Diagnosis of right ventricular myocardial fibrosis using right ventricular myocardial CT attenuation, wall thickness and motion on ECG-gated 320 slice CT in subjects with pulmonary hypertension

Right ventricular (RV) diastolic stiffness is increased in pulmonary arterial hypertension (PAH) patients. We investigated whether RV diastolic stiffness is associated with clinical progression and assessed the contribution of RV wall thickness to RV systolic and diastolic stiffness.Using single-beat pressure–volume analyses, we determined RV end-systolic elastance (Ees), arterial elastance (Ea), RV–arterial coupling (Ees/Ea), and RV end-diastolic elastance (stiffness, Eed) in controls (n=15), baseline PAH patients (n=63) and treated PAH patients (survival >5 years n=22 and survival <5 years n=23).We observed an association between Eed and clinical progression, with baseline Eed >0.53 mmHg·mL-1 associated with worse prognosis (age-corrected hazard ratio 0.27, p=0.02). In treated patients, Eed was higher in patients with survival <5 years than in patients with survival >5 years (0.91±0.50 versus 0.53±0.33 mmHg·mL-1, p<0.01). Wall-thickness-corrected Eed values in PAH patients with survival >5 years were not different from control values (0.76±0.47 versus 0.60±0.41 mmHg·mL-1, respectively, not significant), whereas in patients with survival <5 years, values were significantly higher (1.52±0.91 mmHg·mL-1, p<0.05 versus controls).RV diastolic stiffness is related to clinical progression in both baseline and treated PAH patients. RV diastolic stiffness is explained by the increased wall thickness in patients with >5 years survival, but not in those surviving <5 years. This suggests that intrinsic myocardial changes play a distinctive role in explaining RV diastolic stiffness at different stages of PAH.

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An antifibrotic agent reduces blood pressure in established pulmonary hypertension in the rat

Journal of Applied Physiology ◽

10.1152/jappl.1990.68.4.1542 ◽

1990 ◽

Vol 68 (4) ◽

pp. 1542-1547 ◽

Cited By ~ 21

Author(s):

G. J. Poiani ◽

C. A. Tozzi ◽

J. K. Choe ◽

S. E. Yohn ◽

D. J. Riley

Keyword(s):

Blood Pressure ◽

Pulmonary Hypertension ◽

Right Ventricular ◽

Rheological Properties ◽

Wall Thickness ◽

Pulmonary Arteries ◽

Collagen Content ◽

Ventricular Pressure ◽

Hydroxyproline Content ◽

Collagen Accumulation

We have shown that administration of the antifibrotic agent cis-4-hydroxy-L-proline (cHyp) to rats at the onset of exposure to hypoxia prevents collagen accumulation in pulmonary arteries and the rise in pulmonary blood pressure. In this experiment, we tested whether cHyp is effective when administered after hypertension was already established. Rats were exposed to hypoxia (10% O2) for 21 days. Groups were hypoxic animals treated with cHyp (200 mg/kg sc twice daily) on days 10-21 (hypoxic cHyp) and saline-injected hypoxic animals (hypoxic). On day 21, we measured mean right ventricular pressure, hematocrit, collagen content of main and intrapulmonary arteries, and wall thickness of arterioles. Treatment reduced right ventricular pressure from 21 +/- 1 to 17 +/- 1 mmHg (P less than 0.05), hematocrit from 66 +/- 1 to 56 +/- 1% (P less than 0.05), hydroxyproline content of intrapulmonary arteries from 30 +/- 3 to 11 +/- 2 micrograms/vessel (P less than 0.05), and wall thickness from 27 +/- 3 to 16 +/- 2 microns (P less than 0.05). These results show that vascular collagen content is increased in established pulmonary hypertension and that cHyp treatment is effective in partially preventing the hemodynamic, structural, and biochemical changes if started after pulmonary hypertension is established. cHyp may also affect the rheological properties of blood.

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Ventilatory dysfunction precedes pulmonary vascular changes in monocrotaline-treated rats

Journal of Applied Physiology ◽

10.1152/jappl.1991.70.2.561 ◽

1991 ◽

Vol 70 (2) ◽

pp. 561-566 ◽

Cited By ~ 21

Author(s):

Y. L. Lai ◽

J. W. Olson ◽

M. N. Gillespie

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Wall Thickness ◽

Ventricular Hypertrophy ◽

Right Ventricular Hypertrophy ◽

Functional Study ◽

Pulmonary Vasculature ◽

Pulmonary Vascular Disease ◽

Alveolar Wall ◽

Lung Dysfunction

Rats with established monocrotaline (MCT)-induced pulmonary hypertension also exhibit a profound increase in lung resistance (RL) and a decrease in lung compliance. Because airway/lung dysfunction could precede and influence the evolution of MCT-induced pulmonary vascular disease, it is important to establish the temporal relationship between development of pulmonary hypertension and altered ventilatory function in MCT-treated rats. To resolve this issue, we segregated 47 young Sprague-Dawley rats into four groups: control (n = 13), MCT1 (n = 9), MCT2 (n = 11), and MCT3 (n = 14). Each MCT rat received a single subcutaneous injection of MCT (60 mg/kg) 1 MCT1), 2 (MCT2), or 3 (MCT3) wk before the functional study. At 1 wk after MCT, significant increases in RL and alveolar wall thickness were observed, as was a significant decrease in carbon monoxide diffusing capacity (DLCO). Medial thickness of pulmonary arteries (50-100 microns OD) and right ventricular hypertrophy were not observed until 2 and 3 wk post-MCT, respectively. Coincident with the right ventricular hypertrophy at 3 wk post-MCT were decreased DLCO and increased alveolar wall thickness and lung dry weight. Pressure-volume curves of air-filled and saline-filled lungs showed marked rightward shifts during the 1st and 2nd wk after MCT administration and then decreased at the 3rd wk. These data suggest that MCT-induced alterations in airway/lung function preceded those of pulmonary vasculature and, therefore, implicate airway/lung dysfunctions as potentially contributing to the later development of pulmonary vascular abnormalities.

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Echocardiographic markers of pulmonary hemodynamics and right ventricular hypertrophy in rat models of pulmonary hypertension The first two authors contributed equally to this manuscript.

Pulmonary Circulation ◽

10.1177/2045894020910976 ◽

2020 ◽

Vol 10 (2) ◽

pp. 204589402091097

Author(s):

Fotios Spyropoulos ◽

Sally H. Vitali ◽

Marlin Touma ◽

Chase D. Rose ◽

Carter R. Petty ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Wall Thickness ◽

Ventricular Wall ◽

Right Ventricular Systolic Pressure ◽

Acceleration Time ◽

Non Invasive ◽

Right Ventricular Wall ◽

Ventricular Wall Thickness ◽

Pulmonary Arterial

Echocardiography is the gold standard non-invasive technique to diagnose pulmonary hypertension. It is also an important modality used to monitor disease progression and response to treatment in patients with pulmonary hypertension. Surprisingly, only few studies have been conducted to validate and standardize echocardiographic parameters in experimental animal models of pulmonary hypertension. We sought to define cut-off values for both invasive and non-invasive measures of pulmonary hemodynamics and right ventricular hypertrophy that would reliably diagnose pulmonary hypertension in three different rat models. The study was designed in two phases: (1) a derivation phase to establish the cut-off values for invasive measures of right ventricular systolic pressure, Fulton's index (right ventricular weight/left ventricle + septum weight), right ventricular to body weight ratio, and non-invasive echocardiographic measures of pulmonary arterial acceleration time, pulmonary arterial acceleration time to ejection time ratio and right ventricular wall thickness in diastole in the hypoxic and monocrotaline rat models of pulmonary hypertension and (2) a validation phase to test the performance of the cut-off values in predicting pulmonary hypertension in an independent cohort of rats with Sugen/hypoxia-induced pulmonary hypertension. Our study demonstrates that right ventricular systolic pressure ≥35.5 mmHg and Fulton's Index ≥0.34 are highly sensitive (>94%) and specific (>91%) cut-offs to distinguish animals with pulmonary hypertension from controls. When pulmonary arterial acceleration time/ejection time and right ventricular wall thickness in diastole were both measured, a result of either pulmonary arterial acceleration time/ejection time ≤0.25 or right ventricular wall thickness in diastole ≥1.03 mm detected right ventricular systolic pressure ≥35.5 mmHg or Fulton's Index ≥0.34 with a sensitivity of 88% and specificity of 100%. With properly validated non-invasive echocardiography measures of right ventricular performance in rats that accurately predict invasive measures of pulmonary hemodynamics, future studies can now utilize these markers to test the efficacy of different treatments with preclinical therapeutic modeling.

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Right ventricular relative wall thickness as a predictor of outcomes and of right ventricular reverse remodeling for patients with pulmonary hypertension

The International Journal of Cardiovascular Imaging ◽

10.1007/s10554-016-1004-z ◽

2016 ◽

Vol 33 (3) ◽

pp. 313-321 ◽

Cited By ~ 3

Author(s):

Hiroyuki Sano ◽

Hidekazu Tanaka ◽

Yoshiki Motoji ◽

Yuko Fukuda ◽

Yasuhide Mochizuki ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Wall Thickness ◽

Relative Wall Thickness ◽

Reverse Remodeling

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Efficacy of shear wave elastography for evaluating right ventricular myocardial fibrosis in monocrotaline-induced pulmonary hypertension rats

Journal of Cardiology ◽

10.1016/j.jjcc.2021.01.015 ◽

2021 ◽

Author(s):

Rie Nakayama ◽

Yoichi Takaya ◽

Kazufumi Nakamura ◽

Megumi Kondo ◽

Kaoru Kobayashi ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Shear Wave ◽

Myocardial Fibrosis ◽

Shear Wave Elastography

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Abstract 13077: Higher Occurrence of Right Ventricular Fibrosis in Right Ventricular Outflow Tract-dominant Than Diffuse Hypertrophic Types: A Pulmonary Hypertension Study Using Cardiac Computed Tomography

Circulation ◽

10.1161/circ.142.suppl_3.13077 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Nobusada FUNABASHI ◽

Koya Ozawa ◽

Yoshio Kobayashi

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Wall Thickness ◽

Cardiac Computed Tomography ◽

Systolic Pressure ◽

Right Ventricular Outflow Tract ◽

Outflow Tract ◽

Clinical Severity ◽

Positive Correlations

Introduction: On cardiac CT of pulmonary hypertension (PH), two right ventricular (RV) hypertrophic (RVH) morphological types are seen, namely RV outflow tract-dominant and RV-diffuse. However, clinical significance of this difference is unclear. Hypothesis: These two morphological RVH types have different effects on myocardial characteristics, clinical severity and prognosis in PH patients. Methods: We retrospectively analyzed 43 PH patients (33 females, 55±15yrs, 31 chronic thromboembolic PH (CTEPH), 7 idiopathic pulmonary arterial (PA) hypertension). On CT, RV fibrosis was defined as contrast defects in early phase and abnormal enhancement in late phase. Cases were divided into 3 groups: RV outflow tract-dominant RVH (gp 1), RVH-diffuse (gp 2), and no RVH (gp 3). Mean follow up was 39.3±20.1, 58.3±17.7, 68.2±11.9 months, respectively. Results: There were 6, 26, 11 patients in gps 1, 2, 3, respectively. There were no significant differences in these percentages between CTEPH and idiopathic PA hypertension or between ages ≥60 and <60 yrs. There were no significant differences of R/S wave ratio on ECG V1 lead, maximum RV wall thickness on end-diastole (CT), plasma BNP and estimated PA systolic pressure (PASP) on TTE between gps 1 and 2. There were significant positive correlations between maximum RV wall thickness in end-diastole and plasma BNP in gp 1 (R=0.44) but no correlations in gp 2 (R=0.05). Similarly, there were significant positive correlations between maximum RV wall thickness in end-diastole and estimated PASP in gp 1 (R=0.38) but no correlations in gp 2 (R= -0.08). RV fibrosis was detected in 3 patients (50%) (gp1) and 1 patient (4%) (gp2) (P=0.003). Zero, 2, and 1 patients died due to PH during follow-up periods in gps 1, 2, 3 , respectively, and there were no significant differences in these percentages on Kaplan Meier analysis and log rank testing. Interobserver agreement between two observers was 91% in gp 1 and 77% in both gps 2 and 3. Conclusions: In PH patients, RV outflow tract-dominant RVH was relatively easy to diagnose and manifested with greater occurrence of RV fibrosis than diffuse-type. RV outflow tract-dominant RVH showed significant positive correlations of maximum RV wall thickness in end-diastole with plasma BNP and estimated PASP.

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