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Abstract

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. References

J Clin Hypertens (Greenwich). 2010;12:693–697. ©2010 Wiley Periodicals, Inc.

Left ventricular transient dilatation (TD) during stress myocardial perfusion imaging has been associated with extensive and severe coronary artery disease (CAD). The authors investigated the clinical predictors of TD in patients with nonsignificant CAD. The authors retrospectively studied 134 consecutive patients with exercise (n=59) or dipyridamole (n=75) stress-induced TD who had undergone coronary angiography within 6 months of the test. Significant CAD was defined as diameter stenosis ≥70% in at least one major coronary artery, and significant left main disease as >50% diameter stenosis. Angiographically-significant CAD was found in 126 patients (94%), and nonsignificant CAD in the remaining 8 patients (6%). No differences in gender, history of smoking, hyperlipidemia, family history of CAD, body mass index, and left ventricular ejection fraction were found between patients with significant and nonsignificant CAD. All 8 nonsignificant CAD patients had a history of either hypertension (7/8) or electrocardiographic criteria for left ventricular hypertrophy (1/8), compared with 58% of the hypertensive patients in the significant CAD group (P=.02). Nonsignificant CAD patients were also characterized by lack of diabetes mellitus (P=.05) or prior myocardial infarction (P=.05). Hypertension seems to be an important clinical predictor of TD in patients with nonsignificant CAD.

Transient ischemic dilatation of the left ventricle (TD) during stress myocardial perfusion imaging has been associated with severe and extensive coronary artery disease (CAD).1–7 In addition, TD is considered an independent and incremental prognostic marker of ischemic events.8–10 While the mechanism of TD remains unclear, the most likely explanations for this phenomenon include stress-induced subendocardial hypoperfusion, systolic left ventricular dysfunction and dilatation, and endocardial postischemic stunning,11–14 usually in the presence of obstructive epicardial vessel disease. However, the presence of TD in patients without significant CAD has been previously described and explained by the possible role of hypertension, left ventricular hypertrophy (LVH), and diabetes mellitus.15–20 The aim of this study was to clinically characterize the patients with stress-induced TD and angiographically nonsignificant CAD.

Materials and Methods

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. References

Patient Population

We retrospectively studied 134 consecutive patients (mean age 66.0±3.0 years) referred to the Nuclear Cardiology Unit at the Sheba Medical Center, who demonstrated stress-induced TD during Tl-201 myocardial perfusion imaging and underwent coronary angiography within a mean of 29±11 days (range: from 1 day to 6 months) following the stress test, with no intervening ischemic event between the 2 study tests. Patients with a history of coronary bypass surgery, significant valvular disease, and hypertrophic obstructive or dilated cardiomyopathy were not included in the study analysis. Patients were divided into 2 groups based on their angiographic results: group 1 included 126 patients with angiographically-significant CAD and group 2 the remaining 8 patients with nonsignificant CAD.

Angiographic Analysis

Significant CAD was defined as luminal coronary diameter stenosis of ≥70% in at least one major coronary artery: left anterior descending (LAD), circumflex artery, or right coronary artery. Significant left main disease was defined as luminal diameter stenosis of >50%. Multivessel CAD was defined as either significant left main disease, or 2-vessel or triple-vessel significant CAD.

Stress Test Protocol

Prior to treadmill exercise testing, patients were instructed to withdraw long-acting nitrates for 6 hours, calcium channel blockers for 24–48 hours, and β-blocking agents for 48 hours. Multistage treadmill exercise was performed using the Bruce protocol. Modified 12-lead electrocardiograms were recorded at rest, every 3 minutes thereafter, at peak exercise, and at each minute of the 5-minute recovery time. Fifty nine (44%) patients achieved ≥85% of maximal predicted heart rate. The remaining 75 (56%) patients, who were either unable to exercise or reach 85% of maximum predicted heart rate, underwent dipyridamole stress testing. Prior to dipyridamole pharmacological stress test, patients were instructed to stop caffeine consumption for 24 hours, and xanthine-containing medications for 36 hours. Dipyridamole (0.56 mg/kg) was infused intravenously over a 4-minute period with the patient in the sitting position, after which patients were encouraged to exercise on a treadmill for 3–4 minutes unless contraindicated. Modified 12-lead electrocardiograms were obtained at baseline prior to dipyridamole infusion, every 3 minutes thereafter for an 8-minute period, at peak stress, and at each minute during the 5-minute recovery time. A Tl-201 dose of 2.8–3.1 mCi was injected intravenously, either 1 minute prior to exercise termination or 4 minutes after termination of the dipyridamole infusion. Stress-induced chest pain (angina) and electrocardiographic changes of myocardial ischemia (defined as either the presence of ≥0.1 mV horizontal, downsloping or ≥0.15 mV upsloping ST-segment depression 80 ms after the J-point) during exercise or recovery, were recorded.

TD Assessment

Using the planar anterior views performed immediately before the stress and 4-hour redistribution single-photon emission computed tomography imaging, the TD ratio was calculated, as previously described.1,2 In brief, the epicardial border of the left ventricle was manually assigned by an experienced operator on both stress and redistribution images using an electronic marker. The left ventricular area encompassed by the relevant region was then determined and expressed as a number of pixels. The TD ratio was then calculated by dividing the left ventricular area on the stress images by the left ventricular area on the 4-hour redistribution images. TD was present if the TD ratio reached ≥1.12.1,2

Statistical Analysis

Statistical analyses were carried out using SPSS version 15.01 (SPSS Inc, Chicago, IL). Differences of continuous variables between the 2 groups of patients with significant and nonsignificant CAD were analyzed by independent t-test, differences of ordinal variables were analyzed by Mann–Whitney U, and differences of categorical variables by Fischer exact test. A model of logistic regression was not applied due to the small number of cases in the group of patients with nonsignificant CAD. All tests were 2-sided. The significance level was set at P=.05 (0.95 confidence intervals). P values were presented for all statistical tests.

Results

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. References

Baseline Characteristics

Baseline patient characteristics are shown in Table I. Compared with the patients with significant CAD, the 8 patients with nonsignificant CAD were characterized by a lack of diabetes mellitus (P=.05) or prior myocardial infarction (P=.05); all of them had either hypertension (7/8) or electrocardiographic criteria of LVH (1/8) (P=.02). An example is shown in the Figure. No significant differences in age, gender, hyperlipidemia, body mass index, smoking, family history of CAD, and left ventricle ejection fraction were noted between the 2 groups.

Table I.   Baseline Characteristics of the 2 Groups of Patients With TD
VariableSignificant CAD (n=126)Nonsignificant CAD (n=8)P Value
  1. Abbreviations: BMI, body mass index; CAD, coronary artery disease; SD, standard deviation; LVEF, left ventricle ejection fraction; LVH, left ventricular hypertrophy; PTCA, percutaneous transluminal coronary angioplasty; PVD, peripheral vascular disease; TD, left ventricular transient dilatation.

Age, y, mean ± SD66.4±12.058.9±14.8.09
BMI, mean ± SD27.8±7.531.3±4.1.19
LVEF, mean ± SD, %55.2±8.859.0±5.5.38
Female gender, n/%31.0/24.62.0/25.0.60
Hypertension and/or LVH, n/%73.0/57.98.0/100.02
Diabetes, n/%43.0/34.10.05
Hyperlipidemia, n/%85.0/67.54.0/50.0.44
Smoking, n/%25.0/19.83.0/37.5.36
Family history of CAD, n/%17.0/25.44.0/50.0.21
PVD, n/%17.0/13.52.0/25.0.31
History of coronary procedures and events
 PTCA34 (27.0)1 (12.5).68
 Coronary catheterization51 (40.5)2 (25.0).48
 Prior myocardial infarction440.05
image

Figure Figure.  Example of transient dilatation of the left ventricle (TD) (TD ratio = 1.32) during combined dipyridamole and exercise stress test in a 52-year-old man with hypertension and angiographically normal coronary arteries.

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Angiographic Data

Coronary angiographic data are shown in Table II. Significant and nonsignificant CAD were found in 126 patients (94.0%) and 8 patients (6%), respectively. Incidence of triple-vessel, 2-vessel, and single-vessel CAD was observed in 18.7%, 43.3%, and 32.1% of patients with TD, respectively. Among the 43 patients with single-vessel CAD, 34 (79%) demonstrated LAD disease. Multivessel CAD was observed in 83 patients (61.9%). Among patients with significant left main (SLM) disease (n=18), the coexistence of triple-vessel CAD was found in 10 patients, SLM and 2-vessel disease in 5, SLM with single-vessel disease in 2, and SLM alone in one patient.

Table II.   Coronary Angiography Data in Patients With Transient Dilatation of the Left Ventricle
Extent of CADNo. of Patients (%)
  1. Abbreviations: CAD, coronary artery disease; Cx, circumflex; LAD, left anterior descending; RCA, right coronary artery.

Significant CAD126/134 (94.0)
 Multivessel CAD 83/134 (61.9)
  Significant left main disease 18/126 (14.3)
  3-Vessel CAD 25/134 (18.7)
  2-Vessel CAD 58/134 (43.3)
 Single-vessel CAD 43/134 (32.1)
  LAD disease  34/43 (79.0)
  Cx disease  4/43 (9.0)
  RCA disease   5/43 (12.0)
Nonsignificant CAD 8/134 (6.0)

Discussion

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. References

The current study investigated the clinical characteristics of patients with nonsignificant CAD developing TD during stress myocardial perfusion imaging. Our findings are in accord with previous reports demonstrating that, in the majority of the cases, TD is a marker of severe CAD1–9 with sensitivity up to 94% for significant coronary disease in at least one major artery. Furthermore, in the current study, TD was associated with multivessel CAD in up to two-thirds of the patients, while the involved artery was the LAD in the majority (79%) of patients with TD and single-vessel disease.

Based on our data, the incidence of nonsignificant CAD in patients with TD was approximately 6%. Univariate analysis showed that patients with nonsignificant CAD demonstrated either hypertension or LVH. No diabetes mellitus or history of prior myocardial infarction was seen in this group of patients compared with patients with significant CAD. No differences in age, gender, body mass index, hyperlipidemia, smoking, and values of left ventricular ejection fraction were observed between the 2 groups.

Hypertension and LVH appear to be possible factors for TD development in patients with nonsignificant CAD, in accord with previous reports.17–19 A possible mechanism of stress-induced TD in hypertensive patients without significant CAD could be the reduction of coronary blood flow and impaired perfusion at stress in the hypertrophic myocardium.18 Furthermore, microvascular coronary disease or endothelial dysfunction could be a marker for early stages of coronary disease in hypertensive patients, which could in turn induce TD. A recent study18 concluded that hypertensive response to exercise is associated with a high prevalence of TD in patients without significant perfusion defects at myocardial perfusion imaging, possibly as a result of global subendocardial ischemia induced by this hypertensive response. However, since this study included no coronary anatomy data, it is impossible to determine whether hypertension is the single factor causing TD, or whether “hypertensive responders” have more extensive coronary disease, which could explain the development of TD. In contrast, in our study, where coronary anatomy was obtained in all patients, one could hypothesize that hypertension is the most important clinical factor for TD in patients with nonsignificant CAD.

Left ventricle TD during stress test seems to have similar characteristics found in catecholamine-induced cardiomyopathy (Takotsubo cardiomyopathy). In Takotsubo cardiomyopathy, severe emotional or physical stress precipitates prolonged left ventricle TD and left ventricular dysfunction in patients with nonsignificant CAD, that last for several weeks and may be demonstrated by left ventriculography, echocardiography, and myocardial perfusion imaging study.21,22 One could speculate that in patients with nonsignificant CAD during exercise or vasodilator stress, catecholamine activity is not severe nor sufficiently prolonged to cause TD for days or weeks, but rather only for a shorter time. The question whether hypertensive patients develop stress-induced TD more often than others may be a subject for further studies.

This retrospective single center study was designed to clinically and angiographically characterize patients who developed TD of the left ventricle during treadmill exercise or dipyridamole pharmacological stress test. This study is limited by its relatively small number of patients, especially in the nonsignificant CAD group of patients.

Hypertension seems to be an important clinical predictor of TD in patients with nonsignificant CAD. Additional, larger studies are needed to evaluate the independent role of hypertension, microvascular coronary disease, and endothelial dysfunction in the development of TD during stress myocardial perfusion imaging.

Acknowledgment and disclosure:  The authors wish to thank Mrs Vivienne York for her helpful editorial assistance in the preparation of this manuscript. The authors declare that there are no conflicts of interest regarding the possible publication of this original article.

References

  1. Top of page
  2. Abstract
  3. Materials and Methods
  4. Results
  5. Discussion
  6. References
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