Right Ventricular Load Research Articles

Dapagliflozin and Right Ventricular–Pulmonary Vascular Interaction in Heart Failure With Preserved Ejection Fraction

Increases in pulmonary capillary wedge pressure (PCWP) during exercise reduce pulmonary artery (PA) compliance, increase pulsatile right ventricular (RV) afterload, and impair RV-PA coupling in patients with heart failure with preserved ejection fraction (HFpEF). The effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on pulmonary vascular properties and RV-PA coupling are unknown. To test the effect of dapagliflozin on right ventricular performance and pulmonary vascular load during exertion in HFpEF. Evaluation of the Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction (CAMEO-DAPA) randomized clinical trial demonstrated improvement in PCWP at rest and exercise over 24 weeks with dapagliflozin compared with placebo with participants recruited between February 2021 and May 2022. This secondary analysis evaluates the effects of dapagliflozin on pulsatile pulmonary vascular load and RV-PA coupling using simultaneous echocardiography and high-fidelity invasive hemodynamic testing with exercise. This was a single-center study including patients with hemodynamically confirmed HFpEF with exercise PCWP of 25 mm Hg or greater. Dapagliflozin or placebo for 24 weeks. Pulsatile pulmonary vascular load (PA compliance and elastance) and right ventricular performance (PA pulsatility index, RV systolic velocity [s']/PA mean) during rest and exercise. Among 37 randomized participants (mean [SD] age, 67.4 [8.5] years; 25 female [65%]; mean [SD] body mass index, 34.9 [6.7]; calculated as weight in kilograms divided by height in meters squared), there was no effect of dapagliflozin on PA loading or RV-PA interaction at rest. However, with exercise, dapagliflozin improved PA compliance (placebo-corrected mean difference, 0.57 mL/mm Hg; 95% CI, 0.11-1.03 mL/mm Hg; P = .02) and decreased PA elastance (stiffness; -0.17 mm Hg/mL; 95% CI, -0.28 to -0.07 mm Hg/mL; P = .001). RV function during exercise improved, with increase in PA pulsatility index (0.33; 95% CI, 0.08-0.59; P = .01) and increase in exercise RV s' indexed to PA pressure (0.09 cm·s-1/mm Hg; 95% CI, 0.02-0.16 cm·s-1/mm Hg; P = .01). Improvements in pulsatile RV load and RV-PA coupling were correlated with reduction in right atrial (RA) pressure (PA elastance Pearson r = 0.55; P =.008; RV s'/PA elastance Pearson r = -0.60; P =.002) and PCWP (PA elastance Pearson r = 0.58; P <.001; RV s'/PA elastance Pearson r = -0.47; P = .02). Dapagliflozin increased resistance-compliance time (dapagliflozin, median [IQR] change, 0.06 [0.03-0.15] seconds; placebo, median [IQR] change, 0.01 [-0.02 to 0.05] seconds; P =.046), resulting in higher PA compliance for any exercise pulmonary vascular resistance. Results of this randomized clinical trial reveal that treatment with dapagliflozin for 24 weeks reduced pulsatile pulmonary vascular load and enhanced dynamic RV-PA interaction during exercise in patients with HFpEF, findings that are related to the magnitude of PCWP reduction. Benefits on dynamic right ventricular-pulmonary vascular coupling may partially explain the benefits of SGLT2 inhibitors in HFpEF. ClinicalTrials.gov Identifier: NCT04730947.

Perinatal Cardiac Functional Adaptation in Hypoplastic Left Heart Syndrome: A Longitudinal Analysis

The perinatal transition is characterized by acute changes in cardiac loading. Compared with normal newborn combined cardiac output (CCO), single right ventricular (RV) output of neonates with hypoplastic left heart syndrome (HLHS) is markedly greater. The aim of this study was to examine the mechanisms of cardiac adaptation that facilitate this perinatal transition from late fetal to early neonatal life in HLHS. Prospectively recruited pregnancies complicated by fetal HLHS (n=35) and healthy control subjects (Ctrl; n=17) underwent serial echocardiography in late gestation (38±1weeks) and 6, 24, and 48hours after birth. Cardiac function was assessed using conventional, Doppler tissue, and speckle-tracking echocardiography. Term fetuses with HLHS had RV output comparable with Ctrl CCO via higher stroke volume. Compared with both left ventricular and RV indices of Ctrl, they exhibited globular and dilated right ventricles with reduced relative wall thickness (0.40±0.08 vs 0.49±0.10, P<.01), increased Tei index' (HLHS vs Ctrl left ventricle/Ctrl right ventricle: sphericity index, 0.9±0.25 vs 0.5±0.10/0.6±0.11; RV area index, 28±6 vs 15±3/17±5cm2/m2; Tei index', 0.65±0.11 vs 0.43±0.07/0.45±0.09; P<.0001 for all). Neonates with HLHS generated elevated RV cardiac output compared with Ctrl CCO via higher heart rate and stroke volume, with further RV dilatation, increased longitudinal systolic strain at 48hours (-17±4% vs -14±3%/14±5%) with reduced circumferential and rotational myocardial deformation and altered diastolic function. Neonates with HLHS also demonstrated right atrial enlargement with increased longitudinal strain: 6hours (33±12% vs 26±6%), 24hours (37±15% vs 26± 13%), and 48hours (38±11% vs 24±13%) (P<.0001). Term fetuses with HLHS exhibit altered RV geometry and RV systolic and diastolic functional parameters. After birth, further alterations in these cardiac parameters likely reflect adaptation to acutely altered RV loading from increasing cardiac output and pulmonary artery flow demands.

A computational study of right ventricular mechanics in a rat model of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) presents a significant challenge to right ventricular (RV) function due to progressive pressure overload, necessitating adaptive remodeling in the form of increased wall thickness, enhanced myocardial contractility and stiffness to maintain cardiac performance. However, the impact of these remodeling mechanisms on RV mechanics in not clearly understood. In addition, there is a lack of quantitative understanding of how each mechanism individually influences RV mechanics. Utilizing experimental data from a rat model of PAH at three distinct time points, we developed biventricular finite element models to investigate how RV stress and strain evolved with PAH progression. The finite element models were fitted to hemodynamic and morphological data to represent different disease stages and used to analyze the impact of RV remodeling as well as the altered RV pressure. Furthermore, we performed a number of theoretical simulation studies with different combinations of morphological and physiological remodeling, to assess and quantify their individual impact on overall RV load and function. Our findings revealed a substantial 4-fold increase in RV stiffness and a transient 2-fold rise in contractility, which returned to baseline by week 12. These changes in RV material properties in addition to the 2-fold increase in wall thickness significantly mitigated the increase in wall stress and strain caused by the progressive increase in RV afterload. Despite the PAH-induced cases showing increased wall stress and strain at end-diastole and end-systole compared to the control, our simulations suggest that without the observed remodeling mechanisms, the increase in stress and strain would have been much more pronounced. Our model analysis also indicated that while changes in the RV's material properties-particularly increased RV stiffness - have a notable effect on its mechanics, the primary compensatory factor limiting the stress and strain increase in the early stages of PAH was the significant increase in wall thickness. These findings underscore the importance of RV remodeling in managing the mechanical burden on the right ventricle due to pressure overload.

First experience with real-time magnetic resonance imaging-based investigation of respiratory influence on cardiac function in pediatric congenital heart disease patients with chronic right ventricular volume overload

BackgroundCongenital heart disease (CHD) is often associated with chronic right ventricular (RV) volume overload. Real-time magnetic resonance imaging (MRI) enables the analysis of cardiac function during free breathing.ObjectiveTo evaluate the influence of respiration in pediatric patients with CHD and chronic RV volume overload.Methods and materialsRV volume overload patients (n=6) and controls (n=6) were recruited for cardiac real-time MRI at 1.5 tesla during free breathing. Breathing curves from regions of interest reflecting the position of the diaphragm served for binning images in four different tidal volume classes, each in inspiration and expiration. Tidal volumes were estimated from these curves by data previously obtained by magnetic resonance-compatible spirometry. Ventricular volumes indexed to body surface area and Frank-Starling relationships referenced to the typical tidal volume indexed to body height (TTVi) were compared.ResultsIndexed RV end-diastolic volume (RV-EDVi) and indexed RV stroke volume (RV-SVi) increased during inspiration (RV-EDVi/TTVi: RV load: + 16 ± 4%; controls: + 22 ± 13%; RV-SVi/TTVi: RV load: + 21 ± 6%; controls: + 35 ± 17%; non-significant for comparison). The increase in RV ejection fraction during inspiration was significantly lower in RV load patients (RV load: + 1.1 ± 2.2%; controls: + 6.1 ± 1.5%; P=0.01). The Frank-Starling relationship of the RV provided a significantly reduced slope estimate in RV load patients (inspiration: RV load: 0.75 ± 0.11; controls: 0.92 ± 0.02; P=0.02).ConclusionIn pediatric patients with CHD and chronic RV volume overload, cardiac real-time MRI during free breathing in combination with respiratory-based binning indicates an impaired Frank-Starling relationship of the RV.Graphical

Comparison of novel ventricular pacing strategies using an electro-mechanical simulation platform.

Focus of pacemaker therapy is shifting from right ventricular (RV) apex pacing (RVAP) and biventricular pacing (BiVP) to conduction system pacing. Direct comparison between the different pacing modalities and their consequences to cardiac pump function is difficult, due to the practical implications and confounding variables. Computational modelling and simulation provide the opportunity to compare electrical, mechanical, and haemodynamic consequences in the same virtual heart. Using the same single cardiac geometry, electrical activation maps following the different pacing strategies were calculated using an Eikonal model on a three-dimensional geometry, which were then used as input for a lumped mechanical and haemodynamic model (CircAdapt). We then compared simulated strain, regional myocardial work, and haemodynamic function for each pacing strategy. Selective His-bundle pacing (HBP) best replicated physiological electrical activation and led to the most homogeneous mechanical behaviour. Selective left bundle branch (LBB) pacing led to good left ventricular (LV) function but significantly increased RV load. RV activation times were reduced in non-selective LBB pacing (nsLBBP), reducing RV load but increasing heterogeneity in LV contraction. LV septal pacing led to a slower LV and more heterogeneous LV activation than nsLBBP, while RV activation was similar. BiVP led to a synchronous LV-RV, but resulted in a heterogeneous contraction. RVAP led to the slowest and most heterogeneous contraction. Haemodynamic differences were small compared to differences in local wall behaviour. Using a computational modelling framework, we investigated the mechanical and haemodynamic outcome of the prevailing pacing strategies in hearts with normal electrical and mechanical function. For this class of patients, nsLBBP was the best compromise between LV and RV function if HBP is not possible.

Association of Right Ventricular Myocardial Blood Flow With Pulmonary Pressures and Outcome in Cardiac Amyloidosis

BackgroundCardiac amyloidosis (CA) is a restrictive and infiltrative cardiomyopathy, characterized by increased biventricular filling pressures and low output. Symptoms are predominantly of right heart origin. The role of right ventricular (RV) myocardial blood flow (MBF) in CA has not been studied. ObjectivesThis study aimed to first associate RV MBF measured by using positron emission tomography (PET) with reference standards of RV pressures and then to explore its prognostic value in CA. MethodsCardiac PET was performed at rest in 52 patients with CA and 9 healthy control subjects. MBF was quantified from the right and left ventricles by using 11C-acetate, 15O-water, or both (n = 25). RV pressure was measured invasively or by echocardiography. Associations between biventricular MBF toward symptoms, RV function, and outcome (death or acute heart failure) were studied in patients with CA. ResultsMBF of the right ventricle (MBFRV) and the ratio of MBFRV and MBF of the left ventricle (MBFRV/LV) for the 2 tracers were significantly correlated (r > 0.92). MBFRV was directly correlated with RV systolic pressures with both tracers (P ≤ 0.005). MBFLV was inversely correlated with wall thickness (P < 0.0001). MBFRV/LV was significantly associated with N-terminal pro–B-type natriuretic peptide levels, NYHA functional class, RV pressures, and RV systolic function (all; P < 0.001). Twenty-six cardiac events (25 deaths) occurred during follow-up (median 44 months). MBFRV/LV higher than 56% was associated with a diagnosis of pulmonary hypertension (AUC: 0.96 [95% CI: 0.91-1.00]; P < 0.0001); and predicted outcome with HR: 9.0 (95% CI: 4.2-14.5), P < 0.0001). ConclusionsMeasurements of MBFRV using PET are feasible, as confirmed with 2 different tracers. Imbalance between RV and LV myocardial perfusion is associated with increased RV load and adverse events in cardiac amyloidosis.

Left ventricular hypertrophy, diastolic dysfunction and right ventricular load predict outcome in moderate aortic stenosis.

Predictors of progression of moderate aortic valve stenosis (AS) are incompletely understood. The objective of this study was to evaluate the prognostic value of left ventricular hypertrophy (LVH), diastolic dysfunction, and right ventricular (RV) load in moderate AS. Moderate AS was defined by aortic valve area (AVA), peak transvalvular velocity (Vmax) or mean pressure gradient (PGmean). A total of 131 Patients were divided into two groups according to the number of pathophysiological changes (LVH, diastolic dysfunction with increased LV filling pressures and/or RV load): <2 (group 1); ≥2 (group 2). The primary outcome was survival without aortic valve replacement (AVR). After follow-up of 30 months, the reduction of AVA (-0.06 ± 0.16 vs. -0.24 ± 0.19 cm2, P < 0.001), the increase of PGmean (2.89 ± 6.35 vs 6.29 ± 7.13 mmHg, P < 0.001) and the decrease of the global longitudinal strain (0.8 ± 2.56 vs. 1.57 ± 3.42%, P < 0.001) from baseline to follow-up were significantly more pronounced in group 2. Survival without AVR was 82% (group 1) and 56% (group 2) [HR 3.94 (1.74-8.94), P < 0.001]. Survival without AVR or progression of AS was 77% (group 1) and 46% (group 2) [HR 3.80 (1.84-7.86), P < 0.001]. The presence of ≥2 pathophysiological changes predicted outcome whereas age, comorbidities, LDL-cholesterol did not. The presence of ≥2 pathophysiological changes is a strong predictor of outcome in moderate AS and may be useful for risk stratification, particularly for scheduling follow-up time intervals and deciding the timing of AVR.

Effect of ASD closure on right ventricular function using 3D echocardiography

Atrial septal defect (ASD) is the most common adult congenital heart disease. The left-to-right shunt causes a right ventricular (RV) volume overload. Only little is known about RV remodeling after ASD closure. We aimed to assess RV function using 2D, 3D echocardiography and 3D RV strain before and 1 month after ASD closure. We prospectively included in this monocentric study 9 patients with secundum ASD who underwent percutaneous closure between September 2019 and January 2020. 2D and 3D Echocardiography were performed in all patients before and 1-month after closure. While we initially planned to collect echocardiographic data 3- and 6-months after ASD closure, the COVID-19 pandemic made this impossible. All patients gave their informed consent to the study. Clinical and ultrasound data were collected and anonymized. 3D RV echocardiographic sequences were analyzed by semi-automatic software (Tomtec 4D RV Function, Unterschleissheim, Germany) and output meshes were post-processed to extract regional deformation. Patients’ mean age was 31.0 ± 12.3 years, 44.4% were female. Mean ASD diameter was 16.6 ± 7.4 mm. RV end diastolic diameter and right atrial (RA) area were significantly larger than normal values and decreased significantly after ASD closure (45.8 ± 4.9 vs. 37.8 ± 5.7 mm; P = 0.0009 and 21.4 ± 4.2 vs. 16.3 ± 2.7 cm2; P = 0.01, respectively). 3D RV volumes were significantly lower after ASD closure; respectively 156.3 ± 61.7 vs. 82.9 ± 17.40 mL, P = 0.02 for end diastolic volume and 59.4 ± 19.3 vs. 32.6 ± 9.2 mL, P = 0.01 for end systolic volume. RV function decreases after ASD closure as illustrated by TAPSE (23.3 ± 6.0 vs. 29.1 ± 4.2 mm, P = 0.03) as well as 3D RV strain with a significantly decreased in area strain, longitudinal strain as well as circumferential strain (respectively P = 0.006, P = 0.009 and P = 0.02) (Fig. 1). After percutaneous ASD closure, we demonstrate a decrease in RV function in all strain components using 3D strain. This decrease in RV strain probably illustrates the decrease in RV parietal stretch related to the normalization of RV loading conditions. 3D strain can be useful to assess the RV function evolution in response to different loading conditions.

When right ventricular pressure meets volume: The impact of arrival time of reflected waves on right ventricle load in pulmonary arterial hypertension.

Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. A larger volume at a given pressure generates more wall tension. Return of reflected waves early after the onset of contraction, when RV volume is larger, may augment RV load. We aimed to elucidate: (1) the distribution of arrival times of peak reflected waves in treatment‐naïve PAH patients; (2) the relationship between time of arrival of reflected waves and RV morphology; and (3) the effect of PAH treatment on the arrival time of reflected waves. Wave separation analysis was conducted in 68 treatment‐naïve PAH patients. In the treatment‐naïve condition, 54% of patients had mid‐systolic return of reflected waves (defined as 34–66% of systole). Despite similar pulmonary vascular resistance (PVR), patients with mid‐systolic return had more pronounced RV hypertrophy compared to those with late‐systolic or diastolic return (RV mass/body surface area; mid‐systolic return 54.6 ± 12.6 g m–2, late‐systolic return 44.4 ± 10.1 g m–2, diastolic return 42.8 ± 13.1 g m–2). Out of 68 patients, 43 patients were further examined after initial treatment. At follow‐up, the stiffness of the proximal arteries, given as characteristic impedance, decreased from 0.12 to 0.08 mmHg s mL–1. Wave speed was attenuated from 13.3 to 9.1 m s–1, and the return of reflected waves was delayed from 64% to 71% of systole. In conclusion, reflected waves arrive at variable times in PAH. Early return of reflected waves was associated with more RV hypertrophy. PAH treatment not only decreased PVR, but also delayed the timing of reflected waves.Key points Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. Larger volume at a given pressure causes larger RV wall tension.Early return of reflected waves adds RV pressure in early systole, when RV volume is relatively large. Thus, early return of reflected waves may increase RV wall tension. Wave reflection can provide a description of RV load.In PAH, reflected waves arrive back at variable times. In over half of PAH patients, the RV is exposed to mid‐systolic return of reflected waves. Mid‐systolic return of reflected waves is related to RV hypertrophy.PAH treatment acts favourably on the RV not only by reducing resistance, but also by delaying the return of reflected waves.Arrival timing of reflected waves is an important parameter for understanding the relationship between RV load and its function in PAH.

Utility of Real-Time Three-Dimensional Echocardiography for the Assessment of Right Ventricular Morphology and Function in Large Animal Models.

Real-time three-dimensional echocardiography (RT3DE) enables a noninvasive assessment of right ventricular (RV) morphology. However, no study has evaluated the relationship between RV function obtained by RT3DE and RV pressure-volume loops. This hypothesis-driven, experimental study aimed to assess the utility of RT3DE in the evaluation of RV morphology and function. Ten anesthetized beagle dogs sequentially underwent dobutamine infusion, acute infusion of lactated Ringer’s solution, and furosemide administration to alter RV contractility and loading conditions. RV pressure-volume loop-derived hemodynamic measurements and echocardiography, including two-dimensional speckle-tracking echocardiography and RT3DE, were performed in each study protocol. Bland–Altman analysis showed strong agreement in RV volume, ejection fraction, and stroke volume obtained by right heart catheterization and RT3DE. Multiple regression analyses revealed that the peak myocardial velocity of the lateral tricuspid annulus (RV s’) and global RV longitudinal strain rate were significantly associated with end-systolic elastance (adjusted r2 = 0.66, p < 0.001). RV s’, RV free wall longitudinal strain, and RT3DE-derived stroke volume/end-systolic RV volume ratio were associated with RV pressure-volume loops-derived end-systolic/arterial elastance ratio (adjusted r2 = 0.34, p < 0.001). RT3DE could detect the changes in catheterization-derived RV volume with a strong agreement and might be useful in estimating RV-pulmonary arterial coupling.

Transcriptomic Analysis of Right Ventricular Adaptation and Failure in a Novel Ovine Model of Pulmonary Hypertension

<h3>Purpose</h3> Right ventricular failure (RVF) is a large contributor to morbidity and mortality in pulmonary hypertension (PH). Molecular understanding of RVF may facilitate identification of novel drug and device therapy targets. Using our previously published large animal model of PH-RVF, we performed RNA-seq analysis of RV tissues sampled from healthy sheep, PH sheep, and PH sheep that received mechanical circulatory support (MCS). <h3>Methods</h3> We assessed RV gene expression in adult sheep prior to and after completion of a previously described PH model. Three PH sheep subsequently underwent acute MCS for 3-6 hours. Right ventricular (RV) free wall tissues were collected prior to PA banding and at termination of MCS (pre-PH vs post-PH, N=3 each). One subject experienced severe maladaptive RVF and expired prior to MCS. This maladaptive characterization was based on its mixed venous saturation below 30% and several liters of ascites and pleural effusion found at necropsy. The pre-PH and post-PH RV tissue samples were analyzed for gene expression profile with RNAseq and studied with over-representation analysis to elucidate enriched pathways. <h3>Results</h3> RNAseq identified 358 genes with differential expression between pre-PH and post-PH tissue samples (p < 0.01, >2-fold change). Enrichment analysis showed that these genes were related to cardiomyocyte muscularization and proliferation, indicating adaptation to RV loading. The maladaptive RV sample, even when compared to the other PH sheep that received MCS, demonstrated markedly reduced expression of metabolic genes, especially in fatty acid oxidation. <h3>Conclusion</h3> RV load stress coincides with differential expression of genes related to cardiomyocyte muscularization and proliferation. Observations of reduced expression of fatty acid oxidation genes in a maladaptive subject with RVF warrants further investigation. The role of mechanical support on RV gene expression needs to be further studied in longer-term settings.

COVID-19 Induced Right Ventricular Failure and Right Ventricular Assist Device Support

COVID-19, while primarily recognized for its pulmonary and systemic manifestations, afflicts the cardiovascular system through various abnormalities. Notably, right ventricular (RV) involvement leading to dysfunction and failure is a manifestation seen in up to 20% of severe COVID patients. RV severity correlates with overall COVID severity, serving as a prognostic marker. Data review reveals that RV failure was largely underdiagnosed, particularly early on in the pandemic. The therapy approach for RV failure in patients with COVID should focus on supporting overall RV perfusion pressure, maintaining sinus rhythm, optimizing RV loading conditions and contractility, and addressing anticoagulation and thrombus-related conditions. Beyond medical therapy, cardiac and pulmonary support should be utilized and introduced in a graded, stair-step approach of aggressiveness based on clinical need. This approach is best managed with a care team and defined protocols. Effective devices include right ventricular assistance devices (RVAD), Oxy-RVAD, veno-venous extracorporeal membrane oxygenation, and Impella (Abiomed) devices.

To treat or not to treat pulmonary arteries: epinephrine provocation to unmask right ventricular load

BackgroundPulmonary artery stenosis (PAS) is common in congenital heart disease (CHD). The indication for treatment of PAS is primarily based on invasively measured pressure gradients. Anesthetics used during cardiac catheterization cause systemic and pulmonary hypotension. We hypothesize that this leads to underestimation of right ventricular (RV) pressure load and under treatment of PAS. The aim of this study is to describe the use of epinephrine to unmask RV pressure load in patients with PAS. MethodsAll cardiac catheterizations in which epinephrine was administered to evaluate RV load were included. There was an indication for treatment in case of a right to left ventricular (RV:LV) pressure ratio >0.6. The indication for treatment before and after epinephrine was evaluated to determine its role in clinical decision making. ResultsA total of 74 procedures were included. In all procedures the invasively measured LV pressure was below the awake blood pressure. At baseline, 33 patients had a RV:LV ratio >0.6. In 41 patients the baseline RV:LV ratio was <0.6. After epinephrine bolus, the LV pressure was raised up to the awake blood pressure. In 19 of the 41 patients without baseline indication, this resulted in a RV:LV ratio >0.6 thereby revealing the indication for treatment. No epinephrine related complications were registered. ConclusionThe hypotensive properties of anesthetics during cardiac catheterization may lead to underestimation of RV pressure load. Invasive pressure measurements should be performed under conditions similar to awake conditions. Epinephrine provocation prevented under treatment in 25% of our patients.

The right ventricular-pulmonary circulation coupling in ischaemic heart disease; a stress echocardiography study

Abstract Objectives This study sought to assess the right ventricular (RV) - pulmonary circulation coupling in patients with coronary artery disease (CAD), preserved echocardiographic indices of right ventricular systolic function and normal pulmonary artery systolic pressure (PASP). Background Patients with CAD are at increased risk for developing left, and ultimately right heart failure. The analysis of underlying mechanisms of worsening RV function has been limited to the hemodynamic sequelae of increased left ventricular (LV) filing pressure leading to pulmonary hypertension. It has been reported that evaluation of RV functional state by using the tricuspid annular plane systolic excursion (TAPSE)/PASP ratio as a surrogate for the RV length-force is of clinical prognostic relevance in patients with known pulmonary hypertension; its role has not been extensively explored in other cardiac conditions including myocardial ischaemia. We hypothesized that the TAPSE/PASP ratio may be able to identify early and subtle changes in RV function in patients with CAD, normal estimated resting PASP, and preserved TAPSE. Methods Data were obtained from a prospectively maintained database, and 223 consecutive patients with preserved right ventricular systolic function (TAPSE≥16mm), and normal resting PASP (≤35mmHg), undergoing stress echocardiography (SE) for suspected coronary artery disease were included. Exclusion criteria: non-ischaemia study, severe valvular disease, poor image quality, resting pulmonary hypertension, reduced right ventricular systolic function. Transthoracic 2-D Doppler echocardiogram was performed by an accredited sonographer at rest and during stress phase and reviewed by two cardiologists unaware of clinical data. Results Fifty-three (24%) SE studies were positive for ischaemia and 170 (76%) negative. Demographic characteristics of both groups are shown in Table 1. All patients had TAPSE≥16mm and a PASP≤35mmHg as per inclusion criteria. The mean TAPSE/PASP ratio was significantly lower in patients with a positive SE suggestive of CAD than controls (0.84±0.22 vs 0.93±0.24, P=0.024). The TAPSE/PASP ratio showed significant correlation with the maximum workload (Watts) achieved (r=0.17, P=0.015) and exercise time (min) (r=0.15, P=0.031), and an inverse correlation with age (r=−0.26, P&amp;lt;0.001) and the development of inducible exertional breathlessness (Exp(B) 0.11, 95% CI 0.028–0.457, P=0.002) on SE. Conclusion Resting TAPSE/PASP was reduced in patients with positive SE, compared to controls. Indexing RV function to RV load, with the use of the TAPSE/PASP ratio identified early changes in RV-pulmonary circulation coupling in CAD patients without resting pulmonary hypertension; this may denote the beginning of subclinical RV dysfunction. Funding Acknowledgement Type of funding sources: None. Table 1

The Predictive Value of Right Ventricular Longitudinal Strain in Pulmonary Hypertension, Heart Failure, and Valvular Diseases.

Right ventricular (RV) systolic function has an important role in the prediction of adverse outcomes, including mortality, in a wide range of cardiovascular (CV) conditions. Because of complex RV geometry and load dependency of the RV functional parameters, conventional echocardiographic parameters such as RV fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE), have limited prognostic power in a large number of patients. RV longitudinal strain overcame the majority of these limitations, as it is angle-independent, less load-dependent, highly reproducible, and measure regional myocardial deformation. It has a high predictive value in patients with pulmonary hypertension, heart failure, congenital heart disease, ischemic heart disease, pulmonary embolism, cardiomyopathies, and valvular disease. It enables detection of subclinical RV damage even when conventional parameters of RV systolic function are in the normal range. Even though cardiac magnetic resonance-derived RV longitudinal strain showed excellent predictive value, echocardiography-derived RV strain remains the method of choice for evaluation of RV mechanics primarily due to high availability. Despite a constantly growing body of evidence that support RV longitudinal strain evaluation in the majority of CV patients, its assessment has not become the part of the routine echocardiographic examination in the majority of echocardiographic laboratories. The aim of this clinical review was to summarize the current data about the predictive value of RV longitudinal strain in patients with pulmonary hypertension, heart failure and valvular heart diseases.

Preoperative right ventricular overwork is a major determinant of residual pulmonary arterial hypertension in patients with repaired arterial septal defect

Abstract Funding Acknowledgements Type of funding sources: None. Background The haemodynamic effect of atrial septal defect (ASD) is a chronic volume overload of the right heart and pulmonary vasculature. Pulmonary overcirculation is generally compensated for by the right ventricular (RV) and pulmonary arterial (PA) reserve. However, in a subset of patients, prolonged pulmonary overcirculation insidiously induces obstructive pulmonary vasculopathy, which results in postoperative residual pulmonary arterial hypertension (PAH) after ASD closure. Postoperative PAH is a major concern because it is closely associated with poor outcomes and impaired quality of life. However, to date, no clinically robust predictors of postoperative residual PAH have been clearly identified. Purpose This study sought to assess the haemodynamic characteristics of ASD patients in terms of mechano-energetic parameters and to identify the predictors of postoperative residual PAH in these patients. Methods A total of 120 ASD patients (age: 58 ± 17 years) and 46 normal controls were recruited. As previously reported, the simplified RV contraction pressure index (sRVCPI) was calculated as an index of RV external work by multiplying the tricuspid annular plane systolic excursion (TAPSE) by the pressure gradient between the RV and right atrium. RV- PA coupling was evaluated using TAPSE divided by PA systolic pressure as an index of the RV length-force relationship. These parameters were measured both at baseline and 6 months after ASD closure. Results As expected, baseline sRVCPI was significantly greater in patients with ASD than in controls (775 ± 298 vs. 335 ± 180 mm Hg • mm, P &amp;lt; 0.01), which indicated significant "RV overwork". As a result, RV-PA coupling in ASD patients was significantly impaired compared to that in controls (0.9 ± 0.8 vs. 3.5 ± 1.7 mm/mm Hg, P &amp;lt; 0.01). All 120 ASD patients underwent transcatheter or surgical shunt closure; 15 of them had residual PAH after closure. After 6 months, RV-PA coupling index significantly improved in patients without residual PAH, from 0.96 ± 0.81 to 1.27 ± 1.24 mm/mm Hg (P = 0.02). Furthermore, RV load was markedly reduced, with sRVCPI falling from 691 ± 258 to 434 ± 217 mm Hg • mm, P &amp;lt; 0.01). However, in patients with residual PAH, RV-PA coupling index deteriorated from 0.64 ± 0.23 to 0.53 ± 0.12 mm/mm Hg (P &amp;lt; 0.01). As a result, RV overload was not significantly relieved (sRVCPI; from 971 ± 382 to 783 ± 166 mm Hg • mm, P = 0.22). In a multivariate analysis, baseline pulmonary vascular resistance (hazard ratio 1.009; P &amp;lt; 0.01) and preoperative sRVPCI (hazard ratio 1.003; P &amp;lt; 0.01) revealed to be independent predictors of residual PAH. Conclusion In terms of mechano-energetic function, preoperative "RV overwork" can be used as a robust predictor of an impaired RV-PA relationship in ASD patients. Moreover, periodic assessment of sRVPCI may contribute to the better management for patients with unrepaired ASD. Abstract Figure.

Clinical Significance of Guanylate Cyclase Stimulator, Riociguat, on Right Ventricular Functional Improvement in Patients with Pulmonary Hypertension

Background: Riociguat is a soluble guanylate cyclase stimulator that improves hemodynamics in patients with pulmonary hypertension (PH). Accumulating evidence implicates the additional effect of riociguat on the increase in cardiac output. However, its mechanisms have not been fully understood. This study aimed to investigate whether riociguat could ameliorate right ventricular (RV) contraction as well as hemodynamics. Methods: We studied 45 patients with pulmonary arterial hypertension (14) or chronic thromboembolic pulmonary hypertension (31) and evaluated hemodynamics, using right-sided heart catheterization, before and after the administration of riociguat. RV function was assessed by echocardiography, including speckle-tracking echocardiography. Results: Riociguat significantly improved the WHO functional class and reduced the mean pulmonary arterial pressure and vascular resistance. In addition, the cardiac index increased. RV remodeling was ameliorated after riociguat administration as assessed by the echocardiographic parameters, such as RV diameter and RV area index. RV function, including RV fractional area change and RV global longitudinal strain, also significantly improved, and their improvement was even observed in patients with mild PH after pulmonary endarterectomy or balloon pulmonary angioplasty. Furthermore, covariance analysis revealed that RV global longitudinal strain and RV fractional area change improved after riociguat administration, even with the same mean pulmonary arterial pressure, implicating the improvement of RV contractile function by riociguat, regardless of RV loading. Conclusions: Riociguat not only improved the hemodynamics of patients with PH but also ameliorated the echocardiographic parameters with RV function. RV strain could detect the subtle improvement in mild PH, and riociguat may have a benefit even after intervention, as assessed by speckle-tracking echocardiography.

Acute Unloading Effects of Sildenafil Enhance Right Ventricular–Pulmonary Artery Coupling in Heart Failure

BackgroundPhosphodiesterase-5A inhibitors (PDE5i) are sometimes used in patients with advanced heart failure with reduced ejection fraction before heart transplant or left ventricular assist device implantation to decrease right ventricular (RV) afterload and mitigate the risk of right heart failure. Conflicting evidence exists regarding the impact of these drugs on RV contractility. The aim of this study was to explore the acute effects of PDE5i on ventricular–vascular coupling and load-independent RV contractility. MethodsTwenty-two patients underwent right heart catheterization and gated equilibrium blood pool single photon emission computed tomography, before and after 20 mg intravenous sildenafil. Single photon emission computed tomography and right heart catheterization-derived data were used to calculate RV loading and contractility. ResultsPDE5i induced a decrease in the right atrial pressure (–43%), pulmonary artery (PA) mean pressure (–26%), and PA wedge pressure (PAWP; –23%), with favorable reductions in pulmonary vascular resistance (–41%) and PA elastance (–40%), and increased cardiac output (+13%) (all P < 0.01). The RV ejection fraction increased with sildenafil (+20%), with no change of RV contractility (P = 0.74), indicating that the improvement in the RV ejection fraction was related to enhanced RV–PA coupling (r = 0.59, P = 0.004) by a decrease in the ventricular load. RV diastolic compliance increased with sildenafil. The decrease in the PAWP correlated with RV end-diastolic volume decrease; no relationship was observed with the change in LV transmural pressure, suggesting decreased pericardial constraint. ConclusionsAcute PDE5i administration has profound RV afterload-reducing effects, improves the RVEF, decreases RV volumes, and decreases the PAWP, predominantly through relief of pericardial constraint, without effects on RV chamber contractility. These findings support further study of PDE5i in protection of RV function in advanced heart failure with reduced ejection fraction who are at risk of RV failure.

Does the right ventricle experiment morphologic and functional changes similarly to the left ventricle during pregnancy?

Morphological and functional right ventricular (RV) changes during normal pregnancy remain poorly characterized. Similar to left ventricle, RV load and function are expected to change, and establishing reference values for RV during a healthy pregnancy is critical for the evaluation of pregnancy-related heart disease. The aim of the study was to describe RV adaptation in a prospective cohort. Serial echocardiographic examinations were performed in second trimester (24±2weeks), third (32±2week) trimester, and postpartum (>3months after delivery). Nulliparous women were evaluated as control group. RV linear dimensions, areas, and function were assessed and compared. Forty-three pregnant women were evaluated and compared with nineteen nulliparous women as control. Function parameters decreased along gestation. RV fractional area fell from second to third trimester (52.01±0.92 vs 48.73±0.97, P<.05), as well as tricuspid annular plane systolic excursion (2.62±0.05 vs 2.41±0.05, P<.05); however, RV longitudinal strain (L) decreased earlier, showing main changes from second trimester (26.17±0.86 vs 22.71±0.57, P<.003, control vs second trimester). S'-wave velocity followed a different pattern without changes during pregnancy. RV diameters significantly increased during pregnancy: basal (3.65±0.06 vs 3.90±0.06, P<.05), mid- (2.70±0.06 vs 3.00±0.07, P<.05), longitudinal (6.90±0.09 vs 7.32±0.11, P<.05), and right ventricle outflow tract proximal diameter (3.20±0.06 vs 3.44±0.06, P<.05). RV areas also suffered early variation during pregnancy. In postpartum evaluation, all these changes were reversed. During pregnancy, RV experiments important variations. RV size increases, and its function decreases. Changes in LS were earlier compared with other function measures.

Determinants of Right Ventricular Function Worsening in Advanced HFrEF: Longitudinal Echocardiography and Invasive Hemodynamics Study

Hemodynamic and clinical determinants of right ventricular (RV) dysfunction in heart failure with reduced EF (HFrEF) are poorly understood and were studied mostly on cross-sectional data. We hypothesized that examining changes of RV function and hemodynamic load over time will provide better insight into mechanisms of RV function worsening. From HFrEF patients examined in our cardiac transplant center in the past 10 years, we retrospectively identified patients who underwent twice right heart catheterization, clinical labs and echocardiography with RV function assessment. We examined hemodynamic and clinical factors associated with worsening or stable RV function using correlations and logistic regression (LR) analysis. In 147 HFrEF patients (age 53±9 y, body mass index-BMI: 27±4, 85% males, LV EF: 20±5%), 83% had PH (mPA over 25mmHg) and 56% had moderate/severe RV dysfunction. After median of 412 d (IQR: 182-686), 60 (41%) had RV function worsening, defined as negative change in Tricuspid annular plane systolic excursion (negative Δ TAPSE). SSRI antidepressant use at baseline was associated with RV worsening. The regression of RV load (RV systolic pressure) to RV function (TAPSE) at both visits had negative slope (r=-0.16, p=0.05) and p=0.05) and were superimposable. Strong correlates of RV function decline were the increase of RV arterial elastance (log Ea, PA systolic pressure/stroke volume), serum creatinine, BNP, LV end-diastolic diameter and LA area, and the reduction of PA compliance (PAC, PA SV/PP) or body mass index (Figure). In multivariate LR model (chi2 31) using parameters above, only the increase in log RV Ea, LV-end-diastolic diameter and the reduction in BMI were independently predictive of RV function worsening. Oscillatory RV load, progressive LV dilatation and body weight loss (cardiac cachexia) were independently associated with progressive RV dysfunction in advanced HFrEF.