Ventricular Outflow Tract Obstruction Research Articles

Transaortic septal myectomy at the time of aortic valve replacement for severe aortic stenosis: a case series of 55 cases

Abstract Introduction Symptomatic aortic valve stenosis (AS) is associated with asymmetric basal septal hypertrophy (ABSH) in 10% of cases. In this cohort, it has been suggested that rectification of the left ventricular outflow tract obstruction (LVOTO) by concomitant septal myectomy (CSM) can improve the results of aortic valve replacement (AVR). Objective This study aims to present the technique of AVR with CSM for severe AS with ABSH and to determine the associated early and late post-operative outcomes. Methods Fifty-five patients were prospectively recruited to undergo AVR with CSM between 2011 and 2021 at two centres. The primary outcomes were mortality within 30 days, incidence of post-operative ventricular septal defects (VSD) and prosthetic valve sizing. The secondary outcomes were in-hospital complications, permanent pacemaker implantation (PPI), survival at 15 months and changes on transthoracic echocardiogram. Results Post-operative mortality was 1.8% and this figure was unchanged at 15-month follow-up. No patients developed a post-operative VSD. Intra-operatively, it was found that in 94.6% cases the direct valve sizing increased by one, when compared to the measurement made before CSM. The indexed effective orifice area (iEOA) was > 85 cm2/m2 in 96.4% and no patients had an iEOA ≤ 0.75 cm2/m2. Four patients (7.3%) required PPI due to complete atrioventricular block. Conclusion AVR with CSM is a simple technique that can be utilised in severe AS with ABSH. There does not appear to be an increase in mortality or incidence of iatrogenic VSDs. Importantly, CSM allows for the implantation of a larger aortic valve compared to measurements made before CSM.

Whole exome sequencing reveals genetic landscape associated with left ventricular outflow tract obstruction in Chinese Han population.

Left ventricular outflow tract obstruction (LVOTO), a major form of outflow tract malformation, accounts for a substantial portion of congenital heart defects (CHDs). Unlike its prevalence, the genetic architecture of LVOTO remains largely unknown. To unveil the genetic mutations and risk genes potentially associated with LVOTO, we enrolled a cohort of 106 LVOTO patients and 100 healthy controls and performed a whole-exome sequencing (WES). 71,430 rare deleterious mutations were found in LVOTO patients. By using gene-based burden testing, we further found 32 candidate genes enriched in LVOTO patient including known pathological genes such as GATA5 and GATA6. Most variants of 32 risk genes occur simultaneously rather exclusively suggesting polygenic inherence of LVOTO and 14 genes out of 32 risk genes interact with previously discovered CHD genes. Single cell RNA-seq further revealed dynamic expressions of GATA5, GATA6, FOXD3 and MYO6 in endocardium and neural crest lineage indicating the mutations of these genes lead to LVOTO possibly through different lineages. These findings uncover the genetic architecture of LVOTO which advances the current understanding of LVOTO genetics.

Acute Hemodynamic Compromise After Transcatheter Aortic Valve Replacement Due to Dynamic Left Ventricle Obstruction: A Systematic Review

Acute hemodynamic compromise post-TAVR due to dynamic left ventricle obstruction (LVO), also known as “Suicide left ventricle” is an infrequent but severe complication of transcatheter aortic valve replacement (TAVR) that is poorly defined in the literature.Understanding this complication is essential for its prompt diagnosis and optimal treatment.We conducted a systematic literature review using PubMed, Embase, Web of Science and Medline databases for studies describing acute hemodynamic compromise post-TAVR due to dynamic LVO or suicide left ventricle. Each study was reviewed by two authors individually for eligibility, and a third author resolved disagreements.From a total of 506 studies, 25 publications were considered for the final analysis. The majority of patients suffering from this condition were women, demonstrating a hypertrophic septum, a small ventricle, and hyperdynamic contractility on pre-TAVR echocardiographic assessment. An intraventricular gradient pre-TAVR was found in half of the cases. Acute hemodynamic compromise post-TAVR due to dynamic LVO manifested mainly as significant hypotension and occurred most often immediately after valve deployment. The left ventricle outflow tract (LVOT) was the most common site of obstruction. Advanced therapies were required in nearly 65% of the cases.In conclusion, acute hemodynamic compromise post-TAVR due to dynamic LVO occurred almost invariably in women. Echocardiography prior to TAVR may offer essential information to anticipate this complication. LVOT obstruction appears to carry the highest risk of developing this phenomenon. Advanced therapies should be promptly considered as a bailout strategy in patients with hemodynamic collapse refractory to medical therapy.

Bex-Nikaidoh operation and the impact of double root translocation on outcomes.

The Bex-Nikaidoh operation can effectively relieve left ventricular outflow tract obstruction. However, if a conduit is used for right ventricular outflow tract reconstruction, a late reoperation can be anticipated. We examined the impact of double root translocation on outcomes. We performed a retrospective single-centre study of patients who underwent aortic root translocation between 2006 and 2019. Aortic root translocation was performed in 23 patients at a median age of 1.6 years [interquartile range (IQR) 0.9-2.5]. Concomitant repairs were done in 52.2% of patients (12/23) including the Senning atrial switch in 34.8% (8/23). The right ventricular outflow tract was reconstructed with valved conduits in 39.1% (9/23), direct anastomoses in 4.35% (1/23) and pulmonary autografts in 56.5% of patients (13/23). Aortic cross-clamp time was significantly longer in patients with double root translocation [308 min (IQR 270-259) vs 209 min (IQR 179-281), P = 0.02]; 2 patients in this group required temporary mechanical circulatory support. There were no early deaths. Median follow-up time was 7.5 years (IQR 3.3-10.5). The estimated 10-year survival was 90% [95% confidence interval (CI): 47.3%, 98.5%]. There was no recurrent left ventricular outflow tract obstruction. Freedom from any reoperation was 64.2% (95% CI: 40.8%, 80.3%) at 3 years and 44.5% (95% CI: 21.2%, 65.5%) at 6 years. The main indication for late reoperation was conduit degeneration. Freedom from a right ventricular outflow tract reoperation was significantly higher, and the number of reoperations per patient was lower when a double root translocation had been performed (P = 0.03). The Bex-Nikaidoh operation effectively relieved left ventricular outflow tract obstruction. A double root translocation further increased procedural complexity but was associated with better mid-term freedom from a right ventricular outflow tract reoperation. It should be considered in suitable patients.

Transcatheter mitral valve replacement with Mi-thos system: First-in-human experience.

Transcatheter mitral valve replacement (TMVR) has become an alternative for high-risk patients with severe mitral regurgitation (MR). The aim of this study was to evaluate the safety and feasibility of the Mi-thos TMVR system (NewMed Medical) for high-risk patients with severe MR. This was a prospective, two-center, single-arm early feasibility study. Baseline characteristics, procedural data and 30-day follow-up outcomes were collected and analyzed. The primary endpoint was intraoperative success rate of device implantation. The second endpoints were all-cause mortality and major post-procedural complications. Echocardiographic data were evaluated by an independent core laboratory. Clinical events were adjudicated by a clinical events committee. Ten high-risk patients with severe MR were enrolled at two sites from August 2021 to November 2022. The median age was 70.5 years, and 60% of patients were female. The median Society of Thoracic Surgeons Predicted Risk of Mortality was 9.5%. The Mi-thos TMVR system was successfully implanted via transapical access in all patients. There was no pericedural mortality or major postpericedural complications during the 30-day follow-up. All implanted prosthetic valves had no or trace valvular or paravalvular MR, and the median mitral valve gradient at 30 days was 2.0 mmHg (IQR: 2.0-3.0 mmHg). There was one mild left ventricular outflow tract obstruction. The favorable short-term outcomes of the Mi-thos TMVR system demonstrated that it might be a feasible and safe therapeutic alternative for high-risk patients with severe MR. Nevertheless, further evaluation of the Mi-thos TMVR system is warranted.

Current status of transcatheter intervention for complex right ventricular outflow tract abnormalities.

Various transcatheter interventions for the right ventricular outflow tract (RVOT) have been introduced and developed in recent decades. Transcatheter pulmonary valve perforation was first introduced in the 1990s. Radiofrequency wire perforation has been the approach of choice for membranous pulmonary atresia in newborns, with high success rates, although complication rates remain relatively common. Stenting of the RVOT is a novel palliative treatment that may improve hemodynamics in neonatal patients with reduced pulmonary blood flow and RVOT obstruction. Whether this option is superior to other surgical palliative strategies or early primary repair of tetralogy of Fallot remains unclear. Transcatheter pulmonary valve replacement has been one of the biggest innovations in the last two decades. With the success of the Melody and SAPIEN valves, this technique has evolved into the gold standard therapy for RVOT abnormalities with excellent procedural safety and efficacy. Challenges remain in managing the wide heterogeneity of postoperative lesions seen in RVOT, and various technical modifications, such as pre-stenting, valve ring modification, or development of self-expanding systems, have been made. Recent large studies have revealed outcomes comparable to those of surgery, with less morbidity. Further experience and multicenter studies and registries to compare the outcomes of various strategies are necessary, with the ultimate goal of a single-step, minimally invasive approach offering the best longer-term anatomical and physiological results.

Long-term results after the réparation à l'étage ventriculaire procedure for transposition of the great arteries and double-outlet right ventricle with pulmonary stenosis.

The purpose of this study is to describe the long-term results of the 'réparation à l'étage ventriculaire' (REV) technique for double-outlet right ventricle and transposition of the great arteries (TGA) with pulmonary stenosis (PS). Between 1980 and 2021, 157 patients underwent a REV procedure (median age and weight: 20.8 months and 7.7 kg). The most frequent anatomical presentation was the association between TGA, ventricular septal defect and PS (n = 116, 73.9%). Sixty-seven patients (42.7%) underwent a Rashkind procedure, and 67 patients (42.7%) a prior surgical palliation (including 62 systemic-to-pulmonary artery shunts). Resection of the conal septum and/or ventricular septal defect enlargement was performed in 109 patients (69.4%). Thirteen patients (8.3%) died, including 4 during the first postoperative month and 2 after heart transplant. Overall survival at 40 years was 89.3%. Thirty-seven patients (23.6%) required 68 reinterventions on the right ventricular outflow tract (RVOT), including 49 reoperations, with a median delay of 9 years after the REV (8 months to 27 years). Twenty patients (12.7%) underwent RVOT valvulation (16 surgical and 4 interventional). Freedom from RVOT reintervention and reoperation at 40 years were 60.3% and 62.6%, respectively. Four patients (2.5%) required reoperation for left ventricular outflow tract obstruction, with a median delay of 4.8 years. The REV procedure is a good alternative for TGA and double-outlet right ventricle with PS patients. Only a quarter of the patients required redo surgery on the RVOT. Reoperations for left ventricular outflow tract obstruction are scarce.

General anaesthesia for ventricular septal defect and right ventricular outflow tract obstruction in patient with glut1 deficiency syndrome: A case report

General anaesthesia for ventricular septal defect and right ventricular outflow tract obstruction in patient with glut1 deficiency syndrome: A case report

Pulmonary Valve Replacement Timing Following Initial Tetralogy of Fallot Repair: A Systematic Review.

Pulmonary valve replacement (PVR) is a critical aspect of surgical management for patients with tetralogy of Fallot (ToF). Determining an optimal timeframe for intervention is imperative, as it directly impacts long-term outcomes and the risk of complications in ToF patients. Ventriculotomy with the transannular patch is currently indicated for right ventricular outflow tract obstruction, but the patch itself can lead to pulmonary regurgitation (PR), dyspnea, and cyanosis, among other complications. This investigation seeks to establish an evidence-based timeline to enhance the overall quality of care for individuals with this congenital heart condition. From 2002 to 2022, 21,935 articles regarding the PVR timing for ToF were examined and filtered. The publications were screened using PRISMA guidelines, and 32 studies were included for analysis and review. Among the studies, PVR was strongly indicated for patients who had developed severe PR, especially in asymptomatic patients and those experiencing fatigue and exercise intolerance. Severe PR was associated with arrhythmias such as right bundle branch block, atrioventricular block, and prolonged QRS intervals, in which male sex and high right ventricular end-diastolic volume (RVEDV) were significant predictors of long preoperative QRS duration. Most physicians found RVEDV necessary for making surgical referrals despite a lack of correlation between PR severity and RVEDV or indexed right ventricular end-systolic volume (RVESVi). However, asymptomatic ToF patients with preoperative RVESVi benefited from PVR. Except for some variations in QRS intervals among studies, arrhythmias tended to persist post-op, yet NYHA functional class and RV size improved significantly following PVR. Older age at PVR was found to be associated with adverse cardiac events, whereas early PVR presented with appropriately short QRS intervals. Cardiac function tended to be significantly worse in patients undergoing late PVR versus early PVR, with timelines ranging from one to three decades following initial ToF repair. Choosing the best timeline for PVR largely depends on the patient's baseline cardiopulmonary presentation, and additional quantitative deformation analysis can help predict an appropriate timeline for ToF patients.

Intracardiac Three-Dimensional Image as Surgical Decision-Making Tool of Congenital Heart Disease.

This study aimed to evaluate the anatomical reproducibility of a preoperative intracardiac 3D image (IC image) created using computed tomography, and to investigate its usefulness as a surgical decision-making tool. Between 2012 and 2022, ventricular septal defect (VSD) patients, and double outlet right ventricle (DORV) or transposition of the great arteries (TGA) with pulmonary stenosis (PS) patients who underwent cardiac surgery and had preoperative computed tomography were enrolled. SYNAPSE VINCENT® (Fujifilm) was used to create an IC image which was analyzed retrospectively. In 14 VSD patients, the diagnostic consistency rate in the Soto classification with intraoperative findings was 100% (14/14) for IC image versus 64% (9/14) for transthoracic echocardiography (P = 0.04). The defect size showed a higher correlation coefficient with IC image (0.837, P = 0.001) than with transthoracic echocardiography (0.567, P = 0.034). In 11 DORV/TGA with PS patients, the diagnostic consistency rate in the Lev classification was 100% (9/9) for IC image versus 77% (7/9) for transthoracic echocardiography (P = 0.47). The secondary interventricular foramen (SVF)/left ventricular outflow tract (LVOT) ratio by IC image was significantly smaller in the biventricular-repair group (median 0.71, IQR 0.67-1.06) than in the univentricular-repair group (median 1.79, IQR 1.53-2.42) (P = 0.006). An IC image is useful as a surgical decision-making tool for simple VSDs and complex congenital heart diseases such as DORV or TGA with pulmonary stenosis. The SVF/LVOT ratio determined from the IC image may be a useful indicator for avoiding LVOT obstruction.

1-Year Outcomes Following Transfemoral Transseptal Transcatheter Mitral Valve Replacement: The HighLife TSMVR Feasibility Study

BackgroundA significant number of patients with severe mitral regurgitation (MR) are not suitable for either surgical or transcatheter edge-to-edge repair because of high surgical risk or inappropriate mitral valve anatomy. ObjectivesThe aim of this study was to evaluate the HighLife Trans-Septal Mitral Valve Replacement (TSMVR) system in patients with symptomatic MR and high surgical risk. MethodsThis prospective, multicenter, nonrandomized feasibility study evaluated the safety and performance of the HighLife TSMVR system in patients with moderate to severe or severe symptomatic MR during 1-year follow-up. Echocardiographic data were assessed at an independent core laboratory. ResultsA total of 30 patients (mean age 75.6 years, 27% women, median Society of Thoracic Surgeons score 5.5%) with severe MR (90% with secondary MR, median left ventricular ejection fraction 43%) were treated at 13 sites. In 27 of the 30 patients, the HighLife TSMVR system was implanted successfully (technical success rate 90%). Device success at 30 days was 83%. After 1 year, 5 patients (17%) had died. None of the patients who underwent implantation required mitral valve reintervention. All patients who underwent implantation had no or trace (78%) or mild (22%) MR, the mean gradient of the HighLife valve was 5.1 mm Hg, and there were no signs of left ventricular outflow tract obstruction (mean gradient 2.0 mm Hg). ConclusionsThe 1-year results from the HighLife TSMVR feasibility study demonstrate a high technical success rate, excellent valve function, no left ventricular outflow tract obstruction, and no need for mitral valve reintervention. Additional patient outcomes and longer follow-up are needed to confirm these findings. (Expanded Study of the HighLife 28mm Trans-Septal Trans-Catheter Mitral Valve in Patients With Moderate-Severe or Severe Mitral Regurgitation and at High Surgical Risk; NCT04029363)

Prediction of incident atrial fibrillation in hypertrophic cardiomyopathy

Background and aimAtrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM) with significant effects on outcome. We aim to compare the left atrial (LA) diameter measurement with HCM-AF Score in predicting atrial fibrillation (AF) development in HCM. MethodsFrom the regional cohort of the Campania Region, Italy, 519 HCM patients (38% women, age45 ± 17 years) without history of AF, were enrolled in the study. The primary clinical endpoint was the development of AF, defined as at least 1 episode documented by ECG. ResultsDuring the follow-up (mean 8 ± 6, IQ range 2.5–11.2 years), 99 patients (19%) developed AF. Patients who developed AF were more symptomatic, had higher prevalence of ICD implantation, had larger LA diameter, greater left ventricular (LV) maximal wall thickness and LV outflow tract obstruction (p < 0.01). Both LA diameter and HCM-AF score were higher in patients who developed AF versus those who did not (LA diameter 49 ± 7 versus 43 ± 6 mm; HCM-AF score 22 ± 4 versus 19 ± 4; p < 0.0001); however, ROC curve analysis demonstrated that LA diameter had a significant greater area under the curve than HCM-AF Score (p < 0.0001). At 5 years follow-up, a LA diameter > 46 mm, showed a similar accuracy in predicting AF development of HCM-AF score ≥ 22, which identifies patients at high risk to develop AF. ConclusionOur analysis shows that LA diameter, a worldwide and simple echocardiographic measure, is capable alone to predict AF development in HCM patients.

Transthyretin amyloid cardiomyopathy among patients with hypertrophic cardiomyopathy: clinical, cardiac imaging, and electrocardiographic findings from the TTRACK study

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is often misdiagnosed as hypertrophic cardiomyopathy (HCM). Identifying ATTR-CM in patients with HCM is essential because treatment approaches vary, especially with the availability of disease-modifying therapies for ATTR-CM. In this analysis of the TTRACK study, we investigated clinical, cardiac imaging, and electrocardiogram (ECG) features of ATTR-CM that may heighten suspicion of amyloid disease and prompt further screening in patients with HCM. Purpose Explore the clinical, echocardiogram (echo), magnetic resonance imaging (MRI), and ECG findings of patients with HCM screened for ATTR-CM in the TTRACK study. Methods In this global, multicentre, non-interventional epidemiological study, the prevalence of ATTR-CM was assessed in patients ≥50 years of age with HCM of unknown aetiology (left ventricular [LV] maximum wall thickness ≥15 mm [echo]) using 99mTc-DPD/99mTc-PYP/99mTc-HMDP-labeled bone scintigraphy. Nuclear images were graded based on cardiac vs bone radiotracer uptake following the Perugini system. Monoclonal protein testing was performed to exclude light chain amyloidosis. Results Of 766 eligible patients with scintigraphy data, 521 (68.0%) had no cardiac uptake; 37 (4.8%) had low uptake (grade 1); and 208 (27.2%) had moderate/high uptake (grade 2/3). Among patients with moderate/high uptake (cardiac amyloidosis [CA]), 137 (65.9% of patients with CA; 17.9% of the overall cohort) had confirmed ATTR-CM. Comparing NYHA classification of patients with no cardiac uptake vs those with ATTR-CM, 33.8% and 25.0% were asymptomatic (NYHA class I). Marked numerical differences were observed in some echo findings of patients with no cardiac uptake vs ATTR-CM, including mean LV mass index (155.6 vs 177.0 g/m2) and the proportions of patients with preserved apical strain (57.9% vs 74.2%) and concentric hypertrophic pattern (38.8% vs 77.8%) (Table [A]). Although a smaller percentage of patients with ATTR-CM exhibited LV outflow tract (LVOT) obstruction than patients with no cardiac uptake, 12.5% of patients with ATTR-CM had LVOT obstruction (LVOT gradient &amp;gt;30 mmHg). A substantially lower proportion of patients with no cardiac uptake (54.7%) had late gadolinium enhancement on MRI than those with ATTR-CM (84.6%). Notable ECG differences were seen in PR interval (179.4 vs 196.9 ms) and the proportion with poor precordial R wave progression (21.9% vs 47.9%) (Table [B]). Conclusions In the TTRACK study, conducted in the largest cohort of patients with HCM ever screened for ATTR-CM, approximately 18% of patients ≥50 years of age with HCM had findings indicative of ATTR-CM. Noteworthy differences in some clinical, cardiac imaging, and ECG findings were seen between patients with HCM with and without ATTR-CM, but none appeared to be definitive. These findings suggest that broader screening for amyloid disease with scintigraphy should be considered among all patients with HCM.

Left atrial haemodynamic evaluation using 4D flow cardiac magnetic resonance imaging: application to hypertension and hypertrophic cardiomyopathy

Abstract Introduction Changes in left atrial (LA) hemodynamics have been suggested reflective of left ventricular (LV) disease progression. Kinetic energy (KE), viscous energy loss, and vorticity could be promising indices for the assessment of left atrial dynamics by time resolved four-dimensional cardiac magnetic resonance (4D flow CMR). Hypertrophic cardiomyopathy (HCM) patients are at risk of developing mitral regurgitation and left ventricular outflow tract obstruction, with poor outcome (1). Hypertensive myocardial remodelling has been suggested to be due to complex flow and tissue interactions leading to hypertrophy and diastolic dysfunction (2). Early detection of altered LA hemodynamic abnormalities may help non-invasive assessment, improving their long-term outcome (3). Purpose Quantitative and qualitative evaluation of left atrial hemodynamic metrics by 4D flow CMR in a cohort of HCM patients, hypertensive patients, and healthy controls with no known cardiovascular disease. Methods Eighteen HCM patients (50.0 [±18.2] years, 8 females), twenty-one hypertensive patients (55.2 [±6.2] years, 11 females), and seventeen controls (36.7 [±12.8] years, 1 female) underwent 4D flow CMR. Both patient groups had significantly higher LV-indexed mass, end-diastolic volume, and end-systolic volumes (P &amp;lt; 0.05). A semi-automated pipeline was used to segment the LA including pulmonary inflow and mitral outflow tracts using phase contrast magnetic resonance images derived from the 4D flow acquisition's phase and magnitude images. LA KE, viscous energy loss and vorticity were computed throughout the cardiac cycle. Results The HCM and hypertensive groups demonstrated significantly higher average KE integrated across the cardiac cycle (1.58 ± 0.79 and 1.32 ± 0.50 mJ respectively) compared to controls (1.20 ± 0.47 mJ) (P &amp;lt; 0.05), with the systolic curve in HCM showing the highest peak KE. Qualitatively, KE in the diastolic portion of the cardiac cycle appeared less variable between groups (Figure 1). Vorticity in HCM showed different configurations with loss of the central atrial vortex core (Figure 2). Viscous energy loss was also significantly higher in HCM patients confirming the increase in energy loss (Figure 2). Average KE across the cardiac cycle highly correlated with LA volume and pulmonary capillary wedge pressure calculated by a previously published regression method (4) (Pearson correlation: r= 0.76 and 0.71 respectively P &amp;lt; 0.05). There were also significant correlations with cardiac metrics such as indexed end-diastolic and indexed end-systolic volumes (Pearson correlation: r= 0.54 and 0.52 respectively P &amp;lt; 0.05) as well as indexed LV mass (r= 0.59 P &amp;lt; 0.05). Conclusion Hemodynamic metrics derived from 4D flow CMR may be valuable in establishing valuable predictive metrics of ventricular function. Integration of 4D flow MRI in clinical workflows could provide information that may be indicative of pathological onset before abnormal remodelling.Kinetic energy and viscous energy lossParticle pathlines and vorticity

Ventricular arrhythmia outcomes in hypertrophic cardiomyopathy from a high level myectomy centre

Abstract Background The presence of ≥15% late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (MRI) is used as a prognostic indicator for sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). [1] According to the European Society of Cardiology clinical practice guidelines (2014), septal myectomy is only indicated for symptomatic relief from left ventricular outflow tract obstruction (LVOTO) that is refractory to medical therapy, provided LVOTO gradient ≥ 50 mmHg. [2] At present, there is scarce data correlating the burden of ventricular arrhythmia and sudden cardiac death with LGE percentage or showing benefit of myectomy in reducing the burden of the same. Purpose We aimed to compare the burden of ventricular arrhythmia burden in patients with HCM who underwent septal myectomy compared with those who did not. Methods Adult patients with HCM followed in the advanced heart failure outpatient clinic at Allegheny General Hospital were included in this study. All included patients had cardiac MRI with LGE quantification and data related to cardiac events through devices placed for various indications (such as evaluation of reported palpitations, established supraventricular tachycardia, implantable cardioverter-defibrillator for primary or secondary prevention). Patients were divided into 2 groups: those undergoing myectomy (post myectomy group) and those that did not undergo myectomy (non-myectomy group). Chi square test was used to calculate incidence of premature ventricular contractions (PVCs), non-sustained ventricular tachycardia (NSVT) and sustained ventricular tachycardia (SVT) in the non-myectomy and post myectomy group. Results 76 patients with HCM (interventricular septal thickness ≥1.5 cm and LGE positive) longitudinally followed in the Allegheny General Hospital advanced heart failure outpatient clinic from 2016 to 2022 were included. 37 patients underwent septal myectomy. Baseline characteristics of post myectomy and non-myectomy group were matched and are listed in table 1. Left ventricular mass index was expectedly higher in patients undergoing myectomy. LGE was quantified on cardiac MRI prior to myectomy (mean 16.4% in myectomy group, 14.6% in non-myectomy group). Burden of ventricular arrhythmia (PVCs, NSVT and SVT) was found to be significantly lower in the post myectomy group (n=13, 44.83%) compared to the non-myectomy group (n=36, 92.31%). None of the patients included were noted to have ventricular fibrillation or sudden cardiac death. Conclusion Septal myectomy may reduce the incidence of ventricular arrhythmia and thus impact outcomes related to sudden cardiac death. This is likely a consequence of removal of arrhythmogenic scar tissue. Larger studies are required to further evaluate the burden and correlation of ventricular arrhythmia with scar tissue volume measured on cardiac MRI.

Family screening in hypertrophic cardiomyopathy - clinical and genetic yield at baseline

Abstract Background Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder, often with monogenic inheritance and accordingly, familial aggregation of HCM is common. International guidelines recommend family screening of relatives of patients with HCM to allow pre-symptomatic identification and early interventions. The clinical and genetic yield of implemented screening programs have been scarcely described and might improve by adjustments. We hypothesized that screening can be improved. Purpose To assess the yield of clinical and genetic family screening in HCM at first screening visit. Methods The study was a retrospective study of clinical and genetic cascade screening of adult relatives (age ≥18 years) of HCM probands, screened for familial occurrence of HCM from 2006 to 2022 at a regional assembly of clinics for inherited cardiac diseases (population 2.6 million). We collected demographic, clinical, symptomatic, and genetic characteristics from electronic health records, and a national pedigree database. Diagnostic work-up included a 12-lead ECG, and echocardiography. Relatives of probands carrying a likely pathogenic (LP) or pathogenic (P) variant were also offered cascade genetic testing. Patients and relatives were diagnosed according to the 2014 ESC guidelines. Results We included 603 adult relatives (55% female, mean age 44±15 years) (table 1). At baseline, 118 relatives (20%) fulfilled diagnostic criteria for HCM, and 135 (22%) were carriers of LP/P variants; 78 (13%) of these did not fulfill diagnostic criteria for HCM. Thus, the combined clinical and genetic yield of baseline screening was 33%. A total of 108 (18%) clinically unaffected relatives did not carry the family’s LP/P variant and were discharged from follow-up. This indicates that 50% of the relatives at baseline could be categorized as affected, genetically predisposed or clinically and genetically not at risk. Relatives fulfilling criteria for HCM at baseline were older (51 vs. 42 years, p&amp;lt;0.001), more likely to report cardiopulmonary symptoms (46% vs 16%, p&amp;lt;0.001), be male (59% vs 41%, p&amp;lt;0.001), and have abnormal ECG features (40% vs. 12%, p&amp;lt;0.001), compared to relatives not fulfilling criteria for HCM at baseline. On echocardiography, relatives fulfilling criteria for HCM had a mean maximal wall thickness of 17±4 mm and 14% had left ventricular outflow tract obstruction (gradient at rest/Valsalva≥30 mmHg). Conclusion At baseline screening, one in three relatives of HCM patients were diagnosed with HCM or found to be genetically predisposed to the disease. One in five clinically unaffected relatives not carrying the proband’s disease-causing variant could be discharged from screening. Considering the pattern of inheritance in HCM, the theoretical risk of developing HCM in the remaining 50% of the relatives is low. The non-diagnostic findings may be useful for identification of the remaining truly at-risk relatives.Table 1:Baseline characteristics

Comparing indices of systemic inflammation and cardiac phenotype between hypertensive and non-hypertensive hypertrophic cardiomyopathy

Abstract Background Arterial hypertension (HTN) is associated with excess mortality in hypertrophic cardiomyopathy (HCM), but underlying mechanisms are largely elusive. Purpose The purpose of this study was to investigate the association between HTN and indices of systemic inflammation and cardiac function in a HCM cohort. Methods This was a single-center cross-sectional case-control study comparing 30 adult HCM patients with HTN (HTN+) and 30 sex- and age-matched HCM patients without HTN (HTN-). Echocardiographic measures were assessed using post-processing analyses by a blinded investigator. Results Mean age of the total sample was 54.6±10.1 years, 30% were women. Mean end-diastolic interventricular septum (IVSd) thickness was 2.1±0.4 cm, 18% previously underwent septal reduction therapy, and 47% had left ventricular outflow tract obstruction. HTN+ portrayed more severe IVSd thickness than HTN- [2.2±0.3 cm vs. 2.0±0.4 cm; p = 0.017], while echocardiographic measures of systolic and diastolic function, including speckle-tracking derived parameters, did not differ between groups. Moreover, levels of N-terminal pro B-type natriuretic peptide were balanced between groups. Compared with HTN-, HTN+ patients exhibited higher circulating plasma levels of interleukin-6 [2.8 pg/ml (2.0, 5.4) vs. 2.1 pg/ml (1.5, 3.4); p = 0.008] and high-sensitivity C-reactive protein [2.6 mg/l (1.4, 6.5) vs. 1.1 mg/l (0.9, 2.4); p = 0.004] Conclusion This study demonstrates that HTN is associated with low-grade systemic inflammation among HCM patients. Moreover, this analysis indicates that HTN+ do not exhibit an altered systolic and diastolic function compared to HTN-. Accordingly, the adverse impact of HTN in HCM patients may be a consequence of systemic effects rather than alterations of cardiac function.TableFigure

Long-term effects of mavacamten treatment in obstructive hypertrophic cardiomyopathy (HCM): updated cumulative analysis of the EXPLORER cohort of MAVA-long-term extension (LTE) study up to 120 weeks

Abstract Introduction Mavacamten was efficacious and well tolerated in patients (pts) with obstructive HCM over a median follow-up of 62 weeks in a previous interim analysis of the ongoing MAVA-LTE study (NCT03723655) (data cut-off; August 31, 2021). Here, we report an updated cumulative analysis of the EXPLORER cohort of MAVA-LTE up to 120 weeks. Methods Pts who completed EXPLORER-HCM (NCT03470545) could enroll in MAVA-LTE. All pts initiated the study with mavacamten 5 mg/day per protocol; dose adjustments to 2.5, 10, or 15 mg were based on site-read Valsalva left ventricular outflow tract (LVOT) gradient and LV ejection fraction (LVEF). Results In total, 231 pts (median age, 61 years; 39% female) enrolled in the EXPLORER cohort of MAVA-LTE. Median time on study was 101 weeks at data cut-off (May 31, 2022) with variations due to differences in enrollment timing. At data cut-off, 215 pts remained on treatment (total adjusted exposure: 475 pt-years). Mavacamten dosing of pts who reached week 120 (n=80) was: 2.5 mg (27.5%); 5 mg (31.3%); 10 mg (26.3%); 15 mg (12.5%). Between weeks 48–120, 34 of 231 (14.7%) pts underwent dose adjustments. Mavacamten treatment showed sustained improvements in mean [SD] change from baseline to week 120 in LVOT gradients (resting, −35.3 [33.0] mmHg; Valsalva, −47.0 [37.3] mmHg), left atrial volume index (−8.5 [10.3] mL/m2) and E/e’ average (−3.9 [5.0]) (Table). At week 120, 83.5% of pts had a Valsalva LVOT gradient ≤30 mmHg. Mavacamten was associated with sustained reduction from baseline to week 120 in N-terminal pro B-type natriuretic peptide (NT-proBNP) level (Table); 75.9% of pts improved by ≥1 class New York Heart Association class (Figure). Mean (SD) LVEF decreased by 9.1% (7.1) from baseline to week 120 but remained in the normal range. Since the previous interim analysis (data cut-off: August 31, 2021), 1 additional transient reduction in LVEF &amp;lt;50% occurred resulting in temporary treatment interruption (a total of 13 pts [5.6%] experienced LVEF &amp;lt;50% from study initiation). The pt resumed treatment at a lower dose 4 weeks after the event. In total, 74 serious adverse events (SAE) were reported in 47 pts (20.3%), with 18 new SAEs and 13 additional pts (5.6%) with SAEs since the previous interim analysis, including 1 new SAE (atrial fibrillation) considered drug related. No new safety signals were identified. One additional death (leading to a total of 4) occurred, due to intracranial hemorrhage. Like the previous 3 deaths (due to acute myocardial infarction, cardiac arrest, and bacterial endocarditis) the event was considered unrelated to the study drug. Conclusions Long-term mavacamten treatment up to 120 weeks showed sustained improvements in LVOT obstruction, symptoms, and NT-proBNP levels in pts with symptomatic obstructive HCM consistent with the findings of the parent study. Mavacamten treatment continues to be well tolerated with no new safety signals observed.

Changes in standard of care (SOC) medication during long-term mavacamten treatment for obstructive hypertrophic cardiomyopathy (HCM): results from the EXPLORER cohort of MAVA-Long-Term Extension (LTE)

Abstract Introduction Mavacamten is efficacious and well tolerated in patients with obstructive HCM in the ongoing MAVA-LTE study (NCT03723655) as shown in previous interim analyses. Here, we present exploratory data from the EXPLORER cohort of MAVA-LTE investigating the effect of changes in SOC treatment on the efficacy and safety of mavacamten. Methods Patients who completed EXPLORER-HCM (NCT03470545) could enroll in MAVA-LTE and comprised the EXPLORER cohort. All patients in the EXPLORER cohort received mavacamten. Patients could receive beta blockers or nondihydropyridine calcium channel blockers (verapamil/diltiazem) as SOC treatment. After 24 weeks on study, SOC treatment could be adjusted. A cumulative interim analysis (data cut-off: May 31, 2022) was performed on patients who: received no SOC, discontinued SOC, had any reduction in SOC and had ≥50% reduction in SOC from baseline to data cut-off. Results In total, 231 patients (mean age, 60 years; 39% female) comprised the EXPLORER-LTE cohort (median time on study: 101 weeks at data cut-off). At baseline, 176 patients (76.2%) received beta blockers and 38 (16.5%) received nondihydropyridine calcium channel blockers. At data cut-off, 12 (5.2%) patients had received no SOC treatment from baseline, 11 (4.8%) patients had discontinued SOC, 27 (11.7%) patients had any dose reduction in SOC, 18 (7.8%) patients had a ≥50% reduction in SOC and 14 (6.1%) patients had an increase in SOC. In the no SOC subgroup, mavacamten treatment was associated with improvements from baseline to last visit in resting and Valsalva left ventricular outflow tract (LVOT) gradients, left atrial volume index (LAVI), and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels (Table 1). Improvements in these parameters were also observed in the SOC discontinuation and SOC dose reduction subgroups (Table 1). In the SOC discontinuation subgroup, improvements in resting and Valsalva LVOT gradients, LAVI, and NT-proBNP levels from baseline were maintained after SOC discontinuation (Table 1). SOC medications were discontinued or reduced over a mean (range) period of 63 (9–96) and 62 (3–133) weeks, respectively. At data cut-off, left ventricular ejection fraction remained within the normal range for all patients regardless of the SOC subgroup. Patients who reduced SOC medication had small increases in heart rate (within normal range) from baseline to last visit (Table 2). Overall, blood pressure remained stable across subgroups throughout the observation period (Table 2). No patients experienced worsening of NYHA class from baseline to last visit or from withdrawal to last visit. Conclusions Beneficial and sustained effects on LVOT obstruction, NT-proBNP levels and symptoms in patients with symptomatic obstructive HCM were observed with long-term mavacamten treatment alone or after SOC discontinuation or dose reduction.

Long-term outcomes and risk factors for reoperation after subaortic stenosis resection in children and adults

Abstract Background Sub-valvular aortic stenosis (SAS) is an extremely heterogeneous form of left ventricular outflow tract (LVOT) obstruction, which can lead to aortic valve damage. Although corrective surgery is considered the most effective treatment, rates of recurrence and reoperation are still high. Previous studies have focused on predictors of reoperation in several subgroups of patients with SAS, but rarely in the whole population of patients with SAS. Purpose We sought to describe long-term outcomes after SAS resection and to determine the predictors of reoperation after successful primary resection. Methods We retrospectively reviewed the records of patients who underwent SAS resection between 1994 and 2021 at our institution with at least 12 months’ follow-up. Patients with a single-ventricle physiology and idiopathic hypertrophic cardiomyopathy were excluded. Demographic, surgical and echocardiographic data were analyzed. Outcomes were reoperation after successful primary resection, death and morbidities, including postoperative complete heart block and aortic regurgitation (AR) grade at latest follow-up. Results Seventy-six patients (paediatric, n = 72 and adult, n = 4) who underwent SAS resection were included in the analysis. Median length of postoperative follow-up was 11.1 years (IQR range: 7.3 – 15.7 years), with two late deaths. Reoperation due to recurrent obstruction or severe AR occurred in 24 patients (31.6%). Median time to reoperation was 7.5 years (IQR range: 3.6 – 11 years). Overall freedom from reoperation at 5 years and 10 years was 84.6% and 69.1% respectively. Gender and association with other cardiac defects did not differ significantly between those with reoperation and those without. In multivariate analysis, independent predictors of reoperation were age at first surgery younger than 5 years (HR 3.54, 95% CI 1.06 – 11.83; P = 0.040) and tunnel-type lesions (HR 4.42, 95% CI 1.70 – 11.51; P = 0.002). Three patients (3.9%) had complete heart block and required placement of an implantable pacemaker. Following SAS resection, progression of AR was common (39/68, 57.3%) but only 5 patients (7.3%) developed sufficient regurgitation to require surgical repair or replacement. Conclusions Reoperation is not infrequent after surgical relief of SAS and reaches a plateau after 10 years. Younger age at first surgery and tunnel-type SAS independently predict reoperation. Progression of AR after corrective surgery of SAS is common, but fortunately only a minority of patients develop hemodynamically significant AR requiring reintervention.