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THIS ISSUE:

- Pulmonary Hypertension and Right Heart Dysfunction in Chronic Lung Disease. #1

- Genetics of pulmonary hypertension. #4

- Extracorporeal membrane oxygenation as a novel bridging strategy for acute right heart failure in group 1 pulmonary arterial hypertension. #12

- Assessment of operability of patients with pulmonary arterial hypertension associated with congenital heart disease. #32

- And 37 other recent PHT publications.
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1. Biomed Res Int. 2014;2014:739674. Epub 2014 Jul 24.

Pulmonary Hypertension and Right Heart Dysfunction in Chronic Lung Disease.

Zangiabadi A1De Pasquale CG2Sajkov D1.
Author information: 
1Australian Respiratory and Sleep Medicine Institute, Flinders Medical Centre, Bedford Park, Adelaide, SA 5042, Australia.
2Department of Cardiology, Flinders Medical Centre, Bedford Park, Adelaide, SA 5042, Australia.

Abstract

Group 3 pulmonary hypertension (PH) is a common complication of chronic lung disease (CLD), including chronic obstructive pulmonary disease (COPD), interstitial lung disease, and sleep-disordered breathing. Development of PH is associated with poor prognosis and may progress to right heart failure, however, in the majority of the patients with CLD, PH is mild to moderate and only a small number of patients develop severe PH. The pathophysiology of PH in CLD is multifactorial and includes hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, small vessel destruction, and fibrosis. The effects of PH on the right ventricle (RV) range between early RV remodeling, hypertrophy, dilatation, and eventual failure with associated increased mortality. The golden standard for diagnosis of PH is right heart catheterization, however, evidence of PH can be appreciated on clinical examination, serology, radiological imaging, and Doppler echocardiography. Treatment of PH in CLD focuses on management of the underlying lung disorder and hypoxia. There is, however, limited evidence to suggest that PH-specific vasodilators such as phosphodiesterase-type 5 inhibitors, endothelin receptor antagonists, and prostanoids may have a role in the treatment of patients with CLD and moderate-to-severe PH.
PMCID: PMC4140123 Free PMC Article
  PMID: 25165714 [PubMed - as supplied by publisher]
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2. Diagn Interv Radiol. 2014 Sep-Oct;20(5):414-20. doi: 10.5152/dir.2014.13501.

Flow characteristics of the proximal pulmonary arteries and vena cava in patients with chronic thromboembolic pulmonary hypertension: correlation between 3.0 T phase-contrast MRI and right heart catheterization.

Guo X1Liu MMa ZWang SYang YZhai ZWang CZhai R.
Author information: 
1Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. radiologygg@126.com.

Abstract

PURPOSE:

We aimed to determine the correlation between flow characteristics of the proximal pulmonary arteries and vena cava obtained by 3.0 T phase-contrast magnetic resonance imaging (MRI) and hemodynamic characteristics by right heart catheterization in patients with chronic thromboembolic pulmonary hypertension.

MATERIALS AND METHODS:

Twenty consecutive patients with chronic thromboembolic pulmonary hypertension and 20 sex- and age-matched healthy volunteers were included prospectively. All patients and controls underwent phase-contrast MRI to determine the flow characteristics including peak velocity, mean velocity, and mean blood flow of the proximal pulmonary artery and vena cava. All patients underwent right heart catheterization to determine the hemodynamics.

RESULTS:

Peak velocity and mean velocity of the proximal pulmonary artery were significantly lower in the patient group. In patients, both peak velocity and mean blood flow were sequentially decreased in the main pulmonary artery, left and right pulmonary arteries, and left and right interlobar pulmonary arteries. Inferior vena cava had higher peak velocity, mean velocity, and mean blood flow than superior vena cava. Peak velocity of the main pulmonary artery correlated with mean and diastolic pulmonary artery pressure. Peak velocity of both inferior and superior vena cava strongly correlated with the pulmonary vascular resistance index (PVRI) (r=-0.68, P < 0.001 and r=-0.74, P < 0.001, respectively). Mean velocity of the main pulmonary artery and right pulmonary artery strongly correlated with PVRI and mean pulmonary artery pressure. Mean velocity of the superior vena cava and mean blood flow of the main pulmonary artery strongly correlated with PVRI and right cardiac work index.

CONCLUSION:

Blood flow in the proximal pulmonary artery and vena cava evaluated by phase-contrast MRI correlate with hemodynamic parameters of right heart catheterization and can be used to noninvasively evaluate the severity of chronic thromboembolic pulmonary hypertension and, potentially, to follow up the treatment response.
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  PMID: 25163757 [PubMed - in process]
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3. J Nucl Cardiol. 2014 Aug 27. [Epub ahead of print]

The role of nuclear imaging in pulmonary hypertension.

Ohira H1Beanlands RSDavies RAMielniczuk L.
Author information: 
1Advanced Heart Disease and Pulmonary Hypertension Programs, National Cardiac PET Centre, Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, 40 Ruskin Street, Room 3409, Ottawa, ON, K1Y 4W7, Canada.

Abstract

Pulmonary hypertension (PH) is a disease characterized by a chronic elevation of pulmonary artery pressure from various causes. Pulmonary artery hypertension (PAH) is one of subtype which results in premature death often as a result of right ventricular (RV) dysfunction. In spite of the recent progress in novel cardiac imaging techniques and new drugs for PAH, there remain significant unresolved issues including a need for earlier diagnosis, refinement of risk stratification, and monitoring the effects of treatment. Cardiac and pulmonary imaging with transthoracic echocardiography (TTE) with Doppler, magnetic resonance imaging (MRI), and computed tomography (CT) are done routinely in many clinical centers. However, routine and emerging nuclear techniques may have a pivotal role of assessment of the patient with PH, and is currently the subject of significant research. Potential Roles for Nuclear Imaging in the Evaluation of the PH Patient: (1) Evaluation of cardiac structure and function (RNA) (non-nuclear techniques would include TTE, CT, and MRI). (2) Functional imaging. This includes the use of ventilation-perfusion scintigraphy (V/Q scan) to diagnose chronic thromboembolic pulmonary hypertension (CTEPH), 123l-metaiodobenzylguanidine (MIBG) imaging to evaluate the cardiac sympathetic nervous system (non-nuclear techniques include invasive right heart catheterization and TTE). (3) Measurement of RV perfusion (with gated SPECT studies). (4) Evaluation of cardiac and pulmonary metabolism (PET scans). This review article will summarize the pathophysiology, classification, natural history, and diagnostic approach of PH. Current and emerging nuclear techniques will be discussed under the four themes of evaluation of structure, functional imaging, flow, and metabolism. These will be compared to current and emerging nuclear and non-nuclear diagnostic tests in the evaluation and management of patients with PH. We will also discuss research applications exploring new insights into flow and metabolism in the right heart and lung and the application of new radioligands.
  PMID: 25161042 [PubMed - as supplied by publisher]
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4. Curr Opin Cardiol. 2014 Aug 23. [Epub ahead of print]

Genetics of pulmonary hypertension.

Best DH1Austin EDChung WKElliott CG.
Author information: 
1aDepartment of Pathology, University of Utah School of Medicine bARUP Laboratories, ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah cDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee dDepartments of Pediatrics and Medicine, Columbia University Medical Center, New York, New York eDepartment of Medicine, Intermountain Medical Center, Murray fDepartment of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA.

Abstract

PURPOSE OF REVIEW:

The identification of the genetic basis for heritable predisposition to pulmonary arterial hypertension (PAH) has altered the clinical and research landscape for PAH patients and their care providers. This review aims to describe the genetic discoveries and their impact on clinical medicine.

RECENT FINDINGS:

Since the landmark discovery that bone morphogenetic protein receptor type II (BMPR2) mutations cause the majority of cases of familial PAH, investigators have discovered mutations in genes that cause PAH in families without BMPR2 mutations, including the type I receptor ACVRL1 and the type III receptor ENG (both associated with hereditary hemorrhagic telangiectasia), caveolin-1 (CAV1), and a gene (KCNK3) encoding a two-pore potassium channel. Mutations in these genes cause an autosomal-dominant predisposition to PAH in which a fraction of mutation carriers develop PAH (incomplete penetrance). In 2014, scientists discovered mutations in eukaryotic initiation factor 2 alpha kinase 4 (EIF2AK4) that cause pulmonary capillary hemangiomatosis and pulmonary veno-occlusive disease, an autosomal recessively inherited disorder.

SUMMARY:

The discovery that some forms of pulmonary hypertension are heritable and can be genetically defined adds important opportunities for physicians to educate their patients and their families to understand the potential risks and benefits of genetic testing.
  PMID: 25159282 [PubMed - as supplied by publisher]
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5. Rev Esp Anestesiol Reanim. 2014 Aug 22. pii: S0034-9356(14)00197-2. doi: 10.1016/j.redar.2014.05.015. [Epub ahead of print]

Perioperative management of pulmonary hypertension during lung transplantation (a lesson for other anaesthesia settings).

Rabanal JM1Real MI2Williams M3.
Author information: 
1Servicio de Anestesiología y Reanimación, Hospital Universitario 12 de Octubre, Madrid, Spain. Electronic address:jmrabanal@humv.es.
2Servicio de Anestesiología y Reanimación, Hospital Universitario 12 de Octubre, Madrid, Spain.
3Servicio de Anestesiología y Reanimación, Hospital Universitario Marqués de Valdecilla, Santander, Spain.

Abstract

Patients with pulmonary hypertension are some of the most challenging for an anaesthesiologist to manage. Pulmonary hypertension in patients undergoing surgical procedures is associated with high morbidity and mortality due to right ventricular failure, arrhythmias and ischaemia leading to haemodynamic instability. Lung transplantation is the only therapeutic option for end-stage lung disease. Patients undergoing lung transplantation present a variety of challenges for anaesthesia team, but pulmonary hypertension remains the most important. The purpose of this article is to review the anaesthetic management of pulmonary hypertension during lung transplantation, with particular emphasis on the choice of anaesthesia, pulmonary vasodilator therapy, inotropic and vasopressor therapy, and the most recent intraoperative monitoring recommendations to optimize patient care.
Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.
  PMID: 25156939 [PubMed - as supplied by publisher]
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6. Can J Cardiol. 2014 Apr 18. pii: S0828-282X(14)00280-3. doi: 10.1016/j.cjca.2014.04.014. [Epub ahead of print]

Riociguat: A Novel Therapeutic Option for Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

Mielniczuk LM1Swiston JR2Mehta S3.
Author information: 
1Department of Medicine, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Onatrio, Canada. Electronic address: lmielniczuk@ottawaheart.ca.
2Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
3Pulmonary Hypertension Association (PHA) Canada, Canada; Southwest Ontario PH Clinic, London Health Sciences Centre, London, Ontario, Canada; Division of Respirology, Department of Medicine, Schulich School of Medicine, Western University, London, Ontario, Canada.

Abstract

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are serious and often fatal diseases. The pathophysiology of both diseases is complex and in part is attributed to alterations in the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate pathway. Riociguat, a novel sGC stimulator, acts on this pathway through a dual mechanism of action by directly stimulating sGC in a NO-independent manner and also increasing the sensitivity of sGC to NO. Based on benefits from clinical trials for both PAH and CTEPH, riociguat was approved by Health Canada and the US Food and Drug Administration as the first medical therapy for patients with CTEPH who are deemed inoperable or have residual/recurrent PH after pulmonary endarterectomy (PEA), and as a novel treatment option for patients with PAH. This article reviews the key findings from the phase III trials for riociguat that led to these approvals and the implications this has for the treatment of patients with PAH and CTEPH.
Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
  PMID: 25154043 [PubMed - as supplied by publisher]
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7. Acta Anaesthesiol Taiwan. 2014 Jul 1. pii: S1875-4597(14)00076-9. doi: 10.1016/j.aat.2014.06.002. [Epub ahead of print]

Dexmedetomidine in pulmonary hypertension: A case report.

Nair AS1Kandukuri B2Gopal TV2.
Author information: 
1Department of Anesthesia, Care Hospital, Axon Anesthesia Associates, Hyderabad, India. Electronic address:abhijitnair95@gmail.com.
2Department of Anesthesia, Care Hospital, Axon Anesthesia Associates, Hyderabad, India.
  PMID: 25153071 [PubMed - as supplied by publisher]
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8. J Biomech. 2014 Jul 30. pii: S0021-9290(14)00405-9. doi: 10.1016/j.jbiomech.2014.07.024. [Epub ahead of print]

MRI model-based non-invasive differential diagnosis in pulmonary hypertension.

Lungu A1Wild JM2Capener D3Kiely DG4Swift AJ2Hose DR2.
Author information: 
1University of Sheffield, Cardiovascular Science Department, Sheffield, South Yorkshire, UK. Electronic address:mdp11al@sheffield.ac.uk.
2University of Sheffield, Cardiovascular Science Department, Sheffield, South Yorkshire, UK; INSIGNEO-Institute for in silico Medicine, University of Sheffield, Sheffield, South Yorkshire, UK.
3University of Sheffield, Cardiovascular Science Department, Sheffield, South Yorkshire, UK.
4Pulmonary Vascular Disease Unit, Sheffield, South Yorkshire, UK.

Abstract

Pulmonary hypertension(PH) is a disorder characterised by increased mean pulmonary arterial pressure. Currently, the diagnosis of PH relies upon measurements taken during invasive right heart catheterisation (RHC). This paper describes a process to derive diagnostic parameters using only non-invasive methods based upon MRI imaging alone. Simultaneous measurements of main pulmonary artery (MPA) anatomy and flow are interpreted by 0D and 1D mathematical models, in order to infer the physiological status of the pulmonary circulation. Results are reported for 35 subjects, 27 of whom were patients clinically investigated for PH and eight of whom were healthy volunteers. The patients were divided into 3 sub-groups according to the severity of the disease state, one of which represented a negative diagnosis (NoPH), depending on the results of the clinical investigation, which included RHC and complementary MR imaging. Diagnostic indices are derived from two independent mathematical models, one based on the 1D wave equation and one based on an RCR Windkessel model. Using the first model it is shown that there is an increase in the ratio of the power in the reflected wave to that in the incident wave (Wpb/Wptotal) according to the classification of the disease state. Similarly, the second model shows an increase in the distal resistance with the disease status. The results of this pilot study demonstrate that there are statistically significant differences in the parameters derived from the proposed models depending on disease status, and thus suggest the potential for development of a non-invasive, image-based diagnostic test for pulmonary hypertension.
Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
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  PMID: 25145313 [PubMed - as supplied by publisher]
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9. J Am Heart Assoc. 2014 Feb 28;3(1):e000772. doi: 10.1161/JAHA.113.000772.

Splenectomy is modifying the vascular remodeling of thrombosis.

Frey MK1Alias SWinter MPRedwan BStübiger GPanzenboeck AAlimohammadi ABonderman DJakowitsch J,Bergmeister HBochkov VPreissner KTLang IM.
Author information: 
1Department of Cardiology, Medical University Vienna, Vienna, Austria.

Abstract

BACKGROUND:

Splenectomy is a clinical risk factor for complicated thrombosis. We hypothesized that the loss of the mechanical filtering function of the spleen may enrich for thrombogenic phospholipids in the circulation, thereby affecting the vascular remodeling of thrombosis.

METHODS AND RESULTS:

We investigated the effects of splenectomy both in chronic thromboembolic pulmonary hypertension (CTEPH), a human model disease for thrombus nonresolution, and in a mouse model of stagnant flow venous thrombosis mimicking deep vein thrombosis. Surgically excised thrombi from rare cases of CTEPH patients who had undergone previous splenectomy were enriched for anionic phospholipids like phosphatidylserine. Similar to human thrombi, phosphatidylserine accumulated in thrombi after splenectomy in the mouse model. A postsplenectomy state was associated with larger and more persistent thrombi. Higher counts of procoagulant platelet microparticles and increased leukocyte-platelet aggregates were observed in mice after splenectomy. Histological inspection revealed a decreased number of thrombus vessels. Phosphatidylserine-enriched phospholipids specifically inhibited endothelial proliferation and sprouting.

CONCLUSIONS:

After splenectomy, an increase in circulating microparticles and negatively charged phospholipids is enhanced by experimental thrombus induction. The initial increase in thrombus volume after splenectomy is due to platelet activation, and the subsequent delay of thrombus resolution is due to inhibition of thrombus angiogenesis. The data illustrate a potential mechanism of disease in CTEPH.
PMCID: PMC3959675 Free PMC Article
  PMID: 24584745 [PubMed - indexed for MEDLINE]
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10. J Am Heart Assoc. 2014 Feb 26;3(1):e000520. doi: 10.1161/JAHA.113.000520.

Mechanism of the susceptibility of remodeled pulmonary vessels to drug-induced cell killing.

Ibrahim YF1Wong CMPavlickova LLiu LTrasar LBansal GSuzuki YJ.
Author information: 
1Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, 20057, DC.

Abstract

BACKGROUND:

Pulmonary arterial hypertension remains a devastating disease without a cure. The major complication of this disease is the abnormal growth of vascular cells, resulting in pulmonary vascular remodeling. Thus, agents, which affect the remodeled vessels by killing unwanted cells, should improve treatment strategies. The present study reports that antitumor drugs selectively kill vascular cells in remodeled pulmonary vessels in rat models of pulmonary hypertension.

METHODS AND RESULTS:

After developing pulmonary vascular remodeling in chronic hypoxia or chronic hypoxia/SU-5416 models, rats were injected with antitumor drugs including proteasome inhibitors (bortezomib and MG-132) and daunorubicin. Within 1 to 3 days, these agents reduced the media and intima thickness of remodeled pulmonary vascular walls, but not the thickness of normal pulmonary vessels. These drugs also promoted apoptotic and autophagic death of vascular cells in the remodeled vessels, but not in normal vessels. We provide evidence that the upregulation of annexin A1, leading to GATA4-dependent downregulation of Bcl-xL, is a mechanism for specific apoptotic killing, and for the role of parkin in defining specificity of autophagic killing of remodeled vascular cells. The reversal of pulmonary vascular remodeling increased the capacity of vasodilators to reduce pulmonary arterial pressure.

CONCLUSIONS:

These results suggest that antitumor drugs can specifically kill cells in remodeled pulmonary vascular walls and may be useful for improving the efficacy of current therapeutic strategies to treat pulmonary arterial hypertension.
PMCID: PMC3959719 Free PMC Article
  PMID: 24572252 [PubMed - indexed for MEDLINE]
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11. J Am Heart Assoc. 2014 Feb 3;3(1):e000363. doi: 10.1161/JAHA.113.000363.

Echocardiographic assessment of pulmonary artery systolic pressure and outcomes in ambulatory heart failure patients.

Kalogeropoulos AP1Siwamogsatham SHayek SLi SDeka AMarti CNGeorgiopoulou VVButler J.
Author information: 
1Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University, Atlanta, GA.

Abstract

BACKGROUND:

Pulmonary hypertension (PH) in patients with heart failure (HF) is associated with worse outcomes and is rapidly being recognized as a therapeutic target. To facilitate pragmatic research efforts, data regarding the prognostic importance of noninvasively assessed pulmonary artery systolic pressure (PASP) in stable ambulatory patients with HF are needed.

METHODS AND RESULTS:

We examined the association between echocardiographic PASP and outcomes in 417 outpatients with HF (age, 54 ± 13 years; 60.7% men; 50.4% whites; 24.9% with preserved ejection fraction). Median PASP was 36 mm Hg (interquartile range [IQR]: 29, 46). After a median follow-up of 2.6 years (IQR: 1.7, 3.9) there were 72 major events (57 deaths; 9 urgent heart transplants; and 6 ventricular assist device implantations) and 431 hospitalizations for HF. In models adjusting for clinical risk factors and therapy, a 10-mm Hg higher PASP was associated with 37% higher risk (95% CI: 18, 59; P<0.001) for major events, and 11% higher risk (95% CI: 1, 23; P=0.039) for major events or HF hospitalization. The threshold that maximized the likelihood ratio for both endpoints was 48 mm Hg; those with PASP ≥ 48 mm Hg (N=84; 20.1%) had an adjusted hazard ratio of 3.33 (95% CI: 1.96, 5.65; P<0.001) for major events and 1.47 (95% CI: 1.02, 2.11; P=0.037) for major events or HF hospitalization. Reduced right ventricular systolic function had independent prognostic utility over PASP for adverse outcomes. Right atrial pressure and transtricuspid gradient both contributed to risk.

CONCLUSIONS:

Elevated PASP, determined by echocardiography, identifies ambulatory patients with HF at increased risk for adverse events.
PMCID: PMC3959670 Free PMC Article
  PMID: 24492947 [PubMed - indexed for MEDLINE]
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12. ASAIO J. 2014 Jan-Feb;60(1):129-33. doi: 10.1097/MAT.0000000000000021.

Extracorporeal membrane oxygenation as a novel bridging strategy for acute right heart failure in group 1 pulmonary arterial hypertension.

Rosenzweig EB1Brodie DAbrams DCAgerstrand CLBacchetta M.
Author information: 
1From the *Division of Pediatric Cardiology, Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York; †Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York; and ‡Division of Cardiothoracic Surgery, Department of Surgery, Columbia University, College of Physicians and Surgeons, New York, New York.

Abstract

Patients with group 1 pulmonary arterial hypertension (PAH) and decompensated right heart failure (RHF) were not previously considered for extracorporeal membrane oxygenation (ECMO) as bridge to transplantation (BTT) or bridge to recovery (BTR) because options were limited by long transplantation wait times and perceived inability to wean ECMO. In a retrospective review, we describe our center's multidisciplinary mechanical-medical approach to ECMO as a bridging therapy for PAH (2009-2012). Suitability for ECMO was determined using a defined algorithm. Six patients (age, 32 ± 11 years) underwent mechanical-medical bridging. Two transplant-eligible patients underwent successful BTT. The four patients ineligible for transplantation underwent BTR with escalation of targeted medical therapies before weaning off ECMO. Three of four BTR patients survived to ECMO decannulation (duration, 12 ± 7; range, 7-23 days). In this single-institution experience, mechanical-medical BTT and BTR with ECMO and targeted PAH therapies were used as a novel treatment strategy to successfully manage acute RHF in PAH.
  PMID: 24299971 [PubMed - indexed for MEDLINE]
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13. Pharmacol Ther. 2014 Feb;141(2):172-91. doi: 10.1016/j.pharmthera.2013.10.002. Epub 2013 Oct 14.

Targeted therapies in pulmonary arterial hypertension.

Montani D1Chaumais MC2Guignabert C1Günther S1Girerd B1Jaïs X1Algalarrondo V3Price LC4Savale L1Sitbon O1Simonneau G1Humbert M5.
Author information: 
1Univ. Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
2INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France; Univ. Paris-Sud, Châtenay Malabry, France; AP-HP, Pharmacie, DHU Thorax Innovation, Hôpital Antoine Béclère, Clamart, France.
3Univ. Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Cardiologie, DHU Thorax Innovation, Hôpital Antoine Béclère, Clamart, France.
4National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, Dovehouse Street, London SW3 6LY, UK.
5Univ. Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France. Electronic address: marc.humbert@bct.aphp.fr.

Abstract

Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of small pulmonary arteries that leads to elevated pulmonary arterial pressure and right heart failure. During the last decades, an improved understanding of the pathophysiology of the disease has resulted in the development of effective therapies targeting endothelial dysfunction (epoprostenol and derivatives, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors). These drugs allow clinical, functional and hemodynamic improvement. Even though, no cure exists for PAH and prognosis remains poor. Recently, several additional pathways have been suggested to be involved in the pathogenesis of PAH, and may represent innovative therapies. In this summary, we review conventional therapy, pharmacological agents currently available for the treatment of PAH and the benefit/risk ratio of potential future therapies.
© 2013 Elsevier Inc. All rights reserved.
  PMID: 24134901 [PubMed - indexed for MEDLINE]
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14. Circ Res. 2014 Aug 22. pii: CIRCRESAHA.114.304563. [Epub ahead of print]

Basigin Mediates Pulmonary Hypertension by Promoting Inflammation and Vascular Smooth Muscle Cell Proliferation.

Satoh K1Sato T1Kikuchi N1Omura J1Kurosawa R1Suzuki K1Sugimura K1Aoki T1Nochioka K1Tatebe S1,Miyamichi-Yamamoto S1Miura M1Shimizu T1Ikeda S1Yaoita N1Fukumoto Y1Minami T1Miyata S1Nakamura K2Ito H2Kadomatsu K3Shimokawa H4.
Author information: 
1Cardiovascular Medicine, Tohoku University Graduate School of Medicine.
2Cardiovascular Medicine, Okayama University Graduate School of Medicine.
3Biochemistry, Nagoya University Graduate School of Medicine.
4Cardiovascular Medicine, Tohoku University Graduate School of Medicine shimo@cardio.med.tohoku.ac.jp.

Abstract

Rationale: Cyclophilin A (CyPA) is secreted from vascular smooth muscle cells (VSMCs) by oxidative stress and promotes VSMC proliferation. However, the role of extracellular CyPA and its receptor Basigin (Bsg, encoded by Bsg) in the pathogenesis of pulmonary hypertension (PH) remains to be elucidated. Objective: To determine the role of CyPA/Bsg signaling in the development of PH. Methods and Results: In the pulmonary arteries (PA) of PH patients, immunostaining revealed strong expression of CyPA and Bsg. The PA of CyPA+/- and Bsg+/- mice exposed to normoxia did not differ in morphology compared with their littermate controls. In contrast, CyPA+/-and Bsg+/- mice exposed to hypoxia for 4 weeks revealed significantly reduced right ventricular systolic pressure (RVSP), PA remodeling and RV hypertrophy compared with their littermate controls. These features were unaltered by bone marrow reconstitution. To further evaluate the role of vascular Bsg, we harvested pulmonary VSMCs from Bsg+/+ and Bsg+/- mice. Proliferation was significantly reduced in Bsg+/- compared with Bsg+/+VSMCs. Mechanistic studies demonstrated that Bsg+/- VSMCs revealed reduced extracellular signal-regulated kinase (ERK)1/2 activation and less secretion of cytokines/chemokines and growth factors (e.g. PDGF-BB). Finally, in the clinical study, plasma CyPA levels in PH patients were increased in accordance with the severity of pulmonary vascular resistance. Furthermore, event-free curve revealed that high plasma CyPA levels predicted poor outcome in PH patients. Conclusions: These results indicate the crucial role of extracellular CyPA and vascular Bsg in the pathogenesis of PH.
  PMID: 25149188 [PubMed - as supplied by publisher]
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15. Rev Paul Pediatr. 2014 Jun;32(2):159-63.

Prevalence and profile of congenital heart disease and pulmonary hypertension in Down syndrome in a pediatric cardiology service.

[Article in English, Portuguese]
Mourato FAVillachan LRMattos Sda S.
Author information: 
Unidade de Cardiologia Materno-Fetal, Recife, PE, Brasil.

Abstract

OBJECTIVE:

To determine the frequence and profile of congenital heart defects in Down syndrome patients referred to a pediatric cardiologic center, considering the age of referral, gender, type of heart disease diagnosed by transthoracic echocardiography and its association with pulmonary hypertension at the initial diagnosis.

METHODS:

Cross-sectional study with retrospective data collection of 138 patients with Down syndrome from a total of 17,873 records. Descriptive analysis of the data was performed, using Epi-Info version 7.

RESULTS:

Among the 138 patients with Down syndrome, females prevailed (56.1%) and 112 (81.2%) were diagnosed with congenital heart disease. The most common lesion was ostium secundum atrial septal defect, present in 51.8%, followed by atrioventricular septal defect, in 46.4%. Ventricular septal defects were present in 27.7%, while tetralogy of Fallot represented 6.3% of the cases. Other cardiac malformations corresponded to 12.5%. Pulmonary hypertension was associated with 37.5% of the heart diseases. Only 35.5% of the patients were referred before six months of age.

CONCLUSIONS:

The low percentage of referral until six months of age highlights the need for a better tracking of patients with Down syndrome in the context of congenital heart disease, due to the high frequency and progression of pulmonary hypertension.
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  PMID: 25119745 [PubMed - in process]
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16. Genet Mol Res. 2014 Jul 25;13(3):5695-703. doi: 10.4238/2014.July.25.25.

Pulmonary hypertension in patients with stage 1-3 chronic kidney disease.

Yang QM1Bao XR2.
Author information: 
1Department of Nephrology, Jinshan Hospital, Fudan University, Shanghai, China.
2Department of Nephrology, Jinshan Hospital, Fudan University, Shanghai, China XiaorongBAOcn@163.com.

Abstract

Pulmonary hypertension (PH) secondary to chronic kidney disease (CKD) is common, but in stages 1-3 CKD patients, it remains unclear. We sought to evaluate the prevalence of PH and elucidate the possible pathogenesis in Chinese patients with early stage kidney disease. Doppler-estimated pulmonary systolic artery pressure (PASP) was measured in 101 CKD patients with glomerular filtration rate (GFR) ≥60 mL/min/1.73 m(2) and 27 CKD patients with GFR < 60 mL/min/1.73 m(2). Echocardiographic parameters, plasma brain natriuretic peptide (BNP), and baseline characteristics of patients were recorded. PH was defined as a PASP ≥ 35 mmHg. PH prevalence was 23.76% (24/101) in GFR ≥ 60 mL/min/1.73 m(2) group and 48.15% (13/27) in GFR < 60 mL/min/1.73 m(2) group, P < 0.05. Mean lnBNP was 4.93 ± 1.60 pg/mL in 37 cases with PH and 2.89 ± 1.29 pg/mL in those without, P < 0.01. Left atrial diameter (LA) showed deviation between patients with (43.94 ± 5.81 mm) and without PH (37.76 ± 7.48 mm), P < 0.01. GFR declined significantly in PH group (44.10 ± 22.90 mL/min/1.73 m(2)) compared to non-PH group (75.59 ± 31.62 mL/min/1.73 m(2)), P < 0.01. lnBNP, LA and GFR were independent determinants (r = 0.651, 0.595, -0.488, P < 0.01) of PASP. PH is prevalent among stage 1-3 CKD patients in China. Doppler-estimated PASP is strongly associated with lnBNP, enlarged LA and GFR. Monitoring PASP, plasma BNP and evaluation renal function may help to detect and prevent severe PH in CKD.
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  PMID: 25117327 [PubMed - in process]
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17. Echocardiography. 2014 Aug 8. doi: 10.1111/echo.12690. [Epub ahead of print]

Influence of Pulmonary Vascular Reserve on Exercise-Induced Pulmonary Hypertension in Patients with Systemic Sclerosis.

Suzuki K1Izumo MKamijima RMizukoshi KTakai MKida KYoneyama KNobuoka SYamada HAkashi YJ.
Author information: 
1Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.

Abstract

BACKGROUND:

Exercise-induced pulmonary hypertension (PH) is considered as an early preclinical functional phase of resting PH in systemic sclerosis (SSc). In this study, we investigated the prevalence of exercise-induced PH in patients with SSc and evaluated the influence of pulmonary vascular reserve on exercise-induced PH.

METHODS:

This prospective study included 568 SSc patients. The patients with interstitial lung disease and those with left ventricular dysfunction were excluded (n = 50); finally, 518 patients underwent simple exercise echocardiography using a Master's two-step. Systolic pulmonary artery pressure (SPAP), the ratio of early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e') and pulmonary vascular resistance (PVR) were measured before and after exercise. ΔPVR (the difference between rest and post) was used for the assessment of pulmonary vascular reserve. All patients were stratified into the no exercise-induced PH (SPAP <50 mmHg) or exercise-induced PH (SPAP ≥50 mmHg, n = 133) group.

RESULTS:

Of the study patients, 27% patients were identified as having exercise-induced PH. ΔPVR was higher in the exercise-induced PH than no exercise-induced PH group (0.2 ± 0.3 vs. 0.4 ± 0.4WU, P < 0.0001). A weak correlation was found between postexercise SPAP and postexercise E/e' (r = 0.31, P < 0.0001), whereas a strong correlation was found between postexercise SPAP and postexercise PVR (r = 0.62, P < 0.0001). The analyzed data demonstrated that ΔPVR was independently associated with exercise-induced PH (odds ratio, 3.435; 95% CI, 1.013-11.650, P = 0.033).

CONCLUSIONS:

The present study demonstrated that exercise-induced PH was common in patients with SSc. Exercise-induced PH might be closely associated with the factors affecting reduced pulmonary vascular reserve in patients with SSc.
© 2014, Wiley Periodicals, Inc.
  PMID: 25104236 [PubMed - as supplied by publisher]
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18. J Am Heart Assoc. 2014 Aug 7;3(4). pii: e000748. doi: 10.1161/JAHA.113.000748.

Pulmonary hypertension in mitral regurgitation.

Patel HDesai MTuzcu EMGriffin BKapadia S.
Author information: 
Cleveland Clinic Foundation, Cleveland, OH (H.P., M.D., M.T., B.G., S.K.).
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  PMID: 25103202 [PubMed - in process]
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19. South Med J. 2014 Mar;107(3):144-9. doi: 10.1097/SMJ.0000000000000066.

Submaximal cardiopulmonary exercise testing for the evaluation of unexplained dyspnea.

Bhatt DVKocheril AG.
Author information: 
From the Department of Cardiology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, and the University of Illinois College of Medicine at Urbana-Champaign.

Abstract

OBJECTIVES:

Gas exchange measurements obtained during submaximal exercise have been shown to provide prognostic and diagnostic information in patients with heart failure (HF) and to differentiate heart versus lung limitations in patients with unexplained dyspnea. The aim of our study was to assess the clinical utility of submaximal cardiopulmonary exercise testing using the Shape-HF equipment in identifying the cause of unexplained dyspnea.

METHODS:

A total of 65 patients underwent Shape-HF tests from September 2010 to June 2011 for unexplained dyspnea at our center.

RESULTS:

Of 65 patients, 39 were men and 26 were women. In this study, 23 patients had preexisting asthma or chronic obstructive pulmonary disease (COPD); 19 patients had a pacemaker (8), an implantable cardioverter defibrillator (2), or a cardiac resynchronization therapy defibrillator (CRT-D) (9). The study revealed that submaximal cardiopulmonary exercise testing provided supportive clinical data for deconditioning, pulmonary limitations (eg, COPD, interstitial lung disease, sleep apnea), pulmonary hypertension, and chronotropic incompetence in 21.5%, 23.1%, 13.8%, and 6.2% of patients, respectively. Pulmonary hypertension was confirmed in 55% of patients by echocardiography and lung problems were confirmed in 40% of patients by pulmonary function test and sleep study. Of nine patients with an implanted CRT-D, optimization of atrioventricular and interventricular programming was performed in seven (78%) using gas exchange monitoring while performing a steady state, low-level treadmill walk.

CONCLUSIONS:

Submaximal cardiopulmonary exercise testing has strongly suggested the diagnosis of COPD, interstitial lung disease, pulmonary hypertension, and deconditioning and has led to appropriate testing. Based on prior studies, we also used Shape-HF for its approved purpose of optimizing CRT-D programming in patients with HF, leading to clinical improvement.
  PMID: 24937330 [PubMed - indexed for MEDLINE]
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20. Arthritis Rheumatol. 2014 Jun;66(6):1625-35. doi: 10.1002/art.38390.

Prediction of pulmonary complications and long-term survival in systemic sclerosis.

Nihtyanova SI1Schreiber BEOng VHRosenberg DMoinzadeh PCoghlan JGWells AUDenton CP.
Author information: 
1University College London Medical School, Royal Free Hospital, London, UK.

Abstract

OBJECTIVE:

To assess survival and incidence of organ-based complications in a large single-center cohort of unselected systemic sclerosis (SSc) patients, and to explore predictors of survival and clinically significant pulmonary fibrosis (PF) and pulmonary hypertension (PH).

METHODS:

The study cohort consisted of 398 consecutive SSc patients, followed up for up to 15 years. Cox proportional hazards analysis with demographic, clinical, and laboratory characteristics as predictor variables was used to develop prediction models for pulmonary complications and survival.

RESULTS:

The overall survival estimate at the end of followup was 57% among patients with limited cutaneous SSc (lcSSc) and 50% among patients with diffuse cutaneous SSc (dcSSc) (P = 0.017). We found that greater age at disease onset, dcSSc, lower diffusing capacity for carbon monoxide (DLco), lower hemoglobin levels, higher serum creatinine levels, and the presence of PH or cardiac involvement were independent predictors of worse survival. Over the entire followup period, 42% of dcSSc patients and 22% of lcSSc patients developed clinically significant PF (P < 0.001). The variables that predicted clinically significant PF development were dcSSc, greater age at onset, lower forced vital capacity and DLco, and the presence of anti-topoisomerase I antibody, while the presence of anticentromere antibody was protective. There was no difference in cumulative incidence of PH between the 2 subsets-24% in lcSSc and 18% in dcSSc (P = 0.558). Incidence rates were 1-2% per year. The PH prediction model demonstrated that greater age at onset, increase in serum creatinine levels, lower DLco, and the presence of anti-RNA polymerase III or anti-U3 RNP antibodies were associated with increased risk of PH, while anti-topoisomerase I antibody positivity reduced the hazard.

CONCLUSION:

Our study provides data on long-term outcome of SSc and the timing and frequency of major organ complications. The predictive models we present could be used as clinical tools for patient risk stratification and could facilitate cohort enrichment for event-driven studies.
Copyright © 2014 by the American College of Rheumatology.
  PMID: 24591477 [PubMed - indexed for MEDLINE]
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21. Am J Respir Cell Mol Biol. 2014 Jun;50(6):1118-28. doi: 10.1165/rcmb.2013-0349OC.

Loss of bone morphogenetic protein receptor 2 is associated with abnormal DNA repair in pulmonary arterial hypertension.

Li M1Vattulainen SAho JOrcholski MRojas VYuan KHelenius MTaimen PMyllykangas SDe Jesus Perez V,Koskenvuo JWAlastalo TP.
Author information: 
11 The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Abstract

Occlusive vasculopathy with intimal hyperplasia and plexogenic arteriopathy are severe histopathological changes characteristic of pulmonary arterial hypertension (PAH). Although a phenotypic switch in pulmonary endothelial cells (ECs) has been suggested to play a critical role in the formation of occlusive lesions, the pathobiology of this process is poorly understood. The goal of this study was to identify novel molecular mechanisms associated with EC dysfunction and PAH-associated bone morphogenetic protein receptor 2 (BMPR2) deficiency during PAH pathogenesis. A bioinfomatics approach, patient samples, and in vitro experiments were used. By combining a metaanalysis of human idiopathic PAH (iPAH)-associated gene-expression microarrays and a unique gene expression-profiling technique in rat endothelium, our bioinformatics approach revealed a PAH-associated dysregulation of genes involving chromatin organization, DNA metabolism, and repair. Our hypothesis that altered DNA repair and loss of genomic stability play a role in PAH was supported by in vitro assays where pulmonary ECs from patients with iPAH and BMPR2-deficient ECs were highly susceptible to DNA damage. Furthermore, we showed that BMPR2 expression is tightly linked to DNA damage control because excessive DNA damage leads to rapid down-regulation of BMPR2 expression. Moreover, we identified breast cancer 1 (BRCA1) as a novel target for BMPR2 signaling and a novel modulator of pulmonary EC homeostasis. We show here that BMPR2 signaling plays a critical role in the regulation of genomic integrity in pulmonary ECs via genes such as BRCA1. We propose that iPAH-associated EC dysfunction and genomic instability are mediated through BMPR2 deficiency-associated loss of DNA damage control.
  PMID: 24433082 [PubMed - indexed for MEDLINE]
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22. J Card Fail. 2013 Nov;19(11):746-52. doi: 10.1016/j.cardfail.2013.09.006. Epub 2013 Oct 4.

Dynamic nature of pulmonary artery systolic pressure in decompensated heart failure with preserved ejection fraction: role of functional mitral regurgitation.

Ennezat PV1Maréchaux SBouabdallaoui NLe Jemtel TH.
Author information: 
1Institut Fédératif de Recherche, Université Lille Nord de France, Lille, France. Electronic address: ennezat@yahoo.com.

Abstract

BACKGROUND:

Pulmonary hypertension (PH) is prevalent in decompensated heart failure with preserved ejection fraction (HFpEF). We investigated the effect of a return to a compensated state on pulmonary artery systolic pressure (PASP) and functional mitral regurgitation (FMR).

METHODS AND RESULTS:

Two-dimensional Doppler echocardiography was prospectively performed before initiation of standard therapy and 48 hours later in 37 patients hospitalized for HFpEF-related dyspnea and in 26 patients hospitalized for non-HFpEF-related dyspnea. Left atrial volume index, and E/e' ratio, and PASP were significantly greater and E-wave deceleration time significantly shorter in HFpEF than in non-HFpEF patients. Thirty-two of the 37 HFpEF had FMR on admission whereas none of the non-HFpEF patients had FMR. After 48 hours of therapy, the reduction in PASP was significantly greater in the 26 HFpEF patients who improved than in the 11 HFpEF patients who did not (-24 vs -9 mm Hg, respectively; P < .0001), whereas PASP remained unchanged in non-HFpEF patients. The decrease in PASP correlated in HFpEF patients with reductions in blood pressure, heart rate, left ventricular end-diastolic volume, inferior vena cava diameter, E/A ratio, E/e' ratio, mitral effective regurgitant orifice area (EROA), and E-wave deceleration time. The correlation between PASP and mitral EROA was the only one that remained significant by multivariate analysis.

CONCLUSIONS:

Noninvasive monitoring of PASP and FMR during an episode of HFpEF decompensation reveals that the return to a compensated state is associated with a significant reduction in PASP and FMR.
Copyright © 2013 Elsevier Inc. All rights reserved.
  PMID: 24263118 [PubMed - indexed for MEDLINE]
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23. Am J Respir Crit Care Med. 2014 Jun 15;189(12):1562-4. doi: 10.1164/rccm.201311-2025LE.

Treatment of group I pulmonary arterial hypertension with carvedilol is safe.

Grinnan D1Bogaard HJGrizzard JVan Tassell BAbbate ADeWilde CPriday AVoelkel NF.
Author information: 
11 Virginia Commonwealth University Richmond, Virginia.
  PMID: 24930531 [PubMed - indexed for MEDLINE]
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24. Am J Respir Crit Care Med. 2014 Jun 1;189(11):1435-6. doi: 10.1164/rccm.201311-2019IM.

Better off blue: BMPR-2 mutation, arteriovenous malformation, and pulmonary arterial hypertension.

Soon E1Southwood MSheares KPepke-Zaba JMorrell NW.
Author information: 
11 Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; and.
  PMID: 24881940 [PubMed - indexed for MEDLINE]
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25. Case Rep Cardiol. 2014;2014:427045. doi: 10.1155/2014/427045. Epub 2014 Jul 17.

Accidental left circumflex artery to right lung fistula in a suspected case of pulmonary hypertension.

Alipourparsa S1Khaheshi I1Eslami V1Bozorgmanesh M2Haybar H3.
Author information: 
1Cardiovascular Research Center, Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3Cardiovascular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Abstract

A 56-year-old woman was referred to the cardiology department of the Shahid Modarres hospital. The patient had a history of pulmonary thromboembolism 20 years ago which had been managed by the inferior vena cava filter and since then the patient has been on warfarin. Her chief complaint was chronic dyspnea on exertion (NYHA class II) from several years ago. Right and left heart catheterization was performed for evaluation of pulmonary artery pressure. We found rich collateral formations between LCX as well as RCA and right pulmonary artery, primarily assumed as multiple fistulas. Among patients who have chronic thromboembolic pulmonary hypertension, systemic collateral supply to the pulmonary parenchyma has been previously reported to occur from both bronchial and/or nonbronchial systemic circulations. Our patient had neither signs of heart failure nor myocardial ischemia and, thus, was a candidate for conservative management. The adenosine pulmonary reactivity test was not performed because of low pulmonary pressure which had been estimated to be high.
PMCID: PMC4124836 Free PMC Article
  PMID: 25143836 [PubMed]
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26. EuroIntervention. 2014 Aug 20;10(4):518-25. doi: 10.4244/EIJV10I4A89.

Balloon pulmonary angioplasty: an additional treatment option to improve the prognosis of patients with chronic thromboembolic pulmonary hypertension.

Taniguchi Y1Miyagawa KNakayama KKinutani HShinke TOkada KOkita YHirata KIEmoto N.
Author information: 
1Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Abstract

AIMS:

To evaluate the efficacy and safety of balloon pulmonary angioplasty (BPA) in patients with non-operable chronic thromboembolic pulmonary hypertension (CTEPH) using the results of pulmonary endarterectomy (PEA) for operable patients as a reference, and annotate the role of BPA in the management of CTEPH.

METHODS AND RESULTS:

Data from 53 CTEPH patients were collected retrospectively. Twenty-four operable patients underwent PEA, and 29 non-operable patients underwent BPA. Patients who underwent BPA showed improved mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output (39.4±6.9 to 21.3±5.6 mmHg, 763±308 to 284±128 dyn·s-1·cm-5, 3.47±0.80 to 4.26±1.15 L/min, respectively); patients who received PEA showed similar efficacy (44.4±11.0 to 21.6±6.7 mmHg, 781±278 to 258±125 dyn·s-1·cm-5, 3.35±1.11 to 4.44±1.58 L/min, respectively). The mortality rates of BPA and PEA patients were 3.4% and 8.3%, respectively.

CONCLUSIONS:

The efficacy and safety of BPA for non-operable cases were similar to those achieved using PEA for operable cases. BPA could be an additional treatment option for non-operable CTEPH patients, and most CTEPH patients can be satisfactorily treated by BPA or PEA.
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  PMID: 25138190 [PubMed - in process]
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27. Curr Opin Pediatr. 2014 Aug 16. [Epub ahead of print]

Progress in the diagnosis and management of pulmonary hypertension in children.

Nicolarsen J1Ivy D.
Author information: 
1Department of Pediatrics, University of Colorado and Children's Hospital Colorado, Aurora, Colorado, USA.

Abstract

PURPOSE OF REVIEW:

Pulmonary hypertension is a complex disease that extends beyond merely elevated pulmonary blood pressures and right ventricular dysfunction. Its multiple causes and ever-expanding diagnostic tools and therapeutic approaches make it a heterogeneous disease with widely variable clinical sequelae. There are still many unanswered questions that challenge our understanding of this disease.

RECENT FINDINGS:

The study of pulmonary hypertension in the pediatric patient is as robust as ever, with the creation and inclusion of pediatric-specific disease characteristics in the most recent WHO classification system, improved understanding of the pathophysiology of pulmonary hypertension in pediatric diseases such as bronchopulmonary dysplasia, and increasingly expanding diagnostic tools and management possibilities. Although the use of pulmonary hypertension therapies in children previously often relied on expert opinion and inferences from studies involving adults, pediatric-targeted research is becoming more widely supported and pursued, and has even come under recent debate, which at the very least stimulates further collaboration and discussion.

SUMMARY:

This review will highlight the changes in the pulmonary hypertension classification system, briefly explore pulmonary hypertension in bronchopulmonary dysplasia, and provide updates on the diagnostic and management tools used by experts in the field.
  PMID: 25136947 [PubMed - as supplied by publisher]
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28. Curr Heart Fail Rep. 2014 Aug 19. [Epub ahead of print]

Epidemiology of Pulmonary Hypertension and Right Ventricular Failure in Left Heart Failure.

Thenappan T1Gomberg-Maitland M.
Author information: 
1Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.

Abstract

Pulmonary hypertension (PH) leading to right ventricular failure (RVF) is a common complication of left heart failure irrespective of the left ventricular ejection fraction. PH due to left heart disease is the most common cause of PH. The prevalence of PH and RVF in left heart failure varies depending on the patient population studied, the method used to diagnose PH, and the hemodynamic criteria used to define PH. Elevated left-sided filling pressure and functional mitral regurgitation are the two major determinants of PH in left heart failure. PH is associated with markers of disease severity, advanced symptoms, and worse long-term outcomes including heart failure hospitalization and mortality in left heart failure. RVF has independent, incremental prognostic value over PH for adverse outcomes in left heart failure. PH and RVF may be potential therapeutic targets in patients with left heart failure.
  PMID: 25135469 [PubMed - as supplied by publisher]
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29. Intern Med. 2014;53(16):1829-33. Epub 2014 Aug 15.

Chronic Thromboembolic Pulmonary Hypertension Complicated by a Cavitating Lung Infection Caused by Mycobacterium intracellulare.

Okuda K1Matsui HSuzuki JOhshima NMasuda KYamane ATamura ANagai HAkagawa SOhta K.
Author information: 
1Center for Pulmonary Diseases, National Hospital Organization, Tokyo National Hospital, Japan.

Abstract

A 35-year-old man with a six-month history of progressive exertional dyspnea was referred to our institution. He had been diagnosed with Mycobacterium intracellulare pulmonary infection with lung cavitation two years earlier, and was being followed up without any medications. After being referred to our hospital, he underwent computed tomographic pulmonary angiography, which indicated a pulmonary thrombus and lung cavitation. Furthermore, right heart catheterization confirmed pulmonary hypertension, and we made a diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH). Following successful pulmonary endarterectomy, the patient's symptoms and hemodynamics were significantly improved, with the disappearance of lung cavitation. It is important to suspect CTEPH in patients with unaccountable infectious lung cavities.
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  PMID: 25130120 [PubMed - in process]
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30. Heart Lung. 2014 Jul-Aug;43(4):317-21. doi: 10.1016/j.hrtlng.2014.04.001. Epub 2014 May 10.

Differences in pulmonary function and exercise capacity in patients with idiopathic dilated cardiomyopathy and idiopathic pulmonary arterial hypertension.

Liu WH1Luo Q1Liu ZH2Zhao Q1Xi QY1Zhao ZH1.
Author information: 
1State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China.
2State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China. Electronic address:fuwailiu@hotmail.com.

Abstract

OBJECTIVES:

We observed the pulmonary function and exercise capacity of idiopathic dilated cardiomyopathy (IDCM) and idiopathic pulmonary arterial hypertension (IPAH) patients using cardiopulmonary exercise testing (CPX). We evaluated and compared the two groups.

BACKGROUND:

Pulmonary abnormalities and decreased exercise capacity are common in IDCM and IPAH. Little is known about the differences in these two syndromes.

METHODS:

Sixty-three patients were involved the study, 23 with IDCM and 40 with IPAH. All patients underwent pulmonary function testing at rest and CPX.

RESULTS:

Patients with IPAH had a higher peak respiratory frequency (32.40 ± 7.88 vs 29.60 ± 6.50 b/min), peak dead space volume/tidal volume (29.33 ± 4.55 vs 26.30  ± 3.31%), peak end-tidal partial pressure of O2 (125.18 ± 5.88 vs 115.17 ± 6.06 mm Hg), peak minute ventilation/CO2 production (50.14 ± 13.26 vs 33.50 ± 6.80 L/min/L/min), and a lower peak oxygen uptake (1262.70 ± 333.34 vs 742.76 ± 194.72 ml/min), peak minute ventilation (38.20 ± 13.07 vs 45.33 ± 12.31 L), peak oxygen uptake/heart rate (5.11 ± 1.47 vs 9.43 ± 2.79 ml/b) and peak end-tidal partial pressure of CO2 (23.73 ± 5.39 vs 35.30 ± 5.45 mm Hg) during exercise.

CONCLUSIONS:

Compared to IDCM, patients with IPAH had worse pulmonary function and exercise capacity resulting from severe ventilation/perfusion mismatching and gas exchange abnormalities.
Copyright © 2014 Elsevier Inc. All rights reserved.
  PMID: 24824738 [PubMed - indexed for MEDLINE]
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31. Heart Fail Clin. 2014 Jan;10(1):91-104. doi: 10.1016/j.hfc.2013.09.005.

The exceptional and far-flung manifestations of heart failure in Eisenmenger syndrome.

Opotowsky AR1Landzberg MJBeghetti M.
Author information: 
1Boston Adult Congenital Heart and Pulmonary Hypertension Service, Boston Children's Hospital and Brigham and Women's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.

Abstract

Dramatic advances in the diagnosis and treatment of congenital heart disease (CHD), the most common inborn defect, has resulted in a growing population of adults with CHD. Eisenmenger syndrome (ES) represents the extreme form of pulmonary arterial hypertension associated with CHD, characterized by markedly increased pulmonary vascular resistance with consequently reversed or bidirectional shunting. While ES is a direct consequence of a heart defect, it is a fundamentally multisystem syndrome with wide-ranging clinical manifestations. The introduction of targeted pulmonary hypertension therapies aimed has subtly shifted clinical focus from preventing iatrogenic and other adverse events toward cautious therapeutic activism.
Copyright © 2014 Elsevier Inc. All rights reserved.
  PMID: 24275297 [PubMed - indexed for MEDLINE]
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32. Circ J. 2014;78(1):4-11. Epub 2013 Nov 13.

Assessment of operability of patients with pulmonary arterial hypertension associated with congenital heart disease.

Myers PO1Tissot CBeghetti M.
Author information: 
1Division of Cardiovascular Surgery, Geneva University Hospitals & School of Medicine.

Abstract

Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease, and is now predominantly among patients with uncorrected left-to-right shunts. A growing population is characterized by persistent or recurrent PAH after surgical or interventional correction of left-to-right shunts; the latter having a worse prognosis than other forms of PAH associated with congenital heart disease. New treatments for PAH have been shown to be effective in improving PAH exercise capacity and hemodynamics, raising the hope for making previously inoperable congenital heart defects operable and shifting the framework for the assessment of operability. This review focuses on current methods for assessing operability in PAH associated with congenital heart disease, and the possibility of "treat-and-repair" vs. "repair-and-treat" strategies for patients with inoperable or borderline PAH.
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  PMID: 24225339 [PubMed - indexed for MEDLINE]
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33. Circ J. 2014;78(1):215-21. Epub 2013 Nov 12.

Incremental shuttle walk test as a valuable assessment of exercise performance in patients with pulmonary arterial hypertension.

Irisawa H1Takeuchi KInui NMiyakawa SMorishima YMizushima TWatanabe H.
Author information: 
1Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine.

Abstract

BACKGROUND:

Nearly all clinical trials investigating patients with pulmonary arterial hypertension (PAH) have used the 6-min walk test (6MWT) to evaluate exercise tolerance. The incremental shuttle walk test (SWT), however, has been proposed as a more valid and reproducible alternative to the 6MWT in the evaluation of exercise tolerance in patients with chronic obstructive pulmonary disease. The efficacy of SWT in clinical practice to evaluate the exercise capacity of patients with PAH was investigated.

METHODS AND RESULTS:

The peak oxygen consumption (pVO2) and oxygen consumption at anaerobic threshold (VO2 at AT), the gold standard for measurement of exercise tolerance, 6MWT and SWT were measured in 19 clinically stable PAH patients (WHO functional class II-III) and the data compared. There was a higher correlation between SWT walk distance and pVO2 than between 6MWT walk distance and pVO2 (r=0.866 and 0.765, respectively; P<0.05), and a higher correlation between SWT walk distance and VO2 at AT than between 6MWT walk distance and VO2 at AT (r=0.775 and 0.587, respectively; P<0.05). No adverse events occurred during the exercise tests.

CONCLUSIONS:

SWT is a better reflection than 6MWT of exercise tolerance in PAH patients, and thus is a preferable alternative for assessment of exercise tolerance in PAH patients.
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  PMID: 24225307 [PubMed - indexed for MEDLINE]
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34. Ann Rheum Dis. 2014 Jul;73(7):1340-9. doi: 10.1136/annrheumdis-2013-203301. Epub 2013 May 18.

Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study.

Coghlan JG1Denton CP2Grünig E3Bonderman D4Distler O5Khanna D6Müller-Ladner U7Pope JE8Vonk MC9,Doelberg M10Chadha-Boreham H11Heinzl H12Rosenberg DM11McLaughlin VV6Seibold JR13DETECT study group.
Author information: 
1Cardiology Department, Royal Free Hospital, London, UK.
2Centre for Rheumatology, Royal Free Hospital, London, UK.
3Centre for Pulmonary Hypertension, University Hospital, Heidelberg, Germany.
4Medical University of Vienna, Department of Internal Medicine II, Division of Cardiology, Vienna, Austria.
5Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland.
6Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
7Department of Rheumatology and Clinical Immunology, Justus-Liebig-University Giessen, Kerckhoff Clinic Bad Nauheim, Germany.
8Department of Medicine, Division of Rheumatology, Western University of Canada, London, Ontario, Canada.
9Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
10Global Medical Affairs, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
11Clinical Development, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
12Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
13Scleroderma Research Consultants LLC, Avon, Connecticut, USA.

Abstract

OBJECTIVE:

Earlier detection of pulmonary arterial hypertension (PAH), a leading cause of death in systemic sclerosis (SSc), facilitates earlier treatment. The objective of this study was to develop the first evidence-based detection algorithm for PAH in SSc.

METHODS:

In this cross-sectional, international study conducted in 62 experienced centres from North America, Europe and Asia, adults with SSc at increased risk of PAH (SSc for >3 years and predicted pulmonary diffusing capacity for carbon monoxide <60%) underwent a broad panel of non-invasive assessments followed by diagnostic right heart catheterisation (RHC). Univariable and multivariable analyses selected the best discriminatory variables for identifying PAH. After assessment for clinical plausibility and feasibility, these were incorporated into a two-step, internally validated detection algorithm. Nomograms for clinical practice use were developed.

RESULTS:

Of 466 SSc patients at increased risk of PAH, 87 (19%) had RHC-confirmed PAH. PAH was mild (64% in WHO functional class I/II). Six simple assessments in Step 1 of the algorithm determined referral to echocardiography. In Step 2, the Step 1 prediction score and two echocardiographic variables determined referral to RHC. The DETECT algorithm recommended RHC in 62% of patients (referral rate) and missed 4% of PAH patients (false negatives). By comparison, applying European Society of Cardiology/European Respiratory Society guidelines to these patients, 29% of diagnoses were missed while requiring an RHC referral rate of 40%.

CONCLUSIONS:

The novel, evidence-based DETECT algorithm for PAH detection in SSc is a sensitive, non-invasive tool which minimises missed diagnoses, identifies milder disease and addresses resource usage.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go tohttp://group.bmj.com/group/rights-licensing/permissions.
PMCID: PMC4078756 Free PMC Article
  PMID: 23687283 [PubMed - indexed for MEDLINE]
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35. Eur Respir J. 2014 Aug 19. pii: erj01691-2013. [Epub ahead of print]

Microvascular disease in chronic thromboembolic pulmonary hypertension: a role for pulmonary veins and systemic vasculature.

Dorfmüller P1Günther S2Ghigna MR3Thomas de Montpréville V4Boulate D5Paul JF6Jaïs X7Decante B5Simonneau G7Dartevelle P8Humbert M7Fadel E9Mercier O9.
Author information: 
1Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France Dept of Pathology, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France Both authors contributed equally to this studypeter.dorfmuller@u-psud.fr.
2Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France National Reference Center of Pulmonary Hypertension, Dept of Pulmonology and Intensive Care Unit for Respiratory Diseases, Hôpital Bicêtre, AP-HP, Kremlin-Bicêtre, France Both authors contributed equally to this study.
3Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France Dept of Pathology, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
4Dept of Pathology, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
5Surgical Research Lab, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
6Dept of Radiology, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
7Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France National Reference Center of Pulmonary Hypertension, Dept of Pulmonology and Intensive Care Unit for Respiratory Diseases, Hôpital Bicêtre, AP-HP, Kremlin-Bicêtre, France.
8Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France Dept of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
9Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France Surgical Research Lab, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France Dept of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.

Abstract

Limited numbers of operated patients with chronic thromboembolic pulmonary hypertension (CTEPH) are refractory to pulmonary endarterectomy (PEA) and experience persistent pulmonary hypertension (PH). We retrospectively assessed lung histology available from nine patients with persistent PH (ineffective PEA (inPEA) group) and from eight patients transplanted for distal CTEPH inaccessible by PEA (noPEA group). Microscopically observed peculiarities were compared with the histology of a recently developed CTEPH model in piglets. Pre-interventional clinical/haemodynamic data and medical history of patients from the inPEA and noPEA groups were collected and analysed. Conspicuous remodelling of small pulmonary arteries/arterioles, septal veins and pre-septal venules, including focal capillary haemangiomatosis, as well as pronounced hypertrophy and enlargement of bronchial systemic vessels, were the predominant pattern in histology from both groups. Most findings were reproduced in our porcine CTEPH model. Ink injection experiments unmasked abundant venular involvement in so-called small vessel or microvascular disease, as well as post-capillary bronchopulmonary shunting in human and experimental CTEPH. Microvascular disease is partly due to post-capillary remodelling in human and experimental CTEPH and appears to be related to bronchial-to-pulmonary venous shunting. Further studies are needed to clinically assess the functional importance of this finding.
©ERS.
  PMID: 25142477 [PubMed - as supplied by publisher]
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36. J Am Coll Cardiol. 2014 May 27;63(20):2159-69. doi: 10.1016/j.jacc.2014.02.575. Epub 2014 Mar 26.

Survival differences in pediatric pulmonary arterial hypertension: clues to a better understanding of outcome and optimal treatment strategies.

Zijlstra WM1Douwes JM1Rosenzweig EB2Schokker S1Krishnan U2Roofthooft MT1Miller-Reed K3Hillege HL4Ivy DD3Berger RM5.
Author information: 
1Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
2Columbia University College of Physicians and Surgeons, New York, New York.
3Children's Hospital Colorado, Aurora, Colorado.
4Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
5Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: r.m.f.berger@umcg.nl.

Abstract

OBJECTIVES:

In order to describe survival and treatment strategies in pediatric pulmonary arterial hypertension (PAH) in the current era of PAH-targeted drugs and to identify predictors of outcome, we studied uniformly defined contemporary patient cohorts at 3 major referral centers for pediatric PAH (New York [NY], Denver, and the Netherlands [NL]).

BACKGROUND:

In pediatric PAH, discrepancies exist in reported survival rates between North American and European patient cohorts, and robust data for long-term treatment effects are lacking.

METHODS:

According to uniform inclusion criteria, 275 recently diagnosed consecutive pediatric PAH patients who visited the 3 referral centers between 2000 and 2010 were included.

RESULTS:

Unadjusted survival rates differed between the center cohorts (1-, 3-, and 5-year transplantation-free survival rates: 100%, 96%, and 90% for NY; 95%, 87%, and 78% for Denver; and 84%, 71%, and 62% for NL, respectively; p < 0.001). Based on World Health Organization (WHO) functional class and hemodynamic parameters, disease severity at diagnosis differed between the center cohorts. Adjustment for diagnosis, WHO functional class, indexed pulmonary vascular resistance, and pulmonary-to-systemic arterial pressure ratio resolved the observed survival differences. Treatment with PAH-targeted dual and triple therapy during the study period was associated with better survival than treatment with PAH-targeted monotherapy.

CONCLUSIONS:

Survival rates of pediatric PAH patients differed between 3 major referral centers. This could be explained by differences between the center cohorts in patients' diagnoses and measures of disease severity, which were identified as important predictors of outcome. In this study, treatment with PAH-targeted combination therapy during the study period was independently associated with improved survival.
Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
  PMID: 24681143 [PubMed - indexed for MEDLINE]
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37. J Thorac Cardiovasc Surg. 2014 Sep;148(3):1005-1012.e2. doi: 10.1016/j.jtcvs.2014.06.052. Epub 2014 Jul 5.

Pulmonary endarterectomy for distal chronic thromboembolic pulmonary hypertension.

D'Armini AM1Morsolini M2Mattiucci G3Grazioli V3Pin M4Valentini A5Silvaggio G4Klersy C6Dore R5.
Author information: 
1Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia School of Medicine, Pavia, Italy; Cardiac Surgery, Foundation I.R.C.C.S. Policlinico San Matteo, Pavia, Italy. Electronic address: darmini@smatteo.pv.it.
2Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia School of Medicine, Pavia, Italy.
3Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia School of Medicine, Pavia, Italy; Cardiac Surgery, Foundation I.R.C.C.S. Policlinico San Matteo, Pavia, Italy.
4Cardiac Surgery, Foundation I.R.C.C.S. Policlinico San Matteo, Pavia, Italy.
5Institute of Radiology, Foundation I.R.C.C.S. Policlinico San Matteo, Pavia, Italy.
6Service of Biometry and Clinical Epidemiology, Foundation I.R.C.C.S. Policlinico San Matteo, Pavia, Italy.

Abstract

OBJECTIVES:

Chronic thromboembolic pulmonary hypertension can be cured by pulmonary endarterectomy. Operability assessment remains a major concern, because there are no well-defined criteria to discriminate proximal from distal obstructions, and surgical candidacy depends mostly on the surgeon's experience. The intraoperative classification of chronic thromboembolic pulmonary hypertension describes 4 types of lesions, based on anatomy and location. We describe our recent experience with the more distal (type 3) disease.

METHODS:

More than 500 pulmonary endarterectomies were performed at Foundation I.R.C.C.S. Policlinico San Matteo (Pavia, Italy). Because of recent changes in the patient population, 331 endarterectomies performed from January 2008 to December 2013 were analyzed. Two groups of patients were identified according to the intraoperative classification: proximal (type 1 and type 2 lesions, 221 patients) and distal (type 3 lesions, 110 patients).

RESULTS:

The number of endarterectomies for distal chronic thromboembolic pulmonary hypertension increased significantly over time (currently ∼37%). Deep venous thrombosis was confirmed as a risk factor for proximal disease, whereas patients with distal obstruction had a higher prevalence of indwelling intravascular devices. Overall hospital mortality was 6.9%, with no difference in the 2 groups. Postoperative survival was excellent. In all patients, surgery was followed by a significant and sustained improvement in hemodynamic, echocardiographic, and functional parameters, with no difference between proximal and distal cases.

CONCLUSIONS:

Although distal chronic thromboembolic pulmonary hypertension represents the most challenging situation, the postoperative outcomes of both proximal and distal cases are excellent. The diagnosis of inoperable chronic thromboembolic pulmonary hypertension should be achieved only in experienced centers, because many patients who have been deemed inoperable might benefit from favorable surgical outcomes.
Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
  PMID: 25129589 [PubMed - in process]
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38. Exp Clin Transplant. 2014 Aug;12(4):283-9.

Changes in pulmonary artery pressure affect survival differently in lung transplant recipients who have pulmonary hypertension or chronic obstructive pulmonary disease.

O'Keefe KL1Kilic APope-Harman AHayes D JrKirkby SHiggins RSWhitson BA.
Author information: 
1Department of Surgery, Division of Cardiac Surgery, Wexner Medical Center, Ohio State University, OH, USA.

Abstract

OBJECTIVES:

Pulmonary hypertension and right ventricular dysfunction can complicate lung transplant. Pulmonary artery pressures affect outcome are uncertain during wait list. We evaluated changes in wait list pulmonary artery pressures on survival after lung transplant.

MATERIALS AND METHODS:

We queried the United Network for Organ Sharing/Standard Transplant Analysis and Research registry from 1987 to 2012 for all lung transplants. Recipients with unique pulmonary artery pressure measurements upon listing and transplant were included. Mean pulmonary artery pressure was rated as increased (increase > 5 mm Hg), decreased (decrease > 5 mm Hg), or unchanged (variation < 5 mm Hg).

RESULTS:

There were 23 951 lung transplants and 1677 recipients were included. Diagnoses demonstrated significant changes in mean pulmonary artery pressure during the listing period (P ≤ .0001). In recipients with chronic obstructive pulmonary disease, survival was poorer when mean pulmonary artery pressure was increased than decreased (P ≤ .03). In recipients with primary pulmonary hypertension, survival was poorer when mean pulmonary artery pressure was decreased than increased (P ≤ .02). Proportional hazards analysis showed that increases in mean pulmonary artery pressure independently affected survival (hazard ratio, 0.78; 95% confidence interval, 0.62-0.96).

CONCLUSIONS:

Although the mechanism is unknown, an increase in mean pulmonary artery pressure in patients with chronic obstructive pulmonary disease is associated with poorer survival after lung transplant. In contrast, patients with primary pulmonary hypertension with decreased mean pulmonary artery pressure have poorer survival after lung transplant. In patients with primary pulmonary hypertension, changes in pulmonary artery pressure may be a surrogate for a failing right ventricular function. In chronic obstructive pulmonary disease, the change in pressure suggests an undetermined progressive process. Further study of right ventricular function is warranted to determine the effects of changes in pulmonary artery pressure on lung transplant recipients.
Free Article
  PMID: 25095706 [PubMed - in process]
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39. Scand J Rheumatol. 2014;43(4):314-23. doi: 10.3109/03009742.2013.854407. Epub 2014 Feb 6.

Left heart disease: a frequent cause of early pulmonary hypertension in systemic sclerosis, unrelated to elevated NT-proBNP levels or overt cardiac fibrosis but associated with increased levels of MR-proANP and MR-proADM: retrospective analysis of a French Canadian cohort.

Miller L1Chartrand SKoenig MGoulet JRRich EChin AChartrand-Lefebvre CAbrahamowicz MSenécal JLGrodzicky T.
Author information: 
1Division of Rheumatology, Hospital Centre of the University of Montreal (CHUM) , Montreal, Québec , Canada.

Abstract

OBJECTIVES:

Pulmonary hypertension (PH) causes mortality in systemic sclerosis (SSc). Pulmonary arterial hypertension (PAH) and left heart disease (LHD) are frequent causes of PH. Therefore, we studied PAH and LHD in early PH.

METHOD:

A total of 432 French Canadian SSc patients were studied retrospectively. All underwent screening for PH. We analysed clinical, serological, and radiographic data from 26 patients with early PH diagnosed by right heart catheterization (RHC). SSc patients with (n = 21) and without PH (n = 19) were prospectively re-evaluated by cardiac magnetic resonance imaging (MRI) and serial measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the haemodynamic biomarkers mid-regional pro-atrial natriuritic peptide (MR-proANP) and mid-regional pro-adrenomedullin (MR-proADM).

RESULTS:

The most frequent cause of early PH was LHD (58%). PAH was seen in 34% of patients. No association was found between the type of PH and autoantibodies. Early LHD-PH, but not early PAH, was associated with lower NT-proBNP (p = 0.024), but MR-proANP and MR-proADM levels were higher in early LHD-PH than in patients without PH (p = 0.014 and p = 0.012, respectively). Only one patient had abnormal cardiac MRI explaining LHD-PH.

CONCLUSIONS:

Early PH in SSc, like late PH, is heterogeneous and RHC is essential for determining its underlying cause. The most frequent cause of early PH was LHD. Levels of MR-proANP and MR-proADM, but not NT-proBNP, were increased in early LHD-PH, and may be more reliable than NT-proBNP as a biomarker of early PH in this subgroup of patients. Cardiac MRI did not explain LHD-PH. This study is the first to identify a high frequency of LHD in early PH correlating with normal NT-proBNP levels but increased MR-proANP and MR-proADM levels in SSc patients.
  PMID: 25089008 [PubMed - in process]
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40. Circulation. 2014 Aug 5;130(6):508-18. doi: 10.1161/CIRCULATIONAHA.114.009309.

Update on chronic thromboembolic pulmonary hypertension.

Lang IM1Madani M2.
Author information: 
1From the Department of Internal Medicine II, Division of Cardiology, Vienna, Austria (I.M.L.); and Department of Surgery, Division of Cardiovascular and Thoracic Surgery, University of California-San Diego, La Jolla (M.M.).irene.lang@meduniwien.ac.at.
2From the Department of Internal Medicine II, Division of Cardiology, Vienna, Austria (I.M.L.); and Department of Surgery, Division of Cardiovascular and Thoracic Surgery, University of California-San Diego, La Jolla (M.M.).
  PMID: 25092279 [PubMed - in process]
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41. Curr Opin Pulm Med. 2014 Sep;20(5):400-8. doi: 10.1097/MCP.0000000000000088.

Chronic thromboembolic pulmonary hypertension: evolution in management.

LeVarge BL1Channick RN.
Author information: 
1aDepartment of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center bDepartment of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.

Abstract

PURPOSE OF REVIEW:

Chronic thromboembolic pulmonary hypertension (CTEPH) is an important cause of pulmonary hypertension. Although surgery is potentially curative, some patients present with inoperable disease. In these patients, medical therapies for pulmonary arterial hypertension are increasingly being used.

RECENT FINDINGS:

The pathobiology of CTEPH development remains incompletely understood; however, evidence supports both large and small vessel disorder in patients with the disease. Surgical thromboendarterectomy is an increasingly well tolerated and often curative procedure and is the management strategy of choice for most patients. Although excellent outcomes in surgical management have been noted, the role of medical management in selected patients with inoperable or recurrent or persistent disease after surgery is increasing. A recent large, randomized controlled clinical trial of riociguat in CTEPH demonstrated improvements in exercise capacity, functional class, and hemodynamics. A safe, effective angioplasty approach to CTEPH is being pursued in addition.

SUMMARY:

The approach to CTEPH management in the operable patient remains surgical, without clear benefit to preoperative pulmonary arterial hypertension-specific therapy at this time. Patients with inoperable disease or pulmonary hypertension following thromboendarterectomy, however, should be considered for medical management, with riociguat currently having the strongest evidence specific to CTEPH.
  PMID: 25093673 [PubMed - in process]
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