Left Ventricular Outflow Tract Gradient Reduction Research Articles

Mitral regurgitation in obstructive hypertrophic cardiomyopathy: assessing the impact of mavacamten

Abstract Background Hypertrophic cardiomyopathy (HCM) is a genetic cardiac condition that leads to a hypercontractile state. This, as well as other features of HCM, such as abnormal mitral valve morphology and septal protrusion can lead to left ventricular outflow tract (LVOT) obstruction. Mitral regurgitation (MR) is a frequent finding in patients with hypertrophic cardiomyopathy (HCM), usually due to systolic anterior motion (SAM) of the mitral valve. Patients with outflow obstruction can present with a myriad of symptoms. With the introduction of myosin inhibitors such as mavacamten, reductions in the LVOT gradient and improvement in symptoms has been well documented. However, the impact on SAM and SAM-mediated MR has not been well explored. Objectives We aimed to evaluate whether mavacamten resulted in a change in SAM and subsequently a change in mitral regurgitation, in patients with obstructive HCM from baseline following a period of established mavacamten pharmacotherapy. Methods Transthoracic echocardiography (TTE), which is used to facilitate the safe prescription and monitoring of mavacamten therapy, was retrospectively analysed. Severity of mitral regurgitation (graded as 0-4 to delineate trivial, mild, moderate, moderate to severe and severe disease), grade of SAM (0-3) and LVOT gradients were documented, with baseline studies compared to the most recent follow up scan for the patient in question. MR severity was based on the visual impression of the reporting sonographer, and was reviewed by an imaging cardiologist. Patients had undergone between 4 and 24 weeks of mavacamten pharmacotherapy depending on their time of enrolment into the mavacamten clinic. Concurrent changes in NT-pro BNP were also evaluated. Results 24 patients (female n=4; male n = 20) in the mavacamten clinic underwent retrospective analysis of their echocardiographic parameters. Improvement in the severity of MR occurred in 75% of patients (n=18; p<0.001). In 39% of these patients, severity improved by 2 grades or more. Systolic anterior motion of the mitral valve was downgraded in 75% of patients (n=18; p<0.001), with an improvement by 2 grades or more in 42% of individuals. Mavacamten therapy resulted in a reduction in LVOT gradient at rest (-28.96± 5.124mmHg P=<0.0001) and with Valsalva (-60.95± 7.551mmHg P=<0.0001). Furthermore, a significant reduction in serum NT-proBNP levels was demonstrated from baseline (-975.2± 7.551ng/L P=<0.0001). 1 patient had to discontinue therapy at 4 weeks primarily due to a drop in left ventricular ejection fraction. Conclusion In patients with obstructive HCM, mavacamten resulted in a significant reduction in SAM-mediated mitral regurgitation, with corresponding falls in LVOT gradients. Cardiac myosin inhibitor scanning protocols should include detailed mitral valve assessment, to allow accurate evaluation of both SAM-dependent and SAM-independent MR mechanisms. Severity of mitral regurgitation. Change in grade of SAM.

Long-term follow-up study on obstructive hypertrophic cardiomyopathy patients treated with disopyramide: evidences of a notable trend in symptom control within a real-world clinical setting.

In obstructive hypertrophic cardiomyopathy (HOCM), disopyramide is used in patients who remain symptomatic despite β-blockers or verapamil. However, effectiveness of disopyramide therapy has not been clearly established due to inconsistent definition of responders and the insufficient length of follow-ups reported in literature. To address these shortcomings, we have conducted a retrospective analysis from detailed databases with long follow-up, from two HCM Referral Centers. 62 symptomatic HOCM patients (43% women, age 52 ± 14 years) with left ventricular (LV) outflow tract gradient (LVOTG) ≥ 50 mmHg at rest or during provocation, were recruited from two Italian Centers. Disopyramide was added as second-line therapy in the patients in whom symptoms persisted despite classic pharmacologic treatment. Patients in NYHA class > II at baseline who reached NYHA class II or I, and patients in NYHA class II at baseline who reached NYHA class I or symptoms stabilization were defined as responders. At follow-up, (mean 4.4 years, IQR 1.1-6.6 years), 47 patients (76%) were responders, whereas 15 (24%) were no-responders. Responders showed larger LV diastolic volume index (LVEDVi) at baseline as compared to no-responders (61 ± 14 vs. 49 ± 16 ml, respectively, p = 0.018), and, at follow-up, reached lower LVOTG than no-responders (43 ± 32 vs. 66 ± 28 mmHg, respectively, p = 0.013), with a LVOTG <50 mmHg more represented in responders than in no-responders (75% vs. 25%, respectively; p = 0.004). No side effects requiring discontinuation of the therapy were recorded. HOCM patients treated with disopyramide as second-line therapy in a quite long-follow-up showed a significant improvement of symptoms, which avoided SRT in up to 70% of them. Moreover, our data suggest that a larger LVEDVi at baseline identify the subgroup of patients who benefit the most from the therapy in terms of symptoms and reduction of LVOTG below 50 mmHg during treatment. We will discuss specific situations where disopyramide may be preferred over myosin inhibition to ensure that effective therapeutic options are fully considered and not prematurely dismissed.

The Role of Alcohol Ablation Therapy in Hypertrophic Obstructive Cardiomyopathy Management

Objectives: The following study aims to investigate alcohol septal ablation’s (ASA) role in hypertrophic obstructive cardiomyopathy (HOCM) management, focusing on in-hospital outcomes, efficacy in reducing left ventricular outflow tract (LVOT) obstruction, and safety profiles. Methods: The study, conducted at the Institute of Cardiology, National Hospital of Sri Lanka, included a total of nine HOCM patients. Participants with exercise-induced symptoms, dyspnea/angina, and specific ventricular gradients were included; unidentified septal branches led to exclusion. Diagnostic assessments, including electrocardiogram, contrast echocardiography, and cardiac catheterization, confirmed HOCM. ASA procedures involved careful target septal branch selection, alcohol injection, and post-procedure care with temporary pacemaker monitoring. Results: The study population (N=9) comprised seven males and two females, with a mean age of 40. Pre- and post-ablation measurements showed 78% reduction in LVOT gradient. Immediate complications included chest pain (100%), while 22.2% developed complete heart block. Notably, no mortality occurred during the study. Conclusion: ASA proved safe and effective in managing HOCM, with significant mean reduction in post-ablation LVOT gradient (78%). Complications were generally minor, emphasizing ASA’s viability for symptomatic HOCM patients. While acknowledging the absence of randomized controlled trials comparing ASA with alternative techniques, this study contributes valuable insights to guide collaborative treatment decisions by specialists.

Efficacy and Safety of Mavacamten in the Treatment of Hypertrophic Cardiomyopathy: A Systematic Review.

Current pharmacological options for hypertrophic cardiomyopathy (HCM) are not disease-specific; while it treats symptoms, mavacamten targets the underlying pathology. We aim to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive HCM. This systematic review of the literature followed the PRISMA guidelines. Title/abstract and topics were searched using the following term: "mavacamten". The electronic research literature databases included the Cochrane Library, MedLine, and clinicaltrials.gov from July to August 2022. Primary efficacy endpoint was to assess clinical response at the end of treatment compared with baseline, defined as, at least one New York Heart Association (NYHA) class reduction. Two secondary endpoints from baseline were determined. The first was defined as improvement in mixed venous oxygen pressure (pVO2). The second was defined as reduction of the post-exercise left ventricular outflow tract (LVOT) gradient. We included in our analyses data from four studies that met our review eligibility criteria. There were three randomised placebo-controlled clinical trials and one non-randomised open-label clinical trial. All four studies showed a reduction in NYHA class from mavacamten use. Three out of four studies demonstrated >1 NYHA functional class improvement ranging from 34% to 80%, while only one study showed a smaller percentage of patients remaining at class 3. Three out of four studies measured pVO2 as an outcome, and all three studies noticed an increase in peak oxygen consumption after mavacamten treatment. Additionally, three out of four studies measured post-exercise LVOT gradient reduction as an outcome and all three found significant reduction in the post-exercise LVOT gradient after treatment. The most commonly observed adverse side effects were atrial fibrillation and decreased left ventricular ejection fraction, but all participants recovered without long-term sequelae and only one patient dropped out of the trial. Mavacamten has a greater efficacy than placebo in the treatment of HCM. It also showed promising tolerability and efficacy profiles in the treatment of HCM in adults. The three endpoints used in the evaluation of studies were reduction in NYHA class, increase in pVO2, and post-exercise LVOT gradient reduction. Mavacamten showed greater reduction in NYHA, larger effects on increase of pVO2, and significant reduction of the LVOT gradient. Mavacamten was also found to be well tolerated, like the placebo. The side effect profile was limited for the majority of individuals taking mavacamten. In the future, authors recommended dose-optimisation studies, and studies that evaluate mavacamten both in comparison to, and in conjunction with other current treatments.

Hemodynamic Predictors of Outcome Following Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy.

Alcohol septal ablation (ASA) is a minimally invasive treatment for drug-refractory obstructive hypertrophic cardiomyopathy. Detailed assessment of pressure changes and predictors of mortality and procedure success are not well defined. This is a single-center study evaluating pressure changes and predictors of mortality and procedure success in transseptal ASA. Survival analysis and predictors of mortality were assessed using the Kaplan-Meier analysis and Cox regression, respectively. A total of 156 patients were included (mean age, 67.3 years; 46.8% women). Left atrial (LA) pressure and left ventricular outflow tract (LVOT) gradient decreased, whereas aortic pulse pressure (PP) increased post-ASA. Patients with lower baseline mean LA pressure (<median, 19 mm Hg), LVOT gradient reduction >82% (gradient change median), and PP increase >19% (PP change median) had superior survival. On Cox univariable regression, baseline mean LA pressure >median (19 mm Hg; hazard ratio [HR], 2.09 [95% CI, 1.05-4.18]; P=0.036), residual LVOT gradient (HR, 1.02 [95% CI, 1.01-1.03]; P=0.003), and LVOT gradient percent reduction <median (82%; HR, 2.92 [95% CI, 1.46-5.83]; P=0.002) were predictors of mortality. When adjusting for age and sex, baseline LA v wave >median (28 mm Hg; HR, 2.36 [95% CI, 1.17-4.76]; P=0.016), baseline mean LA pressure >median (19 mm Hg; HR, 2.70 [95% CI, 1.33-5.50]; P=0.006), percentage reduction in gradient <median (82%; HR, 2.74 [CI, 1.37-5.50]; P=0.005), and percentage increase in PP <median (19.3%; HR, 2.09 [CI, 1.05-4.16]; P=0.035) predicted survival free of all-cause mortality. ASA is associated with an acute decrease in the LVOT gradient and LA pressures and increase in aortic PP. Mean LA pressure, percentage decrease in LVOT gradient, and increase in PP are strong predictors of survival free of all-cause mortality following ASA and are important variables for procedural guidance.

First-in-man application of Liwen RF™ ablation system in the treatment of drug-resistant hypertrophic obstructive cardiomyopathy.

This study sought to evaluate the clinical applicability of the Liwen Liu RF™ ablation system for percutaneous intramyocardial septal radiofrequency ablation (PIMSRA). Data on new cardiac radiofrequency ablation devices for the treatment of hypertrophic obstructive cardiomyopathy (HOCM) are limited. From July 2019 to July 2020, a total of 68 patients with drug-resistant HOCM, who underwent PIMSRA with the Liwen RF™ ablation system, which has an ablation electrode of stepless adjustable length, were prospectively enrolled. Safety endpoints included, amongst others, the occurrence of pericardial effusion and/or hemorrhage, cardiac arrhythmias, device failure and procedural death. The reduction in left ventricular outflow tract (LVOT) gradients at 12 months follow-up were used as a surrogate marker for device efficacy. All procedures were technically successful. The total energy output time of the system was 75.8 (IQR: 30.0) min, and the average power was 43.61 ± 13.34 watts. No ablation system error occurred. The incidence of pericardial effusion or hemorrhage, transient arrhythmia and resuscitation was 8.8, 39.7, and 1.5% during procedure, respectively. None of the patients died. During 30-day follow-up, there were no complications with the exception of a pericardial effusion in one patient (1.5%). No further complications were reported after 30 days. The patients' resting [baseline: 75 (IQR: 48) vs. 12-months: 12 (IQR: 19) mmHg, p < 0.001] and provoked [baseline: 122 (IQR: 53) vs. 12-months: 41 (IQR: 59) mmHg, p < 0.001] LVOT gradients decreased significantly during follow-up. In this study, we demonstrate the safety and feasibility of the Liwen RF™ ablation system to treat HOCM. The system allows for significant and sustainable LVOT gradient reduction during 12-months of follow-up. Hence, the Liwen RF™ ablation system is a promising new device that has the potential to become an alternative to existing septal reduction concepts in HOCM patients.

P232 EXERTIONAL BREATHLESSNESS IN HYPERTROPHIC CARDIOMYOPATHY: OBSTRUCTION–INDEPENDENT SYMPTOMS IN A “PARADOXICAL” RESPONSE TO EXERCISE

Abstract A 66–y.o. man with hypertrophic cardiomyopathy presented with residual exertional dyspnea NYHA III a few years after surgical myectomy, mitral valve repair and ICD implantation. Echocardiography showed residual mild septal hypertrophy and mitral regurgitation (MR), and a variable obstruction of left ventricular outflow tract (LVOT), witnessed by a pressure gradient ranging from 15 to 50–70 mmHg (Figure 1). Exercise echocardiography did not suggest exercise–induced LVOT obstruction (LVOTO) or functional MR. We thus performed a thorough invasive hemodynamic evaluation at rest and during exercise. LVOTO was present at rest, with a maximum pressure gradient of 90–100 mmHg and typical “spike–and–dome” configuration of the aortic pulse contour (Figure 2), with LV end–diastolic pressure (LVEDP) at the upper limit of normal (15 mmHg) and normal pulmonary hemodynamics. During exercise, we observed a paradoxical reduction of the LVOTO (30–40 mmHg at peak, Figure 2). Pulmonary hypertension developed during exercise, due to LV diastolic dysfunction, witnessed by a marked increase in pulmonary artery wedge pressure and LVEDP (up to 25 mmHg and 30 mmHg at peak, respectively). Cardiac output (CO) reserve was at the lower limits of normal, mainly due to chronotropic incompetence, responsible for a mildly reduced exercise capacity (peak oxygen consumption was 20 mL/Kg/min, 75% of predicted). Thus, cardiac catheterization confirmed the presence of a relevant LVOTO at rest, that was not directly related to exertional symptoms. These latter were mainly attributable to LV diastolic dysfunction and reduced CO reserve. These findings helped us driving treatment decision in a tailored way: beta–blockers were not uptitrated, because of their negative inotropic effect, and high–risk septal reduction therapies were excluded, since exertional symptoms were unrelated to LVOTO. However, an attempt to reduce LVOTO was done by DDD sequential pacing through the ICD. Pacing could induce mechanical dyssynchrony and reduce LVOTO by increasing the end–systolic LVOT diameter. The simultaneous echocardiographic monitoring highlighted an acute reduction of LVOT gradient from 50–70 mmHg to 20–30 mmHg (Figure 3). This case suggests that, in well–selected cases, patients’ management based on pathophysiological reasoning may help to define the etiopathogenetic mechanism underlying symptoms, and to drive treatment decision in a patient–centered way.

Ecocardiographic comprehensive evaluation of OHCM patients treated with percutaneous ASA

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Alcohol septal ablation (ASA) has been widely accepted as an alternative to surgical myectomy in patients with symptomatic obstructive hypertrophic cardiomyopathy (OHCM) despite optimal medical treatment. The aim of this study was to analyse the effect of ASA on anatomical and functional features analysed by echocardiography, as well as its clinical impact. We further evaluated the safety of procedure. Methods and results Retrospective analysis of consecutive patients submitted to ASA (2009 – 2019) in a single tertiary centre. A dedicated echocardiogram was performed at 3 and 6 months after procedure. Echocardiographic primary endpoint was a &amp;gt; 50% reduction in left ventricular outflow tract (LVOT) gradient (the definition used for successful procedure). Echocardiographic secondary endpoint was improvement in mitral regurgitation. Clinical primary endpoint was defined as a combined endpoint of cardiac death or hospitalization during follow-up (FU). 110 patients were included, 66.4% women, mean age 65.1 ± 12.2 years. Functional class NHYA class III/IV, angina CCS class II/III and syncope were present in 87.3%, 52.7% and 10.0%, respectively. Baseline LVOT gradients at rest and at Valsalva manoeuvre were 93.6 ± 39.8 mmHg and 118.9 ± 44.2 mmHg. Maximum septal thickness was 21.0 ± 3.3 mm, 24.5% had moderate mitral regurgitation and 52.7% showed systolic anterior motion of mitral valve. During hospitalization for ASA, peak creatine kinase after procedure was 1306 ± 816 U/l. 17 (17.1%) patients required permanent PM due to induction of permanent complete heart block. There was one case of inferior myocardial infarction and one case of cardiac tamponade. Echocardiographic primary endpoint was achieved by 83.6% of patients. At 3 and 6-months follow up, LVOT gradients was significantly decreased in successful comparing with unsuccessful procedure group (24.6 ± 23.9 vs 82.0 ± 28.7 mmHg, p = 0.003 and 31.8 ± 34.5 vs 68.6 ± 27.8 mmHg, p = 0.027, respectively). There was no difference in baseline clinical or echocardiographic parameters between both groups. Regarding the echocardiographic secondary endpoint, among patients with moderate mitral regurgitation, 80% improved to mild regurgitation. A significant reduction in basal septal thickness was achieved in most patients, from 21.0 ± 3.3mm to 16.4 ± 2.7 mm after ASA (p = 0.001). During mean FU of 3.4 ± 2.1 years, clinical primary endpoint occurred in 25.5%, mainly in unsuccessful procedure group (50.0% vs 20.7%, p = 0.013). Reintervention was performed for recurrence of symptoms in 14 (12.7%) patients, surgical myectomy in 3 (3.6%) and repeated ASA in 10 (9.1%). Conclusion ASA allows a significant reduction in LVOT gradient and improvement of mitral regurgitation in the majority of patients with OHCM. Systematic and comprehensive echocardiographic evaluation assumes a paramount importance for the evaluation of procedural success. Abstract Figure.

Abstract 10792: Immediate Reduction in Left Ventricular End-Diastolic Pressure During Alcohol Septal Ablation in Patients with Hypertrophic Obstructive Cardiomyopathy

Introduction: Alcohol septal ablation (ASA) is an elective nonsurgical procedure proven to be effective for patients with hypertrophic obstructive cardiomyopathy (HOCM). The intraprocedural change in left ventricular end-diastolic pressure (LVEDP) is unknown. In this study we assessed the hypothesis that LVEDP decreases immediately post ablation during ASA in patients with HOCM independently of the effects of sedation and heart rate. Methods: We retrospectively identified 133 elective ASA procedures for patients with HOCM between 2015 and 2021 at our institution using an internally maintained database. Pre- and post-ablation LVEDP measurements were taken using the pressure tracing corresponding with end-expiratory R wave of the ECG tracing. LVEDP was recorded for post-“a” wave points on the pressure tracing at three distinct points during the procedure: the immediate start of the procedure (Group A), prior to alcohol injection after sedation had taken effect (Group B), and post ablation (Group C). Heart rate (HR) and left ventricular outflow tract gradient (LVOTG) were obtained from the catheterization report. Paired t-tests, ANOVA, and regression analyses were performed using SPSS Statistics. Results: The average patient age was 64 years old; mean NYHA Class 2.7; and 67% were women. There was no difference between LVEDP of Groups A and B (32mmHg, 32mmHg, p=0.92). LVEDP between Groups A and C (32mmHg, 26mmHg, respectively; p&lt;0.001) and Groups B and C (32mmHg, 26mmHg, respectively; p&lt;0.001) were significantly different. There was no correlation between HR and LVEDP for the groups (R2A=0.002, R2B=0.000, R2C=0.054), and similarly, no correlation between the average change in LVEDP and the change in resting or provoked LVOTG (R2=0.033, R2=0.003, respectively). Conclusions: These results support that alcohol septal ablation causes an immediate reduction in LVEDP post-ablation independent of heart rate, reduction in LVOTG, and effects of sedation. In conclusion, this instantaneous change in LVEDP may account for the immediate resolution in symptoms reported by patients with HOCM undergoing ASA.

Long-Term Survival After Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: A 16-Year Experience.

Alcohol septal ablation (ASA) is an accepted treatment for medically refractory hypertrophic obstructive cardiomyopathy (HOCM). The procedural and medium-term outcomes have been reassuring. The iatrogenic targeted septal infarction has raised theoretical concerns about risk of arrhythmia and long-term survival. In this study, we describe the long-term survival in a large cohort of patients from a single referral center and the iterative improvement in procedural technique since its inception. This cohort includes 580 consecutive patients who underwent 664 ASA procedures between the years 1999 and 2015. Procedural details and outcomes are described. Long-term survival is compared with expected survival of demographically similar controls. Fifty-four percent were women and 85% were Caucasian. At the time of ablation, mean age was 57 ± 15 years, septal thickness was 2.1 ± 0.5 cm, and left ventricular outflow tract (LVOT) gradient was 72 ± 40 mm Hg at rest and 102 ± 58 mm Hg with Valsalva provocation. Mean follow-up was 8.0 ± 4.3 years. LVOT gradient reduction >50% was achieved in 94% of patients with reduction in New York Heart Association functional class scores and increase in exercise treadmill duration. Procedural mortality was 0.9%. Over the 16-year period, survival estimates at 1, 5, 10, and 15 years were 98%, 92%, 84%, and 81%, respectively, which are comparable to demographically similar controls. The standardized mortality ratio was 0.84 (95% confidence interval, 0.66-1.06); P=.09. ASA appears to be a safe and effective treatment for symptomatic HOCM refractory to medical therapy with long-term survival comparable to a demographically similar United States population.

A modified endocardial radiofrequency ablation approach for hypertrophic obstructive cardiomyopathy guided by transthoracic echocardiography: a case series.

BackgroundA series of studies showed that endocardial radiofrequency ablation (ERFA) could reduce the left ventricular outflow tract (LVOT) gradient in patients with septal hypertrophy. This study aimed to determine the safety and efficacy of a modified ERFA approach guided by transthoracic echocardiography (TTE) as an alternative to ablation performed under a three-dimensional (3D) electroanatomical system or intracardiac echocardiography (ICE).MethodsTwenty-five patients with hypertrophic obstructive cardiomyopathy (HOCM) underwent ERFA of septal hypertrophy, guided by echocardiography. The LVOT gradient, left ventricular ejection fraction (LVEF), LV thickness, New York Heart Association (NYHA) class, and biochemical laboratory values were recorded before ablation and during follow-up.ResultsThe patients’ peak and stress-induced LVOT gradients were significantly reduced after 12 months of follow-up (resting gradient: from 123.2±17.7 to 15.7±7.8 mmHg, P<0.05; provocative gradient: from 140.2±20.8 to 18.4±8.0 mmHg, P<0.05). Compared with baseline, the septal diameter was reduced slightly after 12 months, but the difference was not significant (24.8±3.5 vs. 24.2±3.4 mm, P>0.05). The reduction in LVOT gradient was associated with an improvement in NYHA functional classification (from 3.0±0.0 to 1.6±0.7, P<0.05), the 6-minute walking distance (413±129 m at baseline; 458±108 m immediately after ERFA; 471±139 m after 12 months, P<0.05), and pro B-type natriuretic peptide levels (from 924.00±139 to 137.45 ±75.73 pg/mL, P<0.05). After the procedure, the patients showed no worsening of LVEF compared with baseline (64%±5.3%), and no cases of bundle branch block nor complete heart block occurred.ConclusionsERFA guided by TTE provides a new treatment option for HOCM which can achieve symptomatic improvement as well as a significant and sustained reduction of the LVOT gradient. Moreover, by avoiding the use of the 3D electroanatomical system or ICE, this treatment has an acceptable cost.

Targeted septal branch microcirculatory embolization with tris-acryl gelatin microspheres in hypertrophic obstructive cardiomyopathy

Abstract Background Alcohol septal ablation (ASA) has been shown to be an effective treatment in patients with hypertrophic obstructive cardiomyopathy (HOCM) who are refractory to medical treatment. ASA may cause some life-threatening complications including conduction disturbances, hemodynamic compromise, ventricular arrhythmias, distant and massive myocardial necrosis. Tris-acryl gelatin microspheres provide consistent and predictable results for effective targeted microcirculatory embolization. Purpose We aimed to report our initial experience in tris-acryl gelatin microspheres for septal ablation in HOCM. Methods Microspheres are biocompatible, hydrophilic, non-resorbable microspheres which are available in a range of calibrated sphere sizes. In our method, after the cannulation of the left anterior descending by a 6F-7F guiding catheter, a 0.014-inch guidewire is introduced through the catheter and advanced into the septal branch. This septal artery is selectively cannulated with a 4F catheter over the guidewire. Selective angiography of the septal artery is performed to show the anatomy and collateral branches to other coronary arteries. Contrast echocardiography is performed to make sure that the pertinent septal artery is the target vessel supplying the hypertrophied septum. A microcatheter is then advanced deep enough into the septal artery through the 4F catheter. Microspheres/contrast solution infused slowly under fluoroscopic guidance into the targeted septal branches initially using coronary arteriolar sized small particles (diameter 100–300 μm); then the particle size was stepped up to larger particles (diameter 300–500 μm) until a complete block of the arteriolar flow is achieved. Results Septal ablation with tris-acryl gelatin microspheres was performed in 6 patients (mean age = 47.8±11.5; 5 males). Immediately after the procedure peak left ventricular outflow (LVOT) gradient reduced significantly both for direct catheter (69.0±13.8 vs. 8.2±3.7 mmHg, P&amp;lt;0.001) and Doppler echocardiographic measurements (78.8±19.9 vs. 12.0±5.1 mmHg, P&amp;lt;0.001). Post-procedure peak serum CK- MB fraction concentration was 82±22 ng/ml (reference range is 0 - 4.9 ng/mL) and peak serum troponin T concentration was 1.2 ng/ml [(interquartile range, 0.4–1.4), (reference range is 0 - 0.017 ng/mL)]. LVOT tract gradient reduction persisted after 6 months follow-up. There was no significant complication during the procedure and within a 6 months follow-up period. Conclusions The novel strategy by targeted septal branch microcirculatory embolization with tris-acryl gelatin microspheres seems to be an efficient and safe approach to HOCM. Further experience is needed in order to assess the long-term efficacy and safety of this technique. Funding Acknowledgement Type of funding source: None

Alcohol Septal Ablation versus Septal Myectomy Treatment of Obstructive Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis.

Surgical myectomy (SM) and alcohol septal ablation (ASA) are two invasive therapies for symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM), despite medical therapy. This meta-analysis aims to compare the efficacy of the two procedures. We searched all electronic databases until February 2020 for clinical trials and cohorts comparing clinical outcomes of ASA and SM treatment of patients with HOCM. The primary endpoint was all-cause mortality, cardiovascular (CV) mortality, sudden cardiac death (SCD), re-intervention, and complications. Secondary endpoints included relief of clinical symptoms and drop of left ventricular outflow tract (LVOT) gradient. Twenty studies (4547 patients; 2 CTs and 18 cohorts) comparing ASA vs. SM with a mean follow-up of 47 ± 28.7 months were included. Long term (8.72 vs. 7.84%, p = 0.42) and short term (1.12 vs. 1.27%, p = 0.93) all-cause mortality, CV mortality (2.48 vs. 3.66%, p = 0.26), SCD (1.78 vs. 0.76%, p = 0.20) and stroke (0.36 vs. 1.01%, p = 0.64) were not different between procedures. ASA was associated with lower peri-procedural complications (5.57 vs. 10.5%, p = 0.04) but higher rate of re-interventions (10.1 vs. 0.27%; p < 0.001) and pacemaker dependency (12.4 vs. 4.31%, p = 0.0004) compared to SM. ASA resulted in less reduction in LVOT gradient (−47.8 vs. −58.4 mmHg, p = 0.01) and less improvement of clinical symptoms compared to SM (New York Heart Association (NYHA) class III/IV, 82.4 vs. 94.5%, p < 0.001, angina 53.2 vs. 84.2%, p = 0.02). Thus, ASA and SM treatment of HOCM carry a similar risk of mortality. Peri-procedural complications are less in alcohol ablation but re-intervention and pacemaker implantations are more common. These results might impact the procedure choice in individual patients, for the best clinical outcome.

Abstract 17141: Mavacamten Improves Left Ventricular Relaxation and Compliance in Obstructive Hypertrophic Cardiomyopathy Through Direct Myosin Modulation

Introduction: Obstructive hypertrophic cardiomyopathy (oHCM) consists of a constellation of LV hypercontractility, LV outflow tract obstruction (LVOTO), and impaired relaxation, often resulting in dyspnea and reduced exercise capacity. In healthy dogs, the novel myosin modulator mavacamten (MAVA), decreased LV hypercontractility and improved compliance. In the PIONEER-HCM clinical study, improvements in post-exercise LVOT gradient, exercise capacity, and symptoms were reported. To examine whether MAVA could also limit residual myosin-actin cross-bridges during diastole, and improve LV compliance, its effects on diastolic indices were evaluated. Methods: In PIONEER-HCM, an open-label, multi-site, prospective study, oHCM subjects received MAVA for 12 weeks at either 10-20 mg/d (n = 11, Cohort A; 10 completed) or at 2-5 mg/d (n = 10, Cohort B). Echo-Doppler indices of LV filling and relaxation were compared at baseline to week 12. The p-values are from Wilcoxon signed rank tests, evaluating the distribution of within-subject 12-wk changes from baseline around a null of zero. Results: MAVA reduced hypercontractility in a dose-dependent fashion, with relief of LVOTO in all subjects achieving plasma MAVA concentration &gt;350 ng/ml (data previously reported). There was also an increase in mitral annular velocity during early diastole (e’ lat ). There was a concomitant reduction in E/e’ lat and increase in LV end-diastolic volume (LVEDV) consistent with improved LV compliance (Table). MAVA improved dyspnea score with a trend towards reduction in NT-proBNP. Conclusions: Administration of MAVA is associated with improvement in measures of myocardial relaxation (e’ lat ) and compliance in parallel with reduction in LVOT gradient. These findings are consistent with preclinical findings reported in healthy dogs and support additional evaluation of MAVA in patients with obstructive or non-obstructive HCM.

Percutaneous Intramyocardial Septal Radiofrequency Ablation for Hypertrophic Obstructive Cardiomyopathy

BackgroundIn patients with disabling symptoms caused by hypertrophic obstructive cardiomyopathy (HOCM), echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) could be a less invasive treatment option. ObjectivesThis study aimed to investigate the safety and efficacy of the PIMSRA for left ventricular outflow tract (LVOT) gradient reduction in HOCM. MethodsThe study enrolled 15 patients with HOCM. These patients underwent electrocardiography, imaging, and blood biochemistry examination over 6 months of follow-up. ResultsAt 6 months of follow-up, patients showed significant reductions in peak LVOT gradients (resting gradient: from 88.00 [66.00] mm Hg to 11.00 [6.00] mm Hg; p = 0.001; stress-induced gradient: from 117.00 [81.00] mm Hg to 25.00 [20.00] mm Hg; p = 0.005) and interventricular septum (IVS) thickness (anterior IVS: from 25.00 [21.00] mm to 14.00 [12.00] mm; p = 0.001; posterior IVS: from 24.00 [21.00] mm to 14.00 [11.50] mm; p = 0.001). The reductions in IVS thickness and LVOT gradients were associated with improvement in New York Heart Association functional classification (from 3.00 [2.00] to 1.00 [1.00]; p < 0.001), total exercise time (from 6.00 [5.50] min to 9.00 [8.00] min; p = 0.007), and pro B-type natriuretic peptide levels (from 924.00 [370.45] pg/ml to 137.45 [75.73] pg/ml; p = 0.028). No patient had bundle branch block or complete heart block. ConclusionsPIMSRA is a safe and effective treatment approach for severe, symptomatic HOCM and results in sustained improvement in exercise capacity, persistent reduction in LVOT gradient, and sustained improvement in cardiac function.

Dyssynchronization reduces dynamic obstruction without affecting systolic function in patients with hypertrophic obstructive cardiomyopathy: a pilot study.

Dyssynchrony from biventricular pacing (BiV) can reduce dynamic obstruction in hypertrophic obstructive cardiomyopathy (HOCM), but its consequences on the left ventricular (LV) systolic function are unknown. We evaluate changes in LV systolic function and assess the effectiveness of BiV in HOCM. Thirteen patients with HOCM (55 [33/75]years, five males) received a BiV device and underwent 2D transthoracic echocardiography before the implantation and at 12months follow-up. Global longitudinal and radial strain, and the timing of segmental displacement curves were measured by commercial speckle-tracking software to assess LV systolic function and dyssynchrony. Peak gradient in the LV outflow tract (LVOT) significantly decreased from 80 [51/100] to 30 [5/66]mmHg (p = 0.005). LV global strain was preserved from baseline to follow-up: 35.1 [20.2/43.8] % vs. 32.6 [27.1/44.1] %, p = NS (radial), and -16.6 [-19.1/-14.4] % vs. -15.7 [-17.0/-14.2] %, p = NS (longitudinal). Dyssynchrony analysis using displacement curves showed inversion of wall motion timing with earlier displacement of the lateral wall at follow-up only in patients with reduction in LVOT gradient. BiV reduces LVOT obstruction in patients with HOCM when dyssynchronization of LV motion and inversion of the timing of LV wall activation are reached. Notably, this does not lead to further deterioration of LV systolic function at mid-term follow-up.

Predictors of Outcome After Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: An Echocardiography and Cardiovascular Magnetic Resonance Imaging Study.

Alcohol septal ablation (ASA) is used for treatment of medically refractory hypertrophic obstructive cardiomyopathy patients with severe left ventricular outflow tract (LVOT) obstruction. The current recommendations restrict the procedure to adults with favorable anatomy and no other coexisting surgically amenable disease. Some patients remain symptomatic with residual LVOT obstruction, thus better patient selection is required. One-hundred and two consecutive subjects with hypertrophic obstructive cardiomyopathy who underwent cardiovascular magnetic resonance imaging, transthoracic echocardiography, and ASA were enrolled in this study. Successful ASA was defined as reduction of LVOT gradient ≥50% of baseline by echocardiographic follow-up 6 months post ASA. The relationships between segmental thickness assessed by cardiovascular magnetic resonance imaging and echocardiography and outcomes of ASA were compared between the 2 groups. The survival rate after ablation was 100% at 6-month follow-up. The LVOT gradient decreased ≥50% of baseline in 72% (73/102) patients. There were good correlations between the reduction of postoperative LVOT gradient and the thickness of basal anterior segment (r=0.371; P<0.001), basal anteroseptal segment (r=0.527; P<0.001), and total thickness of the above 2 segments (r=0.672; P<0.001). The area under the receiver operating curves were 0.68, 0.79 and 0.89 for predictive analysis (all P<0.001). The cutoff thickness of the segment 1+2 was 50.9 mm, which yielded a sensitivity of 86% and specificity of 77%. Both echocardiography and cardiovascular magnetic resonance imaging can be used effectively as noninvasive tools for patient selection for ASA procedure. A significantly thickened septum among hypertrophic obstructive cardiomyopathy patients may be associated with a poor outcome after ASA.

Biventricular Reverse Remodeling After Successful Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy

The aim of the present study was to investigate the long-term effects of alcohol septal ablation (ASA) on left ventricular (LV) and right ventricular (RV) remodeling in patients with obstructive hypertrophic cardiomyopathy (HC) using cardiovascular magnetic resonance (CMR). CMR was performed at baseline and 16 months after ASA in 38 patients with obstructive HC (mean age 48 ± 9 years) despite optimal medical treatment. ASA resulted in significant reductions of LV outflow tract gradient (mean 89 ± 22 vs 24 ± 12 mm Hg, p <0.001) and improvements in New York Heart Association functional class (p <0.001) during the follow-up period. LV remote mass and septal mass decreased from 98.34 ± 37.02 to 84.23 ± 34.71 g and from 77.56 ± 16.40 to 68.43 ± 14.02 g, respectively (p <0.001 for both) at 16-month follow-up. There were significant reductions of RV mass (mean 53.69 ± 7.12 vs 47.49 ± 6.17 g, p <0.001) and improvements in RV end-diastolic volume (mean 110.58 ± 22.47 vs 124.22 ± 24.17 ml, p <0.001) and the RV ejection fraction (p <0.001) during 16-month follow-up. Linear regression analysis showed that LV outflow tract gradient reduction was correlated significantly with LV remote mass reduction (r = 0.475, p = 0.003) and RV mass reduction (r = 0.535, p = 0.001) at 16-month follow-up. In conclusion, successful ASA can lead to positive biventricular reverse remodeling, showing significant reductions of RV and LV mass as well as increased RV and LV end-diastolic volumes during follow-up.

Long-term outcomes of septal reduction for obstructive hypertrophic cardiomyopathy

BackgroundSurgical myectomy and alcohol septal ablation (ASA) aim to decrease left ventricular outflow tract (LVOT) gradient in hypertrophic cardiomyopathy (HCM). Outcome of myectomy beyond 10 years has rarely been described. We describe 20 years of follow-up of surgical myectomy and 5 years of follow-up for ASA performed for obstructive HCM. MethodsWe studied 171 patients who underwent myectomy for symptomatic LVOT obstruction between 1972 and 2006. In addition, we studied 52 patients who underwent ASA for the same indication and who declined surgery. Follow-up of New York Heart Association (NYHA) functional class, echocardiographic data, and vital status were obtained from patient records. Mortality rates were compared with expected mortality rates of age- and sex-matched populations. ResultsSurgical myectomy improved NYHA class (2.74±0.65 to 1.54±0.74, p<0.001), reduced resting gradient (67.4±43.4mmHg to 11.2±16.4mmHg, p<0.001), and inducible LVOT gradient (98.1±34.7mmHg to 33.6±34.9mmHg, p<0.001). Similarly, ASA improved functional class (2.99±0.35 to 1.5±0.74, p<0.001), resting gradient (67.1±26.9mmHg to 23.9±29.4mmHg, p<0.001) and provoked gradient (104.4±34.9mmHg to 35.5±38.6mmHg, p<0.001). Survival after myectomy at 5, 10, 15, and 20 years of follow-up was 92.9%, 81.1%, 68.9%, and 47.5%, respectively. Of note, long-term survival after myectomy was lower than for the general population [standardized mortality ratio (SMR)=1.40, p<0.005], but still compared favorably with historical data from non-operated HCM patients. Survival after ASA at 2 and 5 years was 97.8% and 94.7%, respectively. Short-term (5 year) survival after ASA (SMR=0.61, p=0.48) was comparable to that of the general population. ConclusionLong-term follow-up of septal reduction strategies in obstructive HCM reveals that surgical myectomy and ASA are effective for symptom relief and LVOT gradient reduction and are associated with favorable survival. While overall prognosis for the community HCM population is similar to the general population, the need for surgical myectomy may identify a sub-group with poorer long-term prognosis. We await long-term outcomes of more extensive myectomy approaches adopted in the past 10 years at major institutions.

Will the Mitral Clip become the invasive treatment of choice for hypertrophic obstructive cardiomyopathy?

Left ventricular outflow tract obstruction (LVOTO) in classic hypertrophic obstructive cardiomyopathy is caused by a combination of septal hypertrophy and systolic anterior motion of the mitral valve (SAM). Invasive treatment of hypertrophic obstructive cardiomyopathy (HOCM) is reserved for patients with severe drug refractory symptoms and LVOTO, and has historically aimed to reduce the thickness of the basal septum of the left ventricle as a primary cause of LVOTO (septal reduction therapy). Surgical myectomy is highly successful in decreasing LVOTO and considered the invasive therapy of choice for HOCM. Alcohol-induced localised infarction of the basal septum, also known as alcohol septal ablation (ASA), is a percutaneous alternative in poor surgical candidates. When performed by highly experienced operators, surgical myectomy and ASA both have low mortality and high success rates. Systolic anterior motion of the mitral valve contributes significantly to the development of LVOTO in HOCM patients, and invasive techniques to correct SAM such as mitral valve repair (MVrep) might be as effective as septal reduction therapy in relieving the LVOTO. Until recently, however, MVrep in the treatment of HOCM has been limited to patients undergoing septal myectomy, and have an associated degenerative mitral valve disease. In a large series of HOCM patients undergoing surgical myectomy, only 32 out of 791 patients (4%) had concomitant MVrep or replacement, and all of those patients had associated degenerative mitral disease [1]. Recent reports of using the Alferi edge-to-edge repair in conjunction with septal myectomy in HOCM patients without degenerative mitral valve disease have shown promising results [2–4]. Since the Alferi technique was only performed concomitantly with septal myectomy, it is difficult to know weather surgical edge-to-edge repair of the mitral valve alone is sufficient to treat HOCM pa tients with refractory symptoms. In 2003, a patient with mitral valve prolapse and severe mitral regurgitation was treated with a percutaneous edge-to-edge MVrep using a novel system – the MitraClip. The safety and effectiveness of the MitraClip in treating various causes of mitral regurgitation (MR) is under ongoing investigations. Because SAM of the mitral valve is a major player in the symptomatology of HOCM and patients with this condition usually do not have associated organic mitral valve pathology, it is intuitive to think that the MitraClip can be very effective in treating MR and relieving the LVOTO by reducing or eliminating SAM. However, unfortunately, the published and ongoing trails did not include patients with HOCM. Schafer et al. recently published a very elegant ‘proof of concept’ series of three patients with LVOTO, who underwent an isolated percutaneous edge-to-edge MVrep using the MitraClip without septal ablation [5]. In this small group of patients the MitraClip showed impressive reduction in LVOT gradient both at rest (36.6 ±34.0 mm Hg pre MitraClip vs. 10 ±4.3 mm Hg post MitraClip), and after an extra-systolic beat (123.6 ±34.2 mm Hg pre MitraClip vs. 21.6 ±5.7 post MitraClip). The procedure resulted in a significant reduc tion in MR grade from 2.6 ±0.5 to 0.25 ±0.35, and a dramatic improvement of symptoms. In summary, percutaneous edge-to-edge MVrep is a promising technique in its early stages. The MitraClip and other devices under development might be safe, effective, and attractive ‘mini-invasives’ treatment modalities in HOCM patients with severe refractory symptoms and persistent LVOT gradient.