Coronary Pressure Notch: An Early Non-hyperemic Visual Indicator of the Physiologic Significance of a Coronary Artery Stenosis

The limitations of coronary angiography for defining the functional significance of intermediately severe lesions are well known. Such angiographic presentations frequently require additional testing to determine their clinical relevance. During cardiac catheterization, a pressure sensor angioplasty guidewire can be placed across a stenosis to accurately assess the physiological significance of a coronary lesion by measuring myocardial fractional flow reserve (FFR).¹ Utilizing ratio of the mean pressures distal and proximal to the stenosis during maximal hyperemia, FFR values of 2 The incorporation of a physiological lesion assessment to the anatomic evaluation during cardiac catheterization can eliminate a delay in determining the need for further invasive intervention.^3,4 Arterial stenoses acting as filters may dampen the transmission of pressure waves to the distal vessel, reducing high frequency wave components⁵ manifested by the disappearance of the dicrotic notch.^6-8 Lax et al.⁶ suggested the disappearance of the peripheral arterial pulse wave dicrotic notch correlated with the presence of coronary heart disease. Bollinger et al.⁸ showed the loss of the dicrotic notch in a peripheral arterial pressure tracing is associated with significant peripheral vascular disease. Spectral analysis of the arterial pressure waveform identifies the dicrotic notch as a marker of the high frequency content of the pressure signal.⁵ A recent analysis by Brosh et al.⁹ calculated the transmission of high-frequency components of the intracoronary pressure signal, proximal and distal to a stenosis. This ratio, called the pulse transmission coefficient (PTC) of pressure wave components through a stenosis in the non-hyperemic state, correlated with myocardial fractional flow reserve (FFR) as a marker of ischemia.⁹ This study tested the hypothesis that the disappearance of the coronary pressure notch (dicrotic notch) in the arterial wave distal to the coronary stenosis by visual inspection would also correlate to a significant FFR, and therefore, function as an additional non-hyperemic indicator of lesion significance in the assessment of an intermediate coronary artery stenosis. Method Study population. The study examined 131 lesions in 97 patients who underwent FFR measurements for coronary artery lesions between 40% and 80% angiographic stenosis. The patients were referred for cardiac catheterization for a variety of indications which included patients with stable angina, remote myocardial infarction and asymptomatic patients with positive non-invasive stress testing. FFR measurements were made in all coronary artery locations, including lesions in the left main artery, saphenous vein grafts, the internal mammary artery, lesions of in-stent restenosis. Patients with acute myocardial infarction (1 Heparin (40 units/kg IV) was given before guidewire insertion. In brief, the sensor guidewire is advanced to the coronary ostium, and the pressure signals of the guidewire and guide catheter are matched. The guidewire is then advanced distally beyond the coronary stenosis. Phasic and mean aortic (Pa) and distal coronary (Pd) pressure tracings are recorded for 10 seconds prior to the administration of intracoronary adenosine (18 or 24 mg in the RCA and 24–40 mg in the LCA) to induce maximal hyperemia. Simultaneous Pa and Pd were continuously recorded. FFR was calculated as the ratio of Pd/Pa during maximal hyperemia. FFR measurements were performed in duplicate. For LM ostial lesions, intracoronary adenosine was injected and the guide catheter removed immediately thereafter to avoid catheter-related obstruction to flow. Pressure tracings were recorded at 10 mm/sec and 25 mm/sec paper speed after the catheterization. The pressure waveforms were reviewed by two independent observers without knowledge of the FFR for the presence or absence of a dichrotic notch in the resting distal arterial waveform. A coronary pressure notch was present if there was a distinct incisura, a horizontal line or well defined change in the descent of the distal coronary pressure curve. Figure 1 illustrates pressure waveform with and without a coronary pressure notch. The patients’ stenoses were then divided into two groups depending on the presence or absence of the pressure notch. No patient studied was without an aortic pressure notch. Quantitative coronary angiography. Off-line quantitative coronary analysis was performed using an automated contour detection algorithm in 94 lesions. We were unable to perform analysis on 37 lesions due to technical limitations. Visual assessment of lesion severity in all patients was obtained from two independent reviewers. Statistical analysis. All values are given as mean ± SD. Student’s t-test (unpaired) was used to compare the FFR values between the patient groups with and without the coronary pressure notch. Receiver operator characteristic (ROC) curve analysis was used to obtain the optimum cut-off value of FFR that correlates best with an absent distal pressure notch. The Fisher’s exact test was used to calculate the association between non-invasive stress testing results and both FFR and pressure notch. Results The clinical characteristics of the patients are summarized in Table 1. The group with the distal pressure notch had 64 patients (77 lesions) and the group without the pressure notch had 43 patients (54 lesions). There were no significant differences in the clinical characteristics, or indications for cardiac catheterization between the two groups. The anatomic location of the FFR lesions is listed in Table 2. The quantitative angiographic data and hemodynamics are summarized in Table 3. The mean FFR of all the lesions was 0.82 ± 0.12. The mean FFR of the lesions with a distal coronary pressure notch was 0.88 ± 0.07 and that for the lesions without a distal notch was 0.73 ± 0.12 (p = 0.75 and 23 had FFR >= 0.76. Of the 77 lesions with the distal pressure notch, 2 had FFR >= 0.75 and 75 had FFR >= 0.76 (Table 4). Based on the data, the sensitivity and specificity of an absent distal coronary pressure notch for an FFR >= 0.75 was 94% and 77% respectively. The positive and negative predictive values are 57% and 97%, respectively. Table 5 stratifies patients based on their FFR value. Sixty-seven patients with a pressure notch had FFR values >= 0.81. Stress testing. Only 51 patients (53%) underwent non-invasive stress testing prior to cardiac catheterization. In this small group, 37 patients had positive test results, and 14 patients had negative test results. There was no significant association between stress test results and either the absent pressure notch (p > 0.1) or FFR (p > 0.1) as determined by the Fisher’s exact test. Discussion The main observation in this study is that a hemodynamically significant coronary artery stenosis dampens the transmission of the coronary pressure waveforms distal to a lesion. The loss of the pressure notch in the non-hyperemic coronary artery pressure tracing was associated with an FFR value of 0.76, a physiologically non-significant lesion. These results suggest that the presence of a coronary pressure notch may be a complimentary non-hyperemic indicator to FFR for the physiologic significance of intermediate coronary stenosis. Because of the limitations of coronary angiography, in-lab physiological lesion assessment of indeterminate lesions is may be necessary. In many instances noninvasive stress testing may be negative, inconclusive or not performed prior to coronary angiography and the decision to proceed with coronary revascularization is not clear based on angiography above. FFR is a reliable index of the functional severity of coronary stenosis with a cutoff value of 0.75 and small zone of uncertainty (1,2 However, although FFR is straight forward and well validated, some operators may be reluctant to employ adenosine to induce hypertension because of the time and cost. Brosh et al.⁹ found the pulse transmission coefficient (PTC) as a strong non-hyperemic value correlated to FFR. In the current study, of the 77 lesions with a pressure notch, 75 had a non-significant FFR. There were 8 lesions with a pressured pressure notch with FFR between 0.76 and 0.80, a “gray” zone for deferring revascularization. Eighty-seven percent of the lesions with a distal coronary pressure notch had FFR values > 0.81. The loss of the arterial pressure notch in the coronary artery was similar to peripheral arteries. An early study compared the loss of the peripheral arterial dicrotic notch to coronary artery disease.^5-7 Patients without a peripheral arterial dichrotic notch were more likely to have angiographically and clinically significant coronary artery disease. The presence of a pressure notch in both the coronary and peripheral arteries suggested minimal disease with adequate pressure waveform transmission. In patients with mild lower extremity ischemia, the dicrotic notch was less than prominent than patients with no disease.⁷ Patients with severe ischemia had a dicrotic notch that was not visible in the distal arterial pressure waveforms. Brosh et al.⁹ extended the visual detection of a dichrotic notch to detection of the high frequency components of pressure wave form. A ratio of proximal and distal components produced the pulse transmission coefficient (PTC), which correlated strongly with the FFR. Visual inspection of the pressure waveform provides a gross estimation of the preservation of the high frequency components distal to a stenosis and may also serve as a non-hyperemic marker of lesion significance. Limitations. This study has several limitations. First, examination of the pressure notch is dependent on signal quality. If signal quality is poor, the pressure tracing may be difficult to accurately assess for the presence or absence of a pressure notch. The pulse transmission may be influenced by guide catheter size relative to ostial lumen dimensions. Smaller lumen vessels may not accurately transmit a pressure notch into the distal artery. Diffuse sub-angiographic disease proximal to the assessed stenosis may also alter waveform transmission. Specific vessel compliance may enhance or obscure the pressure notch. Six lesions included in our study were from vein graft stenosis, which also demonstrate a different compliance from arteries. The variables and their effects on pulse frequency components on the dichrotic notch remain under study. Clinical Significance.This study demonstrates that the presence of a dichrotic notch in the distal coronary artery pressure waveform strongly correlates to a non-ischemic threshold FFR (i.e. > 0.76), a finding which may serve as an additional non-hyperemic component in the assessment of indeterminate coronary stenosis. Additionally, the observation of a pressure notch after intervention likely indicates restoration of satisfactory perfusion (i.e. FFR values > 0.81). This detection of a distal pressure notch associated with FFR > 0.81 in > 95% of lesions may be employed when there is suspected pressure drift resulting in a misaligned and offset waveform causing an erroneous pressure gradient. The preserved dichrotic notch would suggest reassessment of the pressure signals before accepting the FFR result.

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