Left Ventricular Outflow Tract Gradient Research Articles

Heterogeneous mechanisms of pulmonary congestion in hypertrophic cardiomyopathy unmasked by comprehensive exercise stress echocardiography

Abstract Background B-lines detected by lung ultrasound (LUS) during exercise stress echocardiography (ESE), indicating pulmonary congestion, are present in 1 out of 3 patients with hypertrophic cardiomyopathy (HCM). Aim To assess the functional and anatomical correlates of exercise B-lines in HCM. Methods We enrolled 191 HCM patients (age 53±15 years, 123 males) consecutively referred for ESE (treadmill in 74, bicycle in 117 patients) in 11 quality-controlled centers from 8 countries. ESE assessment at rest and peak stress included: left ventricular (LV) outflow tract gradient, left atrial (LAVi) and LV end-diastolic volume index (EDVi), mitral regurgitation (MR, score from 0 to 3); E/e'; systolic pulmonary arterial pressure (SPAP) and LV force (LV outflow tract gradient+systolic blood pressure/LV end-systolic volume). B-lines at rest and at peak exercise were assessed by LUS with the 4-site simplified scan. B-lines positivity was considered if the sum of detected B-lines was ≥2. Results LUS was feasible in all subjects. B-lines were present in 55 (29%) patients during stress. When compared to patients without stress B-lines (n=136), patients with B-lines (n=55) at peak exercise had lower peak EDVi (43±17 vs 52±18 ml/m2, p=0.003) higher peak E/e' (16±6 vs 12±5, p<0.001), increase in MR (34 vs 12%, p=0.001), greater stress LAVi (43±14 vs 37±14 ml/m2, p=0.003) and stress SPAP (56±18 vs 40±12 mm Hg p<0.0001): see Figure. Among baseline parameters, the number of B-lines (OR: 7.53, 95% CI 1.21–46.72 p=0.03), LAVi (OR: 1.05, 95% CI 1.00–1.09 p=0.04), and LV force (OR: 1.36, 95% CI 1.04–1.79 p=0.03) were the independent predictors of exercise pulmonary congestion. Conclusion HCM patients with pulmonary congestion on exercise show different, and not mutually exclusive mechanisms of diastolic dysfunction and worsening mitral regurgitation. These different hemodynamic mechanisms may require personalized therapeutic actions beyond a pulmonary decongestion therapy with diuretics. Funding Acknowledgement Type of funding sources: None.

Use of advanced echocardiographic modalities to discriminate preclinical HCM mutation carriers from non-carriers

Abstract Background It is a challenging goal to identify which family members of patients with hypertrophic cardiomyopathy (HCM) will subsequently develop HCM. Previous studies evaluating the utility of two-dimensional conventional Doppler echocardiography in HCM families with a known pathogenic variant identified on genetic testing have been unable to reliably distinguish preclinical genotype-positive, phenotype-negative (G+P−) individuals from their healthy genotype-negative, phenotype-negative (G−P−) relatives. Purpose To determine if advanced echocardiographic modalities can discriminate preclinical HCM mutation carriers (G+P−) from non-carriers (G−P−). Methods A total of 199 participants who had undergone genetic testing from HCM families with a known pathogenic variant were included in the study: 39 G−P−; 58 G+P− and 102 overt HCM patients (G+P+). Speckle tracking echocardiography (STE) and colour M-mode were performed on all participants and longitudinal, circumferential and radial strain, and torsion were compared. Results Patients with overt HCM had the highest septal, posterior wall thickness, septum/posterior wall (Sep/PW) thickness ratio and left ventricular outflow tract (LVOT) gradient and lowest global longitudinal, circumferential and radial strain, and tissue Doppler-derived myocardial systolic and diastolic velocities. Comparing G−P− and G+P− individuals, there were no significant differences in LV cavity size, wall thickness, LVOT gradient, LVEF and tissue Doppler-derived myocardial systolic and diastolic velocities. However, G+P− individuals had significantly higher peak apical rotation, peak twist and colour M-mode flow propagation velocity (Vp). Multivariate linear regression identified two independent predictors (peak apical rotation and Vp), and a regression equation (using multivariate linear regression) {Mutation carrier prediction value = (0.210×peak apical rotation) − (0.002×Vp) + 0.156; r=0.655)} was derived which allowed reliable discrimination of G+P- individuals with a sensitivity of 95.2% and specificity of 94.1% at the optimal cut-off. Conclusion In HCM family members without overt HCM, peak apical rotation and Vp provide good sensitivity and specificity for identifying mutation carriers and may be a clinically useful early marker of HCM before the onset of hypertrophy. Future longitudinal studies involving larger cohorts are required to validate these findings. Funding Acknowledgement Type of funding sources: None.

Clinical, functional and prognostic correlates of excess left ventricular force in hypertrophic cardiomyopathy

Abstract Background Excess force generation during myocardial contraction represents a cardinal feature of hypertrophic cardiomyopathy (HCM). Purpose To evaluate the anatomical, functional and prognostic correlates of left ventricular (LV) force in HCM. Methods We prospectively recruited a consecutive sample of 408 HCM patients with LV ejection fraction (EF) >50%, referred for baseline transthoracic echocardiography in 2 primary HCM centers in Hungary and Italy between 1999 and 2021. LV force was calculated as LV outflow tract gradient+systolic blood pressure/LV end-systolic volume. Patients were followed for a median of 107 months (IQ range, 58–158 months), the study endpoint was all-cause mortality. Results Mean LV force was 6.0±4.6 mm Hg/ml. Receiver-operating characteristic analysis identified 7.5 mm Hg/ml the best cut-off value to predict mortality. LV force >7.5 mm Hg/ml was present in 86 patients (21%), more frequently in women (58 vs 27%, p<0.0001), more often in patients with diabetes (16 vs 6%, p=0.003), beta-blocker (81 vs 58%, p<0.0001), calcium channel-blocker (19 vs 9%, p=0.012) and diuretic therapy (19 vs 8%, p=0.004), compared to patients with LV force ≤7.5 mm Hg/ml. Patients with excess LV force had more advanced NYHA class (1.8±0.7 vs 1.4±0.7, p=0.0001), greater left atrial diameter [(LAd), 46.7±6.6 vs 43.0±7.2 mm, <0.0001], LV maximal wall thickness (23.2±5.5 vs 21.6±5.5 mm p=0.01), LV EF (74.6±6.4 vs 67.0±6.8%, <0.0001), mitral regurgitation grade (1.2±0.7 vs 0.7±0.7, p<0.0001) and E/e' (10.3±5.0 vs 7.8±5.0, p=0.005). During follow-up 43 deaths occurred. All-cause death was more frequent in patients with excess LV force (21 vs 8%, p<0.0001). At multivariable Cox regression analysis, excess LV force was an independent predictor of mortality (HR 2.9, 95% CI 1.14–7.26, p=0.025) independent of age (HR 1.03, 95% CI 1.00–1.05, p=0.022) and LAd (HR 1.07, 95% CI 1.02–1.14, p=0.005). Conclusion LV force with a threshold of 7.5 mm Hg/ml, independently predicts adverse outcome in patients with HCM and preserved systolic function. Excess LV force generation is associated with female sex, diabetes, NYHA class, medications, LAd, LV wall thickness, EF, mitral regurgitation grade and E/e'. Funding Acknowledgement Type of funding sources: None.

Mechano-energetic efficiency in patients with hypertrophic cardiomyopathy with and without sarcomeric mutations

Abstract Background Hypertrophic Cardiomyopathy (HCM) is mainly caused by sarcomeric mutations. In about 40% of cases the causal mutation is unknown. Myocardial mechano-energetic efficiency per unit of left ventricular (LV) mass (MEEi) is an echocardiographic parameter of LV pump performance. Sarcomeric mutations may affect energy efficiency. Purpose We investigated the effects of the presence of sarcomeric mutations on MEEi in patients with HCM. Methods We included 49 genetically screened HCM patients (50±10 years, 27% women) with LV ejection fraction >50%, LV maximal wall thickness >14 mm and no moderate to severe mitral regurgitation. MEEi was calculated as the ratio between stroke volume and heart rate, normalized by LV mass. Echo-LV mass was calculated as LV epicardial minus LV endocardial volumes in 4 and 2 chamber views multiplied by 1.05, a method validated with nuclear magnetic resonance. Results 27 HCM patients carried a sarcomeric mutation (HCM-Sarc; 55%). As shown in the table, patients with and without sarcomeric mutations (HCM-Sarc vs HCM-NoSarc) had similar LV ejection fraction, heart rate, LV mass and LV outflow tract gradient. HCM-Sarc showed early age at diagnosis, higher frequency of HCM family history and significantly reduced MEEi as compared with HCM-NoSarc. Presence of sarcomeric mutation could be predicted by younger age, lower MEEi and by family history of HCM (overall p<0.05). Conclusions In a population of HCM patients, the presence of a sarcomeric mutation is the only determinant of reduced the LV pump performance as estimated by MEEi. MEEi may be used as an imaging biomarker in sarcomeric mutation carriers. Funding Acknowledgement Type of funding sources: None.

Representativeness of EXPLORER-HCM trial and prevalence of eligibility criteria for Mavacamten in a nationwide cohort

Abstract Introduction The EXPLORER-HCM trial evaluated the safety and efficacy of Mavacamten, a cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy (HCM). Mavacamten improved symptoms, exercise capacity and left ventricular outflow tract (LVOT) obstruction. However, the proportion of patients eligible for this therapy in real practice remains unclear. Purpose To determine the prevalence of eligibility criteria for Mavacamten and to describe the profile of patients complying with EXPLORER-HCM criteria in a nationwide cohort. Methods Cross-sectional study including all HCM patients enrolled in a European country-based nationwide registry. Presence of EXPLORER-HCM inclusion [≥18 years, obstructive HCM (LVOT gradient ≥50 mmHg), left ventricular ejection fraction (LVEF) ≥55%, New York Heart Association (NYHA) class II–III] and exclusion criteria [syncope or sustained ventricular tachycardia with exercise] were analyzed. Results Of 1042 patients included in this analysis (57.8% male, mean age at diagnosis 52 years, 39.6% obstructive HCM), 45 met the EXPLORER-HCM inclusion criteria and, after applying exclusion criteria, 30 patients were eligible for therapy with Mavacamten. Eligible patients were all Caucasian, mostly female (63.3%), with a mean age at diagnosis of 58±14 years. All patients presented with heart failure symptoms, and were mostly in NYHA class II (83.3%); 4 patients (13.3%) presented with atrial fibrillation. In the baseline echocardiogram, mean LVEF was 68±9%; mean interventricular septum thickness was 20±4 mm; most patients presented with systolic anterior motion of the mitral valve (96.7%) and mitral regurgitation (96.7%). In cardiac magnetic resonance imaging evaluation, maximal wall thickness was 22±4 mm and 76.9% had late gadolinium enhancement. A pathogenic or likely pathogenic HCM gene variant was identified in 5 patients (MYH7 and MYBPC3 gene mutations). In this group, 86.2% of patients were treated with beta-blockers and 34.5% with calcium channel antagonists. Only 1 patient was on Disopyramide. Septal reduction techniques were used in 43.3% of patients: alcohol septal ablation and septal myectomy were performed in 7 (23.3%) and 6 (20.0%) patients, respectively. Cardioverter-defibrillators were implanted in 2 patients for primary prevention of sudden cardiac death, and 6 patients received a pacemaker for bradycardia indications. Conclusion Specific therapies remain an unmet need in HCM. In this large nationwide cohort, only 2.9% of patients were eligible for therapy with Mavacamten according to EXPLORER-HCM criteria. Among patients complying with the study criteria, invasive septal reduction therapies were offered to a high proportion of patients. Further real-world data are warranted to estimate the proportion of HCM patients that will benefit from Mavacamten. Funding Acknowledgement Type of funding sources: None.

Gender-disparities in patients undergoing alcohol septal ablation for hypertrophic obstructive cardiomyopathy

Abstract Background Alcohol septal ablation (ASA) improves symptoms in patients with hypertrophic obstructive cardiomyopathy (HOCM) but gender-disparities have only rarely been investigated. Purpose To assess gender-disparities regarding outcome and procedure-related aspects in HOCM patients undergoing ASA. Methods and results 1,367 consecutive ASAs between 2002 and 2020 were retrospectively analyzed for sex-differences. Females (47.2%) had more advanced age at the timing of ASA (66.0 years [IQR 55.0–74.0] vs. 54.0 years [IQR 45.0–62.0]; p<0.0001), had more severe symptoms (NYHA class 2.8±0.6 vs. 2.5±0.8 in males; p<0.0001) and shorter distances walked in 6-min-walk-test at baseline (359.0m [IQR 272.3–442.0] vs. 464.4m [IQR 400.0–524.0] in males; p<0.0001). The baseline interventricular septal diameter (IVSD) was higher in males (21.0mm [IQR 19.0–24.0] vs. 20.0mm [IQR 18.0–23.0] in females; p<0.0001). However, the IVSD was higher in females when it was indexed to the body-surface-area (10.9 mm/m2 [IQR 9.7–12.7] vs. 10.2 mm/m2 [IQR 9.0–11.7] in males; p<0.0001). The resting and exercise-induced left ventricular outflow tract gradients (LVOTG) were lower in females when calculated 1–4 days after ASA (resting: 20.0 mmHg [IQR 12.0–37.5] vs. 22.0 mmHg [IQR 13.0–40.0] in males; p=0.0062; exercise-induced: 55.0 mmHg [IQR 30.0–109.0] vs. 71.0 mmHg [IQR 37.0–115.0] in males; p=0.0006). At 6 months follow-up females had lower exercise-induced LVOTG (34.0 mmHg [IQR 21.0–70.0] vs. 43.5 mmHg [IQR 25.0–74.8]; p=0.0072). More females had complete heart block after ASA (20.3% vs. 13.3% in men; p=0.0005) and, hence, more females (17.4%) than males (10.4%; p=0.0002) needed a pacemaker. There were no differences regarding mortality. Conclusion Female HOCM patients had more advanced age, more severe symptoms and a higher IVSD when indexed to BSA at the timing of ASA. However, early hemodynamic response was better in females, but procedure-related complete heart block was more often found in women. Gender-disparities in clinical characteristics and procedural outcome of ASA should be taken into consideration. Funding Acknowledgement Type of funding sources: None.

Mavacamten induces a clinical, hemodynamic, and biomarker response beyond the primary endpoint in EXPLORER-HCM: results from a post hoc machine learning analysis

Abstract Introduction Mavacamten, a first-in-class selective inhibitor of cardiac myosin, was demonstrated in EXPLORER-HCM (NCT03470545) to be superior to placebo in achieving a primary endpoint of either (1) a ≥1.5 mL/kg/min increase in peak oxygen consumption (pVO2) and at least one New York Heart Association (NYHA) class reduction, or (2) a ≥3.0 mL/kg/min pVO2 increase without NYHA class worsening, in adults with obstructive hypertrophic cardiomyopathy (oHCM). However, the observed benefits of mavacamten were broader than the primary endpoint, suggesting a complex effect of the drug beyond improvements in these two parameters. Purpose A post hoc investigation of mavacamten clinical effects beyond the primary endpoint of EXPLORER-HCM. Methods EXPLORER data at week 30 were analyzed to evaluate improvements from baseline in primary (specified above), secondary (e.g. postexercise left ventricular outflow tract gradient and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score) and exploratory endpoints (e.g. circulating NT-ProBNP and cardiac Troponin I). Responses were classified as improved or not improved based on published thresholds, clinical standards and analyses of the EXPLORER data. Patients were grouped according to their improvement status using unsupervised hierarchical clustering. Results The cluster analysis resulted in four main groups with the following trends (Table); Group 1 = patients who met the primary endpoint and showed improvement in secondary/exploratory endpoints; Group 2 = patients with improvement in secondary/exploratory endpoints who did not meet the primary endpoint; Group 3 = patients who met the primary endpoint without substantial secondary/exploratory endpoint responses; Group 4 = patients without appreciable improvement in any endpoint. A substantially larger proportion of patients in Group 1 received mavacamten compared with placebo (88% vs. 12%, respectively). A similar trend was observed in Group 2 patients who exhibited improvements in secondary/exploratory endpoints (85% mavacamten vs. 15% placebo). Group 3 consisted predominantly of placebo-treated patients who met the primary endpoint but had negligible responses to secondary/exploratory endpoints (5% mavacamten vs. 95% placebo). Group 4 consisted predominantly of placebo-treated patients without appreciable clinically relevant responses from this analysis (10% mavacamten vs. 90% placebo). Conclusions Mavacamten was associated with clinical improvements beyond the primary endpoint of EXPLORER-HCM and was predominantly accompanied by amelioration of other measures associated with oHCM pathophysiology. In contrast, most placebo-treated patients who met the primary endpoint did not exhibit improvement in the underlying pathophysiology. These findings suggest a potential underestimation of mavacamten clinical impact based on the primary endpoint and prompt a deeper examination of mavacamten efficacy in patients with oHCM based on other clinically relevant endpoints. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): MyoKardia, Inc., a wholly owned subsidiary of Bristol Myers Squibb

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<0.001), and with peak LVOT gradient (at rest: Pearson r=−0.817; during Valsalva maneuver: r=−0.816, both P<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.

Microvascular dysfunction is associated with impaired myocardial work in obstructive and nonobstructive hypertrophic cardiomyopathy: a multimodality approach

Abstract Introduction Myocardial work is a dynamic non-invasive method for assessing myocardial deformation. Microvascular dysfunction is a hallmark of hypertrophic cardiomyopathy (HCM). We hypothesized that there is an association between impaired myocardial work, evaluated by echocardiography, and left ventricular (LV) ischemia, detected by cardiac magnetic resonance (CMR). Methods Prospective assessment of HCM patients' (P) myocardial strain parameters with 2D speckle-tracking echocardiography. All P underwent CMR protocol (1.5-T) for the analysis of stress perfusion and late gadolinium enhancement (LGE). Perfusion defects were quantified as burden of ischemia (% of LV mass). Results were stratified according to obstructive (oHCM) and nonobstructive (nHCM) HCM as well as according to the presence of significant replacement fibrosis (LGE of ≥15% or <15% of LV mass). Multivariate regression analyses were used to explore the relation between myocardial work and the burden of ischemia. Results 75 P with HCM (63% male, age 55±15 years), 61% with asymmetric septal LVH, 29% with apical LVH, 8% with concentric LVH and 28% exhibiting LV outflow tract obstruction (mean maximal LVOT gradient of 89±60 mmHg). Perfusion defects were found in 68 P (90.7%), with a mean of 22.5±16.9% of LV mass and 29 P (38.7%) had LGE ≥15% of LV mass. A lower global work index (GWI) significantly correlated with higher burden of myocardial perfusion defects (r=−0.520, β-estimate −0.019, 95% CI −0.028 to −0.010, p<0.001). Likewise, impaired values of global work efficiency (GWE) were linked to higher percentage of hypoperfusion (r=−0.477, β-estimate −0.713, 95% CI −1.250 to −0.176, p<0.001). Moreover, impaired global constructive work (GCW) (r=−0.519, β-estimate −0.021, 95% CI −0.030 to −0.013, p<0.001) and a higher global wasted work (GWW) (r=0.280, p=0.017) were associated with a higher burden of perfusion defects (Figure 1). GWI showed a higher correlation with perfusion defects in oHCM P (r=−0.518, p=0.019) vs. nHCM P (r=−0.492, p<0.001), and the same was also found with GWE (oHCM: r=−0.591, p=0.006 vs. nHCM: r=−0.317, p=0.022) (Figure 2A). Furthermore, GCW showed a slightly higher correlation with hypoperfusion in oHCM P (r=−0.564, p=0.010) vs. nHCM P (r=−0.520, p<0.001). There was no significant difference between oHCM and nHCM P regarding GWW. In P with LGE ≥15%, GWI showed a better correlation with perfusion defects (r=−0.489, p=0.007) vs. P with LGE of <15% (r=−0.369, p=0.007). Moreover, GCW showed a higher correlation with hypoperfusion in P with LGE ≥15% (r=−0.455, p=0.013) comparing with P with LGE <15% LV mass (r=−0.359, p=0.019) (Figure 2B). No difference was found regarding GWE and GWW according to LGE burden. Conclusion In our cohort of P with HCM, impaired GWI, GWE and GCW and a higher GWW were significantly correlated with the presence of myocardial ischemia in CMR. This correlation was greater in P with oHCM and in P with LGE of ≥15% of LV mass. Funding Acknowledgement Type of funding sources: None.

Prediction of Sudden Cardiac Arrest After Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: ASA-SCARRE Risk Score

This study aimed to derive a new score, the Alcohol Septal Ablation-Sudden Cardiac ARREst (ASA-SCARRE) risk score, that can be easily used to evaluate the risk of sudden cardiac arrest events (sudden cardiac death, resuscitation, or appropriate implantable cardioverter-defibrillator discharge) after alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy. We analyzed 1,834 patients from the Euro-ASA registry (49% men, mean age 57 ± 14years) who were followed up for 5.0 ± 4.3years (9,202 patient-years) after ASA. A total of 65 patients (3.5%) experienced sudden cardiac arrest events, translating to 0.72 events per 100 patient-years. The independent predictors of sudden cardiac arrest events were septum thickness before ASA (hazard ratio 1.09 per 1mm, 95% confidence interval 1.04 to 1.14, p <0.001) and left ventricular outflow tract (LVOT) gradient at the last clinical checkup (hazard ratio 1.01 per 1mm Hg, 95% confidence interval 1.01 to 1.02, p=0.002). The following ASA-SCARRE risk scores were derived and independently predicted long-term risk of sudden cardiac arrest events: "0" for both LVOT gradient <30mmHg and baseline septum thickness <20mm; "1" for LVOT gradient ≥30mm Hg or baseline septum thickness ≥20mm; and "2" for both LVOT gradient ≥30mm Hg and baseline septum thickness ≥20mm. The C statistic of the ASA-SCARRE risk score was 0.684 (SE 0.030). In conclusion, the ASA-SCARRE risk score may be a useful and easily available clinical tool to predict risk of sudden cardiac arrest events after ASA in patients with hypertrophic obstructive cardiomyopathy.

A novel risk model to predict all-cause mortality in patients undergoing percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy

Background and purpose: Hypertrophic obstructive cardiomyopathy (HOCM) is a global genetic myocardial disease. In clinical practice, an indicator that could be used to identify suitable patients for percutaneous transluminal septal myocardial ablation (PTSMA) and assess their long-term prognosis is important for cardiologists. HOCM patients undergoing PTSMA, poor long-term prognosis has been associated with higher left ventricular outflow tract gradient (LVOTG) and interventricular septal thickness (IVST). In this retrospective, multicenter study, we aimed to investigate the association between TG (TG = IVS thickness × LVOT gradient) index and acute- or long-term outcomes of HOCM patients after PTSMA and further investigate the interaction effects of LVOTG and IVST. Methods: The study design is based on four tertiary centers from Mid-China, and a total of 284 HOCM patients (132 males, average age 54.80 ± 11.98 years) were treated with PTSMA. A new clinic index (TG = IVS thickness × LVOT gradient) was designed. Both 30-day major cardiovascular adverse events and all-cause mortality of the HOCM patients were analyzed. Cox proportional hazards regression model adjusting for potential risk factors was applied to explore the hazard ratio (HR) for all-cause mortality. Results: Total alcohol injection volume was 2.201 ± 1.025 mL. LVOTG and IVST were reduced to 40.11 ± 24.44 mmHg and 17.68 ± 4.07 mm at the last clinical check-up, respectively. Patients with low IVST (≤20 mm) or low TG index (≤1,683) had a higher rate of PTSMA-contributable complications and a higher need for a permanent pacemaker. Within the 903 patient-years follow-up, a total of 21 (9.8%) deaths occurred. The number of deaths per 100 patient-years was 0.65 and 4.06 in the high versus low TG index groups. The 8-year OS rate was 48.95% (95% CI = 39.07%–57.75%) versus 82.63% (95% CI = 74.99%–86.66%) in the high versus low TG groups, respectively (log-rank P &lt; 0.001). The patients with both high LVOTG (&gt;82 mmHg) and high IVST had the highest risk of all-cause mortality (HR: 18.63 vs low LVOTG, 95% CI = 1.09–319.15). Conclusions: The 8-year OS rate was markedly higher in patients with a low TG index (≤1,683) (48.95%) versus in patients with a high TG index (&gt;1,683 group) (82.63%). The TG index could be a useful tool in the evaluation of HOCM patients for suitability for PTSMA.

Improved Outcomes With Transradial Approach in Alcohol Septal Ablation.

Transradial cardiac catheterization is equally effective but has fewer vascular complications than transfemoral catheterization. There is a paucity of data on biradial approach for alcohol septal ablation (ASA). This study seeks to study the differences in procedural outcomes between the transradial vs traditional transfemoral approach in ASA. A total of 274 consecutive patients who underwent ASA were retrospectively assigned to the study subgroups (137 transradial, 137 femoral). Procedural success, reduction in left ventricular outflow tract gradient (LVOTG), contrast volume, fluoroscopy time, and complications were compared between the 2 groups. There were no differences in reduction of resting LVOTG (91% vs 92%; P=.50), provoked LVOTG (80% vs 82%; P=.47) post procedure between transradial vs transfemoral subgroups. Iodinated contrast volume was significantly lower in the transradial group (98 mL vs 111 mL; P=.04), whereas fluoroscopy time was higher in the transradial group (17.42 minutes vs 13.00 minutes; P&lt;.001). The incidence of complications was lower in the transradial group (0.13 vs 0.23; P=.04). ASA via transradial approach is equally effective and associated with significantly less contrast use and fewer complications as compared with the traditional transfemoral approach.

S2653 Recurrent Bleeding Gastrointestinal Angioectasias and Acquired Von Willebrand Deficiency (Heyde’s Syndrome) Developing in the Setting of Mild Hypertrophic Obstructive Cardiomyopathy

Introduction: Heyde’s Syndrome is classically described as a triad of gastrointestinal arteriovenous malformations, aortic stenosis (AS), and acquired von Willebrand syndrome (aVWS). Acknowledged as under-diagnosed, the syndrome is frequently missed even in the presence of classically associated moderate-to-severe AS. Perhaps compounding diagnostic difficulty are more recent reports of alternative forms of structural heart disease, including hypertrophic obstructive cardiomyopathy (HOCM), that, although rarer, are capable of producing the syndrome as well. Case Description/Methods: 68-year-old woman with mild hypertrophic obstructive cardiomyopathy that resulted in 5 years of gastrointestinal bleeding episodes before the discovery of bleeding duodenal angioectasias. Initially diagnosed with “HOCM morphology” without evidence of dynamic obstruction on stress echocardiogram, bleeding episodes began to develop shortly after routine annual surveillance echo demonstrated a progression to mildly increased left ventricular outflow tract (LVOT) gradient. Cardiac magnetic resonance imaging (MRI) not only confirmed mild primary HOCM without secondary cause of hypertrophy, but also demonstrated mild flow acceleration across the LVOT, consistent with the hypothesized hemodynamic turbulence and sheer-stress believed to be the mechanism behind acquired von Willebrand deficiency. Within a year, gastrointestinal bleeding would ensue, beginning a prolonged clinical course with multiple hospitalizations for symptomatic anemia requiring transfusions. The eventual discovery of angioectasias prompted von Willebrand Factor analysis which found evidence of acquired deficiency and confirmed the diagnosis of Heyde Syndrome. The patient was subsequently referred for evaluation and definitive treatment of her HOCM with septal ablation, an intervention with which case series have demonstrated the potential for reversal of von Willebrand Factor deficiency and bleeding episodes. Discussion: Often a delayed diagnosis owing to the seemingly disparate constellation of findings in Heyde’s, this particular case additionally highlights that even more mild states of structural heart disease can provoke the syndrome outside of previously reported severe structural disease. Diagnostic suspicion must remain high and von Willebrand factor analysis considered in the combined presence of GI bleed and mild cardiomyopathy and valvulopathy.

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.

Double chambered left ventricle-Two chambers are not better than one.

In this month's Journal,1 Ali and colleagues present a case series consisting of two adults who underwent surgical resection for a double chamber left ventricle (DCLV). The first case was an 18-year-old female with several years of progressive chest pain and dyspnea who was ultimately found to have both a double chamber right ventricle (DCRV) and DCLV after transthoracic echocardiography (TTE) and cardiac catheterization. She underwent surgical resection of the fibromuscular bands in both ventricles with an uncomplicated postoperative course. The second case was a 27-year-old male with a history of supravalvular aortic stenosis that had been previously addressed who on TTE was found to have aortic regurgitation, aortic stenosis, and DCLV with elevated left ventricular outflow tract and accessory chamber (AC) gradients. He underwent mechanical aortic valve replacement, ascending aorta replacement, and muscle bundle excision with a course notable for delayed sternal closure and retroperitoneal hematoma. Both patients had technically successful operations with band resection and appropriate biventricular function confirmed on TTE. Both survived their index operations and had resolution of their symptoms, with the second patient dying at 6 months due to complications from anticoagulation. The authors should be congratulated for the successful identification and operative treatment of these patients. DCLV is an incredibly rare diagnosis and is even less common than its counterpart DCRV—which is seen in less than 2% of all congenital cardiac anomalies.2 Ali and colleagues successfully differentiated DCLV from other similar pathologies such as left ventricular aneurysms and left ventricular diverticulum. This is critical given their difference in etiology and overall management. Those with asymptomatic DCLV do not require surgical intervention. Symptoms are rare but can present as fatal tachyarrhythmias or heart failure. Patients can also be found to have mid-ventricular obstructions, particularly those with superior–inferior arrangements according to Bao et al.3 Those who are intervened upon typically undergo resection with patch reconstruction or cardiac transplant for large communications.4 Furthermore, diagnosing DCLV can be a challenge in and of itself. Some patients, including the second case of this study, have previous imaging that does not confirm the presence of DCLV.5 This just reiterates the importance of having a high clinical suspicion. Nevertheless, TTE is typically the first test performed and serves as a fairly reliable starting point. Bao et al.3 showed that in their series of nine patients, eight were correctly diagnosed during their initial TTE. Although a tissue diagnosis would be the best confirmatory test, a second imaging modality is typically used to confirm the diagnosis. The authors used cardiac catheterization and magnetic resonance imaging (MRI) in their first and second case, respectively, as their second modality of choice. The advantages of cardiac MRI are stated throughout the literature. It offers high inherent contrast resolution, good spatial and temporal resolutions, a wide field of view, multiplanar imaging capabilities, and the absence of radiation.4, 6 Gadolinium is particularly useful as a similar enhancement of the AC wall compared to the remainder of the left ventricular myocardium supports the diagnosis of DCLV.7 We (Figure 1) commend the authors on their work with this complex patient population. Both cases presented were unique and challenging. The authors demonstrated the ability to address DCLV in addition to the patient's existing congenital abnormalities. Furthermore, they demonstrate the ability to do so through both a transaortic and transmitral approach. DCLV is an incredibly rare diagnosis, making it difficult to establish practice guidelines. One should always pause when deciding when and how to operate on these patients. Still, Ali and colleagues add to the body of literature that suggests operating on DCLV can be done safely and that patients may derive a meaningful benefit. This work was supported by a research grant from NHLBI/NIH (No. T32HL007849). The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. The authors declare no conflict of interest.

Disopyramide is a safe and effective treatment for children with obstructive hypertrophic cardiomyopathy

BackgroundLeft ventricular outflow tract obstruction (LVOTO) is present in 1/3 of children with Hypertrophic Cardiomyopathy (HCM). Disopyramide improves symptoms associated with LVOTO and delays surgical intervention in adults, but it is not licensed in children. AimTo describe a single-centre thirty-year experience of using disopyramide to treat LVOTO-related symptoms in a paediatric HCM cohort. MethodsClinical data were collected for all patients meeting diagnostic criteria for HCM (<18 years) at the time of initiation, 6 months after, and last follow-up or end of disopyramide treatment. It included demographics, clinical history, 12‑lead electrocardiography, and echocardiography. Comparisons between baseline and 6 month follow up, and end of follow up respectively were performed. ResultsFifty-one patients with HCM were started on disopyramide at a mean age 10.2±5.3 years. At 6 months, of those previously symptomatic, 33(86.8%) reported an improvement of symptoms and 12(31.6%) were asymptomatic. PR interval, corrected QT interval and maximal LVOT gradient had not significantly changed, but fewer participants were noted to have systolic anterior motion of the mitral valve 31 (72.1%) vs. 26 (57.80%). Patients were followed up for a median of 1.9 years (IQR 0.83–4.5). Nine patients (17.6%) reported side effects, and eleven patients (33.3%) with initial improvement in symptoms reported a return or worsening of symptoms requiring a change in medication (n = 4, 12.1%) or left ventricular septal myomectomy (n = 7, 21.2%) during follow up. ConclusionDisopyramide is a safe and effective treatment for LVOTO-related symptoms in childhood obstructive HCM. Any delay in the need for invasive intervention, particularly during childhood, is of clear clinical benefit.

Posterior Wall Thickness Associates With Survival Following Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy

BackgroundThe left ventricular (LV) posterior wall thickness (PWT) is a predictor of sudden cardiac death in pediatric patients with hypertrophic cardiomyopathy (HCM), but the prognostic importance of PWT in adults has not been examined. ObjectivesThe goal of this study was to evaluate the association of LV PWT with late survival in adult patients undergoing septal myectomy for obstructive HCM. MethodsThis single-center study reviewed 2,418 patients who underwent transaortic septal myectomy for obstructive HCM. ResultsThe median preoperative PWT was 13 (IQR: 11-15) mm. Patients with PWT >13 mm tended to have systemic hypertension (55.4% vs 49.1%; P = 0.002) and a larger body mass index (median: 30.8 [IQR: 27.1-35.1] kg/m2 vs 29.6 [IQR: 26.1-33.9] kg/m2; P < 0.001). Preoperatively, PWT >13 mm was associated with increased septal thickness (median: 21 [IQR: 18-24] mm vs 19 [IQR: 17-22] mm; P < 0.001), greater maximum instantaneous left ventricular outflow tract (LVOT) gradient at rest (median: 67 [IQR: 36-96] mm Hg vs 47 [IQR: 19-79] mm Hg), and increased likelihood of moderate or greater mitral valve regurgitation (54.3% vs 47.3%; P = 0.001). However, PWT was not related to the severity of limitations measured by New York Heart Association functional class (P = 0.674). After adjusting for baseline covariates, greater PWT was an independent risk factor for late mortality after septal myectomy (P = 0.003). ConclusionsPWT is a newly identified predictor of reduced long-term survival after septal myectomy that is independent of septal thickness and severity of LVOT gradient. Future studies are warranted to investigate the mechanisms underlying the association and the potential usefulness of PWT in patient management.

Twenty years of experience with alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy in Chile

Septal reduction therapies for patients with hypertrophic obstructive cardiomyopathy (HOCM) are accepted in patients with symptoms and LV outflow tract gradient >50 mmHg who do not respond to medical treatment. Alcohol septal ablation is a minimally invasive procedure with promising short- and long-term results

Tissue tracking of segmental strain as a predictor of provoked dynamic left ventricular outflow tract obstruction

BackgroundLeft ventricular outflow tract obstruction (LVOTO) is commonly observed in patients with hypertrophic cardiomyopathy (HCM) or left ventricular hypertrophy (LVH). Some patients develop LVOTO provoked by physical exertion, and hence termed dynamic LVOTO (DLVOTO). However, its precise prevalence and mechanism are still unclear. AimTwo-dimensional speckle tracking echocardiography (2D STE) seems to be helpful for the detection of early LV structural abnormalities. This study aimed to examine the possible role of segmental as well as global longitudinal strain in identifying DLVOTO non-HCM patients as detected by dobutamine stress echocardiography (DSE). Methods and resultsTwo hundred and fifty patients without structural heart disease had undergone conventional transthoracic echocardiography, 2D STE, and DSE. All patients with non-ischemic evidence were divided into two groups according to the DSE results; DLVOTO (+) and DLVOTO (−).Among 250 patients, 50 patients (36%) had shown DLVOTO after DSE (15 males, 35 females; mean age 55±7years). They were compared with 90 non -LVOTO obstruction patients (43 males, 47 females; mean age 57±6years). Based on multivariate logistic regression analysis, the independent predictors of provoked DLVOTO during DSE were resting basal septal longitudinal strain BS-LS average (p < 0.001), resting LA reservoir strain (p < 0.001), and systolic LVOT diameter (p = 0.03). Resting BS-LS average with cut-off - 17.5% was recognized as a critical indicator of DLVOTO, with sensitivity 78%, and specificity 95% (better than systolic LVOT diameter of sensitivity 76%, and specificity 15% and resting LA reservoir strain which showed poor AUC at ROC curve 0.007). ConclusionWe demonstrate that provoked LVOTO during DSE in non HCM symptomatic patients is directly correlated to resting regional LS, where the increased BS-LS of ≥ −17.5% was a key determinant of LVOT gradient provocation. Assessment of baseline BS-LS average might be a bedside simple tool for detection of patients with DLVOTO not able to do DSE.

Primeval outcomes of thoracoscopic transmitral myectomy with anterior mitral leaflet extension for hypertrophic obstructive cardiomyopathy

The transaortic Morrow procedure is the current gold standard for hypertrophic obstructive cardiomyopathy (HOCM) patients who are resistant to maximum drug therapy. It is controversial whether concomitant mitral valve intervention is necessary. Only a few centers apply for concomitant anterior mitral leaflet extension with a bovine or autologous pericardial patch to further decrease systolic anterior motion. Our aim is to assess the primeval outcomes of thoracoscopic transmitral myectomy with anterior mitral leaflet extension (TTM-AMLE) in symptomatic HOCM patients. Between April 2019 and November 2020, 18 consecutive HOCM patients who underwent TTM-AMLE were enrolled in this study. Preoperative, postoperative, and follow-up outcomes were compared and statistically analyzed. The mean age was (50.17 ± 6.18) years and 10 (55.56%) were males. 18 (100%) patients had mitral regurgitation preoperatively, and they all successfully underwent TTM-AMLE with a median cardiopulmonary bypass and aortic cross-clamp time of 200.0 (150.8, 232.0), and 127.5 (116.0, 149.0) min, respectively. The median length of ICU stay was 2.7 (1.4, 5.2) days. The interventricular septum thickness was significantly reduced (from 18.03 ± 3.02 mm to 11.91 ± 1.66 mm, p < .001). There was no perioperative mortality, perforation of ventricular septum, or conversion to sternotomy observed. During a median follow-up of 18 months (IQR, 5-24 months), 1 (5.56%) patient had severe mitral regurgitation due to patch detachment and received reoperation. Moderate degree of mitral regurgitation and more than 50 mmHg in left ventricular outflow tract gradient were found in 2 (11.11%), and 1 (5.56%) patients, respectively. 1 (5.56%) patient who had second-degree atrioventricular block received permanent pacemaker implantation postoperatively. Overall, the maximum left ventricular outflow tract gradient (88.50 [59.50, 112.75] mmHg vs. 10.50 [7.00, 15.50] mmHg, p = .002), left ventricular outflow tract velocity (4.70 [3.86, 5.33] m/s vs. 1.60 [1.33, 1.95] m/s, p < .001) and the degree of mitral regurgitation (6.99 ± 4.47 cm2 vs. 2.22 ± 1.51 cm2 , p = .001) were significantly decreased, with a significant reduction in the proportion of systolic anterior motion (94.44% vs. 16.67%, p < .001). The TTM-AMLE is a safe and effective surgical approach for selected patients with HOCM. In our series, it provides excellent relief of left ventricular outflow tract obstruction, while significantly eliminating mitral regurgitation. The early outcomes of TTM-AMLE are satisfactory, but further studies and longer follow-ups are awaited.