Treatment Of Hypertrophic Obstructive Cardiomyopathy Research Articles

Myosin-Catalyzed ATP Hydrolysis in the Presence of Disease-Causing Mutations: Mavacamten as a Way to Repair Mechanism.

Hypertrophic cardiomyopathy is one of the most common forms of genetic cardiomyopathy. Mavacamten is a first-in-class myosin modulator that was identified via activity screening on the wild type, and it is FDA-approved for the treatment of obstructive hypertrophic cardiomyopathy (HCM). The drug selectively binds to the cardiac β-myosin, inhibiting myosin function to decrease cardiac contractility. Though the drug is thought to affect multiple steps of the myosin cross-bridge cycle, its detailed mechanism of action is still under investigation. Individual steps in the overall cross-bridge cycle must be queried to elucidate the full mechanism of action. In this study, we utilize the rare-event method of transition path sampling to generate reactive trajectories to gain insights into the action of the drug on the dynamics and rate of the ATP hydrolysis step for human cardiac β-myosin. We study three known HCM causative myosin mutations: R453C, P710R, and R712L to observe the effect of the drug on the alterations caused by these mutations in the chemical step. Since the crystal structure of the drug-bound myosin was not available at the time of this work, we created a model of the drug-bound system utilizing a molecular docking approach. We find a significant effect of the drug in one case, where the actual mechanism of the reaction is altered from the wild type by mutation. The drug restores both the rate of hydrolysis to the wildtype level and the mechanism of the reaction. This is a way to check the effect of the drug on untested mutations.

Transapical intramyocardial septal microwave ablation in treatment of hypertrophic obstructive cardiomyopathy: 12-month outcomes of a swine model

BackgroundTo date, the extended Morrow procedure is considered the gold standard treatment for patients with obstructive hypertrophic cardiomyopathy who experience severe symptoms and are unresponsive to medication treatment. We therefore aimed to perform transapical intramyocardial septal microwave ablation to reduce the thickness of the interventricular septum myocardium in a minimally invasive method.MethodsFourteen swine were divided to form either a microwave ablation group (n = 7) or a sham group (n = 7). In the microwave ablation group, a transapical microwave antenna was inserted into the septum to ablate each myocardial segment at 40 W for 1 min, while in the sham group, the same operation was performed but without power output. We used echocardiography, electrocardiogram, during the operation. And added computerized tomography, cardiac nuclear magnetic resonance during follow-up.ResultsSegment hypokinesis was observed in all swine immediately following ablation. Compared with the sham group, the thickness of ablated segments in the ablation group decreased significantly 1 month post-operation (ablation group, 5.53 ± 1.00 mm vs. 8.03 ± 1.15 mm, respectively, P < 0.01; sham group, 8.40 ± 0.94 mm vs. 8.21 ± 1.09 mm, respectively, P = 0.081), and the outcome was still observed 1 year post-operation (ablation group, 3.36 ± 0.85 mm vs. 8.03 ± 1.15 mm, respectively, P < 0.01). No perforation of the septum was observed during the procedure or follow-up, and no heart failure or sudden cardiac death occurred during postoperative feeding.ConclusionsTransapical intramyocardial septal microwave ablation can effectively and safely produce a large region of necrosis. This technique can potentially mimic surgical myectomy while avoiding cardiopulmonary bypass and median sternotomy in high-risk hypertrophic obstructive cardiomyopathy patients.

Innovation in surgical treatment of hypertrophic obstructive cardiomyopathy in children.

Hypertrophic cardiomyopathy is the second most common cardiomyopathy affecting children and adolescents and is the main cause of sudden death of young athletes. The natural prognosis of children with severe hypertrophic obstructive cardiomyopathy is not optimistic, and it is not uncommon for children with hypertrophic obstructive cardiomyopathy who do not respond to medication. Surgical treatment is often the only solution. Conventional surgical methods in the past include classic or modified extended Morrow operation, classic or modified Konno operation, and Ross-Konno operation. In recent years, with the development of minimally invasive surgery, various minimally invasive surgical methods have emerged endlessly. Because the incision of minimally invasive cardiac surgery is significantly smaller than that of traditional surgery, it causes less trauma, recovers quickly after surgery, and has the advantage of no difference in surgical effect compared with traditional median sternotomy. Tally endoscopic transmitral myectomy, RTM, minimally right thoracotomy, and other surgical methods have achieved encouraging results in adults and some older children with hypertrophic obstructive cardiomyopathy. The appearance of transapical beating-heart septectomy has brought the treatment of hypertrophic obstructive cardiomyopathy from the era of cardiopulmonary bypass and cardiac arrest to a new era of minimally invasive beating-heart surgery. In the past, there were few articles about the treatment of children with hypertrophic obstructive cardiomyopathy. This article reviewed the new progress and prognosis of surgical treatment of children with hypertrophic obstructive cardiomyopathy at home and abroad.

Short time effects of two radiofrequency ablation methods on hypertrophic obstructive cardiomyopathy.

Radiofrequency ablation has been applied for the treatment of hypertrophic obstructive cardiomyopathy (HOCM). The two known procedures are percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) and endocardial radiofrequency septal ablation (ERSA). This study presents a retrospective analysis of the PIMSRA and ERSA procedures in patients with drug-refractory HOCM. A total of 28 patients participated in the study, with 12 receiving PIMSRA and 16 receiving ERSA. The objective of our study was to compare the short-term effects of these two radiofrequency ablation procedures. At the 30-day follow-up, the PIMSRA group demonstrated a greater reduction in left ventricular outflow tract peak gradient at rest compared to the ERSA group (22.25 [16.72] mmHg versus 47.75 [21.94] mmHg) (p < .01). The values for the PIMSRA group decreased from 99.33 (32.00) mmHg to 22.25 (16.72) mmHg (p < .01), while the ERSA group decreased from 97.75 (30.24) mmHg to 47.75 (21.94) mmHg (p < .01). Only the PIMSRA group exhibited a decrease in mitral regurgitation (MR). The area of MR decreased from 10.13 (4.12) mm2 to 3.65 (2.80) mm2 in the PIMSRA group (p < .01). Additionally, the PIMSRA group experienced reductions in left atrial diameter (LAD) and left ventricular ejection fraction (LVEF)%. The values for LAD changed from 43.58 (7.53) mm to 37.08 (6.92) mm (p = .03), and the values for LVEF% decreased from 65.75 (6.12) pg/mL to 60.83 (4.06) pg/mL (p = .03). In terms of the two types of radiofrequency ablation methods used in HOCM, it has been observed that PIMSRA demonstrates a more favorable early treatment effect compared to ERSA.

New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2023.

Although cardiovascular diseases are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic cardiovascular disease and heart failure. The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolemia, type 2 diabetes, obesity and heart failure, the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of cardiovascular diseases.

Modified Konno Procedure for left ventricular outflow tract obstruction: report of two cases

Left ventricular outflow tract obstruction with a systolic anterior motion of the mitral valve is a challenging pathology. An intervention, either surgically or with a percutaneous technique is taken into consideration when the pressure gradient reaches critical levels. Subaortic myectomy is still the gold standard treatment modality in these particular patients. Modified Konno procedure may be added to the procedure when a significant gradient persists following subaortic resection, because of its association with increased outflow tract obstruction relief. We herein present our experiences with two cases that underwent modified Konno procedures for the treatment of hypertrophic obstructive cardiomyopathy.

Resource utilization and costs related to the management of obstructive hypertrophic cardiomyopathy under the Brazilian supplementary healthcare system´s perspective: results from a modified Delphi panel

Objective: To generate data on the costs associated with the diagnosis and treatment of obstructive hypertrophic cardiomyopathy (HCM) from the perspective of the private health system in Brazil. Methods:A modified Delphi panel including seven different specialists (three clinical cardiologists with experience in obstructive HCM, two hemodynamicists with experience in septal ablation and two cardiac surgeons with expertise in myectomy), from two Brazilian states (São Paulo and Pernambuco), was conducted between August and November 2022. Two rounds of questions about the use of healthcare resources according to the functional class (NYHA I-IV) and a panel in a virtual platform were conducted to obtain the final consensus. Micro-costing defined costs and unit values were determined based on official price lists. Results: The total diagnosis cost per patient was estimated at BRL 11,486.81. The obstructive HCM management costs analysis showed average annual costs per patient of BRL 17,026.74, BRL 19,401.46, BRL 73,310.07, and BRL 94,885.75 for the functional classes NYHA I, NYHA II, NYHA III, and NYHA IV, respectively. The average costs per patient related to procedures in a year were BRL 12,698.53, BRL 13,462.30, BRL 58,841.67, and BRL 75,595.90 for the functional classes NYHA I, II, III, and IV, respectively. Conclusions: The annual costs of HCM management increased according to the functional class, highlighting the need for safe and effective strategies to improve patient’s NYHA functional class while promoting a decrease in the need for invasive therapies.

Temporal trends, patient characteristics and hospital volume outcomes after alcohol septal ablation and septal myectomy for treatment of obstructive hypertrophic cardiomyopathy

Abstract Background Hypertrophic obstructive cardiomyopathy (HOCM) represents a clinically and morphologically diverse hereditary cardiac disease that is frequently associated with poor prognosis. Nationwide data on septal reduction therapy (SRT), alcohol septal ablation (ASA) and septal myectomy (SM), remains scarce. The aim of this study was to investigate (i) temporal trends, (ii) patient characteristics, (iii) in-hospital outcomes, and associations between institutional procedural volumes and outcomes after ASA and SM in a large-scale nationwide cohort. Methods Using data from the German Federal Bureau of Statistics, this study analyzed all patients with HOCM who were hospitalized for ASA or SM in a nationwide inpatient database in Germany between January 1, 2006, through December 31, 2019. Rates of adverse in-hospital events (in-hospital mortality, need for permanent pacemaker) were examined. Multivariate logistic regression analysis was performed to compare overall outcomes after each procedure based on tertiles of hospital volumes of ASA and SM. Results A total of 8,514 patients underwent SRT, of whom 5,293 (62.2%) underwent ASA and 3,221 (37.8%) SM. Annual numbers for SM and ASA steadily increased over time: ASA procedures increased from 329 in 2006 to 451 in 2019 and SM procedures increased from 191 in 2006 to 222 in 2019, respectively. Patients with SM were older (mean 67.4 vs. 60.2 years), less likely female (56.4% vs. 49.9%), and had a higher burden of comorbidities (e.g., diabetes, atrial fibrillation, heart failure, chronic kidney disease) compared to patients with ASA. Over an observational period of 14 years, the majority of both ASA and SM procedures were performed at hospitals in the lowest volume category (≤20 procedures). The overall in-hospital mortality was higher in patients with SM (6.8%) compared to patients with ASA (0.8%), whereas the need for pacemaker implantation was more often observed in patients with ASA (19.3% vs. 13.1%; p&amp;lt;0.001). The lowest tertile of SM volume among hospitals was independently associated with an increased risk of in-hospital mortality (adjusted odds ratio (lowest vs. highest tertile), 2.64; 95% confidence interval, 1.49-4.66), whereas being in the lowest vs. the highest tertile of ASA by volume was not independently associated with risk of in-hospital mortality and adverse events. Conclusion In this contemporary cohort with more than 8,500 cases of SRT between 2006 and 2019, the majority of SRT was performed at centers with a low volume of SM and ASA procedures. Low SM volume was independently associated with increased in-hospital mortality, whereas low ASA volume was not associated with adverse outcomes. Our findings may help to further understand how institutional SRT procedural volumes affects outcomes and might encourage referral of patients with HOCM to centers of excellence for SRT.

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

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

Clinical Outcomes After the Surgical Treatment of Hypertrophic Obstructive Cardiomyopathy With Left Ventricular Apical Aneurysm.

Left ventricular apical aneurysm (LVAA) is a rare complication of hypertrophic obstructive cardiomyopathy (HOCM). This study aimed to illustrate the clinical characteristics and surgical outcomes of these patients. Patients with HOCM and LVAA who underwent modified extended Morrow myectomy and surgical left ventricular reconstruction (SLVR) between October 2012 and March 2021 were retrospectively recruited. Patients with coronary artery disease were excluded. Clinical characteristics were summarised. Time-to-event outcomes were calculated using the Kaplan-Meier method and compared by a log-rank test. Fifteen eligible patients were identified; the mean age was 39.9±17.2 years and 40.0% of them were female. All patients had dyspnoea, 46.7% presented with syncope and/or chest pain, and 13.3% had a family history of hypertrophic cardiomyopathy. The mean LVAA size was 36.9±12.3 mm in length and 28.5±11.3 mm in width. Echocardiography showed LV outflow tract obstruction in seven (46.7%) patients, mid-cavity LV obstruction in 12 (80.0%), while systolic anterior motion (SAM) was seen in seven (46.7%). The symptoms were resolved in all patients postoperatively. During a median follow-up of 22.0 months, one (6.7%) patient had sudden cardiac death, one (6.7%) had a haemorrhagic stroke, and the LVAA recurrence was 40.0%. Subgroup analysis showed that signs of SAM and larger LVAA (≥30 mm) were associated with an increased tendency for a longer hospital stay. Patients with HOCM and LVAA present with high-risk profiles. Modified extended Morrow myectomy combined with SLVR is useful in relieving the symptoms and improving the prognosis, although there might be recurrent LVAA.

Robotic endoscopic transmitral septal myectomy and concomitant mitral valve repair for hypertrophic obstructive cardiomyopathy

Hypertrophic obstructive cardiomyopathy is a disease of the heart in which the patient develops left ventricular outflow tract obstruction due to the interaction of the mitral valve and the intraventricular septum. Although septal myectomy remains the gold standard treatment for hypertrophic obstructive cardiomyopathy, several other approaches have been described in the literature, such as a transaortic, transapical or transmitral approach via a sternotomy. All of these approaches have been shown to produce reliable reduction in left ventricular outflow tract gradients. Robotic-assisted cardiac surgery has recently become a safe and effective alternative approach to a sternotomy for several intracardiac procedures, especially mitral valve repair and, in experienced centres, septal myectomy.

Diagnosis and Treatment of Obstructive Hypertrophic Cardiomyopathy

Left ventricular outflow obstruction (LVOTO) and diastolic dysfunction are the main pathophysiological characteristics of hypertrophic cardiomyopathy (HCM)LVOTO, may be identified in more than half of HCM patients and represents an important determinant of symptoms and a predictor of worse prognosis. This review aims to clarify the LVOTO mechanism in, diagnosis of, and therapeutic strategies for patients with obstructive HCM.

New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2022.

Cardiovascular diseases (CVD) remain the leading cause of death worldwide and pharmacotherapy of most of them is suboptimal. Thus, there is a clear unmet clinical need to develop new pharmacological strategies with greater efficacy and better safety profiles. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2022 including the approval of first-in-class drugs that open new avenues for the treatment of obstructive hypertrophic cardiomyopathy (mavacamten), type 2 diabetes mellitus (tirzepatide), and heart failure (HF) independent of left ventricular ejection fraction (sodium-glucose cotransporter 2 inhibitors). We also dealt with fixed dose combination therapies repurposing different formulations of "old" drugs with well-known efficacy and safety for the treatment of patients with acute decompensated HF (acetazolamide plus loop diuretics), atherosclerotic cardiovascular disease (moderate-dose statin plus ezetimibe), Marfan syndrome (angiotensin receptor blockers plus β-blockers), and secondary cardiovascular prevention (i.e. low-dose aspirin, ramipril and atorvastatin), thereby filling existing gaps in knowledge, and opening new avenues for the treatment of CVD. Clinical trials confirming the role of dapagliflozin in patients with HF and mildly reduced or preserved ejection fraction, long-term evolocumab to reduce the risk of cardiovascular events, vitamin K antagonists for stroke prevention in patients with rheumatic heart disease-associated atrial fibrillation, antibiotic prophylaxis in patients at high risk for infective endocarditis before invasive dental procedures, and vutrisiran for the treatment of hereditary transthyretin-related amyloidosis with polyneuropathy were also reviewed. Finally, we briefly discuss recent clinical trials suggesting that FXIa inhibitors may have the potential to uncouple thrombosis from hemostasis and attenuate/prevent thromboembolic events with minimal disruption of hemostasis.

Transaortic Shallow Septal Myectomy with Mitral Valve Repair in Treatment of Hypertrophic Obstructive Cardiomyopathy with Severe Interstitial Fibrosis: Compared to Extended Morrow Procedure

Background: There is lack of outcomes of transaortic shallow septal myectomy with mitral valve(MV) repair comparing with extended Morrow procedure in treatment of hypertrophic obstructive cardiomyopathy (HOCM) with severe interstitial fibrosis.

Трансмитральная миоэктомия и протезирование митрального клапана из минидоступа при обструктивной гипертрофической кардиомиопатии

Primary hypertrophic cardiomyopathy is an isolated genetic heart disease characterized by thickening of the myocardium in the absence of an apparent hemodynamic cause. There are two patterns of the obstruction: static, with a muscle band narrowing the outflow tract of the left ventricle, and dynamic, which implies elongation of the anterior mitral valve leaflet. The key to correct treatment of the condition is understanding of the mechanism behind the obstruction. Myectomy is the gold standard of invasive treatment of obstructive hypertrophic cardiomyopathy; it aims to remove the static component of the obstruction. Another common adidition is the mitral valve surgery, aimed at elimination of the obstruction's dynamic component. This article presents a successful mini-invasive transmitral myectomy and mitral valve replacement in a case of obstructive hypertrophic cardiomyopathy with a damaged mitral valve.

Analysis of iPSC-CM Contractility following Mavacamten treatment using MYOCYTER

Hypoplastic Left Heart Syndrome (HLHS) is a rare and complex congenital heart defect characterized by hypoplasia of the left ventricle, proximal aorta, as well as stenosis or atresia of the mitral and/or aortic valves. There is strong evidence for a genetic contribution to HLHS, including our lab’s previous discovery of 19 rare, predicted-damaging MYH6 variants that were significantly enriched in HLHS patients. The MYH6 gene encodes for the α-myosin heavy chain (α-MHC), a key contractile protein in cardiac sarcomere. Variants affecting cardiac MHC isoforms are thought to impact the strength, speed, and patterns of myocardial contractions. Reduced myocardial contractility due to MYH6 variants may impair cardiac blood flow and cause underdevelopment of the left heart. Mavacamten is a novel pharmacological agent that has shown promise in phase III clinical trials for treatment of hypertrophic obstructive cardiomyopathy. Mavacamten selectively acts on cardiac MHC to reduce cardiac muscle contractility. Given this specificity, Mavacamten may offer a promising way to treat diastolic dysfunction in (i.e. hypercontractility) in patients with HLHS, including those with MYH6 variants. We tested the in vitro efficacy of Mavacamten in patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) exhibiting hypercontractility and investigated video-based analysis as a high-throughput method for evaluating iPSC-CM contractility, which would allow for repeated assessment of cells at different timepoints following drug treatment. Many packages for video-based contractility assessment lack precision and can be subject to disturbances such as cellular fragments, movement of cell media, and small differences in media color. They are also complex and require advanced programming knowledge. MYOCYTER is an open-source macro for ImageJ that improves upon previous plugins available by allowing for users to optimize parameters for contractility evaluation, while minimizing background noise. The aim of our study was to determine if MYOCYTER can be reliably used to detect small changes in iPSC-CM contractility following treatment with Mavacamten, and if the workflow is user-friendly enough such that reproducible analysis can be done by a high school science team.Our analysis revealed that MYOCYTER can detect baseline hypercontractility of iPSC-CMs carrying MYH6 variants compared to wild-type iPSC-CMs (p = 0.033). These differences in amplitude were eliminated following five, ten, and fifteen minutes of treatment with 500nM Mavacamten in a single experiment. Our results suggest that this method can be used to further evaluate the effect of myosin modulators, such as Mavacamten, in patient-specific iPSC-CMs. Children's Research Institute This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Surgical treatment for obstructive hypertrophic cardiomyopathy: a five-year single-center experience of 421 cases

Objectives: To examine the short-term and mid-term effects of surgical treatment of obstructive hypertrophic cardiomyopathy (HCM) in one center. Methods: The perioperative data and short-term follow-up outcomes of 421 patients with obstructive HCM who received surgical treatment at Department of Cardiac Surgery, Zhongshan Hospital, Fudan University from January 2017 to December 2021 were analyzed retrospectively. There were 207 males and 214 females, aged (56.5±11.7) years (range: 19 to 78 years). Preoperative New York Heart Association (NYHA) classification included 45 cases of class Ⅱ, 328 cases in class Ⅲ, and 48 cases in class Ⅳ. Fifty-eight patients were diagnosed with latent obstructive HCM and 257 patients had moderate or more mitral regurgitation with 56 patients suffering from intrinsic mitral valve diseases. All procedures were completed by a multidisciplinary team, including professional echocardiologists involving in preoperative planning for proper mitral valve management strategies and intraoperative monitoring. A total of 338 patients underwent septal myectomy alone, and 59 patients underwent mitral valve surgery along with myectomy. A single transaortic approach was used in 355 patients, and a right atrial-atrial septal/atrial sulcus approach was used in 51 other patients. Long-handled minimally invasive surgical instruments were used for the procedures. Student t test, Wilcoxon rank sum test, χ2 test or Fisher exact test were used to compare the data before and after surgery. Results: The aortic cross-clamping time of septal myectomy alone was (34.3±8.5) minutes (range: 21 to 94 minutes). Eighteen patients had intraoperative adverse events and underwent immediate reoperation, including residual obstruction (10 patients), left ventricular free wall rupture (4 patients), ventricular septal perforation (3 patients), and aortic valve perforation (1 patient). Four patients died during hospitalization, and 11 patients developed complete atrioventricular block requiring permanent pacemaker implantation. After discharge, 384 (92.1%) patients received a follow-up visit with a median duration of 9 months. All follow-up patients survived with significantly improved NYHA classifications: 216 patients in class Ⅰ and 168 patients in class Ⅱ (χ2=662.73, P<0.01 as compared to baseline). At 6 months after surgery, follow-up echocardiography showed that the thickness of the ventricular septum ((13.6±2.5) mm vs. (18.2±3.0) mm, t=23.51, P<0.01) and the peak left ventricular outflow tract gradient ((12.0±6.3) mmHg vs. (93.4±19.8) mmHg, 1 mmHg=0.133 kPa, t=78.29, P<0.01) were both significantly lower than baseline values. Conclusion: The construction of the surgical team (including echocardiography experts), proper mitral valve management strategies, identification and management of sub-mitral-valve abnormalities, and application of long-handled minimally invasive surgical instruments are important for the successful implementation of septal myectomy with satisfactory short-and medium-term outcomes.

Man With Progressive Exertional Dyspnea.

A 65-year-old man with a history of hypertension and left ventricular hypertrophy presented with progressive exertional dyspnea for one month. Physical examination showed a blood pressure of 155/82 mmHg, a pulse of 102 beats/min, mild icteric sclera, and a high-pitched midsystolic murmur at the left lower sternal border. Laboratory tests reported a normal hemoglobin level. Electrocardiography was typical for left ventricular hypertrophy, and chest radiography showed mild cardiomegaly without active lung infiltrate (Figure 1). Ultrasonography with the parasternal long-axis view of the heart revealed increased thickness of the interventricular septum and an obvious aortic valve fluttering when the leaflets were open (Figure 2 and Video E1). The aortic valve fluttering during the systolic phase was confirmed by the M-mode echocardiogram (Figure 3).Figure 2Ultrasonography with the parasternal long-axis view of the heart revealed increased thickness of the interventricular septum (asterisk) and an obvious aortic valve fluttering when the leaflets were open (arrow).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3The aortic valve fluttering during the systolic phase (arrows) was shown on the M-mode tracing at the aortic valve in the parasternal long-axis view of the heart.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Hypertrophic obstructive cardiomyopathy. After consultation with cardiovascular specialists, the patient received an elective left ventricular myomectomy for hypertrophic obstructive cardiomyopathy. The fluttering of the cusps of the aortic valve is mostly reported during diastole, and it is associated with flail cusps with significant aortic regurgitation.1Qamar S. Ammar K.A. Paterick T.E. et al.Diastolic fluttering of the aortic valve: pathognomonic M-mode features of flail cusp.Eur Heart J Cardiovasc Imaging. 2013; 14: 204Crossref PubMed Scopus (1) Google Scholar Systolic fluttering of the aortic valve has been reported, which was explained by turbulent systolic flow downstream of an aortic valve.2Becsek B. Pietrasanta L. Obrist D. Turbulent systolic flow downstream of a bioprosthetic aortic valve: velocity spectra, wall shear stresses, and turbulent dissipation rates.Front Physiol. 2020; 11577188Crossref PubMed Scopus (12) Google Scholar Before the widespread use of Doppler echocardiogram, systolic fluttering was used to diagnose a patient with severe aortic stenosis.3Chin M.L. Bernstein R.F. Child J.S. et al.Aortic valve systolic flutter as a screening test for severe aortic stenosis.Am J Cardiol. 1983; 51: 981-985Abstract Full Text PDF PubMed Scopus (8) Google Scholar Systolic fluttering of the aortic valve indicates a large pressure gradient during the systole, which is pathognomonic for hypertrophic obstructive cardiomyopathy.4Pollick C. Shmueli H. Maalouf N. et al.Left ventricular cavity obliteration: mechanism of the intracavitary gradient and differentiation from hypertrophic obstructive cardiomyopathy.Echocardiography. 2020; 37: 822-831Crossref PubMed Scopus (1) Google Scholar Since left ventricular hypertrophy is common in the elderly, recognizing the aortic valve fluttering by clinicians facilitates the correlation of clinical symptoms, consultation, and timely treatment for hypertrophic obstructive cardiomyopathy. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI1YzAxZjJmZDVmYjg2ZTM4ZGFjM2EwMjc4ZDUyMGQ4YiIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc1NzYwNDg4fQ.l8n6GzpnK5MPpC1H1vaaZNBSV9NXyo8dNwHvQgC-HV8KCQK6B7P0Eb2wyRB1OKRFVvXIu8cVL4pTqPEIchOdRO7GgaY6-MTWE-ZZZ8wFG9AaDLZGd3SK_NVRyPuThLWyjmXP5gQXvoFcqAmT3XqT3VZVCRfD5JbkLNTd8kms7lZw2PGWPRexp3Q2d_Dw5dWL8eBCZ5NaEBEAmvhio4GuUNjVoHR7tfEV8q06Hqur4PFADzFXVcNGWW87aGJxI9HcWgK6F86W17-3k0DTUt4BPMMDatDekNdROGq9X_ekBZ_Yv53pq652T6lVJYliLhMQNt19sqJR5r6mY2rzWF6O5A Download .mp4 (2.98 MB) Help with .mp4 files Video E1Ultrasonography with the parasternal long-axis view of the heart revealed a thick interventricular septum indicating left ventricular hypertrophy. In the brightness mode, a remarkable aortic valve fluttering in the systolic phase was noted (white arrow, 00:05). Color Doppler (00:09 to 00:13) demonstrated turbulent flows originating from the left ventricular outflow tract (black arrowheads, 00:10), which was compatible with hypertrophic obstructive cardiomyopathy. (Used with permission of Nin-Chieh Hsu, Taipei City Hospital, Taiwan.)

Surgery for patients with obstructive hypertrophic cardiomyopathy: challenge and future

After more than 60 years of development, with the deepening of the pathophysiological understanding of obstructive hypertrophic cardiomyopathy, the extent and resection thickness of myectomy have increased significantly. Myectomy combined with the correction of anomalies of the mitral valve apparatus has become the standard treatment of obstructive hypertrophic cardiomyopathy. Only a few centers worldwide can routinely perform it due to the difficulty. Because of the advances of new drugs and interventional therapy, the development of surgical treatment faces many challenges. At the same time, generations of cardiovascular surgeons are constantly trying to promote septal myectomy, including developing devices and the surgical field, as well as improving surgical planning by advanced technology. At present, the superior long-term efficacy of septal myectomy has been confirmed. It is necessary to work together to promote the treatment of hypertrophic obstructive cardiomyopathy, so as to guard people's health.

Effect analysis of myectomy guided by personalized three-dimensional reconstruction and printing in the treatment of obstructive hypertrophic cardiomyopathy

Objective: To examine the clinical efficacy of myectomy guided by personalized three-dimensional reconstruction and printing for patients with obstructive hypertrophic cardiomyopathy. Methods: The clinical data of 28 patients with obstructive hypertrophic cardiomyopathy, who underwent septal myectomy guided by personalized three-dimensional reconstruction and printing in the Department of Cardiaovascular Surgery, Guangdong Provincial People's Hospital from May 2020 to December 2021, were retrospectively analyzed. There were 14 males and 14 females, aging (51.1±14.0) years (range: 18 to 72 years). Enhanced cardiac computed tomography images were imported into Mimics software for preoperative three-dimensional reconstruction. The direction of the short axial plane of each segment was marked perpendicularly to the interventricular septum on the long axial plane of the digital cardiac model, then the thickness was measured on each short axial plane. A figurative digital model was used to determine the extent of resection and to visualize mitral valve and papillary muscle abnormalities. Correlation between the length, width, thickness, and volume of the predicted resected myocardium and those of the surgically resected myocardium was assessed by Pearson correlation analysis or Spearman correlation analysis. The accuracy of detecting mitral valve and papillary muscle abnormalities of transthoracic echocardiography and three-dimensional reconstruction was also compared. Results: There was no death or serious complications like permanent pacemaker implantation, re-sternotomy for bleeding, low cardiac output syndrome, stroke, or multiple organ dysfunction syndromes in the whole group. Namely, the obstruction of the left ventricular outflow tract was effectively relieved. The systolic anterior motion of the anterior mitral valve leaflet was absent in all patients after myectomy. The length, width, and thickness of the predicted resected myocardium by three-dimensional reconstruction were significantly positively correlated with the length (R=0.65, 95%CI: 0.37 to 0.82, P<0.01), width (R=0.39, 95%CI: 0.02 to 0.67, P<0.01), and thickness (R=0.82, 95%CI: 0.65 to 0.92, P<0.01) of the surgically resected myocardium, while the relation of the volume of the predicted resected myocardium and the volume of the surgically resected myocardium was a strong positive correlation (R=0.88, 95%CI: 0.76 to 0.94, P<0.01). Importantly, the interventricular septal myocardial thickness measured by preoperative transthoracic echocardiography showed a moderate positive correlation with the volume of surgically resected myocardium (R=0.52, 95%CI: 0.19 to 0.75, P<0.01). During a follow-up of (14.4±6.8) months (range: 3 to 22 months), no death occurred, and 1 patient was readmitted for endocardial radiofrequency ablation due to atrial fibrillation. Conclusion: Personalized three-dimensional reconstruction and printing can not only visualize the intracardiac structure but also guide septal myectomy by predicting the thickness, volume, and extent of resected myocardium to achieve ideal resection.