Right Ventricular Free Wall Thickness 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.

Cardiovascular metrics on CT pulmonary angiography in patients with pulmonary hypertension — re-evaluation under the updated guidelines of pulmonary hypertension

PurposeTo re-assess cardiovascular metrics on computed tomography pulmonary angiography (CTPA) in predicting pulmonary hypertension (PH) under the 2022 ESC/ERS guidelines.Materials and methodsThis observational study retrospectively included 272 patients (female 143, mean age = 54.9 ± 12.5 years old) with suspected PH. 218 patients were grouped to evaluate cardiovascular metrics on CTPA and develop a binary logistic regression model. The other 54 patients were grouped into the validation group to assess the performance of the prediction model under the updated criteria. Based on mean pulmonary artery pressure (mPAP), patients were divided into three groups: group A consisted of patients with mPAP ≤ 20 mmHg, group B included patients with 20 mmHg < mPAP < 25 mmHg, and group C comprised patients with mPAP ≥ 25 mmHg. Cardiovascular metrics among the three groups were compared, and receiver operating characteristic curves (ROCs) were used to evaluate the performance of cardiovascular metrics in predicting mPAP > 20 mmHg.ResultsThe main pulmonary arterial diameter (MPAd), MPAd/ascending aorta diameter ratio (MPAd/AAd ratio), and right ventricular free wall thickness (RVFWT) showed significant differences among the three groups (p < 0.05). The area under curve (AUC) of MPAd was larger than MPAd/AAd ratio and RVFWT. A MPAd cutoff value of 30.0 mm has a sensitivity of 83.1% and a specificity of 90.4%. The AUC of the binary logistic regression model (Z = − 12.98187 + 0.31053 MPAd + 1.04863 RVFWT) was 0.938 ± 0.018. In the validation group, the AUC, sensitivity, specificity, and accuracy of the prediction model were 0.878, 92.7%, 76.9%, and 88.9%, respectively.ConclusionUnder the updated criteria, MPAd with a threshold value of 30.0 mm has better sensitivity and specificity in predicting PH. The binary logistic regression model may improve the diagnostic accuracy.Critical relevance statementUnder the updated criteria, the main pulmonary arterial diameter with a threshold value of 30.0 mm has better sensitivity and specificity in predicting pulmonary hypertension. The binary logistic regression model may improve diagnostic accuracy.Key points• According to 2022 ESC/ERS guidelines, a MPAd cutoff value of 30.0 mm has better sensitivity and specificity in predicting mPAP > 20 mmHg• A binary logistic regression model (Z = − 12.98187 + 0.31053 MPAd + 1.04863 RVFWT) was developed and had a sensitivity, specificity, and accuracy of 92.7%, 76.9%, and 88.9% in predicting mPAP > 20 mmHg.• A binary logistic regression prediction model outperforms MPAd in predicting mPAP > 20 mmHg.Graphical

Association between the TAPSE to PASP ratio and short-term outcome in patients with light-chain cardiac amyloidosis

BackgroundAmyloid light-chain cardiac amyloidosis (AL-CA) patients experiencing RV failure have a poorer prognosis. The echocardiographic ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) serves as a non-invasive proxy for evaluating the coupling between the right ventricle (RV) and pulmonary circulation. The aim of this study was to assess the association between the TAPSE/PASP ratio and short-term outcome in patients with AL-CA. MethodsSeventy-one patients diagnosed with AL-CA were enrolled in this retrospective cohort study.Short-term outcome was defined as 6-month all-cause mortality. Receiver operating characteristic (ROC), logistic regression, and Kaplan-Meier analysis were used in this study. ResultsAmong seventy-one patients with AL-CA (mean age, 62 ± 8 years, 69% male), 17 (24%) died within the first 6 months (mean follow-up period 55 ± 48 days). Linear regression analysis indicated that the TAPSE/PASP ratio was correlated with RV global longitudinal strain (r = −0.655, p < 0.001), RV free wall thickness (r = −0.599, p < 0.001), and left atrial reservoir strain (r = 0.770, p < 0.001). The time-dependent ROC and the area under the curve (AUC) showed that the TAPSE/PASP ratio was a better predictor (AUC = 0.798; 95% confidence interval (CI): 0.677–0.929) of short-term outcome than TAPSE (AUC = 0.734; 95% CI: 0.585–0.882) and PASP (AUC: 0.730; 95% CI: 0.587–0.874). Multivariate logistic regression showed that patients with the worse TAPSE/PASP (< 0.47 mm/mmHg) and lower systolic blood pressure (< 100 mmHg) had the highest risk of dying. ConclusionsThe TAPSE/PASP ratio is associated with the short-term outcome of patients with AL-CA. The combination of TAPSE/PASP ratio < 0.474 mmHg and SBP < 100 mmHg could identify the subgroup of patients with AL-CA at elevated risk of poor prognosis.

Echocardiography machine learning based to improve detection of transthyretin cardiac amyloidosis: The R3M Algorithm

Transthyretin cardiac amyloidosis (ATTR-CA) is an emerging cause of heart failure. The screening of ATTR-CA remains difficult since its echocardiographic features are analogous to those observed in patients with age- and hypertension-related cardiac remodeling. We retrospectively included 264 patients (76 ± 13 years old, 59% male) referred for suspected ATTR-CA. A supervised machine learning diagnosis algorithm differentiating patients with (n = 112) and without (n = 152) ATTR-CA was constructed based on echocardiographic data, and subsequently validated in an external multicenter cohort of 455 patients (76 ± 13 years old, 61% male). Patients with ATTR-CA had a lower systolic function (LVEF 47.4 ± 11 vs. 54.3 ± 12%, P < 0.001), left ventricular (LV) global longitudinal strain (GLS) (11.0 ± 3.7 vs. 14.2 ± 4.5%, P < 0.001) and more significant relative apical longitudinal sparing (RALS) (1.5 ± 1.2 vs. 0.9 ± 0.4, P < 0.001) compared to controls. Machine learning identified right ventricular free wall thickness (RVFWT), RALS, relative wall thickness (RWT), and LV mass index as key variables for identifying ATTR-CA (AUC 0.88 [0.84–0.92]; P < 0.001). The diagnostic value of this R3M (RVFWT, RALS, RWT and LV Mass index) algorithm was good in the validation multicenter cohort with an AUC of 0.79 [0.75–0.83] P < 0.001. The R3M algorithm further improved diagnostic accuracy over the IWT (Increased Wall Thickness) guidelines score (increase in C-index of 0.15 [0.10–0.21], P < 0.001). The simple R3M algorithm based on echocardiographic data exploring RVFWT, apical sparing, and concentric hypertrophy displays good diagnostic accuracy for ATTR-CA and could represent an efficient screening tool (Fig. 1).

GPx3 deficiency exacerbates maladaptive RV remodeling in experimental pulmonary artery banding.

The stressed right ventricle (RV) is particularly susceptible to producing and accumulating reactive oxygen species, leading to extracellular matrix deposition and secretion of natriuretic peptides. The role of specific enzymes with anti-oxidative capacity, like Glutathione peroxidase 3 (GPx3), in RV pathogenesis is currently unknown. Here, we employ a murine model of pulmonary artery banding (PAB) to study the role of GPx3 in isolated RV pathology. Compared to WT mice undergoing PAB surgery, GPx3-deficient PAB mice presented with higher RV systolic pressure and higher LV eccentricity indices. PAB-induced changes in Fulton's Index, RV free wall thickness, and RV fractional area change were more pronounced in GPx3-deficient mice compared to WT controls. Adverse RV remodeling was enhanced in GPx3-deficient PAB animals, evidenced by increased RV expression levels of CTGF, TGF-b and ANP. In summary, GPx3 deficiency exacerbates maladaptive RV remodeling and causes signs of RV dysfunction.

Echocardiographic evaluation of right heart pressure changes in healthy newborns and its follow-up till 12 weeks of life

Background: Right ventricular (RV) pressure undergoes a series of changes from foetal to neonatal period on both left and right heart. Pulmonary velocity acceleration time (PVAccT) measured by trans-thoracic echocardiography has been established as a reliable indicator of RV pressure measurement in neonates. This study aims to throw some light into the changes in the RV pressure by serial PVAccT measurements in the initial 12 weeks of life. Materials and Methods: A cross sectional study was carried out among term new-borns until 12 weeks of age and serial changes in the PVAccT values were recorded, reflecting the mean pulmonary artery pressure (MPAP), and the left ventricular internal diastolic diameter (LVIDD), left atrial diameter (LAD), right ventricular outflow tract (RVOT), right ventricular free wall thickness (RVFWT). Results: There was gradual increase in the mean value of PVAccT with age from birth i.e., 1-3 days (70.08±18.62ms) to 3 months (86.23±17.31ms) (p=&lt;0.05). Mean value of right ventricular outflow tract proximal diameter was also seen to have an increase from day 1-3 (0.92±0.19cm) to 3 months of age (1.09±0.01cm) (p= &lt;0.001). There was an overall decrease in the mean value of the RVFWT from day 1-3 (0.37±.07 cm) to 3 months (0.27±0.07cm) of age after an increase at 1 month (p=&lt;0.05). Statistically significant increase in mean LAD from 1.18±0.29cm to 1.40±0.35 cm and LVIDD from 1.54±0.31cm to1.96±0.27 was seen from birth to 3 months of age. Conclusion: Changes in PVAcct and RV pressure with time from birth to 3 months of age will aid in early diagnosis of persistent pulmonary artery hypertension of new-born (PPHN) or pulmonary arterial hypertension (PAH).

The exercise tolerance dependence on epicardial fat thickness, right ventricular hypertrophy and right ventricular global function in patients with metabolic syndrome

Abstract Background The importance of the evaluation of right compartments of the heart is beyond doubts. Right ventricle (RV) plays one of the leading roles in assessing the prognosis of the patients, especially in the context of metabolic syndrome (MS), insulin resistance and visceral obesity. Several trials highlight the epicardial fat thickness (EFT) as a novel marker of visceral obesity and the proximity to the RV does not exclude its direct effect on ventricular function. More of that, EFT represents a metabolically active organ with a wide range of bioeffects that could potentiate cardiometabolic risk profile in patients with MS and visceral obesity. Purpose The objective of the present study was to evaluate the impact of visceral obesity, RV hypertrophy and RV diastolic and global function on exercise capacity (i.e., exercise duration (ED), metabolic equivalents (METs)) in patients with MS and persevered left ventricular function. Methods We included 97 subjects with MS (mean age 54±8.7 years) and 97 controls without MS (mean age 53±9.6 years, P=0.13). MS was defined by ≥3 criteria of International Diabetes Federation and American Heart Association/National Heart, Lung, and Blood Institute. Using 2D echocardiography we assessed RV diastolic function: the ratio of early and late diastolic tricuspid flow velocities (Et/At), the ratio of early diastolic tricuspid flow velocity and early diastolic tricuspid annular velocity (Et/e't), Et deceleration time (DT); Tei index of RV by pulsed tissue Doppler; RV free wall thickness; epicardial fat thickness (EFT). All the participants underwent exercise ECG stress test (cycle ergometry) and the exercise capacity was determined by ED and METs. Results Et/At, Et/e't, EtDT and Tei index were significantly deteriorated in MS group (all P&amp;lt;0.05). Also, RV free wall thickness and EFT showed significant correlations with parameters of RV diastolic function in patients with MS, respectively: Et/At (r=−0.432, P&amp;lt;0.05; r=−0.523, P&amp;lt;0.01), Et/e't (r=0.334, P&amp;lt;0.01; r=0.291, P&amp;lt;0.01), EtDT (r=0.411, P&amp;lt;0.05; r=0.593, P&amp;lt;0.001). RV Tei index positively correlated with RV free wall thickness (r=0.628, P&amp;lt;0.001) and EFT (r=0.623, P&amp;lt;0.001). In bivariate analysis we found that METs were negatively associated to Et/e't (r=−0.208, P=0.033), EtDT (r=−0.295, P&amp;lt;0.01), RV Tei index (r=−0.515, P&amp;lt;0.001), RV free wall thickness (r=−0.504, P&amp;lt;0.001), EFT (r=−0.646, P&amp;lt;0.05) in MS group. Also, ED showed important negative correlation with the same parameters (all P&amp;lt;0.05). Systolic function of RV did not show statistically significant correlations with METs or ED. Multivariate regression analysis showed that RV free wall thickness, RV Tei index and EFT were independently associated with METs in patients with MS (P&amp;lt;0.05). Conclusions Our findings support that epicardial fat thickness, right ventricular Tei index and right ventricular hypertrophy impact exercise tolerance in patients with metabolic syndrome. Funding Acknowledgement Type of funding sources: None.

Assessment of right ventricular functions in acromegaly: comparison of active disease with remission.

Aim Cardiac involvement in acromegaly is defined as acromegalic cardiomyopathy, an insidious and chronic disease. Previous research on acromegalic cardiomyopathy was largely focused on morphological and functional assessment of the left heart. Since the literature data regarding right heart function in acromegalic patients are limited, we aimed to evaluate the structure and function of the right heart in such patients.Material and Methods We included 43 adult participants as the acromegaly group and 42 individuals as the control group. All patients underwent echocardiographic evaluation. The results were compared between acromegaly and control groups and between active and controlled acromegaly groups.Results The acromegaly group had increased interventricular septum thickness, right ventricular (RV) free wall thickness, right atrium (RA) minor diameter, RV basal and longitudinal diameters, RV end-diastolic and end-systolic areas, E / E' ratio, isovolumetric relaxation time, and RV ejection time. The E / A ratio and E' velocity were reduced. GH and IGF-1 were positively correlated with RV longitudinal diameter, indexed RA minor-axis dimension, and indexed RV end-diastolic area. Patients with active acromegaly had increased RV index of myocardial performance (RVIMP) and isovolumetric contraction time and shortened RV ejection time compared to patients in remission. A RVIMP value of 0.435 predicted active acromegaly with a sensitivity and specificity of 0.83 and 0.64, respectively (p=0.002).Conclusions Increases in the size and diameters of the right heart chambers along with RV free wall thickness may be attributed to acromegalic cardiomyopathy. RVIMP, isovolumetric contraction time, and ejection time are parameters that can be used in the evaluation of active acromegaly disease.

A Measurement-Based Protocol Improves Interrater Agreement and Accuracy of Right Ventricular Systolic Pressure Assessment by Echocardiography in Children: A Call for Quality Improvement

Echocardiographic measurements carry the promise of improving interrater (IR) agreement over subjective assessment. The aim of this study was to assess the effect of implementing a measurement-based protocol on IR agreement and accuracy in reporting of right ventricular (RV) systolic pressure in children. The effect of this reporting protocol on IR agreement in reporting RV dilation, hypertrophy, and systolic function was also evaluated. Five echocardiography readers reported their assessment of RV systolic pressure, dilation, hypertrophy, and systolic function on 40 deidentified echocardiograms using their individual accustomed methods and then using an agreed-upon protocol based solely on RV measurements. IR agreement was assessed using κ statistics. Accuracy of RV systolic pressure ratings was assessed using the McNemar test in comparison with hemodynamic data obtained by cardiac catheterization. The reliability of the RV measurements was assessed using intraclass correlation coefficient (ICC) and coefficient of variation. IR agreement and accuracy of RV systolic pressure assessment improved after using the measurement-based protocol (agreement from 0.39 [95% CI, 0.27-0.5] to 0.62 [95% CI, 0.48-0.76] and accuracy from 18 of 40 to 29 of 40 [P=.03]). IR agreement of RV dilation improved (from 0.36 [95% CI, 0.25-0.48] to 0.63 [95% CI, 0.48-0.79]), while IR agreement of RV hypertrophy (from 0.29 [95% CI, 0.17-0.42] to 0.35 [95% CI, 0.15-0.55]) and RV systolic function (from 0.57 [95% CI, 0.45-0.69] to 0.53 [95% CI, 0.41-0.66]) did not improve. The reliability of the measurements was good (ICC > 0.8), except for RV free wall thickness (ICC=0.62, coefficient of variation=24%) and RV fractional area change (ICC=0.47, coefficient of variation=22%), suggesting a possible reason for the lack of improvement in IR agreement of RV hypertrophy and RV systolic function. Heteroscedasticity was observed in the reliability of RV measurements, with the ICC being significantly lower at larger magnitudes for all RV measurements. Standardization of reporting protocols using RV measurements in place of subjective assessment improved IR agreement and accuracy of RV systolic pressure assessment. Reliable measurements (RV systolic pressure and dilation) resulted in improvement in IR agreement while unreliable measurements (RV hypertrophy and systolic function) did not. Special attention to measurements' reliability and heteroscedasticity of reliability is required when designing clinical protocols to decrease IR disagreement as a source of error.

Cardiopulmonary protection against nicotine‐induced pulmonary hypertension and right ventricular remodeling in mice is not mediated by ovarian hormones

IntroductionElectronic cigarette use has increased globally prompting a joint committee of international cardiovascular research organizations to call for improved understanding of the health effects of nicotine. Our group has previously demonstrated that chronic, inhaled nicotine induces pulmonary hypertension (PH) and right ventricular (RV) remodeling in male but not female mice, suggesting sex differences in nicotine‐related pathology. Clinically, biological females develop PH more often, but have less severe disease than biological males, likely due to the cardiopulmonary protective effects of estrogen. Nicotine is also metabolized more rapidly in biological females due to sex hormone‐mediated differences in cytochrome P450 activity. These findings led us to hypothesize that female mice are protected against nicotine‐induced PH by a sex hormone‐dependent mechanism. Here, we assessed the role of ovarian hormones in a murine model of nicotine‐induced PH.MethodsFemale C57BL/6J mice were ovariectomized (OVX) one week prior to nicotine exposure. Intact and OVX mice were exposed to nicotine vapor or room air for 12 hours per day for 8 weeks. Nicotine exposure was measured using serum cotinine, which was comparable to human electronic cigarette users, and was not significantly different between intact (421 ± 101 ng/mL) and OVX (314 ± 61 ng/mL) mice. Cardiac structure and function were assessed using echocardiography and RV catheterization.ResultsIn contrast to previous findings in male mice, inhaled nicotine does not cause PH (measured by RV systolic pressure, RVSP) in intact female mice (24.0 ± 0.5 mmHg, n=7 in air vs. 22.7 ± 0.4 mmHg, n=9 in nicotine). RVSP was also unaffected by OVX (24.4 ± 0.9 mmHg, n=9 in air vs. 23.6 ± 0.6 mmHg, n=10 in nicotine). RV free wall thickness during diastole (RV FWT;d) was not significantly different between air‐exposed intact mice (0.328 ± 0.023 mm, n=8), nicotine‐exposed intact mice (0.292 ± 0.015 mm, n=10), air‐exposed OVX mice (0.315 ± 0.021 mm, n=8), and nicotine‐exposed OVX mice (0.293 ± 0.013 mm, n=10). RV internal diameter during diastole (RVID;d) was, likewise, not significantly different between air‐exposed intact mice (1.30 ± 0.03 mm, n=8), nicotine‐exposed intact mice (1.34 ± 0.04 mm, n=10), air‐exposed OVX mice (1.23 ± 0.05 mm, n=8), and nicotine‐exposed OVX mice (1.24 ± 0.05 mm, n=10).ConclusionIn this study, we found no differences in serum cotinine, RVSP, RV FWT;d, or RVID;d between intact and OVX females, leading us to conclude that ovarian hormones do not mediate cardiopulmonary protection against nicotine‐induced PH. Due to profound sex differences in clinical PH pathogenesis and nicotine metabolism, further studies (including exploration of androgen‐driven RV remodeling) are necessary to illuminate mechanisms underlying protection from nicotine‐induced pathology in female mice.

Lack of right ventricular hypertrophy is associated with right heart failure in patients with left ventricular failure.

Presence of right heart failure (RHF) is associated with a worse prognosis in patients with left ventricular failure (LVF). While the cause of RHF secondary to LVF is multifactorial, an increased right ventricular (RV) afterload is believed as the major cause of RHF. However, data are scarce on the adaptive responses of the RV in patients with LVF. Our aim was to understand the relationship of right ventricular hypertrophy (RVH) with RHF and RV systolic and diastolic properties in patients with LVF. 55 patients with a left ventricular ejection fraction of 40% or less were included in the present study. A comprehensive two-dimensional transthoracic echocardiographic examination was done to all participants. 12 patients (21.8%) had RHF, and patients with RHF had a significantly lower right ventricular free wall thickness (RVFWT) as compared to patients without RHF (5.3 ± 1.7mm vs. 6.6 ± 0.9mm, p = 0.02) and the difference remained statistically significant after adjusting for confounders (Δx̅:1.34mm, p = 0.002). RVFWT had a statistically significant correlation with tricuspid annular plane systolic excursion (r = 0.479, p < 0.001) and tricuspid annular lateral systolic velocity (r = 0.360, p = 0.007), but not with the indices of the RV diastolic function. None of the patients with concentric RVH had RHF, while 22.2% of patients with eccentric RVH and 66.7% of patients without RVH had RHF (p < 0.01 as compared to patients with concentric RVH). In patients with left ventricular systolic dysfunction, absence of RVH was associated with worse RV systolic performance and a significantly higher incidence of RHF.

ECG in the clinical and prognostic evaluation of patients with pulmonary arterial hypertension: an underestimated value.

Background:Pulmonary arterial hypertension (PAH) is a rare disease leading to right ventricular (RV) failure and manifests in decreasing exercise tolerance. Our study aimed to assess the usefulness of electrocardiographic parameters reflecting right heart hypertrophy as predictors of clinical status in PAH.Methods:The retrospective analysis included 26 patients, mean 49 ± 17 years of age, diagnosed with PAH, and eligible to undergo cardiopulmonary exercise test (CPET). The relations between ECG values and parameters obtained in procedures such as six-minute walk test (6-MWT), echocardiography, right heart catheterization (RHC), and CPET were analyzed.Results:P-wave amplitude in lead II correlated positively with CPET parameter of respiratory response: minute ventilation to carbon dioxide production slope (VE/VCO2 slope; r = 0.436, p = 0.029) and echocardiographic estimated RA pressure (RAP; r = 0.504, p = 0.02). RV Sokolow-Lyon index (RVSLI) positively correlated with echocardiographic parameters reflecting RV function, overload, and afterload–tricuspid regurgitation pressure gradient (TRPG; r = 0.788, p < 0.001), RV free wall thickness (r = 0.738, p < 0.001), and mean pulmonary arterial pressure (mPAPECHO; r = 0.62, p = 0.0016), respectively, as well as VE/VCO2 slope (r = 0.593, p = 0.001) and mPAP assessed directly in RHC (mPAPRHC; r = 0.469, p = 0.0497). R-wave in lead aVR correlated positively with TRPG (r = 0.719, p < 0.001), mPAPECHO (r = 0.446, p = 0.033), and several hemodynamic criteria of PAH diagnosis: positively with mPAPRHC (r = 0.505, p = 0.033) and pulmonary vascular resistance (r = 0.554, p = 0.026) and negatively with pulmonary capillary wedge pressure (r = −0.646, p = 0.004). QRS duration correlated positively with estimated RAP (r = 0.589, p = 0.004), vena cava inferior diameter (r = 0.506, p = 0.016), and RA area (r = 0.679, p = 0.002) and negatively with parameters of exercise capacity: peak VO2 (r = −0.486, p = 0.012), CPET maximum load (r = − 0.439, p = 0.025), and 6-MWT distance (r = −0.430, p = 0.046). ROC curves to detect intermediate/high 1-year mortality risk (based on ESC criteria) indicate RVSLI (cut-off point: 1.57 mV, AUC: 0.771) and QRS duration (cut-off points: 0.09 s, AUC: 703 and 0.1 s, AUC: 0.759) as relevant predictors.Conclusion:Electrocardiography appears to be an important and underappreciated tool in PAH assessment. ECG corresponds with clinical parameters reflecting PAH severity.

484 Echocardiographic patterns in patients with apolipoprotein AI amyloidosis

Abstract Aims Hereditary amyloidosis are rare diseases characterized by extracellular deposition of insoluble fibril proteins in target organs disrupting their structure and function. The APOA1 gene encodes the precursor of apolipoprotein AI (ApoAI), whose mature form is the major component of high-density lipoproteins. There are some clusters of ApoAI amyloidosis (AApoAI) worldwide, including in the Lombardy and Veneto regions. Patients with AApoAI often present with chronic kidney disease, liver and spleen enlargement, with occasional involvement of the heart, peripheral nervous system, and other organs. Patterns of cardiac disease in AApoAI have never been systematically investigated. Methods and results We examined all patients with an established diagnosis of AApoAI referred to a dedicated outpatient clinic in Brescia from 2010 to 2020. The cardiac screening included a transthoracic echocardiogram with 2D speckle-tracking analysis. One-hundred and eighty-nine patients were evaluated [n = 102 (54%) men, median age 55 years (interquartile range 42–67)]. Renal disease was present in 39% and liver disease in 31%. Almost all patients were in sinus rhythm (96%). Median left ventricular ejection fraction (LVEF) was 60% (55–66), and just 2% of patients had LVEF &amp;lt;50%. Diastolic function was preserved, with E/e′ ratio of 7 (6–10). Overall, patients did not display a prominent LV hypertrophy, with median interventricular septal thickness of 11 mm (9–12), a posterior wall thickness of 9 mm (8–11), and a LV mass index of 92 g/m2 (74–111). Global longitudinal strain [−19% (−21 to − 17)], and the mass to strain ratio (MSR) [10.0 (6.8–12.1)] were within normal limits. Ten percent of patients displayed apical sparing, and 19% had a ‘granular sparkling’ appearance of the interventricular septum, which are both echocardiographic red flags of cardiac amyloidosis. Right ventricular (RV) function was preserved [median tricuspid annular plane systolic excursion of 23 mm (20–26)], with a borderline RV free wall thickness [6 mm (5–8)]. A pericardial effusion was present in 11%. Moderate to severe mitral, aortic or tricuspid regurgitation or aortic stenosis were found in 11%, 4%, 6% and no patients, respectively. We found moderately strong correlations between age and several echocardiographic findings, namely: IVS (P &amp;lt; 0.001, r = 0.484), LVMI (P &amp;lt; 0.001, r = 0.459), E/e′ (P &amp;lt; 0.001, r = 0.501), and RV free wall thickness (P &amp;lt; 0.001, r = 0.459). Absolute GLS tended to decrease with age (P &amp;lt; 0.001, r = 0.380), and MSR to increase (P &amp;lt; 0.001, r = 0.357). Conclusions In the largest series of patients with AApoAI so far, minor signs of cardiac disease emerged from transthoracic echocardiography. Nonetheless, some red flags of cardiac amyloidosis were found in some patients. Furthermore, the correlations between age and echocardiographic findings suggested a progressive increase in wall thickness, a decline in systolic and diastolic function, and a greater uncoupling between LV mass and contractility over time.

Abstract 11209: KER-012, a Novel Modified ActrII Ligand Trap, Attenuated Cardiac Pathology in a Pulmonary Arterial Banding Model of Right Ventricle Overload

Pulmonary arterial hypertension (PAH) is a debilitating disorder, characterized by right ventricle (RV) pressure overload, cardiac hypertrophy, and progressive RV dysfunction. PAH is associated with unbalanced TGFß signaling, favoring signaling of SMAD2/3 and opposing SMAD1/5/9. The result is an increase in vascular proliferation and disruption of vascular homeostasis. KER-012 is a modified ActRII ligand trap designed to inhibit ligands that signal through SMAD2/3 to promote restoration of vascular homeostasis. To investigate the cardio-protective effects of RKER-012, a research version of KER-012, we evaluated the effect of treatment in a pulmonary arterial banding (PAB) model. In this study, 8-week-old, male C57BL/6 mice underwent sham or PAB surgery to increase RV pressure and induce cardiac remodeling. The sham cohort received vehicle (VEH) treatment and PAB mice received either vehicle (VEH) or 10 mg/kg RKER-012 twice weekly for 3 weeks. Relative to sham mice, all PAB mice had elevated pulmonary arterial pressures on day 1 (all ps&lt;0.0001) that persisted until day 21 (all ps&lt;0.01), indicating that the PAB procedure was effective. VEH PAB mice also exhibited diminished cardiac function, including increased end systolic pressure volume relationship (ESPVR; +79.3%; p&lt;0.001) and increased myocardial performance index (MPI; +45.6%; p&lt;0.0001) compared to Sham VEH. Additionally, VEH PAB mice had markers of cardiac remodeling, including increased Fulton Indices (+54.8%; p&lt;0.0001), increased RV free wall thickness (RVFWT; +95.8%; p&lt;0.0001) and increased cardiac fibrotic tissue (+529.9%; p&lt;0.0001). In contrast, RKER-012 treatment was cardioprotective and prevented changes in cardiac function and tissue remodeling. In treated mice, there was a trend for decreased ESPVR (-14.2%), decreased MPI (-13.2%, p&lt;0.01), decreased Fulton Index (-13.5%; p&lt;0.01), and decreased RVFWT (-22.9%; p&lt;0.0001) compared to VEH PAB. Treated mice also had reduced cardiac fibrotic tissue (-38.9%, p&lt;0.01). Taken together, these data provide evidence that KER-012 has the potential to reduce cardiac remodeling and improve cardiac performance in pathologies involving constricted pulmonary arterial blood flow and could provide benefit in diseases such as PAH.

Congestive Hepatopathy Secondary to Right Ventricular Hypertrophy Related to Monocrotaline-Induced Pulmonary Arterial Hypertension.

Heart dysfunction and liver disease often coexist. Among the types of cardiohepatic syndrome, Type 2 is characterized by the chronic impairment of cardiac function, leading to chronic liver injury, referred to as congestive hepatopathy (CH). In this study, we aimed to establish a rat model of CH secondary to right ventricular hypertrophy (RVH) related to monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Fifty male Wistar rats were divided into four groups and randomly assigned to control and experimental groups. Three experimental groups were submitted to intraperitoneal MCT inoculation (60 mg/kg) and were under its effect for 15, 30 and 37 days. The animals were then sacrificed, obtaining cardiac and hepatic tissues for anatomopathological and morphometric analysis. At macroscopic examination, the livers in the MCT groups presented a nutmeg-like appearance. PAH produced marked RVH and dilatation in the MCT groups, characterized by a significant increase in right ventricular free wall thickness (RVFWT) and chamber area. At histological evaluation, centrilobular congestion was the earliest manifestation, with preservation of the hepatocytes. Centrilobular hemorrhagic necrosis was observed in the groups exposed to prolonged MCT. Sinusoidal dilatation was markedly increased in the MCT groups, quantified by the Sinusoidal Lumen Ratio (SLR). The Congestive Hepatic Fibrosis Score and the Centrilobular Fibrosis Ratio (CFR) were also significantly increased in the MCT30 group. Hepatic atrophy, steatosis, apoptotic bodies and, rarely, hydropic swelling were also observed. SLR correlated strongly with CFR and RVFWT, and CFR correlated moderately with RVFWT. Our rat model was able to cause CH, related to monocrotaline-induced PAH and RVH; it was feasible, reproducible, and safe.

Impact of obstructive sleep apnea on the right ventricle function

Right ventricular (RV) involvement in obstructive sleep apnea syndrome (OAS) is controversial. The aim of this study was to determine a correlation between echocardiographic parameters of RV function and severity of OSA assessed by the apnea- hypopnea index (AHI). Sixty patients with suspected OSA were enrolled. All patients had overnight polygraphy and an echocardiographic assessment of RV structure and function. Patients were divided into three groups: a control group ( n = 20) with an AHI < 5/h, a group of mild to moderate OSA ( n = 18) with an AHI = 5-30/h and a group of severe OSA ( n = 22) with AHI≥ 30/h. There were no differences of age, body mass index and sex among the three groups. There was no difference in systolic pulmonary pressure. RV free wall thickness, end-diastolic surface and right atrium surface were statistically higher in OSA patients compared with controls. The peak systolic myocardial velocity at tricuspid lateral annulus S’ were significantly lower in patients compared with controls (14.5 ± 3 vs. 12.2 ± 2 cm/s, P < 0.001; respectively). This decrease was greater in patients with severe OSA compared with mild to moderate OSA (11.4 ± 3 vs. 13.0 ± 1 cm/s, P = 0.05, respectively). Right ventricular myocardial performance index (MPI) was significantly higher in OSA compared with controls (0.55 ± 0.12 vs. 0.46 ± 0.14, P = 0.024, respectively) but it was not correlated with the severity of IAH. In OSA patients, there was a significant RV dysfunction independently of pulmonary pressure, although the correlation with the severity of IAH was moderate.

Chronic Inhaled Nicotine‐Induced Pulmonary Hypertension and Right Ventricular Remodeling are Mediated by Angiotensin‐II Type 1 Receptor

Introduction Use of electronic cigarettes is rapidly increasing among youth and young adults, but little is known regarding the long-term cardiopulmonary impacts of these nicotine-containing devices. Our group previously demonstrated that chronic inhaled nicotine induces pulmonary hypertension and right ventricular (RV) remodeling in mice, characterized by increased RV systolic pressure (RVSP) and RV free wall thickness during diastole (RVFWT;d). These changes were associated with upregulated RV angiotensin converting enzyme (ACE), leading us to hypothesize that these nicotine-induced effects are mediated by the renin-angiotensin system. ACE inhibitor and angiotensin-II receptor blocker use in a large retrospective pulmonary hypertension patient cohort was associated with improved survival. Here, we utilized losartan, a specific antagonist of the angiotensin-II type 1 receptor (AT1R), to further explore nicotine's cardiopulmonary effects. Methods: Male C57BL/6 mice received either nicotine vapor or room air for 12 hours per day, and exposure was measured by serum cotinine (559±57 ng/mL; comparable to human cigarette smokers or electronic cigarette users). A subset of mice was treated with losartan via osmotic mini-pump for 8 weeks. Losartan dosage was approximately 5.0 to 6.5 mg/kg/day due to body weight differences throughout the experiment. Cardiac structure and function were assessed using echocardiography and RV catheterization. Results: Chronic inhaled nicotine significantly increased RVSP (40.7±3.5 mmHg, n=11) versus air exposure (25.6±1.0 mmHg, n=11, p<0.005). Mice receiving both losartan and nicotine had significantly reduced RVSP (24.0±1.3 mmHg, n=12, p<0.005) versus nicotine alone. There was no difference in RVSP between air mice and either losartan-infused group (air-losartan: 23.7±1.2 mmHg, n=14). RVFWT;d was increased in nicotine mice (0.44±0.01 mm, n=12) versus air mice (0.31±0.01 mm, n=10, p<0.0001). Losartan infusion of nicotine mice resulted in significantly decreased RVFWT;d (0.34±0.01 mm, n=8, p<0.0001) versus nicotine alone. There was no difference in RVFWT;d between air mice and either losartan-infused group (air-losartan: 0.32±0.01 mm, n=7). Chronic inhaled nicotine increased RV internal diameter during diastole (RVID;d; 1.56±0.04 mm, n=12) versus air mice (1.24±0.07 mm, n=10, p<0.0001), suggesting RV dilation. RVID;d between air-exposed mice receiving losartan (1.23±0.04, n=7) and nicotine-exposed mice receiving losartan (1.44±0.03, n=8) was not significantly different. Neither nicotine nor losartan exposure resulted in changes to left ventricular structure and function. Conclusion: These findings provide the first preclinical evidence that AT1R antagonism can ameliorate chronic inhaled nicotine-induced pulmonary hypertension and RV remodeling.

Angiotensin II type 1 receptor mediates pulmonary hypertension and right ventricular remodeling induced by inhaled nicotine.

Use of electronic cigarettes is rapidly increasing among youth and young adults, but little is known regarding the long-term cardiopulmonary health impacts of these nicotine-containing devices. Our group has previously demonstrated that chronic, inhaled nicotine induces pulmonary hypertension (PH) and right ventricular (RV) remodeling in mice. These changes were associated with upregulated RV angiotensin-converting enzyme (ACE). Angiotensin II receptor blockers (ARBs) have been shown to reverse cigarette smoking-induced PH in rats. ACE inhibitor and ARB use in a large retrospective cohort of patients with PH is associated with improved survival. Here, we utilized losartan (an ARB specific for angiotensin II type 1 receptor) to further explore nicotine-induced PH. Male C57BL/6 mice received nicotine vapor for 12 h/day, and exposure was assessed using serum cotinine to achieve levels comparable to human smokers or electronic cigarette users. Mice were exposed to nicotine for 8 wk and a subset was treated with losartan via an osmotic minipump. Cardiac function was assessed using echocardiography and catheterization. Although nicotine exposure increased angiotensin II in the RV and lung, this finding was nonsignificant. Chronic, inhaled nicotine significantly increased RV systolic pressure and RV free wall thickness versus air control. These parameters were significantly lower in mice receiving both nicotine and losartan. Nicotine significantly increased RV internal diameter, with no differences seen between the nicotine and nicotine-losartan group. Neither nicotine nor losartan affected left ventricular structure or function. These findings provide the first evidence that antagonism of the angiotensin II type 1 receptor can ameliorate chronic, inhaled nicotine-induced PH and RV remodeling.NEW & NOTEWORTHY Chronic, inhaled nicotine causes pulmonary hypertension and right ventricular remodeling in mice. Treatment with losartan, an angiotensin II type 1 receptor antagonist, ameliorates nicotine-induced pulmonary hypertension and right ventricular remodeling. This novel finding provides preclinical evidence for the use of renin-angiotensin system-based therapies in the treatment of pulmonary hypertension, particularly in patients with a history of tobacco-product use.

Cardiac remodelling and heart failure symptoms in patients with apical hypertrophic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Background Although earlier publications suggested a more benign clinical course for patients (pts) with apical hypertrophic cardiomyopathy (ApHCM), recent studies report increased morbidity and mortality, comparable to the prognosis of other HCM variants. Moreover, information regarding cardiac remodelling and its relationship with symptoms in pts with ApHCM is scarce. The aim of our study was to assess left ventricular (LV), right ventricular (RV) and left atrial (LA) remodelling in pts with ApHCM in comparison with non-apical variants of HCM (nonApHCM), and the impact of cardiac remodelling on heart failure symptoms. Methods One hundred fifty-one consecutive pts with HCM (52 ± 16 yrs, 47% men) in sinus rhythm and with preserved LV ejection fraction (16 pts with ApHCM and 135 pts with nonApHCM), were prospectively enrolled. Comprehensive echocardiography was performed in all, including the measurement of maximal LV wall thickness (LVWT), RV free wall thickness (RVWT) and maximal LA volume indexed to body surface area (LAVi). Global LV strain (ɛ), RVɛ, LAɛ and end-diastolic LA strain rate (ASr) were measured using speckle-tracking echocardiography (STE). The ratio of E to average e’ was used to estimate LV filling pressure. The degree of mitral regurgitation (1/2/3) has also been assessed. Heart failure symptoms were defined according to the New York Heart Association (NYHA) classification. Results Forty-eight pts in nonApHCM group had intraventricular obstruction. There were no significant differences between pts with and without ApHCM regarding: age (58 ± 20 vs 52 ± 16 yrs), gender distribution, RVWT, LVɛ (-14.9 ± 2.7 vs -13.9 ± 3.5 %), RVɛ (-19.6 ± 3.6 vs -10.0 ± 5.0%), LAɛ (19.2 ± 5.8 vs 16.4 ± 7.1%)(p &amp;gt; 0.05 for all). Pts with ApHCM had lower values for LVWT (17.2 ± 1.9 vs 21.4 ± 5.2 mm, p = 0.002), E/e’ (12.0 ± 5.8 vs 17.6 ± 8.5, p = 0.02) and LAVi (48 ± 16 vs 61 ± 25, p = 0.03) compared to pts with nonApHCM. Pts with ApHCM had slightly better LA contractile function as assessed by ASr (-1.23 ± 0.50 vs -0.97 ± 0.49 sec-1, p = 0.05). Mitral regurgitation was more often severe in nonApHCM pts (56/42/31 vs 10/4/0, p &amp;lt; 0.001). There was no significant difference between the percentage of symptomatic pts (NYHA class ≥2) in ApHCM vs nonApHCM group (p = 0.3). In the ApHCM group, symptomatic pts had significantly lower ASr compared to asymptomatic pts (-0.98 ± 0.35 vs -1.61 ± 0.46 sec-1, p = 0.01). Conclusions Despite of lower LVWT values, less severe MR and no obstruction, pts with apical HCM have similar prevalence of heart failure symptoms, and similar LV, RV and LA dysfunction compared to pts with non-apical HCM. Symptomatic pts with apical HCM have worse LA contractile function compared to asymptomatic pts.

Effects of Chronic Nicotine Inhalation on Systemic and Pulmonary Blood Pressure and Right Ventricular Remodeling in Mice.

Cigarette smoking is the single most important risk factor for the development of cardiovascular and pulmonary diseases; however, the role of nicotine in the pathogenesis of these diseases is incompletely understood. The purpose of this study was to examine the effects of chronic nicotine inhalation on the development of cardiovascular and pulmonary disease with a focus on blood pressure and cardiac remodeling. Male C57BL6/J mice were exposed to air (control) or nicotine vapor (daily, 12 hour on/12 hour off) for 8 weeks. Systemic blood pressure was recorded weekly by radio-telemetry, and cardiac remodeling was monitored by echocardiography. At the end of the 8 weeks, mice were subjected to right heart catheterization to measure right ventricular systolic pressure. Nicotine-exposed mice exhibited elevated systemic blood pressure from weeks 1 to 3, which then returned to baseline from weeks 4 to 8, indicating development of tolerance to nicotine. At 8 weeks, significantly increased right ventricular systolic pressure was detected in nicotine-exposed mice compared with the air controls. Echocardiography showed that 8-week nicotine inhalation resulted in right ventricular (RV) hypertrophy with increased RV free wall thickness and a trend of increase in RV internal diameter. In contrast, there were no significant structural or functional changes in the left ventricle following nicotine exposure. Mechanistically, we observed increased expression of angiotensin-converting enzyme and enhanced activation of mitogen-activated protein kinase pathways in the RV but not in the left ventricle. We conclude that chronic nicotine inhalation alters both systemic and pulmonary blood pressure with the latter accompanied by RV remodeling, possibly leading to progressive and persistent pulmonary hypertension.