Changes in Right Ventricular Structure and Function Assessed Using Cardiac Magnetic Resonance Imaging in Bosentan-Treated Patients With Pulmonary Arterial Hypertension

Chin, Kelly; Kingman, Martha; Lemos, James A. de; Warner, John J.; Reimold, Sharon C.; Peshock, Ronald M; Torres, Fernando

doi:10.1016/j.amjcard.2008.01.055

Cited by 60 publications

(45 citation statements)

References 16 publications

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“…26 In a small single-center study, a trend toward a treatment (bosentan)-related effect on stroke volume index was seen, and there was no effect on RVEF, LVEDV, or RVEDV. 27 This study highlighted the need for further investigation of CMRI variables associated with RV function and how they relate to variables such as 6MWD. It has also been shown previously that epoprostenol therapy lowered pulmonary vascular resistance but did not affect RV dilatation or hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Changes in Right Ventricular Function Measured by Cardiac Magnetic Resonance Imaging in Patients Receiving Pulmonary Arterial Hypertension–Targeted Therapy

Peacock

Crawley

McLure

et al. 2014

Circ: Cardiovascular Imaging

136

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P ulmonary hypertension (PH) is a hemodynamic and pathophysiological state defined as increased mean pulmonary artery pressure ≥25 mm Hg at rest (assessed by right heart catheterization [RHC]).1 PH can be precapillary (pulmonary wedge pressure ≤15 mm Hg, normal or reduced cardiac output) where the changes occur in the pulmonary arterial circulation or postcapillary (pulmonary wedge pressure >15 mm Hg) where the left ventricle (LV) or the mitral valve is likely to be involved. Clinical Perspective on p 114In precapillary PH, increased pressure in the pulmonary arteries overloads the right ventricle (RV), causing hypertrophy and failure. [2][3][4] Most measures that predict survival in PH relate directly to RV function (eg, right atrial pressure and cardiac index) or correlate with measures related to RV function (eg, exercise capacity and functional class [FC]).5-7 Until recently, little was known about the RV; however, improved imaging techniques have allowed prognostic factors beyond the traditional variables of 6-minute walk distance (6MWD) and FC to be studied to identify factors more directly linked to RV function.During the past 2 decades, several treatments targeting the pathophysiological mechanisms of pulmonary arterial hypertension (PAH) have been introduced.

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Section: Discussionmentioning

confidence: 99%

Changes in Right Ventricular Function Measured by Cardiac Magnetic Resonance Imaging in Patients Receiving Pulmonary Arterial Hypertension–Targeted Therapy

Peacock

Crawley

McLure

et al. 2014

Circ: Cardiovascular Imaging

136

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“…Cardiac MRI is a new noninvasive tool being used for the diagnosis, evaluation, and management of cardiac changes associated with PAH and the effects of therapeutic intervention on RV function and indices (van Wolferen et al, 2007;Chin et al, 2008). Changes in stroke volume, right and left ventricular volumes, and RV mass can be measured in response to therapeutic treatments.…”

Section: Discussionmentioning

confidence: 99%

PRX-08066, a Novel 5-Hydroxytryptamine Receptor 2B Antagonist, Reduces Monocrotaline-Induced Pulmonary Arterial Hypertension and Right Ventricular Hypertrophy in Rats

Porvasnik¹,

Germain²,

Embury³

et al. 2010

J Pharmacol Exp Ther

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Pulmonary arterial hypertension (PAH) is a life-threatening disease that results in right ventricular failure. 5- pyrimidin-4-ylamino)piperidin-1-yl)methyl)-2-fluorobenzonitrile monofumarate (PRX-08066) is a selective 5-hydroxytryptamine receptor 2B (5-HT2BR) antagonist that causes selective vasodilation of pulmonary arteries. In the current study, the effects of PRX-08066 were assessed by using the monocrotaline (MCT)-induced PAH rat model. Male rats received 40 mg/kg MCT or phosphate-buffered saline and were treated orally twice a day with vehicle or 50 or 100 mg/kg PRX-08066 for 5 weeks. Pulmonary and cardiac functions were evaluated by hemodynamics, heart weight, magnetic resonance imaging (MRI), pulmonary artery (PA) morphology, and histology. Cardiac MRI demonstrated that PRX-08066 (100 mg/kg) significantly (P Ͻ 0.05) improved right ventricular ejection fraction. PRX-08066 significantly reduced peak PA pressure at 50 and 100 mg/kg (P Ͻ 0.05 and Ͻ 0.01, respectively) compared with MCT control animals. PRX-08066 therapy also significantly reduced right ventricle (RV)/body weight and RV/left ventricle ϩ septum (P Ͻ 0.01 and Ͻ 0.001, respectively) compared with MCT-treated animals. Morphometric assessment of pulmonary arterioles revealed a significant reduction in medial wall thickening and lumen occlusion associated with both doses of PRX-08066 (P Ͻ 0.01). The 5-HT2BR antagonist PRX-08066 significantly attenuated the elevation in PA pressure and RV hypertrophy and maintained cardiac function. Pulmonary vascular remodeling was also diminished compared with MCT control rats. PRX-08066 prevents the severity of PAH in the MCT rat model. Pulmonary arterial hypertension (PAH)is an elevation in pulmonary vascular resistance caused by vasoconstriction and pulmonary vascular remodeling, resulting in increased pulmonary arterial pressure. Idiopathic PAH has no known underlying cause. PAH can also develop as a consequence of coexisting disease, such as chronic obstructive pulmonary disease, hypoxia, portal hypertension, or HIV infection (Archer and Rich, 2000;Li et al., 2006). PAH is usually progressive and invariably fatal. The median survival without treatment in adult patients with PAH was 2.8 years after diagnosis, and in children the median survival was only 10 months (D'Alonzo et al., 1991). Recent advances in PAH therapies, specifically epoprostenoltreated patients, have resulted in the median survival reaching more than 6 years in adults (Barst et al., 1994) and significant improvement in survival for children with reported rates at 1, 5, and 10 years being 94, 81, and 61%, respectively (Yung et al., 2004). Although survival rates have improved with new therapeutic modalities, the prognosis is still poor and development of more effective therapies is clearly needed.Serotonin or 5-hydroxytryptamine (5-HT) was recognized for playing a role in the development of PAH because a relationship between PAH patients and diet pills such as aminorex, dexfenfluramine (DF), and fenfluramine was observed (Kew, 1970; ...

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“…rV function and stroke volume (SV) are of prognostic value in these patients [2,[4][5][6]. SV is generated from different regional contributions of ventricular function; the longitudinal component caused by longitudinal shortening and atrioventricular plane displacement (aVPD) as well as the radial inward motion of the epicardial walls [7].…”

Section: Introductionmentioning

confidence: 99%

Regional contribution to ventricular stroke volume is affected on the left side, but not on the right in patients with pulmonary hypertension

Ostenfeld

Stephensen

Steding‐Ehrenborg

et al. 2016

Int J Cardiovasc Imaging

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59 ± 9 %, p < 0.0001 and p < 0.01, respectively). This decrease did not differ in patient with ejection fraction (eF) >50 % and <50 % (p = 0.5) and was compensated for by increased lV lateral contribution to lVSV in patients (49 ± 13 % vs. 37 ± 7 %, p = 0.001). Septal motion contributed less to lVSV in patients (5 ± 8 %) compared to controls (8 ± 4 %, p = 0.05). rV aVPD was lower in patients (12.0 ± 3.6 mm vs. 21.8 ± 2.2 mm, p < 0.0001) but longitudinal and lateral contribution to rVSV did not differ between patients (78 ± 17 % and 29 ± 16 %) and controls (79 ± 9 % and 31 ± 6 % p = 0.7 for both) explained by increased rV cross sectional area in patients. lV function is affected in patients with PH despite preserved global lV function. The decreased longitudinal contribution and increased lateral contribution to lVSV was not seen in the rV, contrary to previous findings in patients with volume loaded RVs. Abstract To develop more sensitive measures of impaired cardiac function in patients with pulmonary hypertension (PH), since detection of impaired right ventricular (rV) function is important in these patients. With the hypothesis that a change in septal function in patients with PH is associated with altered longitudinal and lateral function of both ventricles, as a compensatory mechanism, we quantified the contributions of these parameters to stroke volume (SV) in both ventricles using cardiac magnetic resonance (CMr). Seventeen patients (10 females) evaluated for PH underwent right heart catheterization (rHC) and CMr. CMr from 33 healthy adults (13 females) were used as controls. left ventricular (lV) atrioventricular plane displacement (aVPD) and corresponding longitudinal contribution to lVSV was lower in patients (10.8 ± 3.2 mm and 51 ± 12 %) compared to controls (16.6 ± 1.9 mm and 1 3 1244 int J Cardiovasc imaging (2016) 32:1243-1253 trols. The control group has been described in a previous study [11]. The regional ethical review board approved the study and written informed consent was obtained from all patients and healthy volunteers prior to CMr examination. Keywords Right heart catheterizationinvasive measurements were obtained during rHC with a triple-lumen Swan-ganz catheter in supine position and in local anesthesia. Pressures of pulmonary artery (PaP), right atrium, right ventricle and pulmonary artery wedge as well as cardiac output using thermodilution were measured. Precapillary PH was characterized by elevated mean pulmonary arterial pressure (mPaP) ≥25 mmHg and pulmonary artery wedge pressure ≤15 mmHg at normal or reduced cardiac output. Systemic pressure was available using a cuff and sphygmomanometer. Cardiac magnetic resonance imagingImage acquisition all subjects underwent CMr imaging in the supine position and images were acquired during end-expiratory breath-hold covering the entire heart, including both ventricles and atria. a 1.5 Tesla magnetic resonance imaging scanner was used for all studies (Philips achieva, Best, The netherlands). Steady state free precession cine images were ...

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Changes in Right Ventricular Structure and Function Assessed Using Cardiac Magnetic Resonance Imaging in Bosentan-Treated Patients With Pulmonary Arterial Hypertension

Cited by 60 publications

References 16 publications

Changes in Right Ventricular Function Measured by Cardiac Magnetic Resonance Imaging in Patients Receiving Pulmonary Arterial Hypertension–Targeted Therapy

Changes in Right Ventricular Function Measured by Cardiac Magnetic Resonance Imaging in Patients Receiving Pulmonary Arterial Hypertension–Targeted Therapy

PRX-08066, a Novel 5-Hydroxytryptamine Receptor 2B Antagonist, Reduces Monocrotaline-Induced Pulmonary Arterial Hypertension and Right Ventricular Hypertrophy in Rats

Regional contribution to ventricular stroke volume is affected on the left side, but not on the right in patients with pulmonary hypertension

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