Multicenter Standardization of Phase-Resolved Functional Lung MRI in Patients With Suspected Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Detection of pulmonary perfusion defects is the recommended approach for diagnosing chronic thromboembolic pulmonary hypertension (CTEPH). This is currently achieved in a clinical setting using scintigraphy. Phase-resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is an alternative technique for evaluating regional ventilation and perfusion without the use of ionizing radiation or contrast media. PURPOSE: To assess the feasibility and image quality of PREFUL-MRI in a multicenter setting in suspected CTEPH. STUDY TYPE: This is a prospective cohort sub-study. POPULATION: Forty-five patients (64 ± 16 years old) with suspected CTEPH from nine study centers. FIELD STRENGTH/SEQUENCE: 1.5 T and 3 T/2D spoiled gradient echo/bSSFP/T2 HASTE/3D MR angiography (TWIST). ASSESSMENT: Lung signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between study centers with different MRI machines. The contrast between normally and poorly perfused lung areas was examined on PREFUL images. The perfusion defect percentage calculated using PREFUL-MRI (QDPPREFUL ) was compared to QDP from the established dynamic contrast-enhanced MRI technique (QDPDCE ). Furthermore, QDPPREFUL was compared between a patient subgroup with confirmed CTEPH or chronic thromboembolic disease (CTED) to other clinical subgroups. STATISTICAL TESTS: t-Test, one-way analysis of variance (ANOVA), Pearson's correlation. Significance level was 5%. RESULTS: Significant differences in lung SNR and CNR were present between study centers. However, PREFUL perfusion images showed a significant contrast between normally and poorly perfused lung areas (mean delta of normalized perfusion -4.2% SD 3.3) with no differences between study sites (ANOVA: P = 0.065). QDPPREFUL was significantly correlated with QDPDCE (r = 0.66), and was significantly higher in 18 patients with confirmed CTEPH or CTED (57.9 ± 12.2%) compared to subgroups with other causes of PH or with excluded PH (in total 27 patients with mean ± SD QDPPREFUL = 33.9 ± 17.2%). DATA CONCLUSION: PREFUL-MRI could be considered as a non-invasive method for imaging regional lung perfusion in multicenter studies. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

A comprehensive echocardiographic method for risk stratification in pulmonary arterial hypertension.

QUESTION ADDRESSED: Echocardiography is not currently considered as providing sufficient prognostic information to serve as an integral part of treatment goals in pulmonary arterial hypertension (PAH). We tested the hypothesis that incorporation of multiple parameters reflecting right heart function would improve the prognostic value of this imaging modality. METHODS AND MAIN RESULTS: We pooled individual patient data from a total of 517 patients (mean age 52±15 years, 64.8% females) included in seven observational studies conducted at five European and United States academic centres. Patients were subdivided into three groups representing progressive degrees of right ventricular dysfunction based on a combination of echocardiographic measurements, as follows. Group 1 (low risk): normal tricuspid annular plane systolic excursion (TAPSE) and nonsignificant tricuspid regurgitation (TR) (n=129); group 2 (intermediate risk): normal TAPSE and significant TR or impaired TAPSE and nondilated inferior vena cava (IVC) (n=256); group 3 (high risk): impaired TAPSE and dilated IVC (n=132). The 5-year cumulative survival rate was 82% in group 1, 63% in group 2 and 43% in group 3. Low-risk patients had better survival rates than intermediate-risk patients (log-rank Chi-squared 12.25; p<0.001) and intermediate-risk patients had better survival rates than high-risk patients (log-rank Chi-squared 26.25; p<0.001). Inclusion of other parameters such as right atrial area and pericardial effusion did not provide added prognostic value. ANSWER TO THE QUESTION: The proposed echocardiographic approach integrating the evaluation of TAPSE, TR grade and IVC is effective in stratifying the risk for all-cause mortality in PAH patients, outperforming the prognostic parameters suggested by current guidelines.

2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).

Guidelines summarize and evaluate all available evidence on a particular issue at the time of the writing process, with the aim of assisting health professionals in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome, as well as the risk-benefit ratio of particular diagnostic or therapeutic means. Guidelines and recommendations should help health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.

Novel and emerging therapies for pulmonary hypertension.

The development of therapeutic concepts in pulmonary hypertension (PH) is intimately linked with the unraveling of pathogenetic sequelae. This perspective highlights advances in our understanding of the regulation of vasomotion and vascular remodeling that have led to "reverse-remodeling" and regenerative strategies as novel treatment concepts. Progress has been made in understanding redox-dependent signaling; inflammatory sequelae; and transcription factor, ion channel, and metabolic abnormalities, as well as growth factor-dependent hyperproliferation that underlies PH. We are, however, far from understanding the molecular pathways that differentially drive the various vascular phenotypes (intimal thickening, media hypertrophy, adventitial thickening, plexiform lesions, vascular pruning) in this disease. Antiproliferative strategies, transcription factor-based therapies, inflammation/immune cell-focused approaches, and epigenetic modulation-based therapies are all novel treatment concepts for PH. The proangiogenic potential of genetically engineered mesenchymal stem cells and endothelial progenitor cells has been explored as a regenerative strategy. The progress that has been made in identifying important cellular and molecular mechanisms and applying this knowledge to novel therapies is largely restricted to group 1 PH. However, understanding the molecular sequelae underlying PH in groups 2 through 5 PH is also urgently needed.

[Mental distress and wish for psychosomatic treatment of patients with pulmonary hypertension]. / Psychische Belastung und Psychosomatischer Behandlungswunsch von Patienten mit Pulmonaler Hypertonie.

BACKGROUND: The study investigated the level of mental distress in patients with pulmonary hypertension (PH) and assessed the use of and the wish for psychosomatic treatment. METHODS: A total sample of n=187 outpatients participated in the cross-sectional survey. The short form of the Patient Health Questionnaire (PHQ-D), the EuroQol (EQ-5D) and a questionnaire assessing the wish for psychosomatic treatment were applied. RESULTS: 50.6% of the patients exhibited depressive symptoms of varying degrees, 19.2% showed symptoms of major depression. 14.8% of the pa-tients reported panic attacks, and 7.1% demonstrated symptoms of a panic syndrome. Quality of life was low (EQ-5D VAS M=60). Experience with outpatient or inpatient psychotherapy was reported by 23.4% and 8.6% of the patients, respectively. 56.5% reported a wish for psychosomatic treatment. CONCLUSIONS: PH-Patients are more likely to suffer from mild or subthreshold depressive syndromes, but are very interested in psychosomatic treatment. The implementation of psychosomatic interventions into clinical practice would be desirable.

[Updated clinical classification of pulmonary hypertension]. / Pulmoner arter hipertansiyonunun güncel klinik siniflandirilmasi.

In 1998, a clinical classification of pulmonary hypertension (PH) was established, categorizing PH into groups which share similar pathological and hemodynamic characteristics and therapeutic approaches. During the 5th World Symposium held in Nice, France, in 2013, the consensus was reached to maintain the general scheme of previous clinical classifications. However, modifications and updates especially for Group 1 patients (pulmonary arterial hypertension [PAH]) were proposed. The main change was to withdraw persistent pulmonary hypertension of the newborn (YPPH) from Group 1 because this entity carries more differences than similarities with other PAH subgroups. In the current classification, PPHN is now designated number 1". Pulmonary hypertension associated with chronic hemolytic anemia has been moved from Group 1 PAH to Group 5, unclear/multifactorial mechanism. In addition, it was decided to add specific items related to pediatric pulmonary hypertension in order to create a comprehensive, common classification for both adults and children. Therefore, congenital or acquired left-heart inflow/outflow obstructive lesions and congenital cardiomyopathies have been added to Group 2, and segmental pulmonary hypertension has been added to Group 5. Last, there were no changes for Groups 2, 3, and 4. (J Am Coll Cardiol 2013;62:D34-41) a 2013 by the American College of Cardiology Foundation.

[New trial designs and potential therapies for pulmonary artery hypertension]. / Pulmoner arter hipertansiyonunda yeni çalisma tasarimlari ve potansiyel tedaviler.

A greater understanding of the epidemiology, pathogenesis, and pathophysiology of pulmonary artery hypertension (PAH) has led to significant advances, but the disease remains fatal. Treatment options are neither universally available nor always effective, underscoring the need for development of novel therapies and therapeutic strategies. Clinical trials to date have provided evidence of efficacy, but were limited in evaluating the scope and duration of treatment effects. Numerous potential targets in varied stages of drug development exist, in addition to novel uses of familiar therapies. The pursuit of gene and cell-based therapy continues, and device use to help acute deterioration and chronic management is emerging. This rapid surge of drug development has led to multicenter pivotal clinical trials and has resulted in novel ethical and global clinical trial I concerns. This paper will provide an overview of the opportunities and challenges that await the development of novel treatments for PAH. (J Am Coil Cardiol 2013;62:D82-91) ©2013 by the American College of Cardiology Foundation.

Anxiety and depression disorders in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

BACKGROUND: The objective of this prospective study was to assess the prevalence of anxiety and depression disorders and their association with quality of life (QoL), clinical parameters and survival in patients with pulmonary hypertension (PH). METHODS: We prospectively assessed 158 patients invasively diagnosed with pulmonary arterial hypertension (n = 138) and inoperable chronic thromboembolic PH (n = 20) by clinical measures including quality of life (QoL, SF-36 questionnaire), cardiopulmonary exercise testing and six minute walking distance and by questionnaires for depression (PHQ-9) and anxiety (GAD-7). According to the results of the clinical examination and the questionnaires for mental disorders (MD) patients were classified into two groups, 1) with moderate to severe MD (n = 36, 22,8%), and 2) with mild or no MD (n = 122). Patients were followed for a median of 2.7 years. Investigators of QoL, SF-36 were blinded to the clinical data. RESULTS: At baseline the 2 groups did not differ in their severity of PH or exercise capacity. Patients with moderate to severe MD (group 1) had a significantly lower QoL shown in all subscales of SF-36 (p < 0.002). QoL impairment significantly correlated with the severity of depression (p < 0.001) and anxiety (p < 0.05). During follow-up period 32 patients died and 3 were lost to follow-up. There was no significant difference between groups regarding survival. Only 8% of the patients with MD received psychopharmacological treatment. CONCLUSION: Anxiety and depression were frequently diagnosed in our patients and significantly correlated with quality of life, but not with long term survival. Further prospective studies are needed to confirm the results.

The Early Detection of Pulmonary Hypertension.

BACKGROUND: Up to 1% of the world population and 10% of all persons over age 65 suffer from pulmonary hypertension (PH). The latency from the first symptom to the diagnosis is more than one year on average, and more than three years in 20% of patients. 40% seek help from more than four different physicians until their condition is finally diagnosed. METHODS: This review is based on publications retrieved by a selective literature search on pulmonary hypertension. RESULTS: The most common causes of pulmonary hypertension are left heart diseases and lung diseases. Its cardinal symptom is exertional dyspnea that worsens as the disease progresses. Additional symptoms of right heart failure are seen in advanced stages. Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are rare, difficult to diagnose, and of particular clinical relevance because specific treatments are available. For this reason, strategies for the early detection of PAH and CTEPH have been developed. The clinical suspicion of PH arises in a patient who has nonspecific symptoms, electrocardiographic changes, and an abnormal (NT-pro-)BNP concentration. Once the suspicion of PH has been confirmed by echocardiography and, if necessary, differential-diagnostic evaluation with a cardiopulmonary stress test, and after the exclusion of a primary left heart disease or lung disease, the patient should be referred to a PH center for further diagnostic assessment, classification, and treatment. CONCLUSION: If both the (NT-pro-)BNP and the ECG are normal, PH is unlikely. Knowledge of the characteristic clinical manifestations and test results of PH is needed so that patients can be properly selected for referral to specialists and experts in PH.

Hemodynamic and clinical onset in patients with hereditary pulmonary arterial hypertension and BMPR2 mutations.

BACKGROUND: Mutations in the bone morphogenetic protein receptor 2 (BMPR2) gene can lead to idiopathic pulmonary arterial hypertension (IPAH). This study prospectively screened for BMPR2 mutations in a large cohort of PAH-patients and compared clinical features between BMPR2 mutation carriers and non-carriers. METHODS: Patients have been assessed by right heart catheterization and genetic testing. In all patients a detailed family history and pedigree analysis have been obtained. We compared age at diagnosis and hemodynamic parameters between carriers and non-carriers of BMPR2 mutations. In non-carriers with familial aggregation of PAH further genes/gene regions as the BMPR2 promoter region, the ACVRL1, Endoglin, and SMAD8 genes have been analysed. RESULTS: Of the 231 index patients 22 revealed a confirmed familial aggregation of the disease (HPAH), 209 patients had sporadic IPAH. In 49 patients (86.3% of patients with familial aggregation and 14.3% of sporadic IPAH) mutations of the BMPR2 gene have been identified. Twelve BMPR2 mutations and 3 unclassified sequence variants have not yet been described before. Mutation carriers were significantly younger at diagnosis than non-carriers (38.53 ± 12.38 vs. 45.78 ± 11.32 years, p < 0.001) and had a more severe hemodynamic compromise. No gene defects have been detected in 3 patients with HPAH. CONCLUSION: This study identified in a large prospectively assessed cohort of PAH- patients new BMPR2 mutations, which have not been described before and confirmed previous findings that mutation carriers are younger at diagnosis with a more severe hemodynamic compromise. Thus, screening for BMPR2 mutations may be clinically useful.

Effect of exercise and respiratory training on clinical progression and survival in patients with severe chronic pulmonary hypertension.

BACKGROUND: Even though specific agents for the treatment of patients with pulmonary hypertension (PH) are available, in PH patients, physical capacity and quality of life (QoL) are often restricted and survival is reduced. OBJECTIVES: This study prospectively investigated the long-term effects of respiratory and exercise training in patients with severe chronic PH regarding safety, time to clinical worsening and survival. METHODS: Fifty-eight consecutive patients with severe PH on stable disease-targeted medication received exercise and respiratory training in hospital for 3 weeks and continued at home. They were prospectively followed for 24 ± 12 months. Primary endpoints were time to clinical worsening and survival. Adverse events and changes in the 6-min walking test, QoL, WHO functional class and gas exchange were secondary endpoints and were evaluated at baseline and at weeks 3 and 15. RESULTS: All patients tolerated the exercise training well without severe adverse events. In week 15, 6-min walking test results were significantly improved compared to baseline (by 84 ± 49 m, p < 0.001), as well as QoL scores, WHO functional class (from 2.9 ± 0.5 to 2.6 ± 0.6, p < 0.01), peak oxygen consumption (from 12.5 ± 3.0 to 14.6 ± 3.9 ml/min/kg, p < 0.001), heart rate at rest (from 75 ± 12 to 61 ± 18 beats/min, p < 0.001) and maximal workload (from 65 ± 21 to 80 ± 25 W, p < 0.001). Survival at 1 and 2 years was 100 and 95%, respectively. Fifteen events occurred during the follow-up. CONCLUSION: This study indicates that exercise and respiratory training as add-on to medical treatment may improve exercise capacity and QoL, and that they have a good long-term safety in the described setting.

Congestive nephropathy: a neglected entity? Proposal for diagnostic criteria and future perspectives.

Venous congestion has emerged as an important cause of renal dysfunction in patients with cardiorenal syndrome. However, only limited progress has been made in differentiating this haemodynamic phenotype of renal dysfunction, because of a significant overlap with pre-existing renal impairment due to long-term hypertension, diabetes, and renovascular disease. We propose congestive nephropathy (CN) as this neglected clinical entity. CN is a potentially reversible subtype of renal dysfunction associated with declining renal venous outflow and progressively increasing renal interstitial pressure. Venous congestion may lead to a vicious cycle of hormonal activation, increased intra-abdominal pressure, excessive renal tubular sodium reabsorption, and volume overload, leading to further right ventricular (RV) stress. Ultimately, renal replacement therapy may be required to relieve diuretic-resistant congestion. Effective decongestion could preserve or improve renal function. Congestive acute kidney injury may not be associated with cellular damage, and complete renal function restoration may be a confirmatory diagnostic criterion. In contrast, a persistently low renal perfusion pressure might induce renal dysfunction and histopathological lesions with time. Thus, urinary markers may differ. CN is mostly seen in biventricular heart failure but may also occur secondary to pulmonary arterial hypertension and elevated intra-abdominal pressure. An increase in central venous pressure to >6 mmHg is associated with a steep decrease in glomerular filtration rate. However, the central venous pressure range that can provide an optimal balance of RV and renal function remains to be determined. We propose criteria to identify cardiorenal syndrome subgroups likely to benefit from decongestive or pulmonary hypertension-specific therapies and suggest areas for future research.

Identification of right heart-enriched genes in a murine model of chronic outflow tract obstruction.

The right ventricle (RV) differs in several aspects from the left ventricle (LV) including its embryonic origin, physiological role and anatomical design. In contrast to LV hypertrophy, little is known about the molecular circuits, which are activated upon RV hypertrophy (RVH). We established a highly reproducible model of RVH in mice using pulmonary artery clipping (PAC), which avoids detrimental RV pressure overload and thus allows long-term survival of operated mice. Magnetic resonance imaging revealed pathognomonic changes with striking similarities to human congenital heart disease- or pulmonary arterial hypertension-patients. Comparative, microarray based transcriptome analysis of right- and left-ventricular remodeling identified distinct transcriptional responses to pressure-induced hypertrophy of either ventricle, which were mainly characterized by stronger transcriptional responses of the RV compared to the LV myocardium. Hierarchic cluster analysis revealed a RV- and LV-specific pattern of gene activity after induction of hypertrophy, however, we did not find evidence for qualitatively distinct regulatory pathways in RV compared to LV. Data mining of nearly three thousand RV-enriched genes under PAC disclosed novel potential (co)-regulators of long-term RV remodeling and hypertrophy. We reason that specific inhibitory mechanisms in RV restrict excessive myocardial hypertrophy and thereby contribute to its vulnerability to pressure overload.

Stress Doppler echocardiography in relatives of patients with idiopathic and familial pulmonary arterial hypertension: results of a multicenter European analysis of pulmonary artery pressure response to exercise and hypoxia.

BACKGROUND: This large, prospective, multicentric study was performed to analyze the distribution of tricuspid regurgitation velocity (TRV) values during exercise and hypoxia in relatives of patients with idiopathic and familial pulmonary arterial hypertension (PAH) and in healthy control subjects. We tested the hypothesis that relatives of idiopathic/familial PAH patients display an enhanced frequency of hypertensive TRV response to stress and that this response is associated with mutations in the bone morphogenetic protein receptor II (BMPR2) gene. METHODS AND RESULTS: TRV was estimated by Doppler echocardiography during supine bicycle exercise in normoxia and during 120 minutes of normobaric hypoxia (FIO(2)=12%; approximately 4500 m) in 291 relatives of 109 PAH patients and in 191 age-matched control subjects. Mean maximal TRVs were significantly higher in PAH relatives during both exercise and hypoxia. During exercise, 10% of control subjects but 31.6% of relatives (P<0.0001) exceeded the 90% quantile of mean maximal TRV seen in control subjects. Hypoxia revealed hypertensive TRV in 26% of relatives (P=0.0029). Among control subjects, TRV at rest was not related to age, sex, body mass index, systemic blood pressure, smoking status, or heart rate. Within kindreds identified as harboring deleterious mutations of the BMPR2 gene, a hypertensive TRV response occurred significantly more often compared with those without detected mutations. CONCLUSIONS: Pulmonary hypertensive response to exercise and hypoxia in idiopathic/familial PAH relatives appears as a genetic trait with familial clustering, being correlated to but not caused by a BMPR2 mutation. The suitability of this trait to predict manifest PAH development should be addressed in long-term follow-up studies.

[Arrhythmias in patients with pulmonary hypertension and chronic lung disease]. / Herzrhythmusstörungen bei Patienten mit pulmonaler Hypertonie und Lungenerkrankungen.

Pulmonary arterial hypertension (PAH) occurs in 1% of the global population and can be divided in different disease groups. Pathophysiological aspects leading to supraventricular arrhythmias in these patients are due to increased pulmonary and right atrial pressure, increased activity of the sympathetic nervous system leading to right atrial electrical remodeling and ischemia in the right atrium. In the clinical setting these patients present with atrial flutter, atrial fibrillation or with ectopic atrial tachycardia. Regarding ventricular tachycardia there is a lack of data. Occurrence of arrhythmia in these patients leads to a deterioration of PAH, so rhythm control should be the aim. This can be achieved by right atrial ablation, especially in patients presenting with atrial flutter; electric cardioversion or antiarrhythmic drug therapy are without definite guideline recommendations since there are too few clinical trials. Ablation with a transseptal approach in the left atrium is considered rather dangerous and should be avoided. Regarding arrhythmias in patients with chronic lung disease, few data are available. For patients with chronic obstructive pulmonary disease (COPD), there are good data available. These patients often suffer from coronary heart disease, atrial fibrillation, and ventricular tachycardia. Beta-blockers play an important role in COPD patients, even during exacerbation. Interventional therapies are safe but the arrhythmogenic foci often located outside of the pulmonary veins (in the right atrium).

Prognostic Relevance of Nonsustained Ventricular Tachycardia in Patients with Pulmonary Hypertension.

Background. Increased pulmonary vascular resistance in patients with pulmonary hypertension (PH) leads to an increased afterload of right heart and cardiac remodeling which could provide the substrate or trigger for arrhythmias. Supraventricular arrhythmias were associated with clinical deterioration but were not associated with sudden cardiac death (SCD). SCD has been reported to account for approximately 30% of deaths in patients with pulmonary arterial hypertension (PAH). Objective. The role of nonsustained ventricular tachycardia (nsVT) and its prognostic relevance in patients with PH remains unclear. This study evaluated the prognostic relevance of nsVT in patients with PAH and chronic thromboembolic pulmonary hypertension (CTEPH). Methods. Retrospectively, patients with PAH and CTEPH who underwent Holter ECG monitoring and available data of survival were investigated. Results. Seventy-eight (PAH: 55, CTEPH: 23) patients were evaluated. Holter ECG revealed nsVT in 12 patients. Twenty-one patients died during follow-up. In patients with nsVT, tricuspid annular plane systolic excursion was lower (p = 0.001), and systolic pulmonary arterial pressure was higher (p = 0.163). Mean survival of patients without/with nsVT was 155.2 ± 8.5/146.4 ± 21.4 months (p = 0.690). The association between arrhythmias and survival was not confounded by age (p = 0.681), gender (p = 0.752), 6-MW distance (p = 0.196), or arterial hypertension (p = 0.238). Conclusions. In patients with PH, nsVT occurs more often than previously reported, and patients with PH group 1 seem to be more at risk.

Evaluation of the prognostic value of electrocardiography parameters and heart rhythm in patients with pulmonary hypertension.

BACKGROUND: Several studies have analyzed arrhythmias in patients with pulmonary hypertension (PH) and increased P-wave duration was identified as a risk factor for development of atrial fibrillation (AF). METHODS: We retrospectively analyzed the incidence of arrhythmias in patients with an initial diagnosis of PH during long-term follow-up and assessed the prognostic value of electrocardiography (ECG) data. Data from 167 patients were analyzed (Dana Point Classification: Group 1: 59 patients, Group 2: 28 patients, Group 3: 39 patients, Group 4: 41 patients). Clinical, 6-min-ute walk distance test, echocardiography and right heart catheterization data were collected, and baseline/follow-up ECGs were analyzed. RESULTS: Baseline ECGs revealed sinus rhythm in 137 patients. Thirteen patients had newly onset AF during follow-up. In 30 patients, baseline ECG showed AF. Patients with baseline AF showed higher atrial diameters and higher right atrial pressure. Patients with P-wave du-ration > 0.11 s had shorter survival. Other ECG parameters (PQ-interval, QRS-width, QT-/ /QTc-interval) were not associated with survival. Mean survival times were 79.4 ± 5.4 months (sinus rhythm), 64.4 ± 12.9 months (baseline AF) and 58.8 ± 8.9 months (newly onset AF during follow-up) (p = 0.565). CONCLUSIONS: Atrial fibrillation predict adverse prognosis in patients with PH and a longer P-wave (> 0.11 s) is associated with shorter survival time.