Indian J Anaesth. 2018 Apr;62(4):325. doi: 10.4103/ija.IJA_179_18.

Reply to ‘The link between pulmonary hypertension and adverse renal transplant outcome may be renal venous hypertension’.

Solanki SL¹, Goyal VK², Baj B².

Author information:

1. Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India.
2. Department of Anaesthesiology and Critical Care, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India.

Free PMC Article
PMCID: PMC5907446
PMID: 29720766

Conflict of interest statement
There are no conflicts of interest.

Clin Transplant. 2018 Apr 6:e13251. doi: 10.1111/ctr.13251. [Epub ahead of print]

Pulmonary hypertension is not a risk factor for grade 3 primary graft dysfunction after lung transplantation.

Cottini SR¹, Brandi G¹, Pagnamenta A^2,3, Weder W⁴, Schuepbach RA¹, Béchir M^1,5, Huber LC^6,7, Benden C⁶.

Author information:

1. Surgical Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland.
2. Department of Intensive Care Medicine of the Ente Ospedaliero Cantonale (EOC): Intensive Care Unit of Regional Hospital of Mendrisio, Mendrisio, Switzerland.
3. Unit of Clinical Epidemiology, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
4. Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
5. Swiss Paraplegic Center, Nottwil, Switzerland.
6. Division of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
7. Clinic for Internal Medicine, City Hospital Triemli, Zurich, Switzerland.

Abstract

Grade 3 primary graft dysfunction (PGD3) represents the most important risk factor for patient mortality during the first year after lung transplantation (LTX). We investigated whether pretransplant pulmonary hypertension (PH) is a risk factor for the development of PGD3. This retrospective, single-center cohort study included 96 candidates undergoing right heart catheterization (RHC) prior to being listed for LTX between March 2000 and October 2015. Based on their mean pulmonary artery pressure (mPAP) levels, the patients were classified into 3 groups: (1) <25 mm Hg, (2) 25-34 mm Hg and (3) ≥35 mm Hg. Forty-seven patients were classified in group 1, 31 in group 2, and 18 in group 3. Fifteen recipients (16%, 95%-CI 8-23) developed PGD3. In the univariate analysis, the diagnosis of interstitial lung disease (ILD) compared to COPD (OR: 7.06, P = .005), blood transfusion >1000 mL during surgery (OR: 5.25, P = .005), the need for intra-operative cardio-pulmonary bypass (CPB) or extra-corporeal membrane oxygenation (ECMO) (OR: 4, P = .027), mPAP (OR 1.06, P = .007) and serum high density lipoprotein-cholesterol (HDL-C) (OR 0.09, P = .005) were associated with PGD3. In the multivariable logistic regression analysis, only HDL-C (OR 0.10, P = .016) was associated with PGD3 based on our single-center cohort data analysis.

PMID: 29707826

Proc (Bayl Univ Med Cent). 2018 Mar 12;31(2):213-215. doi: 10.1080/08998280.2018.1435112. eCollection 2018 Apr.

Late breast cancer recurrence with bone marrow metastases and acute pulmonary hypertension.

Atwal D¹, Ramos JM², Makhoul I³.

Author information:

1. Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
2. Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
3. Division of Medical Oncology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Abstract

Bone marrow is one of the most common sites of metastasis from breast cancer. Micrometastases to the bone marrow usually evade the systemic therapies used for the treatment of cancer and eventually lead to relapse later in the course of the illness. We report here a unique case of parallel progression of these bone marrow metastases in a patient with breast cancer who had a relapse a few years after treatment of her primary breast cancer, and she presented with diffuse marrow involvement and pulmonary hypertension without any definitive metastases elsewhere.

Free PMC Article
PMCID: PMC5914435
PMID: 29706824

Heart Vessels. 2018 Apr 27. doi: 10.1007/s00380-018-1168-7. [Epub ahead of print]

Usefulness of scoring right ventricular function for assessment of prognostic factors in patients with chronic thromboembolic pulmonary hypertension.

Kamimura Y¹, Okumura N², Adachi S², Shimokata S¹, Tajima F¹, Nakano Y¹, Hirashiki A³, Murohara T¹, Kondo T⁴.

Author information:

1. Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya, 466-8550, Japan.
2. Department of Advanced Medicine in Cardiopulmonary Disease, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya, 466-8560, Japan.
3. Department of Cardiology, National Center for Geriatrics and Gerontology, Morioka-cho 7-430, Obu, 474-8511, Japan.
4. Department of Advanced Medicine in Cardiopulmonary Disease, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya, 466-8560, Japan. takahisa@med.nagoya-u.ac.jp.

Abstract

Right ventricular (RV) function is associated with prognosis in chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to establish an RV dysfunction score using RV echocardiographic parameters to clarify the clinical characteristics in patients with CTEPH and to compare RV dysfunction score with parameters such as World Health Organization (WHO) functional class, hemodynamics, exercise capacity, and plasma BNP level. We enrolled 35 inpatients with CTEPH (mean age, 62 ± 15 years, 15 males). We constructed ‘an RV dysfunction score’ calculated as the summation of each point awarded for the presence of four parameters: tricuspid annular plane systolic excursion (TAPSE) < 16 mm, 1 point; tissue Doppler-derived tricuspid lateral annular systolic velocity (S’) < 10 cm/s, 1 point; right ventricular fractional area change (RVFAC) < 35%, 1 point; and right ventricular myocardial performance index (RV-MPI) > 0.4, 1 point. TAPSE, S’, RVFAC, and RV-MPI was 18.7 ± 4.8 mm, 11.9 ± 3.1 cm/s, 33.5 ± 13.9%, and 0.39 ± 0.2, respectively. The RV dysfunction score was associated with symptom [WHO functional class (p = 0.026)], hemodynamics [mean PAP (p = 0.01), cardiac index (p = 0.009), pulmonary vascular resistance (p = 0.001), and SvO2 (p = 0.039)], exercise capacity [6-min walk distance (p = 0.046), peakVO2 (p = 0.016), and VE/VCO2 slope (p = 0.031)], and plasma BNP level (p = 0.005). This RV dysfunction score using the four RV echocardiographic parameters could be a simple and useful scoring system to evaluate prognostic factors in patients with CTEPH.

PMID: 29704099

J Heart Valve Dis. 2016 Nov;25(6):708-715.

Association of Transforming Growth Factor-β Superfamily Genes with Non-Regression of Pulmonary Artery Hypertension Following Balloon Mitral Valvotomy: A Pilot Study.

Prabhu MA¹, Ismael S², Remani K², Nair R², Koshy L³, Pillai H⁴.

Author information:

1. Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India. Electronic correspondence: mukundaprabhu@gmail.com.
2. Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India.
3. Inter-University Centre for Genomics and Gene Technology, Trivandrum, India.
4. Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India.

Abstract

BACKGROUND AND AIM OF THE STUDY:
Pulmonary arterial hypertension (PAH) is a common accompaniment of rheumatic mitral stenosis (MS), with 70% of patients showing evidence of different grades of PAH. The latter condition is found to be a prognostic factor influencing disease outcome even after interventional or surgical therapy. The cause of the non-regression of PAH following successful balloon mitral valvotomy (BMV) is not clear. Hence, the study aim was to determine if there is an association of mutations in the genes of the TGF-β superfamily and non-regression of PAH in patients who undergo a successful BMV.

METHODS:
Forty-six patients who underwent BMV and fulfilled the recruitment criteria were enrolled prospectively in this case-control study. Among the patients, 27 had non-regression of PAH while 19 had regression of PAH and served as controls. The mean age of the population was 32.63 ± 10.65 years.

RESULTS:
No statistically significant differences were identified in any of the baseline parameters between the two groups. None of the samples had BMPR2 or ACVRL1 mutations. Ten of the patients and four of the controls were positive for Endoglin mutation, but the inter-group difference was not statistically significant (p = 0.25) CONCLUSIONS: The present study – the first of its kind – showed that deletion-duplication mutations in the BMPR2 or ACVRL1 genes may not be associated with non-regression of PAH, even after successful BMV, or in a wider sense serve as a contributor to PAH in rheumatic MS. The association of Endoglin mutation and non-regression of PAH warrants further investigation in a larger population.

PMID: 28290170 [Indexed for MEDLINE]

Biomed Res Int. 2018 Mar 19;2018:3924517. doi: 10.1155/2018/3924517. eCollection 2018.

Health-Related Quality of Life in Pulmonary Hypertension and Its Clinical Correlates: A Cross-Sectional Study.

Reis A¹, Santos M^1,2,3, Vicente M⁴, Furtado I⁵, Cruz C⁵, Melo A¹, Carvalho L^1,5, Gonçalves F^1,5, Sa-Couto P⁶, Almeida L⁷.

Author information:

1. Pulmonary Vascular Disease Unit, Medicine Department, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal.
2. Cardiology Service, Medicine Department, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal.
3. Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of Porto, Porto, Portugal.
4. Department of Health Sciences, University of Aveiro, Aveiro, Portugal.
5. Internal Medicine Service, Medicine Department, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal.
6. Center for Research and Development in Mathematics and Applications, Department of Mathematics, University of Aveiro, Aveiro, Portugal.
7. MedInUP, Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.

Abstract

Background:
Health-related quality of life (HRQoL) impairment is common in pulmonary hypertension (PH), but its clinical predictors are not well established. This study aims to characterize the HRQoL of patients with pulmonary arterial hypertension (PAH) and other precapillary forms of PH (pcPH) and to explore its clinical correlates.

Materials and Methods:
A cross-sectional, observational study of patients with documented PAH and other forms of pcPH. Patients completed two patient-reported outcome measures (PROM): Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and Nottingham Health Profile (NHP). Clinical characteristics were retrieved from electronic medical records.

Results:
Mean CAMPHOR and NHP scores for the study population were indicative of a moderate HRQoL impairment. Patients in World Health Organisation Functional Classes (WHO FC) III/IV showed significantly worse HRQoL. The main clinical correlates of HRQoL were WHO FC, 6-minute walking distance (6MWD), and Borg dyspnoea index. Overall quality of life (QoL), assessed through CAMPHOR’s QoL domain, showed patterns comparable to HRQoL measured by both instruments.

Conclusions:
HRQoL, measured by two different PROMs, is impaired in Portuguese patients with PAH and other forms of pcPH, particularly in patients with increased disease severity. WHO FC, 6MWD, and Borg dyspnoea index are highly correlated with HRQoL and QoL.

Free PMC Article
PMCID: PMC5884279
PMID: 29750153

ERJ Open Res. 2018 May 4;4(2). pii: 00124-2017. doi: 10.1183/23120541.00124-2017. eCollection 2018 Apr.

A stepwise composite echocardiographic score predicts severe pulmonary hypertension in patients with interstitial lung disease.

Bax S^1,2,3, Bredy C⁴, Kempny A^4,5, Dimopoulos K^4,5, Devaraj A^5,6, Walsh S⁷, Jacob J⁶, Nair A⁸, Kokosi M⁹, Keir G^9,10, Kouranos V⁹, George PM⁹, McCabe C², Wilde M^2,3, Wells A^1,9, Li W^4,5,11, Wort SJ^1,2,11, Price LC^1,2,11.

Author information:

1. National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
2. National Pulmonary Hypertension Service, Royal Brompton Hospital, London, UK.
3. Surrey and Sussex NHS Trust, Redhill, UK.
4. Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK.
5. NIHR Cardiovascular Biomedical Research Unit, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
6. Dept of Radiology, Royal Brompton Hospital, London, UK.
7. Dept of Radiology, King’s College Hospital, London, UK.
8. Dept of Radiology, Guy’s and St Thomas’ NHS foundation Trust, London, UK.
9. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK.
10. Princess Alexandra Hospital, Brisbane, Australia.
11. These authors contributed equally.

Abstract

European Respiratory Society (ERS) guidelines recommend the assessment of patients with interstitial lung disease (ILD) and severe pulmonary hypertension (PH), as defined by a mean pulmonary artery pressure (mPAP) ≥35 mmHg at right heart catheterisation (RHC). We developed and validated a stepwise echocardiographic score to detect severe PH using the tricuspid regurgitant velocity and right atrial pressure (right ventricular systolic pressure (RVSP)) and additional echocardiographic signs. Consecutive ILD patients with suspected PH underwent RHC between 2005 and 2015. Receiver operating curve analysis tested the ability of components of the score to predict mPAP ≥35 mmHg, and a score devised using a stepwise approach. The score was tested in a contemporaneous validation cohort. The score used “additional PH signs” where RVSP was unavailable, using a bootstrapping technique. Within the derivation cohort (n=210), a score ≥7 predicted severe PH with 89% sensitivity, 71% specificity, positive predictive value 68% and negative predictive value 90%, with similar performance in the validation cohort (n=61) (area under the curve (AUC) 84.8% versus 83.1%, p=0.8). Although RVSP could be estimated in 92% of studies, reducing this to 60% maintained a fair accuracy (AUC 74.4%). This simple stepwise echocardiographic PH score can predict severe PH in patients with ILD.

Free PMC Article
PMCID: PMC5934528
PMID: 29750141

Conflict of interest statement
Conflict of interest: A. Kempny reports receiving grants from Actelion Global, outside the submitted work. Conflict of interest: K. Dimopoulos reports receiving grants from Actelion, GSK, Pfizer and Bayer, outside the submitted work. Conflict of interest: J. Jacob reports receiving personal fees from Boehringer Ingelheim, outside the submitted work. Conflict of interest: A. Wells reports receiving personal fees from Intermune, Boehringer Inlgeheim, Gilead, MSD, Roche, Bayer and Chiesi, outside the submitted work. Conflict of interest: S.J. Wort reports receiving grants from Actelion, GSK, Pfizer and Bayer, outside the submitted work. Conflict of interest: L.C. Price reports educational grants from Actelion and GSK, during the conduct of the study. Conflict of interest: Dr. George reports personal fees from Roche, personal fees from Boeringer Ingelheim, outside the submitted work.

Acad Radiol. 2018 May 2. pii: S1076-6332(18)30184-3. doi: 10.1016/j.acra.2018.04.002. [Epub ahead of print]

MRI-derived Regional Biventricular Function in Patients with Chronic Thromboembolic Pulmonary Hypertension Before and After Pulmonary Endarterectomy.

Maschke SK¹, Schoenfeld CO¹, Kaireit TF¹, Cebotari S², Olsson K³, Hoeper M³, Wacker F¹, Vogel-Claussen J⁴.

Author information:

1. Diagnostic and Interventional Radiology, Hannover Medical School, OE 8220, Carl-Neuberg-Str. 1, 30625, Hannover, Germany; Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), German Center for Lung Research, Hannover, Germany.
2. Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), German Center for Lung Research, Hannover, Germany; Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
3. Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), German Center for Lung Research, Hannover, Germany; Respiratory Medicine, Hannover Medical School, Hannover, Germany.
4. Diagnostic and Interventional Radiology, Hannover Medical School, OE 8220, Carl-Neuberg-Str. 1, 30625, Hannover, Germany; Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), German Center for Lung Research, Hannover, Germany. Electronic address: vogel-claussen.jens@mh-hannover.de.

Abstract

RATIONALE AND OBJECTIVES:
The aim of this study was to assess regional myocardial function in patients with chronic thromboembolic hypertension (CTEPH) before and after successful pulmonary endarterectomy (PEA) using magnetic resonance imaging.

METHODS:
Twenty-two patients with CTEPH underwent cardiac magnetic resonance imaging before and 12 (11, 17) days after PEA. Mean pulmonary artery pressure was evaluated preoperatively by right heart catheterization and during post-PEA intensive care unit-stay using a Swan-Ganz catheter. Biventricular peak systolic longitudinal, radial, circumferential strain and time-to-peak strain were obtained by tissue-tracking analysis.

RESULTS:
Mean pulmonary artery pressure decreased (46 mm Hg (34.5, 55) to 24 mm Hg (16, 27); P < .0001) and stroke volume increased (P < .0001) after PEA. In the right ventricle (RV) peak radial strain increased in the anterior (P = .04) and in the inferior wall (P = .0012) and slightly missed statistical significance in the lateral wall (P = .051) and septum (P = .07). Circumferential strain increased in the lateral (P = .0002) and inferior wall of the RV (P = .03) and in the lateral as well as in the inferior wall of the left ventricle (P = .01; P = .03). Radial, longitudinal, and circumferential time-to-peak strain shortened (P < .0001) with resynchronization of the ventricles 12 days after PEA.

CONCLUSION:
While biventricular resynchronization and recovery of global predominantly RV function was observed, regional circumferential function mainly improved in the lateral and inferior walls of both ventricles and regional radial function in the RV wall and septum 12 days after PEA, suggesting fibers primarily affected by myocardial stress in patients with CTEPH possibly need a relatively longer recovery time.

Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

PMID: 29730148

Cardiovasc Revasc Med. 2018 Mar 23. pii: S1553-8389(18)30118-0. doi: 10.1016/j.carrev.2018.03.015. [Epub ahead of print]

The predictive value of baseline pulmonary hypertension in early and long term cardiac and all-cause mortality after transcatheter aortic valve implantation for patients with severe aortic valve stenosis: A systematic review and meta-analysis.

Kokkinidis DG¹, Papanastasiou CA², Jonnalagadda AK³, Oikonomou EK⁴, Theochari CA⁴, Palaiodimos L⁵, Karvounis HI², Armstrong EJ⁶, Faillace RT⁵, Giannakoulas G².

Author information:

1. Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA; Division of Cardiology, Denver VA Medical Center and University of Colorado, Denver, USA. Electronic address: damiankokki@gmail.com.
2. 1st Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
3. Division of Cardiology, Medstar, Washington Hospital Center, DC, USA.
4. Cardiology Working Group, Society of Junior Doctors, Athens, Greece.
5. Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
6. Division of Cardiology, Denver VA Medical Center and University of Colorado, Denver, USA.

Abstract

BACKGROUND:
Transcatheter aortic valve implantation (TAVI) is a safe and effective alternative to surgical aortic valve replacement (SAVR) for the treatment of severe aortic valve stenosis (AS). The impact of concomitant baseline elevated pulmonary artery pressures on outcomes after TAVI has not been established, since different studies used different definitions of pulmonary hypertension (PH).

OBJECTIVE:
To determine the association of PH with early and late cardiac and all-cause mortality after TAVI.

METHODS:
We performed a meta-analysis of studies comparing patients with elevated pulmonary artery pressures (defined as pulmonary hypertension or not) versus patients without elevated pulmonary artery pressures undergoing TAVI. We first performed stratified analyses based on the different PH cut-off values utilized by the included studies and subsequently pooled the studies irrespective of their cut-off values. We used a random effects model for the meta-analysis and assessed heterogeneity with I-square. Separate meta-analyses were performed for studies reporting outcomes as hazards ratios (HRs) and relative risks (RRs). Subgroup analyses were performed for studies published before and after 2013. Meta-regression analysis in order to assess the effect of chronic obstructive pulmonary disease and mitral regurgitation were performed.

RESULTS:
In total 22 studies were included in this systematic review. Among studies presenting results as HR, PH was associated with increased late cardiac mortality (HR: 1.8. 95% CI: 1.3-2.3) and late all-cause mortality (HR: 1.56; 95% CI: 1.1-2). The PH cut-off value that was most likely to be associated with worst outcomes among the different endpoints was pulmonary artery systolic pressure of 60 mm Hg (HR: 1.8; 95% CI: 1.3-2.3; I2 = 0, for late cardiac mortality and HR: 1.52; 95% CI: 1-2.1; I2 = 85% for late all-cause mortality).

CONCLUSION:
This systematic review and meta-analysis emphasizes the importance of baseline PH in predicting mortality outcomes after TAVI. Additional studies are needed to clarify the association between elevated baseline pulmonary artery pressures and outcomes after TAVI.

Copyright © 2018 Elsevier Inc. All rights reserved.

PMID: 29724516

Respir Med. 2018 May;138:13-20. doi: 10.1016/j.rmed.2018.03.019. Epub 2018 Mar 16.

Sildenafil added to pirfenidone in patients with advanced idiopathic pulmonary fibrosis and risk of pulmonary hypertension: A Phase IIb, randomised, double-blind, placebo-controlled study – Rationale and study design.

Behr J¹, Nathan SD², Harari S³, Wuyts W⁴, Kirchgaessler KU⁵, Bengus M⁵, Gilberg F⁵, Wells AU⁶.

Author information:

1. Department of Internal Medicine V, University of Munich and Asklepios Fachkliniken Gauting, Comprehensive Pneumology Center Munich, Germany. Electronic address: j.behr@asklepios.com.
2. INOVA Heart and Vascular Institute, Inova Fairfax Hospital, Vienna, VA, USA.
3. U.O. di Pneumologia e Terapia Semi-Intensiva Respiratoria, Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe, MultiMedica IRCCS, Milan, Italy.
4. Department of Pulmonary Medicine, Unit for Interstitial Lung Diseases, University of Leuven, Leuven, Belgium.
5. F. Hoffmann-La Roche Ltd., Basel, Switzerland.
6. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK.

Abstract

BACKGROUND:
Pulmonary hypertension (PH) is commonly observed in patients with advanced idiopathic pulmonary fibrosis (IPF). Despite the availability of therapies for both IPF and PH, none are approved for PH treatment in the context of significant pulmonary disease. This study will investigate the use of sildenafil added to pirfenidone in patients with advanced IPF and risk of PH, who represent a group with a high unmet medical need.

METHODS:
This Phase IIb, randomised, double-blind, placebo-controlled trial is actively enrolling patients and will study the efficacy, safety and tolerability of sildenafil or placebo in patients with advanced IPF and intermediate or high probability of Group 3 PH who are receiving a stable dose of pirfenidone. Patients with advanced IPF (diffusing capacity for carbon monoxide ≤40% predicted) and risk of Group 3 PH (defined as mean pulmonary arterial pressure ≥20 mm Hg with pulmonary arterial wedge pressure ≤15 mm Hg on a previous right-heart catheterisation [RHC], or intermediate/high probability of Group 3 PH as defined by the 2015 European Society of Cardiology/European Respiratory Society guidelines) are eligible. In the absence of a previous RHC, patients with an echocardiogram showing a peak tricuspid valve regurgitation velocity ≥2.9 m/s can enrol if all other criteria are met. The primary efficacy endpoint is the proportion of patients with disease progression over a 52-week treatment period. Safety will be evaluated descriptively.

DISCUSSION:
Combination treatment with sildenafil and pirfenidone may warrant investigation of the treatment of patients with advanced IPF and pulmonary vascular involvement leading to PH.

Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Free Article
PMID: 29724385

Pulm Circ. 2018 Jan 1:2045894018780521. doi: 10.1177/2045894018780521. [Epub ahead of print]

Characteristics and Survival Data from Latvian Pulmonary Hypertension Registry: Comparison of Prospective Pulmonary Hypertension Registries in Europe.

Skride A¹, Sablinskis K², Lejnieks A¹, Rudzitis A², Lang I³.

Author information:

1. Riga Stradins Universitate Medicinas Fakultate.
2. Pauls Stradins Clinical University Hospital.
3. Medizinische Universitat Wien.

PMID: 29767576

Pulm Circ. 2018 Jan 1:2045894018780734. doi: 10.1177/2045894018780734. [Epub ahead of print]

EXPRESS: Interleukin-6 Trans-signaling Contributes to Chronic Hypoxia-Induced Pulmonary Hypertension.

Maston LD¹, Jones DT¹, Giermakowska W¹, Howard TA¹, Ramiro-Diaz JM¹, Resta T¹, Jernigan N¹, Herbert L¹, Maurice AA¹, Gonzalez Bosc LV¹.

Author information:

1. University of New Mexico Health Sciences Center.

PMID: 29767573

Respir Investig. 2018 Mar 13. pii: S2212-5345(18)30014-5. doi: 10.1016/j.resinv.2018.02.004. [Epub ahead of print]

Can results from a Japanese pulmonary hypertension registry have an impact on Western guidelines?

Tanabe N¹.

Author information:

1. Department of Advanced Medicine in Pulmonary Hypertension, Graduate School of Medicine, Chiba University, Japan. Electronic address: ntanabe@faculty.chiba-u.jp.

PMID: 29764745

Eur Radiol. 2018 May 14. doi: 10.1007/s00330-018-5455-6. [Epub ahead of print]

Pulmonary hypertension due to left heart disease: diagnostic and prognostic value of CT in chronic systolic heart failure.

Colin GC¹, Gerber BL², de Meester de Ravenstein C², Byl D³, Dietz A³, Kamga M², Pasquet A², Vancraeynest D², Vanoverschelde JL², D’Hondt AM², Ghaye B³, Pouleur AC².

Author information:

1. Division of Radiology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, 1200, Brussels, Belgium. gc.colin.md@gmail.com.
2. Division of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
3. Division of Radiology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, 1200, Brussels, Belgium.

Abstract

OBJECTIVES:
To evaluate the ability of chest computed tomography (CT) to predict pulmonary hypertension (PH) and outcome in chronic heart failure with reduced ejection fraction (HFrEF).

METHODS:
We reviewed 119 consecutive patients with HFrEF by CT, transthoracic echocardiography (TTE) and right heart catheterization (RHC). CT-derived pulmonary artery (PA) diameter and PA to ascending aorta diameter ratio (PA:A ratio), left atrial, right atrial, right ventricular (RV) and left ventricular volumes were correlated with RHC mean pulmonary arterial pressure (mPAP) . Diagnostic accuracy to predict PH and ability to predict primary composite endpoint of all-cause mortality and HF events were evaluated.

RESULTS:
RV volume was significantly higher in 81 patients with PH compared to 38 patients without PH (133 ml/m2 vs. 79 ml/m2, p < 0.001) and was moderately correlated with mPAP (r=0.55, p < 0.001). Also, RV volume had higher ability to predict PH (area under the curve: 0.88) than PA diameter (0.79), PA:A ratio (0.76) by CT and tricuspid regurgitation gradient (0.83) and RV basal diameter by TTE (0.84, all p < 0.001). During the follow-up period (median: 3.4 years), 51 patients (43%) had HF events or died. After correction for important clinical, TTE and RHC parameters, RV volume (adjusted hazard ratio [HR]: 1.71, 95% CI 1.31-2.23, p < 0.001) and PA diameter (HR: 1.61, 95% CI 1.18-2.22, p = 0.003) were independent predictors of the primary endpoint.

CONCLUSION:
In patients with HFrEF, measurement of RV volume and PA diameter on ungated CT are non-invasive markers of PH and may help to predict the patient outcome.

KEY POINTS:

• Right ventricular (RV) volume measured by chest CT has good ability to identify pulmonary hypertension (PH) in patients with chronic heart failure (HF) and reduced ejection fraction (HFrEF).
• The accuracy of pulmonary artery (PA) diameter and PA to ascending aorta diameter ratio (PA:A ratio) to predict PH was similar to previous studies, however, with lower cut-offs (28.1 mm and 0.92, respectively).
• Chest CT-derived PA diameter and RV volume independently predict all-cause mortality and HF events and improve outcome prediction in patients with advanced HFrEF.

PMID: 29761362

J Cardiovasc Surg (Torino). 2018 Jun;59(3):428-437. doi: 10.23736/S0021-9509.17.10188-6. Epub 2017 Sep 4.

Initial clinical and hemodynamic results of a regional pulmonary thromboendarterectomy program.

Raza F¹, Vaidya A¹, Lacharite-Roberge AS², Lakhter V¹, Al-Maluli H¹, Ahsan I³, Boodram P⁴, Dass C⁵, Rogers F¹, Keane MG¹, Weaver S⁶, Bashir R¹, Toyoda Y⁷, Forfia P⁸.

Author information:

1. Heart and Vascular Institute, Temple University Hospital, Philadelphia, PA, USA.
2. Department of Medicine, Temple University Hospital, Philadelphia, PA, USA.
3. Department of Medicine, Abington Memorial Hospital, Philadelphia, PA, USA.
4. Temple University School of Medicine, Philadelphia, PA, USA.
5. Department of Radiology, Temple University Hospital, Philadelphia, PA, USA.
6. Temple Lung Center, Temple University Hospital, Philadelphia, PA, USA.
7. Department of Cardiovascular Surgery, Temple University Hospital, Philadelphia, PA, USA.
8. Heart and Vascular Institute, Temple University Hospital, Philadelphia, PA, USA – Paul.Forfia@Temple.edu.

Abstract

BACKGROUND:
Pulmonary thromboendarterectomy (PTE) is the treatment of choice for eligible patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, access to CTEPH and PTE care is limited. There is a paucity of published data on PTE efficacy and outcomes from alternative, regional centers of excellence in CTEPH and PTE care in the USA, outside a single national and international referral center.

METHODS:
We performed a retrospective review of patients undergoing PTE at our institution from June 2013 to December 2016 (42 months), and collected clinical, echocardiographic and hemodynamic data on our patients pre- and post-PTE (N.=71).

RESULTS:
Patients age ranged between 20-83 years (mean±SD: 56±16), with 54% of patients female and 61% Caucasians. The predominant symptom was shortness of breath with a median duration of symptoms of 17 months. Following PTE, clinical improvements included a reduction in NYHA class from 3.1±1.1 to 2.2±1.2. There were major improvements in hemodynamics and echocardiographic parameters pre- versus post-PTE: mean pulmonary artery pressure (mmHg) 45±11 to 24±8, cardiac index (L/min/m2) 2.1±0.5 to 2.8±0.5, pulmonary vascular resistance (mmHg/L/min) 8.9±4.5 to 2.8±1.8, ratio of right ventricle (RV): left ventricle (LV) 1.2±0.3 to 0.9±0.2, RV fractional area change (%) 23±14 to 44±13, reduction in the incidence of RV outflow tract Doppler notching and improved pulmonary artery acceleration time (96% to 30%, and 74±19 to 111±21). In-hospital mortality was 4.2% (3 patients).

CONCLUSIONS:
Herein, we report for the first time, the improvements in patient functionality, hemodynamics, right heart function and outcomes at a major regional PTE program.

PMID: 28870062 [Indexed for MEDLINE]

Rheumatology (Oxford). 2018 Mar 1;57(3):441-450. doi: 10.1093/rheumatology/kex182.

Functional disability and its predictors in systemic sclerosis: a study from the DeSScipher project within the EUSTAR group.

Jaeger VK¹, Distler O², Maurer B², Czirják L³, Lóránd V³, Valentini G⁴, Vettori S⁴, Del Galdo F⁵, Abignano G⁵, Denton C⁶, Nihtyanova S⁶, Allanore Y⁷, Avouac J⁷, Riemekasten G⁸, Siegert E⁹, Huscher D¹⁰, Matucci-Cerinic M¹¹, Guiducci S¹¹, Frerix M¹², Tarner IH¹², Garay Toth B¹³, Fankhauser B¹⁴, Umbricht J¹⁴, Zakharova A¹⁵, Mihai C¹⁶, Cozzi F¹⁷, Yavuz S¹⁸, Hunzelmann N¹⁹, Rednic S²⁰, Vacca A²¹, Schmeiser T²², Riccieri V²³, García de la Peña Lefebvre P²⁴, Gabrielli A²⁵, Krummel-Lorenz B²⁶, Martinovic D²⁷, Ancuta C²⁸, Smith V²⁹, Müller-Ladner U¹², Walker UA¹.

Author information:

1. Department of Rheumatology, University Hospital Basel, Basel.
2. Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland.
3. Department of Rheumatology and Immunology, Medical Center, University of Pécs, Pécs, Hungary.
4. Department of Rheumatology, Second University of Naples, Naples, Italy.
5. NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds.
6. Department of Rheumatology, University College London, Royal Free Hospital, London, UK.
7. Department of Rheumatology, University of Paris Descartes, Paris, France.
8. Department of Rheumatology, University Clinic Schleswig-Holstein, Lübeck.
9. Department of Rheumatology and Clinical Immunology, University Hospital Charité.
10. German Rheumatism Research Centre, Berlin, Germany.
11. Department of Rheumatology, University of Florence, Florence, Italy.
12. Department of Rheumatology and Clinical Immunology, Justus-Liebig University Giessen, Kerckhoff Clinic Bad Nauheim, Bad Nauheim, Germany.
13. Federation of European Scleroderma Associations Aisbl, Budapest, Hungary.
14. new-win SW Solutions AG, Suhr, Switzerland.
15. VA Nasonova Institute of Rheumatology, Moscow, Russian Federation.
16. Department of Internal Medicine and Rheumatology, Dr Ion Cantacuzino Clinical Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
17. Rheumatology Unit, Department of Medicine, University of Padova, Padova, Italy.
18. Department of Rheumatology, University of Marmara, Altunizade-Istanbul, Turkey.
19. Department of Dermatology, University of Cologne, Cologne, Germany.
20. Clinica Reumatologie, University of Medicine & Pharmacy, Cluj-Napoca, Romania.
21. II Chair of Rheumatology, University of Cagliari-Policlinico Universitario, Monserrato, Italy.
22. Department of Rheumatology and Immunology, Krankenhaus St Josef, Wuppertal, Germany.
23. Divisione di Reumatologia, Università di Roma La Sapienza, Roma, Italy.
24. Servicio de Reumatología, Hospital Universitario Madrid Norte Sanchinarro, Madrid, Spain.
25. Istituto di Clinica Medica Generale, Ematologia ed Immunologia Clinica, Università Politecnica delle Marche, Ancona, Italy.
26. Endokrinologikum Frankfurt, Frankfurt, Germany.
27. Division of Rheumatology, University Hospital of Split, Split, Croatia.
28. Rheumatology 2 Department, Clinical Rehabilitation Hospital, University of Medicine and Pharmacy ‘Grigore T. Popa’, Iasi, Romania.
29. Faculty of Internal Medicine, Ghent University, Ghent, Belgium.

Comment in
Wildflowers abundant in the garden of systemic sclerosis research, while hopeful exotics will one day bloom. [Rheumatology (Oxford). 2018]

Abstract

Objectives:
The multisystem manifestations of SSc can greatly impact patients’ quality of life. The aim of this study was to identify factors associated with disability in SSc.

Methods:
SSc patients from the prospective DeSScipher cohort who had completed the scleroderma health assessment questionnaire (SHAQ), a disability score that combines the health assessment questionnaire and five visual analogue scales, were included in this analysis. The effect of factors possibly associated with disability was analysed with multiple linear regressions.

Results:
The mean SHAQ and HAQ scores of the 944 patients included were 0.87 (s.d. = 0.66) and 0.92 (s.d. = 0.78); 59% of the patients were in the mild to moderate difficulty SHAQ category (0 ⩽ SHAQ < 1), 34% in the moderate to severe disability category (1 ⩽ SHAQ < 2) and 7% in the severe to very severe disability category (2 ⩽ SHAQ ⩽ 3). The means of the visual analogue scales scores were in order of magnitude: overall disease severity (37 mm), RP (31 mm), pulmonary symptoms (24 mm), gastrointestinal symptoms (20 mm) and digital ulcers (19 mm). In multiple regression, the main factors associated with high SHAQ scores were the presence of dyspnoea [modified New York Heart Association (NYHA) class IV (regression coefficient B = 0.62), modified NYHA class III (B = 0.53) and modified NYHA class II (B = 0.21; all vs modified NYHA class I)], FM (B = 0.37), muscle weakness (B = 0.27), digital ulcers (B = 0.20) and gastrointestinal symptoms (oesophageal symptoms, B = 0.16; stomach symptoms, B = 0.15; intestinal symptoms, B = 0.15).

Conclusion:
SSc patients perceive dyspnoea, pain, digital ulcers, muscle weakness and gastrointestinal symptoms as the main factors driving their level of disability, unlike physicians who emphasize objective measures of disability.

© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

PMID: 28499034 [Indexed for MEDLINE]

PLoS One. 2018 May 15;13(5):e0197112. doi: 10.1371/journal.pone.0197112. eCollection 2018.

Clinical phenotypes and survival of pre-capillary pulmonary hypertension in systemic sclerosis.

Launay D^1,2,3,4, Montani D^5,6,7, Hassoun PM⁸, Cottin V⁹, Le Pavec J^5,7,10, Clerson P¹¹, Sitbon O^5,6,7, Jaïs X^5,6,7, Savale L^5,6,7, Weatherald J^5,6,7,12, Sobanski V^1,2,3,4, Mathai SC⁸, Shafiq M⁸, Cordier JF⁹, Hachulla E^1,2,3,4, Simonneau G^5,6,7, Humbert M^5,6,7.

Author information:

1. Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), Lille, France.
2. Inserm, U995, Lille, France.
3. CHU Lille, département de médecine interne et immunologie clinique, Lille, France.
4. Centre national de référence maladies systémiques et auto-immunes rares (sclérodermie systémique), Lille, France.
5. Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
6. Service de Pneumologie, Hôpital Bicêtre, Assistance Publique Hôpitaux de Paris, Le Kremlin-Bicêtre, France.
7. INSERM UMR S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
8. Division of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University, Baltimore, MD, United States of America.
9. Centre national de référence des maladies pulmonaires rares, hôpital Louis Pradel, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France.
10. Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardio-pulmonaire, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
11. Soladis Clinical Study, Roubaix, France.
12. Division of Respirology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.

Abstract

Pre-capillary pulmonary hypertension (PH) in systemic sclerosis (SSc) is a heterogeneous condition with an overall bad prognosis. The objective of this study was to identify and characterize homogeneous phenotypes by a cluster analysis in SSc patients with PH. Patients were identified from two prospective cohorts from the US and France. Clinical, pulmonary function, high-resolution chest tomography, hemodynamic and survival data were extracted. We performed cluster analysis using the k-means method and compared survival between clusters using Cox regression analysis. Cluster analysis of 200 patients identified four homogenous phenotypes. Cluster C1 included patients with mild to moderate risk pulmonary arterial hypertension (PAH) with limited or no interstitial lung disease (ILD) and low DLCO with a 3-year survival of 81.5% (95% CI: 71.4-88.2). C2 had pre-capillary PH due to extensive ILD and worse 3-year survival compared to C1 (adjusted hazard ratio [HR] 3.14; 95% CI 1.66-5.94; p = 0.0004). C3 had severe PAH and a trend towards worse survival (HR 2.53; 95% CI 0.99-6.49; p = 0.052). Cluster C4 and C1 were similar with no difference in survival (HR 0.65; 95% CI 0.19-2.27, p = 0.507) but with a higher DLCO in C4. PH in SSc can be characterized into distinct clusters that differ in prognosis.

Free PMC Article
PMCID: PMC5953495
PMID: 29763468

Future Cardiol. 2018 May 24. doi: 10.2217/fca-2017-0065. [Epub ahead of print]

Pulmonary hypertension in congenital heart disease.

Pascall E¹, Tulloh RM¹.

Author information:

1. Department of Congenital Heart Disease, Bristol Heart Institute, Upper Maudlin Street, Bristol, BS2 8BJ, UK.

Abstract

Pulmonary hypertension is defined as a mean pulmonary arterial pressure ≥25 mmHg. We focus on its relevance in congenital heart disease, reviewing pathophysiology, diagnosis and management. Pulmonary hypertension is a relatively common complication of congenital heart disease, with adult prevalence between 5 and 10%. A multifactorial cause is recognized, relating to the size and nature of cardiac defect as well as environmental and genetic factors. More complex disease is increasingly recognized rather than pure Eisenmenger complex. Remodeling of the pulmonary vascular bed causes increased pulmonary vascular resistance diagnosed by a collection of investigations including echocardiography, exercise testing, cardiac catheterization, MRI and CT scanning. Management employs disease-modifying medications which are now used with increasing benefit.

Free Article
PMID: 29792339

Clinics (Sao Paulo). 2018 May 17;73:e216. doi: 10.6061/clinics/2018/e216.

Use of direct oral anticoagulants for chronic thromboembolic pulmonary hypertension.

Gavilanes-Oleas FA¹, Alves JL Jr¹, Fernandes CJC¹, Prada LFL¹, Salibe Filho W¹, Terra Filho M¹, Morinaga L¹, Hoette S¹, Jardim C¹, Souza R¹.

Author information:

1. Unidade de Circulacao Pulmonar, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.

Abstract

OBJECTIVES:
Chronic thromboembolic pulmonary hypertension is one of the most prevalent forms of pulmonary hypertension and is a major complication of acute pulmonary embolism. One mainstay of chronic thromboembolic pulmonary hypertension treatment is lifelong anticoagulation. The recent advent of direct oral anticoagulants for acute pulmonary embolism treatment has provided a viable and effective alternative for treating this condition. However, little is known about the efficacy of this new class of drugs for treating chronic thromboembolic pulmonary hypertension. We aimed to evaluate the safety and efficacy of direct oral anticoagulants in the treatment of chronic thromboembolic pulmonary hypertension.

METHODS:
A cohort of chronic thromboembolic pulmonary hypertension patients who initiated treatment with direct oral anticoagulants between June 2015 and November 2016 were enrolled in this study.

RESULTS:
Sixteen patients used rivaroxaban, three used dabigatran and one used apixaban for a mean follow-up of 20.9 months. The mean age was 51 years, and eighteen patients were classified as functional class II/III. Eight patients underwent a pulmonary endarterectomy and exhibited clinical, hemodynamic and functional improvement and currently continue to use direct oral anticoagulants. No episode of venous thromboembolism recurrence was identified during the follow-up period, but there was one episode of major bleeding after a traumatic fall.

CONCLUSIONS:
Although direct oral anticoagulants appear to be a safe and effective alternative for treating chronic thromboembolic pulmonary hypertension, larger studies are needed to support their routine use.

Free PMC Article
PMCID: PMC5938486
PMID: 29791520

J Gerontol A Biol Sci Med Sci. 2018 May 21. doi: 10.1093/gerona/gly068. [Epub ahead of print]

Cardioprotection Induced by Activation of GPER in Ovariectomized Rats With Pulmonary Hypertension.

Alencar AKN¹, Montes GC¹, Costa DG¹, Mendes LVP^1,2, Silva AMS¹, Martinez ST³, Trachez MM¹, Cunha VDMN¹, Montagnoli TL¹, Fraga AGM⁴, Wang H⁵, Groban L⁵, Fraga CAM¹, Sudo RT¹, Zapata-Sudo G¹.

Author information:

1. Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil.
2. Departamento de Farmacologia, Universidade Estácio de Sá, Rio de Janeiro, Brazil.
3. Departamento de Química, Instituto de Química, Campus do Valonguinho, Universidade Federal Fluminense, Niterói – RJ, Brazil.
4. Faculdade de Farmácia da Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Ilha do Fundão Cidade Universitária, Brazil.
5. Departments of Anesthesiology and Internal Medicine-Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Abstract

Pulmonary hypertension (PH) is a disease of women (female-to-male ratio 4:1), and is associated with cardiac and skeletal muscle dysfunction. Herein, the activation of a new estrogen receptor (GPER) by the agonist G1 was evaluated in oophorectomized rats with monocrotaline (MCT)-induced PH. Depletion of estrogen was induced by bilateral oophorectomy (OVX) in Wistar rats. Experimental groups included SHAM or OVX rats that received a single intraperitoneal injection of MCT (60 mg/kg) for PH induction. Animals received s.c. injection of either vehicle or G1, a GPER agonist, (400 µg/kg/day) for 14 days after the onset of disease. Rats with PH exhibited exercise intolerance and cardiopulmonary alterations, including reduced pulmonary artery flow, biventricular remodeling, and left ventricular systolic and diastolic dysfunction. The magnitude of these PH-induced changes was significantly greater in OVX versus SHAM rats. G1 treatment reversed both cardiac and skeletal muscle functional aberrations caused by PH in OVX rats. G1 reversed PH-related cardiopulmonary dysfunction and exercise intolerance in female rats, a finding that may have important implications for the ongoing clinical evaluation of new drugs for the treatment of the disease in females after the loss of endogenous estrogens.

PMID: 29790948

Endocrinol Diabetes Metab Case Rep. 2018 May 16;2018. pii: 18-0012. doi: 10.1530/EDM-18-0012. eCollection 2018.

Right ventricular dysfunction and pulmonary hypertension: a neglected presentation of thyrotoxicosis.

Singarayar CS¹, Siew Hui F¹, Cheong N¹, Swee En G¹.

Author information:

1. Endocrine Unit, Department of Medicine, Selayang Hospital, Selangor, Malaysia.

Abstract

Thyrotoxicosis is associated with cardiac dysfunction; more commonly, left ventricular dysfunction. However, in recent years, there have been more cases reported on right ventricular dysfunction, often associated with pulmonary hypertension in patients with thyrotoxicosis. Three cases of thyrotoxicosis associated with right ventricular dysfunction were presented. A total of 25 other cases of thyrotoxicosis associated with right ventricular dysfunction published from 1994 to 2017 were reviewed along with the present 3 cases. The mean age was 45 years. Most (82%) of the cases were newly diagnosed thyrotoxicosis. There was a preponderance of female gender (71%) and Graves’ disease (86%) as the underlying aetiology. Common presenting features included dyspnoea, fatigue and ankle oedema. Atrial fibrillation was reported in 50% of the cases. The echocardiography for almost all cases revealed dilated right atrial and or ventricular chambers with elevated pulmonary artery pressure. The abnormal echocardiographic parameters were resolved in most cases after rendering the patients euthyroid. Right ventricular dysfunction and pulmonary hypertension are not well-recognized complications of thyrotoxicosis. They are life-threatening conditions that can be reversed with early recognition and treatment of thyrotoxicosis. Signs and symptoms of right ventricular dysfunction should be sought in all patients with newly diagnosed thyrotoxicosis, and prompt restoration of euthyroidism is warranted in affected patients before the development of overt right heart failure.

Learning points:
Thyrotoxicosis is associated with right ventricular dysfunction and pulmonary hypertension apart from left ventricular dysfunction described in typical thyrotoxic cardiomyopathy.Symptoms and signs of right ventricular dysfunction and pulmonary hypertension should be sought in all patients with newly diagnosed thyrotoxicosis.Thyrotoxicosis should be considered in all cases of right ventricular dysfunction or pulmonary hypertension not readily explained by other causes.Prompt restoration of euthyroidism is warranted in patients with thyrotoxicosis complicated by right ventricular dysfunction with or without pulmonary hypertension to allow timely resolution of the abnormal cardiac parameters before development of overt right heart failure.

Free PMC Article
PMCID: PMC5955009
PMID: 29785271

J Pediatr. 2018 May 18. pii: S0022-3476(18)30606-1. doi: 10.1016/j.jpeds.2018.04.052. [Epub ahead of print]

Treprostinil Improves Persistent Pulmonary Hypertension Associated with Congenital Diaphragmatic Hernia.

Lawrence KM¹, Hedrick HL², Monk HM³, Herkert L¹, Waqar LN¹, Hanna BD⁴, Peranteau WH², Rintoul NE⁴, Hopper RK⁵.

Author information:

1. Department of Pediatric General, Thoracic, and Fetal Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA.
2. Department of Pediatric General, Thoracic, and Fetal Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
3. Department of Pharmacy Services, Children’s Hospital of Philadelphia, Philadelphia, PA.
4. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA.
5. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA. Electronic address: rhopper@stanford.edu.

Abstract

OBJECTIVE:
To evaluate the effect of continuous treprostinil in infants with severe pulmonary hypertension associated with congenital diaphragmatic hernia (CDH) on specific markers of pulmonary hypertension severity and to report the safety and tolerability of treprostinil.

STUDY DESIGN:
We conducted a retrospective cohort study of infants with CDH-associated pulmonary hypertension treated with treprostinil from January 2011 to September 2016. Severity of pulmonary hypertension was assessed by echocardiogram and serum B-type natriuretic peptide (BNP) by using time points before initiation and 24 hours, 1 week, and 1 month after treprostinil initiation. Fisher exact tests, Wilcoxon-rank sum tests, and mixed-effects models were used for analysis.

RESULTS:
Seventeen patients were treated with treprostinil for a median of 54.5 days (IQR 44.3-110 days). Compared with the concurrent CDH population (n = 147), infants treated with treprostinil were more likely to require extracorporeal support (76.5% vs 25.2%, P < .0001), to have a longer hospital stay (144 vs 60 days, P < .0001), and to need longer mechanical ventilator support (76.5 vs 30.9 days, P < .0001). Following treprostinil initiation, there was a significant reduction in BNP at 1 week (1439 vs 393 pg/mL, P < .01) and 1 month (1439 vs 242 pg/mL, P = .01). Severity of pulmonary hypertension by echocardiogram improved at 1 month (OR 0.14, CI 95% 0.04-0.48, P = .002). Despite these improvements, overall mortality remained high (35%). There were no adverse events related to treprostinil, including no hypotension, hypoxia, or thrombocytopenia.

CONCLUSIONS:
In this cohort, treprostinil use was associated with improved severity of pulmonary hypertension assessed by echocardiogram and decreased BNP, with no significant side effects.

Copyright © 2018 Elsevier Inc. All rights reserved.

PMID: 29784517

Int J Cardiol. 2018 Aug 1;264:147-152. doi: 10.1016/j.ijcard.2018.02.112.

Chronic thromboembolic pulmonary hypertension: Reversal of pulmonary hypertension but not sleep disordered breathing following pulmonary endarterectomy.

La Rovere MT¹, Fanfulla F², Taurino AE³, Bruschi C³, Maestri R⁴, Robbi E⁵, Maestroni R³, Pronzato C⁶, Pin M⁷, D’Armini AM⁷, Pinna GD⁴.

Author information:

1. Department of Cardiology, Istituti Clinici Scientifici Maugeri, IRCCS Montescano, Montescano, Pavia, Italy. Electronic address: mariateresa.larovere@icsmaugeri.it.
2. Sleep Medicine Unit, Istituti Clinici Scientifici Maugeri, IRCCS Pavia, Pavia, Italy; Respiratory Function and Sleep Unit, Istituti Clinici Scientifici Maugeri, IRCCS Montescano, Montescano, Pavia, Italy.
3. Respiratory Function and Sleep Unit, Istituti Clinici Scientifici Maugeri, IRCCS Montescano, Montescano, Pavia, Italy.
4. Department of Biomedical Engineering, Istituti Clinici Scientifici Maugeri, IRCCS Montescano, Montescano, Pavia, Italy.
5. Department of Cardiology, Istituti Clinici Scientifici Maugeri, IRCCS Montescano, Montescano, Pavia, Italy.
6. Sleep Medicine Unit, Istituti Clinici Scientifici Maugeri, IRCCS Pavia, Pavia, Italy.
7. Unit of Cardio-thoracic Surgery and Pulmonary Hypertension, Foundation IRCCS Policlinico San Matteo, University of Pavia School of Medicine, Pavia, Italy.

Abstract

BACKGROUND:
It has been hypothesized that pre-capillary pulmonary hypertension (PH) may trigger sleep disordered breathing (SDB). In patients with chronic thromboembolic PH (CTEPH), pulmonary endarterectomy (PEA) is potentially effective to improve PH. We assessed the pre- and post-operative prevalence of SDB in CTEPH patients submitted to PEA and the relationship between SDB and clinical, pulmonary and hemodynamic factors.

METHODS:
Unattended cardiorespiratory recording was performed the night before and one month after elective PEA in 50 patients.

RESULTS:
Before the intervention SDB prevalence (obstructive or central AHI ≥ 5/h) was 64%: 18 patients (66% female) had No-SDB, 22 (68% female) had dominant obstructive (dOSA), and 10 (20% female) had dominant central sleep apnea (dCSA). There were no differences in risk factors and the need for supplemental oxygen. Mean right atrial (mRAP) and pulmonary artery pressures (mPAP) showed a more compromised profile from No-SDB to dOSA and dCSA (mRAP: 5.5 ± 3.9 vs 7.0 ± 4.5 vs 9.7 ± 4.3 mm Hg (p = 0.054), mPAP: 39 ± 12 vs 48 ± 11 vs 51 ± 16 mm Hg (p = 0.0.47)). By contrast, cardiac index did not differ. At post-intervention, the prevalence of SDB was 68%: 16 patients had No-SDB, while 30 had dOSA and 4 dCSA, with no relationship with the relief from PH. Interestingly, 5 patients with previous CSA moved to the OSA group and 2 normalized.

CONCLUSIONS:
Prevalence of SDB is high in patients with CTEPH even after resolution of PH. Our data support the hypothesis that pre-capillary PH may trigger CSA but not OSA, and suggest that OSA may play a role in the development of CTEPH.

Copyright © 2018. Published by Elsevier B.V.

PMID: 29776563

Am J Forensic Med Pathol. 2018 Mar;39(1):56-60. doi: 10.1097/PAF.0000000000000369.

Pulmonary Tumor Thrombotic Microangiopathy: Case Report and Review of Literature.

Hutchinson JC, Fulcher JW, Hanna J, Ward ME.

Abstract

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare rapidly progressive fatal disease that is difficult to diagnosis antemortem. Activation of the coagulation cascade and fibrocellular intimal thickening caused by embolism of tumor cells into pulmonary vasculature leads to extensive pulmonary hypertension and eventually death. We describe a case of PTTM with association of a presumed lung adenocarcinoma primary. Although rare in nature, PTTM should be a considered diagnosis with chronic dyspnea of unknown origin, severe pulmonary hypertension coupled with right-side heart failure, in the absence of pulmonary embolism.

PMID: 29232215 [Indexed for MEDLINE]

Eur Heart J. 2017 Jul 7;38(26):2034-2041. doi: 10.1093/eurheartj/ehx034.

Pulmonary arterial hypertension in congenital heart disease: translational opportunities to study the reversibility of pulmonary vascular disease.

van der Feen DE¹, Bartelds B¹, de Boer RA², Berger RMF¹.

Author information:

1. Centre for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children’s Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands.
2. Experimental Cardiology, Department of Cardiology, University Medical Centre Groningen, University of Groningen, Antonius Deusinglaan 1, 9713AV Groningen, The Netherlands.

Abstract

Pulmonary arterial hypertension (PAH) is a progressive and lethal pulmonary vascular disease (PVD). Although in recent years outcome has improved by new treatments that delay disease progression, a cure has not yet been achieved. In PAH associated with congenital heart disease (CHD), remodeling of the pulmonary vasculature reaches an irreversible phenotype similar to all forms of end-stage PAH. In PAH-CHD, however, also an early stage is recognised, which can be completely reversible. This reversible phase has never been recognised in other forms of PAH, most likely because these patients are only diagnosed once advanced disease has developed. We propose that the clinical model of PAH-CHD, with an early reversible and advanced irreversible stage, offers unique opportunities to study pathophysiological and molecular mechanisms that orchestrate the transition from reversible medial hypertrophy into irreversible plexiform lesions. Comprehension of these mechanisms is not only pivotal in clinical assessment of disease progression and operability of patients with PAH-CHD; specific targeting of these mechanisms may also lead to pharmacological interventions that transform ‘irreversible’ plexiform lesions into a reversible PVD: one that is amenable for a cure. In recent years, significant steps have been made in the strive to ‘reverse the irreversible’. This review provides an overview of current clinical and experimental knowledge on the reversibility of PAH, focussing on flow-associated mechanisms, and the near-future potential to advance this field.

PMID: 28369399 [Indexed for MEDLINE]

Chest. 2018 May 16. pii: S0012-3692(18)30736-0. doi: 10.1016/j.chest.2018.05.002. [Epub ahead of print]

Long-term Outcomes in Systemic Sclerosis Associated Pulmonary Arterial Hypertension from the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry (PHAROS).

Kolstad KD¹, Li S², Steen V³, Chung L⁴; PHAROS investigators.

Author information:

1. Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA.
2. Department of Dermatology, Stanford University School of Medicine, Palo Alto, CA.
3. Division of Rheumatology, Georgetown University Medical Center, Washington DC.
4. Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA; Division of Rheumatology, Department of Medicine, Palo Alto VA Health Care System, Palo Alto, CA.

Abstract

BACKGROUND:
Pulmonary arterial hypertension (PAH) is a leading cause of death in patients with systemic sclerosis (SSc). The purpose of this study was to assess long-term outcomes in patients with SSc-PAH.

METHODS:
Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma is a prospective registry of SSc patients at high risk for or with incident pulmonary hypertension based on right heart catheterization (RHC). Incident World Health Organization Group I PAH patients were analyzed. Kaplan-Meier survival curves were generated for the overall cohort and those who died of PAH. Multivariate cox regression models identified predictors of mortality.

RESULTS:
Survival in 160 incident SSc-PAH patients at 1, 3, 5, and 8-years was 95%, 75%, 63%, and 49%, respectively. PAH accounted for 52% of all deaths. When restricted to deaths due to PAH, respective survival rates were 97%, 83%, 76%, and 76%, with 93% of PAH-related deaths occurring within 4 years of diagnosis. Male sex (HR 3.11 95%CI 1.38-6.98), diffuse disease (HR 2.12 95%CI 1.13-3.93), systolic pulmonary artery pressure (PAP) on echocardiogram (HR 1.06 95%CI 1.01-1.11), mean PAP on RHC (HR 1.03 95%CI 1001-1.07), six-minute walk distance (HR 0.92 95%CI 0.86-0.99), and diffusing capacity for carbon monoxide (HR 0.65 95% CI 0.46-0.92) significantly impacted survival on multivariate analysis.

CONCLUSION:
Overall survival in PHAROS was higher than other SSc-PAH cohorts. PAH accounted for more than half of deaths and primarily within the first few years after PAH diagnosis. Optimization of treatment for those at greatest risk of early PAH-related death is crucial.

Copyright © 2018. Published by Elsevier Inc.

PMID: 29777655