Faculty Bibliography

Background Recently the clinical spectrum of hypertrophic cardiomyopathy (HCM) has been expanded to include patients with mild or no thickening of the left ventricle (LV) yet who have outflow tract obstruction at rest or after exercise, principally due to characteristic HCM anterior mitral leaflet (AML) elongation and papillary muscle anomalies. Apical ballooning mimicking a takotsubo syndrome (TTS) wall motion pattern can occur in mild-septal-thickening HCM when latent obstruction becomes unrelenting. The objective of this study is to define the prevalence of anatomic abnormalities characteristic of HCM in an unselected population of patients diagnosed clinically with TTS. Methods We analyzed echocardiograms of 44 admitted TTS patients including studies performed during admission, before the event (n=11, median 515 days before) and after recovery of left ventricular function (n=33, median 92 days, IQR=29-327) and compared them to 60 controls, age-matched normal women. Analysis of 148 echocardiograms was blinded to timing, and patient vs. control status. Results Age was 67+/-12 years, 42 female (95%). During the ballooning event, 13 (30%) had SAM and 9 patients (20%) had LV outflow tract obstruction (LVOTO), gradients 71+/-40 mmHg. Compared to TTS patients without SAM, those with SAM had longer AML (30 vs. 26mm), and thicker septum (16 vs. 12 mm) and less distance from septum to coaptation (19 vs. 27mm), all p <=0.006. Eleven of the SAM patients had >=2 anatomic abnormalities predisposing to obstruction (defined as > 2 SD above normal), and/or an anomalous papillary muscle/chordae. In the 44 TTS patients each parameter differed from controls before, during and after the TTS event. Eight (18%) had abnormal right ventricular wall motion, none of whom were obstructed. Conclusion Thirty percent of unselected TTS patients have SAM and 20% have significant LVOT gradients. This subset had AML abnormalities and septal thickening typical of obstructive HCM and known to predispose to LVOT obstruction. They are phenotypically identical to patients with documented HCM with mild septal thickening and LVOT obstruction, who have experienced episodes of ballooning.
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Cardiac amyloid A (AA) amyloidosis is rare. We present the case of a 72-year-old woman with obstructive hypertrophic cardiomyopathy (HCM) and biopsy-proven renal AA amyloidosis whose dyspnea and exercise intolerance had worsened over the previous year. Her AA amyloidosis was suspected to be secondary to chronic diverticulitis for which she had undergone hemicolectomy and sigmoidectomy 3 years prior. Echocardiographic findings were consistent with worsening left ventricular outflow tract obstruction at rest. Cardiac magnetic resonance imaging revealed patchy areas of midwall late gadolinium enhancement. Right ventricular endomyocardial biopsy did not reveal amyloid deposition, and cardiac technetium-99m pyrophosphate scintigraphy did not suggest transthyretin amyloidosis. The patient underwent septal myectomy with resection of an accessory papillary muscle. Pathological examination of the myectomy specimen was consistent with HCM. In addition, there was a thick layer of diffuse endocardial and vascular amyloid deposition that was identified as AA type by laser-microdissection with liquid chromatography-coupled tandem-mass spectrometry. This case report highlights the presence of 2 distinct disease processes occurring simultaneously and the importance of tissue diagnosis of AA amyloidosis, a condition that is not commonly associated with HCM.

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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