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Predictors of mortality in connective tissue disease-associated pulmonary arterial hypertension: a cohort study.

Prevalence of coronary heart disease and cardiovascular risk factors in a national cross-sectional cohort study of systemic sclerosis

- The effects of phosphodiesterase 5 inhibition on hemodynamics, functional status and survival in advanced heart failure and pulmonary hypertension: A case-control study.

Tadalafil for the treatment of pulmonary arterial hypertension: a double-blind 52-week uncontrolled extension study.

- And 41 other PAH Publications.
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Moore OA, Goh N, Corte T, Rouse H, Hennessy O, Thakkar V, Byron J, Sahhar J, Roddy J, Gabbay E, Youssef P, Nash P, Zochling J, Proudman SM, Stevens W, Nikpour M.Rheumatology (Oxford). 2012 Oct 13. [Epub ahead of print]
 
Predictors of mortality in connective tissue disease-associated pulmonary arterial hypertension: a cohort study.
Ngian GS, Stevens W, Prior D, Gabbay E, Roddy J, Tran A, Minson R, Hill C, Chow K, Sahhar J,Proudman S, Nikpour M.Arthritis Res Ther. 2012 Oct 5;14(5):R213. [Epub ahead of print]
 
Thakkar V, Stevens WM, Prior D, Moore OA, Byron J, Liew D, Patterson K, Hissaria P, Roddy J, Zochling J, Sahhar J, Nash P, Tymms K, Celermajer D, Gabbay E, Youssef P, Proudman SM, Nikpour M. Arthritis Res Ther. 2012 Jun 12;14(3):R143.
 
Ngian GS, Sahhar J, Proudman SM, Stevens W, Wicks IP, Van Doornum S. Ann Rheum Dis. 2012 Apr 24. [Epub ahead of print]
 
   
1. Congenit Heart Dis. 2012 Oct 18. doi: 10.1111/chd.12012. [Epub ahead of print]

Pulmonary Hypertension Associated with Congenital Heart Disease: A Practical Review for the Pediatric Cardiologist.

Kyle WB.

Source

Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, Tex, USA.

Abstract

Pulmonary hypertension (PH) is a complex condition with a broad range of etiologies that result in a common outcome-elevated pulmonary arterial pressure. For the pediatric cardiologist, this entity provides a manifest demonstration of the interrelationship of cardiac and pulmonary physiology. A thoughtful approach must be applied to each patient with PH in order to achieve a thorough understanding of the nature of disease and to proceed with individualized therapy in an appropriate and timely manner. This article aims to provide a clinically relevant, practical review of current literature related to PH in patients with congenital heart disease, including the causes, diagnostic considerations, and an overview of management.
© 2012 Wiley Periodicals, Inc.
  PMID: 23075130 [PubMed - as supplied by publisher]
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2. Int J Clin Pract. 2012 Nov;66(11):1117-1124. doi: 10.1111/j.1742-1241.2012.02997.x.

Design and delivery of an e-learning curriculum for physicians involved in the management of pulmonary hypertension.

Dalton BMcNeil KKeogh AWilliams TProudman SGabbay EKotlyar EWeintraub RKermeen FCelermajer DBoland J.

Source

School of Human Life Sciences, University of Tasmania, Launceston, Tas., Australia Centre for Pulmonary Transplantation and Vascular Disease, The Prince Charles Hospital, Brisbane, Qld, Australia Cardiopulmonary Transplant Unit, St Vincent's Hospital, Sydney, NSW, Australia Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital/Monash University, Melbourne, Vic., Australia Department of Rheumatology, Royal Adelaide Hospital, Adelaide, SA, Australia Advanced Lung Disease Unit and Pulmonary Hypertension Service, Royal Perth Hospital, Perth, WA, Australia Cardiopulmonary Transplant Service, St Vincent's Hospital, Sydney, NSW, Australia Department of Cardiology, The Royal Children's Hospital and Murdoch Children's Research Institute, Melbourne, Vic., Australia Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia St Vincent's Hospital, Sydney, NSW, Australia.

Abstract

Background:  Pulmonary hypertension (PH) is a condition that affects more than 25 million individuals worldwide and causes premature disability and death. Despite advances in our understanding of this condition, education and training of health professionals has not kept pace with the rapid changes in diagnosis and treatment. The net effects of this gap between advancing knowledge and limited educational opportunity likely include clinically significant delays in both the diagnosis and commencement of effective evidence-based treatment - an unacceptable outcome for patients with a lethal condition. Aim:  The Actelion Clinical Excellence Programme (ACEP) is an e-learning postgraduate curriculum, the purpose of which is to educate and mentor healthcare professionals, both theoretically and practically, in the diagnosis and treatment of patients with all forms of PH. This article reports on the development and delivery of the programme and outcomes from its first year of operation. Results:  Forty-three healthcare professionals from 22 institutions were enroled in the first iteration of the programme. In the 6 months from May to October 2011, participants successfully completed 285 lectures and/or activities. Overall, the programme was considered easily accessible, comprehensive in terms of both quality and quantity, provided an efficient means of self-paced learning, and was a highly regarded as reference source. Ninety-five per cent of participants said that they intended to change their clinical practice as a result of the information presented in the programme. Conclusion:  ACEP represents a successful physician-industry partnership, which has resulted in a significant impact on clinical teaching and awareness of PH.
© 2012 Blackwell Publishing Ltd.
  PMID: 23067036 [PubMed - as supplied by publisher]
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3. Lung. 2012 Oct 12. [Epub ahead of print]

Preoperative Echocardiographic-Defined Moderate-Severe Pulmonary Hypertension Predicts Prolonged Duration of Mechanical Ventilation Following Lung Transplantation for Patients with COPD.

Wrobel JPThompson BRSnell GIWilliams TJ.

Source

Faculty of Medicine, Monash University, 55 Commercial Road, Melbourne, VIC, 3004, Australia, jeremywrobel@gmail.com.

Abstract

PURPOSE:

Recent studies have suggested that pretransplant secondary pulmonary hypertension (PHT) may be associated with worse outcomes following lung transplantation. We sought to determine whether COPD patients with secondary PHT have inferior intensive care outcomes following lung transplantation.

METHODS:

This is a single-center, retrospective analysis of all lung transplant recipients between 2000 and 2009 for a primary diagnosis of COPD. Patients were stratified a priori into three pulmonary arterial pressure groups based on right ventricular systolic pressure (RVSP): no PHT (RVSP < 35 mmHg), mild PHT (35 ≤ RVSP < 45 mmHg), and moderate-severe PHT (RVSP ≥ 45 mmHg). Outcome measures were duration of mechanical ventilation, intensive care unit (ICU) length of stay, and PaO(2)/fraction inspired oxygen (PaO(2)/F(I)O(2)) ratio at 24 h posttransplantation.

RESULTS:

A total of 46 COPD lung transplant recipients with documented pretransplant RVSP were included in the analysis, including 18 with no PHT, 20 with mild PHT, and eight with moderate-severe PHT. There were no differences in baseline demographics between the three pulmonary arterial pressure groups. The presence of moderate-severe PHT predicted increased duration of mechanical ventilation (P = 0.024), worse PaO(2)/F(I)O(2) ratio at 24 h (P = 0.027), and a trend toward increased ICU length of stay (P = 0.055). RVSP was the strongest risk factor for duration of mechanical ventilation and ICU length of stay. There was no difference in 1-year survival amongst the three pulmonary arterial pressure groups.

CONCLUSIONS:

Preoperative moderate-severe PHT predicts prolonged duration of mechanical ventilation following lung transplantation in COPD subjects.
  PMID: 23064489 [PubMed - as supplied by publisher]
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4. Int J Cardiol. 2012 Oct 8. pii: S0167-5273(12)01180-1. doi: 10.1016/j.ijcard.2012.09.074. [Epub ahead of print]

The effects of phosphodiesterase 5 inhibition on hemodynamics, functional status and survival in advanced heart failure and pulmonary hypertension: A case-control study.

Reichenbach AAl-Hiti HMalek IPirk JGoncalvesova EKautzner JMelenovsky V.

Source

Department of Cardiology, Institute of Clinical and Experimental Medicine - IKEM, Prague, Czech Republic.

Abstract

BACKGROUND:

The goal was to examine the hemodynamic and clinical effects of long-term therapy with PDE5 inhibitor sildenafil (SILD) in patients with advanced, pre-transplant heart failure (HF) and severe pulmonary hypertension (PH), in comparison to a similar control group (CON).

METHODS:

In this non-randomized, retrospective case-control study, 32 middle-aged patients (81% males) with advanced systolic HF (80%≥NYHA III, 56% ischemic) and severe pre-capillary PH (transpulmonary pressure gradient>15mm Hg) were studied before and after initiation of SILD (dose 73±25mg/day) and were compared to 15 CON patients, matched for key clinical characteristics (including PH severity, age and co-morbidities), not exposed to SILD. Changes at 3months and the long-term outcome were compared between groups.

RESULTS:

SILD significantly reduced pulmonary vascular resistance (-32% vs. baseline), transpulmonary gradient (-25%) and increased cardiac output (+15%) compared to controls, without affecting systemic or ventricular filling pressures. SILD-treated subjects experienced an improvement in NYHA class and had a steady body weight which contrasted with significant weight loss in the CON group (by -4.8%, absolutely by 4.3±6kg). During follow-up (median 349days from baseline), 60% of patients underwent heart transplantation. Two patients in CON group had severe post-transplant failure of the right ventricle, none in SILD group. Overall pre- and peritransplant survival (censored 30days after transplantation) was significantly better in SILD than CON group (93.7 vs 60%, p=0.0048).

CONCLUSIONS:

In patients with advanced HF and severe PH, SILD therapy has beneficial effects on hemodynamics, clinical status, cardiac cachexia, and contributes to improved peri-transplant survival.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
  PMID: 23058346 [PubMed - as supplied by publisher]
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5. Int J Cardiol. 2012 Oct 8. pii: S0167-5273(12)01254-5. doi: 10.1016/j.ijcard.2012.09.133. [Epub ahead of print]

Right atrial volume and phasic function in pulmonary hypertension.

Sato TTsujino IOyama-Manabe NOhira HIto YMYamada AIkeda DWatanabe TNishimura M.

Source

First Department of Medicine, Hokkaido University Hospital, Japan.

Abstract

BACKGROUND:

Few studies have focused on right atrial (RA) structure and function in pulmonary hypertension (PH). We sought to evaluate RA volume and phasic function using cardiac magnetic resonance (CMR), and to examine their clinical relevance in PH.

METHODS:

We prospectively studied 50 PH patients and 21 control subjects. RA volume and indices of phasic function (reservoir volume, ejection fraction [EF], and conduit volume) were evaluated by CMR.

RESULTS:

Maximum RA volume index was significantly higher in PH patients (56 [44-70] ml/m(2)) than in controls (40 [30-48] ml/m(2)) (p<0.001). Reservoir volume index was significantly lower in PH than in controls (p<0.001), but conduit volume index was higher in PH than in controls (p=0.008). RA EF was similar when comparing the two groups (p=0.925). Interestingly, RA EF was increased in PH patients with WHO functional class III patients as compared with controls (p<0.001) but was reduced in advanced PH patients with WHO functional class IV (p<0.01). Maximum RA volume and RA EF significantly correlated with pulmonary hemodynamic indices, atrial and brain natriuretic hormone levels, and CMR-derived right ventricular indices. By contrast, RA reservoir volume correlated with cardiac index and 6-minute walk distance.

CONCLUSIONS:

PH is associated with increased size, decreased reservoir function, and increased conduit function of the right atrium. RA systolic function indicated by RA EF increases in patients with mild to moderate PH but decreases in patients with advanced PH. Varying associations between RA indices and conventional PH indices suggest their unique role in the management of PH.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
  PMID: 23058342 [PubMed - as supplied by publisher]
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6. Int J Immunopathol Pharmacol. 2012 Jul-Sep;25(3):681-9.

Pulmonary hypertension in idiopathic pulmonary fibrosis: prevalence and clinical progress.

Castria DRefini RMBargagli EMezzasalma FPierli CRottoli P.

Source

Respiratory Disease Section, Department of Clinical Medicine and Immunological Sciences, Siena University, Italy.

Abstract

The aims of the present study are to define the prevalence of Pulmonary Hypertension (PH) in a cohort of Idiopathic Pulmonary Fibrosis (IPF) patients, to investigate any correlations between systolic pulmonary artery pressure (PAPs) and functional data, to evaluate clinical progress and to compare long-term survival in IPF patients with and without PH. A population of 126 IPF patients was recruited. A high prevalence of PH (39.7 percent, 50/126), evaluated by echocardiography on the basis of PAPs greater than 36 mmHg, was mainly observed in smokers and female patients. Regression analysis revealed a significant correlation between PAPs greater than 50 mmHg and DLCO/VA (p=0.0294). Mean PAPs was significantly greater one year after onset of PH (p=0.01). 11/21 patients with FVC less than 50 percent had a significant increase in PAPs one year after onset of PH (p=0.02). There was a highly significant difference between survival of IPF patients with and without PH (p=0.0001; hazard ratio = 3.56). This study revealed that PH has a high prevalence in patients with IPF and is associated with increased risk of mortality. Early diagnosis of IPF patients with pulmonary hypertension is important, so that they can be enrolled in waiting lists for lung transplant as soon as possible.
  PMID: 23058018 [PubMed - in process]
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7. Free Radic Biol Med. 2012 Jun 1-15;52(11-12):2312-9. doi: 10.1016/j.freeradbiomed.2012.04.011. Epub 2012 Apr 21.

Obesity-induced tissue free radical generation: an in vivo immuno-spin trapping study.

Khoo NKCantu-Medellin NDevlin JESt Croix CMWatkins SCFleming AMChampion HCMason RPFreeman BAKelley EE.

Source

Department of Pharmacology and Chemical Biology, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA.

Abstract

Assessment of tissue free radical production is routinely accomplished by measuring secondary by-products of redox reactions and/or diminution of key antioxidants such as reduced thiols. However, immuno-spin trapping, a newly developed immunohistochemical technique for detection of free radical formation, is garnering considerable interest as it allows for the visualization of 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-adducted molecules. Yet, to date, immuno-spin trapping reports have utilized in vivo models in which successful detection of free radical adducts required exposure to lethal levels of oxidative stress not reflective of chronic inflammatory disease. To study the extents and anatomic locations of more clinically relevant levels of radical formation, we examined tissues from high-fat (HF) diet-fed mice, a model of low-grade chronic inflammation known to demonstrate enhanced rates of reactive species production. Mice subjected to 20 weeks of HF diet displayed increased free radical formation (anti-DMPO mean fluorescence staining) in skeletal muscle (0.863±0.06 units vs 0.512±0.07 units), kidney (0.076±0.0036 vs 0.043±0.0025), and liver (0.275±0.012 vs 0.135±0.014) compared to control mice fed normal laboratory chow (NC). Western blot analysis of tissue homogenates confirmed these results showing enhanced DMPO immunoreactivity in HF mice compared to NC samples. The obesity-related results were confirmed in a rat model of pulmonary hypertension and right heart failure in which intense immunodetectable radical formation was observed in the lung and right ventricle of monocrotaline-treated rats compared to saline-treated controls. Combined, these data affirm the utility of immuno-spin trapping as a tool for in vivo assessment of altered extents of macromolecule oxidation to radical intermediates under chronic inflammatory conditions.
Published by Elsevier Inc.
  PMID: 22564528 [PubMed - indexed for MEDLINE]
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8. Circ J. 2012;76(7):1744-9. Epub 2012 Apr 13.

Electrocardiogram for the diagnosis of right ventricular hypertrophy and dilation in idiopathic pulmonary arterial hypertension.

Kopeć GTyrka AMiszalski-Jamka TSobień MWaligóra MBrózda MPodolec P.

Source

Department of Cardiac and Vascular Diseases, John Paul II Hospital, Kraków, Poland. gkopec@szpitaljp2.krakow.pl

Abstract

BACKGROUND:

Currently, there are no data on the association between right ventricular (RV) structure and ECG changes specific for idiopathic pulmonary arterial hypertension (IPAH). Therefore, we aimed to assess the accuracy of the recommended ECG criteria for predicting RV hypertrophy (RVH) and dilation in patients with IPAH.

METHODS AND RESULTS:

Twelve-lead ECG and cardiovascular magnetic resonance imaging (CMR) were performed in 23 consecutive patients with IPAH aged 49.8±16.3 years. ECG criteria were referred to RV mass index and RV end-diastolic volume index as measured by CMR. Only the ECG voltage criteria based on R wave amplitude in lead V1, R wave amplitude in aVR, P wave amplitude in II and ventricular activation time in V1 were useful for differentiating between patients with and without RVH. A ventricular activation time in lead V1 of <0.01 s excluded RVH, whereas R in V1 >6 mm, R:S in V1 >1, R in aVR >4 mm, R:S in V5 to R:S in V1 <0.04 and P in II >2.5 mm confirmed the diagnosis. Only the ventricular activation time in V1 correlated with RV dilation and when >0.045s confirmed its diagnosis.

CONCLUSIONS:

Only a few of the recommended ECG criteria proved to be useful in the diagnosis of RVH or RV dilation in patients with IPAH. Changes in the cut-off values improved their accuracy.
Free Article
  PMID: 22498568 [PubMed - indexed for MEDLINE]
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9. Circ J. 2012;76(7):1737-43. Epub 2012 Apr 12.

Prognostic value of cardiac magnetic resonance imaging for idiopathic pulmonary arterial hypertension before initiating intravenous prostacyclin therapy.

Yamada YOkuda SKataoka MTanimoto ATamura YAbe TOkamura TFukuda KSatoh TKuribayashi S.

Source

Department of Diagnostic Radiology, Keio University School of Medicine, Tokyo, Japan.

Comment in

Is magnetic resonance imaging of right ventricular volume useful clinically for evaluation of pulmonary arterial hypertension?Hirashiki A, Kondo T, Murohara T. Circ J. 2012; 76(7):1595-6. Epub 2012 May 26.

Abstract

BACKGROUND:

Because few have reported the prognostic significance of cardiac magnetic resonance imaging (CMR) for idiopathic pulmonary arterial hypertension (IPAH), in this study we evaluated the value of CMR measurements as a prognostic predictor of IPAH before starting intravenous prostacyclin therapy.

METHODS AND RESULTS:

A total of 121 consecutive CMR studies for evaluating right ventricular (RV) function were reviewed. Forty-one patients were diagnosed with IPAH and served as the study group. Factors, such as age, sex, New York Heart Association functional class (NYHAFC), 6-min walk test, plasma brain natriuretic peptide level, serum uric acid level and CMR measurements were analyzed as predictors of first hospitalization and death. The mean follow-up period was 1,350±769 days. Nine patients were hospitalized because of heart failure, and 4 patients died from cardiopulmonary causes. The univariate analyses suggested that the left ventricular (LV) mass index, the left and right ventricular end-diastolic volume indices (LVEDVI, RVEDVI), the LV and RV end-systolic volume indices (LVESVI, RVESVI) and NYHAFC predicted the risk for hospitalization and that RVEDVI, RVESVI and NYHAFC predicted mortality. The multivariate analyses suggested that RVEDVI and NYHAFC are independent predictors of both hospitalization and mortality. The effects of RVEDVI and NYHAFC on hospitalization were not substantially affected by the concomitant medication.

CONCLUSIONS:

In IPAH patients, the RVEDVI predicts both hospitalization for right heart failure and mortality before initiating intravenous prostacyclin therapy.
Free Article
  PMID: 22498565 [PubMed - indexed for MEDLINE]
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10. Circ J. 2012;76(7):1729-36. Epub 2012 Apr 5.

Safety and efficacy of epoprostenol therapy in pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

Ogawa AMiyaji KYamadori IShinno YMiura AKusano KFIto HDate HMatsubara H.

Source

Department of Clinical Science, National Hospital Organization Okayama Medical Center, Okayama, Japan. aiko-oky@umin.ac.jp

Abstract

BACKGROUND:

Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are rare causes of pulmonary hypertension. There is no proven medical therapy to treat these diseases, and lung transplantation is thought to be the only cure. Administration of vasodilators including epoprostenol sometimes causes massive pulmonary edema and could be fatal in these patients.

METHODS AND RESULTS:

Eight patients were treated with epoprostenol for 387.3±116.3 days (range, 102-1,063 days), who were finally diagnosed with PVOD or PCH by pathological examination. The maximum dose of epoprostenol given was 55.3±10.7 ng·kg(-1)·min(-1) (range, 21.0-110.5 ng·kg(-1)·min(-1)). With careful management, epoprostenol therapy significantly improved the 6-min walk distance (97.5±39.2 to 329.4±34.6 m, P<0.001) and plasma brain natriuretic peptide levels (381.3±136.8 to 55.2±14.4 pg/ml, P<0.05). The cardiac index significantly increased from 2.1±0.1 to 2.9±0.3 L·min(-1)·m(-2) (P<0.05). However, pulmonary artery pressure and pulmonary vascular resistance were not significantly reduced. For 4 patients, epoprostenol therapy acted as a bridge to lung transplantation. For the other patients who had no chance to undergo lung transplantation, epoprostenol therapy was applied for 528.0±216.6 days and the maximum dose was 63.9±19.0 ng·kg(-1)·min(-1).

CONCLUSIONS:

This study data suggest that cautious application of epoprostenol can be considered as a therapeutic option in patients with PVOD and PCH.
Free Article
  PMID: 22481098 [PubMed - indexed for MEDLINE]
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11. Respir Res. 2012 Mar 16;13:21. doi: 10.1186/1465-9921-13-21.

Risk factors for morbidity and death in non-cystic fibrosis bronchiectasis: a retrospective cross-sectional analysis of CT diagnosed bronchiectatic patients.

Goeminne PCScheers HDecraene ASeys SDupont LJ.

Source

Laboratory of Pneumology, Katholieke Universiteit Leuven, Leuven, Belgium. pieter.goeminne@student.kuleuven.be

Abstract

INTRODUCTION:

There is a relative lack of information about the death rate and morbidity of non-cystic fibrosis bronchiectasis and most studies are limited due to referral bias. We wanted to assess death rate and morbidity in those patients at our hospital.

METHODS:

Adult patients seen at our department between June 2006 and November 2009 were recruited if the key string "bronchiect-" was mentioned in electronic clinical records and if chest CT imaging was available. Clinical records of all patients with confirmed radiologic diagnosis of bronchiectasis were reviewed and clinical characteristics were analyzed.

RESULTS:

539 patients with a radiographic diagnosis of non-cystic fibrosis bronchiectasis were identified in a retrospective cross-sectional analysis giving a prevalence of 2.6% in our hospital population. A wide range of etiologies was found with idiopathic bronchiectasis in 26%. In the 41 months interval, 57 patients (10.6%) died. We found a median exacerbation rate of 1.94 per year. Bacterial colonization status was associated with more deaths, exacerbation rate, symptoms and reduced pulmonary function. Pulmonary hypertension was found in 48% of our patients.

CONCLUSIONS:

We evaluated a large non-cystic fibrosis bronchiectasis population, and provided new epidemiological data on associations between clinical characteristics and deaths and morbidity in these patients.
PMCID: PMC3379934 Free PMC Article
  PMID: 22423975 [PubMed - indexed for MEDLINE]
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12. Circ Res. 2012 Aug 3;111(4):469-81. doi: 10.1161/CIRCRESAHA.112.266361. Epub 2012 Jun 22.

Enhanced Ca(2+)-sensing receptor function in idiopathic pulmonary arterial hypertension.

Yamamura AGuo QYamamura HZimnicka AMPohl NMSmith KAFernandez RAZeifman AMakino ADong HYuan JX.

Source

Kinjo Gakuin University School of Pharmacy, Nagoya, Japan.

Abstract

RATIONALE:

A rise in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) in pulmonary arterial smooth muscle cells (PASMC) is an important stimulus for pulmonary vasoconstriction and vascular remodeling. Increased resting [Ca(2+)](cyt) and enhanced Ca(2+) influx have been implicated in PASMC from patients with idiopathic pulmonary arterial hypertension (IPAH).

OBJECTIVE:

We examined whether the extracellular Ca(2+)-sensing receptor (CaSR) is involved in the enhanced Ca(2+) influx and proliferation in IPAH-PASMC and whether blockade of CaSR inhibits experimental pulmonary hypertension.

METHODS AND RESULTS:

In normal PASMC superfused with Ca(2+)-free solution, addition of 2.2 mmol/L Ca(2+) to the perfusate had little effect on [Ca(2+)](cyt). In IPAH-PASMC, however, restoration of extracellular Ca(2+) induced a significant increase in [Ca(2+)](cyt). Extracellular application of spermine also markedly raised [Ca(2+)](cyt) in IPAH-PASMC but not in normal PASMC. The calcimimetic R568 enhanced, whereas the calcilytic NPS 2143 attenuated, the extracellular Ca(2+)-induced [Ca(2+)](cyt) rise in IPAH-PASMC. Furthermore, the protein expression level of CaSR in IPAH-PASMC was greater than in normal PASMC; knockdown of CaSR in IPAH-PASMC with siRNA attenuated the extracellular Ca(2+)-mediated [Ca(2+)](cyt) increase and inhibited IPAH-PASMC proliferation. Using animal models of pulmonary hypertension, our data showed that CaSR expression and function were both enhanced in PASMC, whereas intraperitoneal injection of the calcilytic NPS 2143 prevented the development of pulmonary hypertension and right ventricular hypertrophy in rats injected with monocrotaline and mice exposed to hypoxia.

CONCLUSIONS:

The extracellular Ca(2+)-induced increase in [Ca(2+)](cyt) due to upregulated CaSR is a novel pathogenic mechanism contributing to the augmented Ca(2+) influx and excessive PASMC proliferation in patients and animals with pulmonary arterial hypertension.
  PMID: 22730443 [PubMed - indexed for MEDLINE]
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13. J Am Coll Cardiol. 2012 Aug 21;60(8):768-74. doi: 10.1016/j.jacc.2012.05.004. Epub 2012 Jul 18.

Tadalafil for the treatment of pulmonary arterial hypertension: a double-blind 52-week uncontrolled extension study.

Oudiz RJBrundage BHGaliè NGhofrani HASimonneau GBotros FTChan MBeardsworth ABarst RJPHIRST Study Group.

Source

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA. roudiz@labiomed.org

Abstract

OBJECTIVES:

The aim of this study was to evaluate the long-term safety and durability of efficacy of tadalafil for pulmonary arterial hypertension.

BACKGROUND:

Tadalafil is an oral phosphodiesterase-5 inhibitor approved for PAH treatment. In the multicenter, placebo-controlled, randomized, 16-week PHIRST (Pulmonary Arterial Hypertension and Response to Tadalafil) study, tadalafil 40 mg improved exercise capacity and delayed clinical worsening.

METHODS:

Eligible patients from PHIRST received once-daily tadalafil 20 mg (T20 mg) or 40 mg (T40 mg) (n = 357) in the double-blind, 52-week, uncontrolled extension study (PHIRST-2); 293 patients completed PHIRST-2. Durability of efficacy was explored using the 6-min walk distance (6MWD) test. Clinical worsening and changes in World Health Organization functional class were evaluated.

RESULTS:

The safety profile of tadalafil in PHIRST-2 was similar to that in PHIRST, with typical phosphodiesterase-5 inhibitor adverse events. The 6MWDs achieved in PHIRST for the subset of patients receiving T20 mg and T40 mg in both PHIRST and PHIRST-2 (406 ± 67 m [n = 52] and 413 ± 81 m [n = 59] at PHIRST-2 enrollment, respectively) were maintained at PHIRST-2 completion (415 ± 80 m [n = 51] and 410 ± 78 m [n = 59], respectively). Numerically fewer patients who were on T40 mg in PHIRST and PHIRST-2 experienced World Health Organization functional class deterioration (6% [n = 5]) compared with those randomized to T20 mg (9% [n = 7]) across both studies. Post hoc analyses showed that background bosentan use and higher 6MWD at PHIRST baseline were associated with fewer clinical worsening events.

CONCLUSIONS:

Long-term treatment with tadalafil was well tolerated in patients with pulmonary arterial hypertension. In patients receiving either T20 mg or T40 mg, the improvements in 6MWD demonstrated in the 16-week PHIRST study appeared sustained for up to 52 additional weeks of treatment in PHIRST-2. (Pulmonary Arterial Hypertension and Response to Tadalafil Study; NCT00549302).
Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
  PMID: 22818063 [PubMed - indexed for MEDLINE]
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14. J Cardiothorac Vasc Anesth. 2012 Oct 9. pii: S1053-0770(12)00363-1. doi: 10.1053/j.jvca.2012.07.020. [Epub ahead of print]

Hemodynamic Effects of Combination Therapy With Inhaled Nitric Oxide and Iloprost in Patients With Pulmonary Hypertension and Right Ventricular Dysfunction After High-Risk Cardiac Surgery.

Antoniou TKoletsis ENProkakis CRellia PThanopoulos ATheodoraki KZarkalis DSfyrakis P.

Source

Department of Cardiac Anesthesiology, Onassis Cardiac Surgery Center, Athens, Greece.

Abstract

OBJECTIVE:

The purpose of this study was to evaluate the hemodynamic effects of inhaled nitric oxide (NO) plus aerosolized iloprost in patients with pulmonary hypertension/right ventricular dysfunction after cardiac surgery.

DESIGN:

A retrospective study.

SETTING:

A single center.

PARTICIPANTS:

Eight consecutive patients with valve disease and postextracorporeal circulation (ECC) pulmonary hypertension/right ventricular dysfunction.

INTERVENTION:

The continuous inhalation of nitric oxide (10 ppm) and iloprost, 10 μg, in repeated doses.

MEASUREMENTS AND MAIN RESULTS:

The hemodynamic profile was obtained before inhalation, during the administration of inhaled NO alone (prior and after iloprost), and after the first 2 doses of iloprost. Tricuspid annular velocity and tricuspid annular plane systolic excursion were estimated at baseline and before and after adding iloprost. At the end of the protocol, there were significant decreases in pulmonary vascular resistance (p < 0.001), the mean pulmonary arterial pressure (p < 0.001), and the mean pulmonary artery pressure/mean arterial pressure ratio (p = 0.006). Both tricuspid annular velocity (p < 0.001) and tricuspid annular plane systolic excursion (p < 0.001) increased. The cardiac index (p < 0.001) and venous blood oxygen saturation (p = 0.001) increased throughout the evaluation period. Each iloprost dose was associated with further decreases in pulmonary vascular resistances/pressure. By comparing data at the beginning of inhaled NO with those after the second dose of iloprost, the authors noticed decreases in pulmonary vascular resistances (p = 0.004) and the mean pulmonary artery pressure (p = 0.017) and rises in tricuspid annular velocity (p < 0.001) and tricuspid annular systolic plane systolic excursion (p < 0.001).

CONCLUSIONS:

Inhaled NO and iloprost significantly reduced pulmonary hypertension and contributed to the improvement in right ventricular function. Inhaled NO and iloprost have additive effects on pulmonary vasculature.
Copyright © 2012 Elsevier Inc. All rights reserved.
  PMID: 23063102 [PubMed - as supplied by publisher]
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15. J Heart Lung Transplant. 2012 Nov;31(11):1165-70. doi: 10.1016/j.healun.2012.08.009.

Validation of the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) pulmonary hypertension prediction model in a unique population and utility in the prediction of long-term survival.

Cogswell RKobashigawa EMcGlothlin DShaw RDe Marco T.

Source

Division of Cardiology, University of California, San Francisco, San Francisco, California. Electronic address: rebecca.cogswell@ucsf.edu.

Abstract

BACKGROUND:

The Registry to Evaluate Early and Long-Term Pulmonary Arterial (PAH) Hypertension Disease Management (REVEAL) model was designed to predict 1-year survival in patients with PAH. Multivariate prediction models need to be evaluated in cohorts distinct from the derivation set to determine external validity. In addition, limited data exist on the utility of this model in the prediction of long-term survival.

METHODS:

REVEAL model performance was assessed to predict 1-year and 5-year outcomes, defined as survival or composite survival or freedom from lung transplant, in 140 patients with PAH.

RESULTS:

The validation cohort had a higher proportion of human immunodeficiency virus (7.9% vs 1.9%, p<0.0001), methamphetamine use (19.3% vs 4.9%, p<0.0001), and portal hypertension PAH (16.4% vs 5.1%, p<0.0001) compared with the development cohort. The C-index of the model to predict survival was 0.765 at 1 year and 0.712 at 5 years of follow-up. The C-index of the model to predict composite survival or freedom from lung transplant was 0.805 and 0.724 at 1 and 5 years of follow-up, respectively. Prediction by the model, however, was weakest among patients with intermediate-risk predicted survival.

CONCLUSIONS:

The REVEAL model had adequate discrimination to predict 1-year survival in this small but clinically distinct validation cohort. Although the model also had predictive ability out to 5 years, prediction was limited among patients of intermediate risk, suggesting our prediction methods can still be improved.
Copyright © 2012. Published by Elsevier Inc.
  PMID: 23062726 [PubMed - in process]
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1. Thromb Haemost. 2012 Oct 10;108(6). [Epub ahead of print]

Non-invasive algorithms for the diagnosis of pulmonary hypertension.

Bonderman DWexberg PHeinzl HLang IM.

Source

Diana Bonderman, MD, Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria, Tel.: + 43 1 40 400 4614, Fax: + 43 1 40 400 4216, E-mail: diana.bonderman@meduniwien.ac.at.

Abstract

Precapillary pulmonary hypertension (PH) is diagnosed when mean pulmonary arterial pressure (mPAP) equals or exceeds 25 mmHg and the pulmonary capillary wedge pressure (PCWP) is equal or lower than 15 mmHg. Because both parameters can only be derived from invasive hemodynamic assessment, right heart catheter (RHC) is still a gold standard for the diagnosis of PH. Severe precapillary PH corresponds to pulmonary vascular disease and carries a poor prognosis. Unfortunately, due to a generally low specificity of non-invasive estimates of systolic pulmonary pressure, at least 50% of patients with suspicion of PH need to undergo invasive RHC for exclusion of precapillary PH. Therefore, and also in order to manage the growing number of postcapillary PH due to heart and lung disease in the general population, pulmonary and cardiologic diagnostic algorithms combining multiple parameters have been developed. Recent disease scores are reviewed, and an outlook is given on emerging evidence from the DETECT clinical study holding the promise to non-invasively predict precapillary PH in vulnerable patients. These diagnostic trees help limit unnecessary procedures and help differentiate the current categories of PH. However, one has to keep in mind that the diagnosis of PH is still made by hemodynamic assessment.
  PMID: 23052634 [PubMed - as supplied by publisher]
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2. Arthritis Care Res (Hoboken). 2012 Oct 6. doi: 10.1002/acr.21827. [Epub ahead of print]

Dyspnea assessment and pulmonary hypertension in patients with systemic sclerosis: Utility of the UCSD Shortness-of-Breath questionnaire.

Chung LChen HKhanna DSteen VD.

Source

Stanford University, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA. shauwei@stanford.edu.

Abstract

OBJECTIVE:

The UCSD Shortness-of-Breath Questionnaire (SOBQ) has been used to assess dyspnea-related activitylimitation in patients with airway and parenchymal lung disease. We sought to assess the constructvalidity and responsiveness of the SOBQ in systemic sclerosis (SSc) patients with incident pulmonary hypertension(PH) and those at high risk for developing PH.

METHODS:

We used data from 179 patients enrolled in the PHAROS registry with pre-PH, by defined criteria on pulmonary function tests and/or echocardiogram, or definite PH with mean pulmonary artery pressure > 25 mmHg by right heart catheterization within 6 months of enrollment. For this analysis, we included those subjects with complete data for self-reportedmeasures at baseline and 12 months.

RESULTS:

At baseline the SOBQ had strong correlations in the expected directions with the health assessment questionnaire-disability index (HAQ-DI)(r=0.71, p<.0001), dyspnea assessment by visual analogue scale (r=0.71, p<.0001), and SF-36 physical component score (PCS)(r=-0.77, p<.0001) and a moderate correlation with 6 minute walk distance(r=-0.33, p=.0001), Borg dyspnea score (r=0.47, p<.0001), and diffusing capacity (r=-0.33, p<.0001). Change in SOBQ at 12 months correlated in the expected direction with change in HAQ-DI (r=0.54, p<.0001) and change in SF-36 PCS (r=-0.44, p<.0001). Multivariate analysis adjusting for age, gender, and race identified male gender as a significant predictor of death (OR=7.00, 95% CI 1.55 - 31.76), while the SOBQ showed a strong trend toward significance (OR=1.82, 95% CI 0.97 - 3.41).

CONCLUSIONS:

The SOBQ demonstrates good construct validity and responsiveness to change in SSc patients with pulmonary vascular disease.
Copyright © 2012 by the American College of Rheumatology.
  PMID: 23042670 [PubMed - as supplied by publisher]
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3. J Am Soc Echocardiogr. 2012 Oct 3. pii: S0894-7317(12)00752-3. doi: 10.1016/j.echo.2012.09.009. [Epub ahead of print]

Value of Tricuspid Annular Plane Systolic Excursion and Peak Systolic Velocity in Children with Pulmonary Hypertension.

Koestenberger MRavekes W.

Source

Division of Pediatric Cardiology, Department of Pediatrics, Medical University Graz, Graz, Austria.
  PMID: 23041120 [PubMed - as supplied by publisher]
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4. Respiration. 2012 Oct 4. [Epub ahead of print]

Acute Hemodynamic Responses to Supplemental Oxygen and Their Prognostic Implications in Pulmonary Hypertension.

Leuchte HHBaezner CJBaumgartner RAMernitz PNeurohr CBehr J.

Source

Division of Pulmonary Diseases, Department of Internal Medicine I, Ludwig Maximilians University, Klinikum Grosshadern, Munich, Germany.

Abstract

Background: Pulmonary hypertension (PH) of various causes leads to a poor prognosis. Pulmonary vasoreactivity testing during right heart catheterization (RHC) has prognostic and therapeutic consequences. Objective: To characterize the acute hemodynamic response to short-term oxygen supplementation (SHOT) in adult PH patients and its impact on prognosis. Methods: After a stable baseline period, 104 patients with PH [pulmonary arterial hypertension (PAH; n = 56), chronic thromboembolic (PH; n = 22) or respiratory diseases (PH; n = 26)], who were mainly therapy-naïve (86.5%) (mean pO(2) 64.5 ± 1.2 mm Hg), received a standardized SHOT during RHC and hemodynamic response was assessed for its prognostic potential. Results: SHOT significantly reduced heart rate (HR: 78.9 ± 1.5 to 74 ± 1.5 beats/min), cardiac output (4 ± 0.1 to 3.8 ± 0.1 l/min), pulmonary arterial pressure (46.4 ± 1.3 to 42.3 ± 1.3 mm Hg) and pulmonary vascular resistance (10.1 ± 0.5 to 9.6 ± 0.5 Wood units; all p < 0.001) compared to baseline. The magnitude of this effect varied between the different PH groups. During a median follow-up of 25.1 months (range: 0.2-73.3 months), HR <72 beats/min in response to SHOT was associated with a better prognosis in patients with PH due to chronic thromboembolism to the lung and PH from chronic lung disease. Conclusions: SHOT leads to characteristic hemodynamic responses across different forms of PH. The preserved capability to acutely respond to SHOT with HR reduction is of prognostic significance in patients with non PAH PH.
Copyright © 2012 S. Karger AG, Basel.
  PMID: 23037927 [PubMed - as supplied by publisher]
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5. Am J Physiol Cell Physiol. 2012 Oct 3. [Epub ahead of print]

Increased TMEM16A-Encoded Calcium-Activated Chloride Channel Activity Is Associated With Pulmonary Hypertension.

Forrest ASJoyce TCHuebner MLAyon RJWiwchar MJoyce JFreitas NDavis AJYe LDuan DDSinger CAValencik ML,Greenwood IALeblanc N.

Source

University of Nevada, Reno.

Abstract

Pulmonary artery smooth muscle cells (PASMCs) are more depolarized and display higher Ca(2+) levels in pulmonary hypertension (PH). Whether the functional properties and expression of Ca(2+)-activated Cl(-) channels (Cl(Ca)), an important excitatory mechanism in PASMCs, are altered in PH is unknown. The potential role of Cl(Ca) channels in PH was investigated using the monocrotaline (MCT)-induced PH model in the rat. Three weeks post-injection with a single dose of MCT (50 mg/kg IP), the animals developed right ventricular hypertrophy (heart weight measurements and changes in pulmonary arterial flow (pulse-waved Doppler imaging) that were consistent with increased pulmonary arterial pressure and PH. Whole-cell patch experiments revealed an increase in niflumic acid (NFA)-sensitive Ca(2+)-activated Cl(-) current (I(Cl(Ca))) density in PASMCs from large conduit and small intralobar pulmonary arteries of MCT-treated rats versus aged-matched saline-injected controls. Quantitative RT-PCR and Western blot analysis revealed that the alterations in I(Cl(Ca)) were accompanied by parallel changes in the expression of TMEM16A, a gene recently shown to encode for Cl(Ca) channels. The contraction to serotonin of conduit and intralobar pulmonary arteries from MCT-treated rats exhibited greater sensitivity to nifedipine (1 μM), an L-type Ca(2+) channel blocker, and NFA (30 or 100 μM, with or without 10 μM Indomethacin to inhibit cyclooxygenases) or T16A(Inh)-A01 (10 μM), TMEM16A/Cl(Ca) channel inhibitors, than that of control animals. In conclusion, augmented Cl(Ca)/TMEM16A channel activity is a major contributor to the changes in electromechanical coupling of PA in this model of PH. TMEM16A-encoded channels may therefore represent a novel therapeutic target in this disease.
  PMID: 23034390 [PubMed - as supplied by publisher]
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6. Respir Med. 2012 Dec;106(12):1749-55. doi: 10.1016/j.rmed.2012.09.003. Epub 2012 Sep 30.

Diagnostic and prognostic role of biomarkers for pulmonary hypertension in interstitial lung disease.

Andersen CUMellemkjær SNielsen-Kudsk JEBendstrup ESimonsen UHilberg O.

Source

Department of Biomedicine, Aarhus University, Wilhelm Meyers Alle 4, Dk-8000 Aarhus, Denmark. Electronic address: cua@farm.au.dk.

Abstract

BACKGROUND:

Pulmonary hypertension (PH) is an important complication to interstitial lung disease (ILD). The aim of the present study was to investigate the relation of NT-proBNP, fibrin D-dimer, troponin-T, uric acid and exhaled nitric oxide (NO) to the presence of PH and mortality in ILD.

METHODS:

In a previously described cohort of 212 ILD patients of whom 29 had PH, levels of the above mentioned biomarkers were analyzed as routine tests.

RESULTS:

A value of NT-proBNP below 95 ng/l had a negative predictive value for PH of 99% (95% CI: 94-100). Values of troponin-T were higher in patients with PH (median (inter quartile range) = 9 (9-20) vs. 9(9-10) ng/l), and the odds ratio (OR) for PH was increased in patients with abnormal levels of uric acid (OR (95% CI) = 3.1(1.1-8.8)). NT-proBNP and troponin-T values above the 50(th) percentile, and uric acid and fibrin D-dimer values above the 90th percentile were each associated with increased mortality.

CONCLUSIONS:

A value of NT-proBNP below 95 ng/l may be used as a rule-out test for PH in ILD, while an abnormal value of uric acid is a risk factor for PH. NT-proBNP, troponin-T, uric acid and fibrin D-dimer have prognostic value in ILD patients, while exhaled levels of NO do not seem to predict PH or mortality.
Copyright © 2012 Elsevier Ltd. All rights reserved.
  PMID: 23034317 [PubMed - in process]
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7. J Rheumatol. 2012 Jun;39(6):1265-74. Epub 2012 May 15.

Comparison of the diagnostic utility of cardiac magnetic resonance imaging, computed tomography, and echocardiography in assessment of suspected pulmonary arterial hypertension in patients with connective tissue disease.

Rajaram SSwift AJCapener DElliot CACondliffe RDavies CHill CHurdman JKidling RAkil MWild JMKiely DG.

Source

Unit of Academic Radiology, University of Sheffield, Sheffield, UK. s.rajaram@sheffield.ac.uk

Abstract

OBJECTIVE:

Pulmonary arterial hypertension (PAH) is a life-threatening complication of connective tissue diseases (CTD). Our aim was to compare the diagnostic utility of noninvasive imaging modalities, i.e., magnetic resonance imaging (MRI), computed tomography (CT), and echocardiography, in evaluation of these patients.

METHODS:

In total, 81 consecutive patients with CTD and suspected PH underwent cardiac MRI, CT, and right heart catheterization (RHC) within 48 hours. Functional cardiac MRI variables [ventricle areas and ratios, delayed myocardial enhancement, position of the interventricular septum, right ventricular mass, ventricular mass index (VMI), and pulmonary artery distensibility] were all evaluated. The pulmonary artery size, pulmonary artery/aortic ratio (PA/Ao), left and right ventricular (RV) diameter ratio, RV wall thickness, and grade of tricuspid regurgitation were measured on CT. Tricuspid gradient (TG) and size of the RV were assessed using echocardiography.

RESULTS:

In our study of 81 patients with CTD, 55 had PAH, 22 had no PH, and 4 had PH owing to left heart disease. There was good correlation between mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) measured by RHC and VMI derived from MRI (mPAP, r = 0.69, p < 0.001; PVR, r = 0.78, p < 0.001) and systolic area ratio (mPAP, r = 0.69, p < 0.001; PVR, r = 0.68, p < 0.001) and TG derived from echocardiography (mPAP, r = 0.84, p < 0.001; PVR, r = 0.76, p < 0.001). In contrast, CT measures showed only moderate correlation. MRI and echocardiography each performed better as a diagnostic test for PAH than CT-derived measures: VMI ≥ 0.45 had a sensitivity of 85% and specificity 82%; and TG ≥ 40 mm Hg had a sensitivity of 86% and specificity 82%. Univariate Cox regression analysis showed the MRI measurements were better at predicting mortality. Patients with RV end diastolic volume < 135 ml had a better prognosis than those with a value > 135 ml, with a 1-year survival of 95% versus 66%, respectively.

CONCLUSION:

In patients with CTD and suspected PAH, cardiac MRI and echocardiography have greater diagnostic utility than CT in the assessment of patients with suspected PAH, and MRI has prognostic value.
  PMID: 22589263 [PubMed - indexed for MEDLINE]
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8. Am J Respir Crit Care Med. 2012 Jul 15;186(2):181-9. Epub 2012 May 3.

Left ventricular dysfunction induced by nonsevere idiopathic pulmonary arterial hypertension: a pressure-volume relationship study.

Kasner MWestermann DSteendijk PDröse SPoller WSchultheiss HPTschöpe C.

Source

Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, CBF, Hindenburgdamm 30, 12200 Berlin, Germany.

Comment in

The right ventricle in pulmonary hypertension: when good neighbors go bad.Granton J. Am J Respir Crit Care Med. 2012 Jul 15; 186(2):121-3.

Abstract

RATIONALE:

Severe increase in right ventricular pressure can compromise left ventricular (LV) function because of impaired interventricular interaction and aggravate the symptoms.

OBJECTIVES:

To elucidate how nonsevere idiopathic pulmonary arterial hypertension (IPAH) influences LV function because of impaired interventricular interaction.

METHODS:

Invasive pressure-volume (PV) loop analysis obtained by conductance catheterization was performed at rest and during atrial pacing in patients with mild IPAH (n = 10) compared with patients with isolated LV diastolic dysfunction (DD) (n = 10) and control subjects without heart failure symptoms (n = 9).

MEASUREMENTS AND MAIN RESULTS:

Patients with nonsevere IPAH (pulmonary artery pressure mean 29 ± 5 mm Hg) and patients with DD showed preserved systolic (ejection fraction 63 ± 12% and 62 ± 9%) and impaired LV diastolic function at rest (LV stiffness 0.027 ± 0.012 ml(-1) and 0.029 ± 0.014 ml(-1)). During pacing at 120 per minute patients with IPAH and DD decreased their stroke volume (-25% and -30%; P < 0.05) and failed to increase cardiac output significantly. Opposite to patients with DD and control subjects, temporary preload reduction during inferior vena cava occlusion initially induced an expansion of LV end-diastolic volume in IPAH (+7%; P < 0.05), whereas end-diastolic pressure continuously dropped. This resulted in an initial downward shift to the right of the PV loop indicating better LV filling, which was associated with a temporary improvement of cardiac output (+11%; P < 0.05) in the patients with IPAH, but not in patients with DD and control subjects.

CONCLUSIONS:

Mild idiopathic pulmonary arterial pressure impairs LV diastolic compliance even in the absence of the intrinsic LV disease and contributes to the reduced cardiac performance at stress.
  PMID: 22561959 [PubMed - indexed for MEDLINE]
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9. Circulation. 2012 Jul 17;126(3):349-56. Epub 2012 Jun 13.

Validation of 6-minute walk distance as a surrogate end point in pulmonary arterial hypertension trials.

Gabler NBFrench BStrom BLPalevsky HITaichman DBKawut SMHalpern SD.

Source

Center for Clinical Epidemiology and Biostatistics, Philadelphia, PA, USA. gabler@upenn.edu

Comment in

Validation of the 6-minute walk in patients with pulmonary arterial hypertension: trying to fit a square PEG into a round hole?Farber HW. Circulation. 2012 Jul 17; 126(3):258-60. Epub 2012 Jun 13.

Abstract

BACKGROUND:

Nearly all available treatments for pulmonary arterial hypertension have been approved based on change in 6-minute walk distance (Δ6MWD) as a clinically important end point, but its validity as a surrogate end point has never been shown. We aimed to validate the difference in Δ6MWD against the probability of a clinical event in pulmonary arterial hypertension trials.

METHODS AND RESULTS:

First, to determine whether Δ6MWD between baseline and 12 weeks mediated the relationship between treatment assignment and development of clinical events, we conducted a pooled analysis of patient-level data from the 10 randomized placebo-controlled trials previously submitted to the US Food and Drug Administration (n=2404 patients). Second, to identify a threshold effect for the Δ6MWD that indicated a statistically significant reduction in clinical events, we conducted a meta-regression among 21 drug/dose-level combinations. Δ6MWD accounted for 22.1% (95% confidence interval, 12.1%- 31.1%) of the treatment effect (P<0.001). The meta-analysis showed an average difference in Δ6MWD of 22.4 m (95% confidence interval, 17.4-27.5 m), favoring active treatment over placebo. Active treatment decreased the probability of a clinical event (summary odds ratio, 0.44; 95% confidence interval, 0.33-0.57). The meta-regression revealed a significant threshold effect of 41.8 m.

CONCLUSIONS:

Our results suggest that Δ6MWD does not explain a large proportion of the treatment effect, has only modest validity as a surrogate end point for clinical events, and may not be a sufficient surrogate end point. Further research is necessary to determine whether the threshold value of 41.8 m is valid for long-term outcomes or whether it differs among trials using background therapy or lacking placebo controls entirely.
  PMID: 22696079 [PubMed - indexed for MEDLINE]
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10. Circulation. 2012 Jul 17;126(3):258-60. Epub 2012 Jun 13.

Validation of the 6-minute walk in patients with pulmonary arterial hypertension: trying to fit a square PEG into a round hole?

Farber HW.

Comment on

Validation of 6-minute walk distance as a surrogate end point in pulmonary arterial hypertension trials.Gabler NB, French B, Strom BL, Palevsky HI, Taichman DB, Kawut SM, Halpern SD. Circulation. 2012 Jul 17; 126(3):349-56. Epub 2012 Jun 13.
  PMID: 22696078 [PubMed - indexed for MEDLINE]
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1. Circ J. 2012 Sep 28. [Epub ahead of print]

Volumetric and Functional Assessment of Ventricles in Pulmonary Hypertension on 3-Dimensional Echocardiography.

Inaba TYao ANakao THatano MMaki HImamura TShiga TYamazaki TSonoda MKinugawa KShiota TSuzuki J,Takenaka KHirata YNagai R.

Source

Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo.

Abstract

Background: Non-invasive assessment of volume and function on the right ventricle (RV) for pulmonary hypertension (PH) is limited. Methods and Results: Patients with PH (n=23) underwent 3-dimensional (D) echocardiography (3DECHO), with cardiac magnetic resonance imaging to confirm its precision, and right heart catheterization. On linear regression analysis the RV end-systolic volume index (ESVI) was positively correlated with pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP; R=0.42 and 0.46, P=0.03 and 0.03, respectively). The RV end-diastolic volume index (EDVI) was positively correlated with mPAP (R=0.41, P<0.05). The left ventricular (LV) EDVI was inversely correlated with PVR (R=-0.48, P=0.02). The RV ejection fraction was inversely correlated with PVR and mean right atrial pressure (mRAP; R=-0.57, and -0.45, P=0.004, and 0.03, respectively). RVEDVI/LVEDVI and RVESVI/LVESVI (the diastolic and systolic remodeling indices, respectively) had a significantly positive linear relationship with PVR (R=0.67 and 0.55, P=0.0005 and 0.006, respectively), and the former had a significantly positive linear relationship with mRAP (R=0.42, P<0.05). During the recovery process in 1 specific case, the remodeling indices maintained a significant linear relationship with the hemodynamic parameters. Conclusions: Novel indices provided by 3DECHO may be utilized as alternative indicators of hemodynamic changes in PH patients.
Free Article
  PMID: 23018765 [PubMed - as supplied by publisher]
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2. Cardiol Rev. 2012 Sep 25. [Epub ahead of print]

Pulmonary Hypertension in Pregnancy.

Martínez MVRutherford JD.

Source

From the Department of Internal Medicine, Cardiology Division, UT Southwestern Medical Center, Dallas, TX.

Abstract

The presence of pulmonary arterial hypertension (PAH) in pregnancy is rare and signifies a high-risk pregnancy. While the majority of mothers have knowledge of their condition prior to pregnancy, approximately a third of patients are diagnosed during pregnancy. Termination of pregnancy should be discussed, and is often advised, however a significant proportion of patients will choose to proceed with the pregnancy despite increased maternal and fetal mortality. Currently, most pregnant patients receive advanced therapy for treatment of PAH, particularly prostacyclin analogues. Particular attention is paid to volume status and blood loss and there has been a major trend towards delivery by cesarean section under controlled conditions involving an expert multidisciplinary team. The time of greatest maternal risk is in the first month after delivery. Transplantation of these patients in the non-pregnant state may be considered when those with idiopathic pulmonary hypertension have poor functional status despite optimal therapy and their projected two-year survival is < 50%. For patients with Eisenmenger Syndrome, severe symptoms and an unacceptable quality of life may lead to transplantation.
  PMID: 23018670 [PubMed - as supplied by publisher]
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3. Gen Thorac Cardiovasc Surg. 2012 Sep 26. [Epub ahead of print]

Pulmonary vascular disease associated with pulmonary hypertension in 445 patients: diagnosis from lung biopsy and autopsy.

Yamaki S.

Source

Japanese Research Institute of Pulmonary Vasculature, 40-1 Usagisaku, Shiroishi, Miyagi, 989-0228, Japan, syamaki@ff.iij4u.or.jp.

Abstract

PURPOSE:

Diagnosis from lung biopsy or autopsy was performed in 445 patients with congenital (385) or acquired (60) heart disease from all over Japan. The purpose of this study is the presentation of these prospective data collections.

METHODS:

Of the patients with congenital heart disease, 354 were biopsied to determine whether surgery was indicated. Decisions regarding surgery were based on the index of pulmonary vascular disease in simple cardiac anomalies or atrioventricular septal defects (AVSD). In total anomalous pulmonary venous connection (TAPVC), operative indication was determined by the degree of hypoplasia of small pulmonary arteries. Operability of Fontan procedure was based on the degree of residual medial hypertrophy after pulmonary artery banding.

RESULTS:

In patients with simple cardiac anomalies, radical surgery was indicated in 166. Radical surgery was indicated in 50 patients with AVSD. In 26 patients with TAPVC, radical surgery was not indicated in 10. In 68 Fontan candidates, surgery was not indicated in 49. Among 7 patients with tetralogy of Fallot, 1 was not a surgical candidate. Of the 60 acquired heart disease patients, 16 had idiopathic pulmonary arterial hypertension and 36 had chronic thromboembolic pulmonary hypertension. In 6 patients, lung biopsy revealed pulmonary veno-occlusive disease; 2 patients had combined valvular disease.

CONCLUSION:

The cardiac surgeon, pediatric cardiologist, and cardiologist who requested diagnosis from lung biopsy or autopsy were gratified with the results.
  PMID: 23011519 [PubMed - as supplied by publisher]
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4. Prog Cardiovasc Dis. 2012 Sep;55(2):199-217. doi: 10.1016/j.pcad.2012.08.002.

Anesthesia and pulmonary hypertension.

McGlothlin DIvascu NHeerdt PM.

Source

Division of Cardiology, University of California San Francisco, CA. Electronic address: mcglothl@medicine.ucsf.edu.

Abstract

Anesthesia and surgery are associated with significantly increased morbidity and mortality in patients with pulmonary hypertension due mainly to right ventricular failure, arrhythmias, postoperative hypoxemia, and myocardial ischemia. Preoperative risk assessment and successful management of patients with pulmonary hypertension undergoing cardiac surgery involve an understanding of the pathophysiology of the disease, screening of patients at-risk for pulmonary arterial hypertension, analysis of preoperative and operative risk factors, thorough multidisciplinary planning, careful intraoperative management, and early recognition and treatment of postoperative complications. This article will cover each of these aspects with particular focus on the anesthetic approach for non-cardiothoracic surgeries.
Copyright © 2012 Elsevier Inc. All rights reserved.
  PMID: 23009916 [PubMed - in process]
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5. Prog Cardiovasc Dis. 2012 Sep;55(2):187-98. doi: 10.1016/j.pcad.2012.07.001.

Pulmonary hypertension in the intensive care unit.

Poor HDVentetuolo CE.

Source

Division of Pulmonary, Allergy and Critical Care Medicine, New York Presbyterian Hospital, Columbia University College of Physicians and Surgeons, New York, NY.

Abstract

Pulmonary hypertension, a condition that can lead to right ventricular failure and hemodynamic collapse, can be very challenging to manage in critically ill patients who require the intensive care unit. Because of the underlying structure of the right ventricle, significant increases in right ventricular afterload initiate a vicious cycle of degenerating right ventricular function, giving rise to right ventricular failure and cardiogenic shock. In patients with pulmonary hypertension, inciting factors such as sepsis and arrhythmias can exacerbate this process. Important management principles include close monitoring of hemodynamics with both noninvasive and invasive modalities, optimization of right ventricular preload, maintenance of systemic blood pressure, enhancement of right ventricular contractility, reduction of right ventricular afterload, and reversal of identifiable inciting factors. The goal of this review is to discuss these key concepts in managing this difficult patient population.
Copyright © 2012 Elsevier Inc. All rights reserved.
  PMID: 23009915 [PubMed - in process]
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6. Prog Cardiovasc Dis. 2012 Sep;55(2):161-71. doi: 10.1016/j.pcad.2012.07.009.

Computed tomography and cardiac magnetic resonance imaging in pulmonary hypertension.

Stevens GRFida NSanz J.

Source

Montefiore-Einstein Center for Heart and Vascular Care, Albert Einstein College of Medicine, Bronx, NY. Electronic address:gstevens@montefiore.org.

Abstract

Recent advances in imaging technology have allowed for better temporal and spatial resolution in cardiovascular imaging. The idea of a "one-stop shop" for anatomical and functional cardiopulmonary and vascular assessment in patients with pulmonary hypertension is very appealing since diagnostic, prognostic, and therapeutic response can be measured. Modalities, such as computed tomography (CT) and cardiac magnetic resonance (CMR), are better suited to image the right heart and associated structures in multiple projections allowing for three-dimensional data sets and image reconstruction. This review will focus on the use of CT and CMR in the assessment of the right ventricle and pulmonary structures as they relate to pulmonary vascular disease.
Copyright © 2012 Elsevier Inc. All rights reserved.
  PMID: 23009912 [PubMed - in process]
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7. Prog Cardiovasc Dis. 2012 Sep;55(2):128-33. doi: 10.1016/j.pcad.2012.07.004.

Congenital heart disease and pulmonary hypertension: pharmacology and feasibility of late surgery.

Rosenzweig EBBarst RJ.

Source

Columbia University College of Physicians and Surgeons, New York, NY. Electronic address: esb14@columbia.edu.

Abstract

Pulmonary arterial hypertension (PAH) with increased pulmonary vascular resistance (PVR), previously termed pulmonary vascular obstructive disease or pulmonary vascular disease is a frequent complication of congenital heart disease (CHD).While there have been advances in the medical treatments available for classic Eisenmenger syndrome patients who are not suitable for repair, the sub-group of patients with moderate sized congenital systemic to pulmonary shunts and mild to moderately elevated PVR remains challenging. With the development of targeted medical treatments for pulmonary arterial hypertension (PAH), the concept of a combined medical and interventional/surgical approach for patients with PAH associated with CHD (APAH-CHD) has emerged. Careful evaluation and an understanding of the predominant physiologic features will help guide the management of these complex patients and whether late surgical repair is feasible.
Copyright © 2012. Published by Elsevier Inc.
  PMID: 23009909 [PubMed - in process]
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8. Prog Cardiovasc Dis. 2012 Sep;55(2):119-27. doi: 10.1016/j.pcad.2012.08.003.

World Health Organization Group III pulmonary hypertension.

Poor HDGirgis RStuder SM.

Source

New York Presbyterian Hospital, Columbia University College of Physicians and Surgeons, New York, NY.

Abstract

Pulmonary hypertension in the setting of parenchymal lung disease and conditions associated with chronic hypoxemia is commonly encountered in clinical practice and may adversely affect patients' function and mortality. Diagnosis of this subgroup of pulmonary hypertension has evolved but still requires right heart catheterization for confirmation. The primary treatment goal is optimization of the underlying parenchymal lung or hypoxemia-associated condition prior to consideration of pharmacologic therapy. Limited published experience with pulmonary hypertension-specific medications for treatment of WHO Group 3 pulmonary hypertension suggests symptomatic and functional benefit in selected individuals. The potential for worsening ventilation-perfusion matching must be considered in these cases, however, since there is a paucity of data regarding the optimal approach to treatment selection. Ongoing medication trials and further investigation of mechanisms of hypoxic pulmonary vasoconstriction provide hope for these patients who in the past often had only lung transplantation as a potential treatment option.
Copyright © 2012 Elsevier Inc. All rights reserved.
  PMID: 23009908 [PubMed - in process]
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9. Prog Cardiovasc Dis. 2012 Sep;55(2):104-18. doi: 10.1016/j.pcad.2012.07.007.

Pulmonary hypertension and right ventricular dysfunction in left heart disease (group 2 pulmonary hypertension).

Wilson SRGhio SScelsi LHorn EM.

Source

Cardiology Division, Department of Medicine, Weill Cornell Medical College, New York, NY.

Abstract

Group 2 pulmonary hypertension is most frequently caused by left heart disease, a heterogeneous set of disorders. These processes include left ventricular systolic dysfunction, left ventricular dysfunction with preserved ejection fraction and valvular (mitral and/or aortic) diseases. Left heart disease may cause passive backward transmission of pressure leading to elevated left atrial and pulmonary arterial pressures due to a myriad of processes. Increasingly, it has been recognized that some patients may develop pulmonary arterial pressure out of proportion from what is expected. This is believed to be due to increases in vasomotor tone and/or vascular remodeling. Over time patients may go on to develop progressive right ventricular dysfunction, a marker for poor prognosis. This review will explore the different characteristics of these conditions including the incidence, pathophysiology, clinical implications, prognosis and current state of available medical therapies.
Copyright © 2012 Elsevier Inc. All rights reserved.
  PMID: 23009907 [PubMed - in process]
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10. Naunyn Schmiedebergs Arch Pharmacol. 2012 Jul;385(7):657-70. Epub 2012 May 6.

Mast cells: an expanding pathophysiological role from allergy to other disorders.

Anand PSingh BJaggi ASSingh N.

Source

Department of Chemistry, Punjabi University, Patiala 147002, India.

Abstract

The mast cells are multi-effector cells with wide distribution in the different body parts and traditionally their role has been well-defined in the development of IgE-mediated hypersensitivity reactions including bronchial asthma. Due to the availability of genetically modified mast cell-deficient mice, the broadened pathophysiological role of mast cells in diverse diseases has been revealed. Mast cells exert different physiological and pathophysiological roles by secreting their granular contents, including vasoactive amines, cytokines and chemokines, and various proteases, including tryptase and chymase. Furthermore, mast cells also synthesize plasma membrane-derived lipid mediators, including prostaglandins and leukotrienes, to produce diverse biological actions. The present review discusses the pathophysiological role of mast cells in different diseases, including atherosclerosis, pulmonary hypertension, ischemia-reperfusion injury, male infertility, autoimmune disorders such as rheumatoid arthritis and multiple sclerosis, bladder pain syndrome (interstitial cystitis), anxiety, Alzheimer's disease, nociception, obesity and diabetes mellitus.
  PMID: 22562473 [PubMed - indexed for MEDLINE]
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11. Circ J. 2012;76(6):1494-500. Epub 2012 Mar 16.

Platelet level as a new prognostic factor for idiopathic pulmonary arterial hypertension in the era of combination therapy.

Taguchi HKataoka MYanagisawa RKawakami TTamura YFukuda KYoshino HSatoh T.

Source

Division of Cardiology, Department of Medicine, Kyorin University School of Medicine, Tokyo, Japan.

Abstract

BACKGROUND:

The recent development of various effective drugs, such as epoprostenol, sildenafil, and bosentan, has improved the prognosis for patients with idiopathic pulmonary arterial hypertension (IPAH). This study sought to determine survival rates and to identify predictive prognostic factors in patients with IPAH in the current era of combination therapy with new and more effective vasodilators.

METHODS AND RESULTS:

In 65 consecutive IPAH patients treated from 2004 to 2009, hemodynamic parameters were significantly improved and brain natriuretic peptide was significantly decreased by combination therapy (observation period: 35±18 months). The Kaplan-Meier survival curves were determined, and 22 prognostic variables, including 9 hemodynamic variables and 6 biomarkers, were evaluated to obtain the best variables. The 1-year and 3-year survival rates were 98% and 86%, respectively. Only the platelet level was correlated with death (P<0.05), and the platelet level was significantly correlated with mean pulmonary arterial pressure (P<0.01). Patients with a lower platelet level (<20×10(4)/µl (median value)) before treatment had a higher mortality rate compared to the other patients (78% vs. 95% for 3-year survival, P<0.01).

CONCLUSIONS:

Combination therapy contributed to an improvement in the prognosis of IPAH patients. Platelet level is a significant prognostic predictor in this new treatment era.
Free Article
  PMID: 22447010 [PubMed - indexed for MEDLINE]
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12. J Palliat Med. 2012 May;15(5):619-22. Epub 2012 Mar 6.

Epoprostenol use for pulmonary arterial hypertension in the palliative care setting.

Wozencraft CPCoyne PJGrinnan DCMorel TDMuzevich KMSmith TJ.

Source

Department of Internal Medicine, Division of General Medicine, Virginia Commonwealth University, Richmond, Virginia 23298, USA.

Abstract

Prostacyclin analogues such as epoprostenol (Flolan®) are commonly used in the treatment of pulmonary arterial hypertension (PAH). However, their complex administration and significant cost may limit the access that patients with PAH have to palliative and hospice care. We herein report our experience using epoprostenol in a dedicated palliative care unit and present our inpatient protocol for the drug's administration.
  PMID: 22394366 [PubMed - indexed for MEDLINE]
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13. Eur Respir J. 2012 Oct;40(4):1057-9.

Severe pulmonary hypertension leading to heart-lung transplantation and revealing breast cancer.

Madjer TDanner-Boucher IHoreau-Langlard DHaloun ALepoivre TSagan CMagnan A.

Source

Service de pneumologie de l'Hôpital Nord Laennec, Boulevard Jacques Monod, 44093, Nantes Cedex 1, France. E-mail:tania.madjer2@free.fr.
  PMID: 23024331 [PubMed - in process]
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1. Clin Sci (Lond). 2012 Oct;123(8):487-98.

Renin-angiotensin system blockade: a novel therapeutic approach in chronic obstructive pulmonary disease.

Shrikrishna DAstin RKemp PRHopkinson NS.

Source

NIHR Respiratory Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, U.K. dinesh.shrikrishna@nhs.net

Abstract

ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin II receptor blockers) are already widely used for the treatment and prevention of cardiovascular disease and their potential role in other disease states has become increasingly recognized. COPD (chronic obstructive pulmonary disease) is characterized by pathological inflammatory processes involving the lung parenchyma, airways and vascular bed. The aim of the present review is to outline the role of the RAS (renin-angiotensin system) in the pathogenesis of COPD, including reference to results from fibrotic lung conditions and pulmonary hypertension. The review will, in particular, address the emerging evidence that ACE inhibition could have a beneficial effect on skeletal muscle function and cardiovascular co-morbidity in COPD patients. The evidence to support the effect of RAS blockade as a novel therapeutic approach in COPD will be discussed.
  PMID: 22757959 [PubMed - indexed for MEDLINE]
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2. J Am Coll Cardiol. 2012 Sep 25;60(13):1202-3. doi: 10.1016/j.jacc.2012.03.080.

The 6-minute walk test as a primary endpoint in clinical trials for pulmonary hypertension.

Rich S.

Source

Department of Medicine, Section of Cardiology, University of Chicago, Chicago, Illinois. Electronic address:srich@medicine.bsd.uchicago.edu.
  PMID: 22995025 [PubMed - in process]
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