Left Ventricular Outflow Research Articles

Abstract 16702: Myocardial Deformation Analysis in Hypertrophic Cardiomyopathy With Sarcomere Mutations: Insights From 2,221 Patients Within the NHLBI-HCM Registry

Introduction: Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere genes that alter myocardial contractility and relaxation. Three-dimensional myocardial deformation analysis (3D-MDA) may elucidate left ventricular (LV) abnormalities associated with sarcomere genotype status. Hypothesis: We hypothesize that HCM patients with sarcomere mutations have changes in myocardial contractility profiles that are associated with adverse LV architectural changes. Methods: 3D-MDA was measured using validated feature-tracking software applied to 2D cine cardiac MRI studies in 2,221 genotyped patients within the NHLBI HCM Registry. Results: Baseline, cardiac MRI, and 3D MDA-derived strain characteristics stratified by sarcomere status are shown in Table 1. Sarcomere positive patients were younger, had less LV outflow tract obstruction and lower indexed LV mass, but similar LVEF and trend towards higher serum NT-proBNP levels. Maximal wall thickness, measures of diffuse myocardial fibrosis (native T1, extracellular volume fraction) were elevated with corresponding reduction in global radial strain. Global minimum principal and epicardial layer conventional strain values were higher in sarcomere positive patients. Epicardial minimum principal strain was highly correlated with indexed LV mass (r=0.42, P<0.0001), maximal wall thickness (r=0.29, P<0.0001), LVEF (r=-0.33, P<0.0001), late gadolinium enhancement (r=0.22, P<0.0001) and NT-proBNP (r=0.21, P<0.0001) levels in those with sarcomere mutations. Conclusions: Sarcomere positive HCM patients had differences in myocardial deformation strain profiles that were correlated to LV architectural changes and NT-proBNP levels despite lower indexed LV mass. More sensitive measures of contractile dysfunction may help elucidate pathophysiological mechanisms by which sarcomere mutations cause disease progression and adverse clinical outcomes in HCM.

Abstract 15324: Mavacamten Favorably Impacts Key Pathophysiologic Processes in Obstructive Hypertrophic Cardiomyopathy: Results From the EXPLORER-HCM Study

Introduction: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by dynamic LV outflow tract (LVOT) obstruction resulting from ventricular hypertrophy and mitral valve systolic anterior motion (SAM), and by elevated left ventricular (LV) filling pressures, all of which result in a significant morbidity despite medical therapy. Mavacamten (Mava) is a novel inhibitor of cardiac myosin that significantly reduces LVOT gradients in oHCM, noted initially in the phase 2 PIONEER and more recently in the phase 3 EXPLORER-HCM studies. Additional echocardiographic analyses were performed to investigate the effect of Mava on focused measures of cardiac structure and function in oHCM. Methods: EXPLORER-HCM (NCT03470545) was a multicenter, double-blind, placebo-controlled, phase 3 study that randomized symptomatic oHCM patients (LV ejection fraction ≥55% and resting and/or provoked LVOT gradient ≥50 mmHg) 1:1 to Mava vs placebo for 30 weeks. Echocardiograms were performed serially every 2-4 weeks over 30 weeks. Results: In total, 251 patients with oHCM were enrolled and 244 patients completed the study (mean age 58.5; 40.6% female). Compared to placebo, 30-week treatment with Mava led to significant reductions in LA volume index (-7.5 ml/m 2 , p<0.0001), lateral E/e’ (-3.8, p<0.0001), septal E/e’ (-3.4, p<0.0001), and LV mass index (-15.5 g/m 2 , p<0.0001) ( Table ). Significantly more Mava-treated patients achieved resolution of mitral valve SAM compared to placebo (80.9% vs 34.0% of patients; difference of 46.8%; p<0.0001) and mitral regurgitation (MR) (9.0% vs 0.0% of patients; difference of 9.0%; p=0.0006). Conclusions: Treatment with Mava for 30 weeks led to improvement in LV hypertrophy and markers of left-sided filling pressures (LA volume and E/e’). Furthermore, Mava treatment was associated with reduction of SAM and MR. These findings suggest that Mava has beneficial effects on several adverse pathophysiologic processes that are hallmarks of oHCM.

Abstract 13481: South Asian-specific MYBPC3 25bp Intronic Deletion Carriers Demonstrate Hypercontractility and Impaired Diastolic Function Under Exercise Stress

Introduction: A 25bp intronic deletion in MYBPC3 ( Δ25bp ), present in 6% of US South Asians, is a risk allele for late onset left ventricular (LV) dysfunction and hypertrophy. Hypothesis: Asymptomatic Δ25bp carriers have detectable subclinical pathology to development of LV hypercontractility and impaired relaxation. Methods: To evaluate Δ25bp carriers for changes in cardiac function with bicycle exercise stress echocardiography and continuous cardiac monitoring, 16 Δ25bp male carriers (51±2 years) and 10 age- and sex-matched non-carrier (NCs) controls (50±3 years) participated in this pilot study. Of 16 Δ25bp carriers, six carried an additional pathogenic variant D389V in MYBPC3 . Included subjects had no uncontrolled comorbidities. Regression analysis and two-way ANOVA were performed, and 95% confidence interval (CI) and p values were reported. Results: Baseline echocardiographic parameters as well as baseline and monitored exercise heart rate and blood pressure were similar in both groups. The estimated effect of exercise stress and genotype showed that Δ25bp carriers had significantly higher ejection fraction (%) (CI: 4.03±1.64; p<0.0001) and higher LV outflow tract peak velocity (m/s) (CI: 0.15±0.06; p<0.0001) in comparison to NCs. Additionally, stress-induced LV end diastolic diameter did not increase in Δ25bp carriers as compared to NCs with a significant difference between the groups (CI: 0.22±0.11; p=0.0002). E/A ratio, a marker of diastolic function, significantly decreased with exercise in Δ25bp carriers (slope: -0.002; p=0.005) but showed non-significant change in the NCs (slope: -0.0006; p=0.428). Right ventricular systolic excursion velocity s' (m/s) as a marker of right ventricle function increased similarly in both groups, although tricuspid annular plane systolic excursion (cm) increased more dramatically in carriers (slope: 0.004; p=0.0002). Sub-analysis of Δ25bp vs Δ25bp + D389V did not reveal any differences. Conclusions: LV hypercontractility under exercise stress conditions with evidence of diastolic impairment at high workloads is evident among asymptomatic carriers of MYBPC3 Δ25bp allele, suggesting MYBPC3 Δ25bp as a risk allele with sub-clinical pathology prior to late onset LV dysfunction in South Asians .

Abstract 13429: Echocardiographic Predictors of Mitral Transvalvular Gradients After Mitraclip Insertion

Introduction: The MitraClip procedure is a non-surgical alternative for patients with severe mitral regurgitation and high surgical risk. However, the MitraClip may lead to a reduction in the mitral valve orifice area (MVOA) and elevated transmitral mean gradients (TMG). The objectives of this study are to assess the value of baseline MVOA by different imaging methods and explore the value of MVOA indexed for left ventricular (LV) forward stroke volume (SV) to predict postprocedural TMG. Methods: Preprocedural echo images were retrospectively reviewed in 76 consecutive patients. MVOA from 2D transthoracic (MVOA TTE ), 2D transgastric (MVOA TG ) and 3D transesophageal (MVOA 3D ) echocardiography were measured and then indexed by the SV measured by Doppler in the LV outflow tract (MVOA/SV) . Postprocedural TMG was measured at one month and survival rate at one year. Results: Patients with postprocedural TMG >5 mmHg (18/76, 24%) had significantly smaller preprocedural MVOA 3D (3.9±0.9 vs 5.2±1.3 cm 2 , p<0.01) and MVOA TTE (4.9±1.1 vs 5.9±1.5 cm 2 , p=0.02). No significant difference was found for MVOA TG (5.5±1.4 vs 5.9±1.4 cm 2 , p=0.2). Best threshold values for MVOA 3D and MVOA TTE to predict postprocedural TMG >5 mmHg were respectively 3.9 cm 2 (AUC=0.80, IC95%: 0.67-0.94, p<0.01; sensitivity (Se) 62%, specificity (Sp) 87%) and 4,6 cm 2 (AUC=0.69, IC95%: 0.54-0.83, p=0.02; Se 50%, Sp 84%). MVOA/SV from each echocardiographic modality were smaller in patients with postprocedural TMG >5 mmHg (3D: 80 [62-95] vs 113 [99-129] cm 2 /L; TTE: 92 [81-105] vs 130 [100-166] cm 2 /L; TG: 104 [83-123] vs 135 [104-166] cm 2 /L; p<0.01 for all). MVOA/SV 3D was overall the best predictor of postprocedural TMG >5 mmHg, with an optimal threshold of 96 cm 2 /L (AUC=0.86, IC95%: 0.76-0.97, p<0.001; Se 84%, Sp 81%). Patients with MVOA 3D <3.9 cm 2 and MVOA/SV 3D <96 cm 2 /L tend to be at higher risk for mortality at one-year follow-up (69% vs 84%, p=0.14 and 67% vs 87%, p=0.11 respectively). Conclusion: Unlike preprocedural MVOAs assessed by 3D echocardiography, preprocedural MVOAs measured by 2D echocardiographic modalities were poor predictors of high TMG after MitraClip. Preprocedural MVOA 3D <3.9 cm 2 and MVOA/SV 3D <96 cm 2 /L were found to be the best cut-off values to predict postprocedural TMG >5 mmHg.

Systematic cutting of selected secondary mitral valve chordae, in association with a shallow myectomy, in obstructive hypertrophic cardiomyopathy:impact on mitral valve function and patient management

Abstract Introduction Few centers worldwide have large experience with performing an extended septal myectomy in patients with obstructive hypertrophic cardiomyopathy (HCM). Therefore, many HCM patients eligible for surgical relief of left ventricular (LV) outflow gradient do not have access to treatment. In a previous study, cutting fibrotic anterior mitral leaflet secondary chordae, in association with only a shallow myectomy, proved highly effective in moving the mitral valve (MV) apparatus away from the LV outflow tract and relieving the outflow gradient in our HCM patients with mild hypertrophy (<19 mm), a surgical approach that simplifies the operation. Purpose To assess whether chordal cutting is equally effective in improving MV geometry and relieving LV outflow gradient and heart failure symptoms in HCM patients with more marked hypertrophy. Methods Surgical outcome and MV geometry and function were assessed in 226 consecutive HCM patients who underwent systematic cutting of fibrotic anterior mitral leaflet secondary chordae, in association with a shallow myectomy and independently of magnitude of septal thickness, at our center from January 2015 to December 2018. Results Of 226 study patients, 1 (0.4%) died perioperatively. None had iatrogenic septal defect. Postoperatively, LV outflow gradient at rest decreased from 70±36 to 10±2 mmHg (P<0.001). In the 77 patients in whom data on the outflow gradient provoked with physiologic maneuvers after surgery were available, the provocable gradient was 16±10 mmHg. NYHA functional class improved significantly (P<0.001), with the number of patients in class III-IV decreasing from 178 (79%) to 2 (0.9%). No patient had residual severe MV regurgitation and only 4 (1.7%) had moderate-to-severe regurgitation. Quality of the echocardiogram allowed assessment of MV geometry in 212 (94%) patients. In the 62 patients with mild hypertrophy, anterior leaflet-annulus ratio increased 27% postoperatively, from 0.43+0.06 to 0.55+0.06 and MV tenting area decreased 34% from 2.9+0.6 to 1.9+0.4 cm2 (P<0.001), indicating repositioning of MV coaptation away from the outflow tract (with increased outflow tract dimension). Similarly, in 150 patients with marked hypertrophy, anterior leaflet-annulus ratio increased 27% from 0.43+0.05 to 0.55+0.06 and tenting area decreased 28% from 2.9+0.6 to 2.1+0.4 cm2 (P<0.001). Conclusions Our results show that cutting fibrotic anterior mitral leaflet secondary chordae, by moving the MV apparatus away from the LV outflow tract and independently of the magnitude of septal hypertrophy, contributes to improve the results of septal myectomy and reduces the need for a deep septal excision (and associated risk of iatrogenic septal defect) in patients with obstructive HCM. Therefore, chordal cutting could make the myectomy operation more accessible to surgeons, increasing the availability of surgical treatment for HCM patients eligible for invasive abolition of LV outflow obstruction. Funding Acknowledgement Type of funding source: None

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

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

High sensitivity troponin I in hypertrophic cardiomyopathy

Abstract Background ESC guidelines recommend measurement of troponin T in patients with hypertrophic cardiomyopathy (HCM) because high concentrations are associated with cardiovascular events, heart failure and death. The cardiac Troponin I subunit is not expressed in skeletal muscle making it a cardio-specific isoform. The use of troponin biomarkers in management of patients HCM is limited because concentrations only weakly correlate with clinical parameters. Most studies are small, and few have examined their relation with genotype and mortality. Purpose To assess the relationship between high-sensitive troponin I (hsTnI) and characteristics of adults with HCM. Methods Patients included were adults with an established diagnosis of HCM referred to a single centre for genetic testing. Demographic, clinical and imaging data were recorded at baseline. Echocardiography and cardiac magnetic resonance (CMR) were performed according to EACVI standards. Quantification of late gadolinium enhancement (LGE) was performed using the 5 SD quantitative threshold. Genotype was evaluated using a 16 gene panel in an accredited UK laboratory. Pathogenic and likely pathogenic variants were considered as a positive genotype. Serum hsTnI was measured by a two-site electrochemiluminescence immunoassay on a Roche E170 analyser. Normal values for the assay 0–34 ng/L for males and 0–16 ng/L for females. Results 313 patients (n=200, 64% male) median age 57 (IQR 47–68) years were included. hsTnI concentration was abnormal in 69 (22%) patients. An abnormal hsTnI was more common in females (n=36, 32%) compared to males (n=33, 17%, c2 9.9, p<0.05). A pathogenic variant in a sarcomere gene was identified in 95 (30%) individuals. An abnormal hsTnI concentration was associated with higher left ventricular (LV) wall thickness (20mm v 18mm, p<0.05) and LV outflow tract (LVOT) gradient (34 v 22 mmHg) on echocardiography (n=313). Of the patients (n=204) who had a CMR, an abnormal hsTnI concentration was associated with higher LV mass (183 v 156g, p<0.05) and greater % LGE (30 v 16%, p<0.01, n=129). There was no difference in hsTnI between those with a positive or negative genotype. During follow-up, 18 patients died. Of the 9 patients that died with a normal hsTnI, two died suddenly. Conclusions In HCM, patients with abnormal hsTnI concentration have higher LV mass and LVOT gradient and more fibrosis. Whilst mortality is higher in those with abnormal hsTnI, sudden cardiac death may occur with a normal hsTnI. It may not be appropriate to extrapolate hsTnI sex-specific thresholds used in the diagnosis of myocardial infarction to HCM. Funding Acknowledgement Type of funding source: None

Three-dimensional volume-strain loops may reflect fibrosis in hypertrophic cardiomyopathy

Abstract Background Combined plotting of deformation parameters against other indices [e.g. arterial pressure, left ventricular (LV) volume] might offer additional information about different diseases. Especially in hypertrophic cardiomyopathy (HCM) this approach might offer new insights into the various phenotypic and pathophysiologic features of this entity. Purpose Aim of this study was i) to apply strain-volume loops in HCM based on simultaneous frame-by-frame strain and volume changes' recordings acquired by means of three-dimensional (3D) speckle tracking imaging and ii) to investigate potential correlations between these loops and phenotypic features of HCM (including thickness, obstruction and fibrosis). Methods We included 40 HCM patients (54.1±14.3 years, 82.5% male, maximum wall thickness 19.3±4.8mm) who have consecutively undergone 3D-speckle tracking echocardiography and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). Values of 3D strain were plotted vs. volume for each frame to build a strain–volume loop. Peak of radial, longitudinal, and circumferential systolic strain (Rsp, Lsp, and Csp, respectively), systolic slopes of the loops (RsSl, LsSl, CsSl), and strain to end-diastolic volume (EDV) ratio (Rs/V, Ls/V, Cs/V) were computed for the analysis (panel A). Additionally, burden of fibrosis (percentage of LV mass) was defined by LGE extent (>5 standard deviations compared to nulled myocardium) in CMR slices. Results All HCM patients had preserved EF (60.5±5,7%), while 16 (40%) had LV outflow tract obstruction (LVOTO>30 mm Hg at rest). Mean LV mass index was 78.9±14.5 g (evaluated by 3D echocardiography). LGE was observed in 23 patients (57.5%) occupying 5.2±4.5% of LV mass. Concerning strain-volume loops the following values were recorded for radial (Rsp 30.8±9.8%, RsSl 0.4±0.13 and Rs/V 0.25±0.09), longitudinal (Lsp −9.4±3.7%, LsSl 0.12±0.06 and Ls/V 0.08±0.04) and circumferential deformation (Csp −14.2±3.5%, CsSl 0.18±0.05 and Cs/V 0.11±0.03). Among typical HCM characteristics tested (LV mass, LVOTO and LGE), only LV mass presented significant correlations with LsSl (r=−0.41, p<0.01). Interestingly, HCM patients with smaller LVMI and without LGE presented steeper and narrower (difference between systolic and diastolic strain for the same volume) longitudinal strain-volume loops compared to patients with larger LVMIs and fibrosis (panel B). Conclusions Strain-volume loop is an innovative application of 3D deformation imaging in HCM. According to this new non-invasive method, increase of LVMI in HCM is accompanied by less longitudinal contribution to stroke volume, whereas better systolic-diastolic coupling may exclude the presence of underlying fibrosis. Funding Acknowledgement Type of funding source: None

Value of a comprehensive exercise echocardiography assessment for patients with hypertrophic cardiomyopathy

Abstract Background Exercise echocardiography (ExE) may assess left ventricular (LV) systolic and diastolic function, LV outflow tract (LVOT) obstruction and mitral regurgitation (MR). We aimed to assess the feasibility and prognostic value of the assessment of all these issues during exercise in patients with hypertrophic cardiomyopathy (HCM). Methods LV systolic and diastolic function, LVOT gradients, and MR were evaluated during ExE in 285 patients with HCM (age 60±14 years, 168 men) and preserved LVEF (≥50%). Recordings were obtained at rest and peak exercise for regional/global LV systolic function and at rest and within 1.5 min after exercise for the rest of assessments: LVOT gradients, MR and ratio of early LV inflow velocity to early tissue Doppler septal annulus velocity (E/e'). Results Feasibility was 100%, 97%, 98% and 98% for LV systolic function, E/e', LVOT gradients, and MR assessments at exercise, respectively. Thirty-seven patients (13%) had LVOT obstruction at rest, and 76 (27%) developed exercise-induced LVOT obstruction. Mean resting LVEF was 63±3%. New wall motion abnormalities (WMAs) were detected in 38 patients (13%). E/e'>15 was observed in 108 patients at rest (38%) and in 119 at exercise (42%). Corresponding figures for significant MR (moderate or severe) were 20 (7%) and 17 (6%). During follow-up of 3.9±2.5 years, 21 patients had a hard event (cardiac death or transplantation, appropriate discharge of a defibrillator, stroke, myocardial infarction, hospitalization for heart failure), 33 a combined event (hard plus new atrial fibrillation or syncope), and 53 a combined event plus any interventionism. After adjustment, LV wall thickness, resting LVEF, maximal workload in Metabolic Equivalents (METs), and E/e' post-exercise resulted independent predictors of hard events (HR=1.45, 95% CI: 1.21–1.74, p<0.001; HR=0.80, CI: 0.71–0.89, p<0.001; HR=0.73, 95% CI: 0.62–0.86, p<0.001; HR=1.08, 95% CI: 1.02–1.14, p<0.009, respectively). Independent predictors of combined events included also LV wall thickness, resting LVEF, and METs, along with therapy with beta-blockers at the time of ExE (HR=1.29, 95% CI: 1.12–1.50, p=0.001; HR=0.89, CI: 0.81–0.97, p=0.012; HR=0.83, 95% CI: 0.74–0.93, p=0.001; HR=2.51, 95% CI: 1.20–5.25, p=0.015), whereas the model for combined events+any interventionism consisted of beta-blockers, LV wall thickness, LA dimension, METs and new WMAs. (HR=2.15, 95% CI: 1.20–3.86, p=0.01; HR=1.17, 95% CI: 1.03–1.32, p=0.02; HR=1.07, CI: 1.02–1.11, p=0.005; HR=0.90, 95% CI: 0.82–0.98, p=0.01; HR=2.33, 95% CI: 1.17–4.63, p=0.016) Conclusions A comprehensive assessment during ExE is feasible for patients with HCM and provides significant incremental prognostic information Funding Acknowledgement Type of funding source: None

Prognostic role of coronary flow velocity reserve in hypertrophic cardiomyopathy

Abstract Background A reduction in coronary flow velocity reserve (CFVR) related to coronary microvascular dysfunction is a major mechanism for ischemia in hypertrophic cardiomyopathy (HCM). Hypothesis To assess the functional correlates and prognostic value of CFVR during stress echocardiography (SE) in HCM. Methods We enrolled 201 HCM patients (age 51±14 years, 105 male, 52%; maximal wall thickness: 18±3 mm) studied with CFVR during exercise (n=33, 16.4%), dipyridamole (n=89, 44.3%) or adenosine (n=79, 39.3%) SE in 6 certified centers. CFVR was assessed using pulsed wave Doppler sampling in left anterior descending coronary artery. All patients completed the clinical follow-up. Results During SE mean value of CFVR was 2.11±0.46. No patients showed regional wall motion abnormalities during stress. LV outflow tract obstruction (LVOTO) was present in 34 (16.9%) patients at rest and in 47 (23.4%) at peak stress. CFVR was inversely related to age (r=−0.229, p=0.001) and maximal wall thickness (r=−0.197, p=0.031). During a median follow-up of 26 months (IQ range: 12–48 months), 75 events in 63 patients occurred: 10 deaths, 33 new hospital admission for acute heart failure, 8 sustained ventricular tachycardias and 24 atrial fibrillations. Patients in the lowest tertile (≤1.88) showed the worse prognosis with higher incidence of follow-up events compared to median tertile (1.89–2.29) and highest tertile (≥2.30) (see figure). At multivariable analysis, NYHA functional class (HR: 2.234, 95% CI: 1.398–3.517, p=0.001), presence of LVOTO at rest (HR: 2.958, 95% CI: 1.074–3.570, p=0.028) and lowest tertile of CFVR (HR: 2.144, 95% CI: 1.126–4.081, p=0.011) were the independent predictors of follow-up events. Conclusions In HCM patients, reduction in CFVR is associated to a clearly worse outcome. The spectrum of prognostic stratification is expanded if the response is titrated according to a continuous scale. Figure 1 Funding Acknowledgement Type of funding source: None

Intraprocedural mean mitral pressure gradient predicts mortality in percutaneous edge-to-edge mitral repair for functional mitral regurgitation

Abstract Introduction Percutaneous edge-to-edge mitral repair is a safe treatment method for functional (FMR) and degenerative (DMR) mitral regurgitation. Iatrogenic mitral stenosis remains a concern and periprocedural transoesophageal echocardiography is essential for real-time monitoring of mean mitral pressure gradient (intra-MMPG) and to guide clip deployment. Purpose Published data suggests intra-MMPG predicts clinical outcome and mortality only in DMR patients. We sought to validate these findings in a large high-volume UK center cohort with prolonged follow-up and further explore its use to predict mortality in functional MR patients. Methods All consecutive patients who underwent edge-to-edge mitral repair between 2010 and 2020 were analysed. The intra-MMPG and the severity of MR grade from the transoesophageal echocardiogram post-clip deployment (intra-MRgrade) were collected. Statistical analysis using covariates before and after edge-to-edge repair were compared using paired tests and cox regression models were used to assess the relationship of covariates with all-cause mortality. p<0.05 was deemed as statistically significant. Results We analysed data from 246 consecutive patients, 65% were men and mean age was 76±11 years. Pre-procedure LVEF was 49±15%, TAPSE was 16±6 mm, severity of MR was 3.8±0.5, 80% had NYHA III/IV and 45% had FMR. Post procedure, there was a significant reduction in severity of MR grade (3.8±0.5 to 1.7±0.8; p<0.001) and a reduction in LVEF (49±15 to 45±15%; p<0.001). There were significant improvements in NYHA class (3.2±0.6 to 2.0±0.6; P<0.0001) and LV outflow tract VTI (15±5 to 17±4 cm; p<0.001). Patients were followed-up for a median of 1021 days (inter-quartile range 289 to 1555) during which 76 patients died. Multivariate survival analysis (see table) showed that the increase in intra-MMPG was independently associated with mortality for FMR, but not for DMR. Furthermore, higher intra-MRgrade was associated with mortality for FMR patients only. Conclusion Intraprocedural mean mitral pressure gradient (intra-MMPG) predicts mortality in percutaneous mitral edge-to-edge repair for FMR, but not for DMR, herby challenging previously published data. Funding Acknowledgement Type of funding source: None

A rare case of infantile onset Pompe disease with genetic diagnosis

Glycogen storage disease type II, also called Pompe disease or acid maltase deficiency is a disorder of muscle glycogenoses with a wide range of clinical manifestations. It is one of the disorders of glycogen metabolism caused by a deficiency of lysosomal acid α-1, 4-glucosidase (acid maltase) resulting in lysosomal glycogen accumulation in cardiac, skeletal and smooth muscle cells. The pattern of inheritance is autosomal recessive with a gene for enzyme located on chromosome 17q25.2.It is the first recognized lysosomal storage disorder and the first neuromuscular disorder for which enzyme replacement therapy has been approved. We report a case of four month old female child, born to primi gravida third degree consanguineous couple, who presented with history of respiratory illness, hypotonia and developmental delay. Baby was sick needing mechanical ventilation and inotropic support. Echocardiography showed concentric LV hypertrophy with no LV outflow tract obstruction. In view of consanguinity, developmental delay, hepatomegaly and cardiomegaly, provisional diagnosis of a storage disorder, probably infantile Pompe disease was considered. Dried blood spot for α-1, 4-glucosidase enzyme assay confirmed the same. Enzyme replacement therapy was considered, but child progressed to cardiac failure needing prolonged ventilation and expired on day 8 of admission. Whole genome exome sequencing revealed 2 mutations which confirmed the diagnosis. Infantile Pompe disease is fatal without treatment. High index of suspicion and early diagnosis may help in taking advantage of emerging therapeutics, such as ERT which is capable of changing the natural history of the disease.

Left atrial dysfunction as marker of poor outcome in patients with hypertrophic cardiomyopathy

The incremental prognostic value of left atrial (LA) dysfunction, emerging in various clinical contexts, remains poorly explored in hypertrophic cardiomyopathy (HCM). To assess LA strain correlation with outcome in HCM. A cohort of all 307 consecutive patients presenting with HCM between 2007 and 2017 (54±17 years; 34% women), with comprehensive echocardiography at diagnosis and LA peak longitudinal strain (PALS) and LA peak contraction strain (PACS) measurement, was enrolled and occurrence of HCM related cardiac events analysed. Clinically, atrial fibrillation (AF) was present in 13%, New York Heart Association functional class II-III in 54%, and B-type natriuretic peptide (BNP) concentration was 199±278pg/mL. By echocardiography, left ventricular (LV) ejection fraction (EF) was 67±10%, LV thickness 21±5mm and European Society of Cardiology HCM risk score 3±3%, with 109 patients (36%) presenting obstructive HCM (LV outflow gradient 21±32mmHg). LA diameter was 41±8mm [with 109 (36%) presenting LA diameter ≥40mm], LA volume index 50±26mL/m2, PALS 24±13%, PACS 11±7% and LA peak systolic strain rate (LASRs) 1.7±0.6 s-1. In addition to AF, age, BNP, LVEF and LV thickness were all independent determinants of lower PALS, with odd ratios almost unchanged after adjustment (all P ≤0.0004). At a mean follow-up of 21 (range 18-23) months, patients with adverse cardiac events (n=65) presented with more impaired LA function (all P ≤0.0005), with a significant association between impaired PALS and worse outcome, hazard ratio 0.94 [95% confidence interval (CI) 0.92-0.97, P<0.0001]. After comprehensive adjustment, PALS remained strongly associated with worse outcome, adjusted hazard ratio 0.86 (95% CI 0.79-0.94; P=0.0008). The present study, by gathering a unique HCM cohort, suggests a strong link between LA dysfunction and poor outcome, to be further investigated.

The clinical significance of the incorporation of tissue Doppler imaging into low-dose Dobutamine stress echocardiography in patients with aortic stenosis prior to Transcatheter aortic valve implantation

BackgroundLow-dose dobutamine stress echocardiography (DSE) is indicated in patients with low flow (stroke volume index [SVi] < 35 ml/m2) low gradient (mean pressure gradient < 40 mmHg) and left ventricular ejection fraction (LVEF) < 50% aortic stenosis (AS) to assess LV contractile reserve (> 20% increase in SVi) and severity grade of AS. Severe AS is defined by a mean pressure gradient of 40 mmHg occurring at any time during the test when aortic valve area remains < 1.0 cm2.Case presentationThis case report highlights the utility of mitral annular systolic velocity (S′) by tissue Doppler imaging and peak LV outflow tract (LVOT) velocity as markers of LV intrinsic contractile function during DSE in a patient with low flow low gradient AS and reduced EF prior to transcatheter aortic valve implantation (TAVI).ConclusionsMitral annular S′ and peak LVOT velocities are reliable markers of LV intrinsic contractile function and should be incorporated into routine low-dose DSE.

Multimodality imaging in takotsubo syndrome: a joint consensus document of the European Association of Cardiovascular Imaging (EACVI) and the Japanese Society of Echocardiography (JSE)

Takotsubo syndrome (TTS) is a complex and still poorly recognized heart disease with a wide spectrum of possible clinical presentations. Despite its reversibility, it is associated with serious adverse in-hospital events and high complication rates during follow-up. Multimodality imaging is helpful for establishing the diagnosis, guiding therapy, and stratifying prognosis of TTS patients in both the acute and post-acute phase. Echocardiography plays a key role, particularly in the acute care setting, allowing for the assessment of left ventricular (LV) systolic and diastolic function and the identification of the typical apical-midventricular ballooning pattern, as well as the circumferential pattern of wall motion abnormalities. It is also useful in the early detection of complications (i.e. LV outflow tract obstruction, mitral regurgitation, right ventricular involvement, LV thrombi, and pericardial effusion) and monitoring of systolic function recovery. Left ventriculography allows the evaluation of LV function and morphology, identifying the typical TTS patterns when echocardiography is not available or wall motion abnormalities cannot be properly assessed with ultrasound. Cardiac magnetic resonance provides a more comprehensive depiction of cardiac morphology and function and tissue characterization and offers additional value to other imaging modalities for differential diagnosis (myocardial infarction and myocarditis). Coronary computed tomography angiography has a substantial role in the diagnostic workup of patients with acute chest pain and a doubtful TTS diagnosis to rule out other medical conditions. It can be considered as a non-invasive appropriate alternative to coronary angiography in several clinical scenarios. Although the role of nuclear imaging in TTS has not yet been well established, the combination of perfusion and metabolic imaging may provide useful information on myocardial function in both the acute and post-acutephase.

Multimodality Imaging for Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, an inherited autosomal dominant disease, is the most common familial cardiovascular disorder and presents with heterogeneous pathobiological, clinical, and phenotypic features. This review will explore how multimodality cardiovascular imaging offers insight into understanding and identifying these heterogeneous features which are important to reliably diagnose and risk stratify patients with HCM. Beyond the left ventricular (LV) hypertrophy, multimodality imaging is able to fully characterize a number of structural and functional abnormalities seen in HCM such as mitral valve leaflet elongation, abnormal chordal attachment, accessory apical-basal muscle bundle, papillary muscle abnormalities, LV outflow tract (LVOT) obstruction, microvascular dysfunction, and fibrosis. These anatomical and functional abnormalities contribute to the spectrum of different HCM presentations. Recent research shows that various morphological subtypes of HCM present with distinct clinical, genetic, LVOT, and fibrosis characteristics. Late gadolinium enhancement as assessed by cardiac magnetic resonance imaging (CMR) is useful in risk stratification of patients with HCM. In addition, native T1 and extracellular volume may add to prognostication. Strain, as measured by echocardiography and CMR, and novel techniques, such as positron emission tomography, have shown promise in determining prognosis in HCM. Computed tomography evaluates not only for obstructive coronary artery disease, but also for variations in coronary anatomy. Complimentary use of these imaging modalities is crucial in comprehensive evaluation of HCM as well as in diagnosing various features of HCM, differentiating it from other cardiomyopathies, and in identifying prognosis.

Multimodality imaging in takotsubo syndrome: a joint consensus document of the European Association of Cardiovascular Imaging (EACVI) and the Japanese Society of Echocardiography (JSE).

Takotsubo syndrome (TTS) is a complex and still poorly recognized heart disease with a wide spectrum of possible clinical presentations. Despite its reversibility, it is associated with serious adverse in-hospital events and high complication rates during follow-up. Multimodality imaging is helpful for establishing the diagnosis, guiding therapy, and stratifying prognosis of TTS patients in both the acute and post-acute phase. Echocardiography plays a key role, particularly in the acute care setting, allowing for the assessment of left ventricular (LV) systolic and diastolic function and the identification of the typical apical-midventricular ballooning pattern, as well as the circumferential pattern of wall motion abnormalities. It is also useful in the early detection of complications (i.e. LV outflow tract obstruction, mitral regurgitation, right ventricular involvement, LV thrombi, and pericardial effusion) and monitoring of systolic function recovery. Left ventriculography allows the evaluation of LV function and morphology, identifying the typical TTS patterns when echocardiography is not available or wall motion abnormalities cannot be properly assessed with ultrasound. Cardiac magnetic resonance provides a more comprehensive depiction of cardiac morphology and function and tissue characterization and offers additional value to other imaging modalities for differential diagnosis (myocardial infarction and myocarditis). Coronary computed tomography angiography has a substantial role in the diagnostic workup of patients with acute chest pain and a doubtful TTS diagnosis to rule out other medical conditions. It can be considered as a non-invasive appropriate alternative to coronary angiography in several clinical scenarios. Although the role of nuclear imaging in TTS has not yet been well established, the combination of perfusion and metabolic imaging may provide useful information on myocardial function in both the acute and post-acute phase.

Mitral Annular Plane Systolic Excursion: An Early Marker of Mortality in Severe COVID-19

Mitral Annular Plane Systolic Excursion: An Early Marker of Mortality in Severe COVID-19

Outcomes of Patients with Severe Aortic Stenosis and Left Ventricular Obstruction Undergoing Transcatheter Aortic Valve Implantation

Scarce data exist on clinical features and prognosis of patients with severe aortic stenosis (AS), concomitant with left ventricular obstruction (LVO). We aimed to evaluate the prevalence, characteristics, and outcomes in patients with severe AS and LVO undergoing transcatheter aortic valve implantation (TAVI). Consecutive patients with severe AS undergoing TAVI between January 2013 to December 2017 at our institution were included. Significant LVO was defined as resting peak left ventricular (LV) systolic gradient ≥30 mm Hg on pre-TAVI echocardiography. We analyzed the primary composite outcome of all-cause mortality and rehospitalization for heart failure (HHF) at 1-year in patients with LVO and those without LVO in the overall and propensity-matched populations. Among 1,729 patients who underwent TAVI, significant LVO was observed in 31 (1.8%) patients. This group was more likely to be female, had smaller aortic annulus and LV cavity, and received a smaller size of the transcatheter heart valve. The most common phenotype of LV hypertrophy causing LVO was concentric LV hypertrophy (58%), and mid-LV obstruction was more common than LV outflow tract obstruction (77% vs 23%, respectively). After adjustment for baseline differences, the primary outcome was not significantly different between patients with LVO and those without LVO (15% vs 16%, respectively; hazard ratio: 0.83; 95% confidence interval: 0.19 to 3.72; p = 0.809). In conclusion, in patients undergoing TAVI, concomitant LVO was relatively uncommon and occurred more often at mid-LV. The presence of pre-TAVI LVO was not associated with worse outcomes defined as increase all-cause mortality or HHF at 1-year.

Simulation of the Cardiovascular Mechanical System Based on Pressure-Flow Model Rest Condition

Non-invasive measurement method has made rapid developments in the field of biomedical engineering. One of research is impedance cardiography (ICG), which provide information of pulsation basic. By knowing this kind of measurement technique, it will assist inspection of the patient's physiological condition with cardiovascular system. This research is aimed to determine the mechanical characteristics of the cardiovascular system in the human body such as a wave graph of pressure, flow, and volume, based on pressure–flow model in rest condition, and analyze the simulation results by implementing state of the physiology cardiovascular disease. To obtain the wave chart that is modeled by the cardiovascular system using a lumped parameter method, formulate the differential equations of the pressure–flow dynamics equation for an incompressible fluid in a segment of a cylindrical elastic tube and simulate the model using the Simulink toolboxes from Matlab R2008b. The simulation with lumped parameter method resulted wave graphics of pressure, flow, and volume of physiological state a person in rest condition, the left ventricular pressure is 120 mmHg , right ventricular pressure is 30 mmHg , left ventricular outflow is 800 mL / sec and volume in the left ventricle is 160 mL . By implementing the simulation have been developed on the physiological state of cardiovascular disease, hypertension occurs when the arteries resistance R3i = 0.61 mmHg × s mL with the pressure of the left ventricle is 145 mmHg. For coronary heart condition, ventricular pressure decreased until 82 mmHg in the value of the coronary arteries resistance is R3o = 0.852 mmHg × s mL. This research assumed heart haves the character of passive because there is no feedback signal that can compensate if the pressure in the systemic circulation is reduced. The research can be concluded that the graph from simulation shows the results are not much different from the reference chart, this results indicates that the equation and the simulation was able to reflect on the human circulatory physiological circumstances. A little different of a graphic simulation result due to differences in the parameters and assumptions used.