Patients with a positive treadmill exercise test, and normal coronary angiography have long been recognised as an important problem in clinical practice [8–10]. These early studies identified many of the characteristics of what was subsequently characterized as syndrome X [10]. The same denomination was also applied to a syndrome, characterized by insulin resistance, hyperinsulinemia, and diabetes, that is associated with dyslipidemia, hypertension, and abdominal obesity. Hence a more specific terminology comes in use: angina with normal coronary arteriography [11]. Patients with this entity, predominantly women [12], complain of pain that is frequently atypical. It may be precipitated by exertion, although the threshold for precipitating pain is highly variable [13]. Its duration may be uncharacteristically long, and it may be unusually severe and is rarely associated with symptoms such as diaphoresis. Perfusion abnormalities have been observed commonly in patients with chest pain and normal coronary arteriograms, but no consistent correlation could be made among the extent of the defect, the positivity of the exercise test, and exercise tolerance [14]. Thus in many of this patients there is evidence of perfusion abnormalities that are attributed to abnormalities in the microvasculature [15]. However stress echocardiography allways failled to demonstrate segmental wall abnormalities even showing hyperdinamic ventricles[16].
The results of our study, in which 33 (36%) of 91 patients with normal coronary angiogram and positive treadmill exercise test developed intraventricular gradient, suggest that ST-segment depression may be related with the development of IVG during exercise which is possibly involved in the genesis of electrocardiographic changes. The possible association between cardíac X syndrome and the development of IVG during exercise was described before [17, 18] however some of the patients from these studies have arterial hypertension, and left ventricular hypertrophy that by definition of X Syndrome [19] we have excluded and that more frequently developed IVG [3].
The appearance of IVG in our study was associated with morphological determinants like reduced LVOTi, reduced left ventricular diastolic volume, a reduced distance D1, and increased relative left ventricular wall thickness. All these finding translate a proportional small heart that the multivariate model confirms.
The reduced D1 in Group A means an anterior "displacement" of the postero internal papillary muscle that may be involved in the development of IVG and SAM of the mitral valve [20, 21] as described by other authors.
We can admit that this phenomenon is eventually caused by the subtle changes in left ventricle geometric shape and dimensions with more anterior papillary muscles implantation [20, 21], that during exercise, induce and submit the cordae and mitral valve to an abnormal systolic anterior motion and to papillary muscle ischemia. The obstruction to the outflow in left ventricle with the increase in the intraventricular pressure that it causes may contribute, to left ventricular strain and ST-depression in this patients.
The development of intraventricular gradient during exercise may possibly explain the ST changes in a subgroup of patients who have treadmill positive test and normal coronary arteries.
The patients with IVG during exercise had more angina during exercise and were predominantly male, and this may explain why these patients were submitted to coronary angiography much early, after the beginning of the symptons, than patients in Group B. From the all study group 42 patients (46%) reproduced symptoms during ESE, however this fact occured more frequently (22 pts from 33 in group A vs 20 from 58 pts in group B – p = 0.002) in group A, favouring the potencial participation of intraventricular gradient in the occurrence of symptoms.
In our study population, we found a great number of patients that develop SAM of the mitral valve in association with IVG contrarily to other authors [17, 18]. We think that we detect SAM in a greater number of patients because we do echo during all the exercise in treadmill (Additional file 2 and 4) [7]. The magnitude of the IVG that we have detected in our patients is also greater for the same motive (Figure 3).
Additional file 4: Images obtained during exercise test. Images obtained during exercise test showing the position of operator with the cubital border of the right hand attatched to the patient chest wall. (WMV 250 KB)
Four of the 33 patients that developed intraventricular gradient are athletes [22] and we should probably study this phenomenon in this specific population and, if this occurs, also investigate the possible prognostic implications for this event in this particular population [23].
The results of ESE have probably influenced the treatment of the patients once at the end of follow-up a greater percentage of patients are treated with β blockers [24, 25] in group A than in group B (Table 1).
The principal limitations of this study are: 1) no one patient has done a test for provocation of coronary spasm at cath. laboratory even no patient included in the study had segmental wall abnormalities with exercise 2) The presence or absence of ischemia was only evaluated by ESE without use of scintigraphic studies. 3) We excluded all patients with left ventricular hypertrophy and uncontroled arterial hypertension that constitutes a great number of patient in the real world of clinical practice and that should be studied in the future with the same protocol.
