Septal Ablation to Treat Subaortic Dynamic Obstruction Following Transcatheter Aortic Valve Implantation.

Dynamic obstruction of the left ventricle is an unusual complication that can occur after aortic valve replacement. It is important to be aware of this pathology as it requires different management than normal complications and can rapidly lead to death. We present a case of successful resolution following transcatheter aortic valve implantation.

Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing.

BACKGROUND: Patients with refractory, symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy have few therapeutic options. Right ventricular pacing is associated with modest hemodynamic and symptomatic improvement, and LV pacing pilot data suggest therapeutic potential. We hypothesized that site-specific pacing would reduce LVMCO gradients and improve symptoms. METHODS: Patients with symptomatic-drug-refractory LVMCO were recruited for a randomized, blinded trial of personalized prescription of pacing (PPoP). Multiple LV and apical right ventricular pacing sites were assessed during an invasive hemodynamic study of multisite pacing. Patient-specific pacing-site and atrioventricular delays, defining PPoP, were selected on the basis of LVMCO gradient reduction and acceptable pacing parameters. Patients were randomized to 6 months of active PPoP or backup pacing in a crossover design. The primary outcome examined invasive gradient change with best-site pacing. Secondary outcomes assessed quality of life and exercise following randomization to PPoP. RESULTS: A total of 17 patients were recruited; 16 of whom met primary end points. Baseline New York Heart Association was 3±0.6, despite optimal medical therapy. Hemodynamic effects were assessed during pacing at the right ventricular apex and at a mean of 8 LV sites. The gradients in all 16 patients fell with pacing, with maximum gradient reduction achieved via LV pacing in 14 (88%) patients and right ventricular apex in 2. The mean baseline gradient of 80±29 mm Hg fell to 31±21 mm Hg with best-site pacing, a 60% reduction (P<0.0001). One cardiac vein perforation occurred in 1 case, and 15 subjects entered crossover; 2 withdrawals occurred during crossover. Of the 13 completing crossover, 9 (69%) chose active pacing in PPoP configuration as preferred setting. PPoP was associated with improved 6-minute walking test performance (328.5±99.9 versus 285.8±105.5 m; P=0.018); other outcome measures also indicated benefit with PPoP. CONCLUSIONS: In a randomized placebo-controlled trial, PPoP reduces obstruction and improves exercise performance in severely symptomatic patients with LVMCO. REGISTRATION: URL: https://clinicaltrials.gov/study; Unique Identifier: NCT03450252.

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

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

Exercise Testing to Unmask Latent LVOT Obstruction in a Highly Symptomatic Patient With Hypertrophic Cardiomyopathy.

Rest imaging in hypertrophic cardiomyopathy may underestimate or miss left ventricular outflow tract obstruction, leading to suboptimal management decisions that negatively affect symptomatic patients. The 2024 hypertrophic cardiomyopathy guidelines describe exercise stress testing as an important tool to determine overall exercise tolerance and latent, exercise-provoked left ventricular outflow tract obstruction.

Hybrid palliation to promote growth of left ventricle and left ventricular outflow tract.

OBJECTIVES: In patients with borderline left hearts or a severe left ventricular outflow tract obstruction, hybrid palliation can be used to stabilize the patient and postpone biventricular repair (BVR). In this study, we analysed growth of left-sided structures and outcomes of these patients. METHODS: We conducted a retrospective cohort study including patients who received hybrid palliation between January 2010 and September 2023. Echo measurements were collected at hybrid palliation, BVR and last follow-up. Growth of left ventricular structures were analysed. RESULTS: In 38 patients, hybrid palliation was used to promote growth of left ventricular structures. In total, 15 patients received a Ross-Konno/Yasui procedure, while 23 patients received conventional BVR. In patients with a conventional BVR, a significant increase was found in left ventricular volume indexed by body surface area, Z-score of aortic valve and left ventricular outflow tract between hybrid palliation and BVR. Mitral valve Z-score did not increase significantly. After BVR until follow-up, only increase of the aortic valve Z-scores and left ventricular volume indexed by body surface area was found significant. Of all included patients (n = 38), additional surgical procedures were necessary in 8 patients during the interstage period and 15 patients after BVR. Additional catheter interventions were needed in 14 patients in the interstage period and 15 after BVR. Six patients died, with no mortality in the conventional BVR group. CONCLUSIONS: Hybrid palliation as part of a staged BVR is a safe and effective initial step and promotes the growth of left ventricular structures in patients with small left-sided heart structures. Close follow-up is mandatory because extra catheter or surgical interventions are frequently needed.

Transcatheter Pulmonary Valve in Congenital Heart Disease.

Over the last 2 decades, experience with transcatheter pulmonary valve replacement (TPVR) has grown significantly and has become an effective and reliable way of treating pulmonary valve regurgitation, right ventricular outflow (RVOT) obstruction, and dysfunctional bioprosthetic valves and conduits. With the introduction of self-expanding valves and prestents, dilated native RVOT can be addressed with the transcatheter approach. In this article, the authors review the current practices, technical challenges, and outcomes of TPVR.

Outcomes after septal myectomy in a cohort of patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) with left ventricular outflow tract obstruction that doesn't improve with pharmacological management often requires septal myectomy. However, there are few centers with experience in the practice of this procedure in our country. We describe the clinical and echocardiographic characteristics and postoperative outcomes of patients with HCM indicated for septal myectomy at a reference center in Colombia. MATERIALS AND METHODS: Retrospective cohort study. Patients undergoing septal myectomy between 2010 and 2023 were included. Data were collected before and two years after surgery. RESULTS: 18 patients were included. The mean age was 50 years. The predominant functional class was NYHA II/III (94 %). Asymmetric septal variant (83.3 %) was the most frequent as well as obstructive phenotype (88.8 %). After myectomy, 70.5 % improved to NYHA I and 62.4 % had no significant gradient (<30 mmHg), and the most of patient improved SAM. One patient died post-procedure, anymore complications were presented. DISCUSSION/CONCLUSIONS: Septal myectomy is a safe procedure, with clinical and echocardiographic improvement, with low complication rates.

Half-turned truncal switch operation for dextro-transposition of the great arteries with ventricular septal defect and left ventricular outflow tract obstruction and an abnormal coronary pattern.

We describe a surgical technique for a half-turned truncal switch operation in a 5-year-old child with dextro-transposition of the great arteries (D-TGA), a ventricular septal defect, a left ventricular outflow tract obstruction and a complex coronary pattern. The benefit of the half-turned truncal switch is the creation of haemodynamically superior biventricular outflow tracts and the maximal use of an autologous pulmonary valve in the right ventricular outflow tract, thereby avoiding the right ventricular-pulmonary artery conduit.

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

OBJECTIVES: Left ventricular outflow tract obstruction (LVOTO) is a major cause of morbidity and mortality in infants with interrupted aortic arch (IAA). Left Ventricular Outflow Tract (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 (AAb)] with LVOT diameter and reintervention. METHODS: All surgical patients with IAA (2001-2022) were reviewed at a single institution. We compared IAA-A versus IAA-B; IAA with aortic AAb versus none; IAA-B with aberrant subclavian (AAbS) artery versus others. Primary outcomes included LVOT diameter (mm), LVOTO at discharge (≥50 mmHg), and LVOT reintervention. RESULTS: 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) versus none: 5.15 (4.30-5.68), P = 0.006], and combined IAA-B + AAbS [IAA-B + AAbS: 4.00 (3.70-5.02) versus 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). CONCLUSIONS: 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.

Target population for a selective cardiac myosin inhibitor in hypertrophic obstructive cardiomyopathy: Real-life estimation from the French register of hypertrophic cardiomyopathy (REMY).

BACKGROUND: The efficacy of current pharmacological therapies in hypertrophic cardiomyopathy is limited. A cardiac myosin inhibitor, mavacamten, has recently been approved as a first-in-class treatment for symptomatic hypertrophic obstructive cardiomyopathy. AIMS: To assess the profile and burden of cardiac myosin inhibitor candidates in the hypertrophic cardiomyopathy prospective Register of hypertrophic cardiomyopathy (REMY) held by the French Society of Cardiology. METHODS: Data were collected at baseline and during follow-up from patients with hypertrophic cardiomyopathy enrolled in REMY by the three largest participating centres. RESULTS: Among 1059 adults with hypertrophic cardiomyopathy, 461 (43.5%) had obstruction; 325 (30.7%) of these were also symptomatic, forming the "cardiac myosin inhibitor candidates" group. Baseline features of this group were: age 58±15years; male sex (n=196; 60.3%); diagnosis-to-inclusion delay 5 (1-12)years; maximum wall thickness 20±6mm; left ventricular ejection fraction 69±6%; family history of hypertrophic cardiomyopathy or sudden cardiac death (n=133; 40.9%); presence of a pathogenic sarcomere gene mutation (n=101; 31.1%); beta-blocker or verapamil treatment (n=304; 93.8%), combined with disopyramide (n=28; 8.7%); and eligibility for septal reduction therapy (n=96; 29%). At the end of a median follow-up of 66 (34-106) months, 319 (98.2%) were treated for obstruction (n=43 [13.2%] received disopyramide), 46 (14.2%) underwent septal reduction therapy and the all-cause mortality rate was 1.9/100 person-years (95% confidence interval 1.4-2.6) (46 deaths). Moreover, 41 (8.9%) patients from the initial hypertrophic obstructive cardiomyopathy group became eligible for a cardiac myosin inhibitor. CONCLUSIONS: In this cohort of patients with hypertrophic cardiomyopathy selected from the REMY registry, one third were eligible for a cardiac myosin inhibitor.

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.

Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: One of the major determinants of exercise intolerance and limiting symptoms among patients with obstructive hypertrophic cardiomyopathy (HCM) is an elevated intracardiac pressure resulting from left ventricular outflow tract obstruction. Aficamten is an oral selective cardiac myosin inhibitor that reduces left ventricular outflow tract gradients by mitigating cardiac hypercontractility. METHODS: In this phase 3, double-blind trial, we randomly assigned adults with symptomatic obstructive HCM to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for 24 weeks, with dose adjustment based on echocardiography results. The primary end point was the change from baseline to week 24 in the peak oxygen uptake as assessed by cardiopulmonary exercise testing. The 10 prespecified secondary end points (tested hierarchically) were change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), improvement in the New York Heart Association (NYHA) functional class, change in the pressure gradient after the Valsalva maneuver, occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver, and duration of eligibility for septal reduction therapy (all assessed at week 24); change in the KCCQ-CSS, improvement in the NYHA functional class, change in the pressure gradient after the Valsalva maneuver, and occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver (all assessed at week 12); and change in the total workload as assessed by cardiopulmonary exercise testing at week 24. RESULTS: A total of 282 patients underwent randomization: 142 to the aficamten group and 140 to the placebo group. The mean age was 59.1 years, 59.2% were men, the baseline mean resting left ventricular outflow tract gradient was 55.1 mm Hg, and the baseline mean left ventricular ejection fraction was 74.8%. At 24 weeks, the mean change in the peak oxygen uptake was 1.8 ml per kilogram per minute (95% confidence interval [CI], 1.2 to 2.3) in the aficamten group and 0.0 ml per kilogram per minute (95% CI, -0.5 to 0.5) in the placebo group (least-squares mean between-group difference, 1.7 ml per kilogram per minute; 95% CI, 1.0 to 2.4; P<0.001). The results for all 10 secondary end points were significantly improved with aficamten as compared with placebo. The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS: Among patients with symptomatic obstructive HCM, treatment with aficamten resulted in a significantly greater improvement in peak oxygen uptake than placebo. (Funded by Cytokinetics; SEQUOIA-HCM ClinicalTrials.gov number, NCT05186818.).

Left ventricular outflow tract obstruction/hypertrophic cardiomyopathy/takotsubo syndrome: A new hypothesis of takotsubo syndrome pathophysiology.

The pathophysiology of TTS is still elusive. This viewpoint proposes that TTS is an acute coronary syndrome, engendered by an ASNS/catecholamine-induced LVOTO, which results in an enhanced wall stress and afterload-based supply/demand mismatch, culminating in a segmental myocardial ischemic injury state, in susceptible individuals. Such individuals are felt to be particularly women with chronic hypertension, known or latent HCM, or non-HCM segmental myocardial hypertrophy, and certain structural abnormalities involving the LV and the MV apparatus. Recommendations are provided to explore further this hypothesis, while maintaining our focus on all other advanced TTS pathophysiology hypotheses for all patients, or those who do not experience LVOTO, men, the young, and patients with reverse, mid-ventricular, or right ventricular TTS, in whom more prolonged hyperadrenergic stimulation and/or larger amounts of blood-ridden catecholamines, segmental particularities of cardiac innervation and/or density of α-, and ß-adrenergic receptors, pheochromocytoma, neurological chronic or acute comorbidities/catastrophies, coronary epicardial/microvascular vasospasm, and CMD.

New echocardiographic screening tool for left ventricular tract obstruction risk assessment in TMVR.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) is an alternative to conventional surgery to treat severe mitral disease but its use is limited by the risk of left ventricular outflow tract obstruction (LVOTO). Screening depends on ECG-gated computed tomography (CT) that is not widely available and requires contrast. We developed and validated a transthoracic echocardiographic (TTE) method to assess the risk of LVOTO after TMVR with the Tendyne System. METHODS: We measured the LVOT longitudinal area on preoperative TTE dataset of patients screened for TMVR. The LVOT was measured as the box-area included by the aortic valve annulus, the anterior mitral leaflet (AML), the c-septum distance line, and the respective length of the AML on the interventricular septum. We analyzed the correlation between the TTE LVOT-box and the CT-measured neoLVOT area. Prediction performance for eligible patients was tested with ROC curves. RESULTS: Thirty-nine patients were screened, out of 14 patients (36%) not eligible for TMVR, 8 had risk of LVOTO. We found a linear correlation between the TTE LVOT-box and the CT-measured Neo-LVOT (r = 0.6, p = 0.002). ROC curve showed that the method is specific and sensitive and the cut-off value of the measure LVOT-box is 350 mm2. CONCLUSIONS: The proposed method is reliable to evaluate the risk of LVOTO after TMR with the Tendyne System. It is quick and easy and can be used as a first-line assessment in the outpatient clinic. Patients with LVOT-box <350 mm2 should not be further screened with ECG-gated cardiac CT.

Repair of complex transposition of great arteries: What is the best technique to avoid outflow tract obstructions?

OBJECTIVES: This study aimed to evaluate the short-/mid-term outcome of patients with complex dextro (d)-/levo (l)-transposition of the great arteries (TGA), ventricular septal defect and left ventricular outflow tract obstructions. METHODS: A single-centre, retrospective review of all complex dextro-TGA (n = 85) and levo-TGA (n = 22) patients undergoing different surgeries [Arterial switch operation + left ventricular outflow tract obstruction-resection (ASO-R), half-turned truncal switch/Mair (HTTS), Nikaidoh and Rastelli] between May 1990 and September 2022 was performed. Groups were analysed using Kruskal-Wallis test with post hoc pairwise comparison and Kaplan-Meier time-to-event models. RESULTS: A total of 107 patients [ASO-R (n = 20), HTTS (n = 23), Nikaidoh (n = 21), Rastelli (n = 43)] were included, with a median age of 1.0 year (0.5-2.5) and surgical repair median follow-up was 3.8 years (0.3-10.5). Groups did not differ in respect to early postoperative complications/early mortality. Five-year overall survival curves were comparable: ASO-R 78.9% (53.2-91.5), HTTS 75.3% (46.8-89.9), Nikaidoh 85% (60.4-94.9) and Rastelli 83.9% (67.5-92.5), P = 0.9. Highest rates of right ventricular outflow tract (RVOT) reinterventions [33.3% and 32.6% (P = 0.04)] and reoperations [28.6% and 32.6% (P = 0.02)] occurred after Nikaidoh and Rastelli procedures. However, overall freedom from RVOT reinterventions and RVOT reoperations at 5 years did not differ statistically significantly between the groups (ASO-R, HTTS, Nikaidoh and Rastelli): 94.4% (66.6-99.2), 69.1% (25.4-90.5), 67.8% (34-86.9), 64.4% (44.6-78.7), P = 0.2, and 90.0% (65.6-97.4), 91% (50.8-98.7), 65.3% (32.0-85.3) and 67.0% (47.4-80.6), P = 0.3. CONCLUSIONS: Surgical repair of complex dextro-/levo-TGA can be performed with satisfying early/mid-term survival. RVOT reinterventions/reoperations were frequent, with highest rates after Nikaidoh and Rastelli procedures. Left ventricular outflow tract obstruction reoperations were rare with zero events after Nikaidoh and HTTS procedures.

Finite element modeling with patient-specific geometry to assess clinical risks of percutaneous pulmonary valve implantation.

BACKGROUND: Percutaneous pulmonary valve implantation (PPVI) is a non-surgical treatment for right ventricular outflow tract (RVOT) dysfunction. During PPVI, a stented valve, delivered via catheter, replaces the dysfunctional pulmonary valve. Stent oversizing allows valve anchoring within the RVOT, but overexpansion can intrude on the surrounding structures. Potentially dangerous outcomes include aortic valve insufficiency (AVI) from aortic root (AR) distortion and myocardial ischemia from coronary artery (CA) compression. Currently, risks are evaluated via balloon angioplasty/sizing before stent deployment. Patient-specific finite element (FE) analysis frameworks can improve pre-procedural risk assessment, but current methods require hundreds of hours of high-performance computation. METHODS: We created a simplified method to simulate the procedure using patient-specific FE models for accurate, efficient pre-procedural PPVI (using balloon expandable valves) risk assessment. The methodology was tested by retrospectively evaluating the clinical outcome of 12 PPVI candidates. RESULTS: Of 12 patients (median age 14.5 years) with dysfunctional RVOT, 7 had native RVOT and 5 had RV-PA conduits. Seven patients had undergone successful RVOT stent/valve placement, three had significant AVI on balloon testing, one had left CA compression, and one had both AVI and left CA compression. A model-calculated change of more than 20% in lumen diameter of the AR or coronary arteries correctly predicted aortic valve sufficiency and/or CA compression in all the patients. CONCLUSION: Agreement between FE results and clinical outcomes is excellent. Additionally, these models run in 2-6 min on a desktop computer, demonstrating potential use of FE analysis for pre-procedural risk assessment of PPVI in a clinically relevant timeframe.