Characterization of Prostacyclin-associated Leg Pain in Patients with Pulmonary Arterial Hypertension.

RATIONALE: Prostacyclin-associated leg pain is a potentially debilitating adverse effect of prostacyclin therapy for patients with pulmonary arterial hypertension (PAH). However, to our knowledge, this entity has not been systematically studied. OBJECTIVES: To characterize the clinical features and metabolic risk factors for prostacyclin-associated leg pain. METHODS: At one academic medical center, we assembled and analyzed a case series of patients with PAH and prostacyclin-associated leg pain. MEASUREMENTS AND MAIN RESULTS: Over a period of 2 years, we identified 11 patients with PAH and prostacyclin-associated leg pain who agreed to participate in this study. Subjects underwent a standardized clinical evaluation, electrodiagnostic assessment, and serologic screen for metabolic causes of peripheral neuropathy. All 11 patients were female; their mean (SD) age was 50 (±9) years; their median (interquartile range) PAH duration was 56 (20-96) months; and their prostacyclin therapy duration was a median (interquartile range) of 20 (14-36) months. All patients reported leg pain beginning soon after prostacyclin initiation and varying with dose. All described a neuropathic pain in a symmetric, distal, stocking distribution. Neurologic examination revealed a sensory, small-fiber, predominantly peripheral neuropathy in seven (78%) patients. Results of autonomic reflex testing and thermoregulatory sweat testing were abnormal in 82% and 90% of patients, respectively, suggesting small-fiber neuropathy. Serologic evaluation identified a new, previously unrecognized contributor to neuropathy in eight (73%) patients, including vitamin B12 deficiency in six (55%), uncompensated hypothyroidism in three (27%), and diabetes mellitus in one (9%). CONCLUSIONS: Chronic prostacyclin-associated leg pain is associated with a small-fiber neuropathy. Treatable metabolic contributors (vitamin B12 deficiency, thyroid dysfunction, or diabetes) appear to be common possible "second hits" that may be underrecognized. We recommend screening for possible metabolic contributors in patients who have otherwise unexplained leg pain in the setting of PAH and current or anticipated prostacyclin therapy.

Relationship of myocardial perfusion imaging findings to outcome of patients with heart failure and suspected ischemic heart disease.

BACKGROUND: We retrospectively identified heart failure patients with suspected ischemic heart disease who underwent myocardial perfusion imaging (MPI) to examine the relationship of MPI findings to subsequent patient outcomes. METHODS: The study group consisted of 336 patients with heart failure, left ventricular ejection fraction <45%, and suspected ischemic heart disease who underwent MPI during the period of January 1991 to December 31, 1997. Patients were divided in 3 subgroups: group A (n = 137), large fixed perfusion defects; group B (n = 77), large reversible perfusion defects; and group C (n=122), absence of a large reversible or fixed perfusion defect. RESULTS: Overall, the 5-year mortality rate was high at 49.2% +/- 3.1%. Mortality was significantly different (P =.009) among the 3 subgroups. Groups A and B had a similar 5-year mortality rates >50%. Group C had a relatively better, but still substantial 5-year mortality rate of 40%. The overall revascularization rate was low (9.7% in 5 years). CONCLUSION: These results indicate a high 5-year mortality rate in patients with large myocardial perfusion defects (fixed or reversible) and presumably an ischemic etiology for their heart failure. Patients with no large or absent perfusion defects had more favorable survival outcomes.

Long-term outcome and the use of revascularization in patients with heart failure, suspected ischemic heart disease, and large reversible myocardial perfusion defects.

BACKGROUND: The potential role of coronary revascularization in the management of patients with congestive heart failure and suspected ischemic heart disease remains to be defined. Myocardial perfusion imaging can identify patients with ischemic heart disease as the etiology for left ventricular dysfunction who might benefit from revascularization. METHODS: We retrospectively identified heart failure patients with suspected ischemic heart disease who had large reversible perfusion defects to determine their long-term outcome and rate of revascularization. The study group consisted of 77 patients with congestive heart failure, left ventricular ejection fraction <45%, and suspected ischemic heart disease who underwent myocardial perfusion imaging during the period of January 1, 1991, to December 31, 1997, and had large reversible perfusion defects. RESULTS: The 5-year mortality rate was 57.6%. The revascularization rate was only 13% for 5 years of follow-up. The number of patients undergoing revascularization was too small to assess its impact on outcome. CONCLUSION: These results indicate a high 5-year mortality rate and a low utilization of coronary revascularization in patients with heart failure and large reversible perfusion defects. The low rate of revascularization reflects at least in part the absence of the generalizability of the existing literature to the optimal means of treating patients with heart failure and myocardial ischemia and points to the need for a randomized clinical trial.