Ambrisentan and Tadalafil Up-front Combination Therapy in Scleroderma-associated Pulmonary Arterial Hypertension.

BACKGROUND: Scleroderma-associated pulmonary arterial hypertension (SSc-PAH) is a rare disease characterized by a very dismal response to therapy and poor survival. We assessed the effects of up-front combination PAH therapy in patients with SSc-PAH. METHODS: In this prospective, multicenter, open-label trial, 24 treatment-naive patients with SSc-PAH received ambrisentan 10 mg and tadalafil 40 mg daily for 36 weeks. Functional, hemodynamic, and imaging (cardiac magnetic resonance imaging and echocardiography) assessments at baseline and 36 weeks included changes in right ventricular (RV) mass and pulmonary vascular resistance as co-primary endpoints and stroke volume/pulmonary pulse pressure ratio, tricuspid annular plane systolic excursion, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide as secondary endpoints. RESULTS: At 36 weeks, we found that treatment had resulted in significant reductions in median (interquartile range [IQR]) RV mass (28.0 g [IQR, 20.6-32.9] vs. 32.5 g [IQR, 23.2-41.4]; P < 0.05) and median pulmonary vascular resistance (3.1 Wood units [IQR, 2.0-5.7] vs. 6.9 Wood units [IQR, 4.0-12.9]; P < 0.0001) and in improvements in median stroke volume/pulmonary pulse pressure ratio (2.6 ml/mm Hg [IQR, 1.8-3.5] vs. 1.4 ml/mm Hg [IQR 8.9-2.4]; P < 0.0001) and mean ( ± SD) tricuspid annular plane systolic excursion (2.2 ± 0.12 cm vs. 1.65 ± 0.11 cm; P < 0.0001), 6-minute walk distance (395 ± 99 m vs. 343 ± 131 m; P = 0.001), and serum N-terminal pro-brain natriuretic peptide (647 ± 1,127 pg/ml vs. 1,578 ± 2,647 pg/ml; P < 0.05). CONCLUSIONS: Up-front combination therapy with ambrisentan and tadalafil significantly improved hemodynamics, RV structure and function, and functional status in treatment-naive patients with SSc-PAH and may represent a very effective therapy for this patient population. In addition, we identified novel hemodynamic and imaging biomarkers that could have potential value in future clinical trials. Clinical trial registered with www.clinicaltrials.gov (NCT01042158).

Outcomes of ß-blocker use in pulmonary arterial hypertension: a propensity-matched analysis.

The utility and safety of ß-blockers in pulmonary hypertension is controversial. Anecdotal reports suggest that ß-blockers may be harmful in these patients. The aim of our study was to evaluate outcomes of ß-blocker use in pulmonary hypertension.We reviewed patients from our pulmonary hypertension registry between 2000 and 2011. Patients who continued to use ß-blockers were compared to those who never used ß-blockers for all-cause mortality, time to clinical worsening events, defined as death, lung transplantation and hospitalisation due to pulmonary hypertension. We also evaluated the effect of ß-blockers on 6-min walking distance and New York Heart Association (NYHA) functional class.133 patients used ß-blockers and 375 patients never used ß-blockers. Mean±sd age was 57±16 years and the median follow-up period was 78 months. Propensity-matched analysis showed that the adjusted odds ratio (95% CI) for mortality with ß-blocker use was 1.13 (0.69-1.82) and for clinical worsening events was 0.96 (0.55-1.68). No significant difference was noted in probability of survival and time to clinical worsening events. Patients on ß-blockers walked a shorter distance on follow-up 6 min walk test; follow-up NYHA class was similar between groups.Pulmonary hypertension patients receiving ß-blockers had a similar survival and time to clinical worsening events compared to patients not receiving them. Functional outcomes were similar, although ß-blocker use was associated with a tendency towards shorter walking distance.

Electrocardiography at diagnosis and close to the time of death in pulmonary arterial hypertension.

BACKGROUND: Scarce information exits on the electrocardiographic (ECG) characteristics of pulmonary arterial hypertension (PAH) patients close to their death and whether observed abnormalities progress from the time of PAH diagnosis. METHODS: We analyzed the characteristics of the ECG performed at initial diagnosis, during the course of the disease and close to the time of death on consecutive PAH patients followed at our institution between June 2008 and December 2010. RESULTS: We included 50 patients with PAH (76% women) with mean (SD) age of 58 (14) years. Median heart rate (83 vs 89 bpm, P = 0.001), PR interval (167 vs 176 ms, P = 0.03), QRS duration (88 vs 90 ms, P = 0.02), R/S ratio in lead V1 (1 vs 2, P = 0.01), and QTc duration (431 vs 444 ms, P = 0.02) significantly increased from the initial to the last ECG. In addition, the frontal QRS axis rotated to the right (97 vs 112 degrees, P = 0.003) and we more commonly observed right bundle branch block (5% vs 8%, P = 0.03) and negative T waves in inferior leads (31% vs 60%, P = 0.004). No patient had normal ECG at the time of death. CONCLUSIONS: Significant changes progressively occur in a variety of ECG parameters between the time of the initial PAH diagnosis and close to death.

Causes and circumstances of death in pulmonary arterial hypertension.

RATIONALE: The causes and circumstances surrounding death are understudied in patients with pulmonary arterial hypertension (PAH). OBJECTIVES: We sought to determine the specific reasons and characteristics surrounding the death of patients with PAH. METHODS: All deaths of patients with pulmonary hypertension (PH) followed in the Cleveland Clinic Pulmonary Vascular Program were prospectively reviewed by the PH team. A total of 84 patients with PAH (age 58 ± 14 yr; 73% females) who died between June 2008 and May 2012 were included. MEASUREMENTS AND MAIN RESULTS: PH was determined to be the direct cause of death (right heart failure or sudden death) in 37 (44%) patients; PH contributed to but did not directly cause death in 37 (44%) patients; and the death was not related to PH in the remaining cases (n = 7; 8.3%). In three (3.6%) patients the final cause of death could not be adequately assessed. Most patients died in a healthcare environment and most received PH-specific therapies. In our cohort, 50% of all patients with PAH and 75.7% of those who died of right heart failure received parenteral prostanoid therapy. Less than half of patients had advanced healthcare directives. CONCLUSIONS: Most patients with PAH in our cohort died of their disease; however, right ventricular failure or sudden death was the sole cause of death in less than half of patients.

Heart rate recovery predicts clinical worsening in patients with pulmonary arterial hypertension.

RATIONALE: Reduced heart rate recovery after exercise is associated with increased mortality in cardiopulmonary diseases. OBJECTIVES: We sought to evaluate the association between heart rate recovery at 1 minute of rest (HRR1) after 6-min walk test (6MW test) and clinical worsening in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS: HRR1 was defined as the difference in heart rate at the end of 6MW test and at 1 minute after completion of the 6MW test. Between August 1, 2009 and March 30, 2010, 75 consecutive patients with IPAH underwent 6MW test and were included in the analysis. MEASUREMENTS AND MAIN RESULTS: Compared with patients with HRR1 ≥ 16 (n = 45 [60%]), those with HRR1 less than 16 (n = 30 [40%]) were more likely to have clinical worsening (odds ratio, 9.7; 95% confidence interval [CI], 3-30; P < 0.001) and shorter time to first clinical worsening event (TCW) (6.7 mo vs. 13 mo; P < 0.001) during follow-up. By multivariable analysis, the best predictors of clinical worsening were HRR1 less than 16 (hazard ratio, 5.2; 95% CI, 1.8-14.8; P = 0.002) and mean pulmonary arterial pressure (hazard ratio, 1.04; 95% CI, 1.007-1.08; P = 0.02). Compared with the distance walked during the 6MW test (6MWD), HRR1 less than 16 was a better predictor of clinical worsening (C statistic 0.757 vs. 0.703) and TCW (C index 0.730 vs. 0.696). The addition of HRR1 increased the ability of 6MWD to predict clinical worsening events. CONCLUSIONS: HRR1 after 6MW test is a strong predictor of clinical worsening and TCW in patients with IPAH. The addition of HRR1 to 6MWD increases the capacity of 6MWD to predict clinical worsening and TCW in patients with IPAH.

Abnormal platelet aggregation in idiopathic pulmonary arterial hypertension: role of nitric oxide.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare and progressive disease. Several processes are believed to lead to the fatal progressive pulmonary arterial narrowing seen in IPAH including vasoconstriction, cellular proliferation inflammation, vascular remodeling, abnormalities in the lung matrix, and in situ thrombosis. Nitric oxide (NO) produced by NO synthases (NOS) is a potent vasodilator and plays important roles in many other processes including platelet function. Reduced NO levels in patients with IPAH are known to contribute to the development of pulmonary hypertension and its complications. Platelet defects have been implied in IPAH, but original research supporting this hypothesis has been limited. Normal platelets are known to have NOS activity, but little is known about NOS expression and NO production by platelets in patients with IPAH. Here we characterized the phenotype of the platelets in IPAH and show a defect in their ability to be activated in vitro by thrombin receptor activating protein but not adenosine diphosphate. We also show that endothelial NOS (eNOS) levels in these platelets are reduced and demonstrate that NO is an important regulator of platelet function. Thus reduced levels of eNOS in platelets could impact their ability to regulate their own function appropriately.

Pulmonary hypertension before first and second lung transplantation.

BACKGROUND: Pulmonary hypertension (PH) is frequently encountered in patients with advanced lung disease before the first and second lung transplantation. We sought to determine whether there is any relationship between pulmonary hemodynamics obtained before first and second lung transplantation. We also assessed whether PH has prognostic implications in lung transplant patients going for second transplantation. METHODS: We included consecutive adult (16-yr-old or older) patients who underwent lung re-transplantation, between 1997 and 2009, and had right heart catheterization before their first and second lung transplantation. RESULTS: Eighteen patients were included in the study. Age at first transplantation was 50.4 (SD 10.4) yr, and bronchiolitis obliterans syndrome (BOS) in the transplanted lung was the only indication for re-transplantation. PH was observed in 39% of the patients before the first lung transplant and in 56% of the subjects before re-transplantation (p = 0.91). Pre-capillary PH was present in 28% (n = 5) and 33% (n = 6) of the patients before first and second lung transplantation, respectively. None of the hemodynamic variables obtained before the first transplant predicted the development of PH before re-transplantation. PH before re-transplantation did not predict survival or development of BOS after re-transplantation. CONCLUSIONS: PH before initial lung transplantation did not predict the development of PH before the second transplantation. In our cohort, PH before second lung transplantation did not predict outcomes after re-transplantation.

Prevalence and significance of decreased bone density in pulmonary arterial hypertension.

OBJECTIVE: Decreased bone mineral density has been found in the advanced stages of various lung diseases. Limited data are available about prevalence and risk factors for osteoporosis/osteopenia (OP) in pulmonary arterial hypertension (PAH). METHODS: Patients with PAH (either idiopathic or secondary to scleroderma [SSC-PAH]) who underwent bone density testing for lung transplant evaluation were included. Results of bone density testing, demographic data, pulmonary function testing, hemodynamic measures, and 6-minute walk distance test (6MWD) were collected. RESULTS: Thirty-two patients were identified (27 women/5 men, 24 idiopathic PAH/8 SSC-PAH) and OP was found in 22 (69%) patients. Patients with SSC-PAH had more significant indications of OP at all of the measured sites. The OP group had lower FEV1 (P = 0.01) and a significantly lower 6MWD (P = 0.04) as compared with patients with PAH with normal bone density. Hemodynamics indicated no statistically significant differences between the groups other than a lower mean pulmonary artery pressure (P = 0.01) in the OP group. Patients with a history of corticosteroid use and smoking, postmenopausal status, decreased functional capacity (as measured by poor New York Heart Association functional class and 6MWD), SSC-PAH, and need for oxygen during a 6MWD test had an increased risk of OP by univariate logistic regression. CONCLUSIONS: Reduced bone density can be seen in a majority of patients with advanced PAH. Risk factors for reduced bone density include SSC-PAH, reduced 6MWD, need for oxygen during 6MWD testing, reduced FEV1, a history of smoking or corticosteroid use, and postmenopausal status.

Sleep quality, depression, and quality of life in patients with pulmonary hypertension.

Pulmonary hypertension is a disabling disease characterized by progressive functional worsening, right heart failure, and death. Although pulmonary hypertension has been associated with poor quality of life, sleep quality has not been investigated in pulmonary hypertension patients. This was a cross-sectional study in which patients (N = 40) were asked to complete standardized questionnaires to assess sleep quality [using Pittsburgh Sleep Quality Index (PSQI)], insomnia, sleepiness, dyspnea, depression, restless leg syndrome, and quality of life [using Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)] during routine office visits. Baseline hemodynamics, pulmonary function tests, exercise capacity, and transthoracic echocardiogram were analyzed. Pulmonary hypertension functional class was World Health Organization class II [20 (50%)], III [18 (45%)], and IV [2 (5%)], and 29 (72.5%) had poor sleep quality. PSQI score was associated with CAMPHOR symptoms score (R = 0.61, P < 0.001), CAMPHOR activities score (R = 0.38, P = 0.016), CAMPHOR quality-of-life score (R = 0.45, P = 0.004), depression (R = 0.42, P = 0.007), and dyspnea (R = 0.36, P = 0.02). Sleep quality was not associated with age, gender, other comorbidities, pulmonary hypertension etiology, baseline hemodynamics, pulmonary function testing, echocardiographic parameters, or exercise capacity. Poor sleep quality is common in patients with pulmonary hypertension and correlates with depression, dyspnea, and poor quality of life. Improving sleep quality in patients with pulmonary hypertension may improve quality of life.

Safety of diagnostic bronchoscopy in patients with pulmonary hypertension.

BACKGROUND: Patients with pulmonary hypertension (PH) are considered to be at risk for complications associated with flexible bronchoscopy (FB). Although previous reports suggest that transbronchial biopsies increase the risk for hemorrhage in this population, data are limited to survey analyses and isolated reports. OBJECTIVES: It was the aim of this study to describe our experience with FB and to determine if bronchoscopic procedures are associated with adverse events in this population. METHODS: We conducted a retrospective review of patients with diagnosis of PH who underwent FB at the Cleveland Clinic between 2002 and 2005. Patients without PH who underwent FB by the same pulmonary physician were used as controls. RESULTS: A total of 90 patients, PH (n = 45) versus controls (n = 45), were included. The mean systolic pulmonary artery pressure in patients with PH was 58 +/- 7 mm Hg. Patients with PH had higher oxygen requirements at baseline (FiO(2) 0.42 vs. 0.3%; p = 0.01). The total number of procedures was similar between the groups (95 vs. 102). Procedures performed were bronchoalveolar lavage (21 vs. 13), transbronchial biopsies (24 vs. 32) and transbronchial needle aspiration (7 vs. 6). There were no hemodynamic complications or episodes of respiratory failure associated with the procedures. None of the patients had significant hemorrhage and only 2 developed mild bleeding which resolved spontaneously. Similarly, none required hospitalization or transfer to an intensive care unit. CONCLUSIONS: FB can be performed safely in patients with mild to moderate PH. Transbronchial biopsies are not associated with worsening hypoxemia or an increased risk of hemorrhage. Prospective studies with hemodynamic measurements are necessary to confirm these findings.

BMPR2 mutation in a patient with pulmonary arterial hypertension and suspected hereditary hemorrhagic telangiectasia.

Pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia (HHT) are distinct clinical entities caused by germline mutations in genes encoding members of the TGFbeta/BMP superfamily: BMPR2 in PAH and ACVRL1, ENG, or SMAD4 in HHT. When PAH and HHT occasionally co-exist within the same family, ACVRL1 mutations predominate. We report a 36-year-old woman initially diagnosed with PAH at age 24. At 35, following massive hemoptysis, multiple pulmonary arteriovenous malformations were discovered, prompting evaluation for HHT. She met the Curaçao diagnostic criteria for suspected HHT based on additional findings of nasal telangiectases and epistaxis. Mutation analysis of ACVRL1, ENG, and SMAD4 was normal, but a germline nonsense mutation in BMPR2 was identified. This is the first known report of HHT features, particularly pulmonary AVMs, associated with a BMPR2 mutation. It adds further weight to a common molecular pathogenesis in PAH and HHT, and highlights that BMPR2 gene analysis is indicated in patients affected with both HHT and PAH.

Vaso-active therapy can improve 6-min walk distance in patients with pulmonary hypertension and fibrotic interstitial lung disease.

BACKGROUND: Dyspnea and functional limitation in interstitial lung diseases (ILD) are not always adequately explained by the degree of compromise in pulmonary function alone. Pulmonary hypertension (PH) is felt to be a major contributor to morbidity and mortality in these patients. It is not clear whether treatment with newer vaso-active agents benefits patients with PH in the setting of moderate or severe ILD. METHODS: Medical records of patients followed at our institution between July 2001 and June 2005 were reviewed to identify patients with moderate or severe fibrotic ILD and PH. Data regarding demographics, hemodynamics, and clinical characteristics at baseline and during follow-up were collected. RESULTS: We identified 19 patients who met our inclusion criteria and in whom vaso-active therapy [epoprostenol (N=10), bosentan (N=9)] was initiated. Most patients [(15/19(79%)] showed an initial positive response to therapy and improved their 6-min walk distance (6MWD) by >50m (responders) and 12/15 (80%) improved by at least 1 WHO functional class. At 1-year follow-up, 7 of 15 (47%) 'responders' had deteriorated significantly. None of the patients died during 1 year of follow-up. CONCLUSIONS: Epoprostenol and bosentan produced short-term functional benefit in our patients with PH and moderate or severe restrictive ILD. The generalizability of these results awaits the results of larger, prospective, randomized trials in such patients.

Long-term experience after transition from parenteral prostanoids to oral agents in patients with pulmonary hypertension.

BACKGROUND: Long-term follow-up after transition to oral agents from parenteral prostanoid therapy has not been well characterized. METHODS: We reviewed our long-term experience after oral transitioning in patients with pulmonary hypertension. Patients were weaned off parenteral therapy based on a pre-determined outpatient protocol. Data were collected retrospectively after transition had taken place. RESULTS: Twenty-one transitioned patients were identified. Fifteen patients (71.4%) were successfully transitioned (ST): 7 to bosentan, 5 to bosentan and sildenafil, and 3 to sildenafil. Six patients failed transition (FT). None of the patients in the FT group received sildenafil. Prior to transition attempt, patients in the ST group were treated with parenteral agents for a mean of 26 months vs. 16 months in the FT group (p=0.12). Maximal epoprostenol dose was low in both groups (ST 17.8 ng/kg/min vs. FT 14.5 ng/kg/min). Mean duration of oral therapy prior to transition was 11 months. After a mean follow-up of 24 months, most patients on both groups were able to maintain stable 6 min walk distance and hemodynamics. FT was not associated with short- or long-term adverse events. CONCLUSIONS: Oral transition from parenteral prostanoid agents can be safely done in a selected group of patients. Most patients are able to maintain stable functional class and hemodynamics at long follow up regardless of success of transition attempt. Combination therapy with sildenafil appears to be associated with higher likelihood of successful transitioning.

The impact of ambrisentan and tadalafil upfront combination therapy on cardiac function in scleroderma associated pulmonary arterial hypertension patients: cardiac magnetic resonance feature tracking study.

The aim of this study was to evaluate the effect of upfront combination therapy with ambrisentan and tadalafil on left ventricular (LV) and right ventricular (RV) function in patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH). LV and RV peak longitudinal and circumferential strain and strain rate (SR), which consisted of peak systolic SR (SRs), peak early diastolic SR (SRe), and peak atrial-diastolic SR (SRa) were analyzed using cardiac magnetic resonance imaging (CMRI) data from the recently published ATPAHSS-O trial (ambrisentan and tadalafil upfront combination therapy in SSc-PAH). Twenty-one patients completed the study protocol. Measures of RV systolic function (RV free wall [RVFW] peak longitudinal strain [pLS], RVFW peak longitudinal SRs [pLSRs]) and RV diastolic function (RVFW peak longitudinal SRa [pLSRa], RVFW peak circumferential SRe) were improved after treatment. LV systolic function (LV peak global longitudinal strain [pGLS]) and diastolic function (LV peak global longitudinal SRe [pGLSRe]) were also significantly improved at follow-up. Increased 6-min walk distance was significantly correlated with RVFW pLS and pLSRs, while the decrease in N-terminal pro-brain natriuretic peptide was correlated with LV pGLS. Increased cardiac index was associated with improved LV pGLSRe, and reduction in mean right atrial pressure was correlated with improved RVFW pLS and pLSRa. Combination therapy was associated with a significant improvement in both RV and LV function as assessed by CMR-derived strain and SR. Importantly, the improvement in RV and LV strain and SR correlated with improvements in known prognostic markers of PAH. (Approved by clinicaltrials.gov [NCT01042158] before patient recruitment.).

Long-term outcome in a patient with pulmonary hypertension and hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) may be associated with pulmonary hypertension (PH). In the context that little attention has been given to long-term follow-up of such individuals, we report a patient with PH associated with HHT with special attention to clinical features and long-term response to therapy. To our knowledge, this case represents only the second with a 10-year follow-up reported and demonstrates that aggressive therapy can lead to long-term improvement in clinical parameters and survival.

Predictors of nocturnal oxygen desaturation in pulmonary arterial hypertension.

BACKGROUND: Sleep may be associated with significant respiratory compromise in patients with lung disease and can result in hypoxia. In patients with pulmonary arterial hypertension (PAH), nocturnal desaturation may not be reflected in daytime evaluations of oxygenation and can lead to worsening pulmonary hemodynamics. The study was conducted to determine the prevalence and significance of nocturnal oxygen desaturation in patients with PAH. METHODS: A cross-sectional study conducted at the Cleveland Clinic. Patients were followed up at our institution except for the overnight oximetry study done at home. Data regarding degree of nocturnal desaturation, demographics, hemodynamics, pulmonary function, and functional capacity were collected. RESULTS: Forty-three patients (mean age, 47.9 +/- 13.5 years [+/- SD]; 36 women and 7 men) underwent nocturnal oximetry. The etiology of PAH included idiopathic PAH (88%) and PAH associated with connective tissue diseases (12%). The majority of patients were New York Heart Association functional class II (42%) or III (53%). Thirty patients (69.7%) spent > 10% of sleep time with oxygen saturation by pulse oximetry < 90%. Desaturators were older (p = 0.024) and had higher hemoglobin (p = 0.002). Sixteen of 27 patients (59%) without desaturation < 90% during a 6-min walk test were nocturnal desaturators. Nocturnal desaturators had higher brain natriuretic protein (p = 0.004), lower cardiac index (p = 0.03), and higher mean right atrial pressure (p = 0.09), mean pulmonary artery pressure, and pulmonary vascular resistance. On echocardiography, desaturators were more likely to have moderate or severe right ventricular dilation (p = 0.04) and pericardial effusion. Only one patient had significant sleep apnea. CONCLUSIONS: Nocturnal hypoxemia is common in PAH patients and correlates with advanced pulmonary hypertension and right ventricular dysfunction. Approximately 60% patients without exertional hypoxia had nocturnal desaturation. Overnight oximetry should be considered in the routine workup of PAH patients who do not demonstrate exertional desaturation.

Lupus-associated pulmonary hypertension: long-term response to vasoactive therapy.

INTRODUCTION: Pulmonary hypertension (PH) is a serious complication of lupus. The effectiveness of current vasoactive therapy has not been well described. METHODS: Retrospective analysis of 12 patients with lupus-associated PH (age 43+/-10 years, mean+/-SD, all female) treated with pulmonary vasodilators. RESULTS: At baseline, patients had severe PH: median six-minute walk distance (6MWD) 266 m (95% confidence interval [CI], 106 to 362); functional class III (n=7) and IV (n=5); mean pulmonary artery pressure (mPAP) 52 mmHg and cardiac index 2.23 L/min/m(2). Eight patients were started on epoprostenol and 2 each on bosentan or treprostinil. After a mean follow-up of 41+/-25 months, 5 patients were on combination therapy (3 epoprostenol plus bosentan, 1 treprostinil plus bosentan, 1 bosentan plus sildenafil) and 7 were on monotherapy (2 epoprostenol, 4 bosentan, 1 sildenafil); 6MWD increased by 139 m (95% CI, 36 to 259, p=0.007), 8 patients were functional class I or II and 4 were class III; right ventricular systolic pressure (RVSP) decreased by 22 mmHg (95% CI, 6 to 36; p=0.012), mPAP decreased by 18 mmHg (95% CI, 8 to 29; p=0.014), and cardiac index increased by 1.44 L/min/m(2) (95% CI, 0.76 to 2.08; p=0.016). There was no mortality or need for lung transplantation. Therapy was well tolerated. CONCLUSIONS: Vasoactive therapy can achieve sustained clinical and hemodynamic improvement in lupus-associated PH.

Diagnostic strategies for suspected pulmonary arterial hypertension: a primer for the internist.

Pulmonary arterial hypertension should be considered in patients who present with nonspecific symptoms such as dyspnea or dizziness after more common causes have been ruled out. Echocardiography can help in the diagnosis: special attention should be given to assess the tricuspid valve and right ventricular function. Before starting treatment, a patient should undergo right heart catheterization to accurately measure the pressures and assess right ventricular function, which help in appropriate selection of therapy.

Treating pulmonary arterial hypertension: cautious hope in a deadly disease.

Advances have brought cautious hope for patients with this progressive and deadly disease. Intravenous prostanoids are still the most effective long-term medications, but oral options are available for select patients who are closely monitored. General internists and specialists in pulmonary, cardiac, and rheumatic diseases each have their role in managing these patients.