Therapeutic Considerations

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Although the CSFP generally has a good prognosis in relation to subsequent cardiac events, it is associated with considerable morbidity with many patients experiencing recurrent chest pain and therefore requiring antianginal therapy. To date, there is only one published study examining potential therapy for this disorder. In an open-label, observational study, Kurtoglu and coworkers administered dipyri-damole 75 mg three times daily to 25 CSFP patients, with angiography performed at baseline and after 1 month of therapy. Although there are limitations to this study, this group demonstrated resolution of the chest pain and angio-graphic phenomenon with dipyridamole.

From our own clinical experience we have found vera-pamil and oral nitrates to be of limited benefit. However, we have found mibefradil, a unique calcium channel blocker, to be particularly effective. We surveyed the patient's per-

Feature

Table III Summary of Angiographic, Pathophysiological, and Clinical Characteristics of CSFP.

Characteristic

Prevalence

Angiographic findings

Angiographic considerations

Definition No obstructive epicardial coronary disease with delayed distal vessel opacification (delayed opacification may be based upon TIMI flow grade or TIMI frame count) 1% of diagnostic angiograms LAD most frequently affected vessel

Often observed in multiple vessels

Phenomenon persistent at repeat angiography

Pathophysiological considerations

Coronary hemodynamics Increased resting coronary vascular resistance due to

(a) structural obstructive small vessel disease

(b) functional small vessel constriction

Biologic mechanisms Endothelin?

Neuropeptide Y?

Clinical considerations

Presentation Acute coronary syndrome (75% of patients)

Clinical progress Low mortality (concerns over ventricular arrhythmias) Low risk of subsequent myocardial infarction High morbidity (84% experience recurrent angina)

Exercise stress test Ischemic ECG changes in approximately

10-20% of patients

Myocardial scintigraphy Reversible perfusion defect in a third of patients

Potential therapies Dipyridamole

Mibefradil ceived response to mibefradil in 22 patients (56 ± 14 years, 16 males) with CSFP who previously responded poorly to long-acting nitrates and conventional calcium channel blocker therapy. In contrast to the conventional antianginal therapy, all patients reported at least a moderate improvement in their angina frequency with mibefradil, including 73 percent who reported a major improvement. Randomized, double-blind controlled studies are required to corroborate this observational finding.

The disorder differs clinically from syndrome X because patients often present initially as an acute coronary syndrome and seldom have positive stress tests. There is significant associated subsequent morbidity with most patients experiencing recurrent chest pain and thus require prophylactic antianginal therapy. Dipyridamole and mibefradil may be effective therapies but require further evaluation.

Glossary

Coronary slow flow phenomenon (CSFP): An angiographic observation characterized by the delayed opacification of the distal vasculature in the absence of obstructive epicardial coronary disease.

TIMI flow grade: A qualitative index of angiographic coronary flow (graded from 0 to 3) developed by the Thrombolytics in Myocardial Infarction (TIMI) investigators. TIMI-0 flow = occluded vessel; TIMI-1 flow = contrast penetrates the obstruction but does not opacify the distal vessel; TIMI-2 flow = delayed distal vessel opacification; and TIMI-3 flow = normal filling of the distal vasculature (i.e., within three cardiac cycles).

TIMI frame count (TFC): A quantitative angiographic flow index developed by the Thrombolytics in Myocardial Infarction (TIMI) investigators. Flow is assessed by the number of angiographic frames required to opacify a coronary vessel to predefined end points.

References

1. Gibson, C. M., Cannon, C. P., Daley, W. L., Dodge, J. T. Jr, Alexander, B. Jr, Marble. S. J., McCabe, C. H., Raymond, L., Fortin, T., Poole, W. K., and Braunwald, E. (1996). TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation 93(5), 879-888.

2. Beltrame, J. F., Limaye, S. B., and Horowitz, J. D. (2002). The coronary slow flow phenomenon—a new coronary microvascular disorder. Cardiology 97, 197-202. This seminal paper characterizes the clinical features of patients with the coronary slow flow phenomenon, thereby associating a clinical syndrome with the angiographic phenomenon and thus identifying a new disorder.

3. Diver, D. J., Bier, J. D., Ferreira, P. E., Sharaf, B. L., McCabe, C., Thompson, B., Chaitman, B., Williams, D. O., Braunwald, E. (1994). Clinical and arteriographic characterization of patients with unstable angina without critical coronary arterial narrowing (from the TIMI-IIIA trial). Am. J. Cardiol. 74(6), 531-537.

4. Atak, R., Turhan, H., Sezgin, A. T., Yetkin, O., Senen, K., Ileri, M., Sahin, O., Karabal, O., Yetkin, E., Kutuk, E., and Demirkan, D. (2003). Effects of Slow Coronary Artery Flow on QT Interval Duration and Dispersion. Ann. Noninvasive Electrocardiol. 8(2), 107-111.

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