Left Ventricular Septum Research Articles

Determinants of left ventricular structure, filling and long axis function in systemic sclerosis.

Abnormalities of left ventricular (LV) structure, filling and long-axis function have all been reported in subjects with systemic sclerosis (SSc) and a normal LV ejection fraction (EF), but previous study findings have not been consistent. The aim of this study was to identify factors which could have confounded the analyses in previous studies of SSc, and in particular to consider the variables of body surface area (BSA), sex, age, heart rate, blood pressure (BP), disease duration (DD), disease type (limited versus diffuse) and interstitial lung disease (ILD). Echocardiography was performed on 100 subjects with SSc (79 women; age 56±15 years) with a LVEF ≥50% and free of pulmonary arterial hypertension, coronary artery disease, more than mild valvular heart disease and atrial fibrillation. Measurements were performed of the LV end-diastolic dimension (LVEDD) and septal wall thickness (SWT), the transmitral Doppler E, A and deceleration time (DT), and the peak systolic (s') and early diastolic (e') LV long-axis velocities. Multivariate analyses were performed to investigate correlations of the above LV variables with BSA, sex, age, heart rate, BP, DD, disease type, and the presence of ILD. DD varied between 0.1 and 41.2 years, 25% had diffuse and 75% had limited disease, and 37% had ILD. SWT and LVEDD were positively correlated with BSA, SWT was also positively correlated with age and larger in males, and LVEDD was larger in diffuse disease. Age was positively correlated with A and DT, and inversely correlated with E and E/A, and heart rate was inversely correlated with E and E/A. None of E, A, E/A, or DT were independently associated with DD or disease type. Septal and lateral LV wall s' and e' were all inversely correlated with age, and there was a small independent contribution to the prediction of lateral s' from DD, but no association of either s' or e' with disease type. The presence of ILD was not a predictor of any of the LV variables. In SSc there are associations of sex, body size, age and disease type with LV structural variables, of age and heart rate with E/A, and of age with both systolic and early diastolic LV long-axis velocities. Appropriate adjustment for these variables could help to resolve current uncertainties regarding SSc effects on the left ventricle.

Evaluation of Perugini score and myocardial mass and voltage abnormalities in transthyretine cardiac amyloidosis

Abstract Background Transthyretine cardiac amyloidosis (TTR-CA) is an emerging treatable disease in cardiology. Severity of TTR infiltration can be assessed by bone scintigraphy with Perugini score, depending on HPD-Tc99M myocardial intensity uptake. Less is known on how Perugini score interplays with routine cardiac structural parameters, especially cardiac mass and voltage. Aim To evaluate correlation between Perugini score and myocardial mass and voltage abnormalities in patients with TTR-CA. Methods Patients diagnosed with ATTR-CA and addressed to our center for treatment underwent complete evaluation including electrocardiogram (ECG) and transthoracic echocardiography (TTE). Routine electrical and echographic parameters were obtained such as: Sokolow indice (SV1+RV5) in millivolt (mV), PR delay (ms), QRS width (in ms), left ventricular mass (LVM, in grams) and diastolic interventricular septum (dIVS) thickness (in mm). Patients were classified in three categories according to Perugini score: I (cardiac uptake < chest bones), II (cardiac uptake = chest bones) and III (cardiac uptake > bones). Main end-point were LVM and Voltage/Mass ratio (VMR) variations, depending on Perugini score. Results Among the 17 patients included, 14 were male (82.4%) and mean age was 82±8 years old. On ECG, 6 patients (35.3%) had permanent atrial fibrillation (AF). Mean voltage according to Sokolow index, mean PR delay and mean QRS width were respectively 1.5±0.5 mV, 212±54 ms and 113±19 ms. On TTE, mean LVM and mean dIVS width were respectively 333±98 g (188±55 g/m2) and 19±4 mm. Mean voltage/mass ratio (VMR) was 0.48±0.26 uV/g (see table). On bone scintigraphy, 3 patients were scored with Perugini I (17.6%), 4 with Perugini II (23.5%) and 10 with Perugini III (58.8%). According to Pearson test, there was a strong correlation between Perrugini score and LVM (r=+0.56, p=0.03) (graph A), and a strong negative correlation between Perrugini score and VMR (r=−0.70, p=0.003) (graph B). There were a trend for correlation between Perugini score and Voltage according to Sokolow (r=−0.46, p=0.07) and between Perugini score and dIVS width (r=0.49, p=0.07). Conclusion In TTR-CA patients, Perugini score appears to strongly correlate with left ventricle mass and voltage. Larger scale studies are needed to confirm these results. Funding Acknowledgement Type of funding sources: None. ECG and TEE trends according to PeruginiCardiac mass and voltage with Perugini

Are there predictor variables for the diagnosis of transthyretin cardiac amyloidosis?

Abstract Introduction Transthyretin cardiac amyloidosis (ATTR) can be reliably diagnosed in the absence of histology if grade 2 or 3 cardiac uptake is demonstrated on 99mTc-DPD scan (DPD) in the absence of a detectable monoclonal component. Diagnosis requires a high degree of clinical suspicion in the presence of often non-specific findings and that it may be one of the reasons to under-diagnose ATTR. The aim of the study is to identify clinical, analytical and ECG variables that best predict a positive DPD result. Methods This is a multicentre retrospective study including all patients undergoing consecutive 99mTc-DPD scintigraphy in a reference area of 750,000 inhabitants between January 2016 and January 2021 for suspected ATTR. AL amyloidosis patients were excluded. Clinical, analytical, ECG and echocardiographic data were analyzed. We identified variables that independently predicted a positive DPD study using a multivariable logistic regression analysis. Receiver Operating Curve (ROC) analysis and the Area under the Curve (AUC) were calculated to assess the discrimination capacity of the model to predict a positive DPD study. Results DPD scans from a total of 181 patients were analyzed. Mean age of the sample: 78 years (42–96), 100% caucasians, 77% male. 54.7% (N=99) had a positive DPD study (defined as grade 2 or 3 Perugini uptake) and 45.3% (N=82) were negative. Independent predictors of a positive study were age, male gender, left ventricular septum thickness, any grade of atrioventricular block, low QRS voltage, Carpal tunnel syndrome, history of hypotension or need to lower antihypertensive drugs and a NT-proBNP value above 1800 pg/ml (See Table 1). The diagnostic accuracy of the model was excellent, with an AUC of 0.92 (IC 95% 0.87–0.96) (see Figure 1). Conclusions There are clinical-analytical factors and ECG and echocardiogram findings accessible in daily clinical practice that are able to predict a positive result on cardiac scintigraphy requested for suspected ATTR. Identifying these factors may improve the non-invasive diagnosis of ATTR. Funding Acknowledgement Type of funding sources: None. Table 1. Multivariable logistic regression analysFigure 1. ROC curve

Comparative analysis of phasic left atrial strain and left ventricular posterolateral strain to discriminate Fabry cardiomyopathy from other forms of left ventricular hypertrophy

Abstract Background “Classic” echocardiographic signs of Fabry cardiomyopathy (FC), such as left ventricular hypertrophy (LVH) and posterolateral strain deficiency (PLSD) have a low diagnostic accuracy in clinical practice. Purpose Our aim was to evaluate the diagnostic accuracy of phasic left atrial strain impairment compared to PLSD to discriminate FC from other forms of LVH. Methods 40 patients with LVH due to bioptically and genetically confirmed FC or with LVH due to other causes, defined by exclusion of storage diseases, such as Amyloidosis or FC, by myocardial biopsy, were retrospectively analysed. Standard echocardiographic views (Vivid E9, GE, Vingmed, Horton) were used to analyse left atrial (LA) reservoir, conduit, and contraction strain using 2D speckle tracking echocardiography (2DSTE; EchoPAC software, GE) as well as the PLSD, obtained by the mean of deformation values in basal posterior and lateral segments in a 17-segment model. Receiver operating characteristic (ROC) curve analysis and a logistic regression model were performed to assess the diagnostic accuracy of LA and LV strain impairment. Results FC was confirmed in 20 patients by genetic testing and myocardial biopsy. In the LVH group, 12 patients were classified to have hypertrophic cardiomyopathy, two had hypertensive heart disease, and six expressed the pattern of LV hypertrophy combined with borderline myocarditis. LV septum thickness (15.8mm±3.4 in FC; 17.9mm±4.3 in LVH) and left atrial volume index (LAVI) (36.7ml/m2±11.3 in FC; 45.7ml/m2±16.3 in LVH) as well as LVEF (54.2%± 9.8 in FC; 52.5%±7.7 in LVH,) were not statistically different between groups. LV filling parameters such as E/A (1.2±0.5 in FC; 1.2±0.7 in LVH) and E/e' (11.0±4.9 in FC; 13.2±5.3 in LVH) showed a slightly more advanced impairment in the LVH group. Global and regional LV function was not different between groups (LVGLS −13.8±3.7% in FC and −12.8±3.7% in LVH; PLSD −10.7±5.2% in FC and −8.85±3.9% in LVH; p-value?). LA reservoir strain (LASr) and LA conduit strain (LAScd) were significantly impaired in FC compared to the LVH group (LASr 14,6±2.5% in FC and 26.3±8.5% in LVH, p<0.01; LAScd −5.9±2.6% in FC and −15.8±4.7% in LVH, p<0.01). In ROC analysis, LASr, with an area under the curve (AUC) of 0.81 (95% CI 0.64–0.97) and LAScd with an AUC of 0.85 (95% CI 0.71–0.99), respectively, showed the highest diagnostic accuracy to discriminate FC. PLSD, in contrast, held a low diagnostic accuracy with an AUC of only 0.47 (95% CI 0.27–0.68). Conclusion A substantially higher diagnostic accuracy could be shown for LASr and LAScd impairment in discriminating FD and other forms of LVH compared to PLSD. The echocardiographic assessment of phasic LA strain may help to identify FC in patients with unclear LVH. Funding Acknowledgement Type of funding sources: None. ROC analysisRepresentative examples

ELECTROCARDIOGRAPHIC CHARACTERISTICS WITH LEFT BUNDLE BRANCH AREA PACING: A SINGLE CENTER PROSPECTIVE STUDY

<h3>BACKGROUND</h3> Pure left bundle branch (LBB) capture should result in typical RBBB (rsR') morphology. However, numerous paced QRS morphologies are observed during LBB area pacing (LBBAP). There are limited papers describing the various electrocardiographic (ECG) morphologies seen with LBBAP. Objective: To evaluate the various ECG characteristics encountered in LBBAP. <h3>METHODS AND RESULTS</h3> Patients referred for pacemaker implantation between 08/2019-01/2021 were considered for LBBAP. LBBAP was performed by implantation of a Medtronic 3830 lead 2 cms distal to His and confirmed by previously published criteria. Paced QRS morphology and QRS axis was analyzed. Baseline, ECG, and implantation characteristics are summarized in table 1. Of 264 LBBAP ECGs, the most common morphology seen during unipolar tip pacing was an incomplete RBBB pattern (qR) in V1 in 165 (69.9%) patients. rSR' pattern was seen in 9 (3.2%) and a narrow QS pattern in 60 (21.5%) patients. <h3>CONCLUSION</h3> Various ECG morphologies may be encountered during successful LBB area capture and are associated with similar QRSd, pacing characteristics and short-term lead performance. These morphologies are due to capture of various structures (RV or LV septum, capture of LBB, LPF +/- RBB) and are likely due to virtual-electrode effect.

One-Year Committed Exercise Training Reverses Abnormal Left Ventricular Myocardial Stiffness in Patients With Stage B Heart Failure With Preserved Ejection Fraction.

Individuals with left ventricular (LV) hypertrophy and elevated cardiac biomarkers in middle age are at increased risk for the development of heart failure with preserved ejection fraction. Prolonged exercise training reverses the LV stiffening associated with healthy but sedentary aging; however, whether it can also normalize LV myocardial stiffness in patients at high risk for heart failure with preserved ejection fraction is unknown. In a prospective, randomized controlled trial, we hypothesized that 1-year prolonged exercise training would reduce LV myocardial stiffness in patients with LV hypertrophy. Forty-six patients with LV hypertrophy (LV septum >11 mm) and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [>40 pg/mL] or high-sensitivity troponin T [>0.6 pg/mL]) were randomly assigned to either 1 year of high-intensity exercise training (n=30) or attention control (n=16). Right-heart catheterization and 3-dimensional echocardiography were performed while preload was manipulated using both lower body negative pressure and rapid saline infusion to define the LV end-diastolic pressure-volume relationship. A constant representing LV myocardial stiffness was calculated from the following: P=S×[Exp {a (V-V0)}-1], where "P" is transmural pressure (pulmonary capillary wedge pressure - right atrial pressure), "S" is the pressure asymptote of the curve, "V" is the LV end-diastolic volume index, "V0" is equilibrium volume, and "a" is the constant that characterizes LV myocardial stiffness. Thirty-one participants (exercise group [n=20]: 54±6 years, 65% male; and controls (n=11): 51±6 years, 55% male) completed the study. One year of exercise training increased max by 21% (baseline 26.0±5.3 to 1 year later 31.3±5.8 mL·min-1·kg-1, P<0.0001, interaction P=0.0004), whereas there was no significant change in max in controls (baseline 24.6±3.4 to 1 year later 24.2±4.1 mL·min-1·kg-1, P=0.986). LV myocardial stiffness was reduced (right and downward shift in the end-diastolic pressure-volume relationship; LV myocardial stiffness: baseline 0.062±0.020 to 1 year later 0.031±0.009), whereas there was no significant change in controls (baseline 0.061±0.033 to 1 year later 0.066±0.031, interaction P=0.001). In patients with LV hypertrophy and elevated cardiac biomarkers (stage B heart failure with preserved ejection fraction), 1 year of exercise training reduced LV myocardial stiffness. Thus, exercise training may provide protection against the future risk of heart failure with preserved ejection fraction in such patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03476785.

Traumatic Left Ventricular Aneurysm and Ventricular Septal Defect in a Child.

Cardiac injuries following blunt trauma are rare but potentially lethal in children. We present a 23-month-old child who sustained an aneurysm of the left ventricle free wall and ventricular septum with associated ventricular septal defect following blunt trauma. She underwent successful surgical repair 6 weeks following her date of injury. Surgical decision-making surrounding this case is discussed.

Accuracy of electroanatomical mapping-guided cardiac radiotherapy for ventricular tachycardia: pitfalls and solutions.

To analyse and optimize the interobserver agreement for gross target volume (GTV) delineation on cardiac computed tomography (CCT) based on electroanatomical mapping (EAM) data acquired to guide radiotherapy for ventricular tachycardia (VT). Electroanatomical mapping data were exported and merged with the segmented CCT using manual registration by two observers. A GTV was created by both observers for predefined left ventricular (LV) areas based on preselected endocardial EAM points indicating a two-dimensional (2D) surface area of interest. The influence of (interobserver) registration accuracy and availability of EAM data on the final GTV and 2D surface location within each LV area was evaluated. The median distance between the CCT and EAM after registration was 2.7 mm, 95th percentile 6.2 mm for observer #1 and 3.0 mm, 95th percentile 7.6 mm for observer #2 (P = 0.9). Created GTVs were significantly different (8 vs. 19 mL) with lowest GTV overlap (35%) for lateral wall target areas. Similarly, the highest shift between 2D surfaces was observed for the septal LV (6.4 mm). The optimal surface registration accuracy (2.6 mm) and interobserver agreement (Δ interobserver EAM surface registration 1.3 mm) was achieved if at least three cardiac chambers were mapped, including high-quality endocardial LV EAM. Detailed EAM of at least three chambers allows for accurate co-registration of EAM data with CCT and high interobserver agreement to guide radiotherapy of VT. However, the substrate location should be taken in consideration when creating a treatment volume margin.

Association of smoking with indicators of the structure and function of left ventricle of the heart in middle-aged men

Aim. Evaluation of the association of smoking (status, intensity and duration) with indicators of the structure and function of the left ventricle of the heart in a sample of middle-aged men.Material and methods. This study is part of a 32-year prospective cohort observation of men from childhood (11-12 years). 301 (30.0%) representatives of the original population sample aged 41-44 years were included in the study. The examination included a survey on intensity of smoking, anthropometry, measuring blood pressure, pulse rate, echocardiography, and blood lipid analysis.Results. 301 men aged 41-44 included 92 (30.6%) men who had never smoked, 73 (24.3%) men smoked in the past and 136 (45.2%) men currently smoke. 75% of current smokers started smoking before age 19, of which 32.3% started smoking before age 15. The duration of smoking cessation among former smokers was 14.4 (12.5; 16.2) years. The average duration of smoking [average (95% confidence interval)] among former smokers was 14.4 (12.5; 16.2), for current smokers – 25.3 (24.6; 26.0) years. Current smoking was statistically significantly associated with higher mean values of the left ventricular myocardium mass (LVMM), the left ventricular myocardial mass index (LVMMI), the end-systolic and end-diastolic interventricular septum thickness (IVSTs/IVSTd), the end-systolic left ventricular posterior wall thickness (LVPWs), and the intensity and duration of current smoking were associated with higher values of the relative wall thickness of the left ventricle, the end-diastolic interventricular septum thickness, the end-systolic interventricular septum thickness, and with low values of the left ventricular stroke volume index (LV SVI). Multiple regression analysis showed that current smoking has an independent effect on the left ventricular myocardium mass, the left ventricular myocardial mass index and the end-diastolic interventricular septum thickness, and the duration and intensity of smoking has an effect on the index of the left ventricular stroke volume index.Conclusion. Current smoking, duration and intensity in middle-aged men is associated with unfavorable changes in indicators of the structure and function of the left ventricle of the heart. Efforts for primary prevention of smoking should begin as early as childhood and continue into adolescence and young adulthood.

Protocatechuic acid attenuates isoproterenol-induced cardiac hypertrophy via downregulation of ROCK1\u2013Sp1\u2013PKC\u03b3 axis

Cardiac hypertrophy is an adaptive response of the myocardium to pressure overload or adrenergic agonists. Here, we investigated the protective effects and the regulatory mechanism of protocatechuic acid, a phenolic compound, using a mouse model of isoproterenol-induced cardiac hypertrophy. Our results demonstrated that protocatechuic acid treatment significantly downregulated the expression of cardiac hypertrophic markers (Nppa, Nppb, and Myh7), cardiomyocyte size, heart weight to body weight ratio, cross-sectional area, and thickness of left ventricular septum and posterior wall. This treatment also reduced the expression of isoproterenol-induced ROCK1, Sp1, and PKCγ both in vivo and in vitro. To investigate the mechanism, we performed knockdown and overexpression experiments. The knockdown of ROCK1, Sp1, or PKCγ decreased the isoproterenol-induced cell area and the expression of hypertrophic markers, while the overexpression of Sp1 or PKCγ increased the levels of hypertrophic markers. Protocatechuic acid treatment reversed these effects. Interestingly, the overexpression of Sp1 increased cell area and induced PKCγ expression. Furthermore, experiments using transcription inhibitor actinomycin D showed that ROCK1 and Sp1 suppression by protocatechuic acid was not regulated at the transcriptional level. Our results indicate that protocatechuic acid acts via the ROCK1/Sp1/PKCγ axis and therefore has promising therapeutic potential as a treatment for cardiac hypertrophy.

Morphological, Functional, and Tissue Characterization of Silent Myocardial Involvement in Patients With Primary Biliary Cholangitis

Cirrhotic cardiomyopathy is a major complication and cause of morbidity in end-stage primary biliary cholangitis (PBC). However, it is unclear whether there is clinically silent myocardial involvement at the early stage of PBC before cirrhosis and cardiac manifestations. This prospective, three-center, multi-modality cardiac imaging study on the early identification of myocardial impairment in PBC (EARLY-MYO-PBC) was designed to identify silent myocardial impairment in PBC patients without cardiac manifestations. A total of 112 subjects (56 with PBC and 56 age- and sex-matched controls) undergoing cardiovascular magnetic resonance (CMR) were enrolled. Demographic, serologic, and cardiac imaging data were prospectively collected. All participants had no cardiac discomfort or previous heart disease and had normal electrocardiographic findings. Subclinical myocardial involvement, as evidenced by cardiac morphologic, functional, and tissue characterization changes on CMR, including hyperdynamic left ventricular (LV) ejection fraction (median, 75% in PBC patients vs 69% in controls, P= .029), subclinical myocardial edema by T2-short tau inversion recovery (21% vs 2% in controls, P= .001), elevated extracellular matrix indices (30% vs 26% in controls, P < .001), and impaired myocardial viability by positive late gadolinium enhancement (LGE) (36%), was detected in PBC patients. Importantly, a mid-wall "stripe" at the LV septum was identified as a PBC-specific LGE pattern that differs from other known cardiomyopathies. In multivariate analysis, gp210 positivity (odds ratio [OR]= 9.909, P= .010), lower hemoglobin (OR= 0.919, P= .004), and body mass index (OR= 0.638, P= .005) were independent predictors of cardiac abnormalities in PBC. This study demonstrates clinically silent cardiac impairment with specific CMR patterns in PBC, allowing optimal screening for early myocardial impairment and potentially timely therapies. (Trial registration no.: NCT03545672).

Sex-Related Risk of Cardiac Involvement in Hereditary Transthyretin Amyloidosis: Insights From THAOS

ObjectivesBecause patients with ATTRv cardiomyopathy are more likely to be male, this analysis aimed to increase information on associations between sex and genotype, phenotype, and degree of myocardial involvement in ATTRv amyloidosis. BackgroundTransthyretin amyloid cardiomyopathy is a progressive, fatal disease that occurs due to accumulation of wild-type or variant (ATTRv) transthyretin amyloid fibrils in the myocardium. MethodsThe Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing global longitudinal observational survey of patients with ATTR amyloidosis and asymptomatic carriers with TTR mutations. Data from THAOS (data cutoff: January 6, 2020) were analyzed to determine any sex-based differences in genotype, phenotype, and presence of cardiac and neurological symptoms in patients with ATTRv amyloidosis and in patients with ATTRv amyloidosis and cardiomyopathy. ResultsThere were 2,790 patients with ATTRv amyloidosis enrolled in THAOS, with male patients more likely to have symptoms of cardiac involvement and a cardiac phenotype. Male prevalence was greater in patients with more severe cardiac manifestations of disease, as assessed with N-terminal pro–B-type natriuretic peptide, left-ventricular (LV) ejection fraction, mean LV wall thickness divided by height, and LV mass index divided by height. Sex, age at disease onset, and genotype category were identified by multivariate analyses as risk factors for the development of cardiomyopathy (defined as increased LV septum thickness divided by height). ConclusionsIn this analysis, myocardial involvement was more frequent and pronounced in male patients with ATTRv amyloidosis, suggesting that there may be biological characteristics that inhibit myocardial amyloid infiltration in females or facilitate it in males.

B-PO05-037 ELECTROCARDIOGRAPHIC CHARACTERISTICS WITH LEFT BUNDLE BRANCH AREA PACING: A SINGLE CENTER PROSPECTIVE STUDY

Pure left bundle branch (LBB) capture should result in typical RBBB (rsR’) morphology. However, numerous paced QRS morphologies are observed during LBB area pacing (LBBAP). There are limited papers describing the various electrocardiographic (ECG) morphologies seen with LBBAP. To evaluate the various ECG characteristics encountered in LBBAP. Patients referred for pacemaker implantation between 02/2019-02/2021 were considered for LBBAP. LBBAP was performed by implantation of a Medtronic 3830 lead 2 cms distal to His and confirmed by previously published criteria. If unsuccessful, lead was repositioned distally and inferiorly on the septum to capture the left posterior fascicle (LPF). Paced QRS morphology and QRS axis was analyzed. Baseline, ECG, and implantation characteristics are summarized in table 1. Of 274 LBBAP ECGs, the most common morphology seen during unipolar tip pacing was an incomplete RBBB pattern (qR) in V1 in 131 (48%) patients. rSR’ pattern was seen in 38 (14%) and a narrow QS pattern in 34 (12.5%) patients. qR or rsR’ with left axis deviation, i.e., LPF capture was noted in 69 (25%) patients. One patient exhibited monophasic R in lead V1. Unipolar ring pacing resulted in wide QS in all patients due to RV septal capture only. Various ECG morphologies may be encountered during successful LBB area capture and are associated with similar QRSd, pacing characteristics and short-term lead performance. These morphologies are due to capture of various structures (RV or LV septum, capture of LBB, LPF +/- RBB) and are likely due to virtual-electrode effect.

B-PO02-127 OUTCOMES OF CATHETER ABLATION OF VENTRICULAR ARRHYTHMIAS ORIGINATING FROM A LEFT VENTRICULAR FALSE TENDON

Left ventricular false tendons (LV-FT) are chord-like fibromuscular structures that cross the LV cavity and attach between the septum, papillary muscles (PM), or the free wall. Ventricular arrhythmias (VAs) arising from LV-FT have been described in isolated case reports, but data on larger cohorts of patients are insufficient. We investigated the prevalence, electrophysiologic features and outcomes of catheter ablation of LV-FT VAs. We screened 3719 patients undergoing ablation of VAs at our institution between January 2011 and August 2020. Diagnosis of LV-FT origin of the VA was based on detailed activation/pace-mapping guided by intracardiac echocardiography (ICE). A total of 16 (0.4%) patients (age 60±15 years, LVEF 38±16%) with LV-FT VAs were identified. Of these, 9 (56%) had focal PVC/VT from the LV-FT and 7 (44%) scar-related monomorphic VT with critical circuit elements involving the LV-FT. The most common anatomical locations of the LV-FT were between the posteromedial PM and LV septum, between the anterolateral and posteromedial PM and between the LV apex and the mid-septum. Purkinje potentials in sinus rhythm were recorded on the LV-FT at the VA target site in only 1 case. Acute ablation success was achieved in 15 (94%) patients (Figure). After a median follow-up of 1.5 years, the targeted LV-FT VA recurred in 4 (31%). The LV-FT can be a rare site of origin of focal VAs or may contain critical circuit elements of scar-related VTs. Mapping and catheter ablation guided by ICE is successful in eliminating LV-FT VAs in most cases.

B-PO02-135 LEFT VENTRICLE POSTERIOR SUPERIOR PROCESS ECTOPY: RISK OF AV NODE BLOCK DURING ABLATION

Premature ventricular contractions (PVC) originating from the highest portion of the inferior left ventricular (LV) septum are infrequent and challenging to treat with catheter ablation (CA). The incidence and CA risks are ill-defined. We sought to determine the incidence of PVC originating from the posterior superior process (PSP) at our institution. We reviewed our records retrospectively between 1/2018 and 10/2020 for all PVC ablations. We selected all patients who underwent PVC ablation from the PSP region. 370 patients underwent PVC were identified from institutional ventricular tachycardia database. Of the total cohort, four patients (1%) had PVCs ablated from the PSP region. Three of four were male, normal LVEF average 51% and only one had myocardial scarring on imaging studies. Despite different PVC morphologies, EKG had common characteristics including monophasic R in lead I, rS in lead II and slow downsloping QS in aVR (the “RI-rSII-QSaVR” triad). Acutely successful ablation was performed in all four cases. In all but one case, RF ablation at the earliest mapping site was associated with either transient delay in AV conduction or accelerated junctional rhythm. In 6 months follow up, none of the patients had arrhythmia recurrence. Prolonged monitoring in two patients indicated high degree AV block at sleep but none meet the criteria for pacing. PVCs originating from the PSP are rare, occurring in about 1% of referred patients. Even when approached from the left side, attention to proximity to the compact AV node is warranted when ablating in the PSP region. Despite these concerns, success of ablation is high.

Septal late gadolinium enhancement on Cardiac MRI predicts failure to achieve left bundle pacing

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background; Left bundle area pacing is a novel technique that provides direct stimulation of cardiac conduction tissue in order to deliver physiological ventricular activation. The approach for left bundle area pacing is transseptal lead implantation, where the lead is advanced from the right ventricular side of the septum to the left ventricular side to capture the proximal left bundle. Observational data suggests that whilst this is a safe and feasible method, implant success rate is not 100%, and appears to be lower in patients with a cardiac resynchronization therapy (CRT) indication rather than a bradycardia indication for pacing. The mechanisms for failure to advance the lead through the ventricular septum are not well understood. Purpose; We used pre-procedural CMR to determine whether there are features which can help identify patients where lead implantation may be challenging. We assessed whether the extent and location of septal late gadolinium enhancement identified patients in whom left bundle area pacing will be challenging. We hypothesized that the presence of extensive scar in the septum impedes advancing the lead to the left ventricular septum and prevents capture of the left bundle. Methods; Patients underwent cardiac MRI including motion corrected free-breathing late gadolinium enhancement imaging1 before implantation. Scar was quantified using the full height half maximum method and expressed as the overall proportion of myocardial mass in the basal anteroseptal and basal inferoseptal segments, as shown in Figure 1. Left bundle area pacing was then attempted in patients with a CRT indication for pacing. We compared the extent of septal scar between patients in whom left bundle area pacing was achieved and those where there was failure to advance the lead deep into the septum. Results; 12 patients (11 male, 1 female), with average age 72 (IQR 63 to 78) and LVEF 30% (IQR 26 to 33) were studied. There was failure to advance the lead deep into the septum in 4 patients. There was a significantly higher basal septal scar burden in those patients where there was failure to advance the left bundle lead compared to those in which left bundle capture was achieved as shown in Figure 2 (median 55% and 5% respectively, p-value 0.02 by Wilcoxon signed rank test). Conclusion; The presence and extent of late gadolinium enhancement in the basal septum appears to be an important determinant of successful implantation of left bundle pacing lead using current implant technology. This may be because extensive septal scar prevents advancement of the pacing lead through the septum. Cardiac MRI before left bundle area pacing is likely to be useful in procedural planning.

Detection of congestive heart failure by mitral annular displacement in cats with hypertrophic cardiomyopathy – concordance between tissue Doppler imaging–derived tissue tracking and M-mode

IntroductionThe left ventricular systolic longitudinal function, traditionally measured by M-mode–derived mitral annular plane systolic excursion (MAPSE), is reduced in feline hypertrophic cardiomyopathy (HCM) and further reduced in cats with left-sided congestive heart failure (CHF). The objectives of this study were to compare longitudinal displacement measured by tissue tracking (TT-LD) and MAPSE in feline HCM and assess these methods’ ability to differentiate CHF from preclinical HCM. A further objective was to provide preliminary reference intervals for TT-LD. AnimalsEighty-five client-owned cats. MethodsA retrospective case–control study. Anatomical M-mode was used to record MAPSE, and TT-LD was recorded by tissue tracking. ResultsReduced longitudinal displacement measured by either MAPSE or TT-LD was significantly associated with CHF in cats with HCM (p < 0.036). Receiver-operating characteristic analysis indicated that TT-LD (AUC: 92.9%–97.9%) was more sensitive and specific than MAPSE (AUC: 85.8%–89.1%) for the detection of CHF. A diagnostic cut-off of 2.89 mm for maximal TT-LD in the left ventricular septum resulted in a sensitivity and specificity of 100% and 83.3%, while a diagnostic cut-off of 2.41 mm in the left ventricular posterior wall resulted in a sensitivity of 100% and a specificity of 90%. ConclusionsM-mode–derived mitral annular plane systolic excursion and TT-LD were strongly correlated, but not interchangeable. Longitudinal displacement measured by tissue tracking decreased more with disease severity than traditional MAPSE. Longitudinal displacement may help detect CHF in cats with HCM – with the maximal TT-LD of the left ventricular posterior wall achieving the highest AUC value.

Description and Clinical Implications of Myocardial Clefts Using Echocardiography.

BackgroundMyocardial clefts (MCs) are rare anomalies with debatable clinical significance. Increased use of cardiac magnetic resonance (CMR) has led to the appreciation of subtle left ventricular (LV) wall structural defects, and studies showed varying clinical significance, ranging from asymptomatic incidental findings to being considered a novel imaging marker of hypertrophic cardiomyopathy. Sparse data are available about the utility of two-dimensional echocardiography (2DE) to visualize these anomalies. We describe our institutional experience categorizing MCs using 2DE.MethodsThe echocardiography database was retrospectively queried for diagnosing MCs using Synapse® Cardiovascular Picture Archiving and Communication System (PACS) (Fujifilm, Tokyo, Japan). Identified patients were admitted to Detroit Medical Center (DMC) between January 2012 and May 2019. MCs were defined as recesses filled with luminal blood, obliterate during systole, and have U, wedge, and tunnel shapes. Images were interpreted by a cardiologist blinded to the data. Baseline demographics and clinical characteristics were documented. The study was descriptive; no intervention was done.ResultsSixteen patients with a mean age of 62.43 were included; 68.75% were women, and 81.25% were African American. The prevalence of cardiac comorbidities was primary hypertension 12 (75%), coronary artery disease 5 (31.25%), heart failure with reduced ejection fraction (HFrEF) 4 (25.0%), valvular heart disease 4 (25.0%), arrhythmia/heart block 4 (25.0%), and heart failure with preserved ejection fraction (HFpEF) 2 (12.5%). The indications for 2DE evaluation were heart failure/cardiogenic shock 2 (12.5%), acute coronary syndrome 2 (12.5%), syncope/presyncope 2 (12.5%), atypical chest pain 2 (12.5%), and others 8 (50.0%). Twenty-one MCs were visualized in eight segments of LV walls and septum as follows: basal inferior 7, mid inferoseptal 6, mid inferior 3, mid anteroseptal 2, mid inferolateral 1, mid anterolateral 1, basal inferoseptal 1, apical inferoseptal 1, and apical septal 1. Morphology was classified as tunnel in 66.66%, wedge in 23.8%, and U in 9.5%.ConclusionIn various LV and septal walls, MCs detected on 2DE were benign and incidental findings without significant implications for preclinical hypertrophic cardiomyopathy (HCM).

Investigating Insulin Resistance in Pediatric Cardiomyopathy - A Pilot Study

Children with cardiomyopathy are a vulnerable population and understanding the factors that contribute to cardiac dysfunction are of great importance. At the biochemical level, energy utilization by cardiomyocytes during stress may provide insight into the progression of cardiomyopathy. There is a large body of literature that describes insulin resistance in adults with cardiomyopathy (1,2). Extensive literature on the topic in adult individuals exists however investigation in the pediatric population is sparse. The pathophysiology of disease in children and adolescents is unique. To study the role of insulin resistance in pediatric cardiomyopathy, we measured the homeostasis model assessment-estimated insulin resistance (HOMA-IR) at baseline in pre-pubertal patients (age 13-18 years old; mean 16 years old; n = 8) with either hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM). In patients with HCM, greater insulin resistance was positively correlated with greater left ventricular (LV) septal thickness (r = 0.55; p = 0.33; n = 5) and LV posterior wall thickness (r = 0.7; p = 0.19; n = 5) during diastole. As expected, insulin resistance was strongly correlated with BMI (r = 0.84; p = 0.08; n = 5) though greater BMI was not as strongly associated with LV septal thickness (r = 0.59; p = 0.3; n = 5) or posterior wall thickness (r = 0.59; p = 0.3; n = 5). In patients with DCM, insulin resistance was positively correlated with LV end diastolic volume (r = 0.59; p = 0.59; n = 3). Interestingly, there was an observed inverse association between insulin resistance and BMI in DCM (r = -0.85; p = 0.34; n =3). Though our sample population is limited, thus affecting statistical significance, results showed that there was a trend towards greater insulin resistance in patients with poorer cardiac measurements. These findings are consistent with adult literature and the proposition that cardiac dysfunction is an insulin resistant state.

Translational investigation of electrophysiology in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) patients are at increased risk of ventricular arrhythmias and sudden cardiac death, which can occur even in the absence of structural changes of the heart. HCM mouse models suggest mutations in myofilament components to affect Ca2+ homeostasis and thereby favor arrhythmia development. Additionally, some of them show indications of pro-arrhythmic changes in cardiac electrophysiology. In this study, we explored arrhythmia mechanisms in mice carrying a HCM mutation in Mybpc3 (Mybpc3-KI) and tested the translatability of our findings in human engineered heart tissues (EHTs) derived from CRISPR/Cas9-generated homozygous MYBPC3 mutant (MYBPC3hom) in induced pluripotent stem cells (iPSC) and to left ventricular septum samples obtained from HCM patients.We observed higher arrhythmia susceptibility in contractility measurements of field-stimulated intact cardiomyocytes and ventricular muscle strips as well as in electromyogram recordings of Langendorff-perfused hearts from adult Mybpc3-KI mice than in wild-type (WT) controls. The latter only occurred in homozygous (Hom-KI) but not in heterozygous (Het-KI) mouse hearts. Both Het- and Hom-KI are known to display pro-arrhythmic increased Ca2+ myofilament sensitivity as a direct consequence of the mutation. In the electrophysiological characterization of the model, we observed smaller repolarizing K+ currents in single cell patch clamp, longer ventricular action potentials in sharp microelectrode recordings and longer ventricular refractory periods in Langendorff-perfused hearts in Hom-KI, but not Het-KI. Interestingly, reduced K+ channel subunit transcript levels and prolonged action potentials were already detectable in newborn, pre-hypertrophic Hom-KI mice. Human iPSC-derived MYBPC3hom EHTs, which genetically mimicked the Hom-KI mice, did exhibit lower mutant mRNA and protein levels, lower force, beating frequency and relaxation time, but no significant alteration of the force-Ca2+ relation in skinned EHTs. Furthermore, MYBPC3hom EHTs did show higher spontaneous arrhythmic behavior, whereas action potentials measured by sharp microelectrode did not differ to isogenic controls. Action potentials measured in septal myectomy samples did not differ between patients with HCM and patients with aortic stenosis, except for the only sample with a MYBPC3 mutation.The data demonstrate that increased myofilament Ca2+ sensitivity is not sufficient to induce arrhythmias in the Mybpc3-KI mouse model and suggest that reduced K+ currents can be a pro-arrhythmic trigger in Hom-KI mice, probably already in early disease stages. However, neither data from EHTs nor from left ventricular samples indicate relevant reduction of K+ currents in human HCM. Therefore, our study highlights the species difference between mouse and human and emphasizes the importance of research in human samples and human-like models.