Peak Left Ventricular Outflow Tract Gradient Research Articles

Effect of Mavacamten on Chinese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy

Mavacamten has shown clinical benefits in global studies for patients with obstructive hypertrophic cardiomyopathy (oHCM), but evidence in the Asian population is lacking. To evaluate the safety and efficacy of mavacamten compared with placebo for Chinese patients with symptomatic oHCM. This phase 3, randomized, double-blind, placebo-controlled clinical trial was conducted at 12 hospitals in China. Between January 4 and August 5, 2022, patients with oHCM and a left ventricular outflow tract (LVOT) gradient of 50 mm Hg or more and New York Heart Association (NYHA) class II or III symptoms were enrolled and received treatment for 30 weeks. Patients were randomized 2:1 to receive mavacamten (starting at 2.5 mg once daily) or placebo for 30 weeks. The primary end point was change in Valsalva LVOT peak gradient from baseline to week 30. Left ventricular outflow tract gradients and left ventricular ejection fraction (LVEF) were assessed by echocardiography, while left ventricular mass index (LVMI) was determined by cardiac magnetic resonance imaging. Analysis was performed on an intention-to-treat basis. A total of 81 patients (mean [SD] age, 51.9 [11.9] years; 58 men [71.6%]) were randomized. Mavacamten demonstrated a significant improvement in the primary end point compared with placebo (least-squares mean [LSM] difference, -70.3 mm Hg; 95% CI, -89.6 to -50.9 mm Hg; 1-sided P < .001). Similar trends were demonstrated for resting LVOT peak gradient (LSM difference, -55.0 mm Hg; 95% CI, -69.1 to -40.9 mm Hg). At week 30, more patients receiving mavacamten than placebo achieved a Valsalva LVOT peak gradient less than 30 mm Hg (48.1% [26 of 54] vs 3.7% [1 of 27]), less than 50 mm Hg (59.3% [32 of 54] vs 7.4% [2 of 27]), and NYHA class improvement (59.3% [32 of 54] vs 14.8% [4 of 27]). Greater improvements were also observed with mavacamten regarding the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (LSM difference, 10.2; 95% CI, 4.4-16.1), N-terminal pro-B-type natriuretic peptide level (proportion of geometric mean ratio, 0.18; 95% CI, 0.13-0.24), high-sensitivity cardiac troponin I level (proportion of geometric mean ratio, 0.34; 95% CI, 0.27-0.42), and LVMI (mean difference, -30.8 g/m2; 95% CI, -41.6 to -20.1 g/m2). Safety and tolerability were similar between mavacamten and placebo. No patients experienced LVEF less than 50%. Mavacamten significantly improved Valsalva LVOT gradient vs placebo for Chinese patients. All secondary efficacy end points were also improved. Mavacamten was well tolerated with no new safety signals. This study supports the efficacy and safety of mavacamten in diverse populations, including Chinese patients. ClinicalTrials.gov Identifier: NCT05174416.

Patient reported outcomes in obstructive hypertrophic cardiomyopathy undergoing myectomy: Results from SPIRIT-HCM study

BackgroundPatient reported outcomes (PRO) can assess quality of life (QOL) in obstructive hypertrophic cardiomyopathy (oHCM). In symptomatic oHCM patients, we sought to study the correlation between various PROs, their association with physician reported New York Heart Association (NYHA) class and changes after surgical myectomy. MethodsWe prospectively studied 173 symptomatic oHCM patients undergoing myectomy (age 51 years, 62% men) between 3/17–6/20. PROs, including a) Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score b) Patient-Reported Outcomes Measurement Information System [PROMIS] c) Duke Activity Status Index [DASI] & d) European QOL score [EQ-5D], along with NYHA class, 6-min walk test (6MWT) distance and peak left ventricular outflow tract gradient (PLVOTG) were recorded at baseline and 12 month follow-up. ResultsThe median baseline PRO scores (KCCQ summary, PROMIS physical, PROMIS mental, DASI, EQ-5D) were 50, 67, 63, 25, 50, 37, 44, 25 and 0.61, respectively; 6MWT distance was 366 m. There were significant correlations between various PROs (r-values between 0.66 and 0.92, p < 0.001), but only modest correlations with 6MWT and provokable LVOTG (r-values between 0.2 and 0.5, p < 0.01). At baseline, 35–49% patients in NYHA class II had PROs worse than median, while 30–39% patients in NYHA Class III/IV had PROs better than median. At follow-up, a 20 point improvement in KCCQ summary score was observed in 80%, 4 point improvement in DASI score in 83%, 4 point improvement in PROMIS physical score 86% and a 0.04 point improvement in EQ-5D in 85%); along with improvements in NYHA class (67% in Class I) and peak LVOTG (median 13 mmHg) and 6MWT (median distance 438 m). ConclusionsIn a prospective study of symptomatic oHCM patients, surgical myectomy significantly improved PROs, LVOT obstruction, and functional capacity, with a high correlation between various PROs. However, there was high rate of discordance between PROs and NYHA class. Study registrationClinicalTrials.gov: NCT03092843.

Study design and rationale of EXPLORER-CN: a phase III, randomised, double-blind, placebo-controlled clinical study to evaluate the efficacy and safety of mavacamten in Chinese adults with symptomatic obstructive hypertrophic cardiomyopathy

IntroductionHypertrophic cardiomyopathy (HCM) is a primary myocardial disease commonly caused by pathogenic genetic variants encoding sarcomere proteins. Mavacamten, a first-in-class allosteric inhibitor of cardiac-specific myosin, has demonstrated efficacy and safety...

Minimally invasive right infra-axillary thoracotomy for transaortic modified Morrow procedure: a series of 60 cases

Objective: To examine the short-term curative effect with minimally invasive right infra-axillary thoracotomy for transaortic modified Morrow procedure. Methods: The clinical data of 60 patients who underwent video-assisted thoracoscopic transaortic modified Morrow procedure from August 2021 to August 2022 at Department of Cardiovascular Surgery, Zhejiang Provincial People's Hospital were retrospectively analyzed. There were 31 males and 29 females, with the age (M (IQR)) of 54.0(22.3) years (range: 15 to 71 years). The echocardiography confirmed the diagnosis of moderate mitral regurgitation in 30 patients, and severe mitral regurgitation in 13 patients. Systolic anterior motion (SAM) was present preoperatively in 54 patients. All 60 patients underwent transaortic modified Morrow procedure through a right infra-axillary thoracotomy using femorofemoral cardiopulmonary bypass. Surgical procedures mainly included transverse aortic incision, exposure of left ventricular outflow tract (LVOT), septal myectomy, and correction of the abnormal mitral valve and subvalvular structures. Results: All 60 patients underwent the programmatic procedures successfully without conversion to full sternotomy. The cardiopulmonary bypass time was (142.0±32.1) minutes (range: 89 to 240 minutes), while the cross-clamp time was (95.0±23.5) minutes (range: 50 to 162 minutes). The patients had a postoperative peak LVOT gradient of 7.0 (5.0) mmHg (range: 0 to 38 mmHg) (1 mmHg=0.133 kPa). A total of 57 patients were extubated on the operating table. The drainage volume in the first 24 h was (175.9±57.0) ml (range: 60 to 327 ml). The length of intensive care unit stay was 21.0 (5.8)h (range: 8 to 120 h) and postoperative hospital stay was 8 (5) days (range: 5 to 19 days). The postoperative septal thickness was 11 (2) mm (range: 8 to 14 mm). All patients had no iatrogenic ventricular septal perforation or postoperative residual SAM. The patients were followed up for 4 (9) months (range: 1 to 15 months), and none of them needed cardiac surgery again due to valve dysfunction or increased peak LVOT gradient during follow-up. Conclusion: Using a video-assisted thoracoscopic transaortic modified Morrow procedure through a right infra-axillary minithoracotomy can provide good visualization of the LVOT and hypertrophic ventricular septum, ensure optimal exposure of the mitral valve in the presence of complex mitral subvalvular structures, so that allows satisfactory short-term surgical results.

Conduction Disturbances and Arrhythmia Risk After Septal Reduction Therapy with Alternative Agents: A Pilot Study with EVOH-DMSO and Systematic Review.

Surgical septal myectomy and alcohol septal ablation are recommended treatment modalities for alleviating Left ventricular outflow tract (LVOT) gradient in obstructive HCM. Alcohol septal ablation offers advantages over surgery in many ways. However, it is associated with some life-threatening complications. For this purpose, our center used alternative agents for septal artery embolization. This study compared and evaluated conduction system defects and arrhythmia risk after EVOH-DMSO septal ablation with other alternative agents and alcohol septal ablation. Twenty-five patients who received septal reduction therapy with EVOH-DMSO were analyzed retrospectively, and all non-alcoholic agent's septal ablation studies were systematically reviewed and compared. Twenty-five patients (52% female; mean age: 55.8 ± 17.1) with symptomatic obstructive HCM were enrolled. The Peak LVOT gradient was significantly reduced after the procedure (68 vs. 20 mmHg; P <0.001). During the 12-month follow-up, no mortality occurred. The complete atrioventricular block was noted in 2 (8%) patients. The incidence of right bundle branch block (RBBB) increased after the procedure (pre-procedural 2 patients (8%), post-procedural 9 patients (36%) P = 0.002). On ECG and Holter monitorization, no sustained ventricular tachyarrhythmia occurred during follow-up, and no change was found in the frequency of atrial fibrillation. We systematically compared EVOH-DMSO to other non-alcohol agents, and we found that EVOH-DMSO can cause conduction system problems more commonly than other non-alcohol agents. EVOH-DMSO could cause conduction system problems more common than other non-alcohol agents but less than alcohol septal ablation.

An evaluation of mavacamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy in adults

ABSTRACT Introduction Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder leading to hypertrophy of the left ventricle excluding other etiologies. Patients can experience exertional chest pain, dyspnea, syncope or even sudden cardiac death (SCD). Traditional medical management consists of beta blockers (BB), nondihydropyridine calcium channel blockers and disopyramide. Mavacamten, a novel cardiac myosin inhibitor, has recently been shown to improve both quantitative and qualitative measures of obstructive HCM allowing some patients to defer septal reduction therapy. Areas covered This review delves into the pharmacotherapy of mavacamten, the evidence behind this first-in-class drug for HCM, guidance for clinical usage, and possible future uses for cardiac myosin inhibitors. Expert opinion Mavacamten should be incorporated into the standard armamentarium of medications used to treat obstructive HCM. PIONEER-HCM, EXPLORER-HCM and VALOR-HCM demonstrated improvements in peak LVOT gradient both at rest and post-exercise, cardiac biomarkers, New York Heart Association (NYHA) functional class and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Unlike other medications utilized for treatment, mavacamten can delay or even obviate the need for septal reduction therapy.

Abstract 11324: Association of Patient Reported Outcomes With NYHA Class and Functional Capacity in Symptomatic Obstructive Hypertrophic Cardiomyopathy: An Analysis of Spirit-HCM Study

Introduction: Patient reported outcomes (PRO) are used to assess quality of life (QOL) in obstructive hypertrophic cardiomyopathy (oHCM). Hypothesis: In symptomatic oHCM patients, we sought to prospectively study the association between various PROs &amp; their association with physician reported New York Heart Association (NYHA) class. Methods: This was a prospective study (ClinicalTrials.gov: NCT03092843) of symptomatic oHCM patients undergoing myectomy (n=173, mean 51 years, 62% men) between 3/2017 &amp; 6/2020. At baseline, we recorded: a) Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score b) Patient-Reported Outcomes Measurement Information System [PROMIS] score c) Duke Activity Status Index [DASI] &amp; d) European QOL score [EQ-5D], in addition to NYHA class, 6-minute walk test (6MWT) distance &amp; peak left ventricular outflow tract gradient (PLVOTG). Results: The median baseline KCCQ summary, PROMIS physical, PROMIS mental, DASI, EQ-5D scores were 50, 37, 44, 25 &amp; 0.61, respectively; 6MWT distance was 366 m. Figure 1 demonstrates highly significant correlations between various PROs, only modest correlations of PROs with 6MWT &amp; PLVOTG. Figure 2 shows that ~1/3rd patients with NYHA class II had worse than median PROs, while ~1/3 rd in NYHA III/IV had PROs better than median. Conclusions: In symptomatic oHCM patients, there is a high internal correlation between various prospectively recorded PROs but a modest correlation with 6MWT &amp; LVOTG. Also, in symptomatic oHCM, NYHA class incompletely characterizes disease severity, and using a more sensitive metric like PROs may help to better identify patients with impaired QOL who will potentially benefit from myectomy.

Abstract 9337: The Association of Echo Parameters With Health Status in Patients With Obstructive Hypertrophic Cardiomyopathy. Insights From the Explorer-HCM Trial

Introduction: The EXPLORER-HCM trial showed mavacamten, a direct cardiac myosin inhibitor, improved the health status of patients with obstructive hypertrophic cardiomyopathy (HCM). To explore physiologic mechanisms for this improvement, we examined cross-sectional and longitudinal associations of echocardiographic parameters with health status. Methods: EXPLORER-HCM was a 13-country, double-blind randomized trial of mavacamten or placebo for 30 weeks in symptomatic patients with obstructive HCM and peak LVOT gradient ≥50 mmHg. Health status was assessed with the Kansas City Cardiomyopathy Questionnaire-overall summary score (KCCQ-OS, range 0-100, higher=better). Using a series of multivariable linear regression models, we examined the association of 1) echo parameters with KCCQ-OS at baseline and 2) change in echo parameters with change in KCCQ-OS. Nonlinear associations were explored with cubic splines. As this was a mechanistic analysis, treatment was not included. Results: Among 196 patients (mean age 58±12 years, 39% women), mean KCCQ-OS was 67±18 at baseline and 76±19 at 30 weeks; mean change of 10±16 points. At baseline, only interventricular septal thickness (IVST) was significantly associated with KCCQ-OS in adjusted analyses (1.2-point decrease in KCCQ-OS per 1 mm higher IVST; 95% CI -2.2 to -0.2, p=0.015). However, when comparing changes in echo parameters with changes in KCCQ-os, decreases in LVOT gradient at rest, LVOT gradient post-exercise, LVOT gradient with Valsalva, LV mass, posterior wall thickness, and IVST were each associated with significant improvements in KCCQ-OS (FIGURE). Measures of diastolic function were not associated with KCCQ-OS, either cross-sectionally or longitudinally. Conclusions: Among patients with obstructive HCM, reductions in LVOT gradients, LV mass, and wall thickness (IVST&gt;posterior wall) were associated with significant improvements in patients’ symptoms, function, and quality of life.

Abstract 11593: The Critical Role of Transthoracic Echocardiography in the Evaluation of Cardiogenic Shock and Takotsubo Cardiomyopathy

Introduction: Cardiogenic shock occurs in 10% of patients with takotsubo cardiomyopathy (TTC) as a result of severe systolic dysfunction, or left ventricular outflow tract (LVOT) obstruction. Methods: Case report and review of the literature. Results: A 62-year-old female with a history of hypertension and diabetes mellitus presented with lightheadedness, shortness of breath, and chest discomfort. She was hemodynamically unstable, tachycardic, and hypotensive (70/40 mmHg). Her EKG showed sinus tachycardia at 101 BPM with 1 mm ST depression in leads II, III, AVF; V3-V6. Chest radiograph revealed pulmonary edema. High-sensitive troponin was 146.7. She was intubated for respiratory distress and had rapidly increasing vasopressor requirements. Emergent coronary angiography revealed nonobstructive coronary artery disease. A left ventriculogram revealed apical ballooning with an estimated ejection fraction of 25%, consistent with TTC. Transthoracic echocardiogram (TTE) showed severe mid and apical LV hypokinesis with basal hyperkinesis. Additionally, systolic anterior motion (SAM) of the mitral valve (MV) was noted, with a peak LVOT gradient of 7 mmHg. The patient improved clinically, and all support was weaned off. However, she later acutely developed recurrent respiratory distress and hypotension. Repeat TTE showed LVOT obstruction with a gradient of 40 mmHg due to increased basal hyperkinesis and SAM. The choice of vasopressor was switched from norepinephrine to phenylephrine to reduce the obstruction. She clinically improved and metoprolol succinate was added to reduce basal hypercontractility and improve left ventricular filling. Conclusions: Differentiating the mechanism of shock in TTC can easily be accomplished with TTE, and is essential to guiding treatment. The initial acute systolic dysfunction was effectively managed with norepinephrine, dopamine, and an intra-aortic balloon pump. She later developed LVOT obstruction as her systolic function improved. This was recognized with TTE and led to an appropriate change in vasopressor, as norepinephrine would have worsened the obstruction. This highlights the importance of early TTE in patients presenting with undifferentiated shock, especially when TTC is suspected.

Quantification of systolic anterior motion of the mitral valve to predict left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy

Abstract Background In patients with hypertrophic cardiomyopathy (HCM), left ventricular outflow tract obstruction (LVOTO) is associated with an increased risk of heart failure and death (1). It is typically caused by dynamic systolic anterior motion (SAM) of the mitral valve leaflet. SAM can be categorized by echocardiography but diagnostic accuracy is limited by high inter-observer variability. Purpose To investigate the accuracy of echocardiographic parameters quantifying systolic motion of the mitral valve leaflets to identify LVOTO in patients with HCM. Methods We present a cross-sectional analysis of the HyperCard Registry, a prospective single-center cohort study enrolling consecutive patients with suspected or confirmed HCM. For the present analysis, patients with confirmed HCM and a valid standardized transthoracic echocardiographic were included. LVOT gradients were measured at rest and during Valsalva maneuver using continuous wave Doppler. In patients with clinical suspicion of dynamic LVOTO, further provocation maneuvers were conducted. LVOTO was defined as a maximal peak LVOT gradient ≥30 mmHg. Parameters quantifying systolic motion of the mitral valve were measured in parasternal and apical views, both at early and late systole, by an investigator blinded to individual patient characteristics. SAM was visually assessed and categorized into grade 0 (no SAM), I (leaflet motion towards LVOT), II (late systolic septal contact), and III (early systolic septal contact). Results We analyzed 142 patients (59±13 years, 42% women). LVOTO was present in 68 (48%) patients of whom 30 (21% of all) exhibited LVOTO at rest, and 38 (27% of all) had LVOTO only during provocation maneuvers (ie. dynamic LVOTO). SAM was present in 86 patients (60%) and had a sensivitiy, specificity and PPV of LVOTO of 91%, 69% and 73%, respectively (table). The late-systolic distance between mitral leaflet tip and anterior septum (TISls) measured in apical 3-chamber view was best associated with the degree of SAM (F=123, P&amp;lt;0.001), and with peak LVOT gradient (at rest: Pearson r=−0.817; during Valsalva maneuver: r=−0.816, both P&amp;lt;0.001). In ROC analyses (figure), the AUC of TISls for identification of LVOTO and dynamic LVOTO were 0.914 (95% CI 0.868–0.959) and 0.857 (0.786–0.927), respectively. TISls ≤14 mm had a 97% sensitivity for LVOTO and of 94% for dynamic LVOTO. TISls ≤9 mm showed specificity and PPV of 95% and 92% for LVOTO, and 94% and 83% for dynamic LVOTO, respectively. Conclusions Quantification of SAM by TISls showed high diagnostic accuracy in identifying HCM patients with LVOTO. Prospective studies are needed to assess the incremental benefit of this novel parameter in the diagnostic work-up of HCM patients. Funding Acknowledgement Type of funding sources: None.

Current therapies for hypertrophic cardiomyopathy: a systematic review and meta-analysis of the literature.

The aim of this study was to synthesize the evidence on the effect of the current therapies over the pathophysiological and clinical characteristics of patients with hypertrophic cardiomyopathy (HCM). A systematic review and meta-analysis of 41 studies identified from 1383 retrieved from PubMed, Web of Science, and Cochrane was conducted. Therapies were grouped in pharmacological, invasive and physical exercise. Pharmacological agents had no effect on functional capacity measured by VO2max (1.11mL/kg/min; 95% CI: -0.04, 2.25, P<0.05). Invasive septal reduction therapies increased VO2max (+3.2mL/kg/min; 95% CI: 1.78, 4.60, P<0.05). Structured physical exercise programmes did not report contraindications and evidenced the highest increases on functional capacity (VO2max+4.33mL/kg/min; 95% CI: 0.20, 8.45, P<0.05). Patients with left ventricular outflow tract (LVOT) obstruction at rest improved their VO2max to a greater extent compared with those without resting LVOT obstruction (2.82mL/kg/min; 95% CI: 1.97, 3.67 vs. 1.18; 95% CI: 0.62, 1.74, P<0.05). Peak LVOT gradient was reduced with the three treatment options with the highest reduction observed for invasive therapies. Left ventricular ejection fraction was reduced in pharmacological and invasive procedures. No effect was observed after physical exercise. Symptomatic status improved with the three options and to a greater extent with invasive procedures. Invasive septal reduction therapies increase VO2max, improve symptomatic status, and reduce resting and peak LVOT gradient, thus might be considered in obstructive patients. Physical exercise emerges as a coadjuvant therapy, which is safe and associated with benefits on functional capacity. Pharmacological agents improve reported NYHA class, but not functional capacity.

Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy

BackgroundSeptal reduction therapy (SRT), surgical myectomy or alcohol ablation, is recommended for obstructive hypertrophic cardiomyopathy (oHCM) patients with intractable symptoms despite maximal medical therapy, but is associated with morbidity and mortality. ObjectivesThis study sought to determine whether the oral myosin inhibitor mavacamten enables patients to improve sufficiently to no longer meet guideline criteria or choose to not undergo SRT. MethodsPatients with left ventricular (LV) outflow tract (LVOT) gradient ≥50 mm Hg at rest/provocation who met guideline criteria for SRT were randomized, double blind, to mavacamten, 5 mg daily, or placebo, titrated up to 15 mg based on LVOT gradient and LV ejection fraction. The primary endpoint was the composite of the proportion of patients proceeding with SRT or who remained guideline-eligible after 16 weeks’ treatment. ResultsOne hundred and twelve oHCM patients were enrolled, mean age 60 ± 12 years, 51% men, 93% New York Heart Association (NYHA) functional class III/IV, with a mean post-exercise LVOT gradient of 84 ± 35.8 mm Hg. After 16 weeks, 43 of 56 placebo patients (76.8%) and 10 of 56 mavacamten patients (17.9%) met guideline criteria or underwent SRT, difference (58.9%; 95% CI: 44.0%-73.9%; P < 0.001). Hierarchical testing of secondary outcomes showed significant differences (P < 0.001) favoring mavacamten, mean differences in post-exercise peak LVOT gradient −37.2 mm Hg; ≥1 NYHA functional class improvement 41.1%; improvement in patient-reported outcome 9.4 points; and NT-proBNP and cardiac troponin I between-groups geometric mean ratio 0.33 and 0.53. ConclusionsIn oHCM patients with intractable symptoms, mavacamten significantly reduced the fraction of patients meeting guideline criteria for SRT after 16 weeks. Long-term freedom from SRT remains to be determined. (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [VALOR-HCM]; NCT04349072)

Assessing the Hemodynamic Impact of Anterior Leaflet Laceration in Transcatheter Mitral Valve Replacement: An in silico Study.

BackgroundA clinical study comparing the hemodynamic outcomes of transcatheter mitral valve replacement (TMVR) with vs. without Laceration of the Anterior Mitral leaflet to Prevent Outflow Obstruction (LAMPOON) has never been designed nor conducted.AimsTo quantify the hemodynamic impact of LAMPOON in TMVR using patient-specific computational (in silico) models.MaterialsEight subjects from the LAMPOON investigational device exemption trial were included who had acceptable computed tomography (CT) data for analysis. All subjects were anticipated to be at prohibitive risk of left ventricular outflow tract (LVOT) obstruction from TMVR, and underwent successful LAMPOON immediately followed by TMVR. Using post-procedure CT scans, two 3D anatomical models were created for each subject: (1) TMVR with LAMPOON (performed procedure), and (2) TMVR without LAMPOON (virtual control). A validated computational fluid dynamics (CFD) paradigm was then used to simulate the hemodynamic outcomes for each condition.ResultsLAMPOON exposed on average 2 ± 0.6 transcatheter valve cells (70 ± 20 mm2 total increase in outflow area) which provided an additional pathway for flow into the LVOT. As compared to TMVR without LAMPOON, TMVR with LAMPOON resulted in lower peak LVOT velocity, lower peak LVOT gradient, and higher peak LVOT effective orifice area by 0.4 ± 0.3 m/s (14 ± 7% improvement, p = 0.006), 7.6 ± 10.9 mmHg (31 ± 17% improvement, p = 0.01), and 0.2 ± 0.1 cm2 (17 ± 9% improvement, p = 0.002), respectively.ConclusionThis was the first study to permit a quantitative, patient-specific comparison of LVOT hemodynamics following TMVR with and without LAMPOON. The LAMPOON procedure achieved a critical increment in outflow area which was effective for improving LVOT hemodynamics, particularly for subjects with a small neo-left ventricular outflow tract (neo-LVOT).

Double Envelope Through The Aortic Valve: More than Range Ambiguity to Continuous Wave Doppler

A 70-YEAR-OLD MAN (99 kg, 185 cm) presented for aortic valve replacement owing to severe calcific aortic valve stenosis (AS). His AS was diagnosed recently after an investigation for presyncopal symptoms. Transthoracic echocardiogram demonstrated severe AS with peak and mean gradients of 84 and 48 mmHg, respectively. Asymmetric basal hypertrophy with mild left ventricular outflow tract (LVOT) obstruction also were noted. A peak LVOT gradient of 20 mmHg was measured with Valsalva maneuver, and mild mitral regurgitation was observed.

Three dimensional myocardial deformation parameters are associated with functional capacity in hypertrophic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Three-dimensional (3D) echocardiography is an emerging tool for assessment of left ventricular function, with a promising role in the evaluation of cardiomyopathies. Hypertrophic cardiomyopathy (HCM) is often associated with reduced exercise capacity. The aim of this study was to evaluate the importance of 3D myocardial deformation parameters as predictors of exercise capacity in HCM patients (P). Methods This prospective study enrolled P with HCM. Each P underwent a comprehensive transthoracic echocardiogram including 3D speckle-tracking to measure global longitudinal, radial and circumferential strain, twist, torsion and global area strain. Functional capacity was objectively assessed by treadmill cardiorespiratory exercise testing. Results 83 patients with HCM, 50 (60%) male, mean left ventricular ejection fraction (LVEF) of 68 ± 7%, 27 (33%) with obstructive HCM (LV outflow tract [LVOT] gradient of 89 ± 60 mmHg). Impairment in LV myocardial deformation parameters was significantly correlated with lower peak VO2: global longitudinal 3D strain (r=-0.397, p &amp;lt; 0.001), global radial 3D strain (r = 0.336, p = 0.003) and global circumferential 3D strain (r=-0.353, p = 0.002) (Figure 1). Impaired LV twist was significantly correlated with inferior peak VO2 (r = 0.264, p = 0.033) (Fig.2) and peak circulatory power (r = 0.371, p = 0.003). Torsion impairment also significantly associated with lower peak VO2 (r = 0.285, p = 0.021), circulatory power (r = 0.380, p = 0.002), time to ventilatory anaerobic threshold (VAT) (r = 0.369, p = 0.003) and (VE/VCO2 slope)/peak VO2 ratio (r=-0.316, p = 0.012). Furthermore, global area strain impairment showed significant relation with decreased peak VO2 (r=-0.368, p = 0.001), lower exercise duration (r=-0.384, p = 0.001), time to VAT (r=-0.404, p &amp;lt; 0.001), circulatory power (r=-0.272, p = 0.032) and (VE/VCO2 slope)/peak VO2 ratio (r = 0.391, p = 0.002). LV twist (r=-0.135, p = 0.284), torsion (r=-0.120, p = 0.341) and global area strain (r = 0.152, p = 0.235) impairment did not correlate with VE/VCO2 slope. Exercise capacity was not associated with LV mass index (r = 0.209, p = 0.095), LV end-diastolic volume (r = 0.058, p = 0.639), maximum wall thickness (r = 0.041, p = 0.744), LVEF (r=-0.092, p = 0.458), 2D global longitudinal strain (r=-0.024, p = 0.848) or peak LVOT gradient (r=-0.006, p = 0.964). In a subanalysis examining only the nonobstructive (nHCM) P, we found that peak VO2 had a superior correlation with global longitudinal 3D strain (r=-0.420, p = 0.004), global radial 3D strain (r = 0.356, p = 0.016) and global circumferential 3D strain (r=-0.357, p = 0.016) as well as LV twist (r = 0.300, p = 0.046) and torsion (r = 0.336, p = 0.024). Conclusion Although P with HCM often have supranormal LVEF, 3D speckle-tracking echocardiographic imaging has the potential to demonstrate subclinical impairment of LV function. Impaired LV 3D strain, twist, torsion and global area strain were associated with reduced exercise capacity, particularly in nHCM P. Abstract Figure. Peak VO2 and 3D strain parameters Abstract Figure. LV twist, torsion and global area strain

Abstract 12848: Patient-Specific in silico Models Demonstrate Hemodynamic Effect of LAMPOON in Transcatheter Mitral Valve Replacement

Introduction: The purpose of this study was to investigate the hemodynamic impact of LAMPOON (Laceration of the Anterior Mitral leaflet to Prevent Outflow ObstructioN) in transcatheter mitral valve replacement (TMVR) using patient-specific in silico modeling. Methods: Eight subjects from the LAMPOON investigational device exemption trial were included. All subjects were at prohibitive risk of outflow tract obstruction from TMVR based on computed tomography (CT), and underwent successful LAMPOON immediately followed by TMVR. A validated computational fluid dynamics (CFD) model was used to compare simulated hemodynamics and 3D flow patterns between two modeled conditions: 1) TMVR with LAMPOON and 2) TMVR without LAMPOON. Using the post-procedure CT scans, anatomical models of TMVR with LAMPOON were created for each subject. The open transcatheter valve cells were then virtually closed to model TMVR without LAMPOON for each subject. Finally, CFD was performed for each condition to simulate the systolic flow fields. Results: As compared to TMVR without LAMPOON, TMVR with LAMPOON resulted in lower peak velocity, lower peak LVOT gradient, and higher peak LVOT effective orifice area by 13 ± 6% (p=0.004), 28 ± 14% (p=0.008), and 15 ± 8% (p=0.002), respectively. LAMPOON provided flow communication through exposed cells of the transcatheter valve, thereby decreasing the flow constriction and reducing flow stasis in the vicinity of the neo-LVOT (Figure). The hemodynamic benefit of LAMPOON was observed to be greater in subjects with a smaller neo-LVOT area measured post-implant (p&lt;0.001). Conclusions: In silico modeling allowed for a quantitative patient-specific comparison of TMVR with and without LAMPOON, which is impossible to study clinically. The LAMPOON procedure improved simulated hemodynamics in all subjects, with a greater hemodynamic impact observed in subjects with a smaller post-implant neo-LVOT area.

Evaluation of Left Ventricular Outflow Gradients During Staged Exercise Stress Echocardiography Helps Differentiate Pediatric Patients With Hypertrophic Cardiomyopathy From Athletes and Normal Subjects.

Elevated left ventricular outflow tract (LVOT) gradients during exercise can occur in patients with hypertrophic cardiomyopathy (HCM) as well as in athletes and normal controls. The authors' staged exercise protocol calls for imaging at rest and during each stage of exercise to evaluate the mechanism of LVOT obstruction at each stage. They investigated whether this staged approach helps differentiate HCM from athletes and normal controls. They reviewed pediatric exercise stress echocardiograms completed between January 2009 and October 2017 at their center and identified those with gene-positive HCM, athlete's heart, and normal controls. Children with inducible obstruction (those with no LVOT gradient at rest who developed a LVOT peak gradient > 25mm Hg during exercise) were included. LVOT peak gradient, velocity time integral, acceleration time, and deceleration time were measured at rest, submaximal stages, and peak exercise. Compared with athletes, HCM patients had significantly higher LVOT peak gradients at rest (P = .019), stage 1 of exercise (P = .002), and peak exercise (P = .051), as well as a significantly higher change in LVOT peak gradient from rest to stage 1 (P = .016) and from rest to peak (P = .038). The acceleration time/deceleration time ratio of the LVOT Doppler was significantly lower in HCM patients compared with normal controls at peak exercise. The HCM patients who develop elevated LVOT gradients at peak exercise typically manifest early obstruction in the submaximal stages of exercise, which helps to differentiate them from athletes and normal controls.

Transposition of the Great Arteries, Ventricular Septal Defect, and Pulmonary Stenosis: Modified REV versus Rastelli

The objective of this study was to evaluate and compare the results of the modified réparation à l'ètage ventriculaire (REV) and the Rastelli operation for the treatment of transposition of the great arteries (TGA), ventricular septal defect (VSD), and pulmonary stenosis (PS). Records of 38 patients who underwent the modified REV (n = 16) or the Rastelli operation (n = 22) for the treatment of TGA, VSD, and PS between 2010 and 2019 were reviewed. The median age was 2.2 years (range 0.6-8.0 years) and the median weight was 11.3 kg (range 6.4-22.0 kg). No in-hospital death occurred and there were 4 early reoperations (two in each group). Overall survival at 10 years was 97.4% (100% in Modified REV group and 95.5% in Rastelli group, P = 0.39). Freedom from left ventricular outflow tract (LVOT) reoperation was 100% in both groups. Freedom from right ventricular outflow tract (RVOT) reoperation was 100% in Modified REV group and 75.4% in Rastelli group (P = 0.073). Event-free survival was 100% in Modified REV group and 72.0% in Rastelli group (P = 0.048). The most recent echocardiography showed that LVOT peak gradient was less than 10 mmHg in all patients. In Modified REV group, 30.8% of patients (4/13) had either RVOT obstruction (RVOT peak gradient more than 40 mmHg) or moderate or severe pulmonary insufficiency, while conduit stenosis (peak gradient more than 40 mmHg) was found in 25.0% of patients (3/12) in Rastelli group. The modified REV and the Rastelli operation provide satisfactory early results, as well as long-term survival and LVOT performance. However, the modified REV has better RVOT performance.

A systematic review and pooled analysis of septal myectomy and edge-to-edge mitral valve repair in obstructive hypertrophic cardiomyopathy

Left ventricular outflow tract (LVOT) obstruction and systolic anterior motion (SAM) of the mitral valve (MV) occurs in 70% of hypertrophic cardiomyopathy (HCM) patients. In individuals undergoing septal myectomy, concomitant MV surgery is considered for SAM with residual LVOT obstruction or mitral regurgitation (MR); however, the optimal approach remains debated. A literature search was performed in Pubmed, EMBASE, Ovid, and the Cochrane library of published articles through June 2021 reporting on combined septal myectomy and edge-to-edge MV repair for obstructive HCM. Continuous variables were weighted and compared using a student's t-test, and categorical variables using a chi-square test with Yates correction. Six studies with 158 total patients were included. The mean follow-up was 2.8 ± 2.7 years. Compared with pre-operative values, there were significant reductions in the LV ejection fraction (69 ± 10 vs 59 ± 8%), peak LVOT gradient (82 ± 34 vs 16 ± 13 mmHg), prevalence of moderate or greater MR (84 vs 5 %), and presence of SAM (96% vs 0) (p < 0.001 for all). There was no change in LV internal diastolic diameter (4.2 ± 1.3 vs 4.4 ± 1.5 cm, p = 0.32). There were 2 (1%) operative mortalities. At follow-up, the survival rate was 97%, there were 3 (2%) re-operative MV replacements, 4 (3%) patients remained in New York Heart Association functional class III/IV, and 8 (6%) required permanent pacemaker implantation. In conclusion, combined septal myectomy and edge-to-edge MV repair is a safe and effective treatment strategy in carefully selected patients requiring surgical HCM management.

Predictors of right ventricular function and size in patients with hypertrophic cardiomyopathy

We investigated factors associated with right ventricular (RV) function and size in hypertrophic cardiomyopathy (HCM) patients. Two hundred fifty-three consecutive HCM patients and 20 healthy volunteers underwent cardiac magnetic resonance examination. In addition to measuring RV function (ejection fraction—RVEF) and size (end-diastolic volume—RVEDV), each image was inspected for the presence of RV and left ventricular (LV) hypertrophy, and the maximal wall thickness of the left and right ventricles was recorded. HCM patients had higher RVEF and lower RVEDV than healthy volunteers and similar RV mass. The mean RV wall thickness was higher in HCM patients than in controls. LV late gadolinium enhancement (LGE) was present in 89.7% of patients, and RV LGE was present in 3.1% of patients (p < 0.0001). Univariate and multivariable analyses revealed that LVEF, peak LV outflow tract gradient, LV LGE, maximal LV wall thickness, and tricuspid regurgitation (TR) volume by magnetic resonance imaging were positive predictors of RVEF. In addition to TR volume, the only independent predictor of RVEF < 45% was LVEF (odds ratio = 0.80, 95% confidence interval 0.67–0.95). Multivariable analysis revealed that LVEDV and TR volume were positive predictors of RVEDV, whereas negative predictors were RVEF, maximal RV wall thickness, LV LGE, and age. Neither estimated systolic pulmonary artery pressure nor TR grade by echocardiography proved to be predictors of RVEF. There were no differences in either the maximal RV wall thickness or the maximal left ventricular (LV) wall thickness in patients stratified according to NYHA functional class (p = 0.93 and p = 0.15, respectively). There were no differences in mean RV wall thickness in patients categorised based on the number of clinical risk factors for sudden cardiac death (SCD), i.e., non-sustained ventricular tachycardia, family history of SCD, or unexplained syncope (p = 0.79). On the other hand, there was a weak positive association between RV hypertrophy and the estimated probability of SCD at 5 years (rho = 0.16, p = 0.01). RV systolic dysfunction measured as decreased RVEF was uncommon in HCM and was associated with poor LV systolic function. LV also had a significant impact on RV size.