Peak Gradient Research Articles

Disopyramide Revisited for Treatment of Symptomatic Obstructive Hypertrophic Cardiomyopathy: Efficacy and Safety in Patients Treated for at Least 5 Years.

Disopyramide is used to treat heart failure symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM) with known medium-term efficacy and safety, while long-term outcomes are unknown. A total of 92 consecutive patients with symptomatic obstructive HCM with peak left ventricular outflow tract gradients of ≥30 mm Hg at rest or with provocation who were maintained on disopyramide for ≥5 years at 2 dedicated HCM centers were included: 92 patients; mean age, 62.5 years; 54% women; treated with disopyramide for median 7.2 years (left ventricular wall thickness 18±4 mm; median peak outflow gradient 95 mm Hg). At last follow-up, 62 (67%) patients continued disopyramide, including 57 with symptom improvement ≥1 New York Heart Association class. The other 30 (33%) patients discontinued disopyramide due primarily to incomplete symptom resolution and required surgical myectomy or alcohol septal ablation (n=23) at 7.4 years from initiation. With disopyramide, resting left ventricular outflow gradients were reduced by 37% (to median 19 mm Hg), and provoked gradients decreased by 57% (to median 41 mm Hg), with no residual outflow obstruction (<30 mm Hg at rest or with provocation) in 42 (46%) patients and no change in ejection fraction (69%±6% versus 69%±9%, P=0.51). Ventricular tachyarrhythmias and left ventricular systolic dysfunction were uncommon (n=3 and n=1) and were not attributed to disopyramide. Death on disopyramide was exceedingly rare (n=3 [5%]) and non-HCM-related occurring at age ≥90 years. In patients with obstructive HCM, disopyramide is safe and effective at relieving heart failure symptoms from outflow obstruction in a subgroup of patients who were maintained on disopyramide for >5 years.

EVALUATION OF THE RESULTS OF AORTIC VALVE NEOCUSPIDIZATION WITH AUTOLOGOUS PERICARDIUM USING THE OZAKI TECHNIQUE IN AORTIC ROOT SURGERY

HighlightsThe main surgical interventions for aortic valve pathology at the aortic root site are aortic valve replacement and redo replacement. The Ozaki procedure emerged in the last decade; it involves replacement of the aortic valve using autologous pericardium. Despite the fact that many centers perform the Ozaki procedure frequently, there are few studies on the comparative evaluation of its efficacy. This necessitated the present study, which compares three groups of patients operated on using different techniques. Aim. To compare the short- and medium-term results of the Ozaki procedure and aortic valve replacements using mechanical and biological valves.Methods. The retrospective study included 189 patients operated on for aortic malformation at the Cardiac Surgery Department of Sechenov University from 2017 to 2022. Three groups of patients were formed: patients undergoing Ozaki procedure were included in the Ozaki group (70 patients), patients undergoing aortic valve replacement using mechanical prosthesis were included in the Mechanical valve group (62 patients), and patients undergoing aortic valve replacement using biological prosthesis were included in the Biovalve group (57 patients). The Ozaki procedure was performed in case the diameter of the aortic annulus was ≤ 25 mm. All mid-term outcomes were assessed after at least 6 months (mean follow up period was 20 months). The primary end points were mean and peak aortic valve gradient, 30-day mortality in the short-term postoperative period, and midterm mortality (≥ 6 months).Results. The mean gradient in the Ozaki, Biovalve, and Mechanical valve groups were 10.67 ± 7.15, 15.94 ± 21, and 17.87 ± 7.52 mm Hg. The peak gradient in the Ozaki group decreased from 81.7 ± 32.5 to 21.01 ± 13.22 mm Hg (in the in-hospital setting). 6 months after surgery, the peak gradient values were 18.98 ± 16.17 mm Hg. The in-hospital mortality rates in the Ozaki, Mechanical valve and Biovalve groups were 2.86, 5.26, and 6.45%, respectively. The overall mid-term mortality in three groups was 6/189, 3.17% (95% CI: 1.5–6.07), p = 0.172.Conclusion. In the short- and mid-term period, Ozaki procedure is superior to aortic valve replacement techniques in terms of aortic valve pressure gradient and comparable in terms of mortality.

Differential determinants and prognostic value of aortic valve sclerosis over carotid atherosclerosis.

Aortic valve sclerosis (AVS) is a progressive atherosclerotic disease associated with future cardiovascular events (CVE). However, whether its development and prognostic value are independent of arterial atherosclerosis has not been thoroughly investigated. We evaluated the determinants and prognostic value of AVS in conjunction with carotid atherosclerosis. 4688 consecutive patients who underwent carotid ultrasonography and echocardiography were followed for an average of 3.6 ± 1.3 years, excluding those with bicuspid aortic valve, rheumatic heart disease, overt aortic stenosis, and prior aortic valve replacement. AVS was defined as any thickened cusps with hyper-echogenicity but a peak pressure gradient <2.5 m/s. The mean age of the patients was 61.1 ± 11.7 years, with 1836 (39 %) being women. Among them, 523 (11 %) had AVS. AVS was independently correlated with age, diabetes, lower high-density lipoprotein levels, and presence of carotid plaques. Moreover, it was significantly related to atherosclerotic CVE (acute coronary syndromes, and all-cause death; log-rank p = 0.011) and future heart failure (HF) admissions (p < 0.001). In multivariate analyses, AVS was significantly associated with atherosclerotic CVE regardless of age and sex but significantly attenuated by the presence of carotid plaques. Meanwhile, future HF admission was attenuated considerably after adjusting for E/e' and left ventricular (LV) ejection fraction. AVS has prognostic value for future CVE and HF. Atherosclerotic CVE was primarily mediated by vascular atherosclerosis; however, future HF admissions were mainly mediated by concomitant LV systolic and diastolic dysfunction, suggesting that AVS serves as a surrogate marker rather than an independent risk factor.

Clinical utility of quantitative ultrasonography parameters combined with serum cancer antigen 15‑3, human epidermal growth factor receptor 2 and soluble E‑cadherin in diagnosing mass‑type breast cancer.

Contrast-enhanced ultrasonography (CEUS), a newly developed imaging technique, holds certain value in differentiating benign from malignant tumors. Additionally, serum tumor markers also exhibit significant clinical importance in the diagnosis and monitoring of malignant tumors. Reports have indicated abnormal expression of HER-2, CA153 and sE-cad in breast cancer. Early diagnosis of breast cancer facilitates early clinical intervention and enhances the overall quality of life for patients. Therefore, this study aims to explore the clinical value of quantitative CEUS parameters combined with serum levels of CA153, HER-2 and sE-cad in diagnosing mass-type breast cancer. In total, 49 patients with breast cancer (breast cancer group) and 56 patients with benign breast tumors (benign group) were selected as the study participants, while 50 healthy women served as the control group. Ultrasonography was performed on the patients in the breast cancer and benign groups using diagnostic color Doppler ultrasonography. The serum CA15-3, HER-2 and sE-cad levels in all three study groups were measured using a fully automated electrochemiluminescence immunoassay. Pearson's correlation test was used to analyze the correlation between the quantitative ultrasonography parameters and serum CA15-3, HER-2 and sE-cad levels. Logistic multivariate regression analysis was performed to analyze the independent risk factors, and a receiver operating characteristic curve was plotted to assess the diagnostic value of these factors. The peak intensity (PI), wash-in slope (WIS), gradient (Grad) and local mean transit time (mTTI), along with the CA15-3, HER-2 and sE-cad levels in the breast cancer group were significantly higher, and the time to peak (TTP) was significantly lower, compared with those values in the benign and control groups. CA15-3, HER-2 and sE-cad were negatively correlated with TTP in the breast cancer group (all P<0.05) and positively correlated with PI, WIS, Grad and mTTI (all P<0.05). The area under the curve (AUC) values for CA15-3, HER-2, sE-cad, PI, WIS, Grad, mTTI and TTP for the diagnosis of malignant breast cancer were 0.640, 0.730, 0.687, 0.683, 0.692, 0.737, 0.697 and 0.671, respectively. The AUC for the combined diagnosis was 0.919, with a sensitivity of 0.857 and a specificity of 0.911, outperforming each index alone for a single diagnosis. Logistic multivariate regression analysis revealed that HER-2, TTP, PI, WI and Grad were independent risk factors for malignant breast cancer. In conclusion, combining the quantitative ultrasonography parameters with the CA15-3, HER-2 and sE-cad levels facilitated the differential diagnosis of benign and malignant breast lesions, and may provide a reference for clinical treatment in the future.

A Triple Threat: A Case Report Detailing Surgical Management for Hypertrophic Cardiomyopathy, Flail Mitral Valve and Severe Pulmonary Hypertension†.

Pulmonary hypertension is an independent predictor of all-cause mortality in patients with hypertrophic cardiomyopathy managed medically and often precludes patients from undergoing cardiopulmonary bypass due to increased surgical morbidity and mortality. In studies specifically evaluating surgical myectomy, however, survival is favorable in patients with moderate-to-severe pulmonary hypertension. We present a case of a 74-year-old male with six months of dyspnea with minimal exertion. A diagnostic work-up with transthoracic echocardiogram showed asymmetric left ventricular hypertrophy, left ventricular outflow tract obstruction with a peak gradient of 200 mmHg, right ventricular systolic pressure of 99 mmHg, systolic anterior motion of the mitral valve and flail anterior mitral leaflet. The patient was evaluated by a multi-disciplinary team and underwent extended septal myectomy and mitral valve repair with significant improvement in functional capacity post-operatively. While pulmonary hypertension increases the risk of morbidity and mortality during cardiopulmonary bypass, moderate-to-severe pulmonary hypertension in hypertrophic cardiomyopathy with outflow tract obstruction is a unique indication for septal reduction therapy that may not be associated with higher surgical mortality.

Association Between Location of Pulmonary Outflow Obstruction and Right Ventricular Size and Function After Repair of Tetralogy of Fallot, Pulmonary Atresia, and Major Aortopulmonary Collaterals.

Quantification of right ventricular (RV) size and function after tetralogy of Fallot repair is critical for determining timing of reintervention and outcomes. Tetralogy of Fallot patients with pulmonary atresia and major aortopulmonary collateral arteries (TOF/PA/MAPCAs) are a unique group in which the RV is subjected to various loading conditions, allowing for direct comparison. Retrospective evaluation of RV echocardiographic indices in repaired pediatric TOF/PA/MAPCAs patients (2/2002 - 4/2018). Patients were categorized as having conduit stenosis (peak gradient ≥ 2.5m/s) and/or distal pulmonary artery (PA) stenoses (requiring catheter or surgical intervention and > 1/2 systemic RV pressures). A comparison group (N = 9) included distinct age-matched repaired patients without residual lesions. Indexed right heart dimensions were larger in patients with distal PA stenoses (N = 49) compared to conduit stenosis (N = 26), including RV end-diastolic and end-systolic dimensions (p < 0.01), despite earlier time to reintervention (p < 0.0001). RV fractional area change (FAC) was diminished in patients with distal PA stenoses compared to patients without residual lesions (p = 0.006). Patients with conduit stenosis demonstrated a marked decrement in tricuspid annular plane systolic excursion (TAPSE) z-scores. Repaired TOF/PA/MAPCAs patients with residual distal PA stenoses have larger right heart dimensions compared to patients with conduit stenosis, and decreased RV FAC compared to patients without residual lesions at 1-2years after repair, suggesting early surveillance and immediate intervention on stenotic PA segments appears warranted to decrease the risk of further deterioration of RV systolic function.

The crucial role of 18F-FDG PET/CT in diagnosing pulmonary valve endocarditis in patients after transcatheter pulmonary valve implantation: a case report

Abstract Background Patients after transcatheter pulmonary valve implantation (TPVI) are at increased risk for infective prosthetic valve endocarditis. Diagnosis of infective endocarditis (IE) following TPVI is particularly difficult due to impaired visualization of the transcatheter pulmonary valve (TPV) with echocardiography (1). The aim of this case report is to describe the significant role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in diagnosing IE post-TPVI. Case summary A 22-year-old woman presented to the emergency department with fever and chest pain. Relevant past medical history included a left ventricular outflow membrane resection at infancy, a Ross procedure at the age of 4 with post-operative pacemaker implantation and MelodyTM TPVI at the age of sixteen because of pulmonary valve stenosis. Blood tests showed elevated inflammatory markers. Transthoracic echocardiography revealed elevated systolic pulmonary artery pressure of 53mmHg. After 2 days, blood cultures appeared positive for Streptococcus species. Subsequently, transesophageal echocardiography showed an elevated TPV peak gradient (25mmHg). No clear valvular nor pacemaker lead vegetations were identified but could not be ruled out as inspection of the TPV was difficult. However, 18F-FDG PET/CT demonstrated heightened metabolism at the TPV, which confirmed the diagnosis of TPV IE. Intravenous antibiotic treatment was administered, which led to clinical improvement and normalization of the inflammatory markers. Discussion Transthoracic and transesophageal echocardiography often fail to provide adequate assessment, making 18F-FDG PET/CT crucial for diagnosing TPV IE in this case. Important to notice is the possibility of false-negative and false-positive diagnoses and the radiation exposure, particularly in this young population.

ИНФАРКТ МИОКАРДА БЕЗ ОБСТРУКТИВНЫХ ИЗМЕНЕНИЙ КОРОНАРНЫХ АРТЕРИЙ У БОЛЬНОГО С ГИПЕРТРОФИЧЕСКОЙ КАРДИОМИОПАТИЕЙ

Background. Myocardial infarction with non-obstructive coronary arteries is defined by the presence of clinical symptoms and signs of myocardial infarction despite angiographic findings of normal or near-normal coronary arteries. Myocardial infarction with non-obstructive coronary arteries can be classified into myocardial infarction type 1 or type 2. Hypertrophic cardiomyopathy is a possible underlying etiology of myocardial infarction with non-obstructive coronary arteries. The aim. To present the diagnosis of myocardial infarction in a patient with hypertrophic cardiomyopathy. Case descriptions. A clinical case of myocardial infarction with non-obstructive coronary arteries in a man with hypertrophic cardiomyopathy is presented. 57-year-old man presented with retrosternal chest pain that appeared at rest but during an attack of tachyarrhythmia. Electrocardiogram showed right bundle branch block and T inversion in the I, avL, V1-V6. Cardiac troponin T was with a rise and fall in the level. Echocardiography demonstrated asymmetrical septal hypertrophy with thickness of the basal and medium segments of the septum 18 mm, systolic anterior motion of the mitral valve, and left ventricular outflow tract obstruction with a peak systolic pressure gradient of 50 mmHg, diastolic dysfunction of the left ventricle. Coronary angiography revealed stenosis of the left anterior descending artery &lt; 50 %. All these data allow us to diagnose the myocardial infarction with non-obstructive coronary arteries. Type 2 infarction is most likely, however, the absence of an intracoronary imaging does not completely exclude type 1 myocardial infarction. Conclusion. The clinical case demonstrates myocardial infarction in the absence of obstructive coronary artery disease in patient with hypertrophic cardiomyopathy. To exclude plaque disruption intracoronary imaging should be performed.

Comparison of the results of aortic valve neocuspidalization (Ozaki procedure) with aortic valve bioprosthetics in patients with a narrow aortic annulus: a multicenter retrospective study

In aortic valve (AV) replacement surgery in patients with a narrow annulus fibrosus (AF), the likelihood of prosthesis-patient mismatch (PPM) is high. PPM, in turn, significantly affects the hemodynamic and functional capabilities of AV, morbidity and mortality in the postoperative period. The “gold standard” for the treatment of AV diseases is prosthetics with mechanical and biological prostheses. However, there are alternative methods, such as neocuspidalization of AV according to the S. Ozaki (AVNeo) method.Aim: To compare the immediate and medium-term results of AV prosthetics using the S. Ozaki (AVNeo) technique and AV prosthetics with a biological prosthesis in patients with a small aortic annulus.Material and Methods: A retrospective multicenter study of 309 patients with a narrow fibrous ring of the aortic valve (FR AV) who underwent surgery between February 2010 and December 2021 was conducted. Inclusion criteria: prosthetics of AV, FR AV = 21 mm, age 18 years and older. Exclusion criteria: left ventricle ejection fraction ≤ 40%, repeated interventions, mini-stop. 153 patients underwent Aveo and 156 patients underwent AV prosthetics using biological prostheses. After “pseudorandomization” (propensity score matching), 92 patients were selected: 46 patients in the AVNeo group and 46 patients in the biological prosthesis group. The primary endpoint was hospital mortality. Postoperative complications, transvalvular gradients, and medium-term outcomes (three-year overall survival and freedom from surgery on AV) were evaluated as secondary endpoints.Results. There was no statistically significant difference in the duration of surgery (275.9 ± 34.2 min in the AVNeo group and 285.8 ± 37 min in the bioprosthesis group, p &lt; 0.4), artificial circulation (98 min in the AVNeo group and 115 min in the bioprosthesis group, p &lt; 0.3), aortic compression (80 min in the AVNeo group and 93 min in the bioprosthesis group, p &lt; 0.7). Hospital mortality among the studied patients did not differ: in the AVNeo group – 2 (4.3%) and 1 (2.2%) in the bioprosthesis group, p = 1.0. There were no significant differences in postoperative complications: wound surface infection (3 (6.5%) in the AVNeo group and 1 (2.2%) in the bioprosthesis group, p = 0.617), acute kidney injury (1 (2.2%) in the AVNeo group and 0 in the bioprosthesis group, p = 1.0), stroke ( 1 (2.2%) in the AVNeo group and 2 (4.3%) in the bioprosthesis group, p = 1.0), resternotomy for bleeding (0 in the AVNeo group and 2 (4.3%) in the bioprosthesis group, p = 0.495). Permanent pacemaker implantation was not required by any patient. There was also no statistically significant difference in the three-year overall survival and re–operation, in the AVNeo group it was 83% and 92.5% in the bioprosthesis group, p = 0.23; three-year freedom from re-operation was 96.4% in the AVNeo group and 97.1% in the bioprosthesis group, p = 0.27. However, peak and average gradients were statistically less after AVNeo surgery. The peak and average gradients after AVNeo were 12 and 6 mmHg, after prosthetics 32 and 20 mmHg, p &lt; 0.001.Conclusions: There was no statistically significant difference in hospital mortality, postoperative complications, and three-year survival and re-operation. The values of the peak and average pressure gradient at discharge differed statistically significantly in favor of the AVNeo group.

Sitting pressure during wheelchair propulsion and handcycling: effects of backrest angle, movement intensity and cushion type

Purpose: The main aim of this study was to compare sitting pressure (peak pressure index (PPI) and peak pressure gradient (PPG)) between a daily wheelchair and fixed-frame handcycle, thereby assessing the effect of handcycle backrest angle, movement intensity and cushion type. Materials and methods: Twenty able-bodied participants performed static and dynamic (two intensities) tests in a wheelchair and handcycle. A honeycomb wheelchair cushion and standard foam handcycle cushion were used. Handcycle backrest angles were 45° and 60°. The PPI and PPG at the sacro-coccygeal (SC) and ischial tuberosity (IT) regions were determined with a pressure mat. Results: PPI at the IT-region was higher in the 60° handcycle condition than in the wheelchair (p = 0.04), while PPG at the IT-region did not differ significantly between the wheelchair and handcycle conditions (p > 0.05). PPI and PPG were higher at the 45° handcycle SC-region compared to the wheelchair IT-region (p < 0.03). PPI and PPG at the IT-region were higher with the 60° than with the 45° backrest angle (p < 0.01), while at the SC-region PPI was higher with the 45° backrest angle (p = 0.047). No clear influence of movement intensity was found. PPI and PPG at the IT-region and PPI of the SC-region in the handcycle were significantly lower with the wheelchair cushion than with the handcycle cushion (p < 0.01). Conclusion: Overall, sitting pressure was higher in the handcycle compared to the daily wheelchair. For handcyclists using an upright position, it is recommended to use a cushion designed to redistribute pressure, thereby reducing internal tissue pressure and shear.

The role of ion-scale micro-turbulence in pedestal width of the DIII-D wide-pedestal QH mode

Abstract The low-edge rotation, intrinsically ELM-free, and improved confinement wide-pedestal quiescent H-mode (QH-mode), discovered in DIII-D tokamak, has pedestal widths exceeding the EPED-kinetic-ballooning mode (KBM) model scaling typically by at least 25%. Ion-scale ( k y ρ s &lt; 1) microturbulence and its role in setting the pedestal structure is investigated using the radially local δ f gyrokinetic code CGYRO. The electromagnetic trapped electron mode (TEM) is unstable at the pedestal top, while plasma beta ( β e ) is ∼60% below the KBM onset threshold and the electron temperature gradient mode is found to be unstable in the peak gradient region. Nonlinear simulation reveals that the ion-scale turbulence could produce electron energy flux consistent with the flux inferred from power balance at the pedestal top, with a reasonable variation of the local E × B shearing rate; and the local neoclassical transport from NEO is dominant over the simulated turbulent transport in the ion energy flux channel. The simulated ion-scale turbulence produces much lower electron energy flux than inferred from experiment in the pedestal peak gradient region. A correction to the EPED-KBM pedestal width scaling is obtained based on the two-dimensional scan of pedestal top plasma beta ( β e ) and normalized electron density and temperature scale lengths, a / L n e , a / L T e using CGYRO linear simulations. Mode transitions among TEM, micro-tearing mode, ion-temperature gradient mode and KBM, are observed in the 2D scan at the pedestal top. A fixed normalized growth rate for these drift-type modes is taken to determine the pedestal width scaling, which shows good consistency with the QH experimental database on pedestal heights and widths. The onset of KBM instabilities and the local E × B shear suppression criterion set the lower and upper limit for the pedestal width of standard QH-mode, wide-pedestal QH-mode and type-I ELMy H mode. A potentially higher and wider pedestal is expected from the new scaling of pedestal width. This work presents an improved understanding of the ion-scale micro-turbulence of wide-pedestal QH-mode and sheds light on a promising scenario for future reactors, including ITER and beyond.

Differences between echocardiography and cardiac nuclear magnetic resonance parameters in children with bicuspid aortic valve-related aortopathy.

The bicuspid aortic valve (BAV) is the most common congenital heart defect. Patients with BAV frequently develop aortopathy, which depends on the dysfunction and morphotype of the BAV. The aim of our study was to compare the echocardiography and cardiac magnetic resonance (CMR) findings in BAV patients, and to define the risks of BAV dysfunction and aortopathy. The retrospective study included 50 patients (68% male) with BAV, with an average age of 13.6 ± 3.9 years, who underwent a transthoracic echocardiographic examination and CMR at our institute from 2012 to 2020. The BAV types were evaluated significantly differently by echocardiography and CMR (p = 0.013). 54% of patients had BAV insufficiency on echo and 70% on echo CMR. It was more prevalent in males, older patients, and patients with a higher body surface area. By comparing the degree of insufficiency measured by echo (1+, IQR 0-1), and CMR (0, IQR 0-1), a significant difference was observed (p = 0.04), while a moderate positive correlation was proved (rr = 0.4; p = 0.004). Stenosis was registered in 44% of patients by echo, while 58% had stenosis on CMR. The peak pressure gradient measured by echo was significantly higher than the velocity on CMR (41, IQR 22.7-52.5 mmHg vs. 23, IQR 15.5-35.0 mmHg; p = 0.002). Aortopathy was registered in 76% of patients on echo and 78% on CMR; 38% of patients had severe aortic dilatation on echo and 54% on CMR (p = 0.003). Patients with BAV stenosis on echo had more frequent dilatation of the tubular ascending aorta (15/24 pts; p = 0.02). All patients with BAV insufficiency on CMR had aortopathy (p = 0.04) and had enlargement of the sinus of Valsalva and sinotubular junction. In patients with associated coarctation, the development of aortopathy occurred less frequently than those without coarctation (7/39 vs. 32/39; p = 0.003). The Bland-Altman method, a specific type of scatterplot that is used to visualize the results of comparing two measures, demonstrated the existence of agreement between the two methods, and a level of agreement between the methods of 95% was demonstrated. Our study indicated significant differences in the measured BAV morphotype and dysfunction when comparing the two diagnostic methods. On the other hand, moderate to strong correlations were found in the evaluated parameters, which indicates the importance of performing noninvasive diagnostic procedures in the follow-up of these patients.

Functional Mitral Regurgitation Post-Isolated Aortic Valve Replacement.

Background: The management of mitral regurgitation during aortic valve replacement remains a complex question. Secondary mitral regurgitation often improves post-aortic valve replacement without mitral valve surgery, but residual mitral regurgitation can significantly affect long-term outcomes. This study investigates the natural history of mitral regurgitation following isolated aortic valve replacement and identifies prognostic factors for persistent mitral regurgitation. Methods: A retrospective study was conducted on 108 patients who underwent isolated aortic valve replacement. Patients were categorized based on mitral regurgitation improvement. Additionally, patients were divided into patient-prosthesis mismatch and non-patient-prosthesis mismatch groups based on the aortic prosthesis. Preoperative and postoperative echocardiographic data were analyzed. Results: In total, 63% of patients showed mitral regurgitation improvement. The improved functional MR group showed significant reductions in peak and mean transvalvular pressure gradients. In contrast, the patient-prosthesis mismatch group had persistent mitral regurgitation improvement in 59.2% of patients. The non-patient-prosthesis mismatch group exhibited significant structural improvements and a reduction in mitral regurgitation severity in 68.6% of patients. Conclusions: The study shows that aortic valve replacement could significantly improve MR when patient-prosthesis mismatch is avoided. This approach maximizes hemodynamic outcomes, mitigates the risk of residual or worsening mitral regurgitation, and potentially reduces the need for additional mitral valve interventions.

Abstract 4120743: MEK inhibition for recurring pulmonary valve stenosis in RASopathy patients

Backgound: The RASopathies are developmental syndromes resulting from variants in the RAS/mitogen-activated protein (MAPK) cascade. The vast majority of RASopathy-causing variants lead to a gain of function in RAS-MAPK signaling. This has motivated compassionate use of MEK inhibition (MEKi) for rare, but potentially lethal complications such as hypertrophic cardiomyopathy and lymphatic disease. However, the most recurrent cardiac complication in RASopathies is pulmonary valve stenosis (PVS). PVS may require balloon valvuloplasty (BV) and can recur over time. Research question: Can MEKi be successfully used for recurrent PVS in RASopathy-patients? Aim: To report compassionate use of MEKi (trametinib) in recurring RASopathy-associated PVS. Method: Retrospective, single-center study at CHU Sainte Justine, Montreal, from 2021 to 2024. Results: After informed parental consent for off-label compassionate use of trametinib, four patients with recurrence of severe PVS after balloon valvuloplasty (&gt;= 80 mmHg) had a total of 5 treatment episodes. Three patients were female, and one patient was male. The following genotypes were represented: Case 1, RIT1 A77V; case 2, PTPN11 N308D; case 3, RIT1 F82V, del22q11dist; case 4, PTPN11 Q110G, dup Xp22.13 (VUS), dup 16p11.2. Initial BV was carried out between three weeks and 10 months of age. Recurrence of PVS was noted between 4 days and 6 months after BV. Peak gradients at recurrence measured 72 -96 mmHg, and decreased to 40 – 64 mmHg (Dp -10 to -40 mmHg) at one to three months after treatment. Treatment had to be stopped in three cases for cutaneous side effects, with a rapid second recurrence in one case, which again responded to MEKi. PVS residual gradients at latest follow-up ranged from 30 – 69 mmHg. In all four patients, repeat catheter intervention or surgery could be avoided. In three out of four RASopathy patients with severe recurrent PVS after initial BV, we observe mild or moderate residual PVS. The patient with residual severe PS also carries a del22q11.2dist, which renders her haploinsufficient for LZTR1, a potential disease/treatment modifier within the RAS-MAPK cascade. Conclusion: Our results potentially expand the indications for MEKi in selected cases of RASopathy-associated recurrence of PVS and suggest an alternative to surgery or repeat catheterization. However, this case series is limited by the lack of an adequate contemporaneous, genotyped control cohort and its retrospective nature.

Abstract 4138268: The Use of Mavacamten for Management of Post TAVR Obstruction: A Novel Approach to Treatment

Background: Treatment of left ventricular outflow tract (LVOT) obstruction involves a combination of negative inotropic agents. However, these therapies have limitations which may result in insufficient control of symptoms, leading to more invasive options such as surgical septal myectomy or septal alcohol ablation. Mavacamten, a cardiac myosin inhibitor, is currently approved for the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). We present a case of a patient treated with mavacamten in addition to β-blockers (BB) for management of post-TAVR LVOT obstruction. Case: A 76 year old female with a past medical history of hypertension, severe aortic stenosis, and coronary artery disease underwent a Medtronic Evolut TAVR in March 2022. Her TTE post TAVR showed LVOT peak gradient greater than 100 mm Hg, LVEF 75% and severe eccentric mitral regurgitation secondary to systolic anterior motion (SAM) of the mitral valve (MV). After multidisciplinary discussion, the patient was discharged on maximally tolerated BB therapy. Follow up TTE showed persistent obstruction and gradients, so diltiazem was added to her regimen. Her subsequent TTE showed a peak LVOT &gt; 100 mmHg at rest, and severe MR. Given persistent findings, she was started on mavacamten, continued on metoprolol, and tapered off of diltiazem. Her TTE two months after initiation of mavacamten revealed resolution of LVOT gradients, reduction of MR to mild and normal LV and TAVR function. She tolerated the therapy well and endorsed ongoing symptomatic improvement on subsequent follow up. Discussion: With the increasing use of TAVR therapy, there has been a corresponding rise in cases of post-TAVR obstruction that must be managed. As demonstrated by this case, management with BB therapy alone may be suboptimal. Although mavacamten is currently approved in patients with HCM, the obstruction in post-TAVR patients is functionally similar. Thus, this medication was trialed as a supplemental treatment in this patient and yielded positive results. This case highlights the potential benefit of extending use of mavacamten alongside β-blocker therapy for this patient population and suggests the need for future studies.

Contemporary Clinical Characteristics, Imaging, Management, and Surgical and Nonsurgical Outcomes of Adult Patients With Subaortic Stenosis.

Subaortic stenosis (SAS) is characterized by a fibromuscular membrane located just below the aortic valve, causing fixed outflow tract obstruction. There is a paucity of studies evaluating this condition. This cohort study reviewed the contemporary characteristics and outcomes of SAS in adult patients in a single large referral center. We retrospectively studied adult patients with SAS evaluated at our center during 2011 to 2022. The primary outcome was all-cause mortality and heart failure hospitalizations during follow-up, with secondary end points including recurrence of SAS and repeat surgery after initial SAS surgery. Among 484 patients with SAS, key characteristics included mean age 55±18 years, 67.5% female, left ventricular outflow tract peak velocity 352±140 cm/s and gradient 57±40 mm Hg, left ventricular ejection fraction 60%±14%, 54.8% had prior SAS surgery, and 45.1% had surgery during follow-up. Over a median follow-up of 5.5 (1.5-12.3) years, 11.5% (n=56) died, 6.8% (n=33) had heart failure hospitalizations, 8.0% (n=39) experienced SAS recurrence, and 14 (5.9%) underwent repeat SAS surgery. Multivariable analyses identified older age per 10-years (hazard ratio [HR], 1.37 [95% CI, 1.12-1.68]) and baseline New York Heart Association class (HR, 2.48 [95% CI, 1.54-3.99]) to be statistically significantly associated with the primary end point; higher body mass index, New York Heart Association class, and peak left ventricular outflow tract gradient were also statistically significantly associated with SAS recurrence and redo surgery. Almost half of patients with SAS had surgery in the past or during follow-up, and a significant minority had mortality or morbidity events during follow-up. Identified prognosticators warrant further research to guide management.

A Comparative Study of Aortic Valve Neocuspidization Techniques: Formula vs. Template Methods of Neocusp Formation.

The template method (TM), pioneered by Ozaki for aortic valve neocuspidization (AVNeo), has been widely adopted for aortic valve replacement, though it requires specialized instruments. This study introduces a novel formula method (FM), which uses the diameter of the aortic valve fibrous ring (AV-D) to determine the dimensions of the neocusps to be trimmed from autologous without the need for templates, potentially reducing costs and complexity. We aimed to compare the clinical outcomes of the FM with the established TM in patients undergoing AVNeo. A retrospective and prospective study was conducted on 31 patients who underwent isolated AVNeo between January 21, 2019 and December 15, 2022. Patients were divided into two groups: FM (n = 17) and TM (n = 14). The formula for the cusp free margin horizontal length is L1 = AV-D + 10 mm, cusp height is H = AV-D, cusp suture margin is L2 is a parabola that joins L1 and H, and cusp wings to be secured to aortic sinus = 3mm. The primary endpoints were major adverse valve-related events, including cardiac death, reoperation, and infective endocarditis. Secondary endpoints included significant aortic regurgitation, peak pressure gradients, aortic valve area, and New York Heart Association (NYHA) functional class. Intraoperative times, early postoperative outcomes, and mid-term hemodynamic performance were evaluated for both techniques. Both the FM and TM demonstrated comparable intraoperative and postoperative outcomes. The cardiopulmonary bypass time, myocardial ischemia time, and blood loss were similar between the groups. Mid-term outcomes also showed no significant differences in valve function or hemodynamic parameters, with both groups exhibiting substantial reverse left ventricular remodeling. The FM group had a peak pressure gradient of 14.1 ± 4.3 mmHg compared to 18.4 ± 12.0 mmHg in the TM group (p = 0.219). The aortic valve area was 2.43 ± 0.3 cm² in the FM and 2.4 ± 0.2 cm² in the TM (p = 0.890). No significant differences were observed in freedom from reoperation or adverse events. Both techniques showed excellent mid-term hemodynamic performance and comparable intraoperative and postoperative outcomes. The FM for AVNeo provides a cost-effective and practical alternative to the TM, offering similar clinical outcomes without the need for expensive templates; it has the potential to improve the accessibility of AVNeo, particularly in resource-limited settings. However, further research with larger cohorts and long-term follow-up is needed to fully assess the durability and long-term benefits of the FM.

Mid-Term Results of Pulmonary Valve-Sparing Repair for Tetralogy of Fallot With Pulmonary Stenosis.

The transannular patch remains the most common procedure performed for patients with Tetralogy of Fallot (TOF) with pulmonary stenosis. Pulmonary regurgitation has a negative impact on early and late outcomes. To address this issue pulmonary valve-sparing repair (PVSR) has been developed. Our study goal is to evaluate the mid-term outcomes (five years) of PVSR at our institution. The data were collected retrospectively from June 2014 to June 2022. A total of 390 patients had total repair of TOF. Among these, PVSR was performed in 154 (39.4%) patients. The mid-term outcomes on the status of the pulmonary valve gradient, degree of pulmonary regurgitation, reintervention rate, and mid-term survival after PVSR were investigated. The median age at time of TOF repair was 12 (interquartile range [IQR]: 8-48) months and the median weight was 7.9 (IQR: 3.1-49.5) kg. The mean preoperative right ventricular outflow tract (RVOT) gradient was 77 ± 19.6 mm Hg. All patients had a pulmonary valve Z score of more than -2.5. The post-repair mean RV/LV pressure ratio was 0.49 ± 0.12. There was no surgical mortality. The median follow-up was 3 years (6 months to 8 years). The reintervention rate on the pulmonary valve was 4/154 (2.6%) at five years. The freedom from reintervention and from developing moderate pulmonary valve regurgitation at 5 years was 95% (151/154) and 77% (119/154), respectively. Pulmonary valve-sparing repair gives good mid-term outcomes in a specific group of patients with TOF. Reintervention rates are very low and the peak gradient across the pulmonary valve came down in the majority of patients during mid-term follow up. An RVOT gradient more than 40mm Hg at discharge predicts a high risk of need for reintervention. We continue to monitor our patients for the long term outcome.

The Clinical Trajectory of NYHA Functional Class I Patients With Obstructive Hypertrophic Cardiomyopathy.

An improved understanding of the natural history in NYHA functional class I patients with obstructive hypertrophic cardiomyopathy (oHCM) is needed. Using a multicenter registry (SHaRe [Sarcomeric Human Cardiomyopathy Registry]), this study described the natural history in patients with oHCM who were classified as NYHA functional class I at the initial visit compared with patients classified as NYHA functional class II and reported baseline characteristics associated with incident clinical events. Incident events assessed included a composite of NYHA functional class III to IV symptoms, left ventricular ejection fraction<50%, atrial fibrillation, stroke, ventricular arrhythmias, septal reduction therapy, ventricular assist device or transplantation, or death. Factors associated with incident events were determined using Kaplan-Meier, Cox proportional hazards, and restricted cubic spline models. Of 7,964 patients with HCM in SHaRe, 1,239 patients with oHCM met inclusion criteria; 598 were in NYHA functional class I at the initial visit (age 48 ± 17 years; 31.1% female; peak gradient, 75 ± 40mmHg). At 5-year follow-up, the composite event rate of NYHA functional class I patients was 28% compared with 44% (P< 0.001) in 641 NYHA functional class II patients with oHCM (age 54 ± 16 years; 46.5% female; peak gradient, 83 ± 39mmHg). Left atrial (LA) diameter≥45mm (HR: 1.56 [95%CI: 1.14-2.12]; P = 0.005), female sex (HR: 1.61 [95%CI: 1.16-2.24]; P = 0.003), and older age (HR: 1.21 per 10 years [95%CI: 1.09-1.34]; P< 0.001), but not the magnitude of left ventricular outflow tract obstruction, were associated with a higher risk of the composite outcome in NYHA functional class I patients. Although NYHA functional class I patients with oHCM fared better than NYHA functional class II patients, more than one-fourth experienced adverse events over 5-year follow-up, especially if they were older, female, and/or had LA enlargement. Strategies to reduce the rate of clinical outcomes in NYHA functional class I patients warrant further study.

Severity of native pulmonary annular hypoplasia and late outcomes of tetralogy of Fallot: retrospective cohort study.

Pulmonary annular hypoplasia and valvar dysplasia are key morphological features affecting long-term outcomes of tetralogy of Fallot. This retrospective study aimed to analyse factors affecting contemporary long-term outcomes with a focus on pulmonary annular growth and function over time. 131 consecutive isolated tetralogy of Fallot repairs performed between 2004 and 2014 at University Children's Hospital Zurich were included. Median age and weight at the time of repair were 4.8 (interquartile range [IQR] 3.2-6.3) months and 6.1 (IQR 5.1-7) kg, respectively. Based on the severity of native pulmonary annular hypoplasia, the cohort was divided into group 1 (preoperative pulmonary annular Z score < -4; n = 20), group 2 (Z score -2 to -4; n = 56) and group 3 (Z score > -2; n = 54). A transannular patch was used in 88/131 (67.2%) patients: 80%, 67.9% and 61.1% in groups 1, 2 and 3, respectively. The primary outcome was defined as right ventricular outflow tract (RVOT) reoperation or pulmonary valve replacement. Secondary outcome was composite pulmonary valve dysfunction defined as peak gradient >40 mm Hg or severe pulmonary regurgitation at follow-up. A multiple Cox regression model was used to quantify the association of age at tetralogy of Fallot repair, preoperative pulmonary annular Z score and RVOT approach with primary and secondary outcome. Follow-up was 98.5% complete, with a median follow-up duration of 9.6 (95% confidence interval [CI] 9-10.4) years. All patients were alive at last follow-up resulting in 100% survival. 20/131 patients underwent pulmonary valve replacement (14 surgical and 6 catheter interventional) while 5/131 underwent RVOT reoperations other than valve replacement. The Kaplan-Meier 10-year freedom from primary outcome was 85% (95% CI 78-92%); 69% (46-100%), 91% (82-100%) and 84% (74-95%) for groups 1, 2 and 3, respectively (log rank p = 0.16). Composite dysfunction at follow-up was observed in 29.8% (overall): 45%, 28.6% and 25.9% for groups 1, 2 and 3, respectively (p = 0.12). The multiple Cox regression analysis for primary outcome indicated that the use of a transannular patch results in a Hazard Ratio (HR) of 3.3 (95% CI 0.7-14.7, p = 0.13). Additionally, the presence of composite dysfunction at discharge results in a HR of 2.1 (95% CI 0.8-5.4, p = 0.1). Age (in months) with a HR of 0.8 (95% CI 0.6-1, p = 0.06) and group 2 with a HR of 0.4 (95% CI 0.14-1.2, p = 0.11) showed a trend to being protective for the primary outcome. However, the 95% CI of all estimates included the HR of 1. Transannular patch use and composite dysfunction at discharge, although not statistically significant at 5% level, may be associated with pulmonary valve replacement and RVOT reoperation. Avoiding the use of a transannular patch or using reconstructive techniques to achieve a better composite dysfunction at discharge could reduce the primary outcome. Large multicentre studies are needed to demonstrate more precisely the impact of pulmonary annulus Z scores on outcome.