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Vascular Pharmacology Aug 2023Pulmonary arterial hypertension (PAH) is a rare cardiopulmonary disorder, involving the remodelling of the small pulmonary arteries. Underlying this remodelling is the...
Pulmonary arterial hypertension (PAH) is a rare cardiopulmonary disorder, involving the remodelling of the small pulmonary arteries. Underlying this remodelling is the hyper-proliferation of pulmonary arterial smooth muscle cells within the medial layers of these arteries and their encroachment on the lumen. Previous studies have demonstrated an association between excessive mitochondrial fragmentation, a consequence of increased expression and post-translational activation of the mitochondrial fission protein dynamin-related protein 1 (DRP1), and pathological proliferation in PASMCs derived from PAH patients. However, the impact of prostacyclin mimetics, widely used in the treatment of PAH, on this pathological mitochondrial fragmentation remains unexplored. We hypothesise that these agents, which are known to attenuate the proliferative phenotype of PAH PASMCs, do so in part by inhibiting mitochondrial fragmentation. In this study, we confirmed the previously reported increase in DRP1-mediated mitochondrial hyper-fragmentation in PAH PASMCs. We then showed that the prostacyclin mimetic treprostinil signals via either the Gs-coupled IP or EP receptor to inhibit mitochondrial fragmentation and the associated hyper-proliferation in a manner analogous to the DRP1 inhibitor Mdivi-1. We also showed that treprostinil recruits either the IP or EP receptor to activate PKA and induce the phosphorylation of DRP1 at the inhibitory residue S637 and inhibit that at the stimulatory residue S616, both of which are suggestive of reduced DRP1 fission activity. Like treprostinil, MRE-269, an IP receptor agonist, and butaprost, an EP receptor agonist, attenuated DRP1-mediated mitochondrial fragmentation through PKA. We conclude that prostacyclin mimetics produce their anti-proliferative effects on PAH PASMCs in part by inhibiting DRP1-mediated mitochondrial fragmentation.
Topics: Humans; Pulmonary Arterial Hypertension; Cell Proliferation; Dynamins; Pulmonary Artery; Mitochondrial Dynamics
PubMed: 37442283
DOI: 10.1016/j.vph.2023.107194 -
Current Problems in Cardiology Apr 2024The right ventricular (RV) function correlates with prognosis in severe pulmonary artery hypertension (PAH) but which metric of it is most clinically relevant is still... (Review)
Review
The right ventricular (RV) function correlates with prognosis in severe pulmonary artery hypertension (PAH) but which metric of it is most clinically relevant is still uncertain. Clinical methods to estimate RV function from simplified pressure volume loops correlate with disease severity but the clinical relevance has not been assessed. Evaluation of right ventricle pulmonary artery coupling in pulmonary hypertensive patients may help to elucidate the mechanisms of right ventricular failure and may also help to identify patients at risk or guide the timing of therapeutic interventions in pulmonary hypertension. Complete evaluation of RV failure requires echocardiographic or magnetic resonance imaging, and right heart catheterization measurements. Treatment of RV failure in PAH relies on decreasing afterload with drugs targeting pulmonary circulation; fluid management to optimize ventricular diastolic interactions; and inotropic interventions to reverse cardiogenic shock. The ability to relate quantitative metrics of RV function in pulmonary artery hypertension to clinical outcomes can provide a powerful tool for management. Such metrics could also be utilized in the future as surrogate endpoints for outcomes and evaluation of response to therapies. This review of literature gives an insight on RV-PA coupling associated with PAH, its types of measurement and pharmacological treatment.
Topics: Humans; Pulmonary Artery; Heart Ventricles; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Heart Failure
PubMed: 38311275
DOI: 10.1016/j.cpcardiol.2024.102425 -
European Radiology Nov 2023To evaluate the image quality of an ultra-low contrast medium and radiation dose CT pulmonary angiography (CTPA) protocol for the diagnosis of acute pulmonary embolism...
OBJECTIVE
To evaluate the image quality of an ultra-low contrast medium and radiation dose CT pulmonary angiography (CTPA) protocol for the diagnosis of acute pulmonary embolism using a clinical photon-counting detector (PCD) CT system and compare its performance to a dual-energy-(DE)-CTPA protocol on a conventional energy-integrating detector (EID) CT system.
METHODS
Sixty-four patients either underwent CTPA with the novel scan protocol on the PCD-CT scanner (32 patients, 25 mL, CTDI 2.5 mGy·cm) or conventional DE-CTPA on a third-generation dual-source EID-CT (32 patients, 50 mL, CTDI 5.1 mGy·cm). Pulmonary artery CT attenuation, signal-to-noise ratio, and contrast-to-noise-ratio were assessed as objective criteria of image quality, while subjective ratings of four radiologists were compared at 60 keV using virtual monoenergetic imaging and polychromatic standard reconstructions. Interrater reliability was determined by means of the intraclass correlation coefficient (ICC). Effective dose was compared between patient cohorts.
RESULTS
Subjective image quality was deemed superior by all four reviewers for 60-keV PCD scans (excellent or good ratings in 93.8% of PCD vs. 84.4% of 60 keV EID scans, ICC = 0.72). No examinations on either system were considered "non-diagnostic." Objective image quality parameters were significantly higher in the EID group (mostly p < 0.001), both in the polychromatic reconstructions and at 60 keV. The ED (1.4 vs. 3.3 mSv) was significantly lower in the PCD cohort (p < 0.001).
CONCLUSIONS
PCD-CTPA allows for considerable reduction of contrast medium and radiation dose in the diagnosis of acute pulmonary embolism, while maintaining good to excellent image quality compared to conventional EID-CTPA.
CLINICAL RELEVANCE STATEMENT
Clinical PCD-CT allows for spectral assessment of pulmonary vasculature with high scan speed, which is beneficial in patients with suspected pulmonary embolism, frequently presenting with dyspnea. Simultaneously PCD-CT enables substantial reduction of contrast medium and radiation dose.
KEY POINTS
• The clinical photon-counting detector CT scanner used in this study allows for high-pitch multi-energy acquisitions. • Photon-counting computed tomography allows for considerable reduction of contrast medium and radiation dose in the diagnosis of acute pulmonary embolism. • Subjective image quality was rated best for 60-keV photon-counting scans.
Topics: Humans; Reproducibility of Results; Drug Tapering; Tomography, X-Ray Computed; Pulmonary Embolism; Pulmonary Artery; Photons; Phantoms, Imaging
PubMed: 37311805
DOI: 10.1007/s00330-023-09777-9 -
Journal of the American College of... Sep 2023We have followed a consistent, albeit evolving, strategy for the management of patients with pulmonary atresia or severe stenosis and major aortopulmonary collateral...
BACKGROUND
We have followed a consistent, albeit evolving, strategy for the management of patients with pulmonary atresia or severe stenosis and major aortopulmonary collateral arteries (MAPCAs) that aims to achieve complete repair with low right ventricular pressure by completely incorporating blood supply and relieving stenoses to all lung segments.
OBJECTIVES
The purpose of this study was to characterize our 20-year institutional experience managing patients with MAPCAs.
METHODS
We reviewed all patients who underwent surgery for MAPCAs and biventricular heart disease from November 2001 through December 2021.
RESULTS
During the study period, 780 unique patients underwent surgery. The number of new patients undergoing surgery annually was relatively steady during the first 15 years, then increased substantially thereafter. Surgery before referral had been performed in almost 40% of patients, more often in our recent experience than earlier. Complete repair was achieved in 704 patients (90%), 521 (67%) during the first surgery at our center, with a median right ventricular to aortic pressure ratio of 0.34 (25th, 75th percentiles: 0.28, 0.40). The cumulative incidence of mortality was 15% (95% CI: 12%-19%) at 10 years, with no difference according to era of surgery (P = 0.53). On multivariable Cox regression, Alagille syndrome (HR: 2.8; 95% CI: 1.4-5.7; P = 0.004), preoperative respiratory support (HR: 2.0; 95% CI: 1.2-3.3; P = 0.008), and palliative first surgery at our center (HR: 3.5; 95% CI: 2.3-5.4; P < 0.001) were associated with higher risk of death.
CONCLUSIONS
In a growing pulmonary artery reconstruction program, with increasing volumes and an expanding population of patients who underwent prior surgery, outcomes of patients with pulmonary atresia or stenosis and MAPCAs have continued to improve.
Topics: Humans; Aorta; Constriction, Pathologic; Heart Defects, Congenital; Pulmonary Artery; Pulmonary Atresia
PubMed: 37704311
DOI: 10.1016/j.jacc.2023.06.041 -
Pediatric Radiology Dec 2023Four-dimensional flow (4D flow) MRI has become a clinically utilized cardiovascular flow assessment tool. However, scans can be lengthy and may require anesthesia in...
Highly accelerated compressed sensing 4D flow MRI in congenital and acquired heart disease: comparison of aorta and main pulmonary artery flow parameters with conventional 4D flow MRI in children and young adults.
BACKGROUND
Four-dimensional flow (4D flow) MRI has become a clinically utilized cardiovascular flow assessment tool. However, scans can be lengthy and may require anesthesia in younger children. Adding compressed sensing can decrease scan time, but its impact on hemodynamic data accuracy needs additional assessment.
OBJECTIVE
To compare 4D flow hemodynamics acquired with and without compressed sensing.
MATERIALS AND METHODS
Twenty-seven patients (median age: 13 [IQR: 9.5] years) underwent conventional and compressed sensing cardiovascular 4D flow following informed consent. Conventional 4D flow was performed using parallel imaging and an acceleration factor of 2. Compressed sensing 4D flow was performed with an acceleration factor of 7.7. Regions of interest were placed to compare flow parameters in the ascending aorta and main pulmonary artery. Paired Student's t-tests, Wilcoxon signed-rank tests, Bland-Altman plots, and intraclass correlation coefficients were conducted. A P-value of < 0.05 was considered statistically significant.
RESULTS
Mean scan acquisition time was reduced by 59% using compressed sensing (3.4 vs. 8.2 min, P < 0.001). Flow quantification was similar for compressed sensing and conventional 4D flow for the ascending aorta net flow: 47 vs. 49 ml/beat (P = 0.28); forward flow: 49 vs. 50 ml/beat (P = 0.07), and main pulmonary artery net flow: 49 vs. 51 ml/beat (P = 0.18); forward flow: 50 vs. 55 ml/beat (P = 0.07). Peak systolic velocity was significantly underestimated by compressed sensing 4D flow in the ascending aorta: 114 vs. 128 cm/s (P < 0.001) and main pulmonary artery: 106 vs. 112 cm/s (P = 0.02).
CONCLUSION
For both the aorta and main pulmonary artery, compressed sensing 4D flow provided equivalent net and forward flow values compared to conventional 4D flow but underestimated peak systolic velocity. By reducing scan time, compressed sensing 4D flow may decrease the need for anesthesia and increase scanner output without significantly compromising data integrity.
Topics: Humans; Child; Young Adult; Adolescent; Pulmonary Artery; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Aorta; Heart Diseases; Blood Flow Velocity; Reproducibility of Results
PubMed: 37882844
DOI: 10.1007/s00247-023-05788-2 -
The Journal of Heart and Lung... Aug 2023The differential treatment effect of pulmonary artery denervation (PADN) in pulmonary arterial hypertension (PAH) patients with different risk burdens remains unclear.... (Clinical Trial)
Clinical Trial
BACKGROUND
The differential treatment effect of pulmonary artery denervation (PADN) in pulmonary arterial hypertension (PAH) patients with different risk burdens remains unclear. This study aimed to determine the effectiveness of PADN in low vs intermediate-high-risk PAH patients.
METHODS
In total, 128 patients with treatment naive PAH included in the PADN-CFDA trial were categorized into low-risk and intermediate-high-risk patients. The primary endpoint was the between-group difference in the change in 6-min walk distance (6 MWD) from baseline to 6 months.
RESULTS
In the intermediate-high-risk group, those treated with PADN and PDE-5i had a greater improvement in 6 MWD from baseline to 6 months as compared to those treated with sham plus PDE-5i. From baseline to 6 months, pulmonary vascular resistance (PVR) was reduced by -6.1 ± 0.6 and -2.0 ± 0.7 Wood units following PADN plus PDE-5i and sham plus PDE-5i, respectively, along with the significant reduction of NT-proBNP in the intermediate-high-risk group. However, there were no significant differences in 6 MWD, PVR, and NT-proBNP between the PADN plus PDE-5i and sham plus PDE-5i groups among low-risk patients. Moreover, the right ventricular function was equally improved by PADN treatment across the low-, intermediate-, and high-risk groups. Clinical worsening was less with PADN plus PDE-5i treatment during the 6-month follow-up.
CONCLUSIONS
In patients with pulmonary arterial hypertension, pulmonary artery denervation plus PDE-5i improved exercise capacity, NT-proBNP, hemodynamic, and clinical outcomes during the 6-month follow-up among intermediate-high risk patients.
Topics: Humans; Denervation; Familial Primary Pulmonary Hypertension; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Pulmonary Artery; Risk Factors
PubMed: 36990173
DOI: 10.1016/j.healun.2023.03.015 -
International Journal of Cardiology Aug 2023In terms of pathophysiology, tricuspid regurgitation (TR), right ventricular function and pulmonary artery pressure are linked to each other. Our aim was to analyze...
Ratio between right ventricular longitudinal strain and pulmonary arterial systolic pressure: A novel prognostic parameter in patients with severe tricuspid regurgitation.
BACKGROUND
In terms of pathophysiology, tricuspid regurgitation (TR), right ventricular function and pulmonary artery pressure are linked to each other. Our aim was to analyze whether the echocardiography-derived right ventricular free wall longitudinal strain/pulmonary artery systolic pressures (RVFWLS/PASP) ratio can improve risk stratification in patients with severe tricuspid regurgitation (TR).
METHODS
In this single-center retrospective study, 250 consecutive patients with severe TR were enrolled from December 2015 to December 2018. Baseline clinical and echocardiographic parameters were collected. Echocardiography-derived TAPSE/PASP and RVFWLS/PASP were evaluated. The primary endpoint was all-cause mortality.
RESULTS
Out of 250 consecutive patients, 171 meet inclusion criteria. Patients were predominantly female, with several cardiovascular risk factors and comorbidities. RVFWLS/PASP ≤0.34%/mmHg (AUC 0.68, p < 0.001, sensitivity 70%, specificity 67%) was associated with baseline clinical RV heart failure (p = 0.03). After univariate and multivariate analyses, RVFWLS/PASP, but not TAPSE/PASP, independently correlated with all-cause mortality (HR 0.004, p = 0.02). Patients with RVFWLS/PASP >0.26%/mmHg (AUC 0.74, p < 0.001, sensitivity 77%, specificity 52%) showed higher survival rates (p = 0.02). In addition at 24 months follow-up, the Kaplan-Meyer curves showed patients with RVFWLS >14% & RVFWLS/PASP >0.26%/mmHg had the best survival rate compared to patients without.
CONCLUSION
RVFWLS/PASP is independently associated with baseline RV heart failure and poor long-term prognosis in patients with severe TR.
Topics: Humans; Female; Male; Prognosis; Tricuspid Valve Insufficiency; Blood Pressure; Echocardiography, Doppler; Hypertension, Pulmonary; Retrospective Studies; Heart Failure; Ventricular Function, Right; Ventricular Dysfunction, Right; Pulmonary Artery
PubMed: 37149007
DOI: 10.1016/j.ijcard.2023.04.056 -
Journal of the American Heart... Jan 2024Pulmonary hypertension (PH) is highly prevalent in patients with heart failure with preserved ejection fraction (HFpEF), and it is a strong predictor of adverse...
BACKGROUND
Pulmonary hypertension (PH) is highly prevalent in patients with heart failure with preserved ejection fraction (HFpEF), and it is a strong predictor of adverse outcomes. We aimed to determine possible echocardiographic parameters to predict the presence of PH in patients with HFpEF.
METHODS AND RESULTS
A total of 113 patients with HFpEF were prospectively enrolled from November 2017 to July 2022. The patients underwent invasive cardiac catheterization and simultaneous echocardiography at rest and during exercise. The parameters indicating right ventricle-pulmonary artery uncoupling, including tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) and tricuspid annular systolic velocity (TAS')/PASP were calculated. Receiver operating characteristic curve analysis was used to determine the optimal cut-off points of TAPSE/PASP and TAS'/PASP to differentiate patients with HFpEF with PH from those without PH. Sixty-eight patients with HFpEF with PH and 45 without PH were included. Those with PH had lower TAPSE/PASP and TAS'/PASP at rest and during exercise compared with those without PH. Both resting/stress TAPSE/PASP and TAS'/PASP were correlated with rest/exercise pulmonary capillary wedge pressure and mean pulmonary artery pressure. In multivariable regression analysis, TAPSE/PASP remained a significant predictor of exercise pulmonary capillary wedge pressure and mean pulmonary artery pressure. In receiver operating characteristic curve analysis, the optimal cut-off points of TAPSE/PASP and TAS'/PASP to differentiate patients with HFpEF with PH from those without PH were ≤0.62 and ≤0.47, respectively.
CONCLUSIONS
Right ventricle-pulmonary artery uncoupling is closely correlated with abnormal rest/exercise hemodynamics (pulmonary capillary wedge pressure and mean pulmonary artery pressure) in patients with HFpEF. TAPSE/PASP and TAS'/PASP can be useful parameters to detect PH in patients with HFpEF.
Topics: Humans; Hypertension, Pulmonary; Stroke Volume; Heart Failure; Heart Ventricles; Echocardiography, Doppler; Pulmonary Artery; Ventricular Function, Right; Ventricular Dysfunction, Right
PubMed: 38156457
DOI: 10.1161/JAHA.123.030025 -
ESC Heart Failure Apr 2024Pulmonary artery hypertension (PAH) is a chronic vascular disease defined by the elevation of pulmonary vascular resistance and mean pulmonary artery pressure, which... (Review)
Review
Pulmonary artery hypertension (PAH) is a chronic vascular disease defined by the elevation of pulmonary vascular resistance and mean pulmonary artery pressure, which arises due to pulmonary vascular remodelling. Prior research has already established a link between the autonomic nervous system (ANS) and PAH. Therefore, the rebalancing of the ANS offers a promising approach for the treatment of PAH. The process of rebalancing involves two key aspects: inhibiting an overactive sympathetic nervous system and fortifying the impaired parasympathetic nervous system through pharmacological or interventional procedures. However, the understanding of the precise mechanisms involved in neuromodulation, whether achieved through medication or intervention, remains insufficient. This limited understanding hinders our ability to determine the appropriate timing and scope of such treatment. This review aims to integrate the findings from clinical and mechanistic studies on ANS rebalancing as a treatment approach for PAH, with the ultimate goal of identifying a path to enhance the safety and efficacy of neuromodulation therapy and improve the prognosis of PAH.
Topics: Humans; Hypertension, Pulmonary; Pulmonary Artery; Autonomic Nervous System; Sympathetic Nervous System; Pulmonary Arterial Hypertension
PubMed: 38108098
DOI: 10.1002/ehf2.14616 -
Journal of the American College of... Dec 2023
Topics: Humans; Blood Pressure; Pulmonary Artery; Echocardiography; Blood Pressure Determination; Cardiac Catheterization
PubMed: 38030348
DOI: 10.1016/j.jacc.2023.10.006