Rendimiento Académico

Although some aspects of the chest pain experienced by syndrome X patients are typically anginal in nature, certain features are not. For example, pain may come at rest, the duration of pain may be long and anti-anginal agents may afford little relief. Although the prognosis o f syndrome X with regard to future cardiac events is good, many patients continue to take anti-anginal medication, to attend cardiac clinics and to be hospitalised for episodes of severe chest pain (Table 3.1). A minority develop a cardiomyopathy years later (Opherk et al. 1989).

In some patients chest pain may have a non-cardiac origin and the exercise test result does not reflect myocardial ischaemia. In routine clinical practice the exercise test is generally classified as a "false positive" result if coronary angiography fails to demonstrate obstructive coronary artery disease, but such an approach may be erroneous. Simply because the cause of ST segment depression in the absence of coronary artery disease is not readily understood does not imply that the myocardial response to stress is normal. Furthermore, myocardial ischaemia may develop in the absence o f electrocardiographic change, particularly if ischaemia is generalised.

n Follow-up Chest pain Hosptl. MI Death % taking (mean) W S I for CP (cardiac) anti-anginals

Waxier 82 15 mo 0% 49% 51% 3 0 0 25% (1971) Bemiller 37 4.1 yr 0% 20% 80% 0 1 75% (1973) Kemp 200 36 mo 8% 36% 56% 19 0 2 (1973a) Ockene 57 16 mo 12% 46% 42% 0 0 25% (1980) Proudfit 357 10 yr + 2 2 (1980) Dart 88 < 5 yr 0 0 (1980) Pasternak^ 159 42.7 mo 8% 30% 62% 27 1 0 46% (1980) Isner 109 4.3 yr 10% 60% 30% 3 2 64% (1981) Bass 30 3.1 yr 10% 33% 57% 2 0 0 63% (1983) Kemp 3136 7 yr 3 14 (1986) Papanicolaou 1491 6.3 yr 194 2 2 27% (1986) Opherk* 40 48 mo 23% 77% 0% 0 0 (1989)

Table 3.1 Sym ptom s and cardiac events during long-term follow -up in syndrome X. U nless otherwise indicated only data on patients with entirely normal coronary arteriograms are described. Chest pain W=worse, S=same, I=improved; Hosptl. fo r CP=hospitalisation fo r chest pain; MI=myocardial infarction. (+) patients with normal coronary arteries or "insignificant disease". (*) 1 5 /4 0 had le ft bundle branch block (at rest or with stress) and developed signs o f impaired le ft ventricular function during follow -up.

Attempts have been made, with variable success, to distinguish patients with syndrome X from patients with coronary artery disease on the basis of certain features of the exercise test response, for example the time course of ST segment depression (Pupita et al. 1990), the recovery phase o f the ST segment (Gavrielides et al. 1991), the heart rate response during exercise (Galassi et al. 1991a) and by a combination of techniques (Burton et al. 1992). Transient ST segment depression on ambulatory monitoring has also been demonstrated (Kaski et al. 1986; Levy et al. 1986).

Changes in the ST segment during ischaemia may be caused by potassium loss from the myocardium into the extracellular space (Weigand et al. 1979). The ST segment change on exercise in syndrome X may indicate myocardial ischaemia or it may simply represent a localised increase in extracellular potassium concentration due to an abnormality o f potassium exchange (Poole-Wilson 1984). Thallium scintigraphy has been used to identify reversible ischaemia in patients with chest pain and angiographically normal coronary arteries (Meller et al. 1979; Virtanen 1984; Kaul et al. 1986; Flugelman et al. 1991). The reported incidence of perfusion defects is variable, and in one study 52% patients had evidence of stress-induced myocardial perfusion defects (Flugelman et al. 1991). However, because thallium is a potassium analogue, reversible perfusion defects may not be synonymous with myocardial ischaemia.

Evidence of left ventricular dysfunction induced by exercise, pacing or dipyridamole has been sought in syndrome X, but results are inconsistent (Table 3.2). Lactate production during pacing has been observed in a proportion of patients (Arbogast & Bourassa 1973; Boudoulas et al. 1974; Opherk et al. 1981; Greenberg et al. 1987). A fall in coronary sinus oxygen saturation with atrial pacing has also been demonstrated (Crake et al. 1988; Mikuniya et al. 1990),

Stressor Indices o f left ventricular function Normal findings

Arbogast (1973)

10 atrial pacing cardiac index, LVEDP

Levy (1986)

6 exercise & during ambulatory monitoring

PA diastolic pressure

Picano (1987)

19 dipyridamole echo fractional shortening

Nihoyannopoulos 18

(1991) 16

exercise echo atrial pacing + echo

regional wall motion systolic wall thickening

Abnormal findings Gleichmann 15 (1981)

exercise LVEDP, PA pressure,

ejection fraction Opherk (1983a) 37 exercise (18/22 +ve ETT) ejection fraction Legrand (1985)

18 exercise scintigraphy reversible perfusion defect (7) ejection fraction (5/7)‘*‘ Cannon*

(1985a)

26 26

ergonovine + atrial pacing exercise scintigraphy LVEDP ejection fraction Favaro (1987) 32 exercise (13/20 +ve ETT) ejection fraction Nadazdin (1991)

10 dipyridamole echo LV filling pattern

Table 3.2 Indices o f le ft ventricular function in syndrome X . ETT=exercise tolerance test, L V E D P -left ventricular end-diastolic pressure, PA=pulmonary artery. (+) 5 o f the 7 patients with reversible perfusion defects had an abnormal le ft ventricular ejection fraction with exercise, 2 o f the 7 patients had a positive exercise stress test. (*) patients with an abnormal vasodilator response to atrial pacing after intravenous ergonovine.

In the absence o f large coronary artery disease the abnormality must lie distally in the coronary vascular bed. Examination of small blood vessels less than 150 fim in diameter by endomyocardial biopsy has not, in the majority of cases, demonstrated vascular abnormalities (Richardson et al. 1974; Opherk et al. 1981). Where abnormalities have been shown it is likely that these patients suffered from a cardiomyopathy (Mosseri et al. 1986; van Hoeven & Factor 1990). Vessels in the range 150 - 400 ftm diameter cannot be assessed by coronary angiography or light microscopy o f biopsy specimens. This "window" is a potential site of structural or functional abnormality in syndrome X.