hypothesis-generating associations. Given that hypertension was highly prevalent in patients with NVAF and because hypertension represents a fundamental risk factor for the developing of LVH, we cannot establish whether LVH was evident before the development of NVAF. Finally, the present analysis is based on the assumption that walls thickness and geometry are homogenous. This assumption could bias the evaluation of LVH prevalence, even if reduced by the use of 3 different measurements to assess LVM.
      To summarize, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. Ongoing prospective data from the ARAPACIS study will clarify the potential predictive role of LVH in patients with NVAF.

      Disclosures

      Professor Lip served as an advisor or consultant for: Astellas Pharma, Inc.; Bayer HealthCare Pharmaceuticals; BIOTRONIK; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol-Myers Squibb Company; Daiichi Sankyo, Inc.; Merck & Co., Inc.; Pfizer Inc; Portola Pharmaceuticals, Inc.; Sanofi. Served as a speaker or a member of a speakers bureau for: Bayer HealthCare Pharmaceuticals; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol-Myers Squibb Company; Pfizer Inc; Sanofi. All other authors have nothing to disclose.

      Supplementary Data

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