Left Ventricular Outflow Research Articles

Abstract 13312: Can the Extent of Late Gadolinium Enhancement on Cardiac Magnetic Resonance Be Predicted by the 12-Lead Electrocardiogram?

Background: In hypertrophic cardiomyopathy (HCM), late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is an in vivo marker of replacement fibrosis with a continuous relationship between amount of LGE and both risk for sudden death and development of endstage disease. Cost and accessibility can limit routine utilization of CMR. In contrast, electrocardiogram (ECG) is an inexpensive readily available test and identifies patients with myocardial scarring in ischemic heart disease. Its ability to identify presence and extent of LGE in HCM is unknown. Methods: 1983 consecutive HCM patients were included; 62% male, average wall thickness 18 ± 3mm, and 36% with resting LV outflow tract obstruction ≥ 30mmHg. ECGs were analyzed for LV hypertrophy, T wave abnormalities, ST-segment depression or elevations, abnormal Q waves, conduction disease, atrial enlargement and QTc prolongation. Extent of LGE was quantified and expressed as a proportion of total LV myocardium. Results: 822 (41%) had no LGE, while 1161 (59%) had LGE, including 687 (35%) with <5%, 299 (15%) with 5-9%, 92 (5%) with 10-14%, and 83 (4%) with ≥ 15%. Compared to no LGE, Patients with LGE were more likely to have pathologic T wave inversions (55% vs. 36%, p<0.01), positive T waves in aVR (34% vs. 20%, p<0.01), and ST-depressions (29% vs. 21%, p<0.01), with no difference in LV hypertrophy, bundle branch block, pathologic Q waves, first degree AV block, QTc prolongation ≥ 480ms, or ST-elevations (p>0.05). Notably, as extent of LGE increased there was a corresponding progressive increase in the prevalence of both positive T waves in aVR (20% in no LGE to 42% in ≥ 15% LGE, p<0.01) and pathologic T wave inversions (36% in no LGE to 61% in ≥ 15% LGE, p<0.01) but with no incremental differences in ST depressions (p>0.05). In contrast, 43% of patients with LGE did not have either positive T waves in aVR or pathologic T wave inversions, including 34% with ≥ 15% LGE. Conclusion: Most ECG findings including pathologic Q waves have no relation to presence or extent of LGE. While positive T waves in aVR and pathologic T wave inversions are associated with LGE, they have limited sensitivity. These finding support that routinely evaluated ECG abnormalities do not predict presence or extent of scarring in HCM.

Abstract 11615: The Prevalence and Association of Exercise Test Abnormalities With Sudden Cardiac Death and Transplant-Free Survival in Childhood Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) can be associated with an abnormal exercise response. In adults with HCM, an abnormal exercise stress test (EST) is predictive of heart failure outcomes. Our goal was to determine if an abnormal exercise response is associated with adverse outcomes in pediatric HCM patients. Methods: : In an international cohort study with 20 centers (PRIMaCY), children <18 years with primary HCM were included. Abnormal EST was defined as an abnormal heart rate or blood pressure response, arrhythmias and/or ischemic ECG changes on exercise. Sudden cardiac death (SCD) events were defined as a composite of SCD and aborted SCD including appropriate implantable cardioverter defibrillator discharges. Using Kaplan-Meier survival analyses, we analyzed the association of abnormal EST with SCD and transplant-free survival. Results: Of 724 eligible patients, 604 underwent at least one EST on follow-up. There were no differences in clinical characteristics between those with or without an EST. The median age at EST was 13.8yrs (IQR 11.0-15.7yrs), 76% were male, 55% were on beta-blockers. 299 (49.5%) had an abnormal EST. Patients with an abnormal EST had more severe septal hypertrophy, higher left atrial diameter z-scores, higher resting LV outflow gradient at first evaluation, and a higher proportion were genotype-positive (p<0.05) compared to those with a normal EST. An abnormal EST was associated with lower 5-year transplant-free survival (99% vs. 95%, p=0.0082) and lower 5-year freedom from SCD events (96% vs. 92%, p=0.025) (Figure 1). Conclusions: Exercise abnormalities are common in childhood HCM. An abnormal EST in children with HCM was associated with lower transplant-free survival and more SCD events. Further analysis will determine if the inclusion of EST results can increase the predictive accuracy of current pediatric SCD risk prediction models.

The Role of Left Ventricular Ejection Fraction and Left Ventricular Outflow Tract Velocity-Time Integral in Assessing Cardiovascular Impairment in Septic Shock.

Background: the role of echocardiography in septic shock remains controversial, since depressed cardiac afterload may overestimate left ventricular (LV) systolic performance and mask septic cardiomyopathy (SC). We hypothesized that afterload-adjusted LV ejection fraction (LVEF) and LV outflow tract velocity-time integral (VTI) values for given systemic vascular resistances (SVR) could provide novel insights into recognizing and stratifying the severity of SC. Methods: in this observational, monocentric study, we prospectively included 14 mechanically-ventilated patients under septic-shock who all had a Pulse index Continuous Cardiac Output (PiCCO) system in place for hemodynamic monitoring. Echocardiographic and PiCCO longitudinal examinations (71 measurements overall) were performed simultaneously at the onset of septic shock and every 12 h for 60 h overall. Results: VTI-derived stroke volume (SV) and cardiac output (CO) were significantly correlated with PiCCO measurements (r ≥ 0.993, both p < 0.001). LVEF and VTI showed linear and exponential inverse correlation to SVR (R2 = 0.183 vs. 0.507 and p < 0.001 vs. p < 0.001, respectively). The equations LVEF = 86.168 − 0.011 × SVR and VTI = 41.23 × e(−0.0005×SVR) were found to provide “predicted” values for given SVR. Measured to predicted LVEF ratios (for given SVR), the afterload-adjusted LVEF defined the severity of SC (mild ≥ 90%, 80% ≤ moderate < 90% and severe < 80%). Mild SC demonstrated normal/supra-normal LVEF, normal VTI and SVR. Moderate SC showed lower LVEF and SVR, yet increased LV end-diastolic volume (LVEDV), VTI, SV and CO compared with mild SC (all p < 0.05). Severe SC was distinguished from moderate SC by markedly reduced LVEF, LVEDV, VTI, SV, CO and significantly increased SVR (all p < 0.05). LVEF and VTI decreased over time in mild SC, LVEF decreased in moderate SC, and LVEF and VTI increased over time in severe SC (p ≤ 0.038). LVEF and VTI demonstrated significant performance in identifying severe SC [cut-off < 61.5%, area under the curve (AUC) = 1 ± 0.0, sensitivity/specificity = 100/100, p < 0.001 vs. cut-off < 17.9 cm, AUC = 0.882 ± 0.042, sensitivity/specificity = 80/77, p < 0.001, respectively]. VTI but not LVEF demonstrated significant diagnostic performance in identifying both SVR < 800 dynes·s·cm−5 and SVR > 1500 dynes·s·cm−5 (cut-off > 24.46 cm, AUC = 0.889 ± 0.049, sensitivity/specificity = 75/100, p < 0.001; cut-off < 16.8, AUC = 0.0.857 ± 0.082, sensitivity/specificity = 83/86, p = 0.002, respectively).Conclusions: our study suggests that ICU bedside echocardiographic assessment of LVEF, VTI and their adjusted to corresponding SVR values provides valuable insights for the comprehension of SC phenotypes, underlying vasoplegia and cardiac output fluctuations in septic shock.

Evidence of Advanced Pulmonary Vascular Remodeling in Obstructive Hypertrophic Cardiomyopathy With Pulmonary Hypertension

Elevated mean pulmonary artery pressure (mPAP) is common in patients with hypertrophic cardiomyopathy (HCM) and heart failure symptoms. However, dynamic left ventricular (LV) outflow tract obstruction may confound interpretation of pulmonary hypertension (PH) pathophysiologic features in HCM when relying on resting invasive hemodynamic data alone. Do structural changes to the lung vasculature clarify PH pathophysiologic features in patients with HCM with progressive heart failure? Clinical data and ultrarare lung autopsy specimens were acquired retrospectively from the National Institutes of Health (1975-1992). Patients were included based on the availability of lung tissue and recorded mPAP. Discarded tissue from rejected lung donors served as control specimens. Histomorphology was performed on pulmonary arterioles and veins. Comparisons were calculated using the Student t test and Mann-Whitney U test; Pearson correlation was used to assess association between morphometric measurements and HCM cardiac and hemodynamic measurements. The HCM cohort (n= 7; mean ± SD age, 43 ± 18 years; 71%men) showed maximum mean ± SD LV wall thickness of 25 ± 2.8mm, mean ± SD outflow tract gradient of 90 ± 30mmHg, median mPAP of 25mmHg (interquartile range [IQR], 6mmHg), median pulmonary artery wedge pressure (PAWP) of 16mmHg (IQR, 4mmHg), and median pulmonary vascular resistance of 1.8 Wood units (WU; IQR, 2.4 WU). Compared with control samples (n= 5), patients with HCM showed greater indexed pulmonary arterial hypertrophy (20.7 ± 7.2%vs49.7 ± 12%; P< .001) and arterial wall fibrosis (11.5 ± 3.4mm vs21.0 ± 4.7mm; P< .0001), which correlated with mPAP (r= 0.84; P= .018), PAWP (r= 0.74; P= .05), and LV outflow tract gradient (r= 0.78; P= .035). Compared with control samples, pulmonary vein thickness was increased by 2.9-fold (P= .008) in the HCM group, which correlated with mPAP (r= 0.81; P= .03) and LV outflow tract gradient (r= 0.83; P= .02). To the best of our knowledge, these data demonstrate for the first time that in patients with obstructive HCM, heart failure is associated with pathogenic pulmonary vascular remodeling even when mPAP is elevated only mildly. These observations clarify PH pathophysiologic features in HCM, with future implications for clinical strategies that mitigate outflow tract obstruction.

Machine learning evaluation of LV outflow obstruction in hypertrophic cardiomyopathy using three-chamber cardiovascular magnetic resonance

Left ventricular outflow tract obstruction (LVOTO) is common in hypertrophic cardiomyopathy (HCM), but relationships between anatomical metrics and obstruction are poorly understood. We aimed to develop machine learning methods to evaluate LVOTO in HCM patients and quantify relationships between anatomical metrics and obstruction. This retrospective analysis of 1905 participants of the HCM Registry quantified 11 anatomical metrics derived from 14 landmarks automatically detected on the three-chamber long axis cine CMR images. Linear and logistic regression was used to quantify strengths of relationships with the presence of LVOTO (defined by resting Doppler pressure drop of > 30 mmHg), using the area under the receiver operating characteristic (AUC). Intraclass correlation coefficients between the network predictions and three independent observers showed similar agreement to that between observers. The distance from anterior mitral valve leaflet tip to basal septum (AML-BS) was most highly correlated with Doppler pressure drop (R2 = 0.19, p < 10–5). Multivariate stepwise regression found the best predictive model included AML-BS, AML length to aortic valve diameter ratio, AML length to LV width ratio, and midventricular septal thickness metrics (AUC 0.84). Excluding AML-BS, metrics grouped according to septal hypertrophy, LV geometry, and AML anatomy each had similar associations with LVOTO (AUC 0.71, 0.71, 0.68 respectively, p = ns), significantly less than their combination (AUC 0.77, p < 0.05 for each). Anatomical metrics derived from a standard three-chamber CMR cine acquisition can be used to highlight risk of LVOTO, and suggest further investigation if necessary. A combination of geometric factors is required to provide the best risk prediction.

The mitral to aortic/pulmonary velocity-time integral ratio is a simple, feasible and accurate discriminator for echocardiographic evaluation of severe isolated mitral regurgitation

Abstract Background Echocardiographic quantification of mitral regurgitation (MR) remains challenging, requiring dedicated image acquisition, and is limited by potential error from geometric assumptions of annular dimensions. Volume is a product of area and flow and assuming proportional mitral/aortic areas, an increased mitral-inflow volume compared to LV/RV-outflow semi-quantitatively represents greater MR regurgitant volume. Therefore, we investigated the feasibility and diagnostic performance of the mitral-aortic velocity-time integral (VTI) ratio in isolated MR. We also investigated the use of the mitral-pulmonary VTI ratio as an alternative in clinical situations where the LV outflow tract (LVOT) VTI could not be used. Methods We reviewed 166 consecutive patients (54 (33% severe MR by multi-parameter integrated expert opinion)). Pulsed-Doppler VTI at the mitral leaflet tips and the left ventricular outflow and continuous-wave Doppler of the right ventricular outflow tract were measured individually and independently by blinded readers (expert and trainee status) to derive the ratio. Receiver operator characteristic area under the curve (AUC) comparison was calculated and compared with effective regurgitant orifice area (EROA &amp;gt;40 mm), regurgitant volume (RVol &amp;gt;6 0mL), vena contracta (VC &amp;gt;0.7 cm), E-velocity &amp;gt;1.2 cm, systolic flow reversal (SFR), left atrial and ventricular dilatation. Results Increasing ratio was associated with severe MR (AUC 0.94) with optimal threshold defined at 1.3. This provided significant discrimination for severe MR (AUC 0.81) compared to EROA (0.68), VC (0.52), LV dilatation (0.69), LA dilatation (0.70), SFR (0.73), E-velocity (0.68) all p&amp;lt;0.05, with sensitivity 82% and specificity 94%. The mitral-pulmonary VTI ratio demonstrated similar discrimination (AUC 0.92) with optimal threshold defined at 1.14. Excellent inter-observer reproducibility (intra-class correlation 0.97) was seen between trainee and expert readers. There was no difference in AUC comparison by MR mechanism or patient rhythm. Conclusions The mitral-aortic or mitral-pulmonary VTI ratio is a simple, geometric-free parameter feasibly reproducible from routine echocardiographic datasets and is an excellent discriminative tool for severe MR. Readers should consider integration of this parameter in routine reporting. Funding Acknowledgement Type of funding sources: None.

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&amp;lt;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&amp;lt;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.

Mitral valve abnormalities in decedents of sudden cardiac death due to hypertrophic cardiomyopathy and idiopathic left ventricular hypertrophy

Abstract Background The sole identification of left ventricular hypertrophy (LVH) in a young individual that died suddenly may often lead to an erroneous diagnosis of hypertrophic cardiomyopathy (HCM). Emerging data suggests that idiopathic LVH (ILVH) and HCM may be separate entities. Aim We aimed to report on the prevalence and nature of mitral valve (MV) abnormalities, in a cohort of sudden cardiac death (SCD) victims with a post-mortem examination consistent with HCM and ILVH. Methods We reviewed 6860 consecutive cases of SCD referred to our specialist cardiac pathology centre between 1994 and 2020. SCD was defined as death from a cardiovascular cause within 12 hours of apparent well-being. HCM was defined by the presence of LVH, in the absence of abnormal loading conditions and characterised by myocyte disarray at histology. ILVH was defined as unexplained LVH (heart weight &amp;gt;500 g in males and &amp;gt;400 g in females) and left ventricular (LV) wall thickness &amp;gt;15mm, in the absence of myocardial disarray or secondary causes of LVH. The MV was examined for patency, circumference, thickening, nodularity, ballooning, bulging between cords, perforation, and the presence of impact lesions in the LV outflow tract (LVOT) and aortic outlet. Results Of the total cases of SCD, 264 (4%) were due to HCM (mean age 41±18 years, 78% males, LV maximal wall thickness 19±6 mm) (Figure 1). Ante-mortem symptoms were reported in 44 (17%) cases and for the majority (n=217, 82%) HCM was established at post-mortem. Death was attributed to ILVH in 253 (3%) cases (mean age 43±16 years, 80% males, LV maximal wall thickness 18±4 mm). MV abnormalities were found in 58 (22%) decedents with HCM (mean age 38±17 years; 72% males) and in 13 (5%) decedents with ILVH (mean age 55±15 years; 77% male), p&amp;lt;0.001. Amongst the 58 (22%) cases with HCM and MV abnormalities, 15 (6%) cases had multiple MV abnormalities. These included impact lesions associated with thickening of the anterior leaflet of the MV (n=39) and degenerative changes (n=34) such as bulging and ballooning; and thickening and nodularity. Decedents with HCM exhibiting MV abnormalities were younger than decedents with a normal MV (38±17 versus 45±19 years; p=0.08). Among the 253 decedents with ILVH, 13 (5%) cases exhibited MV abnormalities, which largely included degenerative changes (n=12). Among decedents with HCM and ILVH exhibiting MV abnormalities, the former was significantly younger (38±17 versus 55±15; p=0.001). Myocardial fibrosis was observed in 162 (61%) cases of HCM and 99 (39%) cases of ILVH, p&amp;lt;0.001. Conclusions MV abnormalities are over four-fold more common in individuals with HCM than those with ILVH and may be considered as additional macroscopic features to differentiate between these two entities. Furthermore, the inherent descriptive terminologies used when assessing the MV, support a greater emphasis on the standardisation and quantification of MV abnormalities as part of the autopsy in victims of SCD. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Acknowledgements: We thank the charitable organisation, Cardiac Risk in the Young (CRY) who fund and support the CRY Cardiovascular Pathology Unit and CRY database.

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 &amp;lt;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&amp;lt;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&amp;lt;0.001). Moreover, impaired global constructive work (GCW) (r=−0.519, β-estimate −0.021, 95% CI −0.030 to −0.013, p&amp;lt;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&amp;lt;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&amp;lt;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 &amp;lt;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 &amp;lt;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.

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) &amp;gt;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 &amp;gt;7.5 mm Hg/ml was present in 86 patients (21%), more frequently in women (58 vs 27%, p&amp;lt;0.0001), more often in patients with diabetes (16 vs 6%, p=0.003), beta-blocker (81 vs 58%, p&amp;lt;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, &amp;lt;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%, &amp;lt;0.0001), mitral regurgitation grade (1.2±0.7 vs 0.7±0.7, p&amp;lt;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&amp;lt;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 &amp;gt;50%, LV maximal wall thickness &amp;gt;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&amp;lt;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.

Prognosis of hypertrophic cardiomyopathy in Japanese patients with an implantable cardioverter defibrillator -focus on apical hypertrophic cardiomyopathy

Abstract Background Patients with hypertrophic cardiomyopathy (HCM) are at high risk of lethal arrhythmias, and implantable cardioverter defibrillators (ICD) are widely used for prevention of sudden cardiac death (SCD). Apical HCM is a phenotype variant of HCM, with hypertrophy predominantly affecting apex, that was initially described 30 years ago. Apical HCM patients may have different clinical prognosis compared with other subsets of HCM. In previous studies, apical HCM patients seem to have a more benign prognosis than other types of HCM. However, little is known about the long-term outcomes of apical HCM patients and there are many unclear points. Moreover, there are few reports about the clinical prognosis in apical HCM patients with an ICD. Objective The aim of this study is to identify the difference between the prognosis of apical and the other types of HCM patients with an ICD. Methods We retrospectively analyzed the database of our ICD clinic. All subjects underwent ICD implantation between October 2006 and September 2018. We classified HCM patients into LV outflow tract obstruction (LVOTO) and midventricular obstruction (MVO), apical HCM and other non-obstructive types. We divided all the patients into apical and other types of HCM, and examined their background, incidence of appropriate ICD therapies, hospitalization for heart failure, electrical storm and death. Results A total of consecutive 64 Japanese HCM patients with an ICD (follow-up period, 86±24 months; age, 65±14 years; male sex, 83%; left ventricular ejection fraction, 56±14%; LV max wall-thickness, 19±7mm; LV apical aneurysm, 9.4%; 5-year risk of SCD, 4.4±2.1) were enrolled in this study. We classified them into 14 apical HCM and 50 other types of HCM patients. The clinical characteristics and major clinical events of these patients are shown in the Table 1. During the follow-up periods, there were no significant differences in the incidence of electrical storm, hospitalization for heart failure and death between the 2 groups (p=0.11; p=0.60; p=0.39). Appropriate ICD therapies occurred in 6 of 14 (43%) patients with apical HCM and 5 of 50 (10%) patients with other types of HCM (p=0.010). The risk factors of patients with apical HCM patients are shown in Table 2. Conclusions Appropriate ICD therapy was more prevalent in patients with apical HCM, compared to patients with other types of HCM. Aggressive intervention such as catheter ablation for ventricular tachycardia and ventricular fibrillation may be considered in patients with apical HCM and higher score of 5-year risk of SCD. Further studies are needed to clarify the manifestations and long-term outcome of apical HCM patients. Funding Acknowledgement Type of funding sources: None.

Mitral valve abnormalities in decedents of sudden cardiac death due to hypertrophic cardiomyopathy and idiopathic left ventricular hypertrophy.

Mitral valve abnormalities in decedents of sudden cardiac death due to hypertrophic cardiomyopathy and idiopathic left ventricular hypertrophy.

A novel echocardiographic estimate of pulmonary vascular resistance employing the hydraulic analogy to Ohm's law.

Assessment of pulmonary vascular resistance (PVR) is critical for accurate diagnosis and optimal pharmacotherapy in pulmonary hypertension. We aimed to test the diagnostic performance of a novel, Doppler-based method to evaluate PVR based on Ohm's law (PVRecho) using pragmatic estimates of pulmonary capillary wedge pressure (PCWP). Simultaneous right heart catheterization (RHC) and echocardiography was performed in a derivation cohort of 111 patients in sinus rhythm referred for PH evaluation and PVRecho independently validated in 238 patients. PVRecho was calculated using pulmonary artery mean pressure estimates (PAMPecho) obtained from peak tricuspid gradient employing a fixed right atrial pressure estimate, PCWPecho was estimated as 10 or 20mmHg using age-related mitral E/A cut-offs and cardiac output from left ventricular outflow. In the derivation cohort, both PAMPecho and PCWPecho estimates demonstrated excellent agreement with catheterization measurements. PVRecho was highly feasible, demonstrated negligible bias and excellent agreement with PVRRHC (Bias=-0.58, SD 2.2mmHg) and outperformed the Abbas method to identify PVRRHC>3WU (AUC=0.85 vs. 0.70; p=0.02). In the validation cohort, PVRecho preserved good invasive agreement with negligible bias, displayed strong diagnostic performance (AUC=0.84) and significant ability to distinguish isolated post-capillary from combined post- and pre-capillary pulmonary hypertension (PH) subgroups (AUC=0.77). PVRecho based on Ohm's law employing pragmatic estimates of PCWPecho demonstrates excellent agreement with invasive reference standard measurements and strong diagnostic ability to identify elevated PVRRHC. This novel approach may be useful during therapy selection to distinguish PH hemodynamic subgroups.

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

Initial experience of novel over the wire type decapolar catheter for ventricular arrhythmias originating from left ventricular summit.

Previously, direct monitoring of local activation at the communicating vein (CV) has been reported to be useful for the ablation of ventricular arrhythmias (VAs) originating from the left ventricular (LV) summit. In this study, we evaluated the performance of the novel over-the-wire (OTW)-type decapolar catheter for VAs originating from the LV summit. Overall, 17 patients who underwent catheter ablation for idiopathic VAs originating from the LV summit were included in this study. Of these, seven patients underwent mapping of the epicardial LV outflow tract with the novel 2.7 Fr OTW-type decapolar catheter (EPstar FIX AIV), and ten underwent mapping with the standard 2.0 Fr octopolar catheter (EPstar FIX 2F) procedure (AIV group = EPstar FIX AIV and control group = EPstar FIX 2F). No significant differences in the baseline characteristics were observed between the two groups. In the AIV group, all patients achieved successful catheter positioning in the target CV, whereas in the control group, two patients failed to achieve the same. The novel catheter not only advanced to the target vessels using a 0.014-in guidewire but it was also used for contrast injection from the catheter lumen, which enabled accurate and safe positioning. As a result, the earliest activation time preceding QRS onset during the VA, recorded at the CV, was significantly earlier when compared with the control group (44.66 ± 11.23ms vs. 32.16 ± 4.26ms, P = 0.007). Compared with the conventional electrode catheter, this novel multipolar electrode catheter is more effective for mapping local activation at the CV.

Giant Cardiac Rhabdomyoma with Mixed Atrial Tachycardia and Nonsustained Ventricular Tachycardia in a Newborn with Tuberous Sclerosis

Cardiac rhabdomyomas are typically presented in the tuberous sclerosis. Although benign and often associated with spontaneous regression, in rare circumstances huge mass size and critical location can lead to heart failure, ventricular outflow tract obstruction and refractory tachyarrhythmias. An 1-day-old girl was diagnosed as cardiac tumor during perinatal period. At birth, transthoracic echocardiography revealed huge cardiac mass located in septal area of both ventricle measuring 34×30 mm. It protruded into the left ventricular (LV) outflow tract, potentially obstructing it. A surface ECG revealed atrial tachycardia with nonsustained ventricular tachycardia with heart rate of 217 beats per min. The tachyarrhythmias were controlled with intravenous amiodarone. Reduction of the giant cardiac mass was treated with mammalian target of rapamycin pathway inhibitor sirolimus. However, she unfortunately died at 10 days-old because of sudden cardiac arrest maybe due to LV outflow tract obstruction during therapy. Gene analysis revealed TSC2 mutation after death. (Ewha Med J 2022;45(3):e5)

Sex-related differences in left ventricular remodeling and outcome after alcohol septal ablation in hypertrophic obstructive cardiomyopathy: insights from cardiovascular magnetic resonance imaging

BackgroundAlcohol septal ablation (ASA) has been proven to reverse left ventricular (LV) remodeling in hypertrophic cardiomyopathy (HCM). However, there are no studies on the effect of sex on LV remodeling after ASA. We aimed to investigate whether sex differences affect the process of LV remodeling and outcome after ASA.MethodsA total of 107 patients with obstructive HCM (54 men and 53 women, mean age 51 ± 8 years) were recruited. Cardiovascular magnetic resonance (CMR) was performed at baseline and 16 months after ASA. The extent of late gadolinium enhancement (LGE) was measured.ResultsWomen had a higher indexed LV mass and smaller indexed LV end-systolic volumes than men at the time of ASA. After ASA, both men and women exhibited a regression of LV mass, and the percentage of mass regression was greater in men than women (15.3% ± 4.3% vs. 10.7% ± 1.8%, p < 0.001). In multivariable analysis, male sex, higher reduction of LV outflow tract (LVOT) gradient and lower baseline LV mass index were independently associated with greater LV mass regression after ASA. Kaplan–Meier analysis showed significantly higher cardiovascular events in women than in men (p = 0.015). Female sex [hazard ratio (HR) 3.913, p = 0.038] and LV mass preablation (HR, 1.019, p = 0.010) were independent predictors of cardiovascular outcomes.ConclusionsMales with HCM had favorable reverse remodeling with greater LV mass regression post-ASA than female patients. This favorable LV reverse remodeling might provide a mechanistic explanation for the survival advantage in men.

Regional left ventricular endocardial strains estimated from low-dose 4DCT: Comparison with cardiac magnetic resonance feature tracking.

Estimates of regional left ventricular (LV) strains provide additional information to global function parameters such as ejection fraction (EF) and global longitudinal strain (GLS) and are more sensitive in detecting abnormal regional cardiac function. The accurate and reproducible assessment of regional cardiac function has implications in the management of various cardiac diseases such as heart failure, myocardial ischemia, and dyssynchrony. To develop a method that yields highly reproducible, high-resolution estimates of regional endocardial strains from 4DCT images. A method for estimating regional LV endocardial circumferential and longitudinal ( ) strains from 4DCT was developed. Point clouds representing the LV endocardial surface were extracted for each time frame of the cardiac cycle from 4DCT images. 3D deformation fields across the cardiac cycle were obtained by registering the end diastolic point cloud to each subsequent point cloud in time across the cardiac cycle using a 3D point-set registration technique. From these deformation fields, were estimated over the entire LV endocardial surface by fitting an affine transformation with maximum likelihood estimation. The 4DCT-derived strains were compared with strains estimated in the same subjects by cardiac magnetic resonance (CMR); twenty-four subjects had CMR scans followed by 4DCT scans acquired within a few hours. Regional LV circumferential and longitudinal strains were estimated from the CMR images using a commercially available feature tracking software (cvi42). Global circumferential strain (GCS) and global longitudinal strain (GLS) were calculated as the mean of the regional strains across the entire LV for both modalities. Pearson correlation coefficients and Bland-Altman analyses were used for comparisons. Intraclass correlation coefficients (ICC) were used to assess the inter- and intraobserver reproducibility of the 4DCT-derived strains. The 4DCT-derived regional strains correlated well with the CMR-derived regional strains ( : r=0.76, p<0.001; : r=0.64, p<0.001). A very strong correlation was found between 4DCT-derived GCS and 4DCT-derived EF (r=-0.96; p<0.001). The 4DCT-derived strains were also highly reproducible, with very low inter- and intraobserver variability (intraclass correlation coefficients in the range of [0.92, 0.99]). We have developed a novel method to estimate high-resolution regional LV endocardial circumferential and longitudinal strains from 4DCT images. Except for the definition of the mitral valve and LV outflow tract planes, the method is completely user independent, thus yielding highly reproducible estimates of endocardial strain. The 4DCT-derived strains correlated well with those estimated using a commercial CMR feature tracking software. The promising results reported in this study highlight the potential utility of 4DCT in the precise assessment of regional cardiac function for the management of cardiac disease.

Sensitivity of ventricular systolic function to afterload during veno-arterial extracorporeal membrane oxygenation.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) increases afterload to the injured heart and may hinder myocardial recovery. We aimed to compare the sensitivity of left ventricular (LV) systolic function to the afterload effects of peripheral V-A ECMO during the acute and delayed stages of acute myocardial dysfunction. A total of 46 adult patients who were supported by peripheral V-A ECMO between April 2019 and June 2021 were analysed. Serial cardiac performance parameters were measured by transthoracic echocardiography (TTE) on mean day 1±1 of V-A ECMO initiation (n=45, 'acute phase') and mean day 4±2 of V-A ECMO initiation (n=36, 'delayed phase'). Measurements were obtained at 100%, 120%, and 50% of ECMO target blood flow (TBF). LV global longitudinal strain (GLS) significantly improved from -6.1 (-8.9 to -4.0)% during 120% TBF to -8.8 (-11.5 to -6.0)% during 50% TBF (P<0.001). The sensitivity of LV GLS to changes in ECMO flow was significantly greater in the acute phase of myocardial injury compared with the delayed phase [median (IQR) percentage change: 72.7 (26.8-100.0)% vs. 22.5 (14.9-43.8)%, P<0.001]. Findings from other echocardiographic parameters including LV ejection fraction [43.0 (29.1-56.8)% vs. 22.8 (9.2-42.2)%, P=0.012] and LV outflow tract velocity-time integral [45.8 (18.6-58.7)% vs. 24.2 (12.6-34.0)%, P=0.001] were similar. A total of 24 (52.2%) patients were weaned off ECMO successfully. We demonstrated that LV systolic function was significantly more sensitive to the afterload effects of V-A ECMO during the acute stage of myocardial dysfunction compared with the delayed phase. Understanding the evolution of the heart-ECMO interaction over the course of acute myocardial dysfunction informs the clinical utility of echocardiographic assessment in patients on V-A ECMO.