Right Ventricular Systolic Function Research Articles

Exercise Doppler echocardiography to detect early changes in the right ventricular-pulmonary circulation unit after pulmonary embolism

Abstract Introduction After pulmonary embolism (PE), patients frequently complain about reduced exercise capacity and dyspnea on exertion, even without pulmonary hypertension (PH). The underlying condition is often chronic thromboembolic disease, which is caused by residual pulmonary obstruction with preserved resting pulmonary haemodynamics. The symptoms are the consequences of the increased dead space ventilation, exercise-induced PH and right ventricular (RV) dysfunction. We aimed to assess the pathologic differences in the echocardiographic parameters of the RV- pulmonary circulation unit among patients with previous PE and the healthy control group. Furthermore, an objective was to compare the hemodynamic response to stress after different treatment strategies (thrombolysis vs. heparin administration). Methods 21 patients after PE (mean age 58,5±12,1 years; 53% men) have been included in the study. All of them were effectively anticoagulated for at least three months, and none had any signs of PH on echocardiography at rest. The control group included 20 healthy volunteers (mean age 56,9±11,5 years; 55% men). Each patient underwent resting and exercise stress echocardiography on a semi-recumbent bicycle ergometer according to a standardised protocol until the maximally tolerated workload. Echocardiography was performed at rest, at 50 Watt workload and during peak stress. The measurements focused on the RV's systolic function (TAPSE), the estimated pulmonary artery systolic pressure (PASP), and the Doppler measurements in the RV and left ventricular outflow tracts. Pulmonary vascular resistance (PVR) and RV-pulmonary artery coupling (RV-PA) were calculated from the echocardiographic parameters. Results The post-PE group had significantly higher PASP (39,2 ±16,6 vs. 27,7±12,5 mmHg; p<0,05) and PVR (1,5±0,4 vs. 1,1±0,3 Wood Units; p<0,05) at peak stress, than the controls. 55% of post-PE patients remained symptomatic, but there were no significant differences between the symptomatic and asymptomatic groups regarding TAPSE, PASP, RV-PA coupling and PVR. 30% of post-PE patients had thrombolysis. In the patients where thrombolysis was performed, the coupling at peak stress was significantly higher than in heparin-treated patients (1,4±0,1 vs 0,9±0,4 mm/mmHg, p<0,05). Conclusion Post-PE patients without resting PH have higher PVR and PASP than the healthy control group, even after at least 3 months of adequate therapy. Post-PE patients treated with thrombolysis may have more preserved RV-PA coupling than the heparin-treated patients.

The application of supine bicycle exercise stress echocardiograph for identification of susceptibility to acute mountain sickness

Abstract Background Exposure to high altitude is likely to lead to acute mountain sickness (AMS). At present, there are no definite parameters that can accurately predict the occurrence of AMS. Objectives The purposes of this study are (1) to assess the relationship between stress echocardiographic parameters and AMS, (2) to identify the predictors of AMS at sea level by exercise stress echocardiography. Methods A total of 36 healthy adults were enrolled and underwent resting and exercise stress echocardiography on a supine bicycle at sea level. Heart rate (HR) and blood pressure (BP) were monitored during stress echocardiography. Left ventricular (LV) ejection fraction and E/e’ were calculated at rest and peak stage. Other right ventricular systolic function parameters and pulmonary artery pressure (PAP) were calculated at the same time, which included tricuspid regurgitation velocity (TRV), tricuspid annular peak systolic excursion (TAPSE), systolic PAP (sPAP), right ventricular (RV) dimension by 2D, right ventricular area at the end of diastole (RVAD), right ventricular area at the end of systolic (RVAS),RV fraction of area change (FAC), right ventricular outflow tract velocity time integral (RVOT VTI).Pulmonary vascular resistance (PVR) was calculated. All subjects ascended to 3600m within 24 hours by bus. AMS was identified by 2018 Lake Louise Questionnaire Score. Univariable and multivariable logistic regression analysis assessed independent factors associated with AMS. Results At the altitude of 3600m, 13 of 36 subjects had AMS, which defined as AMS (+) group. And the rest was AMS (-) group. There were no significant differences in HR, BP, and LV systolic and diastolic function between the two groups (P > 0.05). TRV, sPAP, and PVR were much higher at peak stage in AMS (+) group (P < 0.05). No significant differences were found in RV systolic function at rest and peak stage between the two groups. By multivariable logistic regression model, PVR and RVAD at peak stage were significantly associated with AMS occurrence (PVR-OR =1.962,95% CI: 0.689-0.973,p =0.002; RVAD-OR =1.962,95% CI: 0.638-0.967,p =0.005;). The cutoff value to predict AMS were 1.55 for PVR (AUC: 0.831) and 11.45 cm2 for RVAD (AUC: 0.802). Conclusions Supine bicycle exercise stress echocardiography is a useful and noninvasive technique to identify subjects susceptible to AMS. Subjects with higher PVR and RVAD at peak stage were associated with susceptibility to AMS.

Serial changes in left and right ventricular global longitudinal strain in symptomatic obstructive hypertrophic cardiomyopathy treated with mavacamten: insights from VALOR-HCM trial

Abstract Background In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM phase 3 randomized, double-blind, placebo-controlled clinical trial demonstrated that mavacamten, reduces the need for septal reduction therapy with sustained improvement in left ventricular outflow tract gradients and symptoms. As a cardiac myosin inhibitor, mavacamten’s mechanism of action reduces myocardial hypercontractility. Global longitudinal strain (GLS), a measure of regional myocardial function, is a more sensitive marker of systolic function and can complement left ventricular ejection fraction (LVEF). Objective We sought to assess serial changes in LV and right ventricular (RV)-GLS in patients enrolled in the VALOR-HCM study. Methods VALOR-HCM included 112 symptomatic obstructive HCM patients (mean 60 years, 51% male, LVEF 68%). Patients assigned to mavacamten at baseline continued the drug for 56 weeks (n=56) and those assigned to placebo crossed over to mavacamten (n=52) from week 16-56 (40-week exposure). LV and RV-GLS assessment was performed according to the current American and European guideline recommendations using a vendor-neutral post processing software. Non-foreshortened apical (4, 3 and 2-chamber) views were used to obtain peak value of LV-GLS. For RV-GLS, RV focused 4-chamber view was used to calculate RV 4-chamber and free wall strain. A more negative strain value is favorable. Results Serial changes in LVEF, average LV-GLS, and RV-GLS (4-chamber and free wall) from baseline to week 56 are shown in the Figure. Despite preserved LVEF at baseline, average baseline LV-GLS was abnormal. There were significant and continued improvements in LV-GLS in the total group from baseline to week 56. 12 patients had transient reduction in LVEF (<50%) requiring temporary drug interruption (permanent discontinuation in 3). The LV-GLS in this subgroup was worse at baseline compared to the total study population, with no significant worsening from baseline through week 56. In the overall population, excluding these 12 patients, LV-GLS demonstrated an improvement sustained through week 56. Both free wall and 4-chamber RV-GLS were abnormal at baseline and remained unchanged from baseline to week 56. Conclusions In the VALOR-HCM trial, despite hypercontractile LVEF at baseline, average baseline LV-GLS was worse than normal reference values. Treatment with mavacamten resulted in an improvement in LV-GLS from baseline through Week 56 (with no significant worsening of LV-GLS in the subgroup who experienced any reduction in LVEF <50%), suggesting a favorable long-term impact on regional LV systolic function due to the reduction of cardiac hypercontractility. Additionally, there was no significant detrimental impact on RV systolic function on serial GLS assessment.Serial changes in LV and RV GLS in VALOR

Cardiovascular (reverse) remodelling induced by pregnancy: looking at the right side of the heart

Abstract Introduction Many studies have focused on pregnancy-induced left ventricular remodelling, overlooking the changes in right cardiac chambers. Purpose To characterize the right cardiovascular (CV) remodelling and reverse remodelling (RR) induced by pregnancy and postpartum, respectively, and the impact of CV risk (CVR) factors on these processes. Methods This prospective cohort was recruited at two tertiary centers from 2019 to 2022, including 51 healthy and 79 obese and/or hypertensive and/or with gestational diabetes and/or smoking habits pregnant women (cardiovascular risk [CVR] group). Women were evaluated by transthoracic echocardiography at the 1st trimester (1T) and 3rd trimester (3T) of pregnancy, as well as one-month (PP1), six-months (PP2), and one-year postpartum (PP3). Generalized linear mixed-effects models were used for the analysis of right CV remodelling and RR and to evaluate the impact of CVR factors on these processes. Results This study included 130 pregnant women, 60.8% primiparous, with a median age of 33 years. Despite all echocardiographic results being within the normality range, we describe the progression of right heart adaptations throughout pregnancy and postpartum (Table 1), namely: 1) Similar enlargement of the right atrium (RA) and right ventricle (RV) dimensions throughout pregnancy, recovering at PP2 except for RA in the CVR group; 2) Preserved RV systolic function throughout pregnancy in both groups, while the postpartum hemodynamic normalization triggers a reduction of (TAPSE) and tricuspid S' wave velocity; 3) Reduced RA strain in both groups during pregnancy, more evident in CVR group, which had a slower postpartum recovery; 4) Preserved RV global longitudinal strain (GLS) throughout follow-up time, being significantly reduced in 3T of CVR group and recovering at PP2; 5) Reduction of tricuspid E/A ratio from 1T to 3T in both groups with an early recovery at PP1, being these values significantly higher in the healthy group, and 6) Steady pulmonary artery systolic pressure (PASP) values throughout follow-up time, showing consistently higher values in the CVR group. Conclusion This study describes the subclinical right cardiac functional and structural changes within the physiological range, which recover 6 months after delivery. CVR factors impact the magnitude of the subclinical RV diastolic function changes, PASP and myocardial deformation (strain) without any impact on classic RV systolic function.

Cardiac structure and function in patients with chronic obstructive pulmonary disease

Abstract Background Chronic obstructive pulmonary disease (COPD) is common and strongly associated with cardiovascular disease, but the pathophysiology has not been fully elucidated. Purpose We aimed to investigate cardiac structure and function in patients with COPD compared to a matched general population. Methods In a prospective cohort study, 796 patients with COPD were included and matched 1:2 on age and sex with controls from a general population study. All participants underwent an examination program including echocardiography. Standardized linear regression coefficients were used to compare cardiac structure and function in patients with COPD vs. controls. Impaired left ventricular (LV) function was defined as a left ventricular ejection fraction (LVEF) <50%, or global longitudinal strain (GLS) <16% (numerical). Impaired right ventricular (RV) function was defined as tricuspid annular plane systolic excursion (TAPSE) <1.7 cm. Diastolic dysfunction was defined as having at least two of the following parameters: E/e’ >14, septal e’ velocity <7cm/s, or lateral e’ velocity <10 cm/s, left atrial volume index (LAVi) >34 mL/m2, or tricuspid regurgitation velocity (TRV) >2.8 m/s. Logistic regression was used to assess associations between having COPD and systolic and diastolic dysfunction. Results Mean age was 70.2 ± 8.3 years and 52% were females. COPD patients had a mean forced expiratory volume in 1 second (FEV1) of 49.4 ± 18.8% predicted. At baseline, 43% of the patients with COPD had hypertension and 10% had diabetes (DM). Additionally, 57% with COPD had cardiovascular disease at baseline, including 12% with ischemic heart disease (IHD), 15% with atrial fibrillation (AF), 6% with heart failure, and 5% with a previous ischemic stroke. Patients with COPD had impaired measures of cardiac structure and function including a lower GLS (COPD vs. controls: 16.3 vs. 19.2%), lower TAPSE (2.3 vs. 2.6 cm), larger LAVi (29.0 vs. 24.7 mL/m2), and higher TRV (2.7 vs. 2.3 m/s), p for all associations <0.001. (See figure). Patients with COPD had a significantly higher prevalence of impaired LV systolic function (OR for GLS <16%: 8.18, 95% CI(6.04; 11.1), p <0.001), impaired RV systolic function (OR for TAPSE <1.7 cm: 2.77, 95% CI(1.63; 4.69), p <0.001), and LV diastolic dysfunction (OR for diastolic dysfunction grade I or higher: 4.00, 95% CI(3.12; 5.13), p <0.001) after adjustment for age, sex, hypertension, smoking, DM, IHD, AF, and lower density lipoprotein. (See figure). Conclusion Patients with COPD had significantly impaired LV and RV systolic function as well as impaired diastolic function compared with individuals from the general population. These findings underscore the importance of recognizing and addressing cardiovascular comorbidities in COPD.

The effect of exercise on RV-PC coupling in asymptomatic patients with significant primary mitral regurgitation

Abstract Background Right ventricular–pulmonary circulation (RV-PC coupling) serves as an index to evaluate RV function in relation to underlying RV afterload. Although impaired RV-PC coupling has been proposed as a predictor of adverse outcomes in heart failure (HF) patients with secondary mitral regurgitation (MR), there is limited data available for patients with primary MR. Purpose The objective of this study was to assess and compare alterations in RV-PC coupling during exercise with bicycle stress echocardiography in individuals with asymptomatic moderate to severe primary MR (MR group) and normal subjects (Control group). Μethods All patients and controls underwent stress echocardiography with a supine bicycle. RV systolic function was evaluated with TAPSE and S’. The non-invasively measured RV-PC coupling was evaluated by indexing TAPSE and S’ to right ventricular systolic pressure (RVSP) during baseline echocardiogram and peak workload stages of bicycle SE. Results Among the 48 patients in the MR group (mean age 53.5±15.16 years, 58.3% female), 39 patients had moderate MR(81.3%), 5 patients had moderate-to-severe MR(10.4%), and 4 patients had severe MR(8.3%). The duration of stress echocardiogram was significantly shorter in the MR group compared to control group (8.11±2.39 min vs 10.5±1.05 min, respectively; p<.001). Left Ventricular Ejection Fraction (LVEF) was within normal limits in both groups {70.7±11.9 % vs 72.6±12.1 %(p=NS} and the dimensions of left ventricular cavity (end-diastolic and end-systolic diameters) were significantly larger in the MR group compared to control group (49.25±5.21 mm vs 45.6±4.08mm (p .016) and 31.81±4.27mm vs 29.07±4.21mm (p .033) respectively}. TAPSE and RVSP increased from baseline to peak dose [23.48 ±3.05mm vs 29.94±3.48mm (p < .001), 8.54±4.56mmHg vs 43.79±5.27mmHg (p < .001), respectively]. There were no significant differences in TAPSE/RVSP and S’/RVSP between the two groups at rest. However, a significantly steady decrease was observed from baseline to peak dose (0.84±0.16 mm/mmHg vs 0.72±0.19mm/mmHg (p <.001) and 0.52±0.11 cm/sec/mmHg vs 0.50±0.15 cm/sec/mmHg (p .004), respectively). Conversely, these parameters did not exhibit a significant decrease in the control group. Finally, there was no significant correlation observed between the changes in the index TAPSE/RVSP , ratio E/E’ and systolic blood pressure. Conclusions RV-PC coupling decreases during exercise in asymptomatic patients with moderate to severe MR, independently of left ventricular dynamic changes. In contrast , there is no significant change in RV-PC coupling observed in the control group. Therefore, future studies should aim to evaluate the incremental role of this novel index not only in the assessment and evaluation of patients with MR but also as a potential prognostic marker.TAPSE/RVSP GraphTable of echocardiographic measurements

Insulin-like growth factor binding protein 2 predicts course of concomitant right-ventricular dilation and tricuspid regurgitation after transcatheter edge-to-edge mitral valve repair

Abstract Aims Right ventricular (RV) dilation and secondary tricuspid regurgitation (TR) are highly prevalent comorbidities in patients with mitral regurgitation and are associated with a worse prognosis. TR improvement after successful transcatheter edge-to-edge mitral valve repair (M-TEER) is reported regularly, however specific factors contributing to the recovery of RV function and TR after M-TEER are poorly understood. Particularly the role of serum biomarkers in this context is unclear. We aimed to identify specific biomarkers associated with the course of concomitant RV dilation and TR after M-TEER. Methods and Results We prospectively included 242 patients undergoing M-TEER at our center and obtained pre-procedural blood samples for biomarker analysis. A commercial multiplex protein assay (Cardiovascular III, Olink, Uppsala, Sweden) was used to quantify expression levels of 92 defined biomarkers. We then analyzed differences in biomarker expression between patients with and without right ventricular reverse remodeling (RVRR) as defined by improvement of concomitant TR by at least one grade and/or downsizing of the basal RV diameter of at least 10%. 242 patients were included in this analysis, 94 had no/mild concomitant TR at baseline, 148 had moderate/severe TR. RV diameters correlated with TR severity and were significantly larger in patients with moderate/severe TR. At baseline, expression of numerous cardiometabolic biomarkers was significantly higher in patients with moderate/severe TR. These included NT-proBNP (1.9-fold, p < 0.001), matrix metalloproteinase 2 (1.4-fold, p < 0.001) as well as insulin-like growth factor binding proteins 1 (1.7-fold, p < 0.001), -2 (1.3-fold, p = 0.001) and -7 (1.4-fold, p < 0.001). Follow-up analysis was performed in patients with initial moderate/severe TR. The course of TR and RV dimensions three months after M-TEER could be assessed in 99 patients (56 with moderate TR, 43 with severe TR). RVRR had occurred in 50 patients (50.5%). Patients without RVRR had a higher prevalence of chronic pulmonary disease (24.5 vs. 2.2%, p < 0.001). No further differences in clinical characteristics were found. Specifically, RV diameter, systolic pulmonary artery pressure (sPAP) and right-ventricular systolic function did not differ substantially between both groups. Strikingly however, the expression of insulin-like growth factor binding protein 2 (IGFBP-2) was significantly higher in patients, who did not develop RVRR (fold change 1.3 compared to patients with RVRR, p = 0.022). After adjustment for covariates IGFBP-2 was independently associated with absence of RVRR (Odds Ratio 2.078, 95% Confidence interval 1.108 – 3.897, p = 0.023). Conclusions In patients undergoing M-TEER with concomitant moderate or severe TR, numerous cardiometabolic biomarkers including IGFBP-2 are upregulated. Higher levels of IGFBP-2 at baseline are independently associated with persistent TR and/or RV dilation after M-TEER.

Interaction between right atrial function reserve and liver stiffness after complete repair of tetralogy of fallot: a pilot study

Abstract Background Impaired right atrial mechanics is reported in patients with repaired tetralogy of Fallot (TOF) and is associated with liver stiffness. However, whether right atrial functional reserve correlates with liver stiffness is unknown. Purpose This study tested the hypothesis that right atrial reserve capacity is limited in patients with repaired TOF and explore its relationships with right ventricular function and liver stiffness. Methods 10 patients (45% male) aged 19.04 ± 3.76 at 16.70 ± 4.30 years after repair and 15 controls (60% male, aged 20.31 ± 1.25 years) were studied. RA mechanics was assessed by speckle-tracking echocardiography (STE) at rest and during bicycle exercise, with quantification of positive, negative, and total strain, and strain rates at ventricular systole (aSRs), early diastole (aSRed), and atrial contraction (aSRac). Right atrial function reserve (RAFR) is calculated as (∆RA total strain x [1-1/ RA total strain at baseline]). RV systolic and diastolic function was quantified using Doppler interrogation and STE. Hepatic shear wave velocity (c) and tissue elasticity (E) were measured using two-dimensional shear wave elastography. Results At rest, patients had significantly lower RA positive, negative and total strain, aSRs and aSRed than control subjects (all P<0.02). Shear wave velocity and hepatic E value were significantly higher in patients than controls (both P<0.02). Compared with controls, patients had significantly lower RA positive, negative and total strain, aSRs, aSRed, and aSRac at exercise (all P<0.05). No significant difference in hepatic shear wave velocity and tissue elasticity were found between patients and control subjects at exercise (all P>0.05). Both baseline liver stiffness indices correlated negatively with RAFR, RA positive and total strain and aSRed at exercise (p<0.05 for all). RV function parameters, including baseline trans-tricuspid early and late diastolic inflow velocity (E, A), systolic, early and late diastolic tricuspid annular velocity (s, e, a), isovolumetric acceleration (IVA), RV systolic and diastolic reserve correlated significantly with RA positive and total strain at exercise (P<0.05 for all). Conclusions In young adults with repaired TOF, right atrial function reserve is impaired, and is associated with increased liver stiffness and RV dysfunction.RA mechanics from rest to exerciseStress RA mechanics and liver stiffness

Impaired right ventricular strain is associated with worse prognosis in patients with liver cirrhosis

Abstract Introduction Cirrhotic cardiomyopathy is a complication of liver cirrhosis accounting for significant morbidity and associated with reduced patient survival. It is characterized by reduced afterload, increased cardiac output, and diastolic dysfunction. However, there are limited data regarding the prognostic significance of right ventricular (RV) mechanics. Novel echocardiographic techniques such as speckle tracking echocardiography can detect subclinical myocardial dysfunction early in the course of non-ischemic myocardiopathies. Purpose To investigate the prognostic role of RV free wall strain (RVFWS) in patients with liver cirrhosis. Methods We prospectively enrolled 70 patients with liver cirrhosis in stable clinical condition. Patients with coronary artery disease, valvular heart disease, ongoing alcohol consumption or poor acoustic window were excluded from the study. Transthoracic echocardiography was performed and RVFWS was calculated from RV focused 4-chamber views using a dedicated software. Since RVFWS was as expected negative in all patients, absolute values were used for all calculations. Clinical and laboratory examination was also performed in all patients and the Model for End-Stage Liver Disease (MELD) score a widely used tool for assessing liver disease severity was calculated. All-cause mortality at 24 months was the primary endpoint and was available in all patients. Results Mean RVFWS in the cohort was 27.4±6.3% and using a lower normal limit of 20%, reduced RVFWS was detected in six patients. According to the Spearman coefficient analysis, RVFWS was correlated with MELD (rho=0.274, p=0.023) indicating increased values in patients with more advanced liver disease. According to the univariate Cox-regression proportion hazard models RVFWS as a continuous variable was not significantly correlated with worse two year survival (HR: 1.01 (0.95-1.08, p=0.658). Interestingly, among conventional echocardiographic parameters basal RV diameter (p=0.004) and right atrial end-systolic area (p=0.008) were associated with increased risk for the primary endpoint. The association of the primary endpoint with other parameters of RV systolic function was also not statistically significant. The Multivatiate Cox Regression survival analysis, which incorporated age, sex, MELD, hemoglobin, systolic blood pressure and cardiac output, showed that among echocardiographic parameters for the evaluation of the RV, only RVFWS showed a tendency to be associated with worse survival (p=0.062). When patients were stratified into tertiles according to RVFWS values, those in the first tertile (with lower absolute RVFWS values) had significantly increased hazard for the primary endpoint (HR: 5.82, 2.18-15.8, P<0.001) (figure 1). Conclusions RVFWS values are within normal limits in most patients with liver cirrhosis. When adjusted for the severity of the liver disease, reduced RVFWS values are associated with worse prognosis in cirrhotics.

Right ventricular myocardial work in heart failure with preserved ejection fraction: insights from invasive cardiopulmonary exercise testing

Abstract Backgrounds Symptoms of heart failure with preserved ejection fraction (HFpEF) is closely related to elevated pulmonary capillary wedge pressure (PCWP) during exercise. The understanding of right ventricle myocardial work, assessing of right ventricular (RV) function utilizing RV pressure–strain loops, in HFpEF is lacking. Methods The study population underwent invasive cardiopulmonary exercise tests, measuring pressures at rest and during exercise to identify HFpEF. Echocardiography assessed LV and RV parameters. Right ventricular myocardial work was calculated using strain-rate and pressure curves, matching them with ECG data. RV global constructive work (RVGCW), RV global work index (RVGWI), RV global wasted work (RVGWW), and RV global work efficiency (RVGWE) were analysed and compared with invasively measured PCWP at resting and peak exercise. Results Between November 2017 and July 2023, 41 patients with adequate data were enrolled, and 21 were diagnosed with HFpEF. There were no significant differences in various echocardiographic parameters between HFpEF and non-HFpEF groups, except higher post-exercise PCWP and mean pulmonary artery pressure. HFpEF patients had higher RVGWW and lower RVGWE. RVGWW and RVGWE had higher predictive ability for HFpEF diagnosis compared to other echocardiographic parameters. While RVGCW (r = 0.0.504, P = 0.001 and r = 0.430, P = 0.006, respectively) and RVGWW correlated (r = 0.408, P = 0.008 and r = 0.621, P <0.001, respectively) with post-exercise ∆PCWP and exercise PCWP, only RVGWW (β=1.981, P=0.044 and β=4.323, p<0.001) being independently associated with both after adjustment for confounding factors. Conclusions RVGWW is a novel parameter that provides an integrative analysis of RV systolic function and correlates more closely with post-exercise ∆PCWP than other standard echocardiographic parameters in HFpEF.

CILP1 and NTproBNP in pulmonary hypertension and right ventricular pressure overload: a translational experimental study

Abstract Introduction Cartilage intermediate layer protein 1 (CILP1) has emerged as a novel marker of right ventricular (RV) dysfunction in pulmonary hypertension (PH), although there is still little evidence on its role in different scenarios of RV pressure overload. The aim of our study was to analyze CILP1 as a biomarker of RV remodeling and PH severity, and compare it with N-terminal pro-brain natriuretic peptide (NTproBNP), in different experimental models of RV pressure overload. Methods Three different experimental models of RV pressure overload compared to a sham procedure were evaluated in 24 Yucatan pigs: chronic postcapillary PH by pulmonary vein banding (M1, n=6); chronic PH by aorto-pulmonary shunting (M2, n=6); RV pressure overload by PA banding (thus without PH) (M3, n=6); and sham procedure (M0, n=6). Animals were evaluated at 8 months after surgery by right heart catheterization, cardiac magnetic resonance (CMR), and blood/histological sampling. Levels of CILP1 and NTproBNP at the RV myocardium and blood were determined with dedicated ELISA and compared among groups by Wilcoxon test with Bonferroni correction. Associations between biomarkers and RV performance indices and pulmonary arterial pressure (PAP) were assessed with Spearman correlation test. Results M1 animals developed chronic postcapillary PH with normal left ventricular (LV) performance and RV maladaptive hypertrophy (RV fibrosis and systolic dysfunction). M2 animals developed chronic precapillary PH associated with LV dilatation and RV maladaptive hypertrophy. On contrast, M3-animals developed severe RV pressure overload (without PH) and hypertrophy but maintained normal RV systolic function. CILP1 and NTproBNP levels were moderately correlated (R=0.56, p=0.002). CILP1 levels in RV myocardium and plasma were significantly higher in M1, whereas NTproBNP plasma levels were significantly higher in M2 (Figure 1). CILP1 in plasma and RV myocardium significantly correlated with PAP, while myocardial CILP1 levels also correlated with RV extracellular volume (RV-ECV) by CMR (Figure 2). NTproBNP myocardial levels correlated with RV ejection fraction and RV-ECV and plasmatic levels correlated with PAP (Figure 2). Conclusions CILP1 levels were increased in the presence of PH and isolated RV dysfunction, whereas NTproBNP levels were increased in the model of PH, RV dysfunction and LV remodeling. Myocardial levels of both peptides correlated with diffuse fibrosis, estimated by CMR, whereas plasmatic levels of both biomarkers correlated with PAP. This suggests that CILP1 may be a more specific marker of RV dysfunction in PH, being less dependent of LV parameters.CILP1 and NTproBNP levels among modelsCorrelation with PAP & RV remodeling

Cardiac structure and function in people with cystic fibrosis

Abstract Background Cystic fibrosis (CF) is an autosomal recessive disease affecting multiple organs, however the extent of cardiac involvement in CF is yet to be determined. The remarkable therapeutic advancements with new highly effective CF transmembrane conductance regulator (CFTR) modulator treatment and subsequent increase in life expectancy substantiates further research. Purpose We aimed to explore the prevalence of abnormalities and potential subclinical alterations in cardiac structure and function in adults with CF compared to matched controls and investigate potential cardiovascular risk factors in people with CF (pwCF). Methods In this cross-sectional study, 104 adult pwCF in Denmark underwent clinical and echocardiographic examination. All participants were matched 1:1 with controls from the general population on age and sex. Uni- and multivariable linear regression models with adjustment for heart rate, FEV1, smoking status, hypertension and CF-related diabetes (CFRD) were used to test for differences in echocardiographic parameters between cases and controls. Abnormal cardiac function was defined as left ventricular ejection fraction (LVEF) <50%, left ventricular (LV) global longitudinal strain (GLS) < 16% or presence of diastolic dysfunction. Uni- and multivariable logistic regression models adjusted for age, sex, homozygous genotype, FEV1/FVC, BMI, smoking status, CFRD, pancreatic insufficiency, hypertension, and ischemic heart disease were performed to assess associations between potential risk factors and cardiac dysfunction in CF. Forest plots were constructed to visually represent the findings. Results Of 104 pwCF, 44% were female, mean age was 34 years, 93% received CFTR modulator treatment, and 91% had mutations with only minimal CFTR function (mutation class I-III). The prevalence of abnormal cardiac function in pwCF was 44% versus 22% in controls. Compared to controls, pwCF were found to have smaller LV dimensions, worse LV diastolic function, and more impaired right ventricle (RV) as well as LV systolic function (Table). After multivariable adjustment, LV diastolic function as well as LV and RV systolic function remained impaired in pwCF as compared to controls. Male sex and decreasing FEV1/FVC ratio remained independently associated with abnormal cardiac function in pwCF (male sex: OR 3.94 (1.56; 9.95), p=0.004 and FEV1/FVC ratio: OR 2.05 per 0.1 unit decrease (1.21; 3.52), p=0.008, respectively) (Figure). Conclusion Both left- and right-sided cardiac alterations were found in pwCF. After adjustments for potential risk factors, both RV and LV systolic measures remained altered in pwCF, compared to controls. Male sex and decreasing pulmonary function evaluated by FEV1/FVC-ratio were identified as factors associated with abnormal cardiac function in pwCF.Figure

Prognostic value of exercise right ventricular-pulmonary arterial coupling in primary mitral regurgitation

Abstract Background Exercise-induced pulmonary hypertension (mPAP/CO slope >3mmHg/L/min) was recently associated with worse outcome in >moderate PMR. However, the prognostic value of right ventricle to pulmonary artery coupling (RVPAc) is unknown. Purpose Assess the prognostic value of RVPAc; determine the additional value of exercise over rest RVPAc and compare these findings to the mPAP/CO slope. Methods Cohort study including consecutive pts submitted to CPET-echo with >moderate PMR, no/discordant symptoms, preserved LV function and without >moderate concomitant valvular disease or atrial fibrillation (AF). Thorough assessment of RV systolic function and RVPAc (TAPSE/sPAP ratio) was obtained by echocardiography using a dedicated RV window. mPAP and CO were obtained by Doppler echocardiography. Primary outcome was the composite of all-cause mortality, cardiovascular hospitalization (CVH), new-onset AF and valvular intervention; secondary outcome was the composite of CVH and new-onset AF. Results A total of 128 consecutive pts (64±11 years, 61% men) underwent CPET-echo. Event-free survival rate was 55% and 46% at 1 and 2 years. Pts that reached the primary combined endpoint were significantly older, had larger left atrium indexed volumes (LAVi), higher proportion of grade 4 MR, lower absolute and normalized peak VO2, and a significantly higher mPAP/CO slope (2,1±0,8 vs.3,7±2,6). They had a significantly lower rest and exercise TAPSE/sPAP, RV global and free wall longitudinal strain, rest and exercise TAPSE and exercise RV free wall S’. Rest and low exercise TAPSE/sPAP scored the highest accuracy in predicting the primary combined endpoint among variables statistically significant in the univariate analysis and therefore were used in the multivariate model. Sequentially adding rest and low exercise TAPSE/sPAP significantly improved the baseline predictive model (age, LAVi and MR grade). Low exercise TAPSE/sPAP and LAVi remained as significant independent variables in the multivariate model. They also correlated with new-onset AF and CVH; with rest and low exercise TAPSE/sPAP constituting significant steps (Fig 2). Replacing low exercise TAPSE/sPAP for mPAP/CO slope in the proposed model only slightly improved its accuracy in predicting the primary and secondary composite outcomes. Adding predicted peak VO2 (≥80% vs <80%) did not significantly improve the accuracy of any of the multivariate models. Low exercise TAPSE/sPAP and mPAP/CO slope both correlated well with peak VO2 and VE/VCO2 slope. Conclusion Decreased rest or exercise TAPSE/sPAP are single point measures of RVPAc, associated with adverse outcome in pts with >moderate PMR and no/discordant symptoms. Low exercise TAPSE/sPAP has independent additional value over rest TAPSE/sPAP in predicting adverse events, with a similar accuracy as mPAP/CO slope. Low exercise TAPSE/sPAP is a potential alternative to mPAP/CO slope in this population and it may be simpler to adopt in clinical practice.Central Illustration

The increased longitudinal basal-to-apical strain ratio in the right ventricular free wall is associated with neonatal pulmonary hypertension.

As a relatively standardized parameter, Ratio bas/api of RVFW was significantly higher in the case of neonatal PH with normal cardiac function and could be regarded as a new indicator for PH. •It has been challenging work to diagnose neonatal pulmonary hypertension (PH), and conventional echocardiography has been widely applied, though it is not sufficient enough. •RV longitudinal strain (RVLS) is primarily used to assess RV systolic function, and its role in diagnosing PH was rarely considered. •The basal-to-apical strain ratio (Ratio bas/api) of RV free wall increased significantly in all infants with PH regardless of causes. •As a relatively standardized parameter, Ratio bas/api could be regarded as a new indicator for diagnosing PH, apart from conventional echocardiographic parameters.

The Relationship Between Right Ventricular Longitudinal Strain and Adverse Outcome in Hypertensive Patients: 10-year Follow-up.

Previous studies showed the importance of right ventricular (RV) remodeling in patients with arterial hypertension and RV longitudinal strain was recognized as very sensitive parameter for detection of subtle cardiac impairment. However, its clinical importance in arterial hypertension has not been established so far. The present study aimed to evaluate the association between RV longitudinal strain (global and free-wall) on adverse outcomes measured by MACE in the large group of hypertensive patients who were followed for mean period of 10 years. This retrospective study finally included 544 hypertensive patients who underwent full echocardiographic examination including 2D speckle tracking imaging. between January 2010 and December 2014. MACE was considered as the primary outcome and it was defined by all-cause mortality, cardiovascular mortality, myocardial infarction, coronary artery by-pass, coronary stent implantation, stroke, development of heart failure, and occurrence of atrial fibrillation during follow-up. Patients who experienced MACE were older than those who did not. There was no difference in demographic and clinical parameters between MACE and non-MACE patients. There was no difference in RV diameter, but MACE patients had higher RV wall thickness. RV systolic function parameters were similar between the two groups. RV global and free-wall longitudinal strain were significantly lower in MACE patients (-22.3 ± 3.6 vs. -24.7 ± 3.9%, p < 0.001 and - 25.8 ± 4.2 vs. -28.1 ± 4.5%, p < 0.001; respectively). Reduced RV GLS [OR 1.10; 95%: 1.02-1.20] and reduced RV free-wall longitudinal strain [OR 1,21; 95%CI: 1.05-1.39] were independently of clinical and echocardiographic parameters related with adverse outcome measured by MACE. RV GLS and RV free-wall longitudinal strain were independently related with adverse outcomes during 10-year follow-up in initially uncomplicated hypertensive patients.

Associations Between Echocardiographic Right Heart Measurements With Short-Term Prognosis in Heart Failure: A Prospective Study.

Echocardiographic right ventricular (RV) dysfunction is a strong risk determinant for prognosis in patients with heart failure (HF). Although parameters of RV systolic function are widely used to define RV dysfunction, there is scarce data to suggest these parameters are best suited to predict HF-related outcomes. We aimed to understand which morphologic or functional parameters are most closely associated with short-term mortality and HF-related hospitalization in patients with HF. A total of 191 patients from eight study centers were included to this study. A detailed echocardiographic examination was done at enrollment, and patients were followed up for 6 months via direct interviews or phone calls. All right-sided echocardiographic parameters other than tricuspid annular plane systolic excursion were associated with outcomes. In a proportional hazards model that included right-heart parameters, RV longitudinal diameter (HR: 1.07, 95%CI: 1.04-1.10, p<0.001), wall thickness (HR: 1.3, 95%CI: 1.13-1.50, p<0.001), and tricuspid annular systolic velocity (HR: 0.90, 95%CI: 0.82-0.96, p=0.02) were found as the independent predictors. However, only RV longitudinal dimension (HR: 1.04, 95%CI: 1.01-1.08, p=0.01) and RV wall thickness (HR: 1.32, 95%CI: 1.10-1.60, p=0.004) were associated with short-term outcomes after adjusting for other clinical and left-sided echocardiographic variables. On a Bayesian logistic regression model that included right-sided echocardiography variables, there was strong evidence for including either RV longitudinal diameter (BF10: 190.4) or wall thickness (BF10: 30.7) to the final model. Parameters of RV morphology were better predictors of short-term outcomes in HF patients.

Características de la insuficiencia tricúspide grave inducida por dispositivos de estimulación intracardiacos

Introduction and aimsTricuspid regurgitation (TR) induced by the implantation of cardiac implantable electronic devices (CIED) is an increasingly common cause of severe TR. Our aim was to describe the echocardiographic phenotypic characteristics of CIED-induced severe TR. MethodsRetrospective cohort study that included patients with severe TR related to CIED diagnosed in the cardiac imaging unit of a Spanish tertiary hospital. Results37 patients with severe TR induced by lead/electrode interference formed our study group. TR was predominantly severe (68%), followed by massive (21%) and torrential (11%). The leaflet most affected by the interference was the septal. 58% of the sample presented severe dilatation of the right atrium (RA) (mean RA area 28cm2). Mean tricuspid annulus measurement was 42mm. The usual parameters for quantifying RV systolic function were on average within the normal range (TAPSE mean 19mm, S’ wave 10mm, FAC 41%), while global RV strain (RVGLS -15%) and free wall strain (RVFWLS -19%) were found reduced. An incipient degree of ventricular/pulmonary arterial uncoupling was evident (mean TAPSE/PSAP 0.34, SGLVD/PSAP 0.27%/mmHg). ConclusionsOur patients with CIED-induced severe TR are characterized by a heterogeneous phenotype with a high prevalence of severe RA and tricuspid annulus dilatation. RVGLS, RVFWLS, and arterial ventricular coupling were the most sensitive parameters for early assessment of RV systolic dysfunction.

Assessment of right ventricular sequelae by speckle tracking echocardiography in recovered COVID-19 patients

Background TTE is the main modality used to assess RV function, but conventional TTE parameters have limited diagnostic value because they may fail to detect early abnormalities in RV systolic function. Due to its ability to detect subclinical impairment of cardiac function, 2D STE has been widely used to investigate RV function. In this study, we aimed to investigate whether there are sequelae of RV function in recovered COVID-19 patients with pulmonary involvement. Methods This is a prospective observational cohort study of 57 healthy volunteers and 54 patients. Participants had no history of chronic illness and no evidence of respiratory or cardiac symptoms. The patients had been hospitalised with COVID-19 with pulmonary involvement but did not require intensive care unit follow-up or non-invasive mechanical ventilation support. TTE was performed. Demographic and clinical characteristics and laboratory test results were collected. Results LVEF, TAPSE, St and FAC were significantly lower in the patient group. LV-LS 3-chamber, LV-GLS, RV-FWS, RV-GLS were significantly lower in the patient group. Conclusions RV-LS and LV-GLS were shown to decrease in the patient group. Although no obvious pathological values were observed in RV parameters on conventional echocardiography, TAPSE, St and FAC values were lower in the patient group.

The effects of percutaneous branch pulmonary artery interventions in biventricular congenital heart disease: study protocol for a randomized controlled Dutch multicenter interventional trial

BackgroundBranch pulmonary artery (PA) stenosis is one of the most common indications for percutaneous interventions in patients with transposition of the great arteries (TGA), tetralogy of Fallot (ToF), and truncus arteriosus (TA). However, the effects of percutaneous branch PA interventions on exercise capacity remains largely unknown. In addition, there is no consensus about the optimal timing of the intervention for asymptomatic patients according to international guidelines. This trial aims to identify the effects of percutaneous interventions for branch PA stenosis on exercise capacity in patients with TGA, ToF, and TA. In addition, it aims to assess the effects on RV function and to define early markers for RV adaptation and RV dysfunction to improve timing of these interventions.MethodsThis is a randomized multicenter interventional trial. TGA, ToF, and TA patients ≥ 8 years with a class IIa indication for percutaneous branch PA intervention according to international guidelines are eligible to participate. Patients will be randomized into the intervention group or the control group (conservative management for 6 months). All patients will undergo transthoracic echocardiography, cardiac magnetic resonance (CMR) imaging, and cardiopulmonary exercise testing at baseline, 6 months, and 2–4 years follow-up. Quality of life (QoL) questionnaires will be obtained at baseline, 2 weeks post intervention or a similar range for the control group, and 6 months follow-up. The primary outcome is exercise capacity expressed as maximum oxygen uptake (peak VO2 as percentage of predicted). A total of 56 patients (intervention group n = 28, control group n = 28) is required to demonstrate a 14% increase in maximum oxygen uptake (peak VO2 as percentage of predicted) in the interventional group compared to the control group (power 80%, overall type 1 error controlled at 5%). Secondary outcomes include various parameters for RV systolic function, RV functionality, RV remodeling, procedural success, complications, lung perfusion, and QoL.DiscussionThis trial will investigate the effects of percutaneous branch PA interventions on exercise capacity in patients with TGA, ToF, and TA and will identify early markers for RV adaptation and RV dysfunction to improve timing of the interventions.Trial registrationClinicalTrials.gov NCT05809310. Registered on March 15, 2023.

Serial Changes in Ventricular Strain in Symptomatic Obstructive Hypertrophic Cardiomyopathy Treated With Mavacamten: Insights From the VALOR-HCM Trial.

In severely symptomatic patients with obstructive hypertrophic cardiomyopathy, VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) demonstrated that mavacamten reduces the need for septal reduction therapy with sustained improvement in left ventricular (LV) outflow tract gradients and symptoms. Global longitudinal strain (GLS), a measure of regional myocardial function, is a more sensitive marker of systolic function. In VALOR-HCM, we assessed serial changes in LV and right ventricular (RV) strain. VALOR-HCM included 112 patients with symptomatic obstructive hypertrophic cardiomyopathy (mean, 60 years; 51% male; LV ejection fraction, 68%). Patients assigned to mavacamten at baseline continued the drug for 56 weeks (n=56) and those assigned to placebo (n=52) transitioned to mavacamten from weeks 16 to 56 (40-week exposure). LV-GLS and RV-GLS assessment was performed using a vendor-neutral software. Non-foreshortened apical (4-, 3-, and 2-chamber) views were used to obtain peak LV-GLS. RV focused 4-chamber view was used to calculate RV 4-chamber and free wall strain. A more negative strain value is favorable. At baseline, the mean LV-GLS, RV 4-chamber, and free wall strain values were -14.7%, -22.2%, and -16.8%, respectively (all worse than reported normal means). In the total study sample, LV-GLS significantly improved from baseline to week 56 (P=0.02). Twelve patients had transient reduction in LV ejection fraction (<50%) requiring temporary drug interruption (including 3 permanent discontinuations). The LV-GLS in this subgroup was worse at baseline versus total study population (-11.4%), with no significant worsening from baseline through week 56 (P=0.64). Both free wall and 4-chamber RV-GLS remained unchanged from baseline to week 56 (P=0.62 and P=0.56, respectively). In VALOR-HCM, treatment with mavacamten improved LV-GLS from baseline through week 56 (with no significant worsening of LV-GLS in patients with a reduction in LV ejection fraction ≤50%), suggesting a favorable long-term impact on regional LV systolic function. Additionally, there was no detrimental impact on RV systolic function. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04349072.