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-
Table III Summary of Angiographic, Pathophysiological, and Clinical Characteristics of CSFP.
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
Coronary hemodynamics Increased resting coronary vascular resistance due to
(a) structural obstructive small vessel disease
(b) functional small vessel constriction
Biologic mechanisms Endothelin?
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
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.
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.
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