Right Ventricular Myocardium Research Articles

A Comparative Study of Rv Function in Anterior And Inferior Stemi

I. Introduction The prognosis of patients with acute myocardial infarction (AMI) is directly related to left ventricular (LV) function and size 1.2 Traditionally, the principal investigated target of clinicians is LV function, with little interest in the right ventricle.However, right ventricular (RV) dysfunction after AMI is also associated with increased risk of morbidity and mortality. 3-5 RV dysfunction has been associated with increased morbidity and mortality in patients with congenital heart disease, valvular disease, coronary artery disease, pulmonary hypertension, and heart failure. 6-8 Right Ventricle (RV) dysfunction may be primarily attributed to abnormality of RV myocardium or secondary to left ventricle (LV) dysfunction, as a consequence of Ventricular Interdependence between the two ventricles, as they are encircled by common muscle fibres, share a common septal wall and are enclosed within a common pericardium. 9 Early recognization of RV dysfunction is warranted but till today it remains a challenging task because of complex structure and asymmetric shape of RV. 10 Most of the previous studies have evaluated RV functions in patients of inferior myocardial infarction. There are only few studies available in literature evaluating RV function in anterior myocardial infarction. Therefore, in the present study conventional echocardiography combined with tricuspid annular plane systolic excursion [TAPSE Fractional area change(FAC), pulsed doppler and TDI were used to evaluate the effect of different infarction sites on RV functional changes in patients with first acute ST-elevation myocardial infarction (STEMI) without concomitant RV infarction.

Myocardial Response to Milrinone in Single Right Ventricle Heart Disease

Empiric treatment with milrinone, a phosphodiesterase (PDE) 3 inhibitor, has become increasingly common in patients with single ventricle heart disease of right ventricular (RV) morphology (SRV); our objective was to characterize the myocardial response to PDE3 inhibition (PDE3i) in the pediatric population with SRV. Cyclic adenosine monophosphate levels, PDE activity, and phosphorylated phospholamban (PLN) were determined in explanted human ventricular myocardium from nonfailing pediatric donors (n=10) and pediatric patients transplanted secondary to SRV. Subjects with SRV were further classified by PDE3i treatment (n=13 with PDE3i and n=12 without PDE3i). In comparison with nonfailing RV myocardium (n = 8), cyclic adenosine monophosphate levels are lower in patients with SRV treated with PDE3i (n = 12, P=.021). Chronic PDE3i does not alter total PDE or PDE3 activity in SRV myocardium. Compared with nonfailing RV myocardium, SRV myocardium (both with and without PDE3i) demonstrates equivalent phosphorylated PLN at the protein kinase A phosphorylation site. As evidenced by preserved phosphorylated PLN, the molecular adaptation associated with SRV differs significantly from that demonstrated in pediatric heart failure because of dilated cardiomyopathy. These alterations support a pathophysiologically distinct mechanism of heart failure in pediatric patients with SRV, which has direct implications regarding the presumed response to PDE3i treatment in this population.

Mesenchymal stem cells preserve neonatal right ventricular function in a porcine model of pressure overload.

Limited therapies exist for patients with congenital heart disease (CHD) who develop right ventricular (RV) dysfunction. Bone marrow-derived mesenchymal stem cells (MSCs) have not been evaluated in a preclinical model of pressure overload, which simulates the pathophysiology relevant to many forms of CHD. A neonatal swine model of RV pressure overload was utilized to test the hypothesis that MSCs preserve RV function and attenuate ventricular remodeling. Immunosuppressed Yorkshire swine underwent pulmonary artery banding to induce RV dysfunction. After 30 min, human MSCs (1 million cells, n = 5) or placebo (n = 5) were injected intramyocardially into the RV free wall. Serial transthoracic echocardiography monitored RV functional indices including 2D myocardial strain analysis. Four weeks postinjection, the MSC-treated myocardium had a smaller increase in RV end-diastolic area, end-systolic area, and tricuspid vena contracta width (P < 0.01), increased RV fractional area of change, and improved myocardial strain mechanics relative to placebo (P < 0.01). The MSC-treated myocardium demonstrated enhanced neovessel formation (P < 0.0001), superior recruitment of endogenous c-kit+ cardiac stem cells to the RV (P < 0.0001) and increased proliferation of cardiomyocytes (P = 0.0009) and endothelial cells (P < 0.0001). Hypertrophic changes in the RV were more pronounced in the placebo group, as evidenced by greater wall thickness by echocardiography (P = 0.008), increased cardiomyocyte cross-sectional area (P = 0.001), and increased expression of hypertrophy-related genes, including brain natriuretic peptide, β-myosin heavy chain and myosin light chain. Additionally, MSC-treated myocardium demonstrated increased expression of the antihypertrophy secreted factor, growth differentiation factor 15 (GDF15), and its downstream effector, SMAD 2/3, in cultured neonatal rat cardiomyocytes and in the porcine RV myocardium. This is the first report of the use of MSCs as a therapeutic strategy to preserve RV function and attenuate remodeling in the setting of pressure overload. Mechanistically, transplanted MSCs possibly stimulated GDF15 and its downstream SMAD proteins to antagonize the hypertrophy response of pressure overload. These encouraging results have implications in congenital cardiac pressure overload lesions.

Higher Plasma Myostatin Levels in Cor Pulmonale Secondary to Chronic Obstructive Pulmonary Disease

ObjectiveTo analyze plasma myostatin levels and investigate their relationship with right ventricular (RV) function in patients with cor pulmonale secondary to chronic obstructive pulmonary disease (COPD).MethodsThe study recruited 81 patients with advanced COPD and 40 age-matched controls. The patients were divided into two groups: those with cor pulmonale and those without. Echocardiography was used to evaluate RV function and morphology, and the value of tricuspid annular plane systolic excursion (TAPSE) less than 16 mm was considered RV dysfunction. Plasma myostatin levels were analyzed by enzyme-linked immunosorbent assay, and B-type natriuretic peptide (BNP) levels were analyzed as a comparison of myostatin.ResultsThe data detected cor pulmonale in 39/81 patients, with the mean value of TAPSE of 14.3 mm. Plasma myostatin levels (ng/mL) were significantly higher in patients with cor pulmonale (16.68 ± 2.95) than in those without (13.56 ± 3.09), and much higher than in controls (8.79±2.79), with each p<0.01. Significant differences were also found in plasma BNP levels among the three groups (p<0.05). Multivariate regression analysis suggested that myostatin levels were significantly correlated with the values of TAPSE and RV myocardium performance index among the COPD patients, and that BNP levels were significantly correlated only with systolic pulmonary arterial pressure, with each p<0.05.ConclusionsPlasma myostatin levels are increased in COPD patients who have cor pulmonale. Stronger correlations of plasma myostatin levels with echocardiographic indexes of the right heart suggest that myostatin might be superior to BNP in the early diagnosis of cor pulmonale in COPD.

Complete recovery of the right ventricle from a large intramyocardial hematoma complicating percutaneous coronary intervention

Right ventricular (RV) intramyocardial hematoma is a potentially life-threatening condition that can complicate percutaneous coronary intervention (PCI). Natural course of RV hematoma and long-term recovery of the affected myocardium have not been described. We present a case of a 70-year-old male with large RV hematoma caused by distal guidewire perforation during PCI of the right coronary artery. Baseline multimodality imaging, serial echocardiography, and long-term follow-up using cardiac magnetic resonance (CMR) imaging were used to investigate the natural course of this rare condition. Despite its massive initial appearance, the hematoma was successfully managed conservatively. Serial echocardiographic examination showed slow gradual resorption of the hematoma. Follow-up CMR performed at 12 months was strikingly normal, showing no late gadolinium enhancement of the RV myocardium indicating lack of significant fibrotic scarring at the site of hematoma resorption.<Learning objective: Right ventricular (RV) free wall hematoma is a potentially life-threatening complication of percutaneous coronary intervention. Multimodality imaging combined with serial echocardiography is useful to study the extent of myocardial involvement and the slow resorption process of the hematoma. This case illustrates that even a sizeable RV intramyocardial hematoma can be managed conservatively if no acute hemodynamic compromise occurs and complete recovery of the myocardium can be expected.>

Right Ventricular Involvement and Recovery After Acute Stress-Induced (Tako-tsubo) Cardiomyopathy

Acute stress-induced (Tako-tsubo) cardiomyopathy is an increasingly recognized but insufficiently characterized syndrome. Here, we investigate the pathophysiology of right ventricular (RV) involvement in Tako-tsubo and its recovery time course. We prospectively recruited 31 patients with Tako-tsubo with predominantly ST-elevation electrocardiogram and 18 controls of similar gender, age, and co-morbidity distribution. Patients underwent echocardiography and cardiac magnetic resonance (CMR) imaging on a 3T Philips scanner in the acute phase (day 0 to 3 after presentation) and at 4-months follow-up. Visually, echocardiography was able to identify only 52% of patients who showed RV wall motion abnormalities on CMR. Only CMR-derived RV ejection fraction (p = 0.01) and echocardiography-estimated pulmonary artery pressure (p = 0.01) identify RV functional involvement in the acute phase. Although RV ejection fraction normalizes in most patients by 4 months, acutely there is RV myocardial edema in both functioning and malfunctioning segments, as measured by prolonged native T1 mapping (p = 0.02 for both vs controls), and this persists at 4 months in the acutely malfunctioning segments (p = 0.002 vs controls). The extracellular volume fraction was significantly increased acutely in all RV segments and remained increased at follow-up compared with controls (p = 0.004 for all). In conclusion, in a Tako-tsubo population presenting predominantly with ST-elevation electrocardiogram, we demonstrate that although RV functional involvement is seen in only half of the patients, RV myocardial edema is present acutely throughout the RV myocardium in all patients and results in microscopic fibrosis at 4-month follow-up.

Carvedilol improves biventricular fibrosis and function in experimental pulmonary hypertension.

Left ventricular (LV) function influences outcomes in right ventricular (RV) failure. Carvedilol reduces mortality in LV failure and improves RV function in experimental pulmonary arterial hypertension (PAH). However, its impact on ventricular-ventricular interactions and LV function in RV afterload is unknown. We investigated effects of carvedilol on biventricular fibrosis and function in a rat model of persistent PAH. Rats were randomized into three groups: Sham controls, PAH, and PAH + carvedilol. Severe PAH was induced by 60 mg/kg subcutaneous monocrotaline. In the treatment group, oral carvedilol (15 mg/kg/day) was started 2 weeks after monocrotaline injection and continued for 3 weeks until the terminal experiment. Echocardiography and exercise performance were performed at baseline and repeated at the terminal experiment with hemodynamic measurements. LV and RV myocardium were analyzed for hypertrophy, fibrosis, and molecular signaling by protein and mRNA analysis. PAH and PAH + carvedilol rats experienced severely elevated pulmonary arterial pressures and RV hypertrophy. Despite similar RV systolic pressures, carvedilol reduced biventricular collagen content (RV fibrosis area; 13.4 ± 6.5 vs. 5.5 ± 2.7 %, p < 0.001) and expression of transforming growth factor-β1 (TGFβ1) (RV TGFβ1/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) ratio; 1.16 ± 0.39 vs. 0.57 ± 0.22, p < 0.01) and connective tissue growth factor (CTGF) (RV CTGF/GAPDH ratio; 0.49 ± 0.06 vs. 0.35 ± 0.17, p < 0.05). RV pro-apoptotic caspase-8 was increased in PAH compared to controls and was significantly reduced in both ventricles compared to PAH animals by carvedilol. Tissue effects were accompanied by improved biventricular systolic and diastolic performance and exercise treadmill distance (36 ± 30 vs. 80 ± 33 m, p < 0.05). In RV pressure-load, carvedilol improves biventricular fibrosis and function through abrogation of TGFβ1-CTGF signaling. • RV afterload caused biventricular injury and dysfunction through TGFβ1-CTGF signaling. • Carvedilol reduced biventricular TGFβ1-CTGF signaling, fibrosis, and apoptosis. • Carvedilol improved cardiac output and biventricular function. • Improved fibrosis and hemodynamics occurred despite persistent RV afterload.

Sex Differences in Immunology: More Severe Development of Experimental Pulmonary Hypertension in Male Rats Exposed to Vascular Endothelial Growth Factor Receptor Blockade.

Background. The epidemiology of pulmonary hypertension (PH) is characterized by a female preponderance, whereas males share higher severity of the disease. Objective. To compare the severity of experimental PH between male and female athymic rats. Methods. PH was induced in 11 male and 11 female athymic rats (resp., SU_M and SU_F groups) using an inhibitor of VEGF-receptors I and II, semaxanib (40 mg/kg). After 28 days, right ventricular (RV) remodeling, systolic function, and hemodynamics were measured using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV myocardium were performed. Results. Four weeks after semaxanib injection, RV end-systolic pressure was higher in SU_M than in SU_F. Males developed marked RV enlargement and systolic dysfunction compared to females. Impairment of RV-PA coupling efficiency was observed only in SU_M. The smooth muscle cells of the pulmonary arteries switched from a contractile state to a dedifferentiated state only in males. Conclusions. Female athymic rats were protected against the development of severe PH. RV-PA coupling was preserved in females through limitation of pulmonary artery muscularization. Control of smooth muscle cells plasticity may be a promising therapeutic approach to reverse established vascular remodeling in PH patients.

Microvascular obstruction complicating acute right ventricular myocardial infarction

This case history describes a man with inferior myocardial infarction (MI) with right-ventricular involvement, treated with a right coronary artery stent. Magnetic resonance showed akinesia of left-ventricular inferior and inferolateral walls and right-ventricular inferior free wall with an impairment of global systolic function. There was late gadolinium enhancement (LGE) of left-ventricular inferior and inferolateral walls with microvascular obstruction (MVO). LGE of the right-ventricular inferior wall was seen with a hypointense core within hyperenhanced myocardium, consistent with MVO of the infarcted right-ventricular myocardium. At follow-up there was persistent akinesia of left-ventricular inferior and inferolateral walls and right-ventricular systolic dysfunction. LGE was still evident with resolution of MVO.

A miR-208-Mef2 axis drives the decompensation of right ventricular function in pulmonary hypertension.

Right ventricular (RV) failure is a major cause of morbidity and mortality in pulmonary hypertension, but its mechanism remains unknown. Myocyte enhancer factor 2 (Mef2) has been implicated in RV development, regulating metabolic, contractile, and angiogenic genes. Moreover, Mef2 regulates microRNAs that have emerged as important determinants of cardiac development and disease, but for which the role in RV is still unclear. We hypothesized a critical role of a Mef2-microRNAs axis in RV failure. In a rat pulmonary hypertension model (monocrotaline), we studied RV free wall tissues from rats with normal, compensated, and decompensated RV hypertrophy, carefully defined based on clinically relevant parameters, including RV systolic and end-diastolic pressures, cardiac output, RV size, and morbidity. Mef2c expression was sharply increased in compensating phase of RVH tissues but was lost in decompensation phase of RVH. An unbiased screening of microRNAs in our model resulted to a short microRNA signature of decompensated RV failure, which included the myocardium-specific miR-208, which was progressively downregulated as RV failure progressed, in contrast to what is described in left ventricular failure. With mechanistic in vitro experiments using neonatal and adult RV cardiomyocytes, we showed that miR-208 inhibition, as well as tumor necrosis factor-α, activates the complex mediator of transcription 13/nuclear receptor corepressor 1 axis, which in turn promotes Mef2 inhibition, closing a self-limiting feedback loop, driving the transition from compensating phase of RVH toward decompensation phase of RVH. In our model, serum tumor necrosis factor-α levels progressively increased with time while serum miR-208 levels decreased, mirroring its levels in RV myocardium. We describe an RV-specific mechanism for heart failure, which could potentially lead to new biomarkers and therapeutic targets.

Structural and mechanical adaptations of right ventricle free wall myocardium to pressure overload.

Right ventricular (RV) failure in response to pulmonary hypertension (PH) is a severe disease that remains poorly understood. PH-induced pressure overload leads to changes in the RV free wall (RVFW) that eventually results in RV failure. While the development of computational models can benefit our understanding of the onset and progression of PH-induced pressure overload, detailed knowledge of the underlying structural and biomechanical events remains limited. The goal of the present study was to elucidate the structural and biomechanical adaptations of RV myocardium subjected to sustained pressure overload in a rat model. Hemodynamically confirmed severe chronic RV pressure overload was induced in Sprague-Dawley rats via pulmonary artery banding. Extensive tissue-level biaxial mechanical and histomorphological analyses were conducted to assess the remodeling response in the RV free wall. Simultaneous myofiber hypertrophy and longitudinal re-orientation of myo- and collagen fibers were observed, with both fiber types becoming more highly aligned. Transmural myo- and collagen fiber orientations were co-aligned in both the normal and diseased state. The overall tissue stiffness increased, with larger increases in longitudinal vs. circumferential stiffness. The latter was attributed to longitudinal fiber re-orientation, which increased the degree of anisotropy. Increased mechanical coupling between the two axes was attributed to the increased fiber alignment. Interestingly, estimated myofiber stiffness increased while the collagen fiber stiffness remained unchanged.The increased myofiber stiffness was consistent with clinical results showing titin-associated increased sarcomeric stiffening observed in PH patients. These results further our understanding of the underlying adaptive and maladaptive remodeling mechanisms and may lead to improved techniques for prognosis, diagnosis, and treatment for PH.

Direct and indirect protection of right ventricular function by estrogen in an experimental model of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) results in right ventricular (RV) dysfunction and failure. Paradoxically, women are more frequently diagnosed with PAH but have better RV systolic function and survival rates than men. The mechanisms by which sex differences alter PAH outcomes remain unknown. Here, we sought to study the role of estrogen in RV functional remodeling in response to PAH. The SU5416-hypoxia (SuHx) mouse model of PAH was used. To study the role of estrogen, female mice were ovariectomized and then treated with estrogen or placebo. SuHx significantly increased RV afterload and resulted in RV hypertrophy. Estrogen treatment attenuated the increase in RV afterload compared with the untreated group (effective arterial elastance: 2.3 ± 0.1 mmHg/μl vs. 3.2 ± 0.3 mmHg/μl), and this was linked to preserved pulmonary arterial compliance (compliance: 0.013 ± 0.001 mm(2)/mmHg vs. 0.010 ± 0.001 mm(2)/mmHg; P < 0.05) and decreased distal muscularization. Despite lower RV afterload in the estrogen-treated SuHx group, RV contractility increased to a similar level as the placebo-treated SuHx group, suggesting an inotropic effect of estrogen on RV myocardium. Consequently, when compared with the placebo-treated SuHx group, estrogen improved RV ejection fraction and cardiac output (ejection fraction: 57 ± 2% vs. 44 ± 2% and cardiac output: 9.7 ± 0.4 ml/min vs. 7.6 ± 0.6 ml/min; P < 0.05). Our study demonstrates for the first time that estrogen protects RV function in the SuHx model of PAH in mice directly by stimulating RV contractility and indirectly by protecting against pulmonary vascular remodeling. These results underscore the therapeutic potential of estrogen in PAH.

0245: Cell therapy to restore overloaded right ventricular function: First promising results using human cardiac progenitors seeded in a patch on the epicardium

Despite the prevalence of right ventricular (RV) failure in congenital heart diseases, cell therapy applied to RV is poorly studied. Our aim is to evaluate in a large animal model of overloaded RV dysfunction such therapy using cardiac progenitors (CP) issued from human embryonic stem cells. A combined overloaded RV dysfunction was created in pigs using a surgical procedure mimicking repaired tetralogy of Fallot. At 4 months, cell therapy was surgically administrated using either multiple transepicardial injections of HUES-24 derived CP into RV myocardium or CP seeded collagen patches sewn on RV free wall. SHAM animals received either multiple transepicardial injections of medium or acellular patches. Myocardial function was determined 3 months later by conductance catheter technique with maximal elastance (Emax) slope. Ventricular arrhythmia risks were tested by programmed ventricular stimulation. A histological study analyzed the structural remodelling. CP fate was studied using anti- Ki67, CD31, CD34, GFP, Islet1 and Connexin 43 antibodies. All pigs were immunosuppressed by Tacrolimus. All pigs survived. Neither complication nor ventricular arrhythmia occurred. In injected animals (SHAM: n=6, HUES-24: n=6) the Emax slope value evoluated similarly in both groups. Whereas total fibrosis increased significantly with time in the SHAM group, it returned to baseline in HUES-24 group. However, CP could not be found. In contrast, in patched animals, CP were found in the patch zone and close to the myocardium. These CP were able to proliferate, migrate, express cardiac markers and establish connexions. Cell therapy using transepicardial injections of human CP seems to have a beneficial effect on overloaded RV tissue remodelling, but this administration mode did not improve myocardial contractility. Seeded patches seem to be more conservative for engrafted cells; their impact on overloaded RV function requires further experiments.

In-vivo assessment of normal T1 values of the right-ventricular myocardium by cardiac MRI

To test feasibility of myocardial T1 mapping of the right ventricle (RV) at systole when myocardium is more compact and to determine the most appropriate imaging plane. 20 healthy volunteers (11 men; 33 ± 8 years) were imaged on a 1.5T scanner (MAGNETOM Avanto, Siemens AG, Erlangen, Germany). A modified look-locker inversion-recovery sequence was acquired at mid-ventricular short axis (SAX), as horizontal long-axis view and as transversal view at systole (mean trigger time 363 ± 37 ms). Myocardial T1 time of the left-ventricular and RV myocardium was measured within a region of interest (ROI) on generated T1-maps. The most appropriate imaging plane for the RV was determined by the ability to draw a ROI including the largest amount of myocardium without including adjacent tissue or blood. At systole, when myocardium is thicker, measurements of the RV myocardium were feasible in 18/20 subjects. Average size of the ROI was 0.42 ± 0.28 cm(2). In 10/18 subjects, short axis was the most appropriate imaging plane to obtain measurements (p = 0.034). Average T1 time of the RV myocardium was 1,016 ± 61 ms, and average T1 of the left-ventricular (LV) was 956 ± 25 ms (p < 0.001). T1 mapping of the RV myocardium is feasible during systole in the majority of healthy subjects but with a small ROI only. SAX plane was the optimal imaging plane in the majority of subjects. Native myocardial T1 time of the RV is significantly longer compared to the LV, which might be explained by the naturally higher collagen content of the RV.

Comparative Electromechanical and Hemodynamic Effects of Left Ventricular and Biventricular Pacing in Dyssynchronous Heart Failure: Electrical Resynchronization Versus Left–Right Ventricular Interaction

The purpose of this study was to enhance understanding of the working mechanism of cardiac resynchronization therapy by comparing animal experimental, clinical, and computational data on the hemodynamic and electromechanical consequences of left ventricular pacing (LVP) and biventricular pacing (BiVP). It is unclear why LVP and BiVP have comparative positive effects on hemodynamic function of patients with dyssynchronous heart failure. Hemodynamic response to LVP and BiVP (% change in maximal rate of left ventricular pressure rise [LVdP/dtmax]) was measured in 6 dogs and 24 patients with heart failure and left bundle branch block followed by computer simulations of local myofiber mechanics during LVP and BiVP in the failing heart with left bundle branch block. Pacing-induced changes of electrical activation were measured in dogs using contact mapping and in patients using a noninvasive multielectrode electrocardiographic mapping technique. LVP and BiVP similarly increased LVdP/dtmax in dogs and in patients, but only BiVP significantly decreased electrical dyssynchrony. In the simulations, LVP and BiVP increased total ventricular myofiber work to the same extent. While the LVP-induced increase was entirely due to enhanced right ventricular (RV) myofiber work, the BiVP-induced increase was due to enhanced myofiber work of both the left ventricle (LV) and RV. Overall, LVdP/dtmax correlated better with total ventricular myofiber work than with LV or RV myofiber work alone. Animal experimental, clinical, and computational data support the similarity of hemodynamic response to LVP and BiVP, despite differences in electrical dyssynchrony. The simulations provide the novel insight that, through ventricular interaction, the RV myocardium importantly contributes to the improvement in LV pump function induced by cardiac resynchronization therapy.

Impaired right ventricular myocardial perfusion and right ventricular dysfunction in patients with pulmonary arterial hypertension: a study of contrast echocardiography and strain imaging

Background: Little is known about right ventricular (RV) dysfunction in patient with pulmonary arterial hypertension (PAH). Recently, RV ischemia has been reported to be a contributory factor in the development of RV dysfunction. The aim of this study is to evaluate RV myocardial perfusion and assess its relationship with RV dysfunction. Methods: This prospective study consisted of 10 consecutive patients (7 female, 51±17 years) with PAH (6 idiopathic PAH (IPAH), and 4 chronic thromboembolic pulmonary hypertension (CTEPH)), and 6 healthy controls (3 females, 37±6 years). Quantitative myocardial contrast echocardiography (MCE) was performed using Philips iE33 imaging system with an S5-1 probe. We depicted the apical four chamber view. A solution of Levovist (300mg/ml) was inravenously administered at a rate of 3ml/min with a volumetric pump. End-systolic images were obtained every four heart beats. The MCE images were analyzed off-line using VoluMap-445 system. The RV myocardium was divided into six segments, at each myocardial segment, calibrated contrast intensity (CI) was determined as the difference (dB) between the mean myocardial CI and cavity CI. 2D speckle tracking echocardiographic study was also performed using Vivid E9 ultrasound system. Results: Among 96 RV myocardial segments, quantitative CI analysis was possible in 86 segments (90%). RV fractional area change was 46% (healthy), 34% (CTEPH) and 25% (IPAH). Mean calibrated CI of RV free wall was -13.4dB, -19.3dB and -22.8dB, respectively (p=0.01). We found good inverse correlation between calibrated CI and longitudinal strain of RV free wall (r=-0.5, p=0.0013). ![Figure][1] Conclusion: Quantitative MCE revealed patients with PAH have impaired RV myocardial perfusion, and this correlated well with the RV longitudinal myocardial dysfunction. [1]: pending:yes

Ventricular interaction rather than electrical resynchronisation determines haemodynamic response to cardiac resynchronisation therapy in dyssynchronous heart failure

Purpose: It is still unclear why left ventricular and biventricular pacing (LVP and BiVP, respectively) have comparative positive effects on haemodynamic function of patients with dyssynchronous heart failure (HF). To enhance understanding of the working mechanism of cardiac resynchronisation therapy (CRT), we assessed haemodynamic and local electromechanical consequences of LVP in comparison to BiVP. Methods: Haemodynamic response to LVP and BiVP (%-change LVdP/dtmax) was measured in 6 dogs with HF and left-bundle branch block (LBBB) and in 40 HF patients with QRS-width ≥120ms, followed by computer simulations of local myofibre mechanics during LVP and BiVP in the failing heart with LBBB. Pacing-induced changes of electrical activation were measured in dogs using contact mapping and in patients using a noninvasive multielectrode epicardial electrocardiographic mapping technique. Results: LVP and BiVP similarly increased LVdP/dtmax in dogs (p=0.33) and in patients (p=0.93), but only BiVP significantly decreased electrical dyssynchrony (Figure). In the simulations, LVP and BiVP increased total ventricular myofibre work to the same extent (Figure). While the LVP-induced increase was entirely due to enhanced right ventricular (RV) myofibre work, the BiVP-induced increase was due to enhanced myofibre work of both the LV and RV. Overall, LVdP/dtmax correlated better with total ventricular myofibre work than with LV or RV myofibre work alone. ![Figure][1] Conclusions: Experimental, human, and computational data support the similarity of haemodynamic response to LVP and BiVP, despite differences in electrical dyssynchrony. The simulations provide the novel insight that, through ventricular interaction, the RV myocardium importantly contributes to the improvement in LV pump function induced by CRT. [1]: pending:yes

Myocardial fibrosis in the right ventricle detected on ECG gated 320 slice CT showed a short term poor prognosis in subjects with pulmonary hypertension

Presence of myocardial fibrosis in the right ventricular (RV) myocardium (RVM) may contribute to a poor prognosis in a subject with Tetralogy of Fallot [1]. If myocardial fibrosis in RVM can be detected in subjects who have other diseases with increased RV pressure, such as pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (PH) (CTEPH), a prognosis may be predicted.

Long-term survivor diagnosed with arrhythmogenic right ventricular cardiomyopathy/dysplasia

The subject was a 70 year-old man who survived for 31 years after being diagnosed with right ventricular cardiomyopathy, having undergone right ventricular (RV) aneurysmectomy at the age of 39. His arrhythmia and syncopal attacks were effectively abolished after the original aneurysmectomy. Although he frequently suffered from right heart failure, hemodialysis improved his status. However, the patient died due to worsening anasarca caused by RV low output syndrome. Autopsy results indicated extensive replacement of the RV myocardium with fibrous and fatty tissues. This case suggests that patients with arrhythmogenic RV cardiomyopathy, but without left ventricular abnormalities and rapid ventricular arrhythmia, have a relatively favorable prognosis, although RV abnormalities may be progressive.

Endothelin Axis Is Upregulated in Human and Rat Right Ventricular Hypertrophy

Right ventricular (RV) function is the most important determinant of morbidity and mortality in pulmonary arterial hypertension (PAH). Endothelin (ET)-1 receptor antagonists (ERAs) are approved therapies for PAH. It is not known whether ERAs have effects on the RV, in addition to their vasodilating/antiproliferative effects in pulmonary arteries. We hypothesized that the ET axis is upregulated in RV hypertrophy (RVH) and that ERAs have direct effects on the RV myocardium. RV myocardial samples from 34 patients with RVH were compared with 16 nonhypertrophied RV samples, and from rats with normal RV versus RVH attributable to PAH. Confocal immunohistochemistry showed that RVH myocardial ET type A (but not type B) receptor and ET-1 protein levels were increased compared with the nonhypertrophied RVs and positively correlated with the degree of RVH (RV thickness/body surface area; r(2)=0.838 and r(2)=0.818, respectively; P<0.01). These results were recapitulated in the rat model. In modified Langendorff perfusions, ERAs (BQ-123 and bosentan 10(-7,-6,-5) mol/L) decreased contractility in the hypertrophied, but not normal RV, in a dose-dependent manner (P<0.01). Patients and rats with PAH have an upregulation of the myocardial ET axis in RVH. This might be a compensatory mechanism to preserve RV contractility, as the afterload increases. ERAs use might potentially worsen RV function, and this could explain some of the peripheral edema noted clinically with these agents. Further studies are required to evaluate the effects of ERAs on the RV in patients with RVH and PAH.