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Supplemental fileCardiac magnetic resonance acquisition protocolScout images were acquired initially to identify the cardiac axes. Subsequently, balanced steady-state free precession images were acquired using the following representative technical parameters: echo time = 1.6 ms, repetition time = 3.3 ms, flip angle = 70°, temporal resolution = 68 ms, and slice thickness = 6 mm (long-axis images) or 8 to 10 mm (contiguous short-axis images encompassing the entire LV volume, from apex to base). For short-axis images, the matrix size varied from 140 to 180 in the x-direction (phase-encoding direction) and 256 in the y-direction. In long-axis images, the matrix size varied from 120 to 210 in the x-direction (phase-encoding direction) and 256 in the y-direction. For patients able to suspend respiration, breath-hold duration was 10 to 15 s, depending on the heart rate; otherwise, images were acquired using 3 signal averages. Subsequently, LGE images were obtained in the same long- and short-axis orientations as in the above-described balanced steady-state free precession images, ～15-20 min after injection of 0.2 mmol/kg of gadolinium dimenglumine (Magnevist, Berlex Imaging, Wayne, New Jersey), using a phase-sensitive inversion recovery spoiled gradient echo sequence with following representative parameters: echo time = 4 ms, repetition time = 8 ms, flip angle = 30°, bandwidth = 140 Hz/pixel, 23 k-space lines acquired every other RR-interval, field of view (varied from 228 to 330 in the x-direction and 260 to 330 in the y-direction), and matrix size (varied from 140 to 180 in the x-direction and 256 in the y-direction). This gave a spatial resolution of 1.5 to 2.1 mm (x-direction) by 1.1 to 1.4 mm (y-direction).Comparison of % LGE measured by 2SD, 6SD and manual tracing. In 20 randomly selected patients from the current study, to test the accuracy of LGE quantification vis-à-vis manual tracing, we measured LGE utilizing 2SD, 6SD and manual assessment. Using 2SD threshold, the mean LGE % was 24.5±7.9%), which was significantly higher when compared to 6SD (20±7.3%) and manual tracings (19.9±7.3%), respectively (both p<0.01). However, there was no significant difference in % LGE measured at 6SD threshold vs. manual tracing (p=0.9). Bland-Altman figures are shown below in supplemental figures 1A-B.Supplemental figure 1: Bland-Altman figures comparing % LGE measured at 2SD vs. manual (A) and 6SD vs. manual (B) Based on the figures above generated from patients in the current study, we can infer that calculating %LGE at 2SD significantly overestimates when compared to manual tracing; while % LGE calculated at 6SD threshold was similar to manual tracing. Reproducibility of LGE measurements at 6SDThere was excellent intra (MD measured twice, at least 1 month apart) and inter-observer (MD and AM, measured at least 1 month apart) reproducibility of LGE measurements, as assessed in 30 randomly selected patients using the Bland-Altman technique.Supplemental figure 2: Bland-Altman analysis testing reproducibility of late gadolinium enhancement in the study sample. Bland-Altman analysis demonstrating excellent a) intra-observer and b) inter-observer reproducibility.Supplemental table 1: Additional Outcomes during longer-term follow up in the study sampleVariableTotal study sample (n=1423)Nonobstructive(n=458)Obstructive (n=965)p-valueNo myectomy(n=279)Myectomy(n=686)Nonsustained ventricular tachycardia95 (7%)46 (10%)17 (6%)32 (5%)<0.01Ventricular tachycardia10 (0.7%)2 (0.4%)3 (1%)5 (0.7%)0.60Atrial fibrillation 72 (5%)18 (4%)10 (4%)44 (6%)0.08Pacemaker67 (5%)13 (3%)6 (2%)48 (7%)<0.001Internal cardioverter defibrillator88 (6%)44 (10%)13 (5%)31 (5%)<0.01Stroke13 (1%)7 (1.5%)4 (1.4%)2 (0.2%)0.26Decompensated congestive heart failure requiring admission15 (1.1%)8 (2%)07 (1%)0.31Primary composite outcome60 (4%)27 (6%)17 (6%)16 (2.3%)<0.01*Secondary composite outcome67 (5%)30 (7%)20 (7%)17 (2.4%)<0.01?* p-value derived from competing risk regression survival analysis? p-value derived from Cox Proportional Hazards survival analysisSupplemental Table 2: Univariable competing risk regression analysis in the total study population (n=1423) based on the Fine-Gray proportional subhazards model (primary composite events=60, additional non SCD deaths=5)VariablesubHazard ratio [95% CI]p-valueAge (for 10 year increase)1.56 [1.05-2.34]0.03Male gender0.91 [0.54-1.54]0.72History of hypertension1.13 [0.66-1.94]0.64History of atrial fibrillation1.99 [0.93-4.26]0.17Syncope1.63 [0.65-4.10]0.29NYHA Class I vs. ≥II1.30 [1.06-1.58]0.01Family history of HCM1.49 [0.33-4.71]0.58Family history of SCD1.36 [0.55-3.35]0.68Medical therapy for HCMHistory of NSVT2.07 [0.97-4.44]0.06ESC risk score1.23 [0.88-1.61]0.23ACC/AHA risk factors1.34 [0.84-1.81]0.32Maximal LV thickness1.03 [0.97-1.07]0.65Indexed LA size1.02 [1.005-1.06]0.04≥ Moderate mitral regurgitation0.81 [0.54-1.74]0.82E/e’ ratio1.01 [0.97-1.08]0.74Maximal LVOT gradient (for every 10 mm Hg increase)1.07 [1.01-1.13]0.004Indexed LV mass (for every 10 g/m2 increase)1.09 [0.99-1.21]0.08LV ejection fraction (for every 1% decrease)1.04 [0.98-1.11]0.14Indexed LV end-systolic volume (for every 10 mm/m2 increase)1.01 [0.97-1.05]0.80LGE None>0 to < 15%≥15%Reference1.41 [0.87-2.39]2.34 [1.29-3.31]0.39<0.001Surgery to relieve LVOT obstruction (in the obstructive HCM subgroup)0.34 [0.19-0.65]<0.001HCM=hypertrophic cardiomyopathy, NSVT=Nonsustained ventricular tachycardia, NYHA=New York Heart Association, ESC=European Society of Cardiology, SCD=sudden cardiac death, ACC/AHA=American College of Cardiology/American Heart Association, LV=left ventricle, LVOT=left ventricular outflow tract, LGE=late gadolinium enhancementSupplemental table 3: Multivariable Cox Proportional Hazards Survival analysis in the entire study population for secondary composite events (all cause death + appropriate ICD discharge), separated into obstructive and nonobstructive subgroups A: Nonobstructive subgroup (n=458, number of secondary composite events=30)VariableHazard ratiop-valueESC % 5-year SCD risk score1.05 [0.76-1.36]0.91% LGENone>0 to < 15%≥15%Reference1.43 [0.83-4.87]2.99 [1.39-5.81]0.320.004B: Obstructive subgroup (n=965, number of secondary composite events=37)ESC % 5-year SCD risk score (continuous variable)1.16 [0.89-1.66]0.28% LGENone>0 to < 15%≥15%Reference1.53 [0.89-5.12]3.05 [1.51-5.97]0.280.003Surgery to relieve left ventricular outflow tract obstruction 0.46 [0.22-0.85]0. 01ESC=European Society of Cardiology, SCD=sudden cardiac death, ACC/AHA=American College of Cardiology/American Heart AssociationFindings were similar if ACC/AHA risk factors were substituted for ESC SCD risk scoreSupplemental table 4: Net reclassification risk tables for primary composite events in various subgroupsA: Obstructed HCM groupI: Reclassification based on ESC risk score + LGE ≥ 15%Patients without primary events during follow-upUpdated model (ESC risk score + LGE ≥ 15%Initial model (ESC risk score)(0-0.0226)(0.0226-0.0341)(0.0341-0.0453)(0.0453-1)% reclassified(0-0.0226)1922315819(0.0226-0.0341)1970038100(0.0341-0.0453)32152046100(0.0453-1)0731055178Patients with primary events during follow-upUpdated model (ESC risk score + LGE ≥ 15%Initial model (ESC risk score)(0-0.0226)(0.0226-0.0341)(0.0341-0.0453)(0.0453-1)% reclassified(0-0.0226)30000(0.0226-0.0341)2004100(0.0341-0.0453)2306100(0.0453-1)034654Categorical NRI 0.34 [95% CI 0.05-0.63], p=0.02II: Reclassification based on ESC risk score + LGE ≥ 15% + myectomyPatients without primary events during follow-upUpdated model (ESC risk score + LGE ≥ 15% + myectomy)Initial model (ESC risk score+ LGE ≥ 15%(0-0.0158)(0.0158-0.0252)(0.0252-0.0363)(0.0363-1)% reclassified(0-0.0158)2032016015(0.0158-0.0252)14348251980(0.0252-0.0363)0144127995(0.0363-1)0291617820Patients with primary events during follow-upUpdated model (ESC risk score + LGE ≥ 15% + myectomy)Initial model (ESC risk score+ LGE ≥ 15%(0-0.0158)(0.0158-0.0252)(0.0252-0.0363)(0.0363-1)% reclassified(0-0.0158)20000(0.0158-0.0252)210383(0.0252-0.0363)0105100(0.0363-1)010185Categorical NRI 0.31 [95% CI 0.10-0.51], p=0.003B: Nonobstructed HCM groupPatients without primary events during follow-upUpdated model (ESC risk score + LGE ≥ 15%)Initial model (ESC risk score)(0-0.048)(0.048-0.0524)(0.0524-0.0633)(0.0633-1)% reclassified(0-0.048)82002523(0.048-0.0524)800029100(0.0524-0.0633)790030100(0.0633-1)501273765Patients with primary events during follow-upUpdated model (ESC risk score + LGE ≥ 15%)Initial model (ESC risk score)(0-0.048)(0.048-0.0524)(0.0524-0.0633)(0.0633-1)% reclassified(0-0.048)400450(0.048-0.0524)2003100(0.0524-0.0633)1004100(0.0633-1)110722Categorical NRI 0.56 [95% CI 0.27, 0.84], p<0.001C: Group that underwent myectomyPatients without primary events during follow-upUpdated model (ESC risk score + LGE ≥ 15%Initial model (ESC risk score)(0-0.0189)(0.0189-0.0237)(0.0237-0.0284)(0.0284-1)% reclassified(0-0.0189)123593227(0.0189-0.0237)1390030100(0.0237-0.0284)1390026100(0.0284-1)27100182287Patients with primary events during follow-upUpdated model (ESC risk score + LGE ≥ 15%)Initial model (ESC risk score)(0-0.0189)(0.0189-0.0237)(0.0237-0.0284)(0.0284-1)% reclassified(0-0.0189)210033(0.0189-0.0237)2000100(0.0237-0.0284)1005100(0.0284-1)030260Categorical NRI 0.48 [95% CI 0.05-0.91], p=0.02ESC=European Society of Cardiology, LGE= late gadolinium enhancement, NRI=net reclassification improvement, CI=confidence intervalNumbers in parenthesis represent probabilities from 0 to 1. Numbers in columns (under the probabilities) represent numbers of patients who were reclassifiedOverall findings were similar when ACC/AHA risk factors were substituted, instead of ESC SCD risk score ................
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