Keywords
INTRODUCTION
Coronary angiography poses certain limitations when used for assessing moderate coronary lesions or the results of percutaneous procedures. In an attempt to supplement the information provided by angiography, several alternative transluminal techniques have been proposed, such as intracoronary ultrasound,1-4 pressure guidewires,5-6 or intracoronary Doppler.7-10 A coronary reserve greater than 2-2.5 after the latter procedure is considered a good physiological result, and no further optimization is generally required.9,10 However, coronary reserve might not be restored immediately after epicardial stenosis disappears. In order to assess how coronary reserve is restored over time after successful revascularization, we serially studied 34 patients angiographically and hemodynamically at baseline, immediately after the procedure, and during follow-up.
PATIENTS AND METHOD
Patients
Our series consisted of 34 patients who fulfilled the following inclusion criteria: a) angina pectoris or inducible ischemia with single-vessel coronary heart disease as the sole cause for symptoms; b) length of the culprit lesion less than 20 mm; c) percutaneous treatment (stenting in 26 patients and balloon angioplasty in eight) that was successful at the first attempt with no major complications; d) postprocedural residual lesion <35%); e) absence of symptoms during follow-up (8±3 months), and f) repeat angiography showing delayed improvement (n=32) or mild restenosis (2 patients showing residual stenosis of 58% and 60%, respectively, at follow-up). Excluded from the study were patients who were treated in the initial 48 h after an acute myocardial infarction (AMI), as well as 6 patients who underwent basal and postoperative Doppler studies and showed clinical recurrence during follow-up. Informed consent was obtained in all cases before diagnostic and therapeutic catheterization.
Coronary angiography and percutaneous revascularization technique
All patients underwent coronary angiography via the femoral artery using conventional catheters (6-7 Fr) and projections. After the diagnostic phase, dilatation of the lesion with balloon angioplasty or stenting (Johnson-Cordis or Multilink Guidant) was performed. During the therapeutic phase, all patients received intravenous heparin (2 mg/kg body weight). In patients who had undergone stent implantation, the device was expanded by a balloon with a diameter slightly larger than the reference vessel, at a mean pressure of 12-14 atmospheres. For a period of 1 month patients were kept on antithrombotic therapy, namely low-molecular-weight heparin (Fragmin 5000/12 h, ticlopidine 500 mg/day, and aspirin 150 mg/24 h). Glycoprotein IIb/IIIa inhibitors were not used in this study. In patients who had undergone only angioplasty, the balloon was chosen according to the same criteria that were used for the stent-treated group. Before and after the procedure quantitative angiography was performed using electronic calibrators, and the points corresponding to the minimal diameter of the lumen (MLD) and reference segment were selected manually.
Coronary flow velocity measurements
We used the Flomap system,11-12 which consists of two different parts: the flow guide wire and the console. The flow-wire is a conventional angioplasty guide measuring 0.014 falta la unidad with a flexible tip bearing a pulsed Doppler transducer that emits 15-MHz signals. The transducer is connected to the console preamplifier cable via a rotor-connector. The console has a Doppler signal-emission/reception system for digital processing, as well as a monitor and a video system for recording the results. The same measuring procedure was followed systematically in all cases; the Doppler guide was placed distal to the lesion, and flow velocities were recorded to obtain the mean peak velocity at baseline. Subsequently, an intracoronary bolus of 24 mg adenosine was injected into the left coronary artery, and a 12 mg bolus was injected into the right coronary artery.13-15 The mean peak velocity was measured again during maximal hyperemia, and coronary flow reserve was assessed by calculating the coefficient given by peak flow velocity divided by basal flow velocity. After the procedure, the study was repeated following the same systematic procedure used at baseline.
Follow-up study
At 8±3 months´ follow-up, a repeat hemodynamic study was performed that included left ventriculogram, coronary angiograms, and measurements of coronary flow velocities and coronary reserve in the treated artery, using the same methods as in the earlier phases of the study.
Statistical analysis
Quantitative data are expressed as the mean±one standard deviation. Student's t test, along with Fisher´s correction for paired or unpaired data, were used, as appropriate, for comparing two means. Analysis of variance was used to compare mean results from the studies performed at baseline, after treatment, and at follow-up, and the Neumann-Keuls test was used for further individual comparisons. P<.05 were considered statistically significant.
Baseline data and immediate angiography results
Baseline data for all 34 patients are summarized in Table 1. The percent stenosis changed from 82±9 to 10±7% (P<.01), and MLD changed from 0.6±0.3 to 3.2±0.5 mm (P<.01).
Serial studies of coronary flow velocities
Figure 1 shows the changes in basaline and post-hyperemia distal flow velocities, before and after the procedure and at follow-up. After revascularization there was a significant increase in basaline flow velocity as well as in peak flow velocity during hyperemia. At follow-up, peak velocity during hyperemia did not fluctuate, and basal velocity showed a modest but significant decrease. Hemodynamic criteria that might affect the assessment of coronary reserve (CR) varied very little from those applied in the study performed immediately after follow-up. Thus, heart rate changed from 67±15 to 66±beats/min, while mean arterial pressure (MAP) increased from 97±16 to 99±14 mm Hg. Figure 2 shows the course of heart rate (at baseline, 1.3±0.4; after the procedure, 2.4±0.7, and at follow-up, 3±0.8), along with the changes in MLD seen with quantitative angiography. Coronary reserve and MLD increased considerably after revascularization. During follow-up, an additional increase in coronary reserve and a slight but significant loss of MLD were noted. In 8 of our patients (23%), CR did not normalize immediately (immediate CR<2). Nevertheless, all such patients attained levels >2 at follow-up. On the other hand, 4 patients with an immediately normal CR (>2) showed a decrease in this parameter at follow-up, although the value was never <2.
Fig. 1. Changes in distal flow velocities (cm/s) obtained under 3 study conditions: before the procedure, after the procedure, and at follow-up.
Fig. 2. Coronary reserve over time along with changes in minimal luminal diameter (mm) under the 3 study conditions.
We carried out a study to identify determinants of increased coronary reserve at follow-up (follow-up CR and post-procedure CR), and all clinical parameters examined (age, sex, and clinical situation) were negative, as were angiographies performed to determine the location of the lesion, its severity, and the involved artery. The type of revascularization (dilatation with balloon angioplasty or stenting) did not appear to be a determinant for increased CR. The only factor that was significantly associated with the latter was the inability to attain a coronary reserve above 2 during the procedure. Patients with a history of myocardial infarction in the treated area showed a tendency toward increased reserve at follow-up, but this tendency was not statistically significant (Figure 3).
Fig. 3. Factors determining increases in coronary reserve at follow-up (follow-up CR CR immediately after procedure). A: optimal or suboptimal immediate coronary reserve. B: presence or absence of a history of myocardial infarction.
DISCUSSION
Doppler techniques have been used to measure coronary flow velocity in patients in whom it may be difficult to decide on a clinical course of action: to treat or not treat moderately severe lesions,7,8 to assess the results of coronary revascularization procedures,9,10 or as a predictive factor after stenting.16 Of all proposed Doppler-based parameters, assessing coronary reserve is the most relevant. Normal coronary reserve reflects the ability of coronary vessels to increase their blood flow up to 4- to 6-fold above baseline after maximal vasodilatation stimulus.17 This compensatory mechanism, which maintains good blood flow, is ebolished when a significant lesion (either native or post-intervention) is present in epicardial vessels. In such cases, vasodilator stimuli do not produce additional vasodilatation, nor do they significantly increase coronary blood flow. Upon suppression of epicardial stenosis, compensatory vasodilatation is no longer necessary, and the ability to respond to stimuli that trigger vasodilatation is restored.18,19 Nevertheless, few studies have sought to determine when coronary reserve is restored after having been undermined by a severe lesion that has been successfully resolved. Our findings suggest that a certain proportion of patients (23%) do not attain normal coronary reserve immediately after effective revascularization, and that there is a transient dissociation between coronary reserve and quantitative angiography. Therefore, coronary reserve measurements obtained immediately after revascularization may underestimate how successful the procedure has actually been.
Decreased coronary reserve after a successful procedure
Aside from the persistence of significant residual stenosis,18,19 the reasons CR is not immediately restored are not fully known. Because CR is a quotient, the reasons may involve a decrease in the numerator (flow velocity after hyperemia) or an increase in the denominator (basal flow velocity):
1. Increased basaline flow velocity: the heart self-regulates arteriolar resistance in response to changes in perfusion pressure. The effect of prolonged distal hypotension caused by acute epicardial stenosis in coronary self-regulation causes prolonged arteriolar vasodilatation and "vasoplexy", or a transient loss of the vascular bed´s self-regulatory capacity (failure to achieve adequate vasoconstriction) in response to the sudden recovery of perfusion pressure. This results increase in basaline coronary blood flow and a decrease in the quotient given by peak flow velocities divided by basaline flow velocities. Earlier studies20-22 support the theory that an increase in basal blood flow is responsible for the decrease in CR after revascularization, as well as the notion that self-regulation is slowly restored.
2. A decrease in flow velocity during hyperemia (Figure 4): microvascular embolization by platelet aggregates or thrombus fragments during dilatation may diminish the microvascular response to adenosine, as well as reducing basal blood flow. Prolonged ischemia and small vessel necrosis also affect the ability to respond to vasodilators, and the concept of "stunned microcirculation"21-24 similar to the concept of the "stunned myocardium", has been suggested. In the acute phase of a myocardial infarction, coronary reserve after revascularization may even improve faster (in 24 h to 2 weeks), at the expense of an increase in flow velocity during hyperemia.23,25,26
Fig. 4. Example of a patient with a lesion in the distal segment of the right coronary artery who underwent stenting. Coronary reserve at follow-up improves significantly at the expense of an increase in flow velocity during adenosine-induced hyperemia.
A substudy of the DEBATE27 study has recently been published in which, in addition to the reasons mentioned above, being older and female turned out to be predictive factors for having a suboptimal reserve after successful revascularization.
Limitations and clinical implications
Despite the fact that the doses of adenosine used in our study are the ones that have been recommended in many of the multicenter studies on this subject,9,16 maximum arteriolar vasodilatation may not have been achieved. However, because the same doses were used under all study conditions, a change in small vessel response has been shown to take place over time. On the other hand, the sample size is small, and perhaps some of the factors having no predictive value may turn out to be predictive in larger series.
Despite these limitations, we believe that CR improves immediately after a successful coronary intervention, but some patients may experience additional improvement in subsequent months. In our group of patients, this delayed improvement in coronary reserve occurred at the expense of a decrease in the basal velocity obtained in the follow-up study and was greater in patients having a low coronary reserve immediately after treatment. Our findings suggest that the use of these Doppler parameters for immediately assessing the results of a percutaneous coronary procedure may be of limited value.
Correspondence: Dr. M. Pan Álvarez-Ossorio.
Servicio de Cardiología, Hospital Reina Sofía,
Avda. Menéndez Pidal, s/n, 14004 Córdoba, Spain.
E-mail: grupo_corpal@arrakis.es