Sex-Based Outcomes of Surgical Myectomy for Hypertrophic Cardiomyopathy: An Analysis t from The National Readmission Database

Introduction: Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease, often resulting in left ventricular outflow tract obstruction, relieved by surgical myectomy. Current treatments are largely palliative and do not target the root causes. Understanding the molecular drivers of the disease could lead to alternative treatment strategies through identification of novel therapeutic targets. Methods: We performed single nuclei RNA-sequencing (snRNA-seq) on thousands of nuclei from 9 patient myectomy samples and septal tissue from 4 unused donor hearts selected randomly without regard to genotype to identify the cell populations and determine the gene expression patterns in individual cells. Each sample was processed individually using Seurat v3 for quality control and normalization. Next, all 13 samples were integrated into a combined dataset for clustering and differential gene expression analysis to identify markers specific to each cluster and to assign cell identities. Results: Our results revealed several clusters of cardiomyocytes with differences in sarcomeric and metabolic gene expression. Several fibroblast populations were also observed. Numerous genes were differentially expressed between the HCM and normal samples. For example, RARRES1 expression was observed in many of the fibroblast populations in the normal samples, but was absent in the HCM samples. RARRES1 is involved in regulating fatty acid metabolism and autophagy, both of which are altered in HCM. Additionally, expression of PLA2G2A was absent in the HCM samples but was present in almost every cell type in the normal controls. PLA2G2A is involved in suppression of RTK mediated hypertrophic signaling, impacts lipid signaling, and has tumor suppressor properties. Thus, both RARRES1 and PLA2G2A may represent novel targets in HCM. Conclusions: This approach reveals novel potential therapeutic targets within common final HCM pathological pathways independent of genotype that have the potential to guide development of alternative treatment strategies. Further analysis of larger datasets using this approach will likely identify even more common pathway targets and identify additional common mechanisms in the pathogenesis of obstructive HCM.

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Abstract 18019: Successful Surgical Management of Severely Symptomatic Hypertrophic Cardiomyopathy Patients With Minimal Septal Hypertrophy

Circulation ◽

10.1161/circ.130.suppl_2.18019 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Raabia N Ahmad ◽

Barry J Maron ◽

Ethan J Rowin ◽

Tammy S Haas ◽

Joseph A Dearani ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Mitral Valve ◽

Valve Replacement ◽

Mitral Valve Replacement ◽

Heart Block ◽

Valve Repair ◽

Outflow Obstruction ◽

Septal Wall ◽

Septal Hypertrophy ◽

Surgical Myectomy

Background: Marked septal hypertrophy is considered a requirement for effective myectomy in obstructive hypertrophic cardiomyopathy (HCM), with mitral valve replacement recommended as the alternative strategy in patients with minimal hypertrophy. However, it remains uncertain whether relief of obstruction can be effectively abolished without mitral valve replacement in patients with minimal septal wall thickening. Methods: Of 500 patients who underwent surgical myectomy from 2004 to January 2014, 21 (4.2%) were identified with a maximum LV wall thickness ≤ 15mm and constitute the study cohort. Results: All 21 patients (56 ± 10 years old; 62% male) were followed for advanced heart failure symptoms refractory to drug therapy with a maximal septal wall thickness of 13.6 ± 1.7 mm (range: 10-15 mm; ≤ 12 mm in 5 patients). Outflow obstruction ≥ 30 mmHg due to mitral valve-septal contact was present after exercise in 17 of 21 patients (range: 50-150 mmHg), and under resting conditions in 4 patients (range: 30-65 mmHg). In all patients, surgical relief of obstruction consisted of muscular resection of the basal septum with revision of abnormal and apically displaced papillary muscles, which were judged intraoperatively to be contributing to obstruction. In addition, in 10 patients (47%) myectomy alone was not sufficient to relieve obstruction due to the limited opportunity for septal reduction and adjunctive mitral valve repair was performed to shorten an elongated anterior leaflet. No patient required mitral valve replacement or incurred a ventricular septal defect. Post-operatively, 4 patients developed complete heart block requiring permanent pacemaker (1 patient with pre-operative right bundle branch block) and 1 had a cerebrovascular event. At most recent follow up 18 ± 19 months post-myectomy, septal thickness was reduced to 10 ± 2 mm, no patient had an outflow gradient at rest or with provocation, and all patients were alive with the majority asymptomatic (class I: n=13; 62% and class II n=8; 38%). Conclusion: In patients with minimal septal hypertrophy, outflow obstruction can be effectively abolished with surgical myectomy and adjunctive mitral valve repair with a small increased risk of heart block, but without the need for mitral valve replacement.

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Abstract 13729: Surgical Myectomy Results in Significantly Improved Long-term Event Rate in Hypertrophic Cardiomyopathy Patients With Severe Left Ventricular Outflow Tract Obstruction

Circulation ◽

10.1161/circ.130.suppl_2.13729 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Milind Y Desai ◽

Nicholas G Smedira ◽

Aditya Bhonsale ◽

Nitesh Ainani ◽

Maran THamilarasan ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Left Ventricular Outflow Tract ◽

Ventricular Outflow Tract ◽

Left Ventricular ◽

Outflow Tract ◽

Long Term Outcomes ◽

Free Survival ◽

Left Ventricular Outflow ◽

Surgical Myectomy

Background: In hypertrophic cardiomyopathy (HCM) with severe left ventricular outflow tract obstruction (LVOTO), surgical myectomy (SM) performed for relief of intractable symptoms is safe and associated with excellent long-term symptom-free survival. In such patients, we sought to determine if SM also results in improvement of long-term outcomes. Methods: We studied 1530 HCM patients with severe LVOTO (50±13 years, 63% men) that were evaluated at our center [excluding <18 years of age, LV ejection fraction (LVEF) <50%, LVOT gradient <30 mm Hg). Clinical, echocardiographic and surgical data were recorded. A composite endpoint of death and/or implantable defibrillator (ICD) discharge was recorded. Results: Hypertension, coronary artery disease (CAD), family history of HCM and syncope were present in 41%, 15%, 17% and 18%, while 73% patients were in Functional Class (FC) ≥ II. Mean LVEF, basal septal thickness, LVOT gradient (resting or provocable) and indexed left atrial dimensions were 62±5%, 2.2±1 cm, 101±39 mm Hg, 2.2±0.4 cm/m2. During 8±6 years of follow-up, 990 (65%) patients underwent SM (of which 65% were isolated SM), while 540 (35%) did not. 94 (6%) patients had alcohol septal ablation (66 in the non myectomy group), while 18% developed atrial fibrillation (AF), and 18% had ICD. There were 169 (11%) events (151 deaths), with 0% 30-day mortality in the SM group. On stepwise multivariable Cox Proportional Hazard analysis, increasing age (Hazard Ratio or HR 1.22 [1.06-1.40]), CAD (HR 1.57 [1.06-2.33]), worsening FC (HR 1.34 [1.05-1.71]) and AF (HR 1.73 [1.23-2.43]) predicted higher events, while SM as a time-dependent covariate (HR 0.58 [0.41-0.81]) was associated with improved event-free survival (all p<0.01). Kaplan-Meier curve showing impact of SM on outcomes is shown in Figure. Conclusion: In HCM patients with severe LVOTO, SM is associated with significant improvement in long-term outcomes when compared to watchful waiting.

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Alcohol septal ablation in hypertrophic cardiomyopathy

Global Cardiology Science and Practice ◽

10.21542/gcsp.2018.30 ◽

2018 ◽

Vol 2018 (3) ◽

Author(s):

Juan José Santos Mateo ◽

Juan R Gimeno

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Interventricular Septum ◽

Ventricular Outflow Tract ◽

Clinical Results ◽

Left Ventricular ◽

Alcohol Septal Ablation ◽

Obstructive Hypertrophic Cardiomyopathy ◽

Left Ventricular Outflow ◽

Surgical Myectomy

Alcohol septal ablation (ASA) has become an alternative to surgical myectomy in obstructive hypertrophic cardiomyopathy since it was first introduced in 1994 by Sigwart. The procedure alleviates symptoms by producing a limited infarction of the upper interventricular septum, resulting in a decrease in left ventricular outflow tract (LVOT) gradient. The technique has been improved over time and the results are comparable with those of myectomy. Initial concerns about long-term outcomes have been largely resolved. In this review, we discuss indications, technical aspects, clinical results and patient selection to ASA.

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Different Histopathologic Diagnoses in Patients With Clinically Diagnosed Hypertrophic Cardiomyopathy After Surgical Myectomy

Circulation ◽

10.1161/circulationaha.119.040129 ◽

2019 ◽

Vol 140 (4) ◽

pp. 344-346 ◽

Cited By ~ 2

Author(s):

Alaa Alashi ◽

Ria M. Desai ◽

Tamanna Khullar ◽

Kevin Hodges ◽

E. Rene Rodriguez ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Surgical Myectomy

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P1771Right ventricular mechanical changes after septal myectomy for obstructive hypertrophic cardiomyopathy. Vector velocity imaging study

European Heart Journal ◽

10.1093/eurheartj/ehz748.0523 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

H Badran ◽

G Soltan ◽

N Faheem ◽

M Ezzat ◽

M H Yacoub

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Nyha Class ◽

Imaging Study ◽

Functional Class ◽

Class Iii ◽

Septal Myectomy ◽

Cardiac Phenotype ◽

Velocity Imaging ◽

Vector Velocity ◽

Surgical Myectomy

Abstract Objectives The impairment of right ventricular (RV) myocardial mechanics is evident in hypertrophic cardiomyopathy (HCM). It is independently influenced by LV mechanics and correlated to the severity of LV phenotype. We investigated the changes in RV global and regional deformation following surgical septal myectomy using vector velocity imaging (VVI). Methods 25 HCM patients, 68% males with mean age (34.5±12 years) were examined before and within two months after surgical myectomy using VVI. In addition to conventional echocardiographic parameters, peak systolic strain (εsys), strain rate (SR) and time to peak εsys (TTP) of regional RV free wall (RVFW) & septal walls were analyzed in longitudinal (long) directions from apical four chamber view and their (Δ)changes were calculated. Similar parameters were quantified in LV from apical 2 & 4 CH views. Intra-V-delay was defined as SD of TTP and inter-V dyssynchrony was estimated from TTP difference between the most delayed LV segment & RVFW. Results All study patients showed improvement of their functional class from NYHA class III to class I and reduction of LVOT gradient to below 20 mmHg except one patient who had 30 mmHg gradients at rest. There was significant reduction of septal thickness, left atrial diameter& volume, LVOT gradient, LVMI, severity of mitral regurgitation, tricuspid annular velocities (P<0.0001), RV diameter (P<0.02) and increase in LV internal dimensions (P<0.001) post myectomy. However, there was significant reduction of RV and LV systolic mechanics; RV global εsys % (from −16.1±4.4 to −12.9±2.9, P<0.0001) and LV global εsys %: from −11.6±2.8 to −9.4±2.2%, P<0.0001) respectively. The magnitude of reduction of RV strain (Δ RV εsys%, Δ SRsys) was directly correlated LV maximal wall thickness (r=0.46, P<0.01) and ΔRV dyssynchrony (TTP-SD), (r=0.4, P<0.05) and negatively correlated to age (r=−0.46, P<0.02), pre-op RV SRsys (r=−0.52, P<0.01) and pre-op LV EF% (r=−0.43, P<0.03). Meanwhile the reduction in RV diastolic mechanics: Δ RV SRe & SRa were directly correlated to PAP and LVOT gradient before surgery (r=0.62, P<0.002). Conclusion Despite improvement of patient functional status and reduction LVOT gradient, RV mechanics shows further deterioration after surgical myectomy. The magnitude of reduction is modestly related to cardiac phenotype and pre-op mechanical function.

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