Apical Aneurysms and Mid–Left Ventricular Obstruction in Hypertrophic Cardiomyopathy

Sherrid, Mark V.; Bernard, Samuel; Patel, Yash; Modi, Vivek; Axel, Leon; Talebi, Sohelia; Ghoshhajra, Brian; Sanborn, Danita Y.; Sarić, Muhamed; Adlestein, Elizabeth; Alvarez, Isabel Castro; Xia, Yuhe; Swistel, Daniel G.; Massera, Daniele; Fifer, Michael A.; Kim, Bette

doi:10.1016/j.jcmg.2022.11.013

Cited by 22 publications

(29 citation statements)

References 18 publications

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“…Apically displaced papillary muscles pull the mitral valve leaflets apically into the cavity, again increasing risk of LVOTO and LVMCO (Fig. 2) [17].…”

Section: Mitral Valve Abnormalities In Hypertrophic Cardiomyopathymentioning

confidence: 99%

The mitral valve in hypertrophic cardiomyopathy

Malcolmson

Shipolini

Mohiddin

et al. 2023

Current Opinion in Cardiology

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Purpose of review Whilst abnormally increased left ventricular wall thickness is the hallmark feature of hypertrophic cardiomyopathy (HCM), anomalies of the mitral valve and supporting apparatus are well documented. This review addresses the clinical importance of mitral valve abnormalities in HCM, their mechanistic associations with symptoms, and therapeutic strategies targeting mitral valve and apparatus abnormalities. Recent findings The normal mitral valve possesses anatomical features facilitating unrestricted blood flow during LV filling, preventing regurgitation during LV systole, and avoiding obstruction of LV ejection. In HCM, a variety of structural and functional abnormalities can conspire to cause deranged mitral valve function, with implications for management strategy. Identification and characterization of these abnormalities is facilitated by multimodality imaging. Alcohol septal ablation (ASA) cannot address primary mitral valve abnormalities, and so is not preferred to surgical intervention if mitral valve abnormalities are present and are judged to make dominant contributions to LV outflow tract obstruction (LVOTO). Two broadly opposing surgical intervention strategies exist, one advocating isolated septal myectomy and the other including adjuvant mitral apparatus modification. Newer, less invasive surgical and transcatheter techniques will expand interventional options. Summary Mitral valve abnormalities are a central pathological feature of HCM. Multimodality imaging is crucial for their identification and characterization prior to therapeutic intervention.

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“…Apically displaced papillary muscles pull the mitral valve leaflets apically into the cavity, again increasing risk of LVOTO and LVMCO (Fig. 2) [17].…”

Section: Mitral Valve Abnormalities In Hypertrophic Cardiomyopathymentioning

confidence: 99%

The mitral valve in hypertrophic cardiomyopathy

Malcolmson

Shipolini

Mohiddin

et al. 2023

Current Opinion in Cardiology

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“…Left ventricular aneurysm (LVA), one of the most severe MI complications, usually results in a significantly lower LVEF and can induce life-threatening symptoms, such as malignant arrhythmia and cardiac rupture ( 4 ). If a paradoxical movement occurs in an apical aneurysm, heart functions, including LVEF and arrhythmia, are exacerbated ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

IL6/adiponectin/HMGB1 feedback loop mediates adipocyte and macrophage crosstalk and M2 polarization after myocardial infarction

Zheng,

Wang,

et al. 2024

Front. Immunol.

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BackgroundDifferences in border zone contribute to different outcomes post-infarction, such as left ventricular aneurysm (LVA) and myocardial infarction (MI). LVA usually forms within 24 h of the onset of MI and may cause heart rupture; however, LVA surgery is best performed 3 months after MI. Few studies have investigated the LVA model, the differences in border zones between LVA and MI, and the mechanism in the border zone.MethodsThe LVA, MI, and SHAM mouse models were used. Echocardiography, Masson’s trichrome staining, and immunofluorescence staining were performed, and RNA sequencing of the border zone was conducted. The adipocyte-conditioned medium-treated hypoxic macrophage cell line and LVA and MI mouse models were employed to determine the effects of the hub gene, adiponectin (ADPN), on macrophages. Quantitative polymerase chain reaction (qPCR), Western blot analysis, transmission electron microscopy, and chromatin immunoprecipitation (ChIP) assays were conducted to elucidate the mechanism in the border zone. Human subepicardial adipose tissue and blood samples were collected to validate the effects of ADPN.ResultsA novel, simple, consistent, and low-cost LVA mouse model was constructed. LVA caused a greater reduction in contractile functions than MI owing to reduced wall thickness and edema in the border zone. ADPN impeded cardiac edema and promoted lymphangiogenesis by increasing macrophage infiltration post-infarction. Adipocyte-derived ADPN promoted M2 polarization and sustained mitochondrial quality via the ADPN/AdipoR2/HMGB1 axis. Mechanistically, ADPN impeded macrophage HMGB1 inflammation and decreased interleukin-6 (IL6) and HMGB1 secretion. The secretion of IL6 and HMGB1 increased ADPN expression via STAT3 and the co-transcription factor, YAP, in adipocytes. Based on ChIP and Dual-Glo luciferase experiments, STAT3 promoted ADPN transcription by binding to its promoter in adipocytes. In vivo, ADPN promoted lymphangiogenesis and decreased myocardial injury after MI. These phenotypes were rescued by macrophage depletion or HMGB1 knockdown in macrophages. Supplying adipocytes overexpressing STAT3 decreased collagen disposition, increased lymphangiogenesis, and impaired myocardial injury. However, these effects were rescued after HMGB1 knockdown in macrophages. Overall, the IL6/ADPN/HMGB1 axis was validated using human subepicardial tissue and blood samples. This axis could serve as an independent factor in overweight MI patients who need coronary artery bypass grafting (CABG) treatment.ConclusionThe IL6/ADPN/HMGB1 loop between adipocytes and macrophages in the border zone contributes to different clinical outcomes post-infarction. Thus, targeting the IL6/ADPN/HMGB1 loop may be a novel therapeutic approach for cardiac lymphatic regulation and reduction of cell senescence post-infarction.

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“…Here, hyperdynamic muscular contraction forms a constricting muscular neck at the point of cavity division. 4 5 High intracavity pressure gradients form across the point of obstruction, often associated with the development of discrete LV apical aneurysms (LVAA), 6 a risk factor for adverse events. 7 Patients with LVMCO are often symptomatic, 8 and first-line pharmacologic therapies (including betablockers, calcium channel antagonists, and disopyramide) aim to reduce LV inotropy and/or increase filling time.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing

Malcolmson,

Hughes,

Husselbury

et al. 2023

Preprint

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BackgroundPatients with refractory symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy (HCM) have few therapeutic options. Right ventricular (RV) pacing is associated with modest hemodynamic and symptomatic improvement, and LV pacing pilot data suggest therapeutic potential. We hypothesized site-specific-pacing would reduce LVMCO gradients and improve symptoms.MethodsPatients with symptomatic-drug-refractory LVMCO were recruited for a randomized blinded trial of personalized prescription of pacing (PPoP). Multiple LV and apical RV pacing sites were assessed during invasive hemodynamic study of multisite pacing. Patient-specific pacing-site and atrioventricular (AV) delays, defining PPoP, were selected on basis of LVMCO gradient reduction and acceptable pacing parameters. Patients were randomized to 6-months of active PPoP or back-up pacing in a cross-over design. The primary outcome examined invasive gradient change with best-site pacing. Secondary outcomes assessed quality of life and exercise following randomization to PPoP.ResultsA total of 17 patients were recruited; 16 of whom met primary endpoints. Baseline NYHA was 3±0.6 despite optimal medical therapy. Hemodynamic effects were assessed during pacing at the RV apex and at a mean of 8 LV sites. The gradients in all 16 patients fell with pacing, with maximum gradient reduction achieved via LV pacing in 14 (88%) patients and RV apex in 2. The mean baseline gradient of 80±29 mmHg, fell to 31±21 mmHg with best-site pacing, a 60% reduction (p<0.0001). One cardiac vein perforation occurred in one case, and 15 subjects entered cross-over; 2 withdrawals occurred during cross-over. Of the 13 completing cross-over, 9 (69%) chose active pacing in PPoP configuration as preferred setting. PPoP was associated with improved 6-minute walking test performance (328.5±99.9 vs 285.8±105.5 meters, p=0.018); other outcome measures also indicated benefit with PPoP.ConclusionsIn a randomized placebo-controlled trial, LV pacing reduces obstruction and improves exercise performance in severely symptomatic LVMCO patients.RegistrationNCT03450252.Clinical PerspectiveWhat is Known?Patients with refractory, symptomatic LVMCO present a significant challenge for clinical management, with very few treatment options.Data on the use of right ventricular (RV) pacing in patients with refractory, symptomatic LVMCO indicate suboptimal therapeutic responses whilst pilot data indicate a potential therapeutic role for LV pacing.What the Study Adds?Personalized prescription of pacing (PPoP) therapy guided by invasive hemodynamics significantly reduced LVMCO gradients and improved exercise performance in the first randomized, placebo-controlled trial in symptomatic LVMCO.This study provides the basis for a multicenter trial of PPoP for LVMCO and for the use of site-specific pacing in managing other forms of HCM.Graphical Abstract

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Apical Aneurysms and Mid–Left Ventricular Obstruction in Hypertrophic Cardiomyopathy

Cited by 22 publications

References 18 publications

The mitral valve in hypertrophic cardiomyopathy

The mitral valve in hypertrophic cardiomyopathy

IL6/adiponectin/HMGB1 feedback loop mediates adipocyte and macrophage crosstalk and M2 polarization after myocardial infarction

Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing

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