Introduction

Patients with chest pain account for more than 6 million ED visits per year in the United States alone (₁). For these patients, the ECG remains the most important initial risk assessment tool. Myocardial ischemia or infarction is highly likely in patients with significant ST segment changes on the ECG or elevation in myocardial markers of necrosis. Identification of high-risk patients is more difficult in those with non ischemic ECG and negative markers on presentation. Because initial evaluation often does not yield a definitive diagnosis, one important aspect of the ED evaluation of the patient with chest pain is risk stratification. Low-risk patients account for nearly 2/3 of those presenting to the ED with chest pain, representing as many as 4 million patients per year in the United States (₂).

One of the most sensitive indices of contractility is the rate of increase of intraventricular pressure during isovolumetric contraction, (left ventricular dP/dt and arterial dP/dt). Dp/dt (dP/dt ^ejc ) represents the rate of change of pressure during ejection (₃,₄,₅,₆). It has been shown that cardiac contractility and dP/dt decreases during acute myocardial ischemia (₃, ₅).

We theorized that a higher value of dP/dt would be found for non ischemic chest pain than during ischemic chest pain because ischemia reduces myocardial contractility, whereas chest pain of non cardiac origin increases dP/dt by the stress of the pain itself. The current study describes a new, noninvasive device that measures central aortic pressure changes (dP/dt ^ejc ), a parameter that could be added to the diagnostic triage of ischemia in the ED, thus decreasing the number of unnecessary admissions.

Methods

Patient Population & Setting:

Study protocol

Measurements

The device

The ascending limb of aortic pressure (dP/dt ^ejc ) was measured noninvasivly with a newly designed, computer-controlled device [CardioWatch Ltd., Matam Advanced Technology Center, Haifa, Israel]. This device consists of 3 components: A sphygmonometric arm cuff attached to an air pressure unit, an array of proprietary sensors attached to the arm at the antecubital space over the brachial artery (Figure 1) and a computerized monitoring system.

Figure 1

Figure 1: Detailed view of the new sensor system and artery with the collapsed region under the cuff. Upstream pressure is systolic pressure.

By applying occlusive pressure over the brachial artery during systole using a noninflatable cuff, a temporary standing fluid column is created by which the rising intra-aortic pressure is transmitted to the periphery with minimal distortion. This standing column of blood may be regarded as though it were a manometric tube installed directly into the aortic arch.

The time intervals required for the aortic pressure wave to overcome a given occlusive brachial pressure applied by a sphyngomanometer on the arm are equal to times needed to reach the same pressure in the central aorta plus the propagation time to the brachial point which is constant in the same patient throughout the measurements. Time intervals are measured from the onset of flow breakthrough at the first sensor to the breakthrough reached at succeeding sensors (Figure 2).

Figure 2

Figure 2: Measurements of the time delay between the first sensor on the array serving as a reference sensor and the onset of brachial artery flow in the subsequent sensors during controlled upper arm deflation. The plot of pressure vs. time delays yields the ascending portion of the arterial wave form.

Applying multiple successive occlusive pressures on the brachial artery from peak systole to diastole and plotting the values against time intervals described above results in the reconstruction of the central aortic pressure curve. We can calculate the dP/dt^ejc, the index used in the present study, from the ascending arterial pressure wave form. Noninvasive systolic pressure wave forms are generated by measuring time delay between the first sensor on the array serving as a reference sensor and the onset of brachial artery flow in the subsequent sensors during controlled upper arm deflation. The delay decreases with falling cuff pressure so that the plot of pressure vs. time delays yields the ascending portion of the arterial wave form (Figure 3). Previously, ECG was used as a reference point instead of the first sensor (₈,₉,₁₀). However, since the delay between onset of R wave on ECG and the first sensor on the arm is constant (130±17 msec), we can use the first sensor instead of ECG (₁₁). The pressure wave thus generated is identical to the pressure wave generated utilizing the ECG reference system with constant delay. These wave forms were validated previously with simultaneously obtained invasive ascending aortic pressure and a correlation coefficient of r = 0.98 was found (₈).

Figure 3

Figure 3: Reconstruction of a pressure waveform in brachial artery

Statistical analysis

Results

We followed 102 patients presenting at the ED with acute chest pain (Figure 4). In 55 patients our device indicated that chest pain was of non cardiac origin (dP/dt ^ejc index above threshold value of ≥150), and, with the exception of 1 patient, coronary origin was ruled out by negative ECG and myocardial enzyme dynamics during the first 24 hours after admission (sensitivity 93%, negative predictive value 98% specificity 61%, positive predictive value 28%, accuracy 66%). The best threshold value for dP/dt ^ejc to rule out ACS was identified by ROC curve analysis when the following criteria were applied: True positive results were considered when patients showed positive enzyme dynamics and/or ECG changes compatible with ischemia and dP/dt ^ejc ≤ 150, true negative results when negative enzyme dynamics and normal ECG and dP/dt ^ejc ≥ 150, false positive results when negative enzyme dynamics and normal ECG and dP/dt ^ejc ≤ 150, false negative results when patients show positive enzymes dynamics and/or ECG changes compatible with ischemia and dP/dt ^ejc ≥ 150.

Figure 4

Figure 4: Noninvasive measurements in 102 patients presenting at the ED with acute chest pain

In 47 patients dP/dt ^ejc index was below threshold value of 150 indicating a high probability for ACS. Within this group 13 patients developed ACS. In 88 patients without ACS, average dP/dt ^ejc was 164 (range 92-232). In 14 patients with confirmed ACS, average dP/dt ^ejc was 127, (range 61-257). The dP/dt ^ejc values were found to be significantly higher in patients without acute ACS (p<0.001). Only one patient with confirmed ACS (1/14), dP/dt ^ejc was found above the threshold value of ≥150.

Discussion

Acute coronary syndromes are associated with an increased risk of cardiac death and acute MI, especially in patients who are not admitted to hospital (two fold risk) (₁₂). Furthermore, early detection of ACS is crucial for taking advantage of treatment. In addition, the inadvertent discharge of patients with ACS may result in adverse medico-legal consequences for physicians. Accordingly, the majority of patients are admitted or kept in observation in special units. The problem increases because the clinical picture of patients with ACS often overlaps that of patients who are subsequently found not to have coronary artery disease, resulting in 55-75% of patients being admitted to hospital unnecessarily (₁₂). Even with this over-admission, up to 2.3% of patients with unstable angina and 2.1% of those with acute myocardial infarction are mistakenly released from the ED (₁₃).

Given the difficulty in the rapid and confident evaluation of patients with suspected ACS using non-diagnostic or normal ECG, different techniques, including echocardiography and radionuclide myocardial perfusion imaging with tc99m- Sestamibi SPECT (MPI) have been developed. Studies using echocardiography in the ED setting allow assesment of most non ischemic causes of acute chest pain, as well as potential mechanical complications of acute MI. These studies have revealed fair sensitivity (78%) for the detection of ACS, but success depends upon the presense of symtoms during the ultrasound study and the extension of the myocardial insult. The specificity of the technique is about 83% (₁₄).

Radionucleide myocardial perfusion imaging with tc99m- Sestamibi SPECT (MPI) is used for evaluating patients presenting with acute chest pain, however, not as a routine measure. Acute MPI has a number of advantages. First, myocardial markers can diagnose only infarction and cannot identify ischemia in the absense of necrosis. Therefore, the sensitivity for identifying non-necrotic events or conditions, such as revasculariztion or significant coronary disease, is higher with MPI than with biomarkers (₁₅). Also, because of the shorter time required for imaging and processing, acute MPI results can be available within 1 to 2 hours after injection rather than the 8 to 9 hr period required for detection of markers of necrosis in blood (₁₆).

Acute MPI has some limitations when used to assess patients with chest pain. Acute infarction, acute ischemia and prior infarction all cause perfusion defects, and differentiation is not possible based on images alone. In a multicenter study, Heller and coworkers found a sensitivity of 90% in 357 patients who underwent acute MPI (₁₇). Negative predictive value (NPV) was equally high, at 99% with only 2 patients who had small non-Q wave myocardial infarctions having negative acute MPI (₁₇).

The newly developed noninvasive device described in this article provides a speedy and simple to use alternative method of ruling out ischemia by accurately measuring the ascending limb of the central arterial pressure (dP/dt ^ejc ), an accepted index of myocardial contractility (₃,₄,₅). Measurements take less than 10 minutes and can be performed by a nurse after half an hour of training. This index is probably influenced by preload and afterload, and it will be affected by poor LVEF. LVEF was not obtained for patients in this study. Because baseline ventricular function /contractility is a crucial factor in dP/dt ^ejc measurements, it is possible that patients with underlying cardiomyopathy and poor ejection fraction were unable to adequately elevate dP/dt ^ejc despite having noncardiac pain. In this initial group of patients reported ventricular function/contractility studies were not obtained. Further studies with a larger number of patients are needed to confirm initial findings

It has been shown that cardiac contractility decreases with a subsequent decrease in left ventricular dP/dt and arterial dP/dt during acute ischemia (₃,₄,₅). Mohr et al (₃) reported a substantial decrease in arterial dP/dt during coronary balloon occlusion. In a previous study we tested the sensitivity of the new device to detect ischemic changes during transient coronary occlusion in 16 patients undergoing PTCA and found that there was a significant decrease in dP/dt ^ejc immediately after balloon inflation (₁₁).

The most appropriate use of noninvasive dP/dt ^ejc measurements may be in the setting of patients with low likelihood of ACS presenting to the ED with acute ischemic symptoms, non-diagnostic ECG and normal myocardial serum enzymes in which early contractility index determination could assist in effective triage decisions, thus avoiding unnecessary admissions.

Summary

Rapid triage of the patient with suspected ACS is challenging. Chest pain and other symptoms suggestive of ischemia remain a nonspecific and frequent presentation to the ED. The vast majority of these patients will not require admission, but identification of the patient with ACS within this population is risky business. The present report depicts preliminary experience with a new noninvasive myocardial contractility index (dP/dt ^ejc ) for ischemia detection that could be added to the diagnostic triage of ischemia in the ED avoiding unnecessary admissions in low risk patients.

Acknowledgments

Correspondence to

Miguel Gorenberg, MD, Head of Nuclear Cardiology Sieff Government Hospital, POB 1008, Safed 13100 Israel email: miggoren@actcom.co.il phone: 972-4-6828841 fax: 972-4-6828745