Left Ventricular Outflow Research Articles

Genotype, phenotype and outcomes of patients with hypertrophic cardiomyopathy referred for ablation of ventricular tachycardia

Abstract Background Sustained monomorphic ventricular tachycardia (SMVT) is the most common ventricular arrhythmia (VA) subtype in patients with hypertrophic cardiomyopathy (HCM) who have received an implantable cardioverter defibrillator (ICD). However, data on catheter ablation (CA) are limited and available series typically report results of non-genotyped patients with relatively mild hypertrophy and/or apical aneurysms. Purpose This study describes genotype, phenotype and outcome of consecutive HCM patients referred for CA ablation of refractory SMVT. Methods and results Nine out of 787 patients referred for catheter ablation of SMVT between 01/2016 – 10/2023 had a HCM phenotype, 8/9 with dominant septal hypertrophy, none with LV outflow tract obstruction, and only 1/9 with an apical aneurysm. The median maximal wall thickness was 25 mm (IQR 20,2 – 26,9 mm) and the median left ventricular ejection fraction 34 % (IQR 26-42%). Six patients had a class IV/V variant in the myosine binding protein C (MYBPC3) gene, in 3 no disease-causing variant was identified. All patients with MYBPC3 mutation presented with an electrical storm/incessant VT refractory to antiarrhythmic drugs (AAD), including amiodarone (6/6) and amiodarone + class I AAD (3/6). In an attempt to control VT, 4/6 patients with a MYBPC3 variant required ≥2 ablation including bail out strategies (transcoronary alcohol-ablation, bipolar ablation, half-saline), surgical substrate resection and intraoperative cryoablation (3/6) and radiotherapy (2/6). After a median follow-up of 25 months (IQR 2-75) after the last intervention, all patients with MYBPC3-variants had VT recurrence, 3/6 died and 1/6 underwent heart transplantation. In contrast, patients without class IV/V variants, did not require bail-out strategies; VT recurred in one (single episode) and one patient died, 24 months after CA. The time course of the disease, management and outcome for patients with and without disease causing mutation is illustrated, with the first ablation as center line (figure). Conclusions Only 1 % of patients referred for CA of SMVT to a high-volume center had a HCM phenotype. A MYBPC3 variant was identified in 67%, and, in contrast to prior reports, 89% had severe hypertrophy. VT free survival appears to be particularly poor in MYBPC3 variant carriers despite availability of all treatment modalities. In these patients, early screening for advanced heart failure management including heart transplantation is important.

GENDER DIFFERENCES IN THE IMPACT OF VENTRICULAR-ARTERIAL COUPLING ON LEFT VENTRICULAR FUNCTION IN PATIENTS WITH HYPERTENSION

Objective: Increased arterial stiffness elevates aortic load, which can have adverse impacts on left ventricular (LV) function and contribute to the onset of heart failure. This impact is known to be more pronounced in women. Optimal coordination between ventricular contraction and the arterial system is required to maintain efficient cardiac function. This study aimed to investigate gender differences in the impact of ventricular-arterial coupling (VAC) on LV function in patients with hypertension at rest and after handgrip exercise. Design and method: Echocardiographic indexes of LV volumes, systolic function, and diastolic function were obtained in the usual way. Effective arterial elastance (EA) and index (EAI) were calculated from stroke volume measured using LV outflow waveform. Effective LV end-systolic elastance (ELV) and index (ELVI) were obtained using the single-beat method. Central aortic pressure waveform was recorded using the applanation tonometry. Characteristic impedance (Zc) of aortic root and reflection magnitude (RM) was calculated after Fourier transformation of both aortic pressure and flow waveforms. Results: Sixty-four patients (31 women and 33 men) with hypertension were enrolled. Women showed higher ELVI (1.33±0.34 vs. 1.10±0.29 mmHg/ml/m2, P=0.004) and EAI (1.14±0.25 vs. 0.93±0.26 mmHg/ml/m2, P=0.001), but VAC was not different (women: 0.88±0.17 vs. men: 0.85±0.11, P=0.431). Zc and RM were not different between women and men. After handgrip exercise, an increase in ELVI (P=0.021) and a decrease in VAC (P=0.035) were observed specifically in men, with no corresponding changes noted in women. In women, VAC was significantly associated with E’ velocity (beta -0.344, P=0.029) and left ventricular global longitudinal strain (beta 0.470, P=0.012) after adjustment, but in men, no association was found. Conclusions: Hypertensive women demonstrated greater stiffness in both the left ventricle and arterial systems, along with impaired LV contractile reserve in response to handgrip exercise, as compared to men. The ventricular-arterial mismatch had a notable impact on LV diastolic and systolic dysfunction only in women, but not in men.

Association between speckle tracking echocardiography and pressure-volume loops during cardiogenic shock development

BackgroundThe relationship between speckle tracking assessed global longitudinal strain (GLS) and Doppler-based echocardiography with basic physiological markers of cardiac function derived from pressure-volume loops is poorly elucidated.ObjectiveWe aimed to describe...

Septic cardiomyopathy phenotype in the critically ill may depend on antimicrobial resistance

BackgroundSepsis is a life-threatening organ dysfunction, and septic cardiomyopathy (SCM) may complicate the course of the disease. Infection with multidrug-resistant (MDR) pathogens has been linked with worse outcomes. This study aims to evaluate SCM in patients with infections caused by different antimicrobial-resistant phenotypes. MethodThis retrospective study included patients with sepsis/septic shock, hospitalized, and intubated in the intensive care unit of the University Hospital of Larissa between January 2022 and September 2023 with echocardiographic data during the first two days after infection onset. The patients were divided into two groups: non-MDR-SCM group and MDR-SCM group. The cardiac function was compared between the two groups. ResultA total of 62 patients were included in the study. Forty-four patients comprised the MDR-SCM and 18 the non-MDR-SCM group. Twenty-six patients (41.9%) presented with left ventricular (LV) systolic dysfunction, and ≤35% right ventricular fractional area change (RVFAC) was present in 56.4%. LV systolic function was more severely impaired in the non-MDR-SCM group (left ventricular ejection fraction, 35.8% ±4.9% vs. 45.6%±2.4%, P=0.049; LV outflow tract velocity time integral, [10.1±1.4] cm vs. [15.3±0.74] cm, P=0.001; LV-Strain, –9.02%±0.9% vs. –14.02%±0.7%, P=0.001). The MDR-SCM group presented with more severe right ventricular (RV) dilatation (right ventricular end-diastolic area/left ventricular end-diastolic area, 0.81±0.03 vs. 0.7±0.05, P=0.042) and worse RV systolic function (RVFAC, 32.3%±1.9% vs. 39.6%±2.7%, P=0.035; tricuspid annular plane systolic excursion, [15.9±0.9] mm vs. [18.1±0.9] mm, P=0.165; systolic tissue Doppler velocity measured at the lateral tricuspid annulus, [9.9±0.5] cm/s vs. [13.1±0.8] cm/s, P=0.002; RV-strain, –11.1%±0.7% vs. –15.1%±0.9%, P=0.002). ConclusionSCM related to MDR infection presents with RV systolic dysfunction predominance, while non-MDR-SCM is mainly depicted with LV systolic dysfunction impairment.

Dynamics of Right Ventricle Pressure During Stress Echocardiography in Patients with Heart Failure with Preserved Ejection Fraction

Shortness of breath during physical exertion is a non-specific symptom that can hide such potentially dangerous diseases as structural or functional bronchopulmonary, coronary heart disease, structural cardiac disease, but the frequent cause is left ventricle diastolic dysfunction due to its significant hypertrophy. Pathogenetic mechanisms leading to this symptom require detailed study for the possibility of a comprehensive approach in the treatment of such patients with the aim of maximally improving their prognosis and quality of life. Objective — evaluate changes in right ventricle systolic pressure during stress echocardiography in patients with LV myocardial hypertrophy and clinical manifestations of heart failure, search for other mechanisms leading to clinical symptoms. Materials and methods. The study included 49 patients with shortness of breath during physical exertion, who underwent further diagnostic examination after exclusion of coronary stenotic lesions by invasive coronary and ventricular angiography. Patients were excluded from bronchopulmonary pathology using spirometry and chest radiography, structural heart pathology using echocardiography, microvascular angina using echocardiography with intravenous dipyridamole infusion, and the change in systolic pressure in the right ventricle was investigated using echocardiography during a physical exercise test. Results and discussion. There were no cases of infiltrative lung changes, signs of emphysema, or other manifestations of significant pathology according to X-ray data. Spirometry also showed the absence of significant functional abnormalities. Echocardiography revealed significant hypertrophy of LV myocar­dium (thickness of IVS — on average (14.1 ± 0.5) mm, posterior wall thickness — on average (13.5 ± 0.3) mm) with the presence of LV diastolic dysfunction and echocardiographic signs of increased end-diastolic pressure in the LV, which was confirmed invasively during coronary and ventricular angiography. In 9 (18.4 %) cases, heart wall thickening was due to hypertrophic cardiomyopathy according to cardiac MRI, these patients had LV outflow tract obstruction and mild pulmonary hypertension at rest. Conducting strain imaging showed the presence of signs of myocardial ischemia (segmental contractility disorder) with varying degrees of severity (from 1 to 5 segments), which spread to the IVS, the apex of the heart and, less often, to the anterior wall of the LV. All patients experienced an increase in pulmonary artery systolic pressure during exercise, on average, from (37.4 ± 2.1) to (47.1 ± 1.6) mm Hg. Conclusions. The pathogenic mechanism underlying shortness of breath in patients with LV myocardial hypertrophy involves transient pulmonary hypertension occurring during exercise due to left ventricular diastolic dysfunction. Another contributing factor is the development of myocardial ischemia during physical exertion, which, in the absence of coronary stenosis and microvascular angina, is attributed to inadequate supply of coronary blood flow volume velocity relative to the significant left ventricular hypertrophy.

Measurement of Turbulent Kinetic Energy in Hypertrophic Cardiomyopathy Using Triple-velocity Encoding 4D Flow MR Imaging.

The turbulent kinetic energy (TKE) estimation based on 4D flow MRI has been currently developed and can be used to estimate the pressure gradient. The objective of this study was to validate the clinical value of 4D flow-based TKE measurement in patients with hypertrophic cardiomyopathy (HCM). From April 2018 to March 2019, we recruited 28 patients with HCM. Based on echocardiography, they were divided into obstructed HCM (HOCM) and non-obstructed HCM (HNCM). Triple-velocity encoding 4D flow MRI was performed. The volume-of-interest from the left ventricle to the aortic arch was drawn semi-automatically. We defined peak turbulent kinetic energy (TKEpeak) as the highest TKE phase in all cardiac phases. TKEpeak was significantly higher in HOCM than in HNCM (14.83 ± 3.91 vs. 7.11 ± 3.60 mJ, P < 0.001). TKEpeak was significantly higher in patients with systolic anterior movement (SAM) than in those without SAM (15.60 ± 3.96 vs. 7.44 ± 3.29 mJ, P < 0.001). Left ventricular (LV) mass increased proportionally with TKEpeak (P = 0.012, r = 0.466). When only the asymptomatic patients were extracted, a stronger correlation was observed (P = 0.001, r = 0.842). TKE measurement based on 4D flow MRI can detect the flow alteration induced by systolic flow jet and LV outflow tract geometry, such as SAM in patients with HOCM. The elevated TKE is correlated with increasing LV mass. This indicates that increasing cardiac load, by pressure loss due to turbulence, induces progression of LV hypertrophy, which leads to a worse prognosis.

THE POSSIBILITY OF PREDICTING LEFT VENTRICULAR DYSFUNCTION IN THE EARLY POSTOPERATIVE PERIOD IN CHILDREN WITH VENTRICULAR SEPTAL DEFECT

Highlights The article reflects data of an original study on the diagnosis of early postoperative dysfunction in children under 1 year of age after correction of a ventricular septal defect. The relationship between troponin I and conventional echocardiographic parameters, left ventricular longitudinal strain (S, % LV), and parameters reflecting central hemodynamics was assessed. The predictive ability of S, % LV in predicting a decrease in cardiac index after surgery was revealed. AbstractAim. To evaluate the possibility of predicting left ventricular (LV) dysfunction in the early postoperative period in children with ventricular septal defect (VSD).Methods. The study included 204 children under 1 year of age with non-restrictive perimembranous VSD. All parameters were evaluated before surgery, 6 hours, 24 hours and 10 days after surgery. 125 healthy children were enrolled as the control group.Results. 6 hours after surgery, there was a statistically significant decrease in LV ejection fraction (EF) (Me 55 [K3 60–K1 45] %, p = 0.0001), stroke index (SI) of LV outflow tract (LVOT) (12, 07 [16.38–8.24] mL/m2, p = 0.0001), and cardiac index (CI) (1.52 [2.08–1.07] L/min/m2, p = 0.0001). Arterial elasticity (AE) increased (21.4 [32.4–15.79] mm Hg/mL, p = 0.002), indicating a significant increase in afterload. Arterial compliance (AC) decreased (0.058 [0.081-0.038] mL/mm Hg, p = 0.0001), whereas ventricular-arterial coupling (VAC) value significantly increased (2 [2.54–1.67], p = 0.009). There was a dependence between LVOT SI and age (Rs = 0.45, p = 0.03), a moderate relationship between LVOT SI and VAC (Rs = –0.59, p = 0.001), a pronounced relationship between LVOT SI and AC (Rs = 0, 93, p = 0.02), pronounced relationship between LVOT SI and AE (Rs = –0.94, p = 0.03), moderate correlation between VAC and SI (Rs = –0.44, p = 0.04), weak relationship between VAC and patient age (Rs = –0.28, p = 0.03). Longitudinal deformity before surgery (b = 0.028; F = 3.9; p = 0.006) and VSD size (b = -0.08; F = 3.4; p = 0.029) were significantly associated with LV SI dynamics 6 hours after surgery. Dependence equation was as follows: 2.8 – 0.08 * VSD + 0.028 * S. A predictive ability to reduce CI 6 hours after surgery was revealed: longitudinal strain (S), % with a threshold “–” 14.3% (sensitivity 96.2%, specificity 81.6%, AUC 0.92, p&lt;0, 00001) and VSD diameter with a threshold of 8 mm (sensitivity 75%, specificity 52%, AUC 0.69, p&lt;0.0001).Conclusion. In the early postoperative period, there is a decrease in systolic and LV pump function. High AE rates are associated with a decrease in AC and an increase in VAC. Preoperative predictors of SI decrease are as follows: S, %&gt; “–” 14.3 and VSD size &gt; 8 mm.

Prediction of incident atrial fibrillation in hypertrophic cardiomyopathy

Background and aimAtrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM) with significant effects on outcome. We aim to compare the left atrial (LA) diameter measurement with HCM-AF Score in predicting atrial fibrillation (AF) development in HCM. MethodsFrom the regional cohort of the Campania Region, Italy, 519 HCM patients (38% women, age45 ± 17 years) without history of AF, were enrolled in the study. The primary clinical endpoint was the development of AF, defined as at least 1 episode documented by ECG. ResultsDuring the follow-up (mean 8 ± 6, IQ range 2.5–11.2 years), 99 patients (19%) developed AF. Patients who developed AF were more symptomatic, had higher prevalence of ICD implantation, had larger LA diameter, greater left ventricular (LV) maximal wall thickness and LV outflow tract obstruction (p < 0.01). Both LA diameter and HCM-AF score were higher in patients who developed AF versus those who did not (LA diameter 49 ± 7 versus 43 ± 6 mm; HCM-AF score 22 ± 4 versus 19 ± 4; p < 0.0001); however, ROC curve analysis demonstrated that LA diameter had a significant greater area under the curve than HCM-AF Score (p < 0.0001). At 5 years follow-up, a LA diameter > 46 mm, showed a similar accuracy in predicting AF development of HCM-AF score ≥ 22, which identifies patients at high risk to develop AF. ConclusionOur analysis shows that LA diameter, a worldwide and simple echocardiographic measure, is capable alone to predict AF development in HCM patients.

A novel technology for heart failure that utilizes the respiratory effort to shift fluids from the lung and alleviate cardiac workloads; feasibility study in sheep

Abstract Introduction Hemodynamic congestion is governed by inflow from RV and drainage through LV. However, ventricle functions are affected by the intrathoracic/pleural pressure: Negative pleural pressure (PPL) increases RV outflow while decreasing LV outflow, and vice versa at high PPL. Cardiac decompensation is associated with an increase in the respiratory effort (the peak-to-peak changes in PPL). We suggest to utilize this respiratory effort to shift fluid out of the lung and alleviate hemodynamic congestion. It is done by pacing the heart when PPL is high and the LV stroke volume is larger than the RV stroke volume. Purpose To test the feasibility of the novel technology in sheep. To verify that it is possible to modify the distribution of the heart beat within the respiratory cycle (slightly modify the rhythm according to the PPL) with insignificant effect on mean heart rate. Methods The utility was validated in sheep (N=9), under spontaneous breathing before and after induction of acute infarction by balloon inflation in the mid-LAD artery. The device senses the intracardiac electrical activity and respiratory effort and paces the right atrium when the PPL is high. The R-R interval of the paced beats was shorter than the sinus R-R interval by less than 10%. The effects of PPL and device pacing on LV and RV stroke-volumes were derived from simultaneous measurements of RV and LV pressure-volume loops, utilizing two impedance catheters (CD-Leycom) within both ventricles. Results The respiratory effort had significant effects on RV and LV outputs before and after infarction. The stroke volumes of the two ventricles were in antiphase! At low PPL the RV output increased while the LV decreased by about 10%, and the opposite occurred at high PPL. The pacing increased cardiac beating probability at high PPL. Sequential pacing for one minute increased the systolic pressure by 5 mmHg while decreasing the pulmonary artery pressure. Based on the pressure-volume loops, each paced breath cycle increased the LV outflow by 1.14 ml and decreased RV outflow by 0.36ml, yielding a shift of 1.5 ml from the lung. Interestingly, it was associated with a decrease in the sinus rate, which further decreased cardiac beating at low PPL and may represent a decrease in sympathetic tone. Conclusions Pacing only 1% of the ∼20,000 daily breath-cycles can shift 300 ml from the lung per day! The technology is agnostic of the heart-failure etiology. Preclinical studies in a model of chronic heart failure are required to further validate the novel approach.

Anatomical, functional and prognostic correlates of resting coronary flow velocity in patients with hypertrophic cardiomyopathy

Abstract Background The clinical significance of baseline peak diastolic coronary flow velocity (CFV) in the left anterior descending coronary artery (LAD) has not been investigated yet in patients with hypertrophic cardiomyopathy (HCM). Aim To assess the anatomical, functional and prognostic correlates of baseline LAD CFV in HCM. Methods 384 consecutive adult HCM patients (age=52+15 years, 164 [43%] females) with no known coronary artery disease from 8 centers in 5 countries were prospectively analyzed. All patients underwent comprehensive transthoracic echocardiography including CFV measurement with pulse wave Doppler in the mid-distal LAD. All patients had preserved left ventricular (LV) function. LV force was calculated as (peak instantaneous LV outflow tract gradient+systolic blood pressure)/LV end-systolic volume. Patients were followed for a median of 50 months (IQ range 18-97 months), the outcome measure was a composite endpoint of all-cause death and acute heart failure. Results The mean CFV was 36±11 cm/s. CFV was positively correlated with LV maximal wall thickness (r=0.375, p&amp;lt;0.001), LV maximal septal thickness (r=0.320, p&amp;lt;0.001), resting LV outflow tract gradient (r=0.274, p&amp;lt;0.001), LV force (r=0.227, p&amp;lt;0.001), mean E/e’ (r=0.479, p&amp;lt;0.001) and heart rate (r=0.221, p&amp;lt;0.001). During follow-up, 54 events occurred (33 all-cause deaths and 21 acute heart failures). Receiver operating characteristic analysis was used to determine the best cut-off value of CFV (&amp;gt;31 cm/s) to predict the composite endpoint. Patients with CFV &amp;gt;31 cm/s had a significantly worse 10-year event-free survival compared to those with CFV ≤31 cm/s, see Figure. Conclusion Higher resting LAD CFV is associated with greater LV wall thickness, higher LV outflow tract gradient, faster heart rate and more elevated left ventricular filling pressures in HCM. Elevated resting CFV may indicate a coronary microcirculation dysfunction either primary or secondary to anatomical (septal hypertrophy), functional (increased myocardial oxygen demand), or autonomic (increased sympathetic drive) determinants. Whatever the underlying endotype, high resting CFV is related to worse prognosis in the long term.Figure.

Non-obstructive hypertrophic cardiomyopathy exhibit subclinical abnormalities in systolic and diastolic ventricular kinetic energy and systolic haemodynamic forces on 4D flow CMR

Abstract Background Patients with non-obstructive hypertrophic cardiomyopathy (nHCM) exhibit a range of anatomical variations including septal, reverse septal, apical, and concentric hypertrophy. Cardiovascular magnetic resonance imaging (CMR) with 4D flow permits assessment of haemodynamic forces (HDF) and kinetic energy (KE) of intraventricular blood flow (1,2). These parameters may indicate subclinical flow inefficiencies which may not be detectable on routine transthoracic echocardiography (3,4). The aim of this study was therefore to investigate if left ventricular (LV) HDF and KE differ between nHCM and controls, and between subgroups of nHCM. Methods Patients with nHCM (n=71) and age- and sex-matched controls (n=20) underwent CMR at 3T (Trio, Siemens) (Table 1). Patients were categorised as phenotype positive (P+) based on presence of hypertrophy (maximum wall thickness ≥15mm, or ≥13mm with a positive family history), and as phenotype negative (P-) referring to pre-hypertrophic sarcomeric variant carriers. Patients with P+ nHCM were classified into subgroups based on the pattern of hypertrophy. Left ventricular HDF and KE were computed over the cardiac cycle using validated modules (1) (Figure 1). Measurements of HDF were based on the Navier-Stokes equations (1), and analysed in three orthogonal directions as root mean square and peak values for systole and diastole. Force ratio was calculated as the sum of the two transverse components divided by the longitudinal component. The Mann-Whitney U test was used for group comparisons, Pearson analysis for correlations, and Fisher’s exact test for binary categorical data. Results P+, P- patients and controls had comparable LV ejection fraction from CMR, LV outflow tract pressure gradients, and diastolic parameters on echocardiography (Table 1). Systolic HDF and force ratio were increased, primarily in the lateral wall-septum direction in septal and reverse septal P+ patients compared to controls, but did not differ in any other directions in P+ compared to P- patients and to controls (Table 1, Figure 1). Diastolic HDF and force ratio did not differ between groups. Systolic KE was increased in P+ patients compared to P- and to controls (Table 1, Figure 1), mainly through increased KE in patients with septal and reverse septal hypertrophy. P+ patients also had increased late diastolic (A-wave) KE relative to P- patients and to controls (Table 1). Both systolic KE and force ratio correlated with maximum wall thickness in patients (r=0.31, p=0.005; r=0.43, p&amp;lt;0.0001). Conclusion In non-obstructive hypertrophic cardiomyopathy, left ventricular HDF and KE analysis from 4D flow CMR detect subclinical flow abnormalities. Increased systolic HDF and KE are linked to the extent and pattern of hypertrophy. Late diastolic A-wave KE was also abnormal in P+ patients despite normal diastolic velocities on echocardiography.Table 1Figure 1

Association between speckle tracking echocardiography and pressure-volume loop derived parameters at increasing levels of myocardial damage in a porcine model of acute cardiogenic shock

Abstract Background Echocardiography is a diagnostic cornerstone in acute cardiovascular care. However, the relationship between speckle tracking assessed global longitudinal strain (LS) and Doppler-based echocardiography with basic physiological markers of cardiac function derived from pressure-volume loops remains poorly elucidated, especially with increasing levels of myocardial damage. Objectives We aimed to describe the association between LS and Doppler-based echocardiography and direct measurements of central hemodynamic parameters from conductance catheter-based pressure-volume loops in an animal model with increasing left ventricular (LV) dysfunction. Methods Twelve Danish landrace pigs weighing 75-80 kg were used. All instrumentations were performed percutaneously, including placement of a conductance catheter in the LV. Progressive LV dysfunction was induced by stepwise embolization trough the left main coronary artery every three minutes until a 50% reduction in cardiac output or mixed venous saturation, compared to baseline, or a mixed venous saturation &amp;lt;30%. Echocardiography was performed through a subxiphoid midline incision, and was done at baseline and 90 seconds after each injection. Results With progressive LV dysfunction, mean cardiac output decreased from 5.6 l/min (SD: 0.9) to 2.1 l/min (SD: 0.9) and mean mixed venous saturation deteriorated from 61.1%(SD: 7.9) to 35.3% (SD: 6.1). Mean LS and LV outflow tract velocity time integral (LVOT VTI) declined from -13.8% (SD 3.0) to -6.1% (SD: 2.0) and 16.9 cm (SD: 2.6) to 7.8 cm (SD: 1.8), respectively (Figure 1). LS and LVOT VTI showed the strongest correlation to stroke work in unadjusted univariate regression (r2=0.53 and r2=0.49, respectively. p&amp;lt;0.01 for both). LS correlated significantly, but modest, with stroke volume (r2=0.46, p&amp;lt;0.01), end-systolic elastance (r2=0.32, p&amp;lt;0.01), systolic blood pressure (r2=0.37, p&amp;lt;0.01), ventriculo-arterial coupling(r2=0.34, p&amp;lt;0.01), and arterial elastance (r2=0.23, p&amp;lt;0.01) (Figure 2). In a multivariate regression analysis, LS showed significant correlation with stroke work, systolic blood pressure, and end-diastolic wall stress (r2=0.60, p&amp;lt;0.01). Conclusion In an animal model of acute progressive LV dysfunction, echocardiographic and conductance catheter-based measurements changed significantly. LS and LVOT VTI displayed the earliest and the largest alterations with increased myocardial damage and LS showed moderate correlations with contractility, arterial elastance and ventriculo-arterial coupling. This indicates that LS is a marker of overall ventricular performance.Echocardiographic changes from baselineScatter plot of LS and hemodynamics

Non-invasive estimation of left ventricular systolic peak-pressure: a prerequisite to calculate of myocardial work in hypertrophic obstructive cardiomyopathy

Abstract Introduction Myocardial work (MW) is an echocardiographic parameter to estimate global and regional myocardial performance. This method utilizes pressure strain loops derived from global longitudinal strain (GLS) and left ventricular systolic pressure (LVSP) estimated by brachial blood pressure (BP). Purpose Since LVSP cannot be equated with BP in pts with HOCM, we investigated whether the LVSP can be calculated non-invasively by combining Doppler echo parameters and the BP. This estimation is mandatory to make MW applicable for HOCM-pts. Methods We studied 20 consecutive pts (8 women, 12 men; mean age 57.0±13.9 years; NYHA class 2.1±0.8) with indication for first alcohol septal ablation. 6 pts had hypertension and 2 pts unexplained syncope. 18 (90%) pts were in sinus rhythm. NTproBNP was 1431 pg/ml (1912 IQR). Echo baseline measurements showed subaortic septal (IVS) thickness of 21.0±5.0 mm and maximal IVS thickness of 24.7±6.3 mm. Pts showed high-normal left ventricular ejection fraction (70.4±10.1%). Left atrial (LA) volume was 101.2±26 ml. All measurements of pressures and gradients were performed in the catheterization laboratory after placement of a 5F Judkins JR4 in the ascending aorta and a 5.2F special pigtail catheter in the apex of LV beyond the obstruction. Simultaneous measurements of BP at left upper arm, echo intraventricular gradients (instantaneous and mean) with CW Doppler (GE Vivid E70), and invasive pressures and gradients (peak-to-peak and mean) of the LV and ascending aorta were performed. Echo and invasive gradients were averaged over 3 cardiac cycles. Finally, we tried to identify an estimation of invasively measured LV systolic pressure by combining systolic BP and echo measured gradients. Results Systolic BP was 143±21 mmHg. Max. CW Doppler gradient was 65±29 mmHg and mean gradient was 31±14 mmHg. Invasive simultaneous measurements at rest showed peak-to-peak gradient of 55±24 mmHg and mean gradient of 34±13 mmHg between apical LV and ascending aorta. Mean LVSP was 190±40 mmHg. Systolic pressure of the ascending aorta was 134±28 mmHg. Adding systolic peripheral BP and maximal echo-gradient mean value was 208±38 mmHg. Adding systolic peripheral BP and echo-mean gradient mean value was 174±26 mmHg. Correlating these values with the invasively measured systolic LV pressure we found a slightly higher correlation of the sum of systolic BP and mean-echo gradient (Pearson correlation coefficient: 0.867 p&amp;lt;0.001) compared with the sum of systolic BP and maximal echo-gradient (Pearson correlation coefficient: 0.851; p&amp;lt;0.001). Bland–Altman plots demonstrated good levels of agreements between invasively measured LVSP and both non-invasively estimated LVSP. Conclusions Non-invasive estimation of LVSP is feasible by combining conventional BP and CW Doppler measured mean LV outflow tract gradient in HOCM. Hereby estimation of MW in pts with HOCM is applicable.

Transthyretin amyloid cardiomyopathy among patients with hypertrophic cardiomyopathy: clinical, cardiac imaging, and electrocardiographic findings from the TTRACK study

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is often misdiagnosed as hypertrophic cardiomyopathy (HCM). Identifying ATTR-CM in patients with HCM is essential because treatment approaches vary, especially with the availability of disease-modifying therapies for ATTR-CM. In this analysis of the TTRACK study, we investigated clinical, cardiac imaging, and electrocardiogram (ECG) features of ATTR-CM that may heighten suspicion of amyloid disease and prompt further screening in patients with HCM. Purpose Explore the clinical, echocardiogram (echo), magnetic resonance imaging (MRI), and ECG findings of patients with HCM screened for ATTR-CM in the TTRACK study. Methods In this global, multicentre, non-interventional epidemiological study, the prevalence of ATTR-CM was assessed in patients ≥50 years of age with HCM of unknown aetiology (left ventricular [LV] maximum wall thickness ≥15 mm [echo]) using 99mTc-DPD/99mTc-PYP/99mTc-HMDP-labeled bone scintigraphy. Nuclear images were graded based on cardiac vs bone radiotracer uptake following the Perugini system. Monoclonal protein testing was performed to exclude light chain amyloidosis. Results Of 766 eligible patients with scintigraphy data, 521 (68.0%) had no cardiac uptake; 37 (4.8%) had low uptake (grade 1); and 208 (27.2%) had moderate/high uptake (grade 2/3). Among patients with moderate/high uptake (cardiac amyloidosis [CA]), 137 (65.9% of patients with CA; 17.9% of the overall cohort) had confirmed ATTR-CM. Comparing NYHA classification of patients with no cardiac uptake vs those with ATTR-CM, 33.8% and 25.0% were asymptomatic (NYHA class I). Marked numerical differences were observed in some echo findings of patients with no cardiac uptake vs ATTR-CM, including mean LV mass index (155.6 vs 177.0 g/m2) and the proportions of patients with preserved apical strain (57.9% vs 74.2%) and concentric hypertrophic pattern (38.8% vs 77.8%) (Table [A]). Although a smaller percentage of patients with ATTR-CM exhibited LV outflow tract (LVOT) obstruction than patients with no cardiac uptake, 12.5% of patients with ATTR-CM had LVOT obstruction (LVOT gradient &amp;gt;30 mmHg). A substantially lower proportion of patients with no cardiac uptake (54.7%) had late gadolinium enhancement on MRI than those with ATTR-CM (84.6%). Notable ECG differences were seen in PR interval (179.4 vs 196.9 ms) and the proportion with poor precordial R wave progression (21.9% vs 47.9%) (Table [B]). Conclusions In the TTRACK study, conducted in the largest cohort of patients with HCM ever screened for ATTR-CM, approximately 18% of patients ≥50 years of age with HCM had findings indicative of ATTR-CM. Noteworthy differences in some clinical, cardiac imaging, and ECG findings were seen between patients with HCM with and without ATTR-CM, but none appeared to be definitive. These findings suggest that broader screening for amyloid disease with scintigraphy should be considered among all patients with HCM.

Identification of novel risk profiles for ventricular arrythmias in hypertrophic cardiomyopathy through clustering analysis including left ventricular strain data

Abstract Aims The excess mortality in hypertrophic cardiomyopathy (HCM) patients is mainly attributed to the occurrence of ventricular arrythmias (VA) and sudden cardiac death (SCD). The prediction of VA remains challenging and could be improved. The aim of the study was to characterize VA risk profile in HCM patients through clustering analysis combining clinical and conventional imaging parameters with information derived from left ventricular longitudinal strain analysis (LV-LS). Methods A total of 434 HCM patients (65% men, mean age 56 years) were retrospectively included from two referral centers from two different countries and followed longitudinally (mean duration 6 years). Mechanical and temporal parameters were automatically extracted from the LV-LS segmental curves of each patient in addition to conventional clinical and imaging data. A total of 287 features were analyzed using a clustering approach (k-means). The first endpoint for ventricular arrythmias (VA) included suspected SCD, aborted cardiac arrest, appropriate ICD therapy (AIT), sustained ventricular tachycardia (SVT) and non-sustained ventricular tachycardia (NSVT) during follow-up. Results 4 clusters were identified with a higher rhythmic risk for cluster 1 and 4 (VA rates of 26%(28/108), 13%(13/97), 12%(14/120), and 31%(34/109) for cluster 1,2,3 and 4 respectively) (Figure 1). These 4 clusters have been mainly separated based on LV strain parameters with severe and homogeneous decrease of myocardial deformation for cluster 4 (global longitudinal strain (GLS) -11%), a small decrease for cluster 2 and 3 (GLS -17.2 and -16.3%, respectively) and a marked mechanical and temporal dispersion for cluster 1 associated with a moderate decrease of the GLS (-15.3%; p &amp;lt;0.0001 for GLS comparison between clusters) (Figure 2). Patients from cluster 4 had the most severe phenotype (mean LV mass index 123 vs. 112 g/m²; p=0.0003) with marked diastolic dysfunction (left atrial volume index (LAVI) 46.6 vs. 41.5 ml/m² for others clusters; p=0.04) and impaired exercise capacity (% predicted peak work 58.6 vs. 69.5%; p= 0.025). Patient from cluster 2 had the less severe phenotype (mean LV mass index 99.6 vs. 121 g/m²; p=0.0001 and LAVI 37.2 vs. 44.3 ml/m²; p=0.04). Patients from cluster 3 and 1 had a moderate phenotype and were older in cluster 3 (mean age 62.1 vs. 54.1 years; p &amp;lt; 0.0001) and had more obstructive form in cluster 1 (peak gradient LV outflow tract ≥ 30 mmHg for 36 vs. 23% of patients; p=0.046) with a larger left atrium size (LAVI 45.8 vs. 41.7 ml/m²; p=0.0023). Conclusion Using a clustering approach processing LV-LS parameters in HCM patients identified 4 clusters with specific LV-strain patterns and different rhythmic risk level. In the future, the automatic extraction and analysis of LV strain parameters could help to improve the risk stratification for SCD in HCM patients.Figure 1:Survival curvesFigure 2:Different strain patterns

Prognostic value of the left ventricular mass index by magnetic resonance imaging in patients with hypertrophic obstructive cardiomyopathy undergoing septal myectomy

Abstract Research background Traditional risk factors for hypertrophic cardiomyopathy (HCM) have limited ability to predict poor survival outcomes in the medium to long term after surgical septal myectomy (septal myectomy) in patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing septal myectomy. Additionally, there is a lack of studies reporting the relationship between left ventricular mass index (LVMI), an index of ventricular remodeling in hypertrophic obstructive cardiomyopathy, and medium to long-term prognostic outcomes after septal myectomy. Research methods: From June 2011 to July 2016, 490 patients with HOCM who completed preoperative cardiac magnetic resonance (CMR) were retrospectively enrolled for mid- to long-term follow-up. The study's primary endpoint included all-cause death. Secondary endpoints included cardiac death and adverse cardiovascular events. Furthermore, CMR measures were applied to study the risk factors for mid- and long-term adverse endpoint events after septal myectomy treatment. Study results: 486 patients with HOCM completed follow-up and were included in the final analysis. Twenty-one patients (4.3%) died during follow-up (median 73.6, maximum 105.6 months), and 66 patients (16.3%) had an adverse cardiovascular event during follow-up. In the Cox proportional risk regression model, the most significant predictor of all-cause mortality after septal myectomy was CMR-LVMI (risk ratio 1.009, 95% confidence interval 1.003-1.015, P=0.018). In receiver operating characteristic (ROC) analysis, LVMI &amp;gt; Cutoffpredicted all-cause death analyzed separately by male and female subgruop(P&amp;lt;0.05). In Cox proportional risk regression models (incorporating age, maximum septal thickness, left atrial diameter, left ventricular end-diastolic dimension, left ventricular ejection fraction, LV outflow tract peak pressure, pulmonary hypertension, LGE positive and LVMI), the most significant predictor after surgical septal resection was LVMI measured by CMR (hazard ratio 1.025, 95% confidence interval 1.009-1.040, P=0.002). From ROC analysis, LVMI &amp;gt;cutoff accurately predicted the occurrence of all-cause mortality analysed separately by male and female (P&amp;lt;0.05). Additionally, K-M survival curve plots suggested that patients with HOCM above the LVMI threshold group had lower all-cause mortality-free survival (Log-rank: P=0.0.025), hear failure related mortality-free survival (Log-rank: P=0.0.014) in the medium to long term after septal myectomy. Conclusions An elevated preoperative left ventricular myocardial mass index suggests adverse ventricular remodeling and is an independent predictor of poor survival outcomes in patients with HOCM in the medium to long term after septal myectomy.ROC analysis of LVMI for all cause deathK-M survival curve devided by LVMI level

Abstract 14190: Simultaneous Analysis of Myocardial Flow Reserve and Intra-Ventricular 4D Flow Using Hybrid 13 N-ammonia Positron Emission Tomography/Magnetic Resonance Imaging in Patients With Coronary Artery Disease

Introduction: Intra-left ventricular (LV) blood flow dynamics is closely related to wall kinetics and myocardial perfusion. 4D flow magnetic resonance imaging (MR) has been developed to simulate and quantify intra-LV blood flow. We aimed to evaluate the usefulness of simultaneous analysis of myocardial flow reserve (MFR) and intra-LV 4D flow measured by hybrid 13 N-ammonia positron emission tomography (PET)/MR in patients with coronary artery disease (CAD). Methods: Forty patients (mean 65±18 years, male 32) with CAD who underwent pharmacological stress PET/MR were enrolled. MFR was calculated from a series of dynamic rest-stress PET scans. Simultaneously, 4D flow MR acquisition was performed during the stress PET scan. The intra-LV 4D flow was visually assessed, where the smooth flow was defined as normal pattern, and random, or reverse flow was defined as abnormal (Figure A). The velocity of LV inflow and outflow were measured. Results: A normal flow pattern was found in 22 patients, while abnormal pattern was found in 18. MFR showed a significant correlation with the velocity of LV inflow and outflow (inflow: R = 0.552, P &lt; 0.001; outflow: R = 0.563, P &lt; 0.001). MFR was significantly lower in the abnormal flow compared to the normal flow (1.484 ± 0.559 vs. 1.931 ± 0.775, P = 0.041, Figure B). Additionally, when analyzing MFR in coronary artery territories, MFR in the left anterior descending artery was significantly lower in the abnormal flow compared to the normal flow (1.405 ± 0.526 vs. 1.881 ± 0.791, P = 0.029, Figure C). Conclusion: Simultaneous analysis of MFR and intra-LV 4D flow has a potential to serve as a novel indicator for assessing the severity of ischemia in patients with CAD.

Abstract 16562: Subclinical Flow Inefficiencies in Non-Obstructive Hypertrophic Cardiomyopathy Subgroups Revealed by 4D Flow Cardiovascular Magnetic Resonance

Background Patients with non-obstructive hypertrophic cardiomyopathy (nHCM) may exhibit flow inefficiencies despite normal flow profiles on transthoracic echocardiogram. We investigated whether left ventricular (LV) kinetic energy (KE) and hemodynamic forces (HDF) on 4D flow CMR are abnormal in nHCM, and examined the impact of genotype and hypertrophy phenotype on flow profiles. Methods 90 participants (70 HCM without echocardiographic outflow tract obstruction and 20 healthy controls) underwent 4D flow CMR. Patients were categorized as phenotype positive (P+) if they had LV hypertrophy (≥15mm or ≥13mm with an HCM family history), or phenotype negative (P-) referring to pre-hypertrophic pathogenic sarcomeric variant carriers. LV KE, HDF and transversal/longitudinal HDF ratio were computed from 4D flow CMR. Results P+ patients and controls were of similar age, but P- were younger. P+, P- and controls had comparable LV ejection fraction on CMR, and LV outflow tract pressure gradients and diastolic velocities on echocardiography (Table 1). Systolic KE was higher in P+ compared to controls (Table 1, Figure 1). Early diastolic KE was higher in P- than P+, reflecting younger P-, but did not differ between P+ and controls. Late diastolic KE was higher in P+ versus P- and controls. Systolic HDF ratio was higher in P+ than controls (Table 1, Figure 1). Diastolic HDF and HDF ratio were similar between P+ and controls. Conclusion Despite comparable flow velocities on echocardiography, nHCM exhibited higher systolic KE and HDF ratio, and late diastolic KE on 4D flow CMR relative to controls. Both the extent and pattern of hypertrophy are important determinants of abnormalities in KE and HDF.

Abstract 11589: Late Complications After Interrupted Aortic Arch Repair

Description of Case: A 38-year-old man with known type B interrupted aortic arch (IAA), bicuspid aortic valve, and a complex surgical history (including IAA repair with an ascending-descending aortic conduit, later conduit graft revision, and left pulmonary artery [LPA] stent) presented after many years of loss to follow-up and was found to have hypertensive urgency. Echocardiogram showed turbulent flow in the proximal descending aorta concerning for arch obstruction. Computed tomography angiography (CTA) (Fig. 1 A–C) showed: narrowed proximal graft anastomosis, dilation of the aortic root and ascending aorta, a large pseudoaneurysm arising from the distal graft anastomosis, and LPA stenosis due to compression from the descending aorta. Following improved hypertension, the patient underwent placement of a left carotid-subclavian bypass graft followed by thoracic endovascular aortic repair (TEVAR) with an endograft positioned across the distal aortic jump graft suture line. CTA one month postoperatively (Fig. 1 D–F) confirmed exclusion of the pseudoaneurysm. Discussion: Type B IAA is considered the most common subtype of IAA among cases diagnosed in infancy, though recent data regarding IAA epidemiology are scarce. IAA is associated with other congenital abnormalities, such as ventricular septal defect (VSD), LV outflow tract abnormalities, and 22q11 deletion syndrome. Additional surgical aortic arch procedures in these patients are not uncommon, perhaps especially among patients who required reintervention for LV outflow tract obstruction. While most studies examining long-term outcomes after IAA repair have not commented specifically on late risk of aneurysm or pseudoaneurysm, such findings have been described in the literature. Additionally, use of polytetrafluoroethylene material in arch repair and arch repair by a method other than direct anastomosis—such as were seen in our patient—have been observed to be risk factors for late reintervention.

Abstract 17626: Apolipoprotein A-IV-Associated Cardiac Amyloidosis: A Classic Presentation of a Rare Condition

Introduction: A 65-year-old male with type one diabetes mellitus underwent a pancreas and kidney transplant approximately seven years ago and has received chronic tacrolimus. He presented with subacute dyspnea on exertion, orthopnea, and edema. His background also includes ongoing chronic kidney disease stage 3A, orthostatic hypotension, and spinal stenosis. On exam, he had abdominal and lower extremity swelling. An echocardiogram showed preserved LVEF, concentric hypertrophy, hyperrefractile myocardium, reduced longitudinal strain with apical sparing, and a tiny pericardial effusion. Hypothesis: His echocardiogram indicated an infiltrative process such as amyloidosis or tacrolimus cardiotoxicity or possibly hypertrophic cardiomyopathy. Methods: Free light chains and protein studies with mass-fixation demonstrated no monoclonal gammopathy. PYP scan was negative for transthyretin amyloidosis. A cardiac MRI showed patchy subendocardial and midmyocardial delayed gadolinium enhancement, supporting the clinical suspicion for cardiac amyloidosis. With the need to exclude tacrolimus toxicity as well, subsequent endomyocardial biopsy revealed apolipoprotein A-IV-associated cardiac amyloidosis (Figure 1). Results: Apolipoprotein A-IV-associated cardiac amyloidosis occurs in about 0.6% of patients with cardiac amyloid and has classic manifestations of LV outflow obstruction, microvascular disease, and especially renal insufficiency. When these features occur in patients with clinical and imaging findings suggesting cardiac amyloidosis despite negative testing for more common types of amyloidosis, clinicians should proceed with endomyocardial biopsy to evaluate for less common forms. Conclusions: We report a rare case of apolipoprotein A-IV-associated cardiac amyloidosis. This case highlights the need for endomyocardial biopsy when clinical suspicion for cardiac amyloidosis persists despite negative testing.