Digital assessment of the epicardial electrocardiogram: novel methodology for a core laboratory for clinical studies.

BACKGROUND: The epicardial electrocardiogram (ECG) is a sensitive marker for cardiac ischemia and has been used as a measure of ischemia in clinical trials. We sought to examine the utility of a central ECG laboratory for determining ischemic-type ST-segment shifts from epicardial ECG recordings obtained from multiple clinical sites. HYPOTHESIS: We speculated that an operator-assisted digital ECG core laboratory is feasible, reliable, and efficient, with the ability for rapid and accurate interpretation of the epicardial ECG. METHODS: The epicardial ECG was recorded via an angioplasty guidewire placed in a coronary artery of a patient undergoing angioplasty. Site investigators visually determined the time-to-onset of 0.1 and 0.3 mm ST-segment elevation, and the maximal ST-segment elevation during balloon inflation, and then compared the measurements with those made at an operator-assisted digital ECG core laboratory. RESULTS: Agreement between the two methods occurred in 78% of the time-to-onset measurements, but in only 39% of the maximal ST-segment measurements. Overall, the visual measurements of the clinical investigators of time-to-onset differed from the digital core laboratory by 11.8 +/- 11.6 s for 0.1 mV, and 15.8 +/- 20.6 s for 0.3 mV. Recorded maximal ST-segment shifts differed by a mean of 0.47 +/- 0.69 mV. CONCLUSION: The magnitude of inconsistency between the ECG core laboratory results using an operator-assisted digital method and the interpretations of clinical investigators using manual caliper-type analysis was surprisingly large. These results support the need for an ECG core laboratory in clinical trials where ECG ST-segment shifts are used as a response variable.

Plasma volume changes with an acute bout of high-intensity exercise in men with chronic congestive heart failure secondary to coronary artery disease.

We assessed plasma volume changes at peak exercise in 17 nonedematous men with chronic congestive heart failure due to coronary artery disease. Our findings suggest that acute exercise is associated with transient decreases in plasma and blood volume in these patients, similar in magnitude to those reported for healthy adults at peak exercise.

Effects of intermittent transdermal nitroglycerin on occurrence of ischemia after patch removal: results of the second transdermal intermittent dosing evaluation study (TIDES-II).

OBJECTIVES: We sought to evaluate the effects of intermittent transdermal nitroglycerin (TD-NTG) on the occurrence of ischemia during patch-off hours in patients with stable angina pectoris receiving a beta-adrenergic blocking agent or calcium antagonist, or both. BACKGROUND: The current recommendations for the use of intermittent TD-NTG may be associated with the occurrence of rebound ischemia. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, crossover trial with three study periods. Tolerability to TD-NTG was assessed in Period I. Seventy-two patients were assigned to receive either double-blind transdermal placebo or maximally tolerated TD-NTG for 2 weeks (Period II) and were then crossed over to the alternative treatment for another 2 weeks (Period III). The patients were instructed to apply medication daily at 8 AM, to remove it at 10 PM and to note symptoms and sublingual nitroglycerin (SL-NTG) use in a diary. The occurrence of ischemia was assessed from patient-perceived angina, symptom-limited exercise treadmill test (ETT) and 48-h ambulatory electrocardiographic (AECG) monitoring. RESULTS: Transdermal NTG (0.2 to 0.4 mg/h) significantly reduced the magnitude of ST segment depression at angina onset during ETT compared with placebo. Total angina frequency was not significantly different between TD-NTG (mean [+/-SD] 3.2 +/- 4.2) and placebo (3.3 +/- 5.2). During patch-off hours, angina frequency increased with TD-NTG (1.1 +/- 2.1) compared with placebo (0.7 +/- 1.6) (p = 0.03). Similar trends for an increase in ischemia after TD-NTG were also observed from AECG analyses. Specifically, ischemia frequency tended to be lower during patch-off hours for placebo than with TD-NTG (0.05 +/- 0.09 vs. 0.08 +/- 0.20 episodes/h, respectively, p = 0.08), even though frequency of ischemia tended to be higher during patch-on hours for placebo than with TD-NTG (0.12 +/- 0.19 vs. 0.07 +/- 0.15 episodes/h, respectively, p = 0.11). During placebo, ischemia frequency decreased 58% (patch-on to patch-off, p = 0.01) compared with a 14% increase with TD-NTG. These changes attenuate the usual circadian variation in ischemia. CONCLUSIONS: An increase in ischemia frequency during patch-off hours after use of intermittent TD-NTG was perceived by patients, and this subjective finding was supported by a corresponding trend for AECG ischemia to increase during these same hours.