Ventricular Outflow Tract Obstruction Research Articles

Mavacamten for Obstructive Hypertrophic Cardiomyopathy: Rationale for Clinically Guided Dose Titration to Optimize Individual Response.

Mavacamten is the first and only cardiac myosin inhibitor approved in 5 continents for the treatment of adults with symptomatic New York Heart Association class II and III obstructive hypertrophic cardiomyopathy. An evidence-based rationale was used to develop individualized mavacamten dosing, guided by commonly used clinical parameters. Echocardiography is recommended as part of routine clinical assessment of patients with hypertrophic cardiomyopathy, and left ventricular (LV) outflow tract gradient and LV ejection fraction are parameters that can be readily assessed and monitored by echocardiography. Therefore, an echocardiography-based, clinically guided dose-titration strategy was developed to optimize patient benefit from mavacamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy while minimizing the risk of LV ejection fraction reduction. Results from clinical trials paired with extensive modeling and simulation analyses support a dose-titration and monitoring strategy based on serial echocardiographic measures of Valsalva LV outflow tract gradient and LV ejection fraction. This dosing approach allows for the identification of the lowest individualized mavacamten dose and exposure required to provide improvements in LV outflow tract obstruction, functional capacity, and symptoms. Mavacamten is primarily metabolized by CYP2C19 (cytochrome P450 2C19), and CYP2C19 metabolizer phenotype has an effect on mavacamten exposure. Therefore, this approach has also been demonstrated to provide a favorable safety profile irrespective of patients' CYP2C19 metabolizer status. The dose-titration strategy includes additional considerations for the potential onset of systolic dysfunction in the context of intercurrent illness, and for the potential of drug-drug interactions with inhibitors and substrates of cytochrome P450 enzymes. This posology is reflected in the mavacamten US prescribing information.

The early and medium-term results of the Ross procedure in pediatric patients

Introduction and objectivesThe Ross method is the preferred surgical treatment for pediatric aortic valve diseases, and its long-term outcomes have been extensively documented. This article presents the results of the Ross and Ross–Konno procedures performed on pediatric patients in our center. MethodsRoss and Ross–Konno procedures were performed on 20 patients in our center between January 2015 and January 2019. ResultsThe patients’ mean age was 10.6 years (range: 23 days to 18 years) and mean weight was 37.6 kg (range: 3–63 kg). Thirteen had aortic valve stenosis, four had aortic valve insufficiency, and three had a mixed disease. The Ross–Konno procedure was used for four patients. The mean cardiopulmonary bypass time was 184.68±60.1 min and the mean cross time was 149±67.8 min. One neonatal patient died in the early postoperative phase due to low cardiac output. The mean follow-up time was 60.15±24.45 months. One patient later underwent reoperation due to conduit stenosis. One patient is being monitored for moderately serious conduit stenosis. At present, of those who underwent the procedure, one has moderate aortic regurgitation, two have mild or moderate aortic regurgitation, and others have minimal aortic regurgitation. No patients required intervention for left ventricular outflow tract obstruction and mortality was not observed in the long term. Conclusion(s)The reintervention rates for autograft and conduit-related cases were low in early and medium-term follow-up, and no significant autograft insufficiency was observed. Ross or Ross–Konno surgery is preferred for aortic diseases in pediatric patients due to its low mortality and satisfactory long-term results.

Predictors of left ventricular outflow tract obstruction after biventricular repair in interrupted aortic arch or aortic coarctation

BackgroundLeft ventricular outflow tract obstruction (LVOTO) re-intervention is a significant cause of morbidity and mortality in patients with coarctation of the aorta (CoA) or interrupted aortic arch (IAA) after aortoplasty. MethodsThis retrospective study analyzed data from neonates with IAA/CoA who underwent biventricular repair between 2012 and 2022. LVOTO events were defined by the detection of color Doppler flow acceleration ≥3.0 m/s at the valvular, subvalvular, or supravalvular regions via transthoracic echocardiography, and the necessity for surgical or catheter intervention to relieve the obstruction. ResultsAmong 121 neonates with CoA/IAA, 16 (13.7%) primary aortoplasty patients developed LVOTO. Additionally, one patient (25%) who underwent a staged Yasui operation developed LVOTO due to a narrowed ventricular septal defect–pulmonary atresia tunnel. During follow-up, 58% of patients with a bicuspid valve and 25% of patients with a subaortic ridge developed LVOTO. The combination of either a bicuspid valve, subaortic ridge, or an aortic valve annulus Z-score < −3.0 predicted a high re-intervention rate (7/8 [87.5%]). ConclusionsIn patients with IAA/CoA, the presence of multiple risk factors, including a bicuspid valve, subaortic ridge, and an aortic valve annulus Z-score < −3.0, is associated with a significantly increased rate of re-intervention for LVOTO.

Effect of Aficamten on Cardiac Structure and Function in Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM CMR Substudy

BackgroundObstructive hypertrophic cardiomyopathy (oHCM) is characterized by left ventricular (LV) hypertrophy, LV outflow tract obstruction, and left atrial dilation, which can be associated with progressive heart failure, atrial fibrillation, and stroke. Aficamten is a next-in-class cardiac myosin inhibitor that reduces outflow tract obstruction by modulating cardiac contractility, with the potential to reverse pathological remodeling and, in turn, reduce cardiovascular events. ObjectivesThis study sought to investigate the effect of aficamten on cardiac remodeling compared with placebo using cardiovascular magnetic resonance (CMR) and its association with key clinical endpoints in the SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) CMR substudy. MethodsSEQUOIA-HCM was a phase 3 double-blind, placebo-controlled trial for adults with symptomatic oHCM who were randomized 1:1 to 24 weeks of aficamten (dose range: 5-20 mg) or placebo. Eligible participants were offered enrollment in the CMR substudy with studies performed at baseline and week 24. Image analysis was performed in a blinded fashion by a core laboratory. ResultsOf the 282 randomized patients, 57 (20%) participated in the substudy, and of those, 50 (88%) completed both baseline and week 24 CMR. Baseline characteristics of the CMR cohort were similar to the overall study population. Of these 50 patients, 21 received aficamten and 29 received placebo. Relative to placebo, patients receiving aficamten demonstrated significant reductions (Δ least-squares mean) in LV mass index (−15 g/m2; 95% CI: −25 to −6 g/m2; P = 0.001), maximal LV wall thickness (−2.1 mm; 95% CI: −3.1 to −1.1 mm; P < 0.001), left atrial volume index (−13 mL/m2; 95% CI: −19 to −7 mL/m2; P < 0.001), native T1 relaxation time (−37 ms; 95% CI: −69 to −5 ms; P = 0.026), indexed extracellular volume fraction (−3.9 g/m2; 95% CI: −7.0 to −0.9 g/m2; P = 0.014), and indexed myocyte mass (−14 g/m2; 95% CI: −23 to −4 g/m2; P = 0.004), while there were no significant changes in LV chamber volumes, LV replacement fibrosis (late gadolinium enhancement mass −0.7 g; 95% CI: −2.9 to 1.6 g; P = 0.54), or extracellular volume (0.7%; 95% CI: −2.2% to 3.6%; P = 0.61). ConclusionsThe CMR substudy of SEQUOIA-HCM demonstrated that treatment with aficamten relative to placebo for 24 weeks resulted in favorable cardiac remodeling. These changes, particularly with regard to LV mass, wall thickness, and left atrial size, could potentially lead to reduced cardiovascular events including heart failure and atrial fibrillation with longer follow-up. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM [SEQUOIA-HCM]; NCT05186818)

The landscape of congenital heart disease treated with the Ross procedure

BackgroundThe Ross procedure has excellent outcomes in the pediatric population. Some series have reported age- and anatomy-dependent outcomes, but a comprehensive analysis stratified by these variables has not been reported to date. We sought to describe the landscape of congenital heart disease (CHD) treated with the Ross procedure and identify the patients best served by this operation. MethodsOver a total of 30 years, 317 pediatric patients underwent the Ross procedure. These patients were stratified into 4 age groups—neonates (age <31 days; n = 21), infants (age 31 days to 1 year; n = 40), children (age 1-12 years; n = 165), and adolescents (age 13-18 years; n = 91)—and 3 anatomic groups—isolated aortic valve (AV) disease (n = 221), Shone complex or multilevel left ventricular outflow tract (LVOT) obstruction (n = 61), and complex CHD (n = 35). The groups were compared across outcomes. ResultsNeonates and infants had the highest rates of Shone syndrome (P < .001), complex CHD (P < .001), concomitant root enlargement (P < .001), and arch procedures (P < .001). Operative mortality and morbidity were 4.4% (n = 14/317) and 14% (n = 44/317), respectively. Both were higher in neonates and infants (P < .001 for both) but lower for patients with isolated AV disease (P < .001 for both). Ten-year survival and freedom from LVOT reintervention were 92% and 81%, respectively, and were significantly better in patients with isolated AV disease compared to those with complex CHD (P < .001 and P = .005, respectively). In neonates and infants with isolated AV disease, operative mortality was 4% (n = 1/23), morbidity was 9% (n = 2/23), 10-year survival was 85.6%, and 10-year freedom from LVOT reintervention was 88.4%. ConclusionsAmong pediatric patients, those with isolated AV disease are best served with the Ross procedure, regardless of age. Complex CHD is associated with lower survival and increased risk of LVOT reintervention.

Cardiac biomarker profiles in dogs with naturally occurring precapillary pulmonary hypertension

Introduction/ObjectivesThis study evaluated circulating amino-terminal pro-B-type natriuretic peptide (NT-proBNP), amino-terminal pro-A-type natriuretic peptide (NT-proANP), and cardiac troponin I (cTnI) concentrations in dogs with precapillary pulmonary hypertension (Pre-PH) and control dogs with respiratory clinical signs but no Pre-PH. AnimalsTwenty-six dogs (17 affected, and 9 controls) were involved in the study. Materials and MethodsThis was a sub-study of a large prospective single-center observational study. Dogs underwent blood sample collection, physical examination, and echocardiographic evaluation. Pre-PH was diagnosed when a calculated right ventricular-to-right atrial pressure gradient (RV:RA PG) measuring ≥40 mmHg was identified echocardiographically, barring right ventricular outflow obstruction and/or left-sided cardiac disease. ResultsTwo, nine, and six dogs had mild, moderate, and severe Pre-PH, respectively. Plasma concentrations of NT-proBNP, NT-proANP, and cTnI were significantly higher in the affected group than in the control group (P=0.020, P=0.009, P=0.011, respectively). There was a positive correlation between RV:RA PG and NT-proBNP (r = 0.52), NT-proANP (r = 0.54), and cTnI (r = 0.67) concentrations. DiscussionPre-PH should be included in the differential diagnosis list of elevated cardiac biomarker concentrations in dogs with respiratory signs. Study LimitationsStrict selection criteria reduced group sizes. There were rare missing data points. The diagnosis of Pre-PH was obtained from Doppler echocardiographic RV:RA PG. The disease process causing Pre-PH was not evaluated histopathologically. ConclusionsCirculating cardiac biomarker concentrations are increased in dogs with Pre-PH and there is a positive correlation between RV:RA PG and NT-proBNP, NT-proANP, and cTnI concentrations.

Rupture of a calcified right ventricle to pulmonary artery homograft by balloon dilation– emergency rescue by venus P-Valve

BackgroundPercutaneous pulmonary valve implantation (PPVI) is a recognized alternative treatment to surgery for patients with dysfunctional right ventricular outflow tracts. Patient selection is essential to avoid serious complications from attempted treatment, such as rupture or dissection, especially of the calcified outflow tracts. We describe a case with an unexpected rupture of a calcified homograft valve and main pulmonary artery, which was treated successfully by emergency implantation of a self-expanding Venus P-Valve (Venus MedTech, Hangzhou, China) without the need for pre-stenting with a covered stent.Case detailsA 13-year-old boy had two previous operations of tetralogy of Fallot, one a total repair and the other a homograft valved conduit for pulmonary regurgitation. He presented with dyspnea and severe right ventricular outflow tract obstruction (RVOTO) and had a calcified outflow tract and main pulmonary artery. In the catheter laboratory, a non-compliant balloon dilation resulted in a contained rupture of the conduit. The patient remained hemodynamically stable, and the rupture was treated with a self-expandable Venus P-Valve without the need for a covered stent combined with a balloon-expandable valve or a further surgical procedure.DiscussionPreprocedural evaluation with an inflating balloon is necessary to examine tissue compliance and determine suitability for PPVI. However, this condition is accompanied by a risk of conduit rupture. Risk factors of this complication are calcification and homograft use. These ruptures are mostly controlled with a prophylactic or therapeutic covered stent, with a low rate of requiring surgery. However, there are severe ruptures which lead to hemothorax and death. In the available literature, there was no similar reported case of conduit rupture, which a self-expandable Pulmonary valve stent has managed. It seems that fibrosis and collagen tissue around the heart, formed after open surgeries, can contribute to the control of bleeding in these cases.Conclusion (clinical Learning Point)The suitability of patients for the PPVI procedure should be examined more carefully, specifically patients with homograft and calcification in their conduit. Furthermore, conduit rupture might be manageable with self-expandable artificial pulmonary valves, specifically in previously operated patients, and the applicability of this hypothesis is worth examining in future research.

Left ventricular outflow tract obstruction in Takotsubo syndrome with cardiogenic shock: prognosis and treatment

BackgroundPatients with Takotsubo syndrome (TTS) who develop cardiogenic shock may present with left ventricular outflow tract obstruction (LVOTO). The prognosis and treatment of this population have not been defined in...

Heart failure risk assessment in patients with hypertrophic cardiomyopathy based on the H2FPEF score.

The aim of this study was to investigate whether the H2FPEF score, which was developed to improve the diagnosis of heart failure (HF) with preserved ejection fraction, is associated with HF outcomes in patients with hypertrophic cardiomyopathy (HCM). Patients with HCM and preserved left ventricular ejection fraction (LVEF ≥50%) were included from a multicentre registry and the H2FPEF score was calculated. Patients were divided into three groups: low (0-1), intermediate (2-5) and high (6-9) H2FPEF score. The primary combined endpoint was a composite of all-cause death and HF admissions, while the secondary endpoints were all-cause death and HF admissions separately. A total of 955 patients were included (age 51 ± 17 years, 310 [32.5%] female). Patients with a high H2FPEF score (n = 105) were more often female, and presented with more symptoms and comorbidities. On echocardiography, patients with a high H2FPEF score had lower LVEF, more impaired diastolic function and more frequently left ventricular outflow tract obstruction. During follow-up (median 90 months [interquartile range 49-176]), 103 (11%) patients died and 57 (6%) patients had a first HF hospitalization. Event-free survival rate for the primary combined and secondary endpoints was lower for patients with an intermediate and high H2FPEF score. On multivariate Cox regression analysis, female sex (hazard ratio [HR] 1.670, 95% confidence interval [CI] 1.157-2.410; p = 0.006), Asian ethnicity (HR 6.711, 95% CI 4.076-11.048; p < 0.001), ischaemic heart disease (HR 1.732, 95% CI 1.133-2.650; p = 0.011), left atrial diameter (HR 1.028, 95% CI 1.005-1.051; p = 0.016) and intermediate (HR 2.757, 95% CI 1.612-4.713; p < 0.001) or high H2FPEF score (HR 3.689, 95% CI 1.908-7.134; p < 0.001) were independently associated with the primary combined endpoint. The H2FPEF score is independently associated with HF outcome in patients with HCM and may be considered for risk stratification.

Concomitant Dynamic, Fixed Left Ventricular Outflow Tract Obstruction and Mitral Regurgitation: A Triple Jet to Decipher

Concomitant Dynamic, Fixed Left Ventricular Outflow Tract Obstruction and Mitral Regurgitation: A Triple Jet to Decipher

Integrated prenatal and postnatal management for neonates with transposition of the great arteries: thirteen-year experience at a single center

BackgroundTransposition of the great arteries (TGA) is the most common cyanotic congenital heart defect in neonates but with low prenatal detection rate. This study sought to review the prenatal diagnosis, associated abnormalities, and mid-term postnatal outcomes of fetuses with TGA and investigate the integrated prenatal and postnatal management for TGA neonates.MethodsA total of 134 infants prenatally diagnosed with TGA in Guangdong Provincial People’s Hospital, China, from January 2009 to December 2022 were included in the study. The prenatal ultrasound data and neonatal records were reviewed to assess the accuracy of prenatal diagnosis. Univariate and multivariate logistic and Cox analyses were used to identify risk factors associated with prognosis in such individuals.ResultsThe population originated from 40 cities in 10 provinces in China, with integrated antenatal and postnatal management rate reaching 94.0% (126/134) and a high accuracy rate (99.3%) of prenatal primary diagnosis. The median period of follow-up was 1.6 [interquartile range (IQR) 0.1–4.3] years. There were 3 (2.2%) postnatal deaths, 118 (88.1%) patients undergoing arterial switch operation (ASO), 3 (2.2%) undergoing Rastelli operations and 5 (3.7%) doing stage operations. Of 118 patients receiving ASO, the major morbidity occurred in 64 patients (54.2%), and right ventricular outflow tract obstruction (RVOTO) in 31 (26.3%). In the multivariate logistic analysis, gestational ages at birth (OR = 0.953, 95% CI 0.910–0.991; p = 0.025) and cardiopulmonary bypass (CPB) time (OR = 1.010, 95% CI 1.000–1.030; p = 0.038) were identified as independent risk factors associated with major morbidity. In the Cox multivariate analysis, aortic cross-clamping time (HR = 1.030, 95% CI 1.000–1.050; p = 0.017) was identified as independent risk factor associated with RVOTO.ConclusionEarlier gestational ages at birth and longer CPB time are significantly associated with increased morbidity. Integrated prenatal and postnatal management is recommended for patients with prenatal diagnosis of TGA.

Pathogenesis and Surgical Treatment of Dextro-Transposition of the Great Arteries (D-TGA): Part II.

Dextro-transposition of the great arteries (D-TGA) is the second most common cyanotic heart disease, accounting for 5-7% of all congenital heart defects (CHDs). It is characterized by ventriculoarterial (VA) connection discordance, atrioventricular (AV) concordance, and a parallel relationship with D-TGA. As a result, the pulmonary and systemic circulations are separated [the morphological right ventricle (RV) is connected to the aorta and the morphological left ventricle (LV) is connected to the pulmonary artery]. This anomaly is included in the group of developmental disorders of embryonic heart conotruncal irregularities, and their pathogenesis is multifactorial. The anomaly's development is influenced by genetic, epigenetic, and environmental factors. It can occur either as an isolated anomaly, or in association with other cardiac defects. The typical concomitant cardiac anomalies that may occur in patients with D-TGA include ventriculoseptal defects, patent ductus arteriosus, left ventricular outflow tract obstruction (LVOTO), mitral and tricuspid valve abnormalities, and coronary artery variations. Correction of the defect during infancy is the preferred treatment for D-TGA. Balloon atrial septostomy (BAS) is necessary prior to the operation. The recommended surgical correction methods include arterial switch operation (ASO) and atrial switch operation (AtrSR), as well as the Rastelli and Nikaidoh procedures. The most common postoperative complications include coronary artery stenosis, neoaortic root dilation, neoaortic insufficiency and neopulmonic stenosis, right ventricular (RV) outflow tract obstruction (RVOTO), left ventricular (LV) dysfunction, arrhythmias, and heart failure. Early diagnosis and treatment of D-TGA is paramount to the prognosis of the patient. Improved surgical techniques have made it possible for patients with D-TGA to survive into adulthood.

Valve-in-valve transcatheter mitral valve replacement versus redo-surgical mitral valve replacement for degenerated bioprosthetic mitral valves: A systematic review and meta-analysis

Bioprosthetic mitral valve degeneration is traditionally treated with Redo-SMVR, but the latest ViV-TMVR procedure offers a less invasive and lower risk alternative. A systematic literature search was conducted on Cochrane Central, Scopus, and Medline (PubMed interface) electronic databases from inception till 15th April 2024. We used risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes. We included a total of eleven studies with 11,931 patients in the final quantitative and qualitative analysis. When comparing ViV-TMVR with Redo-SMVR, no significant difference was found for 30-day mortality (P = 0.13) and 1-year mortality (P = 0.91), whereas patients in the ViV-TMVR showed significantly reduced incidence of stroke (P < 0.00001), In-hospital mortality (P), bleeding complications (P = 0.003), AKI (P = 0.0006), arrhythmias (P = 0.01), LVOT obstruction (P = 0.04), and PPI (P < 0.00001). Furthermore, no significant difference was observed between either group when comparing vascular complications (P = 0.97), 2-year mortality (P = 0.60) and 3-year mortality. ViV-TMVR was associated with a significant risk of paravalvular leakage (P = 0.008). Although, ViV-TMVR reduces the risk of complications associated with Redo-SMVR, larger studies are imperative to reach conclusive results.

Mavacamten in real-life practice: Initial experience at a hypertrophic cardiomyopathy centre.

In clinical trials, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved symptoms in patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). We aimed to share our real-world experience with the efficacy and safety of mavacamten in this patient population. This retrospective, single-centre study included patients with symptomatic oHCM from March 2023 to November 2023. Inclusion criteria were oHCM, age >18years, significant LVOTO (gradient >50mmHg at rest or with Valsalva), New York Heart Association (NYHA) class ≥II despite maximally tolerated medical therapy, and left ventricular ejection fraction (LVEF) >55%. Patients were evaluated by echocardiography, NYHA class, electrocardiography and Holter monitor on each monthly visit for 3months. A total of 31 patients were included in this study. The mean (SD) age was 58 (16.5) years, and 14 (45%) were female. Mean provoked left ventricular outflow tract gradient (LVOTG) reduced by -49.4mmHg (P<0.001) at 4weeks, -59.2mmHg (P<0.001) at 8weeks, and -60.8mmHg (P<0.001) at 12weeks. Twenty-six of the 31 patients (83.8%) achieved an LVOTG ≤30mmHg at Week 12. No major side effects were reported. Sixty-seven percent experienced ≥2 NYHA class improvements, LVEF remained above 55% and no dose titration was made. Our real-world experience aligns with established mavacamten trial outcomes. Continuous vigilance and longitudinal investigations are needed to further assess potential long-term impacts.

Instantaneous Right Ventricular to Pulmonary Artery Systolic Pressure Difference in Cardiac Surgery: A Retrospective and Prospective Cohort Study

BackgroundDuring cardiac surgery, right ventricular outflow tract obstruction (RVOTO) is defined as an instantaneous pressure difference ≥ 6 mm Hg between right ventricular systolic pressure (RVSP) and pulmonary artery systolic pressure (PASP), for ≥ 5 minutes. Risk factors for RVOTO remain poorly understood. This cohort study was designed to evaluate the incidence, characteristics, and outcomes of the patients who experienced RVOTO. MethodsInstantaneous pressure difference between RVSP and PASP was measured by means of a pulmonary artery catheter with a right ventricular port during cardiac surgery from a retrospective (n = 295) and a prospective (n = 105) cohort. ResultsFrom the retrospective and prospective cohorts, respectively, incidence of RVOTO was 30.2% and 36.2% before cardiopulmonary bypass (CPB) initiation and 43.7% and 47.6% after CPB separation. Before CPB initiation, patients with RVOTO had higher cardiac output (4.2 ± 1.5 vs 3.8 ± 1.1 L/min; P = 0.033) and received more inhaled epoprostenol (79% vs 61%; P = 0.005) and inotropes (66% vs 51%; P = 0.016) compared with those without RVOTO. After CPB separation, patients with RVOTO had higher heart rate (62 ± 15 vs 58 ± 13 beats/min; P = 0.011), cardiac output (4.1 ± 1.4 vs 3.7 ± 1.1 L/min; P = 0.003), and CPB duration (90 ± 45 vs 77 ± 30 min, P = 0.014), had lower fluid balance (758 ± 1123 vs 1063 ± 1089 mL; P = 0.021), and were more exposed to intratracheal milrinone (12% vs 4%; P = 0.015) compared with those without RVOTO. The time with persistent organ dysfunction (TPOD) at 28 days after surgery was similar among patients who had an RVOTO event, before CPB initiation or after CPB separation, compared with those who did not. ConclusionsRVOTO is common in cardiac surgery. However, it is not associated with longer TPOD.

Posterior Leaflet Mitral Valve Repair with Septal Myectomy For Hypertrophic Cardiomyopathy

Posterior Leaflet Mitral Valve Repair with Septal Myectomy For Hypertrophic Cardiomyopathy

Eighteen-Month Real-World Experience Using Mavacamten for Treatment of Obstructive Hypertrophic Cardiomyopathy in a Racially Diverse Population.

Patients with obstructive hypertrophic cardiomyopathy have increased symptomatic burden. Mavacamten was recently approved for treatment of obstructive hypertrophic cardiomyopathy based on 2 randomized controlled trials. However, its use under real-world conditions and in diverse populations is under-studied. This was a prospective observational cohort study of patients seen at the Johns Hopkins HCM center and prescribed mavacamten for obstructive hypertrophic cardiomyopathy between July 7, 2022 and January 6, 2024. Patients were followed longitudinally, with serial echocardiography and clinical evaluation as mandated by the risk evaluation and mitigation strategy program. Sixty-six patients received mavacamten (mean age 59 years, 47% male, 29% non-White [Black, Hispanic/Latino, Asian, Native Hawaiian or Pacific Islander], 47% obese). Before treatment, all patients had New York Heart Association class II (51.5%) or III (48.5%) heart failure symptoms. Initial maximum peak left ventricular outflow tract gradient was 107±46 mm Hg. Median treatment duration was 9 months. For patients on mavacamten after ≥6 months (n=43), symptoms improved by ≥1 New York Heart Association class in 72% of patients, and peak left ventricular outflow tract gradient decreased by 80±46 mm Hg, eliminating hemodynamically significant left ventricular outflow tract obstruction in 79.1% of patients. Mavacamten was temporarily discontinued in 3 patients due to left ventricular ejection fraction decrease <50%. There were no medication-related adverse events. Effectiveness and safety were similar between White and non-White patients, but symptomatic relief was attenuated in patients with body-mass index ≥35 kg/m2. Mavacamten was effective and safe when used under real-world conditions in a racially diverse population of symptomatic patients with obstructive hypertrophic cardiomyopathy. Patients with comorbid obesity were less likely to experience symptomatic improvement while on mavacamten.

From Left Ventricular Outflow Tract Obstruction to Mitral Obstruction.

From Left Ventricular Outflow Tract Obstruction to Mitral Obstruction.

Three-dimensional anatomic features of the mitral valve that predict systolic anterior motion occurring during dobutamine stress echocardiography.

Left ventricular outflow tract obstruction related to systolic anterior motion (SAM) of the mitral valve is a common complication of dobutamine stress echocardiography (DSE). However, the mechanisms underlying SAM have not been fully characterized. The objective of the present study was to use three-dimensional echocardiography to identify anatomic features of the mitral valve that predispose to SAM during DSE. We retrospectively evaluated consecutive patients included prospectively in our database and who had undergone 3D echocardiography (including an assessment of the mitral valve) before DSE. Patients who had developed SAM during DSE (the SAM+ group) were matched 2:3 with patients who did not (the SAM- group). One hundred patients were included (mean age: 67±10). Compared with SAM- patients (n=60), SAM+ patients (n=40) had a lower mitral annular area, a smaller perimeter, and a smaller diameter (p<.01 for all, except the anteroposterior diameter). The SAM+ group had also a narrower mitral-aortic angle (126±12° vs. 139±11° in the SAM- group; p<.01) and a higher posterior mitral leaflet length (1.4±.27cm vs. 1.25±.29, respectively; p<.01). Furthermore, the mitral annulus was more spherical, more flexible, and more dynamic in SAM+ patients than in SAM- patients (p<.05 for all). In a multivariate analysis of anatomic variables, the mitral-aortic angle, the mitral annular area, and posterior leaflet length were independent predictors of SAM (p ≤ .01 for all). In a multivariate analysis of standard echo and hemodynamic variables, the presence of wall motion abnormalities at rest (p<.01) was an independent predictor of SAM. SAM during DSE is multifactorial. In addition to the pharmacologic effects of dobutamine on the myocardium, 3D echocardiographic features of the mitral valve (a smaller mitral annulus, a narrower mitral-aortic angle, and a longer posterior leaflet) appear to predispose to SAM.

The Fate of the Left Ventricular Outflow Tract Following Interrupted Aortic Arch Repair.

Objectives: To examine the probability of left ventricular outflow tract (LVOT) reintervention following interrupted aortic arch (IAA) repair in neonates with LVOT obstruction (LVOTO) risk. Methods: This retrospective multicenter study included 150 neonates who underwent IAA repair (2003-2017); 100 of 150 (67%) had isolated IAA repair (with ventricular septal defect closure) and 50 of 150 (33%) had concomitant LVOT intervention: conal muscle resection (n = 16), Ross-Konno (n = 7), and Yasui operation (n = 27: single-stage n = 8, staged n = 19). Demographic and morphologic characteristics were reviewed. Factors associated with LVOT reoperation were explored using multivariable analysis. Results: Concomitant LVOT intervention was more likely in neonates with type B IAA, bicuspid aortic valve, aberrant right subclavian artery, smaller aortic valve annulus, and ascending aorta dimensions. On follow-up, five-year freedom from LVOT reoperation was highest following Ross-Konno (100%), 77% following Yasui (mainly for neo-aortic regurgitation), 77% following isolated IAA repair (mainly for LVOTO), and 47% following IAA repair with concomitant conal resection, P = .033. While all patients had low peak LVOT gradient at time of discharge, those who had conal resection developed higher gradients on follow-up (P = .007). Ross-Konno and Yasui procedures were associated with higher right ventricular outflow tract (RVOT) reoperation. In the cohort following isolated IAA repair, aortic sinus Z score was associated with LVOT reoperation. Conclusions: Both Yasui and Ross-Konno operations effectively mitigate late LVOTO risk. The highest risk of reintervention for LVOTO was associated with conal muscle resection while the lowest risk is associated with Ross-Konno. The RVOT reoperation risk in patients who had Ross-Konno or Yasui does not seem to affect survival.