Tuhin K. Chaudhuri

Right ventricular infarction: Identification by hemodynamic measurements before and after volume loading and correlation with noninvasive techniques

To evaluate the potential occurrence of right ventricular infarction, 53 patients with acute inferior transmural myocardial infarction were studied within 36 hours of symptoms by right heart catheterization, equilibrium radionuclide angiography and two-dimensional echocardiography. Technetium-99m pyrophosphate myocardial scintigraphy was performed 3 days after the onset of symptoms. The hemodynamic standard for right ventricular infarction was defined as both a right atrial pressure of 10 mm Hg or more and a right atrial/pulmonary artery wedge pressure ratio of 0.8 or more. Eight (15%) of the 53 patients had hemodynamic measurements at rest characteristic of right ventricular infarction, and 6 (11%) additional patients met these criteria after volume loading (p less than 0.05). Nineteen (37%) of the 51 patients who had radionuclide angiography had right ventricular dysfunction manifested by both a reduced right ventricular ejection fraction (less than 40%) and right ventricular regional wall motion abnormalities (akinesia or dyskinesia). An abnormal radionuclide angiogram was observed in 12 of 13 patients with hemodynamic measurements indicating right ventricular infarction. In 12 patients with an abnormal radionuclide angiographic study, right ventricular ejection fraction improved 6 to 12 weeks after infarction (27 +/- 7 to 36 +/- 9%, p less than 0.01). Twenty-two (49%) of the 45 patients with adequate two-dimensional echocardiograms had a right ventricular regional wall motion abnormality. An abnormal two-dimensional echocardiogram was seen in 9 of 11 patients with hemodynamic measurements characteristic of right ventricular infarction. Technetium-99m pyrophosphate scintigraphy was positive for right ventricular infarction in 3 of 12 patients who had hemodynamic measurements indicating right ventricular infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Limitations of thallium-201 myocardial perfusion scintigrams.

SUMMARY The reliability of myocardial perfusion scintigrams with thallium-201 (201TI) for detecting areas of hypoperfusion was assessed in 16 closed-chest dogs. Variable areas of ischemia were produced either by occluding or stenosing the left anterior descending coronary artery. Cardiac scintigrams taken in four projections were compared with regional myocardial perfusion maps. Segmental concentrations and segmental perfusions were quantitated by counting the emissions from 201TI and the microspheres in each of 96 segments of the left ventricle. In addition, studies with a phantom were performed. The results indicate: 1) The emissions from 201TI and from microspheres correlated well in ischemic segments (r = 0.93 ± SE 0.02). 2) Seven of twelve ischemic hearts had definitely abnormal scintigrams and in each of these the hypoperfused zone was greater than 4.9 grams and perfusion was decreased by more than 45%. 3) In the phantom, abnormal scintigrams could be detected in the presence of lesser deficits than in the dogs. The limitation of the thallium perfusion scintigrams will be the inconsistent detection of small perfusion deficits.

Short- and long-term efficacy of high-dose oral diltiazem for angina due to coronary artery disease: a placebo-controlled, randomized, double-blind crossover study.

The effects of oral diltiazem (360 mg/day) on exercise tolerance, left ventricular performance, and plasma lactate and catecholamine levels were studied in 13 patients with atherosclerotic coronary artery disease in a placebo-controlled, randomized, double-blind protocol. Exercise duration to the onset of ischemic ST segment depression, time to angina pectoris, and time to peak exercise improved by 120, 174, and 144 sec, respectively (p less than .0001). Left ventricular ejection fraction, as determined by radionuclide angiography, increased in patients at rest from 52 +/- 11% (mean +/- SD) during placebo therapy to 58 +/- 11% during diltiazem therapy (p less than .001); at peak exercise ejection fraction increased from 44 +/- 11% during placebo treatment to 52 +/- 15% during diltiazem therapy (p less than .01). The mean plasma norepinephrine level in patients at rest increased from 498 +/- 221 pg/ml during placebo treatment to 667 +/- 272 pg/ml during diltiazem therapy (p less than .05). Resting standing blood pressure and supine and standing diastolic blood pressures decreased significantly with diltiazem. In all 10 patients followed over a long term, oral diltiazem caused persistent improvement in exercise performance at 12 to 20 weeks, without evidence of placebo effects. Thus, diltiazem is highly effective in divided doses of 360 mg/day for the therapy of chronic angina pectoris due to coronary artery disease.

Noninvasive quantitation of valvular regurgitation by gated equilibrium radionuclide angiography.

R-wave synchronous equilibrium radionuclide angiography (RNA) is a noninvasive method that provides time-activity curve count information proportional to ventricular volumes and is used for relative volume comparisons within the left or right ventricle to derive the ejection fraction. Comparison of the ventricular count output between both ventricles may permit quantitation of the relative amount of valvular regurgitation, i.e., the regurgitant fraction. We performed resting gated RNA in 30 consecutive patients undergoing cardiac catheterization and quantitative contrast ventriculography for aortic or mitral valvular regurgitation. RNA regurgitant fraction correlated well with cardiac catheterization regurgitant fraction (r 0.85). In 11 patients imaged before and 1-4 months after successful valve replacement, the regurgitant fraction declined from 0.68 ± 0.11 to −0.09 ± 0.13 (p < 0.001). In 20 control patients without valvular regurgitation, the calculated regurgitant fraction did not exceed 0.20. We conclude that valvular regurgitation may be accurately detected, quantitated and followed serially after therapeutic intervention using gated RNA.

Phase I and Pharmacokinetic Study of Pemetrexed Administered Every 3 Weeks to Advanced Cancer Patients With Normal and Impaired Renal Function

PURPOSE This phase I study was conducted to determine the toxicities, pharmacokinetics, and recommended doses of pemetrexed in cancer patients with normal and impaired renal function. PATIENTS AND METHODS Patients received a 10-minute infusion of 150 to 600 mg/m2 of pemetrexed every 3 weeks. Patients were stratified for independent dose escalation by measured glomerular filtration rate (GFR) into four cohorts ranging from > or = 80 to less than 20 mL/min. Pemetrexed plasma and urine pharmacokinetics were evaluated for the first cycle. Patients enrolled after December 1999 were supplemented with oral folic acid and intramuscular vitamin B12. RESULTS Forty-seven patients were treated with 167 cycles of pemetrexed. Hematologic dose-limiting toxicities occurred in vitamin-supplemented patients (two; 15%) and non-supplemented patients (six; 18%), and included febrile neutropenia (four patients) and grade 4 thrombocytopenia (two patients). Nonhematologic toxicities included fatigue, diarrhea, and nausea, and did not correlate with renal function. Accrual was discontinued in patients with GFR less than 30 mL/min after one patient with a GFR of 19 mL/min died as a result of treatment-related toxicities. Pemetrexed plasma clearance positively correlated with GFR (r2 = 0.736), resulting in increased drug exposures in patients with impaired renal function. With vitamin supplementation, pemetrexed 600 mg/m2 was tolerated by patients with a GFR > or = 80 mL/min, whereas patients with a GFR of 40 to 79 mL/min tolerated a dose of 500 mg/m2. CONCLUSION Pemetrexed was well tolerated at doses of 500 mg/m2 with vitamin supplementation in patients with GFR > or = 40 mL/min. Additional studies are needed to define appropriate dosing for renally impaired patients receiving higher dose pemetrexed with vitamin supplementation.

Clinical and prognostic importance of persistent precordial (V1-V4) electrocardiographic ST segment depression in patients with inferior transmural myocardial infarction.

Forty-three consecutive patients with acute inferior transmural myocardial infarction but no history or electrocardiographic evidence of prior myocardial infarction were evaluated prospectively to assess the clinical and prognostic importance of persistent precordial (V1-V4) ST segment depression. Patients were evaluated within 24 hr of admission by history, physical examination, cardiac enzyme levels, right heart catheterization, and radionuclide angiography; all were followed for 1 year. Ten of the 43 patients (group I) had persistent anterior precordial ST segment depression, defined as 1 mm or greater in one or more precordial leads (V1-V4) 24 hr after admission to the coronary care unit, and 33 patients (group II) did not. Clinical variables that differed between groups I and II, respectively, included mean age (67 +/- 9 [+/- 1 SD] vs 59 +/- 8 years; p less than .01), incidence of Killip class II to IV (100% vs 33%; p less than .001), and average peak creatine kinase concentration (2878 +/- 1139 vs 1511 +/- 1034 IU/liter; p less than .001). Hemodynamic differences between groups I and II included a higher pulmonary arterial wedge pressure (19 +/- 4 vs 11 +/- 5 mm Hg; p less than .001) and a lower cardiac index (2.0 +/- 0.5 vs 2.6 +/- 0.7 liters/min/m2; p less than .05). An evaluation of left ventricular ejection fraction and wall motion index by radionuclide angiography showed that group I had a lower ejection fraction (44 +/- 11% vs 53 +/- 10%; p less than .05) and higher wall motion index (1.7 +/- 0.4 vs 1.4 +/- 0.3; p less than .05) compared with group II.(ABSTRACT TRUNCATED AT 250 WORDS)

First transit and equilibrium radionuclide angiography in patients with inferior transmural myocardial infarction: Criteria for the diagnosis of associated hemodynamically significant right ventricular infarction

To define radionuclide criteria for identifying hemodynamically significant right ventricular infarction, 33 consecutive men with inferior transmural infarction were evaluated prospectively by right heart catheterization and first transit and equilibrium radionuclide angiography within 36 hours of the onset of symptoms. Hemodynamically significant right ventricular infarction was present in 6 of the 33 patients (Group I); the remaining 27 patients did not demonstrate the hemodynamics characteristic of right ventricular infarction (Group II). A right ventricular ejection fraction of less than 40% separated Group I and Group II patients by equilibrium (p = 0.003) but not by first transit (p = NS) radionuclide angiography. However, a right ventricular ejection fraction of less than 35% separated Group I and II patients by both techniques (p = 0.02 and p = 0.005, respectively). The presence of a right ventricular regional wall motion abnormality on either first transit or equilibrium radionuclide angiograms separated Group I and II patients (p less than 0.001). The combination of both a right ventricular ejection fraction of less than 40% and a regional wall motion abnormality separated Group I and II patients using either equilibrium (p less than 0.001) or first transit (p = 0.02) radionuclide angiography. It is concluded that in patients with acute inferior transmural myocardial infarction, a right ventricular regional wall motion abnormality alone or in combination with a right ventricular ejection fraction of less than 40% by either first transit or equilibrium radionuclide angiography is a useful criterion for establishing the presence of hemodynamically significant right ventricular infarction, while its absence argues against the diagnosis of right ventricular infarction.

Two Drug Interaction Studies Evaluating the Pharmacokinetics and Toxicity of Pemetrexed When Coadministered with Aspirin or Ibuprofen in Patients with Advanced Cancer

Purpose: Pemetrexed is an antimetabolite that is structurally similar to methotrexate. Because nonsteroidal anti-inflammatory drugs (NSAID) impair methotrexate clearance and increase its toxicity, we evaluated the pharmacokinetics and toxicity of pemetrexed when coadministered with aspirin or ibuprofen in advanced cancer patients. Experimental Design: In two independent, randomized, crossover drug interaction studies, cancer patients with a creatinine clearance (CrCl) ≥60 mL/min received an NSAID (aspirin or ibuprofen) with either the first or the second dose of pemetrexed (cycle 1 or 2). Pemetrexed (500 mg/m2) was infused i.v. on day 1 of a 21-day cycle, and all patients were supplemented with oral folic acid and i.m. vitamin B12. Aspirin (325 mg) or ibuprofen (400 mg; 2 × 200 mg) was given orally every 6 hours, starting 2 days before pemetrexed administration, with the ninth and final dose taken 1 hour before infusion. Pemetrexed pharmacokinetics with and without concomitant NSAID treatment were compared for cycles 1 and 2. Results: Data from 27 patients in each study were evaluable for the analysis of pemetrexed pharmacokinetics. Coadministration of aspirin did not alter pemetrexed pharmacokinetics; however, ibuprofen coadministration was associated with a 16% reduction in clearance, a 15% increase in maximum plasma concentration, and a 20% increase in area under the plasma concentration versus time curve but no significant change in Vss compared with pemetrexed alone. No febrile neutropenia occurred in any patient, and no increase in pemetrexed-related toxicity was associated with NSAID administration. Conclusions: Pemetrexed (500 mg/m2) with vitamin supplementation is well tolerated and requires no dosage adjustment when coadministered with aspirin (in patients with CrCl ≥60 mL/min) or ibuprofen (in patients with CrCl ≥80 mL/min).

Resolution of Stress-Induced Myocardial Ischemia During Aggressive Medical Therapy as Demonstrated by Single Photon Emission Computed Tomography Imaging

A 50-year-old man with typical Canadian Cardiovascular Class III angina pectoris had coronary angiography that demonstrated an 80% mid-left anterior descending coronary artery stenosis. …

Autoradiographic studies of distribution in the liver of 198Au and 99mTc sulfur colloids

There are observable differences in the way in which the liver handles 198Au and 99mTc-sulfur colloids. Studies were made with serial autoradiography following intravenous injection of these two colloids into mice. 198Au colloid passes through three distinct stages of phagocytosis by Kupffers cells. In sharp contrast, 99mTc-sulfur colloid does not.