Continuous recording of coronary sinus oxygen saturation during atrial pacing in patients with coronary artery disease or with syndrome X.

Coronary sinus oxygen saturation was measured continuously during incremental atrial pacing in 34 patients undergoing cardiac catheterisation. In eleven patients with normal coronary arteriograms, negative exercise tests, and no ST segment depression on the electrocardiogram, an increase in the rate of atrial pacing transiently decreased coronary sinus oxygen saturation but within 20 s oxygen saturation returned to the control value. In six patients with coronary artery disease ST segment depression developed during atrial pacing. The coronary sinus oxygen saturation fell and remained reduced until pacing was discontinued. The size of the fall of coronary sinus oxygen saturation increased with increasing heart rate. In seven patients with coronary artery disease the ST segments were unaltered during atrial pacing and coronary sinus oxygen saturation did not fall. Ten patients with syndrome X were studied. In six ST segment depression developed on atrial pacing. In five, three of whom developed ST segment depression, the changes in coronary sinus oxygen saturation during atrial pacing were similar to those observed in patients without any evidence of coronary artery disease. In three, all of whom developed ST segment depression, coronary sinus oxygen saturation gradually increased throughout the period of atrial pacing. In two patients coronary sinus oxygen saturation fell in a manner similar to that observed in patients with obstructive coronary artery disease who developed ST segment depression on pacing. Thus regulation of coronary blood flow in normal persons in response to an increase of heart rate is rapid. Oxygen extraction across the coronary bed can increase by up to 30% and a persistent increase in oxygen extraction is an indicator of myocardial ischaemia. The term "syndrome X" does not describe a homogeneous group of patients but in the majority coronary sinus oxygen saturation does not fall despite symptoms and changes on the electrocardiogram, indicating that inadequate coronary blood flow is not the dominant mechanism.     

Continuous monitoring of coronary sinus oxygen saturation during pacing loading in patients with syndrome X

To determine whether patients with syndrome X suffer from myocardial ischemia, coronary sinus oxygen saturation was continuously measured during pacing loading in 31 patients. Subjects were categorized by groups as syndrome X (11 patients), effort angina (14), and old myocardial infarction and valvular heart disease (6). Pacing loading induced evidence of ischemia in all syndrome X patients and in eight of the 11 patients with effort angina, while there was no such evidence in those with old myocardial infarction and valvular heart disease. Coronary sinus oxygen saturation in syndrome X decreased significantly from 44.2 +/- 5.8% to 33.5 +/- 4.4% (p less than 0.01), and it decreased from 47.0 +/- 4.9% to 31.2 +/- 4.0% (p less than 0.01) in effort angina with induced ischemic evidence, indicating that a significant reduction in coronary sinus oxygen saturation reflects the presence of myocardial ischemia. In the group with old myocardial infarction and valvular heart disease, coronary sinus oxygen saturation remained nearly unchanged during pacing. The pattern of depression of coronary sinus oxygen saturation during pacing was steeper in effort angina than in syndrome X. Therefore, we conclude that, although syndrome-X may not be a homogeneous group of patients, most of them may develop myocardial ischemia due to reduced vasodilator reserves of the small coronary artery.     

Regional myocardial perfusion during atrial pacing in patients with coronary artery disease.

Regional myocardial perfusion (RMP) was measured with 133xenon and a multiple-crystal scintillation camera at rest and during atrial pacing in 24 patients with normal coronary arteriograms or less than 50% lesions, Group I, and in 24 with significant (greater than 50% lesions) left coronary artery disease (CAD), Group II. Pacing induced increases in the double product (DP) of heart rate and systolic blood pressure, an index of myocardial oxygen consumption, were not different for Groups I and II. In Group I average mean LV perfusion rate was subnormal at rest but rose from 49 to 73 ml/100 g-min during pacing to 150/min without angina. A response index (RI), (deltaMP X 10(3)/deltaDP), averaged 2.93. Twenty patients in Group II developed angina during pacing. The average mean LV perfusion rose less than in Group I, from 48 to 64 ml/100 g-min (P less than 0.05) and the average RI, 1.76, was lower (P less than 0.01). In 19 of these patients, average RMP distal to the major coronary lesion increased from 46 to 58 ml/100 g-min; this increase during pacing was significantly less than in the remainder of the LV of 48 to 66 ml/100 g-min (P less than 0.05). Average regional RIs were 1.39 and 2.18, respectively. In three patients the presence of collaterals termed adequate by radiological criteria was not associated with preferential decreases in the distal regional RI. The data support the hypothesis that in some patients with CAD, angina pectoris results when an obstructive coronary lesion restricts the total or regional myocardial blood flow response to an increased rate of myocardial oxygen consumption.     

Effects of atrial pacing on arterial and coronary sinus endothelin-1 levels in syndrome X

Syndrome X may be caused by a coronary microvascular dysfunction, possibly due to abnormalities in coronary endothelial function. Previous studies suggested that endothelin-1 (ET-1) might be involved in the pathogenesis of syndrome X. Baseline arterial and coronary sinus ET-1 levels were measured in 13 patients with syndrome X (10 women, 52+/-7 years) and in 8 control patients (5 women, 46+/-11 years). ET-1 was also measured after atrial pacing in 12 patients with syndrome X and all controls. To simultaneously assess the activity of nitric oxide, guanosine 3'-5'-cyclic monophosphate (cGMP) was also measured in 11 patients with syndrome X and 7 controls. Baseline arterial (2.27+/-0.46 vs. 1.90+/-0.22 pg/ml, p<0.05) and coronary sinus (2.03+/-0.43 vs. 1.68+/-0.28 pg/ml, p = 0.06) ET-1 plasma levels were higher in patients than in controls. After pacing, arterial ET-1 levels did not change in either group and coronary sinus ET-1 levels were also unchanged in controls. In contrast, coronary sinus ET-increased significantly in response to atrial pacing in patients with syndrome X (p = 0.023), and differences between coronary sinus ET-1 levels of patients with syndrome X and controls after pacing became highly significant (2.22+/-0.45 vs. 1.69+/-0.20 pg/ml, respectively, p = 0.006). No significant differences in arterial and coronary sinus cGMP concentrations were found between the 2 groups, both at baseline and after pacing. Our findings suggest that an increased vasoconstrictor activity of microvascular endothelium is present in at least some patients with syndrome X and may be involved in the pathogenesis of the syndrome.     

Antiischemic and metabolic effects of glutamate during pacing in patients with stable angina pectoris secondary to either coronary artery disease or syndrome X.

The effects of glutamate on anginal threshold, cardiac metabolism and hemodynamics were studied in 11 patients with stable angina pectoris, positive stress test results, and pacing-induced myocardial lactate release due to coronary artery disease (CAD) (n = 9) or syndrome X (n = 2). Data were obtained before, during and after 2 identical periods of coronary sinus pacing, the second being preceded by an intravenous injection of monosodium glutamate 1.2 (n = 7) or 2.5 (n = 4) mg/kg body weight. After glutamate administration, pacing time to onset of angina increased from mean +/- standard deviation 103 +/- 53 to 166 +/- 71 seconds (p less than 0.01) and ST-segment depression after pacing decreased from 2.3 +/- 1.0 to 1.6 +/- 1.1 mm (p less than 0.01). Arterial glutamate concentration increased 60% (p less than 0.01) after the low dose and 150% (p less than 0.01) after the high dose of glutamate. Regardless of dose, myocardial glutamate uptake increased by 25% (p less than 0.01). Pacing-induced cardiac release of lactate diminished 50% (p less than 0.05), whereas the releases of xanthine and hypoxanthine were unchanged by glutamate. Arterial free fatty acids decreased 20% (p less than 0.01). Circulating levels and cardiac exchanges of alanine, glucose and citrate were unchanged. Glutamate did not influence heart rate, arterial blood pressure, coronary blood flow, coronary vascular resistance or myocardial oxygen consumption. One patient complained of short-lasting burning sensations after receiving the high glutamate dose. In conclusion, augmented provision of glutamate enhances pacing tolerance in stable angina, presumably by a metabolic improvement of cardiac energy production during ischemia.     

Reproducibility of metabolical parameters during successive coronary sinus pacing in patients known to have coronary artery disease

We have studied the reproducibility of myocardial extraction ratios of lactate, glucose and free fatty acids in patients with stable angina during atrial pacing. Two pacing periods, separated by an interval of 45 min, were imposed. The individual data were highly reproducible for lactate. Mean values for glucose and for free fatty acids were closely similar in the two successive tests, but the individual response was not so highly reproducible. We recommend the demonstration of the reproducibility of events during pacing in studies in which the effects of the therapeutic interventions are being assessed. This is especially so when observations are made in a small number of patients.     

Continuous measurement of coronary sinus oxygen saturation in patients with effort angina and vasospastic angina]

Coronary sinus oxygen saturation (CSO2-Sat) was measured continuously using a fiberoptic catheter system during interventional catheterization, i.e., pacing stress test and ergonovine provocation test to determine whether such measurement can detect myocardial ischemia. Subjects consisted of 24 patients who underwent routine cardiac catheterization; 14 patients with effort angina, 3 with old myocardial infarction and 3 with valvular heart disease were assigned to pacing stress test, and 4 with vasospastic angina were assigned to ergonovine provocation test. The results were as follows: 1. Among 14 patients with effort angina, ischemic electrocardiographic changes occurred in 10 patients during pacing stress test. Of these 10 patients, CSO2-Sat decreased in 8 with ischemic electrocardiographic changes. All patients with decrease in CSO2-Sat had significant left coronary artery stenosis. CSO2-Sat continued to decrease throughout intervention and never came back to the baseline. Decrease in CSO2-Sat was more than 5% in most of the cases. 2. In all patients with vasospastic angina, coronary vasospasm was induced by the ergonovine provocation test. CSO2-Sat declined (> 5%) gradually, preceding anginal pain and ischemic ST segment changes. The present study suggests that continuous monitoring of coronary sinus oxygen saturation may be useful in detecting myocardial ischemia at its early stage, except for patients with right coronary artery disease.     

High-density mapping of left atrial endocardial activation during sinus rhythm and coronary sinus pacing in patients with paroxysmal atrial fibrillation

INTRODUCTION: This study was designed to record global high-density maps of left atrial endocardial activation during sinus rhythm and coronary sinus pacing. METHOD AND RESULTS: Noncontact mapping of the left atrium was performed in nine patients with paroxysmal atrial fibrillation undergoing pulmonary vein ablation procedures. High-density isopotential and isochronal activation maps were superimposed on three-dimensional reconstructions of left atrial geometry. Mapping was repeated during pacing from sites within the coronary sinus. Earliest left atrial endocardial activation occurred anterior to the right pulmonary veins in seven patients and on the anterosuperior septum in two patients. A line of conduction block was seen in the posterior wall and inferior septum in all patients. The direction of activation in the left atrial myocardium overlying the coronary sinus was different from the electrogram sequence in the coronary sinus catheter in 6 of 9 patients. During coronary sinus pacing, activation entered the left atrium a mean (SD) of 41 (13) ms after the pacing stimulus at a site 12 (10) mm from the endocardium overlying the pacing electrode. Lines of conduction block were present in the posterior wall and inferior septum. CONCLUSION: In patients with paroxysmal atrial fibrillation, lines of conduction block are present in the left atrium during sinus rhythm and coronary sinus pacing. Electrograms recorded in the coronary sinus infrequently correspond to the direction of activation in the overlying left atrial myocardium.     

Characteristics of right atrial activation during coronary sinus pacing

INTRODUCTION: Anatomic and electrical connections between the left atrium and right atrium (RA) have been described. The relationship between coronary sinus (CS) pacing site and RA activation has not been examined. METHODS AND RESULTS: Fifteen anesthetized swine underwent high-density noncontact mapping of the RA during pacing from up to five different sites within the CS. Isopotential mapping identified the site of earliest RA depolarization and the pattern of subsequent activation. Hearts were excised and endocardial dissection performed. Earliest RA activation occurred at the CS os with proximal CS pacing sites and at Bachmann's bundle at distal pacing sites. The mean depth at which a shift in earliest RA activation site occurred was 46 +/- 13 mm (range 21 to 63 mm). RA activation times following earliest activation at the CS and Bachmann's bundle were 40 +/- 4 msec and 51 +/- 6 msec (P < 0.002). Conduction delay or block was recorded at the lateral cavotricuspid isthmus, terminal crest, and tendon of Todaro. Latest RA activation always occurred in the high anterolateral atrium after ascending the anterolateral wall. The lateral RA was activated by the wavefront that traversed the posterior wall rather than by the wavefront crossing the cavotricuspid isthmus, even with earliest RA activation at the CS os. CONCLUSION: The site of earliest RA activation during CS pacing is dependent upon the pacing depth within the CS. In the porcine heart, areas of conduction delay influence RA activation patterns and timings. These findings may have implications for patients undergoing assessment of radiofrequency ablation of atrial flutter.     

Left ventricular ejection power in coronary artery disease during atrial pacing.

Peak and mean left ventricular ejection power were measured during atrial pacing in 6 normal subjects (group I), 6 patients with coronary artery disease without myocardial infarction (group IIa), and 10 patients with coronary artery disease after myocardial infarction (group IIb). Pacing rates were 80 and 120/min. Power was determined by computer analysis of pressure, volume, and time. Data were normalised by end-diastolic volume and left ventricular muscle mass. Peak left ventricular ejection power normalised by end-diastolic volume values at a pacing rate of 120 min were significantly lower in group IIa and IIb than in normal subjects. Mean muscle mass in normal subjects was 179 g and in group IIa 216 g (P smaller than 0.05). Peak power normalised by muscle mass in normal subjects tended to increase at 120/min whereas in group IIa it declined by 26 per cent (P less than 0.001). These data indicate that the energy output of the left ventricle at rest may be the same in patients with significant coronary artery disease as in normal subjects. Increasing the heart rate from 80 to 120/min in a normal myocardium augments power but in coronary artery disease it remains static or falls.     

Left ventricular ejection power in coronary artery disease during atrial pacing.

Peak and mean left ventricular ejection power were measured during atrial pacing in 6 normal subjects (group I), 6 patients with coronary artery disease without myocardial infarction (group IIa), and 10 patients with coronary artery disease after myocardial infarction (group IIb). Pacing rates were 80 and 120/min. Power was determined by computer analysis of pressure, volume, and time. Data were normalised by end-diastolic volume and left ventricular muscle mass. Peak left ventricular ejection power normalised by end-diastolic volume values at a pacing rate of 120 min were significantly lower in group IIa and IIb than in normal subjects. Mean muscle mass in normal subjects was 179 g and in group IIa 216 g (P smaller than 0.05). Peak power normalised by muscle mass in normal subjects tended to increase at 120/min whereas in group IIa it declined by 26 per cent (P less than 0.001). These data indicate that the energy output of the left ventricle at rest may be the same in patients with significant coronary artery disease as in normal subjects. Increasing the heart rate from 80 to 120/min in a normal myocardium augments power but in coronary artery disease it remains static or falls.     

Feasibility and safety of transeophageal atrial pacing stress echocardiography in patients with known or suspected coronary artery disease

To investigate the feasibility and safety of the transesophageal atrial pacing stress test combined with echocardiography (TAPSE) 1,727 TAPSE tests were performed on 1,641 patients consecutively referred to our echocardiographic laboratory for nonexercise stress testing (1,319 men; mean age 60 ± 9 years; 34% of whom were outpatients). Wall motion abnormalities were present at baseline echocardiography in 975 cases (56%). TAPSE was feasible in 1,648 cases (95.4%). It was not feasible in 79 patients due to failure of positioning the transnasal catheter (n = 11), the patient's intolerance of esophageal stimulation (n = 24), failure to obtain any or stable atrial capture (n = 36), or because the echocardiogram could not be evaluated at the peak of the test (n = 8). TAPSE was diagnostic in 1,584 cases (96% of the feasible tests, 92% of all attempts). TAPSE was nondiagnostic in 64 cases (4% of the feasible tests) due to second-degree atrioventricular type I block resistance to atropine administration with failure to achieve 85% of the age-predicted maximum heart rate (n = 59) or due to side effects, such as arrhythmias (n = 3) or hypertension (n = 2), which required premature interruption of the test. There were no major complications (death, myocardial infarction, or life-threatening arrhythmias). There were 28 instances of minor complications that comprised transient arrhythmias, including atrial fibrillation (n = 8), paroxysmal supraventricular tachycardia (n = 6), automatic atrial tachycardia (n = 1), sinus arrest (n = 1), atrioventricular junctional rhythm (n = 2), ectopic atrial rhythm (n = 2), nonsustained ventricular tachycardia (maximum 6 beats, N = 3), hypotension (n = 1), and hypertension (n = 4) leading to interruption of the test. Only 5 complications hampered a diagnostic result, whereas 18 occurred during or after a positive test and 5 during a negative, but diagnostic, test. Thus, TAPSE is a highly feasible and very safe stress test. It gives high percentage of diagnostic tests and may represent a valid alternative to pharmacologic stressors.     

Radionuclide left ventricular function curve during atrial pacing in normal subjects and in patients with coronary artery disease

We used radionuclide angiography during right atrial pacing to assess left ventricular function in 7 normal subjects and 20 patients with coronary artery disease. A left ventricular function curve relating stroke volume to end-diastolic volume was plotted for each patient. The normal pacing ventricular function curve was a straight line passing through the origin of axes. The pacing ventricular function curve was abnormal in 18 of the 20 patients with coronary artery disease, and three different shaped curves were obtained, reflecting decreased contractile force for the same end-diastolic volume during ischemia. Cardiac output and blood pressure do not change during atrial pacing, thus the Frank-Starling relationship is evaluated by this method during almost experimentally controlled conditions. Relating stroke volume to end-diastolic volume, and not end-diastolic pressure, distinguishes between overall left ventricular systolic function and left ventricular compliance.     

The effects of atrial pacing on the signal-averaged electrocardiogram in patients with coronary artery disease

The effects of atrial pacing on the signal-averaged electrocardiogram were studied in 14 patients with remote myocardial infarction and a history of cardiac arrest or sustained ventricular tachycardia (group I) and in 13 patients with coronary artery disease and no history of sustained ventricular tachyarrhythmia (group II). Recordings of the signal-averaged electrocardiogram were obtained at control and during atrial pacing at rates of 80, 100, and 120 beats/min. All patients had recordings analyzed from at least two paced rates. At control, the mean high frequency total duration of the QRS complex (HFTD) was significantly longer in group I versus group II patients (123 +/- 5.6 versus 111 +/- 3.5 msec, p less than 0.05). Although the duration of the QRS signal under 40 microV (D40) was higher in group I versus group II patients (42 +/- 4.7 versus 32.4 +/- 3.5 msec) and the root mean square amplitude of the terminal 40 msec QRS (RMSA) was lower in the group I patients (27 +/- 7.5 versus 38.1 +/- 8.8 microV), these differences did not achieve statistical significance. There was no effect of atrial pacing on the measured signal-averaged parameters of HFTD, D40, and RMSA. Although there was a difference between group I and group II at each paced rate analyzed, atrial pacing did not help to further stratify the groups. In patients with coronary artery disease, atrial pacing is not a useful method of stratifying high-risk patients. Changes in serial signal-averaged electrocardiograms from the same patient are not due to heart rate variability.     

Diagnosis of coronary artery disease by thallium 201 myocardial scintigraphy during atrial pacing

Rapid atrial pacing may reveal myocardial ischemia but the sensitivity for the diagnosis of coronary artery disease is not high enough for routine use. Therefore, the value of atrial pacing coupled with Thallium 201 scintigraphy was evaluated. Sixty-two patients (53 men and 9 women) referred for investigation of angina or chest pain were divided into two groups: a control group of 13 patients (9 men and 4 women, average age: 57.1 years) with insignificant coronary lesions (less than 50%) (N = 5) or normal coronary angiography (N = 8), and a group of 49 patients (44 men and 5 women, average age: 55.5 years) 27 of whom had a history of myocardial infarction (17 posterior, 10 anterior). Coronary angiography showed single vessel disease in 44.9% of cases, double vessel disease in 34.7% and triple vessel disease in 18.4% of cases, and 1 patient with left main stem disease. All 62 patients underwent the same study protocol which comprised: incremental atrial pacing (to the calculated maximal heart rate), Thallium 201 myocardial scintigraphy immediately after pacing and during the redistribution phase, and coronary angiography. The sensitivities of anginal pain (36.7%) and ECG changes during atrial pacing (57.1%) were too low for the diagnosis of myocardial ischemia. On the other hand, Thallium 201 scintigraphy with atrial pacing was more sensitive (87.8%) and specific (84.6%) for coronary artery disease. Stenosis of the left anterior descending artery was diagnosed with a sensitivity of 96.4% and that of the right coronary artery with a sensitivity of 90.9%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevated plasma endothelin-1 levels in coronary sinus during rapid right atrial pacing in patients with slow coronary flow

The aim of the study was to evaluate whether there was an imbalance between endothelin-1 (ET-1) and nitric oxide (NOx) release and diffuse atherosclerotic changes existed in patients with slow coronary flow (SCF). Baseline and post-atrial pacing coronary sinus ET-1 and NOx levels were measured in 19 patients with SCF (11 female, 56 +/- 9 years) and in 14 control subjects (nine female, 54 +/- 7 years). All patients underwent subsequent intravascular ultrasound (IVUS) investigation at the same setting with right atrial pacing. Baseline arterial (12.4 +/- 9.9 vs. 6.3 +/- 5.1 pg/ml, P<0.005) and coronary sinus (12.2 +/- 11.1 vs. 6.4 +/- 6.9 pg/ml, P<0.005) ET-1 plasma levels were higher in patients than in controls. After atrial pacing, concentration of ET-1 level from coronary sinus (24.7 +/- 14.6) significantly increased as compared to baseline (12.4 +/- 9.9, P<0.0001) and control levels (5.3 +/- 6.3, P<0.0001). Additionally, coronary sinus ET-1 level increased significantly with atrial pacing compared to femoral artery ET-1 level (16.3 +/- 8.5, P<0.005) in patients with SCF. After atrial pacing, the femoral artery ET-1 level also increased in patients compared to control level (P<0.0001). No significant differences in arterial and coronary sinus NOx plasma levels were found between the two groups, both at baseline and after pacing. Upon IVUS investigation, the common finding was longitudinally extended massive calcification throughout the epicardial arteries in patients with SCF. Mean intimal thickness was 0.59 +/- 0.18 mm. The data of this study suggest that increased ET-1 levels and insufficient NOx response, as well as the pathological data of IVUS may be associated with coronary microvascular dysfunction and may be the manifestation of early diffuse epicardial atherosclerosis in these patients with SCF.