Exercise Echocardiography Predicts Future Development of Pulmonary Hypertension in a High-risk Cohort of Patients with Systemic Sclerosis.

OBJECTIVE: To evaluate whether a positive exercise echocardiogram (EE) predicts future development of pulmonary arterial hypertension (PAH) in a high-risk cohort of patients with systemic sclerosis (SSc). METHODS: Patients with SSc with features associated with an increased risk for PAH were recruited into a prospective, observational cohort. All patients underwent clinical assessment and EE. A positive EE was defined as an increase of ≥ 20 mmHg in the right ventricular systolic pressure with exercise. All patients with positive EE underwent right heart catheterization (RHC). RESULTS: The study included 85 patients. In the positive EE cohort, 10 of 43 patients (23%) developed resting pulmonary hypertension (PH) on RHC over a mean 4-year followup period [4 with PAH, 5 with pulmonary venous hypertension (PVH), and 1 with PH associated with interstitial lung disease]. In the persistently negative EE cohort, only 3 of 42 patients (7%) developed resting PH (1 PAH, 2 PVH; p = 0.04). Of the remaining 33 patients in the positive EE group who did not develop resting PH, 22 (67%) had a persistently positive EE over an average 5-year followup period. CONCLUSION: In this high-risk cohort of patients with SSc, a positive EE may predict the future development of resting PH. In addition, a majority of patients may have a persistently positive EE for years without progression to resting PH. Finally, a consistently negative EE may identify patients at low risk for future PH.

Plasma levels of retinoids, carotenoids and tocopherols in patients with mild obstructive sleep apnoea.

BACKGROUND AND OBJECTIVE: OSA is associated with increased incidence of cardiovascular diseases. Pathogenic mechanisms of vascular diseases include thickened vascular walls due to the increased number of smooth muscle cells (SMC). Retinoic acid (RA) suppresses the growth of SMC, and reduced retinoid levels are associated with vascular diseases. Oxidant signalling promotes SMC growth, thus antioxidant levels may also influence the development of cardiovascular diseases. The present study tested the hypothesis that plasmas from OSA patients contain altered levels of retinoids, carotenoids and tocopherols. METHODS: Plasma samples were taken before and after sleep from patients with OSA (mostly mild) without known cardiovascular diseases and from control subjects. Levels of retinoids, carotenoids and tocopherols were measured using sensitive gas chromatograph-mass spectrometry and high pressure liquid chromatography methods and total antioxidant capacity was assessed fluorometrically. RESULTS: Results showed that plasmas from patients with OSA had significantly lower retinyl palmitate and 9-cis RA compared with control subjects, while levels of retinol, all-trans RA and 13-cis RA were indifferent. All-transbeta-carotene and 9-cisbeta-carotene were also lower in OSA patients. Levels of all-trans RA and 13-cis RA in OSA patients were reduced after sleep compared with before sleep. OSA patients showed significantly higher delta-tocopherol compared with controls. Treatment of cultured human vascular SMC with post-sleep OSA patient plasmas promoted cell growth, but not in controls. CONCLUSIONS: Mild OSA exhibits altered levels of specific retinoids, carotenoids and tocopherols, which may be markers and/or mediators for the increased susceptibility of patients to vascular diseases.

Exercise-induced pulmonary arterial hypertension in patients with systemic sclerosis.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is the most common cause of scleroderma-related deaths. New medications for PAH patients make it necessary to identify patients with high risk factors for PAH. This study looks at the use of an exercise echocardiogram in identifying patients who may have PAH and may be candidates for early therapeutic intervention. METHODS: This study included 54 scleroderma patients with symptoms suggesting they were at risk for pulmonary hypertension, including dyspnea on exertion, diffusing capacity of the lung for carbon monoxide (Dlco)<60% of predicted, FVC<70% of predicted, percentage of predicted FVC/percentage of predicted Dlco (FVC%/Dlco%) ratio>1.6, or resting right ventricular systolic pressure (RVSP)>35 mm Hg. The exercise echocardiogram protocol involved the standard Bruce stress echocardiogram protocol with remeasurement of the RVSP within 1 min of stopping exercise. A positive exercise test result was defined as an increase of at least 20 mm Hg in the RVSP with exercise. Right-heart catheterization with exercise was performed in those with a positive exercise test result. RESULTS: Resting mean RVSP was 34.5 mm Hg, which increased to 51.4 mm Hg with exercise; 44% had at a positive exercise test result, which correlated with a low Dlco, high FVC%/Dlco% ratio (p<0.001), a positive anti-centromere antibody, and RVSP>35 mm Hg (p<0.05). PAH was confirmed by right-heart catheterization in 81% of patients: 19% at rest and 62% of patients with exercise. CONCLUSIONS: Exercise-induced pulmonary hypertension is a common finding in patients at high risk for PAH. This may be a sensitive way to identify patients with early PAH. Long-term follow-up and early treatment should be studied in these patients.

End-of-life decision making in 42 patients with amyotrophic lateral sclerosis.

OBJECTIVE: To determine when end-of-life issues were discussed with patients afflicted with amyotrophic lateral sclerosis (ALS). METHODS: This was a retrospective analysis of ALS patients referred to the neuromuscular clinic at Georgetown University Hospital. Patients were seen by a pulmonologist and a neurologist at the initial diagnosis or referral, and every 2-3 months thereafter. End-of-life discussions were addressed at each visit. Other variables recorded included the amount of time afflicted with ALS, serial pulmonary function test results, and the subjective level of bulbar dysfunction. RESULTS: We saw 43 patients (age range 39-94 y) between June 1999 and September 2004. One patient was on a ventilator at the initial visit, and was therefore excluded from the study. Discussion about the patients' end-of-life care preferences were initiated at the first pulmonary visit with 40 patients. With 2 patients, end-of-life decisions were discussed at the second office visit. Twenty-five patients chose do-not-resuscitate and do-not-intubate (DNR/DNI) orders after the initial end-of-life discussion with the pulmonologist. Five other patients chose DNR/DNI orders during subsequent clinic visits. Four patients were still undecided at their last clinic visit. Six patients were lost to follow-up before a decision was made. Two patients requested full ventilatory support. Both the forced vital capacity and the level of bulbar dysfunction were not statistically different between the patients who chose DNR/DNI and the patients who were either undecided or requested full ventilatory support. CONCLUSIONS: Decisions about end-of-life care are often delayed in patients with ALS. These patients' final decisions seem to be independent of their level of respiratory insufficiency or bulbar function, and most related to the physician addressing end-of-life care decisions in a timely manner.

Outcome and code status of lung cancer patients admitted to the medical ICU.

OBJECTIVES: To determine the outcome of lung cancer patients admitted to the medical ICU (MICU), to examine their code status at MICU admission and prior to death, and to determine which subspecialty physician was responsible for the change in code status. DESIGN: Retrospective chart review study. SETTING: A 19-bed MICU in a tertiary-care university hospital. PATIENTS: Consecutive patients with a diagnosis of lung cancer admitted to the MICU from July 2002 to June 2004. MEASUREMENTS AND MAIN RESULTS: Forty-seven patients with a diagnosis of lung cancer accounted for 53 MICU admissions. Mean (+/- SD) age at MICU admission was 65 +/- 10 years. Sixty-six percent were male. Eighty-three percent had non-small cell lung cancer (NSCLC); 64% of these were stage IV NSCLC. The most common organ system implicated on MICU admission was pulmonary, with 38% of patients presenting with pneumonia. Overall MICU mortality was 43%, and in-hospital mortality was 60%. Patients who required mechanical ventilation or had more advanced lung cancer stage had the worst prognosis, with mortality rates of 74% and 68%, respectively. Seventy-four percent of patients were "full code" at MICU admission. Subsequently, the code status was changed to "do not resuscitate" in 49% of these cases. The pulmonary/critical care physician was involved in this change 96% of the time and was the sole physician in 65% of cases. CONCLUSIONS: This study confirms that patients with lung cancer admitted to the MICU have a high mortality. Despite this, the majority of patients are full code on MICU admission. Pulmonary/critical care physicians play an important role in the end-of-life decision making of lung cancer patients admitted to the MICU, perhaps because of their availability in the MICU and also because of their sense of responsibility in maintaining and withdrawing life support.