Clinical Diagnosis of Pulmonary Hypertension

Rich, Jonathan D.; Rich, Stuart

doi:10.1161/circulationaha.114.006971

Cited by 104 publications

(62 citation statements)

References 66 publications

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“…This contrasts with the etiology of left heart failure patients, which is usually due to intrinsic LV dysfunction rather than LV pressure overload. In contrast, PAH is by definition a pressure overload state 46. A second reason to believe that colchicine might be beneficial in the RV failure associated with PAH is the finding that colchicine reduces adverse pulmonary vascular remodeling (Figure 6) in addition to its direct beneficial effect on RV function through increased JPH2 expression.…”

Section: Discussionmentioning

confidence: 99%

Colchicine Depolymerizes Microtubules, Increases Junctophilin‐2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension

Prins

Tian

et al. 2017

JAHA

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BackgroundPulmonary arterial hypertension (PAH) is a lethal disease characterized by obstructive pulmonary vascular remodeling and right ventricular (RV) dysfunction. Although RV function predicts outcomes in PAH, mechanisms of RV dysfunction are poorly understood, and RV‐targeted therapies are lacking. We hypothesized that in PAH, abnormal microtubular structure in RV cardiomyocytes impairs RV function by reducing junctophilin‐2 (JPH2) expression, resulting in t‐tubule derangements. Conversely, we assessed whether colchicine, a microtubule‐depolymerizing agent, could increase JPH2 expression and enhance RV function in monocrotaline‐induced PAH.Methods and ResultsImmunoblots, confocal microscopy, echocardiography, cardiac catheterization, and treadmill testing were used to examine colchicine's (0.5 mg/kg 3 times/week) effects on pulmonary hemodynamics, RV function, and functional capacity. Rats were treated with saline (n=28) or colchicine (n=24) for 3 weeks, beginning 1 week after monocrotaline (60 mg/kg, subcutaneous). In the monocrotaline RV, but not the left ventricle, microtubule density is increased, and JPH2 expression is reduced, with loss of t‐tubule localization and t‐tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves t‐tubule morphology in RV cardiomyocytes. Colchicine therapy diminishes RV hypertrophy, improves RV function, and enhances RV–pulmonary artery coupling. Colchicine reduces small pulmonary arteriolar thickness and improves pulmonary hemodynamics. Finally, colchicine increases exercise capacity.ConclusionsMonocrotaline‐induced PAH causes RV‐specific derangement of microtubules marked by reduction in JPH2 and t‐tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves both t‐tubule architecture and RV function. Colchicine also reduces adverse pulmonary vascular remodeling. These results provide biological plausibility for a clinical trial to repurpose colchicine as a RV‐directed therapy for PAH.

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Section: Discussionmentioning

confidence: 99%

Colchicine Depolymerizes Microtubules, Increases Junctophilin‐2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension

Prins

Tian

et al. 2017

JAHA

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“…1,2 Growing evidence suggests that pulmonary arterial compliance plays a critical role in the pathogenesis of PAH and right ventricular failure. 3 Decreased pulmonary arterial compliance causes premature reflection of waves from the distal pulmonary vasculature, leading to increased pulsatile right ventricular afterload and altered right ventricular-pulmonary artery (RV-PA) coupling.…”

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confidence: 99%

Pulmonary Pulse Wave Transit Time is Associated with Right Ventricular–Pulmonary Artery Coupling in Pulmonary Arterial Hypertension

et al. 2016

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Pulmonary pulse wave transit time (pPTT), defined as the time for the systolic pressure pulse wave to travel from the pulmonary valve to the pulmonary veins, has been reported to be reduced in pulmonary arterial hypertension (PAH); however, the underlying mechanism of reduced pPTT is unknown. Here, we investigate the hypothesis that abbreviated pPTT in PAH results from impaired right ventricular-pulmonary artery (RV-PA) coupling. We quantified pPTT using pulsed-wave Doppler ultrasound from 10 healthy age-and sexmatched controls and 36 patients with PAH. pPTT was reduced in patients with PAH compared with controls. Univariate analysis revealed the following significant predictors of reduced pPTT: age, right ventricular fractional area change (RV FAC), tricuspid annular plane excursion (TAPSE), pulmonary arterial pressures (PAP), diastolic pulmonary gradient, transpulmonary gradient, pulmonary vascular resistance, and RV-PA coupling (defined as RV FAC/mean PAP or TAPSE/mean PAP). Although the correlations between pPTT and invasive markers of pulmonary vascular disease were modest, RV FAC (r = 0.64, P < 0.0001), TAPSE (r = 0.67, P < 0.0001), and RV-PA coupling (RV FAC/mean PAP: r = 0.72, P < 0.0001; TAPSE/mean PAP: r = 0.74, P < 0.0001) had the strongest relationships with pPTT. On multivariable analysis, only RV FAC, TAPSE, and RV-PA coupling were independent predictors of pPTT. We conclude that shortening of pPTT in patients with PAH results from altered RV-PA coupling, probably occurring as a result of reduced pulmonary arterial compliance. Thus, pPTT allows noninvasive determination of the status of both the pulmonary vasculature and the response of the RV in patients with PAH, thereby allowing monitoring of disease progression and regression.Keywords: pulse wave velocity, right ventricular-pulmonary artery coupling, echocardiography. Pulmonary arterial hypertension (PAH) is a lethal disease, characterized by pathological pulmonary vascular remodeling, that leads to elevated pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR), decreased pulmonary arterial compliance, and eventual right ventricular failure and death.1,2 Growing evidence suggests that pulmonary arterial compliance plays a critical role in the pathogenesis of PAH and right ventricular failure. 3 Decreased pulmonary arterial compliance causes premature reflection of waves from the distal pulmonary vasculature, leading to increased pulsatile right ventricular afterload and altered right ventricular-pulmonary artery (RV-PA) coupling. 3-5 Both loss of pulmonary arterial compliance and impaired RV-PA coupling are clinically important, because they are associated with increased mortality in patients with pulmonary hypertension. 6-11Pulse wave velocity, defined as the velocity of pressure waves traveling through the arterial system, correlates inversely with arterial compliance in the systemic circulation.12 With decreasing compliance, pulse wave velocity increases, and the time taken by the pressure wave to travel between...

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“…This showed that pulmonary hypertension occurs in the smokers by added mechanisms to that caused by COPD. Jugular venous pressure was looked after in this study as raised jugular venous pressure is usually found in patients with pulmonary hypertension and should be looked early for proper evaluation of the patients [14].…”

Section: Discussionmentioning

confidence: 99%

Study the Pulmonary Hypertension among Heavy Smokers Young Adult Males before the Clinical Evidences of Chronic Lung Disease

Naser¹,

Hadi²,

Ibrahim³

et al. 2017

J Clin Exp Cardiolog

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Clinical Diagnosis of Pulmonary Hypertension

Cited by 104 publications

References 66 publications

Colchicine Depolymerizes Microtubules, Increases Junctophilin‐2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension

Colchicine Depolymerizes Microtubules, Increases Junctophilin‐2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension

Pulmonary Pulse Wave Transit Time is Associated with Right Ventricular–Pulmonary Artery Coupling in Pulmonary Arterial Hypertension

Study the Pulmonary Hypertension among Heavy Smokers Young Adult Males before the Clinical Evidences of Chronic Lung Disease

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