1. CLINICAL DATA AND OUTCOMES
1.1 Patient Population: Our HCM Registry (JHH-HCM Registry) is approved by the Institutional Review Boards of the Johns Hopkins Hospital (JHH) and the University of California San Francisco (UCSF). Patients were enrolled in the JHH-HCM Registry during their first visit to the Johns Hopkins HCM-Center of Excellence[15] if they met the standard diagnostic criteria for HCM, namely, maximal LV wall thickness ≥15 mm[16] in the absence of uncontrolled hypertension, valvular heart disease and HCM phenocopies (amyloidosis, storage disorders).[17]
We performed a retrospective study of all HCM patients from the JHH-HCM Registry, who were evaluated between January 1, 2003 to March 31, 2017. Clinical data including symptoms, comorbidities, medications, history of arrhythmias were ascertained by the examining physician (MRA, TPA) during the initial clinic visit, and during each follow up visit. Rest and treadmill exercise stress-echocardiography (ECHO) and cardiac magnetic resonance imaging (CMR) were performed at the first clinic visit as part of patients’ clinical evaluation. Patients who were asymptomatic or had stable symptoms were followed yearly; symptomatic patients were followed more frequently (every 1-3 months) until symptom management was achieved. During yearly follow up visits, patients underwent treadmill exercise-echocardiography and 24h Holter monitoring or ICD interrogation. Patients with an ICD had remote device monitoring and device interrogation performed every 6 months, or more frequently if they were symptomatic or experienced ICD discharges. Patients (without ICD) who had palpitations without evidence of arrhythmias on Holter monitor or exercise-electrocardiogram (EKG), were provided event monitors to document cardiac rhythm during symptoms. A subset of HCM patients (n=145) were referred for perfusion-13NH3-PET imaging after ruling out obstructive coronary artery disease by coronary angiography – these pateints had angina, ventricular arrhythmias and/or exertional dyspnea despite optimal therapy.
Atrial fibrillation : Atrial fibrillation was diagnosed if atrial fibrillation/flutter of any duration was present on 12-lead EKG, telemetry, pacemaker/ICD interrogation, or Holter/event monitoring. Paroxysmal atrial fibrillation (PAF) was defined as AF that terminated spontaneously or with intervention in ≤ 7 days of AF onset[18]; persistent AF was defined as AF that lasted >7 days and terminated spontaneously or with treatment; permanent AF was defined as AF that persisted despite treatment to restore sinus rhythm.[19] Atrial fibrillation was diagnosed by review of rest/stress EKGs, event recorder data, Holter monitor data and/or implantable cardioverter defibrillator (ICD) interrogation; a detailed chart review was performed to confirm this criterion. Patients with PAF had confirmed termination of AF within the 7-day window, either by Holter monitor or EKG. Review of medical records, Holter monitor/event recorder studies and ICD interrogations was performed in patients from the No-AF group to ensure no documented history of AF prior to their first clinic visit and during follow up.
1.2 Cardiac imaging: Transthoracic echocardiography was performed using a GE Vivid 7 or E-9 ultrasound machine and a multi-frequency phased-array transducer. Left atrial diameter (anteroposterior) was measured in the parasternal long-axis view at the level of the aortic sinuses, perpendicular to the aortic root long axis, by using the leading-edge to leading–edge convention, just before mitral valve opening (LV end-systole).[20] Echocardiographic images for two dimensional speckle tracking strain analysis were acquired prospectively at frame rates of 50-90 Hz. Longitudinal strain/strain rate was analyzed from the apical two-, three-, and four-chamber views using EchoPAC 112 .[21] Cardiac magnetic resonance (CMR) imaging was performed using a 1.5T system at the first clinic visit. The contrast agent, gadopentetate dimeglumine was used at 0.2 mmol/kg.[22] Left ventricular mass and late gadolinium enhancement (LV-LGE) were quantified using QMass software (QMass 7.4; Medis, Leiden, The Netherlands). Cardiac 13NH3-PET/CT imaging was performed using a GE Discovery VCT PET/CT System and a 1-day rest/stress protocol, as described previously.[23] Please refer to the Supplementary file, Section A1 for detailed methods for rest/stress echocardiography, CMR and PET/CT imaging.
1.3 Cardiovascular events during followup: All analyses were blinded to AF outcome. Cardiovascular adverse events, including AF, stroke, heart failure, sustained ventricular tachycardia (VT), ventricular fibrillation (VF) and death were documented in the HCM Registry. All-cause mortality statistics for our study population were obtained by linking our database to the Social Security Death Index. A detailed description of methods is provided in the Supplementary file, Section A2 .
1.4 Statistics: Descriptive statistics were performed on patient demographics, hemodynamics, echocardiographic and CMR parameters and cardiovascular events, stratified by the presence/absence of AF. Continuous variables are presented as mean ± standard deviation and categorical variables as the total number and percentage. Comparisons between patients with/without AF was performed using the independentt test for continuous variables and the Fischer exact test for categorical variables. Statistical analyses were performed using STATA 14 (StataCorp LP, College Station, Texas).