The current exercise tolerance test (ETT) criteria predominantly assess changes in ST-segment deviation (i.e., a systolic component of the cardiac cycle). Because diastolic dysfunction precedes that of systolic dysfunction during myocardial ischemia and most coronary flow is diastolic, the addition of electrocardiographic markers of diastolic time might improve the ETT sensitivity and specificity for detecting significant coronary artery disease. Among consecutive patients who had an ETT and subsequently underwent coronary angiography, we evaluated the diastolic time by assessing the TP and TQ segments and TP/RR and TQ/RR ratios in each ETT stage. Coronary artery disease was defined angiographically as significant (≥70% lumen occlusion), intermediate (>50% but <70% lumen occlusion), or nonsignificant (≤50% lumen occlusion). Of the 48 study patients, hypertension and hyperlipidemia appeared highly prevalent. TP, TQ, TP/RR, and TQ/RR correlated significantly with RR and changed with each ETT stage. Although TP and TQ were not significantly associated with significant coronary artery disease, TP/RR and TQ/RR proved to be, particularly beyond stage 2. When TQ/RR of ≤0.39 and TP/RR of ≤0.13 were used, their individual sensitivities and specificities were reasonably comparable to that of traditional ETT criteria (79% sensitivity and 44% specificity at our institution). Adding TQ/RR of ≤0.39 and/or TP/RR of ≤0.13 to existing ETT criteria improved its sensitivity to 100% and specificity to 86%. In conclusion, the addition of diastolic time indexes of TP/RR and TQ/RR significantly improved the overall ETT diagnostic value above the guideline-oriented, perhaps “traditional,” criteria for the diagnosis of myocardial ischemia. Such parameters should be widely investigated further for clinical accuracy and compatibility.
The exercise tolerance test (ETT) is 1 of the most commonly used noninvasive investigations to determine coronary artery disease (CAD) in the adult population. The Standard Bruce protocol and the Modified Bruce protocol (for deconditioned and elderly patients) are the most widely used ETT protocols, for which the results are principally dependent on exercise-induced ST-segment deviations on the electrocardiogram (ECG) per current guidelines recommended by the American College of Cardiology and American Heart Association. However, because ST-segment deviations, according to the myocardial ischemic cascade, occur only after systolic left ventricular dysfunction resulting from an “upstream” hemodynamically significant coronary artery occlusion, the use of such electrocardiographic predictors can rarely be as accurate as a more “upstream” assessment of this cascade. Because left ventricular diastolic dysfunction precedes that of systolic dysfunction during myocardial ischemia, it might be better to use electrocardiographic markers that actually represent diastole rather than systole, which often rely solely on ST-segment and T-wave changes. We thus evaluated the electrocardiographic markers that represent the diastolic period or time (DT), such as the TP and TQ segments toward predicting CAD in patients undergoing ETT and subsequent coronary angiography.
Methods
We retrospectively identified all consecutive, unselected patients who had an ETT at our tertiary care teaching hospital, Saint Vincent Hospital (Worcester, Massachusetts), from January 1, 2008 to December 31, 2009. The patients who did not subsequently undergo cardiac catheterization to determine the coronary anatomy were excluded. The patients with incomplete medical records and those with a history of coronary artery bypass grafting were also excluded.
The following variables were collected from the medical records: age, gender, medical history, baseline ECG, ETT data, and cardiac catheterization results. Established CAD risk factors per the American College of Cardiology/American Heart Association and Adult Treatment Panel III guidelines, including age (men ≥45 years, women ≥55 years or premature menopause without estrogen replacement therapy), family history of premature CAD (myocardial infarction or sudden death before 55 years old in a male first-degree relative and before 65 years old in a female first-degree relative), current cigarette smoking, hypertension (blood pressure >140/90 mm Hg or antihypertensive medication), high-density lipoprotein cholesterol <40 mg/dl, were also documented.
The baseline 12-lead ECGs at rest were recorded in the supine position using a Marquette 2000 electrocardiograph (Marquette Electronics, Milwaukee, Wisconsin) standardized at 25 mm/s and 10 mm/mV. The ECGs were independently evaluated for TP segment and TQ segment duration to the nearest 10 ms in the precordial leads. The measurements were determined visually by a blinded single read (R.V.) using a calibrated magnifying graticule (Pfizer Consumer Products Division, Pfizer, Morris Plains, New York) at fourfold magnification. The assessment was restricted to the precordial leads for standardization and ease of comparability because often, ST-segment changes that occur in inferior limb leads can reflect false-positive results and can be susceptible to limb motion artifacts. In addition, myocardial ischemic ST-segment changes are often most pronounced and commonly observed in the precordial leads. The TP and TQ segments were measured manually at rest (baseline supine), before testing (baseline upright), after testing (recovery supine), and during each stage of ETT (1 minute after onset of stage). The TP segment was defined as the beginning of the isoelectric TP baseline to the beginning of the P deflection, and the TQ segment was defined as the beginning of the isoelectric TP baseline to the beginning of the Q deflection of the QRS complex. To minimize heart rate variability, instead of relying solely on the TP and TQ segments, we also calculated the TP/RR and TQ/RR ratios.
CAD, as determined by angiographic coronary artery stenosis, was defined as significant (≥70% lumen occlusion), intermediate (>50% but <70% lumen occlusion), and nonsignificant (≤50% lumen occlusion) by visual assessment or quantitative analysis (i.e., “QCA analysis” of the arterial segment by board-certified interventional cardiologists who were unaware of the ETT results and study measurements). Statistical analysis was performed using the chi-square test (Statistical Package for Social Sciences, version 16.0, SPSS, Chicago, Illinois). A p value ≤0.05 was considered significant.
Results
During the study period, 2,125 consecutive patients underwent ETT for various presentations. Of those, 92 subsequently underwent cardiac catheterization for evaluation of myocardial ischemia. From that subset, 48 consecutive patients who met our inclusion criteria formed our final study sample. The mean interval between the ETT and cardiac catheterization was 1.32 months (median 0.36). Hypertension and hyperlipidemia were highly prevalent in this predominantly male cohort ( Table 1 ). Of the 48 patients, 41 (85.4%) had ≥2 risk factors per the American College of Cardiology/American Heart Association and Adult Treatment Panel III guidelines. including 35 (73%) in the high-risk age group. Of the 48 patients, 32 (59%) demonstrated a positive ETT result and 21 (44%) proved to have significant CAD ( Table 1 ).
| Variable | Value |
|---|---|
| Age (years) | 57.1 ± 12 |
| Men | 33 (69%) |
| Known history of coronary artery disease | 7 (15%) |
| Diabetes mellitus | 10 (21%) |
| Hypertension ⁎ | 33 (69%) |
| Hyperlipidemia † | 27 (56%) |
| Cigarette smoking | 8 (17%) |
| Alcohol use | 5 (10%) |
| Family history of premature coronary artery disease | 13 (27%) |
| High-risk age group (male ≥45 years, female ≥55 years or premature menopause without estrogen replacement therapy) | 35 (73%) |
| Positive exercise tolerance test result | 32 (59%) |
| Significant coronary artery disease on coronary angiogram | 21 (44%) |
| Single vessel | 15 (31%) |
| Double vessels | 5 (10%) |
| Triple vessels | 1 (2%) |
| Left main | 0 |
| Percutaneous coronary intervention performed | 11 (23%) |
⁎ Defined as persistent elevated blood pressure ≥140 mm Hg systolic and/or ≥90 mm Hg diastolic or treatment of persistent elevated blood pressure.
† Defined as elevated low-density lipids >100 dl for high risk, >100–140 dl for intermediate risk, and >140 dl low risk of CAD per American College Cardiology and American Heart Association guidelines.
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