Abnormal autonomic control of the cardiovascular system in syndrome X

doi:10.1016/0002-9149(94)90177-5

The American Journal of Cardiology

Volume 73, Issue 16, 15 June 1994, Pages 1174-1179

https://doi.org/10.1016/0002-9149(94)90177-5 Get rights and content

Abstract

Anomalies of autonomic control of the coronary circulation may play a role in the development of syndrome X (angina pectoris, ischemia-appearing results on exercise test, and normal coronary arteriograms). Twenty-six patients with syndrome X and 20 healthy sex- and age-matched control subjects were studied by means of analysis of heart rate variability during 24-hour Hotter monitoring. Spectral and nonspectral parameters of heart rate variability were investigated. Mean heart rate was similar in patients with syndrome X and in control subjects. Patients with syndrome X had significantly lower standard deviation of all normal RR intervals, a lower percentage of adjacent normal RR intervals >50 ms in difference (126.4 ± 22 vs 149 ± 43 ms, p <0.05; 6.3 ± 4 vs 11.2 ± 7%, p <0.05; respectively), and a trend toward lower values of time-domain parameters. Lower values of total power and low frequency were also observed in patients with syndrome X (1273 ± 693 vs 1790 ± 989 ms², p <0.05; 406 ± 176 vs 729 ± 455 ms², p <0.01, respectively). An inverse correlation between heart rate and measures of heart rate variability was found in syndrome X but not in control subjects. High- and low-frequency power showed a similar circadian pattern in syndrome X patients and control subjects. Patients and control subjects were then allocated into 2 groups according to the median RR duration: syndrome X1 and control 1 with high mean heart rate, and syndrome X2 and control 2 with low mean heart rate. The syndrome X1 group had a significantly lower standard deviation of all normal RR intervals, root-mean-square difference of successive RR intervals, percentage of adjacent normal RR intervals >50 ms different, and high and low frequency than did the syndrome X2, control 1, and control 2 groups. In conclusion, patients with syndrome X have a sympathovagal balance shifted toward sympathetic predominance that is more evident in those with an increased mean heart rate. This dysfunction appears to persist throughout the 24 hours and may indicate heterogeneity in autonomic function in syndrome X.

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Coronary lumen volume to myocardial mass ratio in primary microvascular angina
2017, Journal of Cardiovascular Computed Tomography
Microvascular angina (MVA) is an incompletely understood clinical entity. Computational analysis of coronary Computed Tomography Angiography (CTA) has shown an association between low coronary lumen volume to myocardial mass (V/M) ratio and lower Fractional Flow Reserve values, independent of plaque measures. We hypothesized that low V/M ratio may be present in patients with MVA.
A retrospective case-control analysis was performed using patients fulfilling guideline criteria for MVA with controls matched for age, gender, coronary risk factors and atherosclerotic plaque burden. V/M was extracted off site (Heartflow Inc; Redwood City, CA) employing allometric scaling laws that allow the definition of the coronary circulation beyond the epicardium. FFR_CT values were calculated in the major epicardial coronary arteries for each group.
A total of 30 patients with MVA and 32 matched controls were included in the study. Mean total coronary lumen volume (2302 mm³ ± 109 vs 2978 mm³ ± 134, p < 0.001) and mean myocardial mass (90.4 g ± 13.7 vs 100.4 g ± 20.1, p = 0.029) were lower in MVA patients compared to controls. Mean V/M ratio was significantly lower in MVA compared to controls (25.6 mm³/g ± 5.9 vs 30.0 mm³/g ± 6.5, p = 0.007; c-statistic 0.69). V/M ratio did not differ significantly between subclasses of angina severity (p = 0.747). No difference in mean nadir FFR_CT values was found between MVA and control groups in the LAD (0.86 ± 0.07 vs 0.83 ± 0.07, p = 0.154), LCX (0.90 ± 0.05 vs 0.90 ± 0.06, p = 0.240) and RCA (0.90 ± 0.04 vs 0.90 ± 0.03, p = 0.773) vessels.
Patients with microvascular angina demonstrate a significantly lower coronary CTA-derived coronary volume/myocardial mass ratio than asymptomatic controls.
Effects of neuropeptide Y on coronary artery vasomotion in patients with microvascular angina
2017, International Journal of Cardiology
Citation Excerpt :
Recently, it has been reported that in patients with microvascular angina the abnormal vasodilator response affects not only the coronary vascular smooth muscle but also the systemic vasculature [14]. The reason for the abnormal behaviour of the microcirculation in microvascular angina is unknown, but it has been suggested that an increased sympathetic drive may play a pathogenic role [12,15,16]. Neuropeptide Y (NPY), a 36 aminoacid peptide [17] endogenous to human coronary arteries [18], has been shown to increase coronary vascular resistance in animal models [19].
Patients with microvascular angina (exertional angina, positive exercise tests and normal coronary arteriograms) usually have a reduced coronary blood flow reserve. Neuropeptide Y (NPY) is a potent endogenous vasoconstrictor involved in modulation of coronary vasomotor tone and may play a role in microvascular angina.
We compared the effects of NPY (0.2–1.0 pmol/kg, intracoronary) on the vasomotor response of proximal and distal segments of the coronary arteries in 7 patients with microvascular angina, 9 with chronic stable angina, and 9 control individuals. The coronary response to the administration of ergonovine was also assessed in 9 other patients with microvascular angina. Computerized coronary artery diameter measurements were carried out before (baseline) and after the administration of the vasoactive agents.
Mean baseline coronary lumen diameters were similar in control, microvascular angina, and coronary artery disease patients. NPY constricted proximal coronary segments by 8 ± 2%, 5 ± 2% and 6 ± 3% and distal segments by 14 ± 2%, 11 ± 2% and 10 ± 2% in control, microvascular angina, and coronary artery disease patients, respectively (p = NS between groups). In patients with microvascular angina, ergonovine constricted proximal coronary segments by 7 ± 1.5% and distal segments by 12.5 ± 3% (p = NS vs. NPY). During NPY administration four microvascular angina patients developed chest pain, ST segment depression, and a marked lengthening of the contrast medium run off, in the absence of epicardial coronary artery spasm. Control individuals and coronary artery disease patients did not experience chest pain, ST segment shifts, or lengthening of the run off during NPY administration. Ergonovine administration caused chest pain and lengthening of the contrast run-off, in the absence of epicardial coronary artery spasm, in one microvascular angina patient.
Exogenous NPY causes mild epicardial coronary artery constriction which is similar in patients with non-cardiac chest pain, microvascular angina and coronary artery disease. Myocardial ischemia and marked lengthening of the contrast run off in response to NPY occurred in microvascular angina patients but not in control or coronary artery disease patients. An abnormal constrictor response to NPY at the microcirculation level could be the mechanism underlying the ischemic manifestations observed in patients with microvascular angina.
The vasomotor response of proximal and distal coronary artery segments was studied in twenty five patients: 7 microvascular angina, 9 chronic stable angina, and 9 control subjects. Computerized measurements of coronary diameters were carried out before and after the intracoronary administration of neuropeptide Y (NPY) and ergonovine. Constriction of epicardial arteries in response to NPY was mild and not significantly different in control, microvascular angina and coronary artery disease patients. Ergonovine-induced epicardial coronary artery constriction was similar to that of NPY. However, NPY caused transient myocardial ischemia in patients with microvascular angina (probably through constriction of the small intramyocardial vessels), but not in control subjects or coronary artery disease patients.
Opium addiction as an independent risk factor for coronary microvascular dysfunction: A case-control study of 250 consecutive patients with slow-flow angina
2016, International Journal of Cardiology
Citation Excerpt :
MCD involves a phenomenon in which maximal hyperemic extrinsic stimuli (e.g., adenosine) enhance coronary volumetric blood flow less than 2.5-folds, which is the lower limit of normal flow reserve in coronary arteries free of significant obstructive CAD [4]. The etiology of microvascular angina is likely multi-factorial, however several contributory pathogenic mechanisms have been proposed, including endothelial dysfunction, insulin resistance [5], abnormal autonomic control [6], altered cardiac sensitivity [7] and estrogen deficiency [8]. Women (usually during per menopausal period) develop signs and symptoms of myocardial ischaemia more than men, but also exhibit obstructive CAD to a lesser extent than men when investigated with coronary angiography [9,10].
Approximately 20% to 30% of patients who undergo coronary angiography for assessment of typical cardiac chest pain display microvascular coronary dysfunction (MCD). This study aimed to determine potential relationships between baseline clinical characteristics and likelihood of MCD diagnosis in a large group of patients with stable angina symptoms, positive exercise test and angiographic ally normal epicardial coronary arteries.
This cross-sectional study included 250 Iranian with documented evidence of cardiac ischemia on exercise testing, class I or II indication for coronary angiography, and either: (1) angiographically normal coronary arteries and diagnosis of MCD with slow-flow phenomenon, or (2) normal angiogram and no evidence of MCD. All patients completed a questionnaire designed to capture key data including clinical demographics, past medical history, and social factors. Data was evaluated using single and multivariable logistic regression models to identify potential individual patient factors that might help to predict a diagnosis of MCD.
125 (11.2% of total) patients were subsequently diagnosed with MCD. 125 consecutive control subjects were selected for comparison. The mean age was similar among the two groups (52.38 vs. 53.26%, p = ns), but there was a higher proportion of men in the study group compared to control (42.4 vs. 27.2%, p = 0.012). No significant relationships were observed between traditional cardiovascular risk factors (diabetes, hypertension, and dyslipidemia) or body mass index (BMI), and likelihood of MCD diagnosis. However, opium addiction was found to be an independent predictor of MCD on single and multivariable logistic regression model (OR = 3.575, 95%CI: 1.418–9.016; p = 0.0069).
We observed a significant relationship between opium addiction and microvascular angina. This novel finding provides a potential mechanistic insight into the pathogenesis of MCD with slow-flow phenomenon.
Autonomic findings in takotsubo cardiomyopathy
2016, American Journal of Cardiology
Takotsubo cardiomyopathy (TC) often occurs after emotional or physical stress. Norepinephrine levels are unusually high in the acute phase, suggesting a hyperadrenergic mechanism. Comparatively little is known about parasympathetic function in patients with TC. We sought to characterize autonomic function at rest and in response to physical and emotional stimuli in 10 women with a confirmed history of TC and 10 age-matched healthy women. Sympathetic and parasympathetic activity was assessed at rest and during baroreflex stimulation (Valsalva maneuver and tilt testing), cognitive stimulation (Stroop test), and emotional stimulation (event recall, patients). Ambulatory blood pressure monitoring and measurement of brachial artery flow–mediated vasodilation were also performed. TC women (tested an average of 37 months after the event) had excessive pressor responses to cognitive stress (Stroop test: p <0.001 vs baseline and p = 0.03 vs controls) and emotional arousal (recall of TC event: p = 0.03 vs baseline). Pressor responses to hemodynamic stimuli were also amplified (Valsalva overshoot: p <0.05) and prolonged (duration: p <0.01) in the TC women compared with controls. Plasma catecholamine levels did not differ between TC women and controls. Indexes of parasympathetic (vagal) modulation of heart rate induced by respiration and cardiovagal baroreflex gain were significantly decreased in the TC women versus controls. In conclusion, even long after the initial episode, women with previous episode of TC have excessive sympathetic responsiveness and reduced parasympathetic modulation of heart rate. Impaired baroreflex control may therefore play a role in TC.
Usefulness of impairment of cardiac adrenergic nerve function to predict outcome in patients with cardiac syndrome X
2010, American Journal of Cardiology
Patients with cardiac syndrome X (CSX) have an excellent long-term prognosis, but a significant number show worsening angina over time. Previous studies have found a significant impairment of cardiac uptake of iodine-123-meta-iodobenzylguanidine (MIBG) on myocardial scintigraphy, indicating abnormal function of cardiac adrenergic nerve fibers. The aim of this study was to assess whether cardiac MIBG results can predict symptomatic outcome in patients with CSX. Cardiac MIBG scintigraphy was performed in 40 patients with CSX (mean age 58 ± 5 years, 14 men). Cardiac MIBG uptake was measured by the heart/mediastinum uptake ratio and a single photon-emission computed tomographic regional uptake score (higher values reflected lower uptake). Clinical findings, exercise stress test parameters, sestamibi stress myocardial scintigraphy, and C-reactive protein serum levels were also assessed. At an average follow-up of 79 months (range 36 to 144), no patient had died or developed acute myocardial infarction. Cardiac MIBG defect score was significantly lower in patients with worsening versus those without worsening of angina status (13 ± 7 vs 38 ± 28, p = 0.001), in those with versus those without hospital readmission because of recurrent chest pain (15 ± 9 vs 35 ± 29, p = 0.01), and in those who underwent versus those who did not undergo repeat coronary angiography (11 ± 7 vs 36 ± 27, p = 0.001). Significant correlations were found between quality of life (as assessed by the EuroQoL scale) and heart/mediastinum ratio (r = 0.48, p = 0.002) and cardiac MIBG uptake score (r = −0.69, p <0.001). No other clinical or laboratory variable showed a significant association with clinical end points. In conclusion, in patients with CSX, abnormal function of cardiac adrenergic nerve fibers, as assessed by an impairment of cardiac MIBG uptake, identifies those with worse symptomatic clinical outcomes.
Microvascular Angina and the Continuing Dilemma of Chest Pain With Normal Coronary Angiograms
2009, Journal of the American College of Cardiology
Citation Excerpt :
The clinical implications of these findings, however, are uncertain: similar abnormalities of coronary microvascular function may exist in asymptomatic subjects who have no indication for cardiac catheterization and invasive study of coronary dynamics. Several conditions have been proposed to account for coronary microvascular dysfunction, including altered autonomic tone (34,35), insulin resistance (36–38), enhanced ion transport across cell membranes (39), increased endothelin-1 release (40,41), estrogen deficiency (42), and endothelial dysfunction (43–45). In many cases, patients were selected for invasive study based on an abnormal test result, such as from treadmill stress ECG or nuclear perfusion imaging, consistent with inducible ischemia.
Since initial reports over 4 decades ago, cases of patients with angina-like chest pain whose coronary angiograms show no evidence of obstructive coronary artery disease and who have no structural heart disease continue to be a common occurrence for cardiologists. Many features of this patient population have remained constant with successive reports over time: a female predominance, onset of symptoms commonly between 40 and 50 years of age, pain that is severe and disabling, and inconsistent responses to conventional anti-ischemic therapy. Because patients may have had abnormal noninvasive testing that led to performance of coronary angiography, investigators have sought to show an association of this syndrome with myocardial ischemia. Abnormalities in coronary flow and metabolic responses to stress have been reported by several groups, findings consistent with a microvascular etiology for ischemia and symptoms, but others have questioned the presence of ischemia, even in patients selected for abnormal noninvasive testing. Despite considerable efforts by many groups over 4 decades, the syndrome remains controversial with regard to pathophysiology, diagnosis, and management.

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Abnormal autonomic control of the cardiovascular system in syndrome X

Abstract

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