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).