J Med Imaging Radiat Oncol. 2019 Apr 25. doi: 10.1111/1754-9485.12893. [Epub ahead of print]

Turbulent flow artefact mimicking central pulmonary emboli in pulmonary hypertension: A report of two cases.

Pascoe HM¹, Pascoe D^1,2, McCusker MW^1,2, Heinze SB^1,2.

Author information:

1. Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
2. University of Melbourne, Melbourne, Victoria, Australia.

Abstract

Many artefacts can mimic pulmonary emboli (PE) on CT pulmonary angiography (CTPA), most commonly in the peripheral pulmonary arteries (PA’s). We describe flow-related artefact mimicking PE in the central PA’s of two patients, both with pulmonary arterial hypertension (PAH). To our knowledge, this is the first report of this PE mimic in the central PA’s.

© 2019 The Royal Australian and New Zealand College of Radiologists.

PMID: 31021530

J Card Surg. 2019 Apr 24. doi: 10.1111/jocs.14052. [Epub ahead of print]

Extracorporeal membrane oxygenation after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.

Sugiyama K¹, Suzuki S², Fujiyoshi T², Koizumi N², Sato M², Ogino H².

Author information:

1. Department of Cardiac Surgery, Aichi Medical University, Nagakute, Aichi, Japan.
2. Department of Cardiovascular Surgery, Tokyo Medical University, Tokyo, Japan.

Abstract

BACKGROUND:
Pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH) but can result in respiratory and cardiac complications that may require extracorporeal membrane oxygenation (ECMO). We reviewed our experience with ECMO in patients undergoing PEA.

METHODS AND RESULTS:
Between January 2012 and August 2015, 35 patients underwent PEA for CTEPH. In all, four patients (11%) required veno-arterial (V-A) ECMO support due to severe cardiac and respiratory failure, including severe reperfusion pulmonary edema and persistent pulmonary hypertension. No significant differences in preoperative characteristics were found between patients who required ECMO and those who did not require ECMO. ECMO support was associated with a significantly higher incidence of postoperative respiratory complications, a longer intensive care unit stay, increased in-hospital mortality, residual pulmonary hypertension, and postoperative balloon pulmonary angioplasty (BPA). The postoperative mean pulmonary artery pressure and pulmonary vascular resistance were significantly higher in patients requiring ECMO. All patients requiring ECMO were successfully weaned off ECMO support (100%), and three of them were discharged from the hospital alive (75%).

CONCLUSIONS:
Patients with CTEPH may benefit from ECMO after PEA for cardiac and respiratory complications. A prompt decision to use V-A ECMO is critical for a successful outcome in these patients.

© 2019 Wiley Periodicals, Inc.

PMID: 31017313

Int J Cardiol Heart Vasc. 2019 Apr 15;23:100360. doi: 10.1016/j.ijcha.2019.100360. eCollection 2019 Jun.

Outcome of atrial fibrillation ablation in pulmonary hypertension: Is pulmonary hypertension a modifiable risk factor?

Linz D¹, Dobrev D².

Author information:

1. Centre for Heart Rhythm Disorders, South Australian Health and Medical Research Institute (SAHMRI), University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia.
2. Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany.

Free PMC Article
PMCID: PMC6465768
PMID: 31016225

Exp Lung Res. 2019 Apr 23:1-12. doi: 10.1080/01902148.2019.1605426. [Epub ahead of print]

Opposite alterations of endothelin-1 in lung and pulmonary artery mirror gene expression of bone morphogenetic protein receptor 2 in experimental pulmonary hypertension.

Veteskova J¹, Kmecova Z¹, Malikova E¹, Doka G¹, Radik M¹, Vavrinec P¹, Krenek P¹, Klimas J¹.

Author information:

1. a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Comenius University in Bratislava , Bratislava , Slovakia.

Abstract

AIM OF THE STUDY:
Endothelin-1 (ET-1) overexpression was suggested to play a role in pulmonary hypertension (PH). However, the roles of ET-1 in early stages of PH remain unexplored. We examined the expression of ET-1 and relevant disease progression markers in the pulmonary artery and the lungs during the development of PH induced by monocrotaline (MCT).

MATERIAL AND METHODS:
Male 12-weeks-old Wistar rats were administered with MCT (60 mg/kg, s.c.) or saline (CON). We measured right ventricular pressure (RVP) by catheterization under tribromoethanol anesthesia; hemoglobin oxygen saturation, breathing rate were measured by pulse oximetry in conscious animals. Rats were sacrificed 1, 2 or 4 weeks after MCT. mRNA levels of ET-1, its receptors, inflammatory markers IL-1beta, TNFalpha, IL-6 and genes related to VSMC proliferation or lung damage (Bmpr2, nestin, Pim1, PAI-1, TGFbeta-1) were analyzed by RT-qPCR.

RESULTS:
RVP and breathing rate increased and hemoglobin oxygen saturation decreased after MCT only at week 4. Lung weight was increased at all time points. ET-1 was upregulated in the pulmonary artery at weeks 1 and 4, while being clearly suppressed in the lungs at all times. Bone morphogenetic protein receptor 2 followed a similar pattern to ET-1. PAI-1 markedly increased in the MCT lungs (but not pulmonary artery) from week 1 to 4. Nestin peaked at week 2 in both tissues. TGFbeta-1 increased in both tissues at week 4. ET-1 expression did not correlate with other genes, however, Bmpr2 tightly negatively correlated with PAI-1 in the lungs, but not pulmonary artery of MCT groups.

CONCLUSIONS:
ET-1 overexpression in the pulmonary artery preceded development of PH, but it was clearly and unexpectedly downregulated in the lungs of monocrotaline-treated rats and showed no correlation to disease progression markers. We speculate that endothelin-1 may play opposing roles in the lungs vs pulmonary artery in monocrotaline-induced PH.

PMID: 31012341

Medicine (Baltimore). 2019 Apr;98(16):e14965. doi: 10.1097/MD.0000000000014965.

Effect of beraprost on pulmonary hypertension due to left ventricular systolic dysfunction.

Wang L^1,2, Zhu X¹, Zhao LP¹, Wang M¹, Liu X¹, Chen Y¹, Chen J¹, Xu W¹.

Author information:

1. Department of Cardiology, The Second Affiliated Hospital of Soochow University.
2. Emergency Department, The Seventh People’s Hospital of Suzhou, China.

Abstract

Beraprost is used to treat peripheral chronic arterial occlusive disease. However, the efficacy and safety of beraprost in patients with pulmonary hypertension (PH) due to left ventricular systolic dysfunction (PH-HFrEF) remains unknown. The primary objective of this study was to determine the effects of beraprost on PH-HFrEF.We prospectively recruited patients with PH-HFrEF as determined by echocardiography and right cardiac catheterization. Beraprost sodium was given orally (1 μg/kg/d) added to the usual treatment, and patients were evaluated at 1-year follow-up.Twenty-five patients were recruited with baseline systolic pulmonary artery pressure (PAP) of 49.5 ± 10.8 mm Hg. Systolic PAP results at 3, 6, 9, and 12 months were 39.1 ± 8.1, 30.4 ± 5.2, 27.7 ± 3.0, and 27.0 ± 4.7 mm Hg, respectively, which were all significantly lower than systolic PAP at baseline (P < .05). Left ventricular ejection fraction results at 6 months (43.5 ± 7.0%), 9 months (47.0 ± 5.5%), and 12 months (48.2 ± 4.8%) were significantly higher than at baseline (34.7 ± 9.2%) (P < .05). Six-minute walking distance at 3 months (282.8 ± 80.6 m), 6 months (367.1 ± 81.2 m), 9 months (389.8 ± 87.1 m), and 12 months (395.7 ± 83.4 m) increased with time, and all were significantly higher than baseline (190.1 ± 75.5 m) (P < .05). One patient developed atrial fibrillation and recovered to sinus rhythm after intravenous administration of amiodarone. There were no instances of cardiac-related death, severe bleeding, or severe impairment of liver function.Routine oral administration of beraprost sodium added to the usual treatment may improve cardiopulmonary hemodynamics and exercise capacityin patients with PH-HFrEF.

Free Article
PMID: 31008926 [Indexed for MEDLINE]

Eur J Radiol. 2019 May;114:137-145. doi: 10.1016/j.ejrad.2019.03.014. Epub 2019 Mar 20.

The feasibility in estimating pulmonary vascular resistance by cardiovascular magnetic resonance in pulmonary hypertension: A systematic review and meta-analysis.

Chen H¹, Xiang B¹, Zeng J¹, Luo H¹, Yang Q².

Author information:

1. Department of Radiology, The Yongchuan Affiliated Hospital, Chongqing Medical University, Yongchuan District, Chongqing, PR China.
2. Department of Radiology, The Yongchuan Affiliated Hospital, Chongqing Medical University, Yongchuan District, Chongqing, PR China. Electronic address: flyingfish0331@163.com.

Abstract

PURPOSE:
Cardiac magnetic resonance (CMR) is a substitute technique for noninvasively assessing pulmonary hemodynamics. Some preliminary studies have shown that CMR has the potential to quantify pulmonary vascular resistance (PVR). However, the evaluative value has not been well established. The purpose of the systematic review is to assess the feasibility of CMR in the measurement of PVR in patients with pulmonary hypertension (PH).

METHODS:
Studies were retrieved from multiple databases. Methodological evaluation of CMR and right heart catheterization (RHC) in estimating PVR were obtained from included studies. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was used to assess the quality of studies. The results of comparisons of continuous variables are reported as weighted mean difference (WMD), together with the corresponding 95% confidence intervals (CIs). Summary correlation coefficient (r) values were extracted from each study, and 95% CIs were calculated after Fisher’s z transformation. Sensitivity analysis was conducted to investigate potential heterogeneity.

RESULTS:
A total of 15 studies were included in the systematic review, and 6 of these studies were included in the meta-analysis. The pooled WMD with fixed-effects analysis revealed no statistical significance between PVR-CMR and PVR-RHC in patients with PH (WMD = 0.278 WU; 95% CI: -0.415 to 0.972; p = 0.431). The pooled r value for all studies was 0.85 (95% CI: 0.81, 0.89), and notable heterogeneity was evident. The pooled r value after the exclusion of one heterogeneous article was 0.81 (95% CI: 0.74, 0.87) and was not significantly heterogeneous.

CONCLUSIONS:
CMR and RHC have good consistency in the testing of PVR in the meta-analysis. The systematic review shows that completely noninvasive evaluation of PVR with CMR in patients with pH is feasible.

Copyright © 2019 Elsevier B.V. All rights reserved.

PMID: 31005164

Sleep. 2019 Apr 20. pii: zsz100. doi: 10.1093/sleep/zsz100. [Epub ahead of print]

Positive Airway Pressure Therapy Reduces Pulmonary Hypertension in Patients Admitted for Acute Heart Failure with Pulmonary Hypertension and Obstructive Sleep Apnea. The ASAP-HF Pilot Trial.

Sharma S¹, Fox H², Aguilar F¹, Mukhtar U¹, Willes L³, Bozorgnia B¹, Bitter T², Oldenburg O².

Author information:

1. Albert Einstein Medical Center, Sidney Kimmel Medical School, Philadelphia, PA, USA.
2. Clinic for Cardiology, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
3. Willes Consulting Group, Inc., Encinitas, CA.

Abstract

Pulmonary hypertension(PH) is extremely common in acute decompensated heart failure (ADHF) patients and predicts increased mortality. Obstructive sleep apnea (OSA) is highly prevalent in CHF patients, may contribute to further elevated pulmonary pressures.

OBJECTIVES:
This study evaluates the impact of positive airway pressure (PAP) therapy on PH in patients admitted for ADHF with OSA.

METHODS:
A two center randomized control trial comparing standard of care(SOC) therapy for ADHF versus addition of PAP therapy in patients with concomitant OSA.

RESULTS:
Twenty-one consecutive patients were enrolled with 1:1 randomization to SOC versus SOC plus 48 hour PAP therapy protocol.In the intervention arm the mean pulmonary artery systolic pressure (PASP) difference before therapy and after 48 hours of PAP therapy was -15.8 ± 3.2 (58.6 ± 2.5 mmHg to 42.8 ± 2.7 ) versus the SOC arm where the mean PASP difference was -5.2 ± 2.6 ( 62.7 ± 3.3 mmHg reduced to 57.5 ± 3.9) ( p=0.025). In addition ejection fraction (EF) in the intervention arm improved (3.4 ± 1.5 % versus -0.5 ± 0.5 %) (p=0.01). Significant improvement was also noted in tricuspid annular plane systolic excursion (TAPSE) and right ventricular (RV) systolic area in the intervention arm but not in NT pro BNP or six minute walk distance.

CONCLUSIONS:
In patients with ADHF and OSA, addition of 48hrs of PAP-therapy to SOC treatment significantly reduced PH. In addition, PAP-therapy was able to improve right and left ventricular function.

© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

PMID: 31004141

Med Sci Monit. 2019 Jan 26;25:746-753. doi: 10.12659/MSM.912766.

Triglyceride-to-High-Density Lipoprotein Cholesterol Ratio and Systemic Inflammation in Patients with Idiopathic Pulmonary Arterial Hypertension.

Jonas K¹, Magoń W¹, Podolec P¹, Kopeć G¹.

Author information:

1. Department of Cardiac and Vascular Diseases, Faculty of Medicine, Jagiellonian University Medical College, John Paul II Hospital in Cracow, Cracow, Poland.

Abstract

BACKGROUND
Idiopathic pulmonary arterial hypertension (IPAH) patients are characterized by elevated triglyceride (TG)-to-HDL cholesterol (HDL-C) ratio, which has been proposed to be an important prognostic factor in this population. The mechanism of this phenomenon remains unknown. We therefore investigated the potential determinants of increased TG/HDL-C ratio in IPAH patients.

MATERIAL AND METHODS
We prospectively recruited consecutive clinically stable IPAH patients between January 2016 and February 2017. Patients with diabetes or using statins were excluded. Anthropometric measurements included body mass index (BMI) and skinfold thickness; body fat mass was calculated using age and sex-specific equations. We assessed lipid profile, homeostatic model assessment of insulin resistance (HOMA-IR), serum adipokine levels (adiponectin, resistin, leptin, and visfatin), and circulating cytokines (IL-1β, IL-6, MCP-1, and TNF-α).

RESULTS
We assessed 47 IPAH patients: 9 of them had been diagnosed with diabetes and 10 were treated with statins; therefore, were excluded them from further analysis. Age, sex distribution, and BMI were similar irrespectively of TG/HDL-C ratio. Patients with increased TG/HDL-C ratio (>3) as compared to patients with TG/HDL-C ≤3 were characterized by higher levels of IL-1β, MCP-1, and IL-6. TG level was correlated with IL-1β (R=0.76, p<0.001), IL-6 (R=0.52, p=0.005), TNF-α (R=0.62, p<0.001), and MCP-1 (R=0.63, p<0.001). IL-1β was also inversely correlated with HDL-C (R=-0.44, p=0.02). We found no differences in concentration of fasting glucose, insulin, HOMA-IR, body fat content, or adipokine levels between patients with higher and lower TG/HDL-C ratios.

CONCLUSIONS
In IPAH patients, elevated TG/HDL-C ratio is a marker of systemic inflammation.

Free PMC Article
PMCID: PMC6359883
PMID: 30683836 [Indexed for MEDLINE]

Mol Cell Biochem. 2019 May;455(1-2):169-183. doi: 10.1007/s11010-018-3480-z. Epub 2018 Dec 3.

CPT1 regulates the proliferation of pulmonary artery smooth muscle cells through the AMPK-p53-p21 pathway in pulmonary arterial hypertension.

Zhuang W¹, Lian G², Huang B³, Du A², Gong J², Xiao G², Xu C², Wang H², Xie L^4,5.

Author information:

1. Department of Cardiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China.
2. Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, People’s Republic of China.
3. Department of Geriatric, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China.
4. Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, People’s Republic of China. ldxie@hotmail.com.
5. Department of Geriatric, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China. ldxie@hotmail.com.

Abstract

Abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) plays a dominant role in the development of pulmonary arterial hypertension (PAH). Some studies and our previous work found that disturbance of fatty acid metabolism existed in PAH. However, the mechanistic link between fatty acid catabolism and cell proliferation remains elusive. Here, we identified an essential role and signal pathway for the key rate-limiting enzyme of mitochondrial fatty acid β-oxidation, carnitine palmitoyltransferase (CPT) 1, in regulating PASMC proliferation in PAH. We found that CPT1 was highly expressed in rat lungs and pulmonary arteries in monocrotaline-induced PAH, accompanied by decreased adenosine triphosphate (ATP) production and downregulation of the AMPK-p53-p21 pathway. Platelet-derived growth factor (PDGF)-BB upregulated the expression of CPT1 in a dose- and time-dependent manner. PASMC proliferation and ATP production induced by PDGF-BB were partly reversed by the CPT1 inhibitor etomoxir (ETO). The overexpression of CPT1 in PASMCs also promoted proliferation and ATP production and subsequently inhibited the phosphorylation of AMPK, p53, as well as p21 in PASMCs. Furthermore, AMPK was activated by ETO, which increased the expression of p53 and p21, and the proportion of cells in the cell cycle G2/M phase in response to PDGF-BB stimulation in PASMCs. Our work reveals a novel mechanism of CPT1 regulating PASMC proliferation in PAH, and regulation of CPT1 may be a potential target for therapeutic intervention in PAH.

PMID: 30511343 [Indexed for MEDLINE]

Eur Respir J. 2019 Apr 25. pii: 1802095. doi: 10.1183/13993003.02095-2018. [Epub ahead of print]

French experience of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

Brenot P^1,2,3, Jaïs X^4,3,5, Taniguchi Y^1,3,5, Alonso CG^1,2,3, Gerardin B^1,2,3, Mussot S^1,3,6, Mercier O^1,3,6, Fabre D^1,3,6, Parent F^1,3,5, Jevnikar M^1,3,5, Montani D^1,3,5, Savale L^1,3,5, Sitbon O^1,3,5, Fadel E^1,3,6, Humbert M^1,3,5, Simonneau G^1,3,5.

Author information:

1. Univ. Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
2. Service de Radiologie, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
3. Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
4. Univ. Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France xavier.jais@gmail.com.
5. AP-HP, Service de Pneumologie, Centre de Référence de l’Hypertension Pulmonaire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
6. Service de Chirurgie Thoracique, Hôpital Marie Lannelongue, Le Plessis Robinson, France.

Abstract

AIMS:
To evaluate safety and efficacy of balloon pulmonary angioplasty (BPA) in a large cohort of patients with chronic thromboembolic pulmonary hypertension (CTEPH).

METHODS AND RESULTS:
From 2014 to 2017, 184 inoperable CTEPH patients underwent 1006 BPA sessions. Safety and efficacy during the first 21 months (initial period) were compared with those of the last 21 months (recent period). A total of 154 patients had a full evaluation after a median duration of 6.1 months. Overall, there was a significant improvement in NYHA functional class, 6-min walk distance (mean change, +45 m), and a significant decrease in mean pulmonary artery pressure (PAP) and in pulmonary vascular resistance (PVR) by 26% and 43%, respectively. The percentage decrease of mean PAP and PVR were 22% and 37% in the initial period versus 30% and 49% in the recent period, respectively (p<0.05). The main complications included lung injury (LI) which occurred in 9.1% of 1006 sessions (13.3% in the initial period versus 5.9% in the recent period, p<0.001). Per-patient multivariate analysis revealed that baseline mean PAP and the period during which BPA procedure was performed (recent versus initial period) were the strongest factors related to the occurrence of LI. Three-year survival was 95.1%.

CONCLUSION:
This study confirms that a refined BPA strategy improves short-term symptoms, exercise capacity and hemodynamics in inoperable CTEPH patients with an acceptable risk-benefit ratio. Safety and efficacy improve over time, underscoring the unavoidable learning curve for this procedure.

Copyright ©ERS 2019.

PMID: 31023842

Lancet. 2019 Mar 9;393(10175):1056-1070. doi: 10.1016/S0140-6736(18)33207-0.

Multimodality imaging in ischaemic heart failure.

Bax JJ¹, Di Carli M², Narula J³, Delgado V⁴.

Author information:

1. Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands. Electronic address: j.j.bax@lumc.nl.
2. Departments of Radiology and Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, NY, USA.
3. Icahn School of Medicine at Mount Sinai, New York, NY, USA.
4. Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands.

Abstract

In heart failure, extensive evaluation with modern non-invasive imaging modalities is needed to assess causes, pathophysiology, and haemodynamics, to determine prognosis and consider therapeutic options. This systematic evaluation includes a stepwise assessment of left ventricular size and function, the presence and severity of coronary artery disease, mitral regurgitation, pulmonary hypertension, right ventricular dilation and dysfunction, and tricuspid regurgitation. Based on this imaging-derived information, the need for specific therapies besides optimised medical therapy can be determined. The need for revascularisation, implantation of an implantable cardiac defibrillator, and mitral or tricuspid valve repair or replacement, can be (partially) guided by non-invasive imaging. Importantly, randomised controlled trials on the use of non-inasive imaging to guide therapy are scarce in this field and most non-pharmacological therapies are based on expert-consensus, but whenever trials are available, they will be addressed in this paper.

Copyright © 2019 Elsevier Ltd. All rights reserved.

PMID: 30860031 [Indexed for MEDLINE]

Surg Case Rep. 2019 Apr 11;5(1):59. doi: 10.1186/s40792-019-0616-7.

Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension with active Crohn’s disease.

Sugiyama K¹, Suzuki S², Maruno K², Fujiyoshi T², Koizumi N², Ogino H².

Author information:

1. Department of Cardiac Surgery, Aichi Medical University Hospital, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan. kayotaro3@gmail.com.
2. Department of Cardiovascular Surgery, Tokyo Medical University Hospital, 6-7-1, Nishishinjuku, Shinjuju, Tokyo, 160-0023, Japan.

Abstract

BACKGROUND:
Anticoagulation control in active inflammatory bowel disease (IBD) is challenging because of hypercoagulation and bleeding complications. The strategy for treating chronic thromboembolic pulmonary hypertension (CTEPH) in IBD remains controversial because only a few studies have reported its successful treatment (Kim and Lang. Eur Respir Rev 21: 27-31, 2012, Bonderman, et al. Circulation 115: 2153-8, 2007). We describe a case of CTEPH with active Crohn’s disease successfully treated with pulmonary endarterectomy (PEA).

CASE PRESENTATION:
A 49-year-old man with CTEPH had undergone balloon pulmonary angioplasty four times; however, severe pulmonary hypertension remained. Moreover, he had Crohn’s disease, and sufficient anticoagulant therapy could not be performed because of frequent melena. He also had frequent episodes of intestinal ileus resulting in malnutrition. After strict anticoagulant control with warfarin, PEA was performed safely with strict control of the activated coagulation time. After PEA, his pulmonary hypertension improved to a normal range, and he underwent abdominal surgery for the recurrent intestinal ileus.

CONCLUSION:
PEA for CTEPH with active IBD is challenging, but feasible. The strict anticoagulant control is critical for active IBD patients. Safety of taking direct oral anticoagulants is unclear because there are no parameters for monitoring the level of anticoagulation.

Free PMC Article
PMCID: PMC6459446
PMID: 30976945

Circ J. 2019 Apr 9. doi: 10.1253/circj.CJ-18-1155. [Epub ahead of print]

Correlation of Right Ventricular Wall Stress With Plasma B-Type Natriuretic Peptide Levels in Patients With Pulmonary Hypertension.

Uchiyama N¹, Yuasa T¹, Miyata M¹, Horizoe Y¹, Chaen H¹, Kubota K¹, Takasaki K¹, Mizukami N², Kisanuki A³, Ohishi M¹.

Author information:

1. Department of Cardiovascular Medicine and Hypertension, Kagoshima University Graduate School of Medicine and Dental Sciences.
2. Department of Clinical Laboratory, Kagoshima University Medical and Dental Hospital.
3. Department of Health Sciences, Kagoshima University Faculty of Medicine, Kagoshima University.

Abstract

BACKGROUND:
This study was designed to investigate the relationship between right ventricular wall stress (RVWS) and plasma B-type natriuretic peptide (BNP) levels in patients with pulmonary hypertension (PH). Methods and Results: The 57 consecutive PH patients and 8 control subjects were enrolled. Right heart catheterization (RHC), echocardiography, and BNP measurements were performed, and RVWS and left ventricular wall stress (LVWS) were calculated with the formula based on Laplace’s law. Systolic RVWS and end-diastolic RVWS were higher in PH patients compared with controls (systolic RVWS: 77±41 vs. 17±5 kdynes/cm2(P<0.0001), end-diastolic RVWS: 15±12 vs. 8±2 kdynes/cm2(P<0.0005)). Univariate analyses showed that logBNP at baseline correlated with systolic RVWS (r=0.58, P<0.0001) and end-diastolic RVWS (r=0.61, P<0.0001). We performed multivariate regression analysis and determined that end-diastolic RVWS was an independent determinant of logBNP in patients with PH. In addition, change in plasma BNP levels after treatment correlated with change in systolic RVWS (r=0.70, P<0.0001) and change in end-diastolic RVWS (r=0.68, P<0.0001).

CONCLUSIONS:
Both systolic and end-diastolic RVWS were elevated in patients with PH, and correlated with the symptoms of PH. End-diastolic RVWS was an independent determinant of plasma BNP levels in PH patients.

Free Article
PMID: 30971626

Ann Card Anaesth. 2019 Apr-Jun;22(2):215-220. doi: 10.4103/aca.ACA_123_18.

Perioperative management of a patient with double orifice mitral valve with supramitral ring with subaortic membrane with ventricular septal defect and severe pulmonary hypertension: Report of a rare case.

Datt V¹, Khurana P¹, Aggarwal S², Mishra S³, Sujith CN¹, Virmani S¹.

Author information:

1. Department of Anaesthesiology and Intensive Care and Cardiothoracic and Vascular Surgery and Cardiology, GB Pant Hospital (GIPMER) and Jaypee Hospital, New Delhi, India.
2. Department CTVS, GB pant Hospital (GIPMER), New Delhi, India.
3. Department of Cardiology, Jaypee Hospital, New Delhi, India.

Abstract

Double-orifice mitral valve (DOMV) is an unusual congenital anomaly characterized by a mitral valve with a single fibrous annulus with two orifices or rarely two orifices with two separate mitral annuli opening into the left ventricle. We present a first report of a patient with a DOMV with supramitral ring (SMR), subaortic membrane (SAM), a large ventricular septal defect (VSD) with more than 50% aortic override, and severe pulmonary arterial hypertrophy (PAH). This patient underwent excision of the SAM, and SMR, with closure of the VSD together under cardiopulmonary bypass (CPB). However postoperatively, the patient developed an irreversible fatal pulmonary hypertensive crisis (PHC), immediately after transferring the patient to the cardiac intensive care unit from the operating room (OR). The PHC was refractory to intravenous and inhaled milrinone and nitroglycerine and intravenous adrenaline, dobutamine, norepinephrine, vasopressin, patent foramen oval (PFO), and CPB support. The management of DOMV and perioperative pulmonary hypertension is discussed.

Free PMC Article
PMCID: PMC6489406
PMID: 30971608

Conflict of interest statement
None

Ann Card Anaesth. 2019 Apr-Jun;22(2):136-142. doi: 10.4103/aca.ACA_83_18.

Terlipressin versus norepinephrine to prevent milrinone-induced systemic vascular hypotension in cardiac surgery patient with pulmonary hypertension.

Abdelazziz MM¹, Abdelhamid HM¹.

Author information:

1. Department of Anesthesia, Ain Shams University, Cairo, Egypt.

Abstract

Introduction:
Milrinone at inotropic doses requires the addition of a vasoconstrictive drug. We hypothesized that terlipressin use could selectively recover the systemic vascular hypotension induced by milrinone without increasing the pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (MPAP) as norepinephrine in cardiac surgery patients.

Patients and Methods:
Patients with pulmonary hypertension were enrolled in this study. At the start of rewarming a milrinone 25 μg/kg bolus over 10 min followed by infusion at the rate of 0.25 μg/kg/min. Just after the loading dose of milrinone, the patients were randomized to receive norepinephrine infusion at a dose of 0.1 μg/kg/min (norepinephrine group) or terlipressin infusion at a dose of 2 μg/kg/h (terlipressin group). Heart rate, mean arterial blood pressure (MAP), central venous pressure, MPAP, systemic vascular resistance (SVR), PVR, cardiac output were measured after induction of anesthesia, after loading dose of milrinone, during skin closure, and in the intensive care unit till 24 h.

Results:
Milrinone decreased MAP (from 79.56 ± 4.5 to 55.21 ± 2.1 and from 78.46 ± 3.3 to 54.11 ± 1.1) and decreased the MPAP (from 59.5 ± 3.5 to 25.4 ± 2.6 and from 61.3 ± 5.2 to 25.1 ± 2.3) in both groups. After norepinephrine, there was an increase in the MAP which is comparable to terlipressin group (P > 0.05). Terlipressin group shows a significant lower MPAP than norepinephrine group (24.5 ± 1.4 at skin closure vs. 43.3 ± 2.1, than 20.3 ± 2.1 at 24 h vs. 39.8 ± 3.8 postoperatively). There is a comparable increase in the SVR in both group, PVR showed a significant increase in the norepinephrine group compared to the terlipressin group (240.5 ± 23 vs. 140.6 ± 13 at skin closure than 190.3 ± 32 vs. 120.3 ± 10 at 24 h postoperatively).

Conclusion:
The use of terlipressin after milrinone will reverse systemic hypotension with lesser effect on the pulmonary artery pressure.

Free PMC Article
PMCID: PMC6489405
PMID: 30971593

Eur Radiol. 2019 Apr 8. doi: 10.1007/s00330-019-06188-7. [Epub ahead of print]

Combined automated 3D volumetry by pulmonary CT angiography and echocardiography for detection of pulmonary hypertension.

Melzig C^1,2, Wörz S³, Egenlauf B⁴, Partovi S⁵, Rohr K³, Grünig E^2,4, Kauczor HU^1,2, Heussel CP^1,2,6, Rengier F^7,8,9.

Author information:

1. Department of Diagnostic and Interventional Radiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
2. Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.
3. Biomedical Computer Vision Group, BIOQUANT, IPMB and German Cancer Research Center (DKFZ), University of Heidelberg, Heidelberg, Germany.
4. Centre for Pulmonary Hypertension, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany.
5. Department of Radiology, Section of Interventional Radiology, Cleveland Clinic Foundation, Cleveland, OH, USA.
6. Department of Radiology, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany.
7. Department of Diagnostic and Interventional Radiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. fabian.rengier@web.de.
8. Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany. fabian.rengier@web.de.
9. Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. fabian.rengier@web.de.

Abstract

OBJECTIVES:
To assess the diagnostic accuracy of automated 3D volumetry of central pulmonary arteries using computed tomography pulmonary angiography (CTPA) for suspected pulmonary hypertension alone and in combination with echocardiography.

METHODS:
This retrospective diagnostic accuracy study included 70 patients (mean age 66.7, 48 female) assessed for pulmonary hypertension by CTPA and transthoracic echocardiography with estimation of the pulmonary arterial systolic pressure (PASP). Gold standard right heart catheterisation with measurement of the invasive mean pulmonary arterial pressure (invasive mPAP) served as the reference. Volumes of the main, right and left pulmonary arteries (MPA, RPA and LPA) were computed using automated 3D segmentation. For comparison, axial dimensions were manually measured. A linear regression model was established for prediction of mPAP (predicted mPAP).

RESULTS:
MPA, RPA and LPA volumes were significantly increased in patients with vs. without pulmonary hypertension (all p < 0.001). Of all measures, MPA volume demonstrated the strongest correlation with invasive mPAP (r = 0.76, p < 0.001). Predicted mPAP using MPA volume and echocardiographic PASP as covariates showed excellent correlation with invasive mPAP (r = 0.89, p < 0.001). Area under the curves for predicting pulmonary hypertension were 0.94 for predicted mPAP, compared to 0.90 for MPA volume and 0.92 for echocardiographic PASP alone. A predicted mPAP > 25.8 mmHg identified pulmonary hypertension with sensitivity, specificity, positive and negative predictive values of 86%, 93%, 95% and 81%, respectively.

CONCLUSIONS:
Automated 3D volumetry of central pulmonary arteries based on CTPA may be used in conjunction with echocardiographic pressure estimates to noninvasively predict mPAP and pulmonary hypertension as confirmed by gold standard right heart catheterisation with higher diagnostic accuracy than either test alone.

KEY POINTS:

• This diagnostic accuracy study derived a regression model for noninvasive prediction of invasively measured mean pulmonary arterial pressure as assessed by gold standard right heart catheterisation.
• This regression model using automated 3D volumetry of the central pulmonary arteries based on CT pulmonary angiography in conjunction with the echocardiographic pressure estimate predicted pulmonary arterial pressure and the presence of pulmonary hypertension with good diagnostic accuracy.
• The combination of automated 3D volumetry and echocardiographic pressure estimate in the regression model provided superior diagnostic accuracy compared to each parameter alone.

PMID: 30963276

Lung. 2019 Apr 8. doi: 10.1007/s00408-019-00222-7. [Epub ahead of print]

Real-Life Experience with Selexipag as an Add-On Therapy to Oral Combination Therapy in Patients with Pulmonary Arterial or Distal Chronic Thromboembolic Pulmonary Hypertension: A Retrospective Analysis.

Berlier C¹, Schwarz EI¹, Saxer S¹, Lichtblau M¹, Ulrich S^2,3.

Author information:

1. Clinic of Pulmonology, University Hospital of Zurich, Zurich, Switzerland.
2. Clinic of Pulmonology, University Hospital of Zurich, Zurich, Switzerland. silvia.ulrich@usz.ch.
3. Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. silvia.ulrich@usz.ch.

Abstract

BACKGROUND:
Patients with pulmonary arterial hypertension (PAH) and distal chronic thromboembolic pulmonary hypertension (CTEPH) who still reveal risk factors of worse prognosis on double combination therapy may benefit from add-on therapy with the novel oral selective prostacyclin receptor agonist selexipag.

METHODS:
We reviewed all patients with PAH/distal CTEPH in the Zurich cohort who received selexipag as add-on to oral combination therapy and retrieved New York Heart Association (NYHA) functional class, 6-min walk distance (6MWD), NT-pro-BNP, quality of life questionnaires (CAMPHOR and EuroQoL), tricuspid pressure gradient (TPG) by echocardiography and cardiopulmonary exercise test parameters (power output and oxygen uptake).

RESULTS:
Twenty-three patients with PAH/CTEPH (20/3), 14 females, median (quartiles) age 56 (46; 66) years received an oral triple therapy containing selexipag at a median dose of 2000 (1600; 3100) mcg during 221 (113; 359) days. The following parameters were stabilized from baseline to last FU: 6MWD (440 (420; 490) to 464 (420; 526) m), NYHA class (three to two), NT-pro-BNP (326 (167; 1725) to 568 (135; 1856) ng/l), TPG, power output, and oxygen uptake. Quality of life reflected by the CAMPHOR and EuroQoL improved.

CONCLUSIONS:
Early initiation of triple oral combination therapy including selexipag in PAH/CTEPH with intermediate risk factor profile may help to stabilize functional class, exercise performance, and pulmonary hemodynamics in a real-life setting and potentially improves quality of life. Whether these beneficial effects can be truly attributed to the addition of selexipag should be addressed in future randomized controlled trials.

PMID: 30963265

Respir Med. 2019 Apr;150:131-135. doi: 10.1016/j.rmed.2019.03.003. Epub 2019 Mar 16.

Use of red cell distribution width in a population at high risk for pulmonary hypertension.

Petrauskas LA¹, Saketkoo LA², Kazecki T¹, Saito S², Jaligam V³, deBoisblanc BP⁴, Lammi MR⁵.

Author information:

1. Louisiana State University Health Sciences Center, School of Medicine, New Orleans, LA, USA.
2. Comprehensive Pulmonary Hypertension Center-University Medical Center, New Orleans, LA, USA; Tulane University School of Medicine, New Orleans Scleroderma and Sarcoidosis Patient Care and Research Center, New Orleans, LA, USA.
3. Louisiana State University Health Sciences Center, Section of Cardiology, Medical Director of Cardiology-JenCare NOLA, New Orleans, LA, USA.
4. Comprehensive Pulmonary Hypertension Center-University Medical Center, New Orleans, LA, USA; Louisiana State University Health Sciences Center, Section of Pulmonary/Critical Care and Allergy/Immunology, New Orleans, LA, USA.
5. Comprehensive Pulmonary Hypertension Center-University Medical Center, New Orleans, LA, USA; Louisiana State University Health Sciences Center, Section of Pulmonary/Critical Care and Allergy/Immunology, New Orleans, LA, USA. Electronic address: mlammi@lsuhsc.edu.

Abstract

BACKGROUND:
Pulmonary hypertension (PH) often presents with non-specific symptoms making early diagnosis difficult. Red cell distribution width (RDW) is a parameter routinely reported on an automated complete blood cell count that has been associated with numerous disease states. The purpose of this study was to further evaluate RDW as a biomarker for PH in at-risk populations.

METHODS:
In a retrospective, cross-sectional analysis of patients seen at a PH center over 1 year, we examined both patients with PH and patients at risk for but without PH (e.g. systemic sclerosis, [SSc]). We also studied a group of age-and sex-matched, non-diseased controls. Relevant characteristics were compared among the 3 groups using one-way ANOVA. Similar comparisons were made across World Health Organization (WHO) PH groups 1-4.

RESULTS:
RDW was highest in the PH patients (n = 181), intermediate in the at-risk for PH patients (n = 52), and lowest in matched controls (n = 100) (15.9 ± 2.8 vs 14.8 ± 2.8 vs 14.2 ± 1.1%, respectively; p < 0.0001). There were no significant differences in RDW across WHO PH groups (p = 0.50). SSc patients with PH had significantly higher RDW values compared to SSc patients without PH (16.0 ± 2.2 vs 14.4 ± 1.9%, respectively; p = 0.03).

CONCLUSIONS:
RDW is significantly higher in PH patients, without regard to disease etiology, when compared to age- and sex-matched non-diseased controls. Importantly, RDW is also higher in PH patients compared to at-risk patients, particularly in the SSc cohort. The ease of obtaining RDW as a biomarker may help detect incident PH at earlier stages among patients who are at high risk for development of PH.

Copyright © 2019 Elsevier Ltd. All rights reserved.

PMCID: PMC6461373 [Available on 2020-04-01]
PMID: 30961939

Respir Med. 2019 Apr;150:126-130. doi: 10.1016/j.rmed.2019.03.004. Epub 2019 Mar 15.

Outcomes of lung disease-associated pulmonary hypertension and impact of elevated pulmonary vascular resistance.

Awerbach JD¹, Stackhouse KA², Lee J³, Dahhan T⁴, Parikh KS¹, Krasuski RA⁵.

Author information:

1. Duke University Medical Center, Division of Cardiovascular Medicine, Durham, NC, USA.
2. Best Israel Deaconess Medical Center, Boston, MA, USA.
3. The Cleveland Clinic, Cleveland, OH, USA.
4. Duke University Medical Center, Division of Pulmonary and Critical Care Medicine, Durham, NC, USA.
5. Duke University Medical Center, Division of Cardiovascular Medicine, Durham, NC, USA. Electronic address: richard.krasuski@duke.edu.

Abstract

BACKGROUND:
The clinical characteristics, hemodynamic changes and outcomes of lung disease-associated pulmonary hypertension (LD-PH) are poorly defined.

METHODS:
A prospective cohort of PH patients undergoing initial hemodynamic assessment was collected, from which 51 patients with LD-PH were identified. Baseline characteristics and long-term survival were compared with 83 patients with idiopathic pulmonary arterial hypertension (iPAH).

RESULTS:
Mean age (±standard deviation) of LD-PH patients was 64 ± 10 years, 30% were female and 78% were New York Heart Association class III-IV. The LD-PH group was older than the iPAH group (64 ± 10 vs 56 ± 18 years, respectively, P = 0.003) with a lower percentage of women (30% vs 70%, P = 0.007). LD-PH patients had smaller right ventricular sizes (P = 0.02) and less tricuspid regurgitation (P = 0.03) by echocardiogram, and lower mean pulmonary arterial pressures (mPAP) (P = 0.01) and pulmonary vascular resistance (PVR) (P = 0.001) at catheterization. Despite these findings, mortality was equally high in both groups (P = 0.16). 5-year survival was lower in patients with interstitial lung disease compared to those with obstructive pulmonary disease (P = 0.05). Among the LD-PH population, those with mild to moderately elevated mPAP and those with PVR <7 Wood units demonstrated significantly improved survival (P = 0.04 and P = 0.001, respectively). Vasoreactivity was not associated with improved survival (P = 0.64). A PVR ≥7 Wood units was associated with increased risk of mortality (hazard ratio (95% confidence interval), 3.59 (1.27-10.19), P = 0.02).

CONCLUSIONS:
Despite less severe PH and less right heart sequelae, LD-PH has an equally poor clinical outcome when compared to iPAH. A PVR ≥7 Wood units in LD-PH patients was associated with 3-fold higher mortality.

Copyright © 2019 Elsevier Ltd. All rights reserved.

PMID: 30961938

Pulm Circ. 2019 Apr 8:2045894019846433. doi: 10.1177/2045894019846433. [Epub ahead of print]

EXPRESS: Ambrisentan for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH).

Escribano-Subias P¹, Bendjenana H², Curtis P², Lang I³, Vonk-Noordegraaf A⁴.

Author information:

1. CIBERCV, Hospital Universitario 12 de Octubre.
2. GSK.
3. Medizinische Universitat Wien.
4. VU University Medical Center.

PMID: 30957635

Mol Genet Metab Rep. 2019 Mar 22;19:100468. doi: 10.1016/j.ymgmr.2019.100468. eCollection 2019 Jun.

Pulmonary hypertension may be secondary in carriers of compound heterozygous FOXRED1 variants.

Finsterer J¹.

Author information:

1. Krankenanstalt Rudolfstiftung, Postfach 20, 1180 Vienna, Austria.

Free PMC Article
PMCID: PMC6433998
PMID: 30956948

Lancet Respir Med. 2019 Apr 4. pii: S2213-2600(19)30111-0. doi: 10.1016/S2213-2600(19)30111-0. [Epub ahead of print]

An insider view on the World Symposium on Pulmonary Hypertension.

Humbert M¹, Galiè N², McLaughlin VV², Rubin LJ², Simonneau G².

Author information:

1. Service de Pneumologie et Soins Intensifs, CHU de Bicêtre, F-94275, Le Kremlin-Bicêtre, France. Electronic address: marc.humbert@aphp.fr.
2. Service de Pneumologie et Soins Intensifs, CHU de Bicêtre, F-94275, Le Kremlin-Bicêtre, France.

PMID: 30956061

Med Clin North Am. 2019 May;103(3):413-423. doi: 10.1016/j.mcna.2018.12.002.

Pulmonary Hypertension.

Kim D¹, George MP².

Author information:

1. Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver CO 80206, USA.
2. Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver CO 80206, USA. Electronic address: georgem@njhealth.org.

Abstract

Pulmonary hypertension (PH) is a chronic and progressive disease that presents like many other lung diseases, often leading to a delay in diagnosis, and therefore a delay in optimal therapy. This article provides a review of PH for internists, covering clinical presentation, diagnostic algorithm, different types of PH, and overview of treatments. In addition, it emphasizes the importance of early referral to, and partnership between, PH specialists and physicians on the front lines to improve early diagnosis and optimize management of these complex patients.

Copyright © 2019 Elsevier Inc. All rights reserved.

PMID: 30955510 [Indexed for MEDLINE]

Methodist Debakey Cardiovasc J. 2018 Oct-Dec;14(4):298-300. doi: 10.14797/mdcj-14-4-298.

Reversed Pulsus Paradoxus in Right Ventricular Failure.

Malahfji M¹, Arain S².

Author information:

1. HOUSTON METHODIST HOSPITAL, HOUSTON, TEXAS.
2. MCGOVERN MEDICAL SCHOOL, UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, HOUSTON, TEXAS.

Abstract

Reversed pulsus paradoxus was first described in 1973 as a rise in peak systolic pressure on inspiration in patients with idiopathic hypertrophic subaortic stenosis or isorhythmic ventricular rhythm and in patients with left ventricular systolic dysfunction on positive pressure ventilation. Positive pressure ventilation, for example, may impel blood from the pulmonary capillaries and venules into the left atrium. This may increase left ventricular preload and accelerate ventricular emptying, which in turn may cause the systolic arterial pressure to rise during inspiration. We observed this phenomenon in a patient with a large pericardial effusion, right ventricular failure, and pulmonary arterial hypertension, and we noted the lack of echocardiographic features of tamponade in the presence of right ventricular hypertrophy and pulmonary hypertension. This case report discusses the subsequent occurrence of acute congestive heart failure after pericardiocentesis.

Free PMC Article
PMCID: PMC6369612
PMID: 30788016 [Indexed for MEDLINE]

Conflict of interest statement
Conflict of Interest Disclosure: The authors have completed and submitted the Methodist DeBakey Cardiovascular Journal Conflict of Interest Statement and none were reported.

Scand Cardiovasc J. 2018 Dec;52(6):378-382. doi: 10.1080/14017431.2019.1567934. Epub 2019 Feb 6.

Iron deficiency in pulmonary arterial hypertension associated with congenital heart disease.

Yu X¹, Zhang Y¹, Luo Q¹, Liu Z¹, Zhao Z¹, Zhao Q¹, Gao L¹, Jin Q¹, Yan L¹.

Author information:

1. a Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.

Abstract

OBJECTIVES:
We aimed to investigate the prevalence of iron deficiency (ID) in congenital heart disease associated with pulmonary arterial hypertension (CHD-PAH) and to explore the influence of ID on CHD-PAH patients. What was associated with ID in these patients was also looked into.

DESIGN:
One hundred and fifty-three patients who were newly diagnosed with CHD-PAH were enrolled. Patients were divided into iron-deficient and iron-replete groups according to the following criteria. ID was defined as transferrin saturation <20% in male and transferrin saturation <25% in female. Clinical data of all participants were collected and compared. Logistic regression was performed to explore factors associated with ID in CHD-PAH.

RESULTS:
Thirty-nine percent of 153 CHD-PAH patients were founded with ID. Iron-deficient group had greater proportion of female patients, shorter six minutes walking distance (6-MWD), higher N-terminal pro-brain natriuretic peptide levels, lower creatinine levels, greater ratio of diastolic right ventricle diameter to left ventricle diameter. Female (OR = 15.44, 95%CI 4.91-48.54, p < .01), 6-MWD (OR = 0.99, 95%CI 0.98-1.00, p = .02) and mean right atrial pressure (OR = 1.13, 95%CI 1.02-1.26, p = .02) were independently associated with ID in the overall CHD-PAH patients. Menstruation was independently associated with ID in the female subgroup (OR = 3.88, 95%CI 1.09-13.84, p = .04).

CONCLUSIONS:
ID was highly prevalent in CHD-PAH patients. Worse exercise tolerance and right heart function were observed in iron-deficient patients with CHD-PAH. Female, 6-MWD, mean right atrial pressure and menstruation are important variables indicating the presence of ID in CHD-PAH.

PMID: 30632395 [Indexed for MEDLINE]

BMC Pulm Med. 2018 Dec 29;18(1):197. doi: 10.1186/s12890-018-0769-3.

Endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor.

Naito A^1,2, Sakao S³, Lang IM⁴, Voelkel NF⁵, Jujo T^1,6, Ishida K⁷, Sugiura T¹, Matsumiya G⁷, Yoshino I⁸, Tanabe N¹, Tatsumi K¹.

Author information:

1. Department of Respirology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba City, 260-8670, Japan.
2. Department of Advancing Research on Treatment Strategies for respiratory disease, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-Ku, Chiba City, 260-8670, Japan.
3. Department of Respirology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba City, 260-8670, Japan. sakaos@faculty.chiba-u.jp.
4. Department of Internal Medicine II, Cardiology, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.
5. Victoria Johnson Center for Obstructive Lung Disease, Virginia Commonwealth University, 1101 East Marshall Street, Sanger Hall, Richmond, VA, 23298-0565, USA.
6. Department of Advanced Medicine in Pulmonary Hypertension, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba City, 260-8670, Japan.
7. Department of Cardiovascular Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba City, 260-8670, Japan.
8. Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba City, 260-8670, Japan.

Abstract

BACKGROUND:
Impaired angiogenesis is assumed to be an important factor in the development of chronic thromboembolic pulmonary hypertension (CTEPH). However, the role of endothelial cells (ECs) in CTEPH remains unclear. The aim of this study was to investigate the angiogenic potential of ECs from pulmonary endarterectomy (PEA) specimens.

METHODS:
We isolated ECs from PEA specimens (CTEPH-ECs) and control EC lines from the intact pulmonary arteries of patients with peripheral lung cancers, using a MACS system. These cells were analyzed in vitro including PCR-array analysis, and the PEA specimens were analyzed with immunohistochemistry. Additionally, the serum HGF levels were determined in CTEPH patients.

RESULTS:
A three-dimensional culture assay revealed that CTEPH-ECs were highly angiogenic. An angiogenesis-focused gene PCR array revealed a high expression of hepatocyte growth factor (HGF) in CTEPH-ECs. The high expression of HGF was also confirmed in the supernatant extracted from PEA specimens. The immunohistochemical analysis showed expression of HGF on the surface of the thrombus vessels. The serum HGF levels in CTEPH patients were higher than those in pulmonary thromboembolism survivors.

CONCLUSION:
Our study suggests that there are ECs with pro-angiogenetic character and high expression of HGF in PEA specimens. It remains unknown how these results are attributable to the etiology. However, further investigation focused on the HGF pathway may provide novel diagnostic and therapeutic tools for patients with CTEPH.

Free PMC Article
PMCID: PMC6310963
PMID: 30594174 [Indexed for MEDLINE]

Heart Vessels. 2019 May 2. doi: 10.1007/s00380-019-01420-2. [Epub ahead of print]

Residual pulmonary hypertension is associated with clinical outcomes in patients with acute pulmonary thromboembolism.

Ibe T¹, Wada H², Sakakura K¹, Yoshimura S¹, Ito M¹, Ugata Y¹, Yamamoto K¹, Seguchi M¹, Taniguchi Y¹, Momomura SI¹, Fujita H¹.

Author information:

1. Division of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama, Saitama, 330-8503, Japan.
2. Division of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama, Saitama, 330-8503, Japan. wadahiro@jichi.ac.jp.

Abstract

In patients with acute pulmonary thromboembolism (PTE), the influence of residual pulmonary hypertension (PH) has not been well investigated. The aim of this study was to compare clinical characteristics between patients with and without residual PH, and to investigate the association between residual PH and clinical outcomes after acute phase in acute PTE. We included acute PTE patients who underwent echocardiogram after acute phase between January 2009 and December 2016. These patients were divided into residual PH and non-residual PH groups according to the value of estimated right ventricular systolic pressure (eRVSP) by echocardiogram after acute phase (the residual PH group: eRVSP ≥ 40 mmHg, the non-residual PH group: eRVSP < 40 mmHg). Kaplan-Meier survival curves were applied to investigate whether the residual PH were associated with PTE-related death or recurrent PTE in patients with acute PTE. A total of 49 patients with acute PTE were allocated into the residual PH group (n = 10) and non-residual PH group (n = 39). Median follow-up period for 49 patients was 7 months. The event-free survival rate was significantly lower in the residual PH group as compared with the non-residual PH group (p = 0.003), whereas there was no statistical significance between two groups stratified by initial PH or not (p = 0.97). Residual PH after acute phase was significantly associated with mid-term PTE-related death or recurrent PTE in patients with acute PTE.

PMID: 31049674

Pulm Circ. 2019 May 2:2045894019851904. doi: 10.1177/2045894019851904. [Epub ahead of print]

EXPRESS: Pulmonary Hypertension Subjects Exhibit Right Ventricular Transient Exertional Dilation during Supine Exercise Stress Echocardiography.

El Yafawi R¹, Rancourt D, Hacobian M¹, Atherton D¹, Cohen M¹, Wirth JA¹.

Author information:

1. Maine Medical Center.

PMID: 31044665

Heart Fail Rev. 2019 May 1. doi: 10.1007/s10741-019-09798-x. [Epub ahead of print]

Advances in targeted therapy for chronic thromboembolic pulmonary hypertension.

Zhang Y¹, Yu X¹, Jin Q¹, Luo Q¹, Zhao Z¹, Zhao Q¹, Yan L¹, Liu Z².

Author information:

1. Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Rd, Xicheng District, Beijing, 100037, China.
2. Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Rd, Xicheng District, Beijing, 100037, China. zhihongliufuwai@163.com.

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by unresolved thrombi in the pulmonary arteries and microvasculopathy in nonoccluded areas. If left untreated, progressive pulmonary hypertension will induce right heart failure and, finally, death. Currently, pulmonary endarterectomy (PEA) remains the only method that has the potential to cure CTEPH. Unfortunately, up to 40% of patients are ineligible for this procedure for various reasons. In recent years, refined balloon pulmonary angioplasty (BPA) has become an alternative option for inoperable CTEPH patients, and it may be another curative treatment in the future, particularly in combination with prior PEA. Nevertheless, 23% of patients still suffer from persistent PH after BPA. Given that CTEPH shares many similarities with idiopathic pulmonary arterial hypertension (PAH), targeted drugs developed for PAH are also attractive options for CTEPH, especially for inoperable or persistent/recurrent CTEPH patients. To date, riociguat, macitentan, and subcutaneous treprostinil are the only drugs proven by randomized control trials to be capable of improving the exercise capacity (6-min walking distance) of CTEPH patients. In this review, we summarize the achievements and unresolved problems of PAH-targeted therapy for CTEPH over the last decade.

PMID: 31044326

Heart Lung. 2019 Apr 24. pii: S0147-9563(18)30521-1. doi: 10.1016/j.hrtlng.2019.04.001. [Epub ahead of print]

Balloon pulmonary angioplasty attenuates sleep apnea in patients with chronic thromboembolic pulmonary hypertension.

Kohno T¹, Fukuoka R², Kawakami T², Kataoka M², Kimura M², Sano M², Fukuda K².

Author information:

1. Division of Cardiology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan. Electronic address: kohno.a2@keio.jp.
2. Division of Cardiology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

Abstract

BACKGROUND:
Balloon pulmonary angioplasty (BPA) improves pulmonary hemodynamics in chronic thromboembolic pulmonary hypertension (CTEPH) patients. However, whether it affects the severity of sleep apnea (SA) remains unknown. We investigated the effect of BPA on the severity of SA in CTEPH patients.

METHODS:
We studied 13 patients with CTEPH who had an apnea hypopnea index (AHI) > 10 before BPA and underwent a second polygraph test 6 months after the last BPA session.

RESULTS:
BPA decreased pulmonary vascular resistance, mean pulmonary artery pressure (PAP), and plasma B-type natriuretic peptide levels, and increased the 6-minute walking distance. BPA decreased the AHI (from 20.9 [13.9-35.7] to 16.3 [7.7-21.8] times/hour, P = 0.023) and hypopnea index (from 13.2 [8.4-22.5] to 6.4 [3.8-10.9] times/hour, P = 0.013), but not the obstructive, central, or mixed apnea index. The change in AHI correlated with that in mean PAP, but not with the change in body mass index or other parameters of hemodynamics.

CONCLUSIONS:
BPA-induced improvement in hemodynamics was associated with the attenuation of SA in patients with CTEPH and SA. Therefore, close attention should be paid to SA in CTEPH patients, and SA should be re-evaluated after BPA to avoid overestimating its severity.

Copyright © 2019 Elsevier Inc. All rights reserved.

PMID: 31029378

Am J Respir Crit Care Med. 2019 Apr 30. doi: 10.1164/rccm.201903-0689ED. [Epub ahead of print]

Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction Patients: Where to Draw the Line.

Simon MA^1,2, Maron BA³.

Author information:

1. University of Pittsburgh School of Medicine, 12317, Department of Medicine, Division of Cardiology, Pittsburgh, Pennsylvania, United States.
2. University of Pittsburgh ; simonma@upmc.edu.
3. Brigham and Women’s Hospital Biomedical Research Institute, 278479, Boston, Massachusetts, United States.

PMID: 31038986