Ventricular Outflow Obstruction Research Articles

Insights into calcific aortic valve stenosis: a comprehensive overview of the disease and advancing treatment strategies

Aortic valve stenosis is a disease characterized by thickening and narrowing of the aortic valve (AV), most commonly due to calcification, which leads to left ventricular outflow obstruction called calcific aortic valve disease (CAVD). CAVD presents as a progressive clinical syndrome with cardiorespiratory symptoms, often with rapid deterioration. The modern-day pathophysiology of CAVD involves a complex interplay of genetic factors, chronic inflammation, lipid deposition, and valve calcification, with early CAVD stages resembling atherosclerosis. Various imaging modalities have been used to evaluate CAVD, with a recent trend of using advanced imaging to measure numerous AV parameters, such as peak jet velocity. Significant improvements in mortality have been achieved with transcatheter AV repair, but numerous therapeutics and modalities are being researched to delay the progression of CAVD. This article aims to provide a comprehensive review of CAVD, explore recent developments, and provide insights into future treatments with various novel modalities.

Transcatheter Myotomy to Reduce Left Ventricular Outflow Obstruction

BackgroundLeft ventricular outflow tract (LVOT) obstruction is a source of morbidity in hypertrophic cardiomyopathy (HCM) and a life-threatening complication of transcatheter mitral valve replacement (TMVR) and transcatheter aortic valve replacement (TAVR). Available surgical and transcatheter approaches are limited by high surgical risk, unsuitable septal perforators, and heart block requiring permanent pacemakers. ObjectivesThe authors report the initial experience of a novel transcatheter electrosurgical procedure developed to mimic surgical myotomy. MethodsWe used septal scoring along midline endocardium (SESAME) to treat patients, on a compassionate basis, with symptomatic LVOT obstruction or to create space to facilitate TMVR or TAVR. ResultsIn this single-center retrospective study between 2021 and 2023, 76 patients underwent SESAME. In total, 11 (14%) had classic HCM, and the remainder underwent SESAME to facilitate TMVR or TAVR. All had technically successful SESAME myocardial laceration. Measures to predict post-TMVR LVOT significantly improved (neo-LVOT 42 mm2 [Q1-Q3: 7-117 mm2] to 170 mm2 [Q1-Q3: 95-265 mm2]; P < 0.001; skirt-neo-LVOT 169 mm2 [Q1-Q3: 153-193 mm2] to 214 mm2 [Q1-Q3: 180-262 mm2]; P < 0.001). Among patients with HCM, SESAME significantly decreased invasive LVOT gradients (resting: 54 mm Hg [Q1-Q3: 40-70 mm Hg] to 29 mm Hg [Q1-Q3: 12-36 mm Hg]; P = 0.023; provoked 146 mm Hg [Q1-Q3: 100-180 mm Hg] to 85 mm Hg [Q1-Q3: 40-120 mm Hg]; P = 0.076). A total of 74 (97.4%) survived the procedure. Five experienced 3 of 76 (3.9%) iatrogenic ventricular septal defects that did not require repair and 3 of 76 (3.9%) ventricular free wall perforations. Neither occurred in patients treated for HCM. Permanent pacemakers were required in 4 of 76 (5.3%), including 2 after concomitant TAVR. Lacerations were stable and did not propagate after SESAME (remaining septum: 5.9 ± 3.3 mm to 6.1 ± 3.2 mm; P = 0.8). ConclusionsWith further experience, SESAME may benefit patients requiring septal reduction therapy for obstructive hypertrophic cardiomyopathy as well as those with LVOT obstruction after heart valve replacement, and/or can help facilitate transcatheter valve implantation.

Aortic dilation in adults with repaired tetralogy of Fallot: a single-centre study.

Tetralogy of Fallot is the most prevalent cyanotic CHD. With the advent of advanced surgical methods, the majority of tetralogy of Fallot patients reach adulthood. However, many need re-intervention for the residual anomalies including residual right ventricular outflow obstruction, pulmonary regurgitation, residual ventricular septal defects, and progressive aortic dilatation. Aortic dilation could lead to aortic regurgitation or dissection requiring surgical correction. In the current study, we aimed to determine the prevalence and outcomes of aortic root dilatation in adults with repaired tetralogy of Fallot in our tertiary care centre. In this retrospective study, 730 consecutive patients with history of repaired tetralogy of Fallot were included. Aortic diameter at the level of annulus, the sinus of Valsalva, sinotubular junction, and the ascending aorta as measured by echocardiography were evaluated. Prevalence of outcomes necessitating re-intervention including aortic regurgitation and dissection were recorded. The mean size of annulus, sinus of Valsalva, sinotubular-junction, and ascending aorta in the latest available echocardiography of patients were 2.4+/-0.4 cm, 3.3+/-0.5 cm, 2.9+/-0.5cm, and 3.2+/-0.5cm, respectively. Prevalence of dilatation of sinus of Valsalva, dilation of Ascending aorta, sinotubular-junction, and aortic annulus was 28.7%, 21%, 8.3%, and 1 %, respectively. Five patients had severe aortic regurgitation (0.6%) and underwent surgical repair. One of these patients presented with acute aortic dissection. Aortic dilation is common in tetralogy of Fallot but prevalence of redo surgery for aortic dilation, regurgitation, and adverse events including acute dissection is low.

Ventricular septal defect following mitral valve replacement.

Mitral valve surgery (MVS), with repair preferred to replacement, is a common procedure for the treatment of severe primary mitral regurgitation related to leaflet prolapse. Structural complications after MVS include left ventricular outflow obstruction, paravalvular leak and atrial septal defect. Intraoperative transoesophageal echocardiography and predischarge transthoracic echocardiography (TTE) specifically screen for these complications. Ventricular septal defect (VSD), a known complication after aortic valve surgery, is rarely reported after MVS. Recently, unsuccessful valvuloplasty prior to replacement was suggested as a risk factor. We present such a case and explore mechanisms with advanced cardiac imaging. In this case, the patient was found to have an elongated membranous septum that likely predisposed her to septal injury. Finally, we provide guidance on specific transoesophageal/transthoracic echocardiography views to avoid a missed diagnosis.

Hemodynamics in Adults with Systemic Right Ventricles: Differences Between Congenitally Corrected and Complete Transposition of the Great Arteries.

Despite their anatomical differences, congenitally corrected (ccTGA) and complete transposition of the great arteries (d-TGA) post-atrial switch are frequently studied together and managed similarly from a medical standpoint due to the shared systemic right ventricle (sRV). The aim was to assess differences in their underlying hemodynamics. The studyis aretrospective review of 138 adults with ccTGA or d-TGA post-atrial switch undergoing cardiac catheterization at Mayo Clinic, MN between 2000 and 2021. ccTGA was categorized into isolated or complex ccTGA depending on concomitant ventricular septal defect and/or left ventricular outflow obstruction. There were 53 patients with d-TGA (91% post-Mustard procedure), 51 with complex and 34 with isolated ccTGA. Isolated ccTGA patients were older (51.8 ± 13.1years) than those with d-TGA (37.5 ± 8.3years) or complex ccTGA (40.8 ± 13.4years). There were no differences in sRV or left ventricular size and function across groups. The ccTGA group more commonly had ≥ moderate tricuspid regurgitation than those with d-TGA; ≥ moderate mitral and ≥ moderate pulmonary regurgitation were most prevalent in complex ccTGA. There were no differences in sRV end-diastolic pressure (sRVEDP) or PAWP between groups. However, the ratio of PAWP:sRVEDP was higher in those with d-TGA compared to those with ccTGA. Cardiac index was higher in the d-TGA group than both groups of ccTGA patients with the latter showing higher indices of ventricular afterload. In conclusion, despite sharing a sRV, adults with d-TGA and ccTGA have substantial differences in hemodynamics and structural/valvular abnormalities. Further investigation regarding disease-specific responses to heart failure therapy in those with d-TGA and ccTGA is warranted.

Percutaneous Closure of Hemodynamically Significant Postoperative Residual Ventricular Septal Defects.

The experience with percutaneous closure of postoperative residual ventricular septal defects (VSDs) is expanding with improved device technology and techniques. To report our experience with percutaneous closure of residual VSDs after cardiac surgeries. Retrospective clinical data review of patients who had percutaneous closure of postoperative residual VSDs at our institution between 2010 and 2022. Patients' demographics, procedural, and follow-up data were looked at. Twelve patients (50% males) with a median age of 9.2years (range 0.9-22) were identified. Baseline surgeries were 8 tetralogy of Fallot corrections, 2 pulmonary bandings for large muscular VSD (mVSD) including 1 coarctation repair, 1 atrioventricular septal defect repair, 1 sub-aortic membrane resection-induced iatrogenic VSD, 1 isolated VSD closure, and 1 additional mVSD. Median duration between baseline surgery and percutaneous VSD closure was 2.2years (range 0.2-8.3). Residual VSD shunting was secondary to surgical patch leakage in 8/12 patients. The median angiographic defect diameter was 6.8mm (range 4.8-14). The defect was balloon-calibrated in 3/12 patients. Defects were tackled retrogradely in 3/9 patients. Amplatzer Membranous VSD occluder (n = 1), Lifetech Multifunctional (n = 5), Membranous (n = 1) and muscular VSD occluders (n = 2) and Occlutech Membranous (n = 1) and Muscular (n = 2) VSD occluders were used. The procedure was successful in 10/12 patients. Two devices embolized to the pulmonary artery and were snare-retrieved. Both patients were referred for surgery. The median follow-up was 1.3years (range 0.1-12). Six-month ultrasound showed one trivial residual shunt and one mild right ventricular outflow obstruction. One patient is receiving targeted therapy for pulmonary hypertension at 2years of follow-up. Transcatheter closure of postoperative residual VSDs is a feasible yet challenging intervention. Procedural complications can be encountered.

Neurodevelopmental outcomes in congenital heart disease: usefulness of biomarkers of brain injury

IntroductionAt present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. MethodsProspective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: 1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; 2) clinical and laboratory data from the immediate postnatal and perioperative periods; 3) treatments and complications; 4) neurodevelopment (Bayley-III scale) at age 2 years. Resultsthe study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. Conclusionschildren with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer followups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.

Features of left ventricular outflow obstruction in patients with different phenotypes of hypertrophic cardiomyopathy

Features of left ventricular outflow obstruction in patients with different phenotypes of hypertrophic cardiomyopathy

Structural and Functional Impact of Adrenoceptor Beta-1 Gene Polymorphism in Patients with Hypertrophic Cardiomyopathy and Response to Beta-Blocker Therapy.

Hypertrophic cardiomyopathy (HCM) is a genetically inherited cardiac disorder with diverse clinical presentations. Adrenergic activity, primarily mediated through beta-adrenoceptors, plays a central role in the clinical course of HCM. Adrenergic stimulation increases cardiac contractility and heart rate through beta-1 adrenoceptor activation. Beta-blocker drugs are recommended as the primary treatment for symptomatic HCM patients to mitigate these effects. This prospective study aimed to investigate the impact of common ADRB-1 gene polymorphisms, specifically serine-glycine at position 49 and arginine-glycine at position 389, on the clinical and structural aspects of HCM. Additionally, the study explored the association between these genetic variations and the response to beta-blocker therapy in HCM patients. A cohort of 147 HCM patients was enrolled, and comprehensive assessments were performed. The findings revealed that the Ser49Gly polymorphism significantly influenced ventricular ectopic beats, with beta-blocker therapy effectively reducing them in Ser49 homozygous patients. Moreover, natriuretic peptide levels decreased, particularly in Ser49 homozygotes, indicating improved cardiac function. Left ventricular outflow obstruction, a hallmark of HCM, was also reduced following beta-blocker treatment in all patient groups. In contrast, the Arg389Gly polymorphism did not significantly impact baseline parameters or beta-blocker response. These results emphasize the role of the Ser49Gly polymorphism in the ADRB-1 gene in shaping the clinical course and response to beta-blocker therapy in HCM patients. This insight may enable a more personalized approach to managing HCM by considering genetic factors in treatment decisions. Further research with larger populations and longer follow-up periods is needed to confirm and expand upon these findings.

Intermittent Pre-Syncope after Surgical Correction of Aortic Stenosis Caused by Left Ventricular Outflow Obstruction by Elongated Mitral Leaflets

Left ventricular outflow obstruction (LVOTO) is a potential complication following surgical replacement of the aortic valve. We present an 88-year-old man who experienced periodic episodes of pre-syncope following aortic valve replacement. The underlying cause was identified as LVOTO resulting from elongated mitral valve leaflets. The diagnosis was established using stress echocardiography, which detected transient LVOTO with moderate rise in heart rate. The medical approach involved administering beta-blockers and optimising hydration consumption. The patient's symptoms and quality of life showed considerable improvement during the six-month follow-up period. Timely identification and intervention are essential in managing left ventricular outflow tract obstruction (LVOTO) after aortic valve replacement, to mitigate the risk of potential adverse cardiac events.

Perioperative and Anesthetic Considerations in Shone's Complex.

Shone's complex is a congenital cardiac disease consisting of the following four lesions: parachute mitral valve, supravalvar mitral ring, subaortic stenosis, and aortic coarctation. Though not all components are required for a diagnosis, the end result is both left ventricular inflow and outflow obstruction, which typically present in patients as congestive heart failure. The complex pathology requires careful management and surgical decision-making to ensure an optimal outcome. This review will focus on the anatomy, physiology, and perioperative anesthetic management of patients with Shone's complex.

Rare case of primary intra-cardiac myxosarcoma with left ventricular outflow and inflow obstruction.

Rare case of primary intra-cardiac myxosarcoma with left ventricular outflow and inflow obstruction.

Neurodesarrollo a los 2 años en cardiopatía congénita: utilidad pronóstica de los marcadores de daño cerebral

IntroductionAt present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. MethodsProspective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. ResultsThe study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. ConclusionsChildren with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer followups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.

Computed Tomographic Evaluation of Congenital Left Ventricular Outflow Obstruction.

Congenital left ventricular outflow obstruction represents a multilevel obstruction with several morphological forms. It can involve the subvalvular, valvar, or supravalvular portion of the aortic valve complex, and may coexist. Computed tomography (CT) plays an important supplementary role in the evaluation of patients with congenital LVOT obstruction. Unlike transthoracic echocardiography and cardiovascular magnetic resonance (CMR) imaging, it is not bounded by a small acoustic window, needs for anaesthesia or sedation, and metallic devices. Current generations of CT scanners with excellent spatial and temporal resolution, high pitch scanning, wide detector system, dose reduction algorithms, and advanced 3-dimensional postprocessing techniques provide a high-quality alternative to CMR or diagnostic cardiac catheterization. Radiologists performing CT in young children should be familiar with the advantages and disadvantages of CT and with the typical morphological imaging features of congenital left ventricular outflow obstruction.

Nuclear magnetic resonance spectroscopy to quantify major extracellular matrix components in fibro-calcific aortic valve disease

AbstractFibro-calcific aortic valve disease (FCAVD) is a pathological condition marked by overt fibrous and calcific extracellular matrix (ECM) accumulation that leads to valvular dysfunction and left ventricular outflow obstruction. Costly valve implantation is the only approved therapy. Multiple pharmacological interventions are under clinical investigation, however, none has proven clinically beneficial. This failure of translational approaches indicates incomplete understanding of the underlying pathomechanisms and may result from a limited toolbox of scientific methods to assess the cornerstones of FCAVD: lipid deposition, fibrous and calcific ECM accumulation. In this study, we evaluated magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy to both, qualitatively and quantitatively assess these key elements of FCAVD pathogenesis. NMR spectra showed collagen, elastin, triacylglycerols, and phospholipids in human control and FCAVD tissue samples (n = 5). Calcification, measured by the hydroxyapatite content, was detectable in FCAVD tissues and in valve interstitial cells under procalcifying media conditions. Hydroxyapatite was significantly higher in FCAVD tissues than in controls (p &lt; 0.05) as measured by 31P MAS NMR. The relative collagen content was lower in FCAVD tissues vs. controls (p &lt; 0.05). Overall, we demonstrate the versatility of NMR spectroscopy as a diagnostic tool in preclinical FCAVD assessment.

Aficamten-A Second in Class Cardiac Myosin Inhibitor for Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy is an under-recognized disease with a genetic component that results in abnormal and often asymmetric thickening of the left ventricle in addition to decreased compliance and progressive fibrosis of the myocardium. It further poses significant complications related to dynamic left ventricular outflow obstruction over time in a significant majority. The medical management of obstructive hypertrophic cardiomyopathy has evolved over the decades as our understanding has grown. Traditionally, the mainstay in management has included the use of various negative inotropic agents. In contrast, the cardiac myosin inhibitors, aficamten and mavacamten, are novel therapies targeting cardiac contractility at the sarcomere level that have demonstrated improvement in clinical outcomes for patients, and mavacamten (Bristol Myers Squibb, Inc.) has now been approved by the Food and Drug Administration for the treatment of symptomatic obstructive HCM. Aficamten (Cytokinetics, Inc.) is the second in class cardiac myosin inhibitor that is currently being evaluated in ongoing phase III clinical trials, and is the subject of this review.

Migration and Thrombosis of Injectable Pulmonary Valve

Pulmonary valve replacement is required after tetralogy of Fallot or surgery performed for relief of right ventricular outflow obstruction. Interventional methods are more preferable for patient comfort in medical practice. Here we introduce a 14-year-old male patient who developed complications of migration and thrombosis after intervention for pulmonary valve replacement, and was successfully treated with a second operation.

Successful treatment of severe subaortic stenosis with left ventricular dysfunction in children

Link of Video Abstract: https://youtu.be/tHcMqNHfLyYBackground: Subaortic stenosis (SAS) is the second most common form of left ventricular outflow obstruction, accounting for 14% of LVOT obstruction in the general population. This obstruction is in the area of the heart under the aortic valve. While only a few cases have been reported in pediatrics, SAS is a gradually progressive disorder rarely seen at birth and infancy. This case study aims to evaluate the successful treatment of severe SAS with left ventricular dysfunction in children Case Presentation: We present the case of an 8-year-old boy who presented with shortness of breath on exertion and diaphoresis 3 months ago. Transthoracic echocardiography revealed severe aortic stenosis (PG 69.86 mmHg) with discrete tissue in the anterior LVOT and left ventricular systolic function decreased (EF Teich 29.44%), with global hypokinetic. Transesophageal echocardiography (TEE) results in severe subvalvular AS with a fixed subaortic membrane (PG 51.16 mmHg; Stenotic area 0.1 cm2), anterior to the aortic valve 1 cm long. There was mild mitral regurgitation and moderate tricuspid regurgitation. The patient then undergoes successful medical treatment and surgical subaortic membrane resection with tricuspid repair. After one year's operation, the patient remained stable, in good condition and free of symptoms. Conclusion: Subaortic stenosis is a gradually progressive disorder and could develop into heart failure with significant left ventricular dysfunction. Monitoring is an important aspect, given the nature of disease progression. Successful management of a patient with subaortic stenosis involves a multidisciplinary approach, including an early diagnosis, a comprehensive understanding of cardiac pathophysiology, risk factors of recurrence, optimal medical management and surgical strategy.

Outra falha de bioprótese valvar cirúrgica: uma segunda solução transcateter valve-in-valve

Transcatheter mitral valve-in-valve replacement has recently emerged as an increasingly common alternative for high surgical risk patients. We report a case of a successful transseptal transcatheter mitral valve-in-valve replacement for the treatment of a bioprosthetic mitral valve degeneration and severe regurgitation, in an 86-year-old patient who had undergone transcatheter aortic valve-in-valve procedure 6 years ago. This case emphasizes the crucial role of a careful preoperative assessment using multimodality imaging to plan the procedure, in a patient with higher risk of left ventricular outflow obstruction due to the previous transcatheter aortic valve-in- valve procedure.

William Syndrome Associated with Hypertrophic Cardiomyopathy and Severe Left Ventricular Outflow Obstruction: A Rare Case Report

William Syndrome Associated with Hypertrophic Cardiomyopathy and Severe Left Ventricular Outflow Obstruction: A Rare Case Report