Ventricular Free Wall Research Articles

Comparison of cardiovascular metrics on computed tomography pulmonary angiography of the updated and old diagnostic criteria for pulmonary hypertension in patients with chronic thromboembolic pulmonary hypertension.

In the 2022 European Society of Cardiology (ESC) and the European Respiratory Society (ERS) guidelines, the diagnostic criteria for pulmonary hypertension (PH) included a reduced mean pulmonary artery pressure (mPAP) of 20 mmHg (mPAP >20 mmHg). This study aimed to reassess cardiovascular metrics on computed tomography pulmonary angiography (CTPA) for chronic thromboembolic pulmonary hypertension (CTEPH) to optimize the timely diagnosis of patients with suspected PH. Patients with suspected CTEPH who underwent CTPA and right heart catheterization (RHC) between January 2019 and December 2022 in China-Japan Friendship Hospital were retrospectively included. They were grouped into CTEPH and non-PH groups according to the new and old criteria (2022 and 2015 ESC/ERS guidelines) for the diagnosis of PH. Cardiovascular metrics including the main pulmonary artery diameter (MPAd), Cobb angle, and right ventricular free wall thickness (RVWT), among others, were measured. The correlation of these metrics with hemodynamic data was analyzed with Spearman rank correlation analysis, while the differences in cardiovascular metrics between the updated (mPAP >20 mmHg) and old PH criteria (mPAP ≥25 mmHg) were compared with independent samples t-test or the Mann-Whitney test. Receiver operator characteristic (ROC) curve analysis was performed for the prediction model. The study enrolled 180 patients (males n=86; age 55.5±12.0 years old). According to the old guidelines, 119 patients were placed into the PH group (mPAP ≥25 mmHg) , while according to the new guidelines, 130 patients were placed into the PH group (mPAP >20 mmHg). Cardiovascular metrics on CTPA between the updated and old guidelines were comparable (P>0.05). Compared to other metrics, an MPAd of 30.4 mm exhibited the highest area under the curve (AUC: 0.934±0.021), with a sensitivity of 0.88 and specificity of 0.90. MPAd [odds ratio (OR) =1.271], transverse diameter of the right ventricle (RVtd; OR =1.176), Cobb angle (OR =1.108), and RVWT (OR =3.655) were independent factors for diagnosing CTEPH (P<0.05). Cobb angle, right and left ventricular transverse diameter ratio, and right and left ventricular area ratio moderately correlated with mPAP (r=0.586, r=0.583, r=0.629) and pulmonary vascular resistance (PVR) (r=0.613, r=0.593, r=0.642). Cardiovascular metrics on CTPA were comparable between the new and old guidelines for CTEPH diagnosis. Cardiovascular metrics on CTPA can noninvasively assess the hemodynamics of patients with CTEPH.

Heart failure in patients with hypertrophic obstructive cardiomyopathy

Hypertrophic cardiomyopathy is a hereditary cardiac disease, diverse in clinical manifestations, cardiac structure and natural progression. Patients with disease are associate with a broad range of clinical presentations, from patients who are asymptomatic, accidentally discovered during routine examination, to patients with chest pain, dyspnea, syncope, and even sudden death. We are presenting the clinical case of a young male patient with hypertrophic cardiomyopathy with rather large left ventricular wall thickness about 37mm who was hospitalized with severe dyspnea accompanied by tachycardia episodes and hypotension. The patient underwent electrical cardioversion, Doppler echocardiography, stress Doppler echocardiography with treadmill, cardiac MRI, basic blood tests, coronary CT angiography and ventriculography. The results showed the patient had a very high NT-proBNP level of 16,271 pg/mL; echocardiography showed asymmetric left ventricular hypertrophy, a maximum resting LVOT gradient of 28 mmHg, increasing to 64mmHg at peak stress, preserved left ventricular systolic function and grade III left ventricular diastolic dysfunction; greatly increased left ventricular mass of 199.6 g/m2, and delayed contrast enhancement involving the subendocardium of both ventricles and transecting the left ventricular free wall on cardiac MRI. We also discuss various treatment option for this young man.

Intratracheally Administered Peptide-Modified Lipid Admixture Containing Fasudil and/or DETA NONOate Ameliorates Various Pathologies of Pulmonary Arterial Hypertension.

This study examined the therapeutic potential of a combination therapy using fasudil, a Rho-kinase inhibitor, and DETA NONOate (DN), a nitric oxide donor, delivered as a lipid admixture modified with a cyclic homing peptide known as CAR (CAR-lipid mixture) for the treatment of pulmonary arterial hypertension (PAH). CAR-lipid mixtures were initially prepared via a thin-film hydration method and then combined with fasudil, DN, or a mixture of both. The therapeutic efficacy of this drug-laden lipid mixture was evaluated in a Sugen/Hypoxia (Su/Hx) rat model of PAH by measuring RV systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), Fulton indices, and assessing right ventricular (RV) functions, as well as evaluating pulmonary vascular morphology. Rats that received no treatment exhibited increases in RVSP, mPAP, Fulton indices, and changes in RV functional parameters. However, the treatment with the CAR-lipid mixture containing either fasudil or DN or a combination of both led to a decline in mPAP, RVSP, and Fulton indices compared to saline-treated rats. Similarly, rats that received these treatments showed concurrent improvement in various echocardiographic parameters such as pulmonary acceleration time (PAT), tricuspid annular plane systolic excursion (TAPSE), and ventricular free wall thickness (RVFWT). A significant decrease in the wall thickness of pulmonary arteries larger than 100 µm was observed with the combination therapy. The findings reveal that fasudil, DN, and their combination in a CAR-modified lipid mixture improved pulmonary hemodynamics, RV functions, and pathological alterations in the pulmonary vasculature. This study underscores the potential of combination therapy and targeted drug delivery in PAH treatment, laying the groundwork for future investigations into the optimization of these treatments, their long-term safety and efficacy, and the underlying mechanism of action of the proposed therapy.

Capturing the Influence of Conduction Velocity on Epicardial Activation Patterns Using Uncertainty Quantification.

Individual variability in parameter settings, due to either user selection or disease states, can impact accuracy when simulating the electrical behavior of the heart. Here, we aim to test the impact of inevitable uncertainty in conduction velocities (CVs) on the output of simulations of cardiac propagation, given three stimulus locations on the left ventricular (LV) free wall. To understand the role of physiological variability in CV in simulations of cardiac activation, we generated detailed maps of the variability in propagation simulations by implementing bi-ventricular activation simulations and quantified the effects by deploying robust uncertainty quantification techniques based on polynomial chaos expansion (PCE). PCE allows efficient stochastic exploration with reduced computational demand by utilizing an emulator for the underlying forward model. Our results suggest that CV within healthy physiological ranges plays a small role in the activation times across all stimulation locations. However, we noticed differences in variation coefficients depending on the stimulation site, i.e., LV endocardium, midmyocardium, and epicardium. We observed low levels of variation in activation times near the earliest activation sites, whereas there was higher variation toward the termination sites. These results suggest that CV variability can play a role when simulating healthy and diseased states.

Heterogeneous cardiac sympathetic innervation gradients promote arrhythmogenesis in murine dilated cardiomyopathy.

Ventricular arrhythmias (VAs) in heart failure are enhanced by sympathoexcitation. However, radiotracer studies of catecholamine uptake in failing human hearts demonstrate a proclivity for VAs in patients with reduced cardiac sympathetic innervation. We hypothesized that this counterintuitive finding is explained by heterogeneous loss of sympathetic nerves in the failing heart. In a murine model of dilated cardiomyopathy (DCM), delayed PET imaging of sympathetic nerve density using the catecholamine analog [11C]meta-Hydroxyephedrine demonstrated global hypoinnervation in ventricular myocardium. Although reduced, sympathetic innervation in 2 distinct DCM models invariably exhibited transmural (epicardial to endocardial) gradients, with the endocardium being devoid of sympathetic nerve fibers versus controls. Further, the severity of transmural innervation gradients was correlated with VAs. Transmural innervation gradients were also identified in human left ventricular free wall samples from DCM versus controls. We investigated mechanisms underlying this relationship by in silico studies in 1D, 2D, and 3D models of failing and normal human hearts, finding that arrhythmogenesis increased as heterogeneity in sympathetic innervation worsened. Specifically, both DCM-induced myocyte electrical remodeling and spatially inhomogeneous innervation gradients synergistically worsened arrhythmogenesis. Thus, heterogeneous innervation gradients in DCM promoted arrhythmogenesis. Restoration of homogeneous sympathetic innervation in the failing heart may reduce VAs.

Evolution and prognostic value of left ventricular deformation and myocardial work parameters in transthyretin amyloid cardiomyopathy.

Wild-type transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized condition. It remains challenging to estimate the extent of disease and the prognosis for most patients. Myocardial work is a sensitive echocardiographic approach that improves the characterization of myocardial damage. We investigate the parameters of myocardial deformation and work in ATTR-CM patients and their changes over time. We analysed clinical, electrocardiographic, biological, and echocardiographic characteristics in 113 patients [median age 82 (77-85), 90.4% male] diagnosed with wild-type ATTR-CM based on international consensus at a single centre. We compared the data at baseline and 18-month follow-up. Thirty-four patients died and 12 were hospitalized for heart failure at a median follow-up of 935 days (interquartile range 691-1159 days). Left ventricular end-diastolic diameter, left atrial strain during reservoir phase (LASRES), left ventricular longitudinal strain, global work index (GWI), global constructive work significantly decreased from baseline to 18 months, while left ventricular wall thickness increased. Left ventricular ejection fraction, right ventricular free wall strain (FWS), global wasted work (GWW), and global work efficiency did not alter significantly. Strain parameters were identified as prognostic on baseline evaluation using a multivariate analysis: GWI, GWW, FWS, and LASRES. They were significantly associated with the risk of death and hospitalization for heart failure. Multi-chamber strain assessment may improve the surveillance of patients with ATTR-CM, and myocardial work parameters may improve clinical risk stratification in this population.

Normal age- and sex-based values of right ventricular free wall and four-chamber longitudinal strain by speckle-tracking echocardiography: from the Copenhagen City heart study.

To promote the implementation of right ventricular (RV) longitudinal strain in clinical practice, we sought to propose normal values for RV free wall (RVFWLS) and four-chamber longitudinal strain (RV4CLS) and investigate the association with clinical and echocardiographic parameters in participants from the general population. Participants from the 5th Copenhagen City Heart Study (2011-2015)-a prospective cohort study-with available RV longitudinal strain measurements were included. RVFWLS and RV4CLS were assessed using two-dimensional speckle-tracking echocardiography. In total, 2951 participants were included. Amongst 1297 participants without cardiovascular disease or risk factors (median age 44, 63% female), mean values of RVFWLS and RV4CLS were -26.7% ± 5.2 (95% prediction interval (PI) -36.9, -16.5) and -21.7% ± 3.4 (95%PI -28.4, -15.0), respectively. Women had significantly higher absolute values of RVFWLS and RV4CLS than men (mean -27.5 ± 5.5 vs. -25.4 ± 4.5, p < 0.001 and -22.3 ± 3.5 vs. -20.6 ± 3.0, p < 0.001, respectively). Absolute values of RVFWLS but not RV4CLS decreased significantly with increasing age in unadjusted linear regression. Tricuspid annular plane systolic excursion, RV s' and left ventricular global longitudinal strain were the most influential parameters associated with both RVFWLS and RV4CLS in multiple linear regression. Participants with cardiovascular disease (n = 1531) had a higher proportion of abnormal values of RVFWLS and RV4CLS compared to the healthy population (8% vs. 4%, p < 0.001 and 8% vs. 3%, p < 0.001, respectively). This study proposed normal age- and sex-based values of RVFWLS and RV4CLS in a healthy population sample and showed significant sex differences in both measurements across ages.

Effects of inhaled seralutinib on right ventricular-pulmonary arterial (RV-PA) coupling and right heart function in pulmonary arterial hypertension (PAH)

Abstract Background Impaired RV-PA coupling portends a poor prognosis in PAH, and right ventricular free wall strain/systolic pulmonary artery pressure (RVFWS/sPAP) has been reported as a measure of RV-PA coupling. Furthermore, increased RVFWS and right atrial area (RAA), as well as decreased pulmonary artery compliance (PAC) are associated with increased mortality risk in PAH. Seralutinib is a novel, small molecule kinase inhibitor that targets PDGFR, CSF1R, and c-KIT administered via dry powder inhaler. TORREY, a phase 2, double-blind, randomised, placebo-controlled study of inhaled seralutinib in patients with PAH (NCT04456998) met its primary endpoint, demonstrating a significant reduction in pulmonary vascular resistance (PVR) from baseline (BL) to Week 24 compared to placebo. In addition, seralutinib significantly decreased NT-proBNP. Purpose To test the hypothesis that seralutinib would improve RVFWS/sPAP and other measures of right heart function after 24 weeks of treatment compared to placebo in the TORREY study. Methods Eighty-six patients with WHO Group 1 PH (Functional Class II, III), ages ≥18 years, pulmonary vascular resistance ≥400 dyne*s/cm5, and on stable PAH standard of care therapy (the majority of whom were on double and triple therapy with approved PAH medications) were enrolled. Right heart catheterisation (RHC) and full echocardiography were performed at BL and Week 24 and at BL, Week 12, and Week 24, respectively; both were analysed in a blinded central laboratory. To calculate RVFWS/sPAP, the pulmonary artery systolic pressure from RHC was used. PAC was calculated from RHC data with the formula (SV/(PAS-PAD)). Statistical analysis was performed using ANCOVA. Results At Week 24, the change in RVFWS/sPAP was lower in the seralutinib group compared to placebo (Table). The changes in RVFWS and RAA were lower in the seralutinib group vs placebo at Week 12 and Week 24 (Table). Change in NT-proBNP correlated with change in RAA (r = 0.43). At Week 24, change in PAC was greater in the seralutinib group (-0.02 ± 0.085 placebo, 0.19 ± 0.089 seralutinib; LSMD 0.22 (0.104) p = 0.04). There was no effect of seralutinib on left ventricular ejection fraction. Conclusion Treatment with seralutinib was associated with a significant reduction of RVFWS/sPAP. In addition, significant differences in RVFWS itself, RAA, and PAC were observed. These treatment effects support improved RV-PA coupling and right heart function. In conjunction with concordant reductions in PVR and NT-proBNP, these data suggest potential favourable effects of seralutinib in PAH. Seralutinib is in clinical development as a potential new treatment option for patients with PAH.

Reduced systolic flow efficacy in left ventricular dyssynchrony evident by blood speckle imaging

Abstract Introduction Intraventricular vortices facilitate efficient blood flow in a healthy heart. Changes in the blood flow pattern can cause energy loss and inefficient filling or ejection. Thus changes, or reduction in vorticity may therefore be of importance for cardiac function. Blood speckle imaging (BSI) is a novel blood flow visualization tool based on echocardiography, partially overcoming the angel dependency of conventional colour Doppler. BSI tracks speckles generated by the moving blood cells, similar to myocardial speckle tracking, but requires a very high frame rate limiting penetration. Dyssynchrony in left bundle branch block (LBBB) affects the systolic functions but there is limited insight into how LBBB alters the blood flow vorticity. Purpose We investigated the effect of dyssynchrony on blood flow hemodynamics using blood speckle imaging. Methods In eight anesthetized canine mongrels, left ventricular flow was visualized using BSI. A qualitative visual assessment of vortices during the cardiac cycle, together with a quantitative assessment based on kinetic energy loss and vorticity were made. Regional myocardial function parameters were measured by sonomicrometry. Peak septal flash strain in isovolumetric contraction (IVC) was measured by sonomicrometry (figure) as an indicator of dyssynchrony. Assessments were made at baseline, under right ventricular free wall pacing (RV pacing) mimicking LBBB, after induced LBBB by ablation and under cardiac resynchronization therapy (CRT). Results During IVC at baseline all animals had a central ventricular vortex. However during RV pacing and LBBB it was distorted in various patterns. RV pacing significantly reduced the number of vortices in systole and disrupted the central vortex in IVC (1.0±0.0 vs 0.4±0.5, p=0.01). Energy loss (EL) in systole increased (40.2±12.5 vs 55.3±23.3 mW/m, p&amp;lt;.05). Septal end systolic strain was significantly reduced (-8.8±5.1 vs -1.9±7.3 %, p&amp;lt;0.01) and septal flash strain was significantly increased (1.0±1.4 vs 7.7±3.6 and 6.6±3.8 [ER1] [ER2] %, p&amp;lt;0.01) in RV pacing and LBBB. CRT caused a realignment of the central vortex (0.8±0.5 vs0.3±0.5, p=0.03). The change in energy loss was not significant, but numerically reduced (55.4±38.8 vs 76.4±48.9 mW/m, p=0.06). See table and figure 1. Conclusions The main systolic vortex in IVC was disrupted during septal flash by RV pacing and LBBB, altering the flow pattern compared to baseline. The resultant unstructured flow pattern had increased energy loss in systole, indicating a less efficient flow pattern and less preservation of energy. It should be further explored if this is of importance to understand the reduced LV function and LV remodelling during dyssynchrony.Figure 1Table 1

In patients with atrial cardiomyopathy long-lasting atrial fibrillation is associated with unfavorable structural changes in right chambers and worse outcome

Abstract Background The main factor responsible for atrial cardiomyopathy (ACM) is atrial fibrillation (AF). It is known that AF causes remodeling of the left atrium but its effects on the right heart chambers and mortality are not well studied. Purpose To assess the echocardiographic characteristics of patients with atrial cardiomyopathy with long-standing and paroxysmal AF and their impact on survival. Methods From 624 consecutive patients with AF only 173 met the inclusion criteria for atrial cardiomyopathy, defined as severely dilated left atrium with indexed left atrial volume (LAVI) &amp;gt;48 ml/m2, preserved left ventricular systolic function, without significant valvular disease or left ventricular hypertrophy. The mean age of the studied population was 73,7 ± 9,5 years, 59% women. The patients were divided into two groups according to the presence of persistent or permanent AF (long-standing AF) - Group 1 (n = 87) or paroxysmal AF - Group 2 (n = 86). All patients underwent a comprehensive echocardiography with volumetric and speckle tracking analysis on enrollment and were followed for cardiovascular outcomes, including mortality 24 months. Results The group with long-standing AF had more dilated right atrium (indexed right atrial volume- RAVI 41.9 ± 24.4 vs. 33 ± 13.5 ml/m2; P=0.003), lower reservoir strain of the right atrium (13.1% ± 8.6 vs. 19.7% ± 10.6; P&amp;lt;0.001) and lower right ventricular free wall strain (18.1% ±7.3 vs. 21.2% ± 7.1; P=0.006). Over a median follow up of 18 months (7-29) 16 patients (18%) from Group 1 died compared to 6 patients (7%) from Group 2 (P=0.022). The presence of more than mild tricuspid regurgitation (OR 4.53; CI: 2.37-8.67; P&amp;lt;0.001), heart failure (OR 3.44; 95% CI: 1.83-6.48; P&amp;lt;0.001), and long-standing AF (OR 3.00, 95% CI: 1.41-8.09; P=0.028) were associated with worse mid-term survival. Conclusion Patients with ACM and long-standing AF have more advanced structural changes of the right atrium and the right ventricle and worse prognosis. The presence of more than mild tricuspid regurgitation, heart failure, and long-standing AF are predictors of poor outcome.

Qp/Qs in ostium secundum atrial septal defect mitigates right ventricular dysfunction in patients with secondary pulmonary hypertension

Abstract Background Ostium-secundum atrial septal defect (OS-ASD) can potentially lead to pulmonary hypertension (PH) and associated right ventricle (RV) - pulmonary artery (PA) uncoupling. This, in turn, may eventually result in RV systolic dysfunction. Notwithstanding, whether the characteristics of the OS-ASD could mitigate this relationship is unclear. Purpose To evaluate a potential interaction of the OS-ASD shunt (Qp/Qs ratio) on the relationship with RV–PA coupling and RV systolic function in patients with secondary PH. Methods We designed a cross-sectional study of 63 adult patients with OS-ASD in which we performed a conventional transthoracic echocardiogram using Vivid 9X-clear equipment (GE Vingmed Ultrasound, Horten, Norway). We evaluated the OS-ASD shunt and other echocardiographic parameters, including the tricuspid annular plane systolic excursion (TAPSE), the systolic pulmonary artery pressure (sPAP) ratio and the right ventricular free wall longitudinal strain (RVFWLS). Polynomic adjusted correlations were performed to model the relationship between the TAPSE/sPAP ratio and the RVFWLS, then we evaluated an interaction effect of the OS-ASD shunt (Qp/Qs ratio), respectively adjusted for age, sex, body mass index, body surface area and right atrial area. Results In our study, 49 (78%) subjects were male, with a mean age of 41.8 (±15) years; 7.94% (n=5) had mild PH, 42.9% (n=27) had moderate PH and 49.2% (n=31) had severe PH. Mean echocardiographic parameters were: TAPSE 24.5 (±5.1) mm , sPAP of 55.9 (±20.7) mmHg, TAPSE/sPAP 0.49 (±0.2) mm/mmHg, RVFWLS -25.6 (±6.6) % and Qp/Qs 2.9 (±0.9). We observed a quadratic relationship between the TAPSE/sPAP ratio and the RVFWLS (r=0.691, p &amp;lt; 0.001; Figure 1). OS-ASD shunt had a positive interaction effect (β=10.9, 95% CI: 2.09-19.6, p=0.018) on the relationship between TAPSE/sPAP and RVFWLS after adjusting for covariates (Figure 2). Conclusions In conclusion, in patients with OS-ASD, the RV systolic function decreases as the RV-PA uncoupling increases, as reflected in the quadratic regression between the TAPSE/sPAP and the RVFWLS. Moreover, the increase in OS-ASD shunt decreases RVFWLS values in relationship to the TAPSE/sPAP ratio as observed in the interaction model. These results could suggest that the OS-ASD characteristics could potentially mitigate RV dysfunction in patients with secondary PH.Figure 1.Quadratic regressionFigure 2.Interaction model

Right ventricular longitudinal strain in transthyretin cardiac amyloidosis (ATTR-CA)

Abstract Transthyretin cardiac amyloidosis (ATTR-CA) is a life-threatening condition characterized by a restrictive phisiology. This condition can be hereditary (ATTRv) or acquired (ATTRwt). Left ventricular global longitudinal strain (LVGLS) measured with speckle-tracking echocardiography (STE) has been well described and it appears to be significantly lower in ATTR-CA than in other hypertrophic phenotypes, presenting with a typical "apical sparing" pattern. Furthermore, LVGLS can predict prognosis among patients with ATTR-CA beyond LVEF. Few studies investigated the role of right ventricular longitudinal strain in ATTR-CA. The aim of this study is to describe right ventricular (RV) involvement in patients with ATTR-CA with the use of STE and to explore its prognostic implications. We retrospectively analyzed echocardiographic images of 221 patients with ATTR-CA evaluated between 1995 and 2019 at our Centre. Since the right ventricular free wall strain (RVFWSL) is the current standard parameter being evaluated when performing STE, we chose it as variable of interest among the others collected. Finally, univariate and multivariate linear regression analyses were used to analyze variables related with clinical events such as heart failure and death. The median age of our cohort was 76,7 years old and they were predominantly males. Among these, most patients had a diagnosis of ATTR-CA wild-type (only 32,1% of study population was affected by ATTRv). At STE, LVGLS was abnormal in both ATTRwt patients (-12%; IQR: -13,75% -10,15%) and ATTRv patients (-12,5%; IQR: -15,5% -10,73%) with no significant difference between groups (p= 0,1715). Furthermore, STE showed impaired right ventricular longitudinal function in both aetiologies, but with a different grade of involvement as the median RVFWLS was -19,8% (IQR: -25,1% -13,9% ) in the ATTRv group and -16,4% in the ATTRwt group (IQR: -21,65% -12,2%) (p=0,043). In our study, a right ventricular apical sparing pattern was not observed. In the univariate analysis, RVFWLS and other parameters such as age, eGFR, tricuspid regurgitation and LVGLS were significantly associated with heart failure, so they were forced into multivariable analysis, but RVFWLS did not show an independent correlation with the endpoint, although a certain trend toward significance could be observed (HR 1,037 95%CI 0.998 - 1.077; p=0,063). Finally, we explored the association between our collected variables and death. At univariate analysis, RVFWLS showed a strong correlation with death (HR 1,034; 95%CI 1.005 - 1.064; p= 0,021), together with NYHA class, eGFR, LVEF and LVGLS. Notably, RVFWLS predicted death at our multivariable regression analysis (HR 1.041 95%CI 1.010 - 1.072; p= 0,008). RVFWLS is an emerging parameter to evaluate RV dysfunction which appears significantly impaired in patients with ATTR-CA. In this setting, it might have not only a diagnostic role, but also a prognostic power, although further data are needed.

Monitoring patisiran and inotersen treatment with quantitative SPECT/CT in hereditary transthyretin amyloid cardiomyopathy

Abstract Background Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). Purpose We aimed to determine treatment effects on myocardial amyloid load determined by quantitative single photon emission computed tomography/computed tomography (SPECT/CT) in patients with ATTRv-related cardiomyopathy (ATTRv-CM) and to identify nuclear imaging biomarkers to quantify and monitor response to therapy. Methods ATTRv-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid ([99mTc]-DPD) scintigraphy and SPECT/CT imaging before and after 12 months of treatment with patisiran (n=5) or inotersen (n=4). Results Patisiran-treated patients had a significant reduction in cardiac uptake as measured by standardized uptake values (SUVpeak: 7.98 g/mL ±0.87 vs. 6.50 g/mL ±1.59, p=0.025, Figure 1A; SUVmax: 8.80 g/mL ±0.94 vs. 6.96 g/mL ±1.59, p=0.009, Figure 1B; SUVmean: 5.64 g/mL ±1.01 vs. 4.42 g/mL ±1.26, p=0.016, Figure 1C). Patients treated with inotersen showed evidence of stabilization in cardiac SUV uptake (SUVpeak: 8.56 g/mL ±2.25 vs. 7.99 g/mL ±1.90, p=0.665; SUVmax: 9.29 g/mL ±2.39 vs. 8.79 g/mL ±2.03, p=0.719; SUVmean: 5.07 g/mL ±1.46 vs. 4.86 g/mL ±0.95, p=0.834) but had significant deterioration in left ventricular (LV) function (LV cardiac index: 3.39 L/min/m2 ±0.04 vs. 2.94 L/min/m2 ±0.01, p=0.028, Figure 1D). Comparison of cardiac SUV uptake and longitudinal cardiac function revealed significant correlations between longitudinal changes in cardiac SUVpeak and LV global longitudinal strain (r=-0.658, p=0.027, Figure 1E) and right ventricular free wall longitudinal strain (r=-0.771, p=0.008, Figure 1F). Conclusions In conclusion, using serial quantitative SPECT/CT imaging, we demonstrated that patisiran treatment significantly reduces cardiac SUV uptake in ATTRv-CM patients, indicating regression of cardiac TTR amyloid. Our data suggest that quantitative SPECT/CT imaging may be a valid tool to quantify and monitor response to disease-specific RNAi therapeutic agents in ATTRv-CM patients.Figure 1Graphical Abstract

Right ventricular free wall strain and tricuspid annular plane systolic excursion for the prediction of left sided cardiotoxicity in lymphoma patients treated with anthracycline-based chemotherapy

Abstract Background The diagnosis of cardiotoxicity (CT) related to cancer therapy has gained significance due to its impact on morbidity and mortality. The 2022 cardio-oncology European Society of Cardiology (ESC) Guidelines defined CT as symptomatic if a patient has clinical heart failure or asymptomatic based on changes in the ejection fraction (EF) or global longitudinal strain (GLS). The role of right ventricular parameters, such as tricuspid annular plane systolic excursion (TAPSE) and right ventricular free wall strain (RVFWS), in predicting CT is unknown. AIM Evaluate if TAPSE and RVFWS can predict the development of CT in lymphoma patients treated with anthracyclines. Methods For this prospective observational study, Hodgkin &amp; non-Hodgkin lymphoma patients (n=222) treated with anthracyclines were recruited from 2013 to 2021 and were followed for one year. Echocardiographic variables TAPSE and RVFWS were measured at baseline(T0), during treatment(T1), and up to 1 year after chemotherapy completion(T2). CT was defined according to the ESC guidelines excluding GLS changes. We performed: Kruskal-Wallis test to find differences at baseline values, logistic regression to evaluate the association of TAPSE and RVFWS with CT, area under the curve (AUC) of the receiving operator characteristic (ROC) to measure the discriminative test ability and two sample proportion test to calculate the negative predictive value (NPV). A p-value &amp;lt;0.05 was considered significant. Results 222 patients were enrolled and 23 developed CT: 4.5% (n=10) at T1 and 6.2% (n=13) at T2. The median of RVFWS at T0 was significantly different in patients who developed CT compared to those who did not at T1 (CT-22% vs. no CT-27% p=0.04) and T2 (CT -23%, no CT -26.5% p=0.03). RVFW values at T0 were associated with CT at T1 (OR, 1.281 95% CI,1.09-1.52 p=0.002) and T2 (OR 1.23 95% CI,1.07-1.44 p=0.003). At T0 RVFWS cutoff value of -24% had an AUC of 0.85 for the prediction of CT at T1, with a sensitivity of 83% and specificity of 76% (p=0.03). At T0, RVFWS cutoff of -25% had an AUC of 0.80 for the prediction of CT at T2, with a sensitivity of 75% and specificity of 60%, (p=0.04). RVFWS absolute values &amp;gt;26% at T0 and T1 had an NPV of 100% for the development of CT in T1 and T2. The median TAPSE at T0 was significantly different in patients who developed CT at T1 compared to those who did not (CT patients 18.7 mm vs no CT patients 23.6 mm p=0.04). TAPSE values at T0 were associated with CT development at T1 but not at T2 OR 0.76 (95% CI,0.66-0.87 p=&amp;lt;0.001). At T0, TAPSE cutoff of 21.6 mm had an AUC of 0.77 for the prediction of CT at T1, with a sensitivity of 77% and specificity of 70% (p=0.03). Conclusions Baseline absolute RVFWS values &amp;lt;24% and &amp;lt;25% were associated with CT at T1 and T2, respectively. Values &amp;gt;26% had an excellent NPV for the development of CT. Baseline TAPSE values &amp;lt;21.6 were associated with CT at T1. These parameters should be evaluated in other cancer populations.TAPSE and RVFWS association with CTRVFWS and TAPSE at T0 to predict CT

Prevalence and risk factors of left ventricular diastolic dysfunction in systemic sclerosis patients: insights from new echocardiographic parameters

Abstract Background Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by excessive extracellular matrix deposition and fibrosis that can affect the skin, blood vessels, and internal organs, including the heart. Primary heart involvement in SSc refers to the presence of cardiac fibrosis, inflammation, and dysfunction in the absence of pulmonary hypertension (PH). Although PH is usually considered the major risk factor for death in SSc patients, diastolic dysfunction has been proposed as an independent predictor of mortality, which may be more robust than PH. Purpose Early identification and management of heart complications in SSc patients are crucial to prevent further deterioration and improve treatment outcomes. However, myocardial damage caused by SSc is often poorly understood, and the long-term effects and prognosis remain unknown. Methods We conducted a cross-sectional study of 69 patients (p) with SSc diagnosis evaluated between February 2022 and February 2023. We analyzed the prevalence of left ventricular diastolic dysfunction (LVDD) as recommended by the 2016 ASE/EACVI guidelines. We compared the presence of risk factors associated with LVDD and its association with other echocardiographic findings. Of the 69p, 24 (34.8%) had LVDD, 41 (59.4%) had normal diastolic function, and 4 (5.8%) had undetermined diastolic dysfunction. Older age (mean age 69.7 ± 11.2 vs 57 ± 12.8; p &amp;lt; 0.01), arterial hypertension (50% vs 22%; p = 0.02), higher body mass index (28.3 ± 8 vs 24.6 ± 4.5; p = 0.02), and higher NTproBNP levels (131 [64-403] vs 97 [45-163]; p = 0.047) were significantly associated with LVDD. The absence of antitopoisomerase (scl70 0% vs 22.2%; p = 0.021) and the presence of anticentromere (CENP-A 81% vs 55.6%; p = 0.05) and (CENP-B 85.7% vs 55.6%; p = 0.02) antibodies were also significantly associated with LVDD. Additionally, classical parameters of ventricular function, such as left ventricular ejection fraction (LVEF 63.5 ± 4.2 vs 63.4 ± 3.7; p = 0.9) or tricuspid annular plane systolic excursion (TAPSE 20.6 ± 2.3mm vs 21.2 ± 2.4mm; p = 0.32), were not associated with LVDD. However, impairment of the right ventricular free wall strain (-23.8 ± 4 vs -27 ± 2.8; p = 0.017), and lower left atrial strain reservoir function (27.7 ± 10 vs 38.4 ± 12.7; p = 0.05) were significantly associated with LVDD. Conclusion LVDD is highly prevalent in patients with systemic sclerosis, particularly in elderly patients with a higher body mass index and those affected by arterial hypertension. These patientes have higher values of NTproBNP. Futhermore, antitopoisomerases antibodies are less likely to be expressed and anticetromere antibodies are more likely to be expressed . These findings highlight the importance of regular cardiovascular monitoring in SSc patients and the potential value of using new echocardiographic parameters to identify those at risk for LVDD.

Three-dimensional-printed heart model can determine univentricular repair strategy in borderline double-outlet right ventricle

BackgroundAs double-outlet right ventricle has a wide pathophysiology spectrum, its comprehensive treatment strategy is determined based on relevant factors, such as the location and size of the ventricular septal defect, ventricular volume, and relationship of the great arteries. However, for borderline double-outlet right ventricle cases, it is occasionally difficult to decide the treatment strategy preoperatively. Recently, advances in 3D printing technology based on computed tomography have enabled the creation of 3D heart models of congenital heart disease that can precisely reproduce the anatomical structure of each patient even for complex anomalies. Herein, we describe a young patient in whom univentricular repair could be decided after confirming the 3D heart model and intracardiac structure under direct vision.Case presentationWe describe a 3-year-old girl who was diagnosed with double-outlet right ventricle and severe pulmonary valve stenosis at birth and who underwent a left modified Blalock–Taussig shunt at 2 years of age. Preoperative examination revealed a borderline condition for biventricular repair characterized by a small left ventricle volume and side-by-side relationship of the great artery. After a preoperative discussion using a 3D heart model, we concurred that an intraoperative assessment would be made as to whether biventricular repair was possible or not. After confirming the intracardiac structure under direct vision, we assessed that intraventricular rerouting was not possible owing to the high risk of subvalvular aortic stenosis as there was no tissue that could be incised between the right ventricular free wall and the primary interventricular foramen, as indicated in the 3D heart model. Thus, atrial septostomy and Glenn anastomosis were performed.ConclusionsWe report a 3-year-old girl with a borderline double-outlet right ventricle in whom a univentricular repair strategy could be decided after confirming the 3D heart model and intracardiac structure under direct vision. A 3D-printed heart model can be useful in patients whose repair strategy is difficult to judge for the borderline double-outlet right ventricle.

Abstract 18186: Four Chambers Strain Analysis in Patients Admitted With Acute Heart Failure: A New Characterization of Heart Involvement?

Introduction: In heart failure (HF), most of the data available on myocardial strain focused on the left ventricle (LV). Very few data concern the other cavities. Hypothesis: We hypothesized that all cardiac cavities are involved in HF and thus we evaluated all chambers strain profiles in patients admitted with acute HF. Methods: We prospectively evaluated 95 patients hospitalized for HF. Patients were divided into preserved left ventricle ejection fraction (LVEF) (LVEF ≥50%, HFpEF n=24), mildly reduced LVEF ((LVEF 41-49%, HFmrEF n=17), and reduced left ventricular ejection fraction (LVEF) (LVEF ≤40%, HFrEF n=54). In addition to the usual two-dimensional echocardiographic parameters, LV global longitudinal strain, left and right atrial strain (reservoir, conduit, contractile strain), right ventricular free wall strain were determined using speckle tracking transthoracic echocardiography at admission. Results: Patients with HFrEF were younger in comparison with patients with HFmrEF and HFpEF, (respectively 66.3 ± 14.2, 78.3.0 ±8.7, 75.6 ± 10.2 years p&lt;0.001). Table 1 summarizes the main Doppler and echocardiographic comparisons. Myocardial strain analyses demonstrated that patients with HFrEF had significant lower LV global, right ventricular strain, left atrial reservoir strain, left and right atrial conduit strain (Figure 1). Conclusions: Beyond the alteration of LV function, HFrEF involves alteration of right ventricle, left and right atrial functions. Strain analysis is an interesting tool in addition to conventional echocardiographic parameters to assess heart function in heart failure. The prognostic impact of these finding remains to be studied.

Abstract 14350: Prognostic Impact of Right Ventricular Free Wall Longitudinal Strain in Tricuspid Regurgitation: A Systematic Review and Meta-Analysis

Introduction: Traditional echocardiography is limited in the early assessment of right ventricular (RV) dysfunction, especially in cases of tricuspid regurgitation (TR). In this context, right ventricular free wall longitudinal strain (RVFWLS) has emerged as a promising tool to enhance this evaluation. Hypothesis: We aimed to conduct a systematic review and meta-analysis to investigate whether impaired RVFWLS in patients with moderate to severe TR is associated with an increased risk of all-cause mortality and heart failure (HF) hospitalization. Methods: We searched Pubmed, Embase and Cochrane for studies that examined our clinical question. Two reviewers performed study selection, data extraction and assessment of bias. RVFWLS was evaluated as a binary variable: normal/near-normal vs. impaired. The latter was defined as a RVFWLS &gt; -17%. Statistical analysis was performed using Review Manager 5.4.1. We calculated pooled hazard ratios (HR) with 95% confidence intervals (CI) under a random effects model. We also performed a subgroup analysis of multivariable analyses to minimize the effect of confounding variables. Results: We included 1,523 patients from 5 cohort studies. The mean follow-up ranged from 2.2 to 3.9 years. Mean age ranged to 62 to 84 years and 1,462 (96%) had functional TR. All-cause mortality (HR 1.06; 95% CI 1.02-1.10; p=0.002) and the composite of all-cause mortality or HF hospitalizations (HR 1.10; 95% CI 1.03-1.18; p=0.006) were significantly higher in patients with impaired RVFWLS compared with normal or near-normal RVFWLS. When considering only the multivariable analyses, patients with reduced RVFWLS also had a higher adjusted risk of all-cause mortality (HR 1.05; 95% CI 1.02-1.08; p=0.003). Conclusions: Our findings indicate that RVFWLS is an independent prognostic factor for all-cause mortality among patients with moderate to severe TR. The use of RVFWLS to guide management of this population warrants further investigation.

Abstract 15246: Myocardial Deformation for Prediction of Major Arrhythmic Events in Patients With Non-Ischemic Cardiomyopathy and Primary Prevention Implantable Cardioverter Defibrillators

Introduction: Sudden cardiac death is a major cause of mortality in patients with non-ischemic cardiomyopathy (NICM). Implantable cardioverter-defibrillator (ICD) is an established prophylactic measure. But, optimal identification of patients with greatest likelihood of benefiting poses ongoing challenges. Objective: To assess the prognostic value of myocardial deformation for predicting ICD intervention while accounting for competing mortality risk. Methods: 180 NICM patients eligible for primary prevention ICD underwent cardiac magnetic resonance (CMR). Myocardial strains (left ventricular radial, circumferential, longitudinal; left atrial; and right ventricular free wall longitudinal strain (RV GLS)) were measured via CVI42 feature tracking. In a multivariable Fine-Gray competing risk model, incremental values of strains were assessed, adding to a baseline model based on clinical features and late gadolinium enhancement (LGE). The primary endpoint was ventricular tachycardia/fibrillation treated with ICD intervention, including shocks or anti-tachycardia pacing. Results: 159 patients with ICD (117 male; 54 ± 13 years) were included for final analysis (follow-up: 1176±960 days; median: 896). 26 patients met the primary endpoint. RV GLS showed a statistically significant difference between patients with and without events (-12.5% ± 5 vs -16.4% ± 5.5, p = 0.001). Univariate analyses revealed that LGE and RV GLS were significantly associated with outcome, even after accounting for competing risk (LGE: HR=3.69, 95% CI=1.28-10.62; RV GLS: HR=2.04, 95% CI=1.30-3.22). Adding RV GLS to the baseline model improved its prognostic value, with a c statistic improvement from 0.678 to 0.730. RV GLS hazard ratio remained significant in multivariate analysis after accounting for competing risk (HR=1.73, 95% CI=1.12-2.66) (Table 1). Conclusions: In NICM, RV GLS provides additional predictive value above LGE and clinical features for ICD intervention.

Abstract 13724: Multiparameter Right Ventricular Dysfunction Predicts Worse Prognosis in Heart Failure With Preserved Ejection Fraction - Lessons From the PARAGON-HF Trial

Introduction: Impaired tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC) and right ventricular free wall longitudinal strain (RVFWLS) have been individually associated with a worse prognosis in patients with heart failure with preserved ejection fraction (HFpEF). However, these parameters measure different aspects of RV function and understanding their cumulative effect may provide insights into the overall impact of RV dysfunction (RVD) in HFpEF patients. Goal: Assess the association between the number of echocardiographic RVD parameters and clinical outcomes. Methods: Patients from the echocardiographic sub-study of the PARAGON-HF trial with adequate image quality (N=809, 53% women, mean age 74±8 years) were categorized based on the number of measures of RVD, which included TAPSE &lt;1.7 cm, FAC &lt;35% or RVFWLS &lt;20% (absolute value). Associations with total HF hospitalizations (HFH) and CV death, total HFH alone, first HFH or CV death, all-cause death and CV death were assessed by Groups, after accounting for confounders. Results: A total of 348 patients (43%) in Group 0 (no abnormal parameter), 355 (44%) in Group 1 (one abnormal parameter) and 106 (13%) in Group 2 (two or more abnormal parameters) were identified. After multivariable adjustment ( Table ), Group 2 was significantly associated with an increased risk of total HFH and CV death (RR 2.13, 95%CI 1.13-4.01), first HFH or CV death (RR 2.07, 95%CI 1.15-3.73), all-cause death (RR 2.61, 95%CI 1.19-5.74) and CV death (RR 3.08, 95%CI 1.14-8.31). The treatment effect of sacubitril/valsartan for total HFH and CV death was not modified by RVD Group (p-value for interaction=0.94). Conclusions: The presence of two or more RVD parameters was associated with a significantly worse prognosis, while an isolated RVD measure was not. These findings suggest that a more comprehensive approach to assessment of RV function may have better prognostic value in HFpEF.