Classification Of Pulmonary Arterial Hypertension Research Articles

Effects of Pomegranate Extract Supplementation (Punica granatum L.) on Clinical Manifestations of Pulmonary Arterial Hypertension in Children with Acyanotic Congenital Heart Disease

Background: Pulmonary arterial hypertension (PAH) in congenital heart disease (CHD) mechanism includes vasoconstriction and vascular remodeling. In Indonesia, sildenafil as a vasodilator is the only standard treatment for PAH. Research on pomegranate extract showed its potential as an anti-inflammatory and anti-proliferative agent that could work synergically with sildenafil in reducing pulmonary arterial pressure (PAP) Objective: To investigate the effect of pomegranate supplementation in the clinical manifestation of PAH in children with acyanotic CHD. Methods: This study was a randomized controlled clinical trial that compared the clinical manifestation of PAH in children with acyanotic CHD who received standard therapy for PAH and pomegranate extract supplementation with the placebo group. Observations were carried out over three months, and pre-and post-test evaluations were conducted to assess changes in PAP, functional classification of PAH, body weight, systolic blood pressure, heart rate, respiratory rate, and oxygen saturation in both groups. Statistical analysis was undertaken using the Wilcoxon, Mann-Whitney, and Spearman correlation tests. Results: There was no significant difference in PAP reduction between the pomegranate and placebo groups (p = .44) and no significant difference in the functional classification of PAH in the placebo and pomegranate groups (p = .55). There was a considerable reduction in the respiratory rate in the pomegranate group (p = .017). Respiratory rate was positively correlated with the functional classification of PAH (p = .011). Conclusion: There was a significant reduction in the respiratory rate in the pomegranate group that correlated with the functional classification of PAH.

Evaluation and classification of pulmonary arterial hypertension.

In early 2019, the 6th World Symposium on Pulmonary Hypertension (WSPH) released an updated document highlighting the advances in the last five years. During the quinquennial event many experts worked together to suggest new changes in the disease diagnosis and management. Since inception of the WSPH in 1973, this is the first time when the hemodynamic definition of pulmonary hypertension (PH) has been updated. These proceedings have re-defined the different hemodynamic types of PH that occur with the left heart disease along with introduction to the genetic testing as part of pulmonary arterial hypertension (PAH) evaluation. Objective of this review is to highlight the evaluation and diagnosis of PAH based on the proceedings of the 6th WSPH. Accurate early diagnosis and subsequent management of PH is necessary, as despite of treatment advances, survival remains suboptimal.

Risk classification of pulmonary arterial hypertension by echocardiographic combined assessment of pulmonary vascular resistance and right ventricular function.

Which combination of clinical parameters improves the prediction of prognosis in patients with pulmonary arterial hypertension (PAH) remains unclear. We examined whether combined assessment of pulmonary vascular resistance and right ventricular function by echocardiography is useful for classifying risks in PAH. In 41 consecutive patients with PAH (mean age of 48.9 ± 17.3years, 31 females), a 6-min walk test, pulmonary function test, and echocardiography were performed at baseline and during PAH-specific therapies. The study endpoint was defined as a composite of cardiovascular death and hospitalization for PAH and/or right ventricular failure. During a follow-up period of 9.2 ± 8.7months, 18 patients reached the endpoint. Multivariate regression analysis showed that the ratio of tricuspid regurgitation pressure gradient to the time-velocity integral of the right ventricular outflow tract (TRPG/TVI) and tricuspid annular plane systolic excursion (TAPSE) during PAH-specific treatment were independent prognostic predictors of the endpoint. Using cutoff values indicated by receiver operating characteristic analysis, the patients were divided into four subsets. Multivariate analyses by Cox's proportional hazards model adjusted for age, sex and body mass index indicated that subset 4 (TRPG/TVI ≥ 3.89 and TAPSE ≤ 18.9mm) had a significantly higher event risk than did subset 1 (TRPG/TVI < 3.89 and TAPSE > 18.9mm): HR = 25.49, 95% CI 4.70-476.97, p < 0.0001. Combined assessment of TRPG/TVI and TAPSE during adequate PAH-specific therapies enables classification of risks for death and/or progressive right heart failure in PAH.

Classification of Pulmonary Arterial Hypertension by Genetic and Familial Testing.

Classification of Pulmonary Arterial Hypertension by Genetic and Familial Testing.

Pulmonary Arterial Hypertension: A Review Article

Pulmonary arterial hypertension (PAH) is characterized by the mean pulmonary artery pressure of more than 25 mmHg and pulmonary artery wedge pressure of less than 15 mmHg evidenced by right-heart catheterization. In the classification of PAH, some subgroups are defined as primary or secondary PAH based on the underlying etiologies of the disease. Early episodes of PAH have been reported to occur at younger ages and in women in idiopathic or familial forms with the survival rate of 1-3 years. According to recent registries, the affected patients are older and have better survival rates. Some of the key elements in the pathophysiology of PAH include intima and media proliferation, vascular remodeling, and blood coagulation, which could increase the defiance of pulmonary vascularity, so that the cellular and molecular pathways would be able to induce PAH through specific mechanisms. Although no pathognomonic signs and symptoms have been reported in the literature, the most prominent manifestations of PAH are associated with disorders such as heart failure. Currently, PAH is known as a severe and occasionally life-threatening multifactorial clinical condition. Considering endothelial dysfunction, vasoconstriction, inflammatory reactions, and platelet aggregation as the main pathophysiological arms of the disease, specific treatment approaches have been proposed to inhibit these manifestations. These methods result in the effective treatment response, as well as the proper early and late outcomes of PAH. Due to the high incidence of cardiovascular diseases and the associated progressive life-threatening conditions, such as heart failure and PAH in the Iranian population, identification of the etiological, pathophysiological, diagnostic, and novel therapeutic approaches for PAH is essential to the proper management of this clinical condition.

Treatment Considerations for Pulmonary Arterial Hypertension and Assessment of Treatment Response

The process of considering initial treatment options for a patient with pulmonary arterial hypertension (PAH), implementing that treatment, and reassessing response can be conceived as a 7-step process. A patient-centered approach, conducted in the context of a pulmonary hypertension care team, implements these steps in a thoughtful and well-organized fashion.Step 1: Perform a thorough diagnostic evaluationStep 2: Consider patient PAH classification and comorbiditiesStep 3: Assess risk profileStep 4: Develop a nuanced understanding of patient goals and preferencesStep 5: Create an initial treatment strategyStep 6: Implement a proactive longitudinal follow-up care planStep 7: Adjust treatment approach based on clear metrics of effectiveness and tolerability The burgeoning array of treatment options for PAH provides the opportunity to tailor therapy to the needs of individual patients, but also demands that the clinician develop a cogent strategy for initiating therapy, monitoring therapeutic response, and addressing side effects of therapy. In this review, we seek to provide a practical framework for approaching this challenge.

Safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension: a sub-group analysis based on Japan post-marketing surveillance

Objective: To evaluate the long-term safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension (PAH) in real-world clinical practice.Methods: This is an observational surveillance of PAH patients receiving tadalafil in the contracted sites. A sub-group analysis was performed of 391 pediatric PAH patients (<18 years) who were included from 1,704 total patients in this surveillance. Safety was assessed from the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included change in World Health Organization (WHO) functional classification of PAH, cardiac catheterization (pulmonary arterial pressure: PAP), and echocardiography (tricuspid regurgitation pressure gradient: TRPG). Survival rate was also measured.Results: The mean patient age was 5.7 ± 5.34 years. Associated PAH (APAH) and idiopathic PAH (IPAH) accounted for 76.0% and 17.6%, respectively, of the PAH patients. Patients were followed for up to 2 years. Among 391 patients analyzed for safety, the overall incidence rate of ADRs was 16.6%. The common ADRs (≥ 1%) were headache (2.8%), hepatic function abnormal, platelet count decreased (1.3% each), and epistaxis, (1.0%). Eleven patients (2.8%) reported 16 SADRs. Three patients died secondary to SADRs. For the effectiveness analysis, the incidence of WHO functional class improvement at 3 months, 1 year, and 2 years after the initiation of tadalafil and last observation in pediatric patients were 16.5%, 19.7%, and 16.3%, respectively. Both PAP and TRPG showed a statistically significant reduction at last observation.Conclusion: This manuscript reveals the use of tadalafil in the real-world pediatric population with an acceptable safety profile in Japan.

Safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension: Japanese post-marketing surveillance data

Objective: To evaluate the long-term safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension (PAH) in real-world clinical practice.Methods: This prospective, multicenter, noninterventional, post-marketing surveillance included patients with PAH who were observed for up to 2 years after initiation of tadalafil. Safety was assessed by analyzing the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included the assessment of the change in World Health Organization (WHO) functional classification of PAH, 6-minute walk test, cardiac catheterization, and echocardiography.Results: Among 1676 patients analyzed for safety, the overall incidence of ADRs was 31.2%. The common ADRs (≥1.0%) were headache (7.0%), diarrhea (1.9%), platelet count decreased (1.8%), anemia, epistaxis, and nausea (1.6% each), flushing (1.3%), hepatic function abnormal (1.1%), hot flush, and myalgia (1.0% each). The common SADRs (≥0.3%) were cardiac failure (0.7%), interstitial lung disease, worsening of PAH, and platelet count decreased (0.3% each). Among 1556 patients analyzed for effectiveness, the percentages of patients with improvement of WHO functional class at 3 months, 1 year, and 2 years after the initiation of tadalafil, and last observation were 17.1%, 24.8%, 28.9%, and 22.5%, respectively. At all observation points (except pulmonary regurgitation pressure gradient at end diastole at 3 months), the mean 6-minute walk distance, cardiac catheterization, and echocardiogram measurements showed statistically significant improvement.Conclusion: This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in patients with PAH in Japan.

Treatment of Pulmonary Arterial Hypertension Using Initial Combination Therapy of Bosentan and Iloprost.

Monotherapy and sequential combination therapy have been widely used in the treatment of pulmonary arterial hypertension (PAH). There is limited evidence for initial combination therapy in patients with PAH, particularly those with World Health Organization (WHO) functional class III or IV. Twenty-seven consecutive treatment-naive PAH subjects with WHO functional class III or IV PAH were randomized into 3 groups with a 1:1:1 ratio: a combination therapy group with 125 mg of bosentan twice daily plus 10 μg of iloprost 4-6 times/d; a bosentan monotherapy group with 125 mg of bosentan twice daily; and a iloprost monotherapy group with 10 μg of iloprost 4-6 times/d. Clinical and hemodynamic data were collected at baseline, 6 weeks, and 3 months. The primary end point was the change in the 6-min walk distance (6MWD) from baseline values. At baseline, there were no differences in demographics, WHO classification, hemodynamics, classification of PAH, or 6MWD among the 3 groups. The 6MWD significantly improved in the combination therapy group compared with the bosentan monotherapy and iloprost monotherapy groups at week 6 (P = .001) and after 3 months (P < .001), respectively. Secondary end points significantly improved in the combination therapy group for mean pulmonary artery pressure, cardiac index, and WHO functional classification after 3 months of treatment and for N-terminal pro-brain natriuretic peptide, Minnesota Living with Heart Failure questionnaire scores, and PaO2 after 6 weeks and 3 months of treatment, compared with the monotherapy groups. Initial combination therapy in treatment-naive PAH subjects with WHO functional class III or IV can significantly improve 6MWD, hemodynamics, and quality of life compared with monotherapy. Further studies with large samples and placebo controls are required to assess the tolerability and efficacy of initial combination therapy in patients with PAH. (ClinicalTrials.gov registration NCT01712997).

The Action of Smooth Muscle Cell Potassium Channels in the Pathology of Pulmonary Arterial Hypertension.

Many different types of potassium channels with various functions exist in pulmonary artery smooth muscle cells, contributing to many physiological actions and pathological conditions. The deep involvement of these channels in the onset and exacerbation of pulmonary arterial hypertension (PAH) also continues to be revealed. In 2013, KCNK3 (TASK1), which encodes a type of two-pore domain potassium channel, was shown to be a predisposing gene for PAH by genetic mutation, and it was added to the PAH classification at the Fifth World Symposium on Pulmonary Hypertension (Nice International Conference). Decreased expression and inhibited activity of voltage-gated potassium channels, particularly KCNA5 (Kv1.5), are also seen in PAH, regardless of the cause, and facilitation of pulmonary arterial contraction and vascular remodeling has been shown. The calcium-activated potassium channels seen in smooth muscle cells also change from BKca (Kca1.1) to IKca (Kca3.1) predominance in PAH due to transformation and have effects including the facilitation of smooth muscle cell migration, enhancement of proliferation, and inhibition of apoptosis. Elucidation of these roles for potassium channels in pulmonary vasoconstriction and remodeling may help bring new therapeutic strategies into view.

Rare and life-threatening cardiovascular complication of chronic thromboembolic pulmonary hypertension diagnosed by trans-thoracic echocardiography

An 83-year-old female was admitted to the cardiac care unit of Hopital Emile Muller (Mulhouse, France) due to acute respiratory distress. She had a history of recurrent pulmonary emboli that had led to group-IV chronic thromboembolic pulmonary hypertension (CTEPH) according to the classification of pulmonary arterial hypertension (PAH) set by the World Health Organization (WHO). CTEPH was treated from 2013 with long-term oxygen therapy and oral anticoagulation. She presented with a dramatic increase in dyspnoea accompanied by acute chest pain with dorsal irradiation. She was in respiratory distress with blood saturation at 70% in ambient air. She showed signs of right-heart failure (turgid jugular veins, lowerlimb oedema). Under 5 l of O2, arterial blood gases were 81 mm Hg for paO2 and 50 mm Hg for paCO2, whereas bicarbonate was −29 mmol/l, brain natriuretic peptide was 167 ng/l, and D-dimer was 1151 ng/ml. Right-axis deviation with right ventricular hypertrophy was found upon electrocardiography. Chest radiography revealed reticular/ nodular densities in the right base with alveolar opacity in the left base, which led us to suspect pneumonia. Trans-thoracic echocardiography (TTE) demonstrated: normal left ventricular ejection fraction;

Pulmonary Veno-Occlusive Disease: A Rare Cause of Pulmonary Hypertension

Supported by CVPath Institute, Inc. (Gaithersburg, MD). Accepted for publication November 25, 2014. Disclosures: R.V. receives research support from Abbott Vascular, BioSensors International, Biotronik, Boston Scientific, Medtronic, MicroPort Medical, OrbusNeich Medical, SINO Medical Technology, and Terumo Corporation; has speaking engagements with Merck; receives honoraria from Abbott Vascular, Boston Scientific, Lutonix, Medtronic, and Terumo Corporation; and is a consultant for 480 Biomedical, Abbott Vascular, Medtronic, and W.L. Gore. K.Y. reports no conflicts of interest relevant to the topic of this manuscript. Address correspondence to Renu Virmani, M.D., CVPath Institute, Inc., 19 Firstfield Rd., Gaithersburg, MD 20878. E-mail: rvirmani@cvpath.org. Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension (PH), characterized by increased pulmonary artery pressure contributing to right heart failure and death. Historically, PVOD has been described by diverse terms, such as isolated pulmonary venous sclerosis, obstructive disease of the pulmonary veins, or venous form of primary pulmonary hypertension (PPH). The true incidence of PVOD is uncertain, considering that a large number of PPH cases are misclassified. The estimated frequency of PVOD is between 5% to 25%; however, 10% incidence of PVOD in a pooled analysis of seven studies totaling 465 PPH cases examined between 1970 and 1991 has also been reported. The noninvasive diagnosis of PVOD in cases confirmed by histology-identified clinical features of pulmonary arterial hypertension (PAH) include: >10 pack per year smoking history, high-resolution CT showing nodular ground glass opacities, septal lines, lymph node enlargement, and pleural effusion with occult alveolar hemorrhage confirmed by bronchoalveolar lavage. In 1975, the World Health Organization (WHO) further classified pulmonary hypertension (PH) into primary or secondary PH. In 1998, the WHO established a clinical classification of PH to include five groups, which share similar pathological and hemodynamic etiologies and therapeutic approaches to treatment. The clinical classification of PH includes i) PAH, ii) PH due to left heart disease, iii) PH due to lung disease and/or hypoxia, iv) chronic thromboembolic pulmonary hypertension, and v) PH with unclear multifactorial mechanism. This consensus has remained the same with some modifications published in 2009 and during the 2013 meeting of the Fifth World Symposium. Major categories of PAH include sporadic or idiopathic PAH, heritable PAH, and PAH attributed to drugs and toxins, congenital heart disease, and others. The PAH classification also includes PVOD classified as Group 1, which is

Investigating cardiac MRI based right ventricular contractility as a novel non-invasive metric of pulmonary arterial pressure.

BACKGROUNDWe test the hypothesis that cardiac magnetic resonance (CMR) imaging-based indices of four-dimensional (4D) (three dimensions (3D) + time) right ventricle (RV) function have predictive values in ascertaining invasive pulmonary arterial systolic pressure (PASP) measurements from right heart catheterization (RHC) in patients with pulmonary arterial hypertension (PAH).METHODSWe studied five patients with idiopathic PAH and two age and sex-matched controls for RV function using a novel contractility index (CI) for amplitude and phase to peak contraction established from analysis of regional shape variation in the RV endocardium over 20 cardiac phases, segmented from CMR images in multiple orientations.RESULTSThe amplitude of RV contractility correlated inversely with RV ejection fraction (RVEF; R2 = 0.64, P = 0.03) and PASP (R2 = 0.71, P = 0.02). Phase of peak RV contractility also correlated inversely to RVEF (R2 = 0.499, P = 0.12) and PASP (R2 = 0.66, P = 0.04).CONCLUSIONSRV contractility analyzed from CMR offers promising non-invasive metrics for classification of PAH, which are congruent with invasive pressure measurements.

A Proof of Concept for the Detection and Classification of Pulmonary Arterial Hypertension through Breath Analysis with a Sensor Array

A Proof of Concept for the Detection and Classification of Pulmonary Arterial Hypertension through Breath Analysis with a Sensor Array

Future Breakthroughs in the Genetics of Pulmonary Arterial Hypertension

Future Breakthroughs in the Genetics of Pulmonary Arterial Hypertension

Hemodynamics in Pulmonary Arterial Hypertension: Current and Future Perspectives

Right heart catheterization (RHC)-determined pulmonary hemodynamics are mandatory for the diagnosis and classification of pulmonary hypertension (PH) and can be used to assess response to PH-specific therapy and inform clinical decision-making. PH is diagnosed in patients with a mean pulmonary arterial pressure of ≥25 mm Hg at rest, with a further classification of pulmonary arterial hypertension (PAH) in patients with a pulmonary artery wedge pressure of ≤15 mm Hg and, often, reduced cardiac output. In addition, a number of hemodynamic variables, either measured directly with RHC or subsequently derived, have been shown to have prognostic significance in PAH, with different variables having more prognostic significance in specific patient populations. Although there is no hemodynamic definition of exercise-induced PAH, measurement of certain hemodynamic variables during exercise may identify an intermediary phenotype between healthy individuals and overt PAH at rest and may have prognostic implications. However, although exercise hemodynamics may be a closer reflection of the true resistive component of the pulmonary vasculature and its ability to respond to therapy, the lack of standardized protocols limits application in routine clinical practice.

Pulmonary Hypertension: Diagnosis and Management

Pulmonary arterial hypertension is a progressive, symptomatic, and ultimately fatal disorder for which substantial advances in treatment have been made during the past decade. Effective management requires timely recognition and accurate diagnosis of the disorder and appropriate selection among therapeutic alternatives. Despite progress in treatment, obstacles remain that impede the achievement of optimal outcomes. The current article provides an overview of the pathobiologic mechanisms of pulmonary arterial hypertension, including genetic substrates and molecular and cellular mechanisms, and describes the clinical manifestations and classification of pulmonary arterial hypertension. The article also reviews established approaches to evaluation and treatment, with emphasis on the appropriate application of calcium channel blockers, prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors. In addition, the authors discuss unresolved issues that may complicate patient management, such as the clinical importance of mild or exercise-related pulmonary arterial hypertension, and they identify avenues by which treatment may advance in the future through the use of combination treatment, outcomes assessment, and exploration of alternative pharmacologic strategies.

Other causes of pulmonary arterial hypertension: pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis, porto-pulmonary hypertension, HIV- associated pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension (PAH) is included in Group 1 of PAH classification, while pulmonary veno-occlusive disease (PVOD), pulmonary capillary hemangiomatosis (PCH), portopulmonary hypertension (PoPH) and HIV-associated PAH constitute the subgroups of Group I PAH disorders. PVOD has similar clinical presentation, hemodynamic characteristics and genetic background with PAH although main pathology is in venules and definite diagnosis is done by biopsy although not recommended due to high risk of bleeding. PCH, a rare idiopathic lung disorder, causes PAH in young adults and mostly is diagnosed after death by autopsy. PoPH is defined as PAH due to primary chronic liver disease associated with intrapulmonary vascular dilatations and hypoxia. HIV associated PAH is a rare complication of HIV-infection, and it is seen especially in HIV-infected patients with intravenous drug abuse.

Pulmonary hypertension: diagnosis and management.

Pulmonary arterial hypertension is a progressive, symptomatic, and ultimately fatal disorder for which substantial advances in treatment have been made during the past decade. Effective management requires timely recognition and accurate diagnosis of the disorder and appropriate selection among therapeutic alternatives. Despite progress in treatment, obstacles remain that impede the achievement of optimal outcomes. The current article provides an overview of the pathobiologic mechanisms of pulmonary arterial hypertension, including genetic substrates and molecular and cellular mechanisms, and describes the clinical manifestations and classification of pulmonary arterial hypertension. The article also reviews established approaches to evaluation and treatment, with emphasis on the appropriate application of calcium channel blockers, prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors. In addition, the authors discuss unresolved issues that may complicate patient management, such as the clinical importance of mild or exercise-related pulmonary arterial hypertension, and they identify avenues by which treatment may advance in the future through the use of combination treatment, outcomes assessment, and exploration of alternative pharmacologic strategies.

Abstract 6167: Appropriate Timing Enhances the Utility of Plasma Brain Natriuretic Peptide in Predicting Survival in Pulmonary Arterial Hypertension

Background: The natural course of pulmonary arterial hypertension (PAH) is characterized by progressive functional worsening leading to right heart failure and death. Since plasma brain natriuretic peptide (BNP) levels correlate with right ventricular dysfunction, we sought to evaluate the use of BNP as a prognostic indicator in PAH. Methods and Results: We examined our prospective pulmonary hypertension registry for patients who underwent right heart catheterization (RHC) between 1998 and 2008. The BNP values from the time of catheterization until date of last visit or death were analyzed in relationship to overall survival. Of the 626 patients who underwent RHC, 559 met the Venice classification of PAH: 83% category I, 10% category III, 5% category IV, and 2 % category V. Baseline mean pulmonary artery pressures were 47±16 mm Hg and cardiac index 2.6±1 l/min/m 2 . During follow up, patients were treated with prostanoids (27%), endothelin blockers (31%), PDE5 inhibitors (40%), calcium channel blockers (2%), and 56% received combination therapy. BNP values during the first 6 months were higher in patients who died in the first 2 years (n=108) compared to patients surviving more than 5 years (n=82) but the levels had no correlation to survival [R 2 =0.03, p=0.2]. Interestingly, the strongest predictor for survival was the BNP level obtained 12–14 months from RHC [R 2 =0.7, p=0.0001]. All patients who survived over 5 years had BNP value less than 150 ng/L at 12 months and all patients with BNP values &gt;330 ng/L at 12 months were dead by 2 years. Furthermore, there was an accelerated rate of increase in BNP levels in patients who did not survive past 2 years [BNP rise rate (ng/L/month): non- survivors 33 ± 14 while, long-term survivors 0.3 ± 1; p=0.008]. Conclusions: In patients with pulmonary arterial hypertension, initial BNP levels do not appear to have prognostic significance. BNP levels at 1 year, however, are strong predictors of early mortality or long term survival. The rate of rise in BNP levels is a novel concept that may be a useful management tool before the 1 year time point.