Vitamin D(2) analog (Paricalcitol; Zemplar) for treatment of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is often a pernicious disorder associated with pancytopenia in the elderly; therapeutic approaches need to balance their toxicities versus the symptoms of the disease. 1,25(OH)(2)-Vitamin-D(3) [1,25(OH)(2)D(3)] inhibits proliferation and induces differentiation of leukemic cells in vitro. Small clinical trials of 1,25(OH)(2)D(3) have shown modest efficacy in MDS; hypercalcemia prevented the administration of doses that have been shown to be effective in vitro. Paricalcitol [19-nor-1,25(OH)(2)D(2), Zemplar] has been approved by the FDA for treatment of secondary hyperparathyroidism. This Vitamin D analog is unique because it has little hypercalcemic potential; but in vitro, it has strong anti-leukemic activity. We conducted a clinical trial of oral paricalcitol to 12 MDS patients whose disease varied between an IPSS of low to high. Drug was well-tolerated in all patients. No responses were observed according to international working group (IWG) criteria. However, the platelet count of 1 of the 12 individuals rose from 53,500 to 120,000/microl blood over 5 weeks; but the patient succumbed to a fatal fungal infection. In summary, paricalcitol given as a single agent to MDS patients is therapeutically not very efficacious; further trials of the Vitamin D analog should be considered in combination with other approaches.

A novel finding to assess ischemia in pacing stress echocardiography (PASE).

BACKGROUND: Normalization of heart rate post-pacing stress echocardiography (PASE) could enable evaluation of effect of ischemia on diastolic function. METHODS: We examined the effect of pacing on left ventricular (LV) filling in 55 patients who underwent a transesophageal PASE. Pulse wave Doppler of mitral inflow was obtained at baseline and during transition from peak pacing to up to three beats immediate post pacing. RESULTS: Thirty-four patients (62%; 62 +/- 12 years) had normal (NL) PASE, wall motion score index (WMSI) 1 +/- 0 at baseline and during PASE. Sixteen patients (29%; 64 +/- 12 years) had ischemic (ISCH) PASE, WMSI 1.07 +/- 0.08 at baseline and 1.40 +/- 0.21 during PASE. Five patients (9%; 81 +/- 5 years) had abnormal (ABN) PASE, WMSI 1.55 +/- 0.34 at baseline and 1.55 +/- 0.34 during PASE. The ABN group had the most pronounced decrease in deceleration time (DT) seen in all three post-PASE beats (221 +/- 29 ms at baseline vs. 145 +/- 46, 144 +/- 26 and 144 +/- 18 ms at beats 1, 2, and 3, P < 0.005 from baseline for all). The DT reduced significantly at post-PASE beat 1 from baseline (234 +/- 45 ms vs. 158 +/- 36 ms, P = 0.02) in the ISCH group, whereas no significant change in DT occurred in the NL group (239 +/- 74 ms vs. 222 +/- 58 ms, P = 0.14) at beat 1. CONCLUSION: In ISCH and ABN ventricles the duration of early diastolic filling decreased post-pacing. This new finding of a shortened deceleration time (DT) may be a marker of an ischemic response in PASE reflecting abnormal LV compliance.

Stress echocardiography in octogenarians: transesophageal atrial pacing is accurate, safe, and well tolerated.

The feasibility and diagnostic accuracy of transesophageal pacing stress echocardiography for detection of inducible myocardial ischemia were evaluated in 161 patients 80 years of age or older (mean 84 +/- 3.9, range 80-97). The pacing time was 5.5 +/- 2.5 minutes with a total test time of 37 +/- 7 minutes. The mean achieved heart rate was 96 +/- 7% (83%-121%) of maximum predicted with an average rate pressure product of 21,560 +/- 5175 beats/min x mm Hg. There were minor adverse events in 8% of cases and no major complications occurred. Patient acceptance was high. When compared with myocardial single photon emission computed tomography, pacing stress echocardiography had a sensitivity of 89% and a specificity of 93% for the detection of myocardial ischemia, and 91% agreement (kappa = 0.80, P < .001). We demonstrate that pacing stress echocardiography is safe and accurate for detection of myocardial ischemia and, thus, a reliable substitute to exercise and pharmacologic stress testing in octogenarians.