Enhanced prognostic stratification of patients with left ventricular hypertrophy with the use of single-photon emission computed tomography

BACKGROUND: Patients with left ventricular hypertrophy (LVH) are at increased risk of future cardiovascular events. Little is known about risk stratification of these patients with the use of myocardial perfusion imaging. This study sought to assess the prognostic stratification of patients with LVH by using myocardial perfusion single-photon emission computed tomography (SPECT). METHODS AND RESULTS: We studied 633 consecutive patients with electrocardiographic evidence of LVH who underwent dual isotope myocardial perfusion SPECT (rest thallium 201/stress technetium 99m sestamibi) and were followed up for a mean period of 22 +/- 7 months. During the follow-up period, 67 events (35 cardiac deaths and 32 nonfatal myocardial infarctions) occurred (6% annual event rate). The results of the perfusion scan significantly risk-stratified the population; patients with normal scans had a low rate of nonfatal myocardial infarction and cardiac death (<1% per year of follow-up). The rates of cardiac events increased significantly as a function of the scan result: 4.9% in patients with mildly abnormal scans and 10. 3% in moderately to severely abnormal scans. Cox proportional hazards analysis demonstrated that after adjusting for pretest likelihood of coronary artery disease (the most predictive clinical variable; chi(2) = 15.5, P <.001), summed stress score (the most predictive nuclear variable; chi(2) = 18, P <.0001) added significant incremental prognostic information (global chi(2) increased from 15.5 to 36; P <.001). CONCLUSIONS: In patients with LVH with an overall high cardiac event rate, SPECT provided enhanced stratification by adding significant incremental prognostic information over clinical and historic variables.     

Gene transfer in lymphoid cells: expression of the Thy-1.2 antigen by Thy-1.1 BW5147 lymphoma cells transfected with unfractionated cellular DNA.

We have transferred the gene coding for the Thy-1.2 alloantigen into a Thy-1.1-bearing T-cell lymphoma. BALB/c thymocyte DNA, precipitated with calcium phosphate, was used to effect the transfer. We report the stable transformation of lymphoid cells by total cellular DNA. To our knowledge, this has not been previously reported. Transient expression of the transfected gene could be detected by flow cytofluorometry, and 5% (range, 1.5%-11%) of the recipient cells had Thy-1.2 antigen detectable on their surface 48 hr after transfer. "Stable" transformants were isolated by repeatedly selecting for cells expressing the Thy-1.2 antigen, by use of fluorescence-activated cell sorting or "panning." No metabolic selection was required. The transferred gene, detected by Southern blotting, encoded a product that is indistinguishable from the normal antigen by immunoprecipitation and NaDod-SO4/PAGE.     

Systemic lupus erythematosus-associated pulmonary hypertension: good outcome following sildenafil therapy

A 46-year-old woman with systemic lupus erythematosus (SLE) and concomitant severe pulmonary hypertension (PH) is described. Other secondary causes of PH including thromboembolism, phospholipid syndrome, valvular disease and interstitial pulmonary involvement were ruled out. Owing to her lack of clinical response to conventional therapy, sildenafil was begun at increasing doses up to 400 mg daily. Both clinical and hemodynamic improvement ensued. This appears to be the first clinical report of the use of sildenafil in SLE followed by resolution of severe PH.     

Correlation between electrocardiographic subtypes of anterior myocardial infarction and regional abnormalities of wall motion

BACKGROUND: Examination of the electrocardiogram is the most widely used means for diagnosis and early stratification of risk of acute myocardial infarction (AMI). The classical classification of the subtypes of anterior AMI is based on results of studies comparing the electrocardiograms recorded at various stages, mostly in the subacute or chronic stage of AMI, with autopsy findings. Reports regarding the correlation between electrocardiographic findings in the acute phase and regional abnormality of wall motion (AWM) detected by echocardiographic evaluation are sparse. OBJECTIVE: To investigate the relationship between the electrocardiographic and two-dimensional echocardiographic findings regarding patients with their first anterior AMI. DESIGN AND METHODS: We studied 58 patients, 44 men and 14 women of mean age 61.5 +/- 14.6 years, with their first anterior AMI who had undergone two-dimensional echocardiographic evaluation within 48 h of admission. Deviation of ST-segment trace from baseline was measured manually 0.06 s after the J point for all leads on the admission electrocardiogram. ST-segment elevation in the various leads was correlated to the incidence of regional AWM detected by echocardiography. RESULTS: ST-segment elevations > or = 0.1 mV in V1 leads were found for 21 (36.2%) patients. Basal anterior, basal anteroseptal, and basal septal AWM were seen more often for patients with than they were for patients without ST-segment elevation in V1 (57 versus 16%, P=0.003; 43 versus 13.5%, P=0.03; 43 versus 11%, P=0.01 respectively). In contrast to ST-segment elevation in lead V1, the only statistically significant difference in prevalence in the presence of regional AWM between patients with (n = 48) and without (n = 10) ST-segment elevation > or = 0.2 mV in lead V2 was in the inferoapical region (87.5 versus 40%; P=0.003). ST-segment elevation > or = 0.1 mV in leads aVL and V5 was found for 11 (19%) and 23 (40%) patients, respectively. There was no correlation between either lateral or apical regional AWM and the presence of ST-segment elevation in the anterolateral leads except for mid-lateral AWM, which was more often detected for patients with than it was for patients without ST-segment elevation in aVL leads (36.3 versus 6.4%, P=0.026). CONCLUSIONS: ST-segment elevation in lead V1 during the acute phase of anterior AMI is associated with a high incidence of regional AWM in the basal anterior, anteroseptal, and anterior regions, whereas ST-segment elevation in lead V2 is more often associated with AWM in the inferoapical region. ST-segment elevation in aVL leads is related to mid-lateral regional AWM.     

Acute hemodynamic effect of oral nifedipine in severe chronic congestive heart failure

The temporal hemodynamic effects of oral nifedipine after a single dose of 20 to 40 mg were evaluated in 11 patients with severe chronic congestive heart failure (left ventricular ejection fraction 0.22 +/- 0.7 [mean +/- standard deviation]). Nifedipine significantly reduced systemic vascular resistance, from 1,850 +/- 493 to 1,315 +/- 398 dynes s cm-5 at 1 hour (29%), to 1,410 +/- 246 at 3 hours and to 1,523 +/- 286 at 6 hours (p less than 0.05). Cardiac index increased 21%, from 2.07 +/- 0.46 to 2.51 +/- 0.83 liters/min/m2 at 1 hour, to 2.38 +/- 0.53 liters/min/m2 at 3 hours (p less than 0.05) and to 2.24 +/- 0.41 liters/min/m2 at 6 hours. The group response of stroke volume to nifedipine was smaller. A peak increase of 17% was seen 3 hours after initiation of therapy (22.6 +/- 7.2 versus 25.5 +/- 6.1 ml/m2). This difference did not reach statistical significance. Mean blood pressure declined significantly, from 94 +/- 20 to 80 +/- 13 mm Hg at 1 hour, to 83 +/- 15 mm Hg at 3 hours and to 86 +/- 17 mm Hg at 6 hours (p less than 0.05) and was associated with no significant change in heart rate. The marked decrease in blood pressure resulted in a decrease in rate-pressure product from 12,272 +/- 4,230 to 10,500 +/- 2,074 mm Hg/min at 1 hour, to 10,374 +/- 2,735 mm Hg/min at 3 hours and to 11,047 +/- 3,813 mm Hg/min at 6 hours (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Identification of a telomere-binding activity from yeast.

In yeast, the ends of the chromosomes (telomeres) terminate in repeated poly(C1-3A) sequences. We have identified a yeast activity that binds specifically to these poly(C1-3A) repeats. An agarose gel binding assay was used to detect and characterize this activity in cell extracts using both cloned telomere DNA and yeast genomic DNA as substrates. The activity appears to bind specifically to poly(C1-3A) sequences, despite their different primary sequences, yet does not bind specifically to telomeric repeats, such as poly(C4A2), poly(C4A4), and poly (C1-8T) from other lower eukaryotes.     

Incremental cost-effectiveness of exercise echocardiography vs. SPECT imaging for the evaluation of stable chest pain.

AIMS: Technological advances in cardiac imaging have led to dramatic increases in test utilization and consumption of a growing proportion of cardiovascular healthcare costs. The opportunity costs of strategies favouring exercise echocardiography or SPECT imaging have been incompletely evaluated. METHODS AND RESULTS: We examined prognosis and cost-effectiveness of exercise echocardiography (n = 4884) vs. SPECT (n = 4637) imaging in stable, intermediate risk, chest pain patients. Ischaemia extent was defined as the number of vascular territories with echocardiographic wall motion or SPECT perfusion abnormalities. Cox proportional hazard models were employed to assess time to cardiac death or myocardial infarction (MI). Total cardiovascular costs were summed (discounted and inflation-corrected) throughout follow-up. A cost-effectiveness ratio < Dollars 50,000 per life year saved (LYS) was considered favourable for economic efficiency. The risk-adjusted 3-year death or MI rates classified by extent of ischaemia were similar, ranging from 2.3 to 8.0% for echocardiography and from 3.5 to 11.0% for SPECT (model chi2 = 216; P < 0.0001; interaction P = 0.24). Cost-effectiveness ratios for echocardiography were < Dollars 20,000/LYS when the annual risk of death or MI was < 2%. However, when yearly cardiac event rate were > 2%, cost-effectiveness ratios for echocardiography vs. SPECT were in the range of Dollars 66,686-Dollars 419,522/LYS. For patients with established coronary disease (i.e. > or = 2% annual event risk), SPECT ischaemia was associated with earlier and greater utilization of coronary revascularization (P < 0.0001) resulting in an incremental cost-effectiveness ratio of Dollars 32,381/LYS. CONCLUSION: Health care policies aimed at allocating limited resources can be effectively guided by applying clinical and economic outcomes evidence. A strategy aimed at cost-effective testing would support using echocardiography in low-risk patients with suspected coronary disease, whereas those higher risk patients benefit from referral to SPECT imaging.