Outflow Tract Research Articles

Association between echocardiographic velocity time integral ratio of mitral valve and left ventricular outflow tract and clinical outcomes post transcatheter edge-to-edge mitral valve repair

BackgroundResidual mitral regurgitation (MR) is frequent after transcatheter edge-to-edge repair (TEER). There is controversy regarding the clinical impact of residual MR and its quantitative assessment by transthoracic echocardiography (TTE), which is often challenging with multiple eccentric jets and artifact from the clip. The utility of the velocity time integral (VTI) ratio between the mitral valve (MV) and left ventricular outflow tract (LVOT), (VTIMV/LVOT), a simple Doppler measurement that increases with MR, has not been assessed post TEER. MethodsBaseline characteristics, clinical outcomes, and TTE data from patients who underwent TEER between 2014 and 2021 across three academic centers were retrospectively analyzed. Post-procedure TTEs were evaluated for VTIMV/LVOT in the first three months after TEER. One-year outcomes including all-cause and cardiac mortality, major adverse cardiac events, and MV reintervention were compared between patients with high VTIMV/LVOT (≥2.5) and low (<2.5). ResultsIn total, 372 patients were included (mean age 78.7 ± 8.8 years, 68 % male, mean pre-TEER ejection fraction of 50.5 ± 14.7 %). Follow up TTEs were performed at a median of 37.5 (IQR 30–48) days post-procedure. Patients with high VTIMV/LVOT had significantly higher all-cause mortality (HR 2.10, p = 0.003), cardiac mortality (HR 3.03, p = 0.004) and heart failure admissions (HR 2.28, p < 0.001) at one-year post-procedure. There was no association between raised VTIMV/LVOT and subsequent MV reintervention. ConclusionHigh VTIMV/LVOT has clinically significant prognostic value at one year post TEER. This tool could be used to select patients for consideration of repeat intervention.

Genetic variations in PTPN11 lead to a recurrent Left Ventricular Outflow Tract Obstruction phenotype in childhood hypertrophic cardiomyopathy

ObjectiveLeft ventricular septal myotomy provides a favorable prognosis for children with hypertrophic obstructive cardiomyopathy (HOCM). However, some children still suffer from recurrent left ventricular outflow tract obstruction (LVOTO) after surgery. Poor prognosis exists for HOCM caused by PTPN11 mutation. Therefore, the aim of this study was to determine the clinical features of recurrent obstruction in children with HOCM caused by pathogenic mutations in the PTPN11 gene. MethodsA total of 56 children were diagnosed with HOCM underwent septal myectomies. Whole exome sequencing of 49 pediatric cardiomyopathies associated genes (including PTPN11) were performed. We performed hematoxylin-eosin(H&E), Masson, and wheat germ agglutinin (WGA)staining of tissues positive for PTPN11 and those negative for PTPN11 were conducted. ResultsWhole exome sequencing results showed 11 PTPN11 mutation (19.6%) children. In long-term follow-up (median 37 months, maximum 9 years), children with PTPN11 mutation had 6(54.5%) recurrent LVOTO compared with other groups (P=.015), but similar survival rates(P=.514). The mean postoperative time to recurrent obstruction was 22±27 months. Children with PTPN11 mutation were 9-fold more likely to experience the risk associated with recurrent obstruction (95% CI = 1.77-45.81, P<.001). H&E, Masson and WGA staining also revealed more cardiomyocyte hypertrophy in PTPN11 mutation tissues. See Figure 4 for a graphical abstract of the study. ConclusionChildren with PTPN11 mutation-associated hypertrophic cardiomyopathy have a higher risk of recurrent LVOTO.

Peculiarities of the evolution of pulmonary hypertension in patients with ischemic heart failure 12 months after myocardial revascularization

Pulmonary hypertension (PH) associated with left heart disease is common and has an important impact on disease progression, morbidity and mortality. We aimed to identify the particularities of PH evolution in patients with ischemic heart failure during 12 months after myocardial revascularization (MRev) by coronary artery bypass grafting or percutaneous coronary angioplasty.Methods: The research included 281 patients undergoing MRev (mean age=63.2±9.7 years, 76.5%- men). Follow up period - 12.6±1.6 months. The patients were divided according to the echocardiographic probability of PH (PHPr) into 3 groups: low PHPr (117 patients), intermediate PHPr (74 patients), high PHPr (90 patients). Results. The prevalence of PH 12 months after MRev constituted 69.7%, increasing by 10% compared to the initial period. We highlighted a negative evolution of PHPr during 1 year after MRev: 42.8% of patients with initially low PHPr and 54.1% of those with intermediate PHPr had a higher degree of PHPr. The peak tricuspid regurgitation velocity and the pulmonary artery systolic pressure did not change significantly during 12 months after the acute event. The negative evolution of PHPr was determined by the negative dynamics of additional echocardiographic signs suggestive for PH: the right atrium area (+2,2±0.4mm), the right ventricular outflow tract acceleration time (-7.6±1.2ms), the inferior vena cava diameter (+0.55±0.2mm). During 12 months after MRev, 5 patients died, all of them had high PHPr (p&lt;0.01), and the hospitalization rate was significantly higher in this group (high PHPr - 57.1%, intermediate PHPr - 43.2%, low PHPr - 38.7%, p&lt;0.05). Conclusions: The PH prevalence 12 months after MRev was 69.7%, increasing by 10% compared to the initial period. A negative evolution of PHPr was noted during 1 year follow up. Patients with high and intermediate PHPr had a higher rate of hospitalizations during the 12 months after MRev and all deceased patients had high PHPr.

Use of two- and three-dimensional echocardiography for assessment of the left ventricular outflow tract and aortic orifice areas in dogs

Introduction/objectivesIn clinical practice, dogs are screened for subaortic stenosis (SAS) using two-dimensional (2DE) and Doppler echocardiography. There is no accepted antemortem diagnostic criterion to distinguish between mild SAS and unaffected, therefore additional means of evaluating the left ventricular outflow tract (LVOT) and aorta may be desirable. This study sought to determine and compare LVOT and aortic orifice areas using 2DE and three-dimensional echocardiography (3DE) in apparently healthy dogs of various breeds and somatotypes. Animals, materials, and methodsSixty-nine healthy, privately-owned dogs. The LVOT and aortic orifice areas were determined using 2DE aortic valve (AV) diameter-derived area; the continuity equation (CE); and 3DE planimetry of the LVOT, AV, sinus of Valsalva, and sinotubular junction. Orifice areas were indexed to body surface area (BSA). ResultsObtaining 3DE images and performing planimetry were feasible in all dogs. The mean indexed area measured using the 2DE AV diameter (2.85 cm2/m2) was significantly lower than that derived from 3DE AV planimetry (3.85 cm2/m2; mean difference, 1.00 cm2/m2; P<0.001). There was poor agreement between the effective area calculated using the CE and the anatomic areas calculated using 2DE AV diameter and 3DE planimetry. The area calculated using the CE was less than all other calculations of area. Interobserver and intraobserver repeatability and reproducibility for 3DE planimetry were excellent. ConclusionsMethods for determining aortic orifice areas in dogs are not interchangeable, and this must be taken into account if these methods are investigated in the evaluation of dogs with SAS in the future.

Prevention of SAM phenomenon after reconstructive mitral valve surgery

Systolic anterior motion (SAM) of the mitral valve (MV) can be a life-threatening condition. The SAM can result in severe left ventricular outflow tract obstruction and/or mitral regurgitation and is associated with up to 20% risk of sudden death (which is substantially lower in hypertrophic cardiomyopathy (HCM)).The mechanisms of SAM are complex and depend on the functional status of the ventricle. The SAM can occur in all cases, but is typically observed in patients with HCM or following MV repair.Echocardiography (2D, 3D and stress) has a central diagnostic role as the application of echocardiographic SAM predictors allows the incorporation of prevention techniques during surgery and post-operative SAM assessment.MRI (magnetic resonance imaging) has a special role in understanding the dynamic nature of SAM, especially in anatomically atypical hearts (including HCM).This article describes what the clinician needs to know about SAM ranging from pathophysiological mechanisms and imaging modalities to conservative (medical) and surgical approaches and their respective outcomes.A stepwise approach consisting of medical therapy, followed by aggressive volume loading and beta-adrenoreceptor blockers. Surgery is the final option. The correct choice of surgical technique requires an understanding of the anatomical substrate of SAM.

Unmasking Obstruction in Hypertrophic Cardiomyopathy With Postprandial Resting and Treadmill Stress Echocardiography

Latent left ventricular outflow tract obstruction (LVOTO) is an important cause of symptoms in patients with hypertrophic cardiomyopathy (HCM) but can be challenging to provoke. To examine the value of postprandial resting and stress echocardiography and utilization of invasive or enhanced drug therapies (surgical myectomy, alcohol septal ablation, disopyramide, and mavacamten) in patients with postprandial LVOTO. Consecutive HCM patients without LVOTO underwent routine and postprandial echocardiography at rest, with provocation (Valsalva and standing) and after symptom-limited treadmill stress. Among 252 patients (mean age, 58years, 39% women), postprandial LVOT gradients were higher compared with routine echocardiography at rest (median, 9.0 [0-38.0] vs 0 [0-14.0] mm Hg; P<.0001) and with provocation (18.5 [0-70.3] vs 1.5 [0-41.0] mm Hg; P<.0001). Postprandial exercise stress echocardiogram (PPXSE) gradients were higher in a subset of 44 patients who underwent both postprandial and fasting stress echocardiography (47.0 [5.3-81.0] vs 17.5 [0-46.0] mm Hg; P<.0001). In total, 49 (19.5%) patients achieved the ≥50mm Hg threshold under routine conditions (rest/provocation); 90 (35.7%) additional patients achieved postprandial gradients ≥50mm Hg (rest/provocation/exercise), 38 (15.1%) with PPXSE alone. A total of 71 patients were treated with 91 invasive or enhanced drug therapies, 32 (45.1%) of whom had gradients ≥50mm Hg only after eating (rest/provocation) and 8 (11.3%) only with PPXSE, with symptom relief in the majority. Postprandial echocardiography was useful at unmasking LVOTO in more than one-third of patients who did not have high gradients otherwise. Eating before echocardiography is a powerful provocative tool in the evaluation of patients with HCM.

The developmental processes of ventricular septal defects with outflow tract malalignment

Ventricular septal defects (VSD) with outflow tract (OFT) malalignment are a common group of congenital heart diseases with varying severity. The developmental process of these defects is challenging to understand due to the complex nature of cardiac morphogenesis and the difficulties in visualizing the temporal and spatial changes that occur during pathogenesis. However, recent advancements in imaging techniques, such as high-resolution episcopic microscopy, have provided valuable insights into the normal septation of ventricular chambers and OFT alignment. Building upon this knowledge, we have utilized lightsheet microscopy, another innovative imaging method, to further investigate the developmental processes that lead to abnormal formation of the ventricular septum and the malalignment of arterial roots with the ventricular chambers. Our study highlights endocardial cushion hypoplasia and insufficient rotation of the outflow tract as two interrelated central factors contributing to the pathogenesis of these defects. This finding has the potential to enhance our understanding of the etiology of congenital heart diseases and may contribute to the development of improved diagnostic and therapeutic strategies in the future.

Ibrutinib, a Bruton's tyrosine kinase inhibitor, regulates ventricular electromechanical activities and enhances arrhythmogenesis

BackgroundIbrutinib, a Bruton's tyrosine kinase inhibitor used in cancer therapy, exerts ventricular proarrhythmic effects; however, the underlying mechanisms remain unclear. Excitation-contraction coupling (E-C) disorders are pivotal for the genesis of ventricular arrhythmias (VAs), which arise mainly from the right ventricular outflow tract (RVOT). In this study, we aimed to comprehensively investigate whether ibrutinib regulates the electromechanical activities of the RVOT, leading to enhanced arrhythmogenesis, and explore the underlying mechanisms. MethodsWe utilized conventional microelectrodes to synchronously record electrical and mechanical responses in rabbit RVOT tissue preparations before and after treatment with ibrutinib (10, 50, and 100 nM) and investigated their electromechanical interactions and arrhythmogenesis during programmed electrical stimulation. The fluorometric ratio technique was used to measure intracellular calcium concentration in isolated RVOT myocytes. ResultsIbrutinib (10–100 nM) shortened the action potential duration. Ibrutinib at 100 nM significantly increased pacing-induced ventricular tachycardia (VT) (from 0% to 62.5%, n = 8, p = 0.025). Comparisons between pacing-induced VT and non-VT episodes demonstrated that VT episodes had a greater increase in contractility than that of non-VT episodes (402.1 ± 41.4% vs. 232.4 ± 29.2%, p = 0.003). The pretreatment of ranolazine (10 μM, a late sodium current blocker) prevented the occurrence of ibrutinib-induced VAs. Ibrutinib (100 nM) increased late sodium current, reduced intracellular calcium transients, and enhanced calcium leakage in RVOT myocytes. ConclusionIbrutinib increased the risk of VAs in the RVOT due to dysregulated electromechanical responses, which can be attenuated by ranolazine or apamin.

Perioperative echocardiography in minimally invasive surgery for hypertrophic obstructive cardiomyopathy.

Hypertrophic obstructive cardiomyopathy (HOCM) is clinically symptomatic and prone to malignant arrhythmias and sudden cardiac death (SCD). Currently, an effective treatment is surgical resection of the hypertrophic ventricular septum to relieve the left ventricular outflow tract (LVOT) obstruction and mitral insufficiency. Our center performs an innovative, minimally invasive right infra-axillary thoracotomy for transaortic septal myectomy. Minimally invasive procedures rely more on perioperative transesophageal echocardiography (TEE). This study aimed to explore the use of echocardiography during the perioperative period of surgical intervention for HOCM. Between August 2021 and April 2022, 27 patients with HOCM underwent cardiac surgery at our hospital. Minimally invasive transaortic septal resection (Morrow myectomy) was performed from the right axilla. The extent of myectomy and need for mitral valve repair were based on perioperative TEE assessment and surgical findings. The demographic parameters and clinical data of patients were recorded. The cardiopulmonary bypass time, aortic cross-clamp, and mechanical ventilation times were calculated. TEE was used to assess ventricular wall thickening and anatomical abnormalities of mitral regurgitation, assist in intravenous catheterization, and assess the postoperative gradients of the LVOT. Among the 27 patients with HOCM who underwent transaortic septal myectomy by minimally invasive right infra-axillary thoracotomy, 16 had LVOT obstruction, 2 had mid-LV obstruction, and 9 had both LVOT and mid-LV involvement. TEE provides information about the fine structure of the LV cavity and the etiology of the obstruction. In all cases, LVOT obstruction and mitral valve systolic anterior motion were resolved postoperatively, and the degree of mitral regurgitation was significantly reduced. Perioperative echocardiography provides valuable information regarding the complex etiology of LVOT obstruction during minimally invasive right infra-axillary thoracotomy for transaortic septal myectomy. It helps determine the extent of septal resection and assess the need for concomitant mitral valve repair.

Association of left ventricular outflow tract size with arch morphology in interrupted aortic arch.

Left ventricular outflow tract obstruction (LVOTO) is a major cause of morbidity and mortality in infants with interrupted aortic arch (IAA). LVOT development may be flow-mediated, thus IAA morphology may influence LVOT diameter and subsequent reintervention. We investigated the association of IAA morphology (type and presence of aortic arch aberrancy) with LVOT diameter and reintervention. All surgical patients with IAA (2001-2022) were reviewed at a single institution. We compared IAA-A versus IAA-B; IAA with aortic arch aberrancy (AAb) versus none; IAA-B with aberrant subclavian artery (AAbS) versus Others. Primary outcomes included LVOT diameter (mm), LVOTO at discharge (≥50mmHg), and LVOT reintervention. Seventy-seven infants (mean age 10±19 days) were followed for 7.6 (5.5-9.7) years. Perioperative mortality was 3.9% (3/77) and long-term mortality was 5.2% (4/77). Out of 51 IAA-B (66%) and 22 IAA-A (31%) patients, 30% (n = 22) had AAb. Smaller LVOT diameter was associated with IAA-B [IAA-A: 5.40 (4.68-5.80), IAA-B: 4.60 (3.92-5.50), p = 0.007], AAb [AAb: 4.00 (3.70-5.04) vs None: 5.15 (4.30-5.68) p = 0.006], and combined IAA-B+AAbS [IAA-B+AAbS: 4.00 (3.70-5.02) vs Other: 5.00 (4.30-5.68), p = 0.002]. The likelihood of LVOTO was higher among AAb (N = 6 (25%) vs N = 1 (2%), p = 0.004) and IAA-B+AAbS (N = 1 (2%) vs N = 6 (30%), p = 0.002). Time-to-event analysis showed a signal towards increased LVOT reintervention in IAA-B+AAbS (p = 0.11). IAA-B and AAb are associated with small LVOT diameter and early LVOTO, especially in combination. This may reflect lower flow in the proximal arch during development. Most reinterventions occur in IAA-B+AAbS, hence these patients should be carefully considered for LVOT intervention at the time of initial repair.

In vivo calcium and voltage mapping of the zebrafish heart

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders (FWO) Purpose Inherited cardiac arrhythmias are characterized by a disturbance in the normal electrical functioning of the heart due to a dysfunction of cardiac ion channels, accessory proteins and/or structural components. This complex process is difficult to model in vitro, while in vivo mouse models differ substantially from humans with regards to cardiac electrophysiology. Thus, there is a need for alternative disease models in cardiac arrhythmia research. The zebrafish heart shows remarkable similarity to humans in its electrocardiogram and action potential (AP) morphology. Due to the optical translucency of zebrafish larvae, it is possible visualize the cardiac calcium and voltage dynamics across their entire hearts in vivo by use of genetically encoded calcium and voltage indicators (GECI and GEVI). We combined the fast kinetics of a next generation voltage reporter (Ace2N-mNeon) with a spectrally compatible calcium sensor (R-GECO) to create a sensitive high throughput method for in vivo characterization of the cardiac AP. Methods Ace2N-mNeon and R-GECO were expressed under control of a myocardial specific promoter via the Tol2kit system. The effect of sensor expression on normal physiology was assessed by patch clamp experiments. Fluorescence recordings were obtained with a Leica SP8 DLS microscope and a custom-built light sheet microscope. Our zebrafish sensor line was validated by experiments with quinidine drug exposure, as well as a novel model for long QT syndrome (LQTS) with a knock-in (KI) mutation in the cacna1c gene. Results Sensor expression did not significantly alter cardiac electrophysiology. The tg(myl7:Ace2N-mNeon/R-GECO) line demonstrated alterations in the heart rate, depolarization and repolarization induced by quinidine exposure. We observed a significantly prolonged ventricular repolarization in the LQTS KI line. Three-dimensional optical maps of AP characteristics across the entire zebrafish heart exhibited the physiological characteristics of the zebrafish cardiac electrophysiology, with activation initiated at the atrial venous pole and propagated towards the ventricular outflow tract, prolonged repolarization in the ventricles compared to the atria and slowed depolarization in the atrio-ventricular canal. Conclusion By expressing Ace2N-mNeon and R-GECO in the zebrafish heart, we were able to accurately detect drug- and mutation induced alterations in the cardiac AP, as well as AP characteristics across the entire heart, without compromising normal cardiac electrophysiology. Our transgenic line will provide a promising assay for future studies of cardiac arrhythmia.

Right ventricular outflow tract cardiomyocytes possess distinct calcium handling and contractile properties

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Rembrandt Research Grant 2021 Background The right ventricular outflow tract (RVOT) is the predominant site of origin of idiopathic ventricular tachycardia. Idiopathic ventricular tachycardias are typically sensitive to adenosine, consistent with triggered activity caused by delayed afterdepolarizations due to intracellular Ca2+ overload. The distinct properties of RVOT myocytes explaining increased susceptibility to Ca2+ overload and triggered activity are unknown. Purpose To identify distinct RVOT electrophysiological properties including Ca2+ handling and its molecular underpinnings. Methods and Results Experiments were performed using freshly isolated cardiomyocytes from the RVOT and right ventricular (RV) apex of adult rabbit hearts. To identify distinct RVOT electrophysiological properties, we employed the perforated patch clamp methodology and measured action potentials and L-type Ca2+ current. Action potentials of RVOT myocytes were significantly shorter compared to RV myocytes, particularly at lower pacing frequency. L-type Ca2+ current peak density was significantly lower in RVOT myocytes compared to RV myocytes (34.0 ± 9.1% at 0 mV). However, voltage-dependencies of L-type Ca2+ current activation and inactivation were not statistically different. Next we measured intracellular Ca2+ transients using the fluorescent Ca2+ indicator indo-1 and found that Ca2+ transient amplitudes were significantly lower in RVOT myocytes compared to RV myocytes. To investigate a relationship between RVOT myocyte Ca2+ handling and contractility, we performed unloaded sarcomere shortening measurements using the Cytocypher Multicell system. Shortening of relaxation time following increased pacing frequency (1-2 Hz) was significantly larger for RVOT myocytes compared to RV myocytes. To identify molecular factors explaining the distinct properties of RVOT myocytes, we performed RNA-seq analysis of differential gene expression using the DESeq2 method. RVOT and RV transcriptomic profiles consisted of 30 differentially expressed genes (adjusted p ≤ 0.05). One of genes significantly higher expressed by the RV was synaptotagmin (SYT1), a Ca2+ sensor and positive regulator of the cardiac L-type Ca2+ channel through inhibition of syntaxin 1A [Ref. 1, 2]. Conclusion RVOT cardiomyocytes possess distinct electrophysiological and contractile properties, reflected by shorter action potentials, lower Ca2+ transient amplitudes, and larger shortening of relaxation time upon increasing pacing frequency. The RVOT and RV have similar but distinct gene expression signatures. Future experiments will focus on determining the role of SYT1 and other genes in regulation of the L-type Ca2+ current and Ca2+ handling in RVOT myocytes.Distinct properties of RVOT myocytes.Transcriptomic profile of the RVOT.

Evaluation of mavacamten in patients with hypertrophic cardiomyopathy.

We aimed to comprehensively assess the safety and efficacy of mavacamten in hypertrophic cardiomyopathy (HCM) patients. A systematic review and meta-analysis was conducted, and efficacy [changes in postexercise left ventricular outflow tract (LVOT) gradient, left ventricular ejection fraction (LVEF), peak oxygen consumption (pVO 2 ), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS), and the proportion of patients exhibiting an improvement of at least one New York Heart Association (NYHA) functional class from baseline)], safety (total count of treatment-emergent adverse events and SAEs, as well as the proportion of patients experiencing at least one adverse event or SAE), and cardiac biomarkers (NT-proBNP and cTnI) outcomes were evaluated. We incorporated data from four randomized controlled trials, namely EXPLORER-HCM, VALOR-HCM, MAVERICK-HCM, and EXPLORER-CN. Mavacamten demonstrated significant efficacy in reducing the postexercise LVOT gradient by 49.44 mmHg ( P = 0.0001) and LVEF by 3.84 ( P < 0.0001) and improving pVO 2 by 0.69 ml/kg/min ( P = 0.4547), KCCQ CSS by 8.11 points ( P < 0.0001), and patients with at least one NYHA functional class improvement from baseline by 2.20 times ( P < 0.0001). Importantly, mavacamten increased 1.11-fold adverse events ( P = 0.0184) 4.24-fold reduced LVEF to less than 50% ( P = 0.0233) and 1.06-fold SAEs ( P = 0.8631). Additionally, mavacamten decreased NT-proBNP by 528.62 ng/l ( P < 0.0001) and cTnI by 8.28 ng/l ( P < 0.0001). Mavacamten demonstrates both safety and efficacy in patients with HCM, suggesting its potential as a promising therapeutic strategy for this condition. Further research is warranted to confirm these results and explore its long-term effects.

The smooth-walled human RVOT contains trabeculations that cause conduction delay

Abstract Funding Acknowledgements None. Background The right ventricular outflow tract (RVOT) is the outlet from the right ventricle and is the initiating substrate of life-threatening arrhythmias. While the luminal wall of the RVOT is often assumed to be without the complex trabecular meshwork that characterizes the right ventricular free wall, the anatomy of the RVOT is an understudied subject. Aim to investigate whether trabeculations occur in the RVOT and to assess whether this impacts electrical propagation. Methods Human hearts were investigated using high-resolution MRI, histology, RNA-sequencing, and optical and electrical mapping. Results We used high-resolution MRI and serial sectioning to reconstruct the macroscopic details of the human RVOT and identified cases exhibiting much trabeculation. The smooth lumen of the RVOT varied between 9% and 23% of the total RV anterior surface (N=11). Histological analysis on additional six hearts indicated that the RVOT compact layer is thinner when trabeculations are present. RNA sequencing of four human donor hearts revealed enrichment in the subendocardial region of 88 genes associated with cardiac conduction and trabeculations (P adjusted&amp;lt;0.05). Finally, we selected two human donor hearts showing trabeculations in the RVOT from which we generated wedge preparation and performed optical and electrical mapping. The trabecular regions demonstrated high degree of fractionation when compared to non-trabeculated regions, which coincided with delayed activation. Conclusion Trabeculations are found in the RVOT, and their extent varies among individuals. This impacts on the thickness of the compact wall in the RVOT, restricting the depth of tissue at which clinical interventions can be performed, as well as influencing electrical propagation and possible arrhythmogenicity.

Role of Transesophageal Echocardiography in Differentiating Dynamic versus Fixed Left Ventricular Outflow Tract Obstruction in Complete Transposition of Great Arteries: A Rare Case Report

Role of Transesophageal Echocardiography in Differentiating Dynamic versus Fixed Left Ventricular Outflow Tract Obstruction in Complete Transposition of Great Arteries: A Rare Case Report

Alcohol septal ablation for hypertrophic obstructive cardiomyopathy: do mitral valve leaflet length, septal thickness, or sex affect the outcome?

This retrospective cohort study aimed to assess whether basal septal wall thickness (BSWT), anterior (AML) and posterior (PML) mitral leaflet length, or sex were associated with remaining left ventricular outflow tract obstruction (LVOTO) in patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing alcohol septal ablation (ASA). One hundred fifty-four patients who underwent ASA at the Karolinska University Hospital in Stockholm, Sweden, between 2009 and 2021, were included retrospectively. Anatomical and hemodynamic parameters were collected from invasive catheterization before and during ASA, and from echocardiography (ECHO) examinations before, during, and at 1-year follow-up after ASA. Linear and logistic regression models were used to assess the association between sex, BSWT, AML, PML, and outcome, which was defined as the remaining LVOTO (≥ 30 mmHg) after ASA. The median follow-up was 364 days (interquartile range 334–385 days). BSWT ≥ 23 mm (n = 13, 12%) was associated with remaining LVOTO at follow-up (p = 0.004). Elongated mitral valve leaflet length (either AML or PML) was present in 125 (90%) patients. Elongated AML (> 24 mm) was present in 67 (44%) patients, although AML length was not associated with remaining LVOTO at follow-up. Elongated PML (> 14 mm) was present in 114 (74%) patients and was not associated with remaining LVOTO at follow-up. No significant sex differences were observed regarding the remaining LVOTO. ECHO measurement of BSWT can be effectively used to select patients for successful ASA and identify those patients with a risk of incomplete resolution of LVOTO after ASA.Graphical abstract

Cardiac myosin inhibitor, CK-586, minimally reduces systolic function and ameliorates obstruction in feline hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) remains the most common cardiomyopathy in humans and cats with few preclinical pharmacologic interventional studies. Small-molecule sarcomere inhibitors are promising novel therapeutics for the management of obstructive HCM (oHCM) patients and have shown efficacy in left ventricular outflow tract obstruction (LVOTO) relief. The objective of this study was to explore the 6-, 24-, and 48-hour (h) pharmacodynamic effects of the cardiac myosin inhibitor, CK-586, in six purpose-bred cats with naturally occurring oHCM. A blinded, randomized, five-treatment group, crossover preclinical trial was conducted to assess the pharmacodynamic effects of CK-586 in this oHCM model. Dose assessments and select echocardiographic variables were assessed five times over a 48-h period. Treatment with oral CK-586 safely ameliorated LVOTO in oHCM cats. CK-586 treatment dose-dependently eliminated obstruction (reduced LVOTOmaxPG), increased measures of systolic chamber size (LVIDs Sx), and decreased select measures of heart function (LV FS% and LV EF%) in the absence of impact on heart rate. At all tested doses, a single oral CK-586 dose resulted in improved or resolved LVOTO with well-tolerated, dose-dependent, reductions in LV systolic function. The results from this study pave the way for the potential use of CK-586 in both the veterinary and human clinical setting.

The Appraisal of Adults with Congenital Heart Disease: Lesson from Comparison of Surgical Outcomes.

The population of adults with congenital heart disease (ACHD) is constantly growing. There seems to be a consensus that these patients are difficult to manage especially if compared to patients with acquired heart disease. The aim of this study is to compare outcomes and results of cardiac surgery in ACHD patients with a reference population of adults with acquired cardiac disease. Retrospective study of 5053 consecutive patients older than 18years hospitalized for cardiac surgery during a 5-years period in our Institution. Two groups of patients were identified. Group I: 419 patients operated for congenital heart disease; Group II: 4634 patients operated for acquired heart disease. In each Group were identified low, medium, and high-risk patients, according to validated scores. Right ventricular outflow tract surgery was the most frequent procedure in Group I, while coronary artery by-pass grafting was the most common in Group II. Patients with ACHD were younger (37.8 vs. 67.7years), with higher number of previous operations (32.1% vs. 6.9%), had longer post-ICU hospital stay (11 vs. 8days) but had lower ICU stay (1 vs. 2days), shorter assisted mechanical ventilation (12 vs. 14h) and lower surgical mortality (1 vs. 3.7%) (all p < 0.001). No differences were found in term of post-operative complications (12.4 vs. 15%). The surgical treatment of ACHD patients can be done with excellent results and if compared with acquired cardiac disease patients they have better results with shorter ICU stay and lower mortality.

Characteristics and outcomes associated with sarcomere mutations in patients with hypertrophic cardiomyopathy: A systematic review and meta-analysis

BackgroundHypertrophic cardiomyopathy (HCM) is an inherited heart disease that can lead to sudden cardiac death. Impact of genetic testing for the prognosis and treatment of patients with HCM needs to be improved. We conducted a systematic review and meta-analysis to investigate the characteristics and outcomes associated with sarcomere genotypes in index patients with HCM. MethodsA systematic search was conducted in Medline, Embase, and Cochrane Library up to Dec 31, 2023. Data on clinical characteristics, morphological and imaging features, outcomes and interventions were collected from published studies and pooled using a random-effects meta-analysis. ResultsA total of 30 studies with 10,825 HCM index patients were included in the pooled analyses. The frequency of sarcomere genes in HCM patients was 41%. Sarcomere mutations were more frequent in women (p < 0.00001), and were associated with lower body mass index (26.1 ± 4.7 versus 27.5 ± 4.3; p = 0.003) and left ventricular ejection fraction (65.7% ± 10.1% vs. 67.1% ± 8.6%; p = 0.03), less apical hypertrophy (6.5% vs. 20.1%; p < 0.0001) and left ventricular outflow tract obstruction (29.1% vs. 33.2%; p = 0.03), greater left atrial volume index (43.6 ± 21.1 ml/m2 vs. 37.3 ± 13.0 ml/m2; p = 0.02). Higher risks of ventricular tachycardia (23.4% vs. 14.1%; p < 0.0001), syncope (18.3% vs. 10.9%; p = 0.01) and heart failure (17.3% vs. 14.6%; p = 0.002) were also associated with sarcomere mutations. ConclusionsSarcomere mutations are more frequent in women, and are associated with worse clinical characteristics and poor outcomes.

Accuracy of pace-mapping using an automated template matching module for site of origin identification of idiopathic outflow tract premature ventricular contractions

Abstract Background Activation mapping (AM) is the preferred approach to identify the premature ventricular complexes (PVC) site of origin (SOO) but it is limited when PVCs are infrequent. Pace-mapping (PM) is often used in combination with AM. Yet, relying on PM as sole guide for ablation requires a high accuracy for detecting the PVC SOO. Limited data exists on the accuracy of automated PM using PASO™ for identifying the SOO of idiopathic PVCs, particularly in the left ventricular outflow tract (LVOT). In two cohorts with both idiopathic and non-idiopathic PVCs, a PASO™ &amp;gt;94% was associated with ablation success. Purpose This study evaluated the accuracy of PM using the automated digital pace-matching module integrated in the CARTO mapping system for identifying the SOO of idiopathic outflow-tract PVCs. It also compared its accuracy in the LVOT versus the right ventricular outflow tract (RVOT). Methods Consecutive patients undergoing successful ablation of idiopathic outflow-tract PVCs were prospectively included. AM and PM were performed with a 3.5mm tip catheter. PM was conducted at 2mA, 5mA, or 10mA output, selecting the lowest output that captured at each site. Ablation was performed at the site of earliest bipolar local activation time. The PVC SOO was defined as the site of acute ablation success. The distance between the best PM (BPM) and the SOO and the areas defined by PM ≥98%, ≥96%, and ≥94% were measured. Long-term success was defined by a ≥80% reduction in PVC burden at 3-month follow-up. Results In total, 27 patients were included; 18 had PVCs from the RVOT and 9 from the LVOT. All procedures were acutely successful after a median of 2 (IQR 1-3) radiofrequency applications (RFA) in the RVOT and one (IQR 1-2) RFA in the LVOT. In the RVOT, the median BPM was 98.1% (98.0-98.6), the median distance from the BPM to the SOO was 3.5 mm (IQR 0–8.5mm) and the areas of PM ≥98%, ≥96%, ≥94% were 1.2cm2 (0.5 – 1.8), 3.4cm2 (1.5-4.7) and 7.1cm2 (4.9-11.1). In the LVOT, the median BPM was 95.5% (IQR 94.9 – 97.8%) and the median distance from the BPM to the SOO was 8 mm (IQR 2–15mm). Only 3/9 patients with LVOT PVCs had a BPM ≥96% (1/9 ≥98%) and in all 3, the PVC SOO was coincident with the BPM site. From the remaining 6 patients, 5 had a BPM ≥94% but only in 2/5 the PVC SOO was within the area defined by the BPM site. In 26/27 (96%) patients, no PVC recurrence was documented after 3 months (median burden 0% [IQR 0-0]). Conclusions The accuracy of using the best pace-match provided by PASO™ for identifying the PVC SOO in the RVOT is high, making it a suitable target for limited ablation when activation mapping is not possible because of insufficient PVCs. In the LVOT, the best pace-match is frequently lower than in the RVOT and it misses the PVC SOO in almost half of the patients. The previously suggested PM &amp;gt;94% cut-off seems to be insufficient to identify the PVC SOO in both the RVOT and LVOT.TablePacemap