Faculty Bibliography

Background Takotsubo syndrome (TTS) mimics acute myocardial infarction in the absence of culprit coronary artery disease and is more common in women. Spontaneous coronary artery dissection (SCAD) shares a predilection for women, can result in left ventricular wall motion abnormalities similar to TTS, and may manifest subtle angiographic findings. The aim of this study was to determine the frequency of SCAD misdiagnosed as TTS. Methods and Results Coronary angiograms of patients presenting with a provisional diagnosis of TTS were retrospectively reviewed by an independent expert blinded to left ventriculography and the specific purpose of the study to assess for SCAD. TTS was defined using European Society for Cardiology criteria. SCAD was categorized according to the Saw angiographic classification. Among 80 women with a provisional diagnosis of TTS, 2 (2.5%) met angiographic criteria for definite SCAD. Both dissections were located in the distal left anterior descending coronary artery and classified as type 2b. The wall motion abnormality was apical in both cases. An additional 7 patients (9%) had angiography that was indeterminate for SCAD. Clinical characteristics of patients with and without SCAD were similar. Conclusions Among patients with a provisional diagnosis of TTS, definite SCAD in the left anterior descending coronary artery was present in 2.5% of cases, and coronary angiography was indeterminate for SCAD in an additional 9%. Careful review of coronary angiography may avoid missed diagnoses of SCAD in patients with myocardial infarction, nonobstructive coronary arteries, and wall motion abnormalities consistent with TTS. Intracoronary imaging maybe considered to establish a definitive diagnosis of SCAD when angiography is inconclusive.

Disopyramide is effective and safe in patients with obstructive hypertrophic cardiomyopathy. However, its cellular and molecular mechanisms of action are unknown. We tested disopyramide in cardiomyocytes from the septum of surgical myectomy patients: disopyramide inhibits multiple ion channels, leading to lower Ca transients and force, and shortens action potentials, thus reducing cellular arrhythmias. The electrophysiological profile of disopyramide explains the efficient reduction of outflow gradients but also the limited prolongation of the QT interval and the absence of arrhythmic side effects observed in 39 disopyramide-treated patients. In conclusion, our results support the idea that disopyramide is safe for outpatient use in obstructive patients.

Background: Despite the increased prevalence of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM), the efficacy of radiofrequency ablation (RFA) has been characterized over limited follow-up intervals (~1 year). Several large meta-analyses note that patients with HCM have substantially higher rates of arrhythmia recurrence after RFA, compared to patients without HCM. The implication of confirmed HCM mutations on ablation efficacy has similarly only been assessed in small-scale studies.
Objective(s): To assess arrhythmia recurrence after RFA in patients with HCM and paroxysmal AF (PAAF) or persistent AF (PEAF) as well as its relation to their genetic background and LVOT gradient.
Method(s): Arrhythmia recurrence after RFA was assessed in 66 HCM patients and compared to 343 patients without HCM. AF recurrence was defined as AF on EKG or >30s of AF on ICD/pacemaker interrogation or on monitoring devices after a 3-month blanking period. Kaplan-Meier analysis was performed to compare arrhythmia recurrence rate and timing.
Result(s): The EF of HCM patients was higher than that of the non-HCM patients in both the PAAF and PEAF groups (65.5 and 63.0% vs 61.4 and 53.3%, respectively, p<0.001); within the HCM group, the clinical characteristics of the genetically (+) HCM group (n=14) did not differ from those of the genetically (-) group (n=12). Arrhythmia recurrence at 1 year in PAAF and PEAF was not significantly different between HCM and non-HCM patients (18% vs 11%, p=0.2, and 33% vs 26%, p=1), nor was mean time to arrhythmia recurrence (PAAF 193+/-48 vs 181+/-59 days, p=0.8, and PEAF 175+/-58 vs 168+/-20 days, p=0.6). Recurrence rates over the entire follow-up period of the HCM patients were 54 and 85% in the PAAF and PEAF groups (1076+/-187 and 1050+/- 201 days of follow-up), respectively. Amongst HCM patients with LVOT gradients >70mmHg (PAAF, n = 8, and PEAF, n = 3) longer-term rates of arrhythmia recurrence were similar at 88% and 67% (p=0.9).
Conclusion(s): Arrhythmia recurrence at 1 year following AF ablation in HCM patients is similar to that of non-HCM AF patients regardless of the type of AF. Absolute rates of atrial arrhythmia recurrence in HCM patients at >3 years post ablation are considerable. Confirmed HCM mutations and severe LVOT gradients do not modify the outcome of AF ablation.
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Background: Left ventricular outflow tract (LVOT) obstruction is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM). AV sequential pacing has not demonstrated benefit for patients with medication-refractory LVOT obstruction in prospective, randomized clinical trials, although these trials did not include transthoracic echocardiogram (TTE) guided optimization or concomitant pharmacotherapy with disopyramide.
Objective(s): To evaluate efficacy of a standardized TTE guided AV optimization protocol for patients with persistent LVOT obstruction despite AV sequential pacing for reduction in LVOT gradient.
Method(s): Outcomes of 20 consecutive HCM patients with medication refractory LVOT gradients who were not surgical candidates and underwent AV sequential pacing from 8/2014 to 6/2017 were analyzed. ECG guided AV intervals were determined by the implanting cardiac electrophysiologist at the time of implant. Patients with incomplete response to initial settings underwent Doppler TTE guided AV optimization.
Result(s): All patients received maximally tolerated disopyramide and beta or calcium channel blockade. Following initial implant, 8 of 20 (40%) of patients had complete elimination of LVOT gradient with, and 12 of 20 (60%) had incomplete response and underwent TTE guided optimization. Compared to initial ECG guided programming, the TTE optimized sensed AV delays were shorter in all patients (mean reduction 51 +/- 48ms). Following TTE guided AV optimization, 9 of 12 patients had elimination of LVOT gradient, and 3 of 12 patients had 82.6 +/- 5.2% reduction in LVOT gradient. Patients undergoing TTE optimization had significant reduction in NYHA heart failure class (1.0 +/- 0 vs. 2.2 +/- 0.7, p=0.004).
Conclusion(s): TTE guided AV optimization shows promise as a means of improving outcomes in patients with incomplete response to medical therapy including disopyramide and AV sequential pacing for reduction of LVOT gradient in HCM.
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Background Hypertrophic cardiomyopathy is defined as unexplained left ventricular ( LV ) hypertrophy (wall thickness ≥15 mm) and is prevalent in 0.2% of adults (1:500) in population-based studies using echocardiography. Cardiac magnetic resonance imaging ( MRI ) allows for more accurate wall thickness measurement across the entire ventricle than echocardiography. The prevalence of unexplained LV hypertrophy by cardiac MRI is unknown. MESA (Multi-Ethnic Study of Atherosclerosis) recruited individuals without overt cardiovascular disease 45 to 84 years of age. Methods and Results We studied 4972 individuals who underwent measurement of regional LV wall thickness by cardiac MRI as part of the MESA baseline exam. American Heart Association criteria were used to define LV segments. We excluded participants with hypertension, LV dilation (≥95% predicted end-diastolic volume) or dysfunction (ejection fraction ≤50%), moderate-to-severe left-sided valve lesions by cardiac MRI , severe aortic valve calcification by cardiac computed tomography (aortic valve Agatston calcium score >1200 in women or >2000 in men), obesity (body mass index >35 kg/m²), diabetes mellitus, and current smoking. Sixty-seven participants (aged 64±10 years, 9% female) had unexplained LV hypertrophy (wall thickness ≥15 mm in at least 2 adjacent LV segments), representing 1.4% (1 in 74) participants, 2.6% of men and 0.2% of women. Prevalence was similar across categories of race/ethnicity. Hypertrophy was focal in 17 (25.4%), intermediate in 44 (65.7%), and diffuse in 5 (7.5%) participants. Conclusions The prevalence of unexplained LV hypertrophy in a population-based cohort using cardiac MRI was 1.4%. This may have implications for the diagnosis of patients with hypertrophic cardiomyopathy and will require further study.

Background: Hypertrophic cardiomyopathy is defined as unexplained left ventricular (LV) hypertrophy (wall thickness >= 15 mm) and is prevalent in 0.2% of adults (1:500) in population-based studies utilizing echocardiography. Cardiac magnetic resonance imaging (MRI) allows for more accurate wall thickness measurement across the entire ventricle than echocardiography. However, the prevalence of unexplained LV hypertrophy has not been examined in a cohort utilizing cardiac MRI. The Multi-Ethnic Study of Atherosclerosis (MESA) recruited individuals without overt cardiovascular disease 45-84 years of age. Method(s): We studied 4,972 individuals who underwent measurement of regional LV wall thickness by cardiac MRI as part of the MESA baseline exam. American Heart Association criteria were used to define LV segments. We excluded participants with hypertension, LV dilation (>= 95% predicted end-diastolic volume) or dysfunction (ejection fraction <= 50%), moderate-severe left-sided valve lesions by cardiac MRI or severe aortic valve calcification by cardiac computed tomography (aortic valve Agatston calcium score > 1,200 in women or > 2,000 in men), diabetes mellitus and current smoking. Result(s): 67 participants (age 64 +/- 10 years, 9% female) had unexplained LV hypertrophy (wall thickness >= 15 mm in at least 2 adjacent LV segments), representing 1.4% (1 in 74) participants, 2.6% of men and 0.2% of women. Prevalence was similar across categories of race/ethnicity. Hypertrophy was focal (2 segments) in 17 (25.4%), intermediate (3 to 7 segments) in 44 (65.7%) and diffuse (>= 8 segments) in 5 (7.5%) participants. The most commonly hypertrophied segments in each level were the basal anterior septal (46%), midventricular anterior lateral (40%) and apical lateral (33%) segments. Conclusion(s): The prevalence of unexplained LV hypertrophy in a population-based cohort utilizing cardiac MRI was 1.4%. This may have implications for diagnosis and management of patients with hypertrophic cardiomyopathy and will require further study.2019 American College of Cardiology Foundation. All rights reserved

BACKGROUND:Acute left ventricular (LV) apical ballooning with normal coronary angiography occurs rarely in obstructive hypertrophic cardiomyopathy (OHCM); it may be associated with severe hemodynamic instability. METHODS, RESULTS/UNASSIGNED:We searched for acute LV ballooning with apical hypokinesia/akinesia in databases of two HCM treatment programs. Diagnosis of OHCM was made by conventional criteria of LV hypertrophy in the absence of a clinical cause for hypertrophy and mitral-septal contact. Among 1519 patients, we observed acute LV ballooning in 13 (0.9%), associated with dynamic left ventricular outflow tract (LVOT) obstruction and high gradients, 92 ± 37 mm Hg, 10 female (77%), age 64 ± 7 years, LVEF 31.6 ± 10%. Septal hypertrophy was mild compared to that of the rest of our HCM cohort, 15 vs 20 mm (P < 0.00001). An elongated anterior mitral leaflet or anteriorly displaced papillary muscles occurred in 77%. Course was complicated by cardiogenic shock and heart failure in 5, and refractory heart failure in 1. High-dose beta-blockade was the mainstay of therapy. Three patients required urgent surgical relief of LVOT obstruction, 2 for refractory cardiogenic shock, and one for refractory heart failure. In the three patients, surgery immediately normalized refractory severe LV dysfunction, and immediately reversed cardiogenic shock and heart failure. All have normal LV systolic function at 45-month follow-up, and all have survived. CONCLUSIONS:Acute LV apical ballooning, associated with high dynamic LVOT gradients, may punctuate the course of obstructive HCM. The syndrome is important to recognize on echocardiography because it may be associated with profound reversible LV decompensation.