The nature of the background in radionuclide ventriculography: deductions from the mathematical behaviour of the ejection fraction.

The relationship between the ejection fractions calculated from 'uncorrected' radionuclide time activity curves (UEF) and angiographic ejection fractions (AEF) in 200 catheterized patients yielded the regression equation AEF = 1.74 UEF + 0.21. It follows from this linear relationship that the left ventricular ejection fraction can be estimated by linear regression without explicit background correction: RREF = 1.74 UEF + 0.21, where RREF is the radionuclide regression ejection fraction. We first investigated the possibility that changes in photon self-attenuation within the cardiac chambers cause the observed mathematical characteristics of the cardiac background, B. Self-attenuation was calculated for cylindrical and spherical ventricular models. The results were insensitive to the particular geometry and would have only a small effect on the observed EF. Alternatively, the 'background' may result from extra-ventricular radiation scattering from the heart into the detector. If we assume that B should be proportional to the ventricular scattering volume, Bd = Kd EDC for diastole and Bs = Ks ESC for systole, the background corrected ejection fraction will be BCEF = K UEF + (1-K) where K = (1-Ks)/(1-Kd). This agrees with the form of the empirical regression equation.

Asymmetric distribution of left ventricular asynergy in coronary artery disease and its relation to coronary stenoses.

In 100 patients with coronary artery disease (CAD), the prevalence and severity of asynergy was determined for 9 left ventricular (LV) segments by both radionuclide and contrast angiography. The anterior, septal and lateral LV walls had significantly more prevalent and more severe asynergy in the medial segments than in the basal segments. In contrast, the inferior LV wall exhibited equally severe asynergy in both the medial and basal segments. In general, asynergy was most severe in the apical, medial septal, medial inferior and basal inferior LV segments. This asymmetric distribution of LV asynergy could not be explained by the distribution of occlusions or significant stenoses in the arterial tree, which were relatively uniformly distributed among the left anterior descending (32%), left circumflex (29%) and right (26%) coronary arteries. It is postulated instead that the asymmetric distribution of LV asynergy results from asymmetry of the coronary arterial tree supplying the left ventricle and that the prevalence of asynergy in an LV segment is directly related to its vascular distance from the coronary ostia. Unlike the relatively direct supply of the left anterior descending and circumflex arteries to the basal segments of the anterior, septal and lateral LV walls, the arterial supply to the basal inferior wall begins only after the right or dominant circumflex artery has traversed the length of the atrioventricular groove, significantly increasing its susceptibility to the pressure attenuation and occlusive jeopardy of more proximal stenoses.

No increase in serum digoxin concentration with high-dose diltiazem.

The effect of incremental diltiazem dosing during concomitant digoxin administration over a four-week period in eight healthy adult volunteers (mean age, 28 +/- 4 years) was studied. The study group received 0.25 mg of digoxin twice daily for two days, after which they received 0.25 mg daily for the duration of the study. Following baseline electrocardiographic evaluation and measurement of trough digoxin levels, all subjects received 120 mg of diltiazem daily for one week, then 240 mg daily for one week, followed by 360 mg daily for one week. Resting electrocardiographic parameters (heart rate, P-R interval), renal function, electrolyte values, and digoxin and diltiazem concentrations were measured weekly. Daily administration of 360 mg of diltiazem plus 0.25 mg of digoxin resulted in a significant decrease in heart rate (from 68 +/- 9 beats per minute to 61 +/- 10 beats per minute; p less than 0.05), a marginal increase in P-R interval (from 169 +/- 22 msec to 179 +/- 21 msec; p = 0.08), and no significant change in trough serum digoxin concentration (from 0.85 +/- 0.08 ng/ml to 0.90 +/- 0.08 ng/ml; p = NS). The administration of up to 360 mg of diltiazem per day with 0.25 mg of digoxin per day was not associated with significant increases in serum digoxin concentrations in healthy subjects.

Prevalence and severity of circumflex coronary artery disease in electrocardiographic posterior myocardial infarction.

To determine the coronary anatomy responsible for electrocardiographic posterior myocardial infarction, the prevalence and severity of disease in the right coronary and left circumflex coronary arteries were compared in 21 patients with electrocardiographic posterior infarction (17 of whom had associated inferior infarction) and 23 patients with isolated electrocardiographic inferior infarction. Significant circumflex coronary artery disease (greater than or equal to 75% stenosis) was more prevalent in patients with posterior or inferoposterior infarction (17 of 21) than in those with isolated inferior infarction (11 of 23) (p less than 0.02). Significant right coronary artery disease was less prevalent in patients with posterior or inferoposterior infarction (16 of 21) than in those with isolated inferior infarction (23 of 23) (p less than 0.05). Among the 21 patients with posterior or inferoposterior infarction, disease was more severe in the circumflex coronary artery in 10 and the right coronary artery in 5 and was of equal severity in 6. Among the 23 patients with isolated inferior infarction, the more diseased artery was the right coronary artery in 21 and the circumflex artery in 2 (p less than 0.001 by chi-square analysis). Variant patterns of coronary artery dominance accounted for only 4 of the 17 patients with inferoposterior infarction. These data suggest that the likely substratum for electrocardiographic posterior or inferoposterior infarction is severe circumflex coronary artery disease, usually in association with significant right coronary artery disease. The pattern of tall, wide R waves in leads V1 or V2 (RV1,2) in patients with inferior infarction is highly predictive of at least two vessel coronary artery disease.

Beneficial effects of high-dose diltiazem in patients with persistent effort angina on beta-blockers and nitrates: a randomized, double-blind, placebo-controlled cross-over study.

The effects of orally administered diltiazem combined with maximally tolerated doses of beta-blockers and nitrates were assessed in 12 patients, who during stress testing exhibited persistent effort angina and continued objective evidence for inducible myocardial ischemia. Patients performed multistage semisupine exercise on a bicycle ergometer during equilibrium-gated radionuclide angiography after consecutive 2 week treatment periods of placebo or diltiazem 90 mg qid (mean dose 340 mg/day) combined with maximally tolerated propranolol (mean dose 178 mg/day) and isosorbide dinitrate (mean dose 137 mg/day). All medications (including diltiazem or placebo) were administered four times daily for the duration of the study. Diltiazem or placebo was administered according to a double-blind design, with randomized cross-over at the end of each 2 week treatment period. The average number of angina attacks decreased during the double-blind cross-over phase of the trial (7 +/- 7 episodes/week at baseline vs 4 +/- 3 on placebo vs 2 +/- 2 on diltiazem; p = .08). Angina pectoris was abolished during peak exercise in eight of 12 patients on diltiazem (p less than .05 vs placebo). Diltiazem increased total exercise duration from 276 +/- 92 to 310 +/- 78 sec (p less than .005 vs baseline). Diltiazem likewise increased the time to onset of angina from 231 +/- 84 sec at baseline to 305 +/- 77 sec (p less than .005), as well as the time to the onset of 1 mm ischemic ST segment depression (p = .01). Diltiazem decreased heart rate at rest, during submaximal workload, and at peak exercise (p less than .05), and decreased systolic blood pressure at peak exercise only (p less than .05). A significant decline in rate-pressure product at submaximal and peak exercise was noted (p less than .05). At any given workload there was significantly less ST segment depression during submaximal (p = .05) and peak exercise (p less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)

Nifedipine-induced hypotension and myocardial ischemia in refractory angina pectoris.

Combined nitrate/beta-blocker/nifedipine therapy is commonly used to treat refractory angina pectoris. We have observed "paradoxical" myocardial ischemia in ten patients with refractory angina (seven receiving combined beta-blocker and nitrate therapy, and three receiving nitrate treatment alone) in whom nifedipine (mean dosage, 92 mg/day; range, 60 to 120 mg/day) induced a decrease in blood pressure, angina pectoris (10/10 patients), and ischemic ECG changes (7/10 patients). These ten patients, all of whom regularly reported angina within 20 to 30 minutes of nifedipine ingestion, were prospectively studied before and after usual nifedipine dose administration, while blood pressures, heart rate, and ECGs were recorded. Mean systolic BP fell from 109 to 94 mm Hg after nifedipine (P less than .001, paired t test); mean heart rate increased from 64 to 68 beats per minute (P less than .05); seven patients developed transient ECG changes (five with ST-T wave depression and two with ST-T wave elevation) during the hypotensive period. Nifedipine may provoke angina and myocardial ischemia in certain patients with refractory angina pectoris receiving concomitant beta-blocker and nitrate therapy.

Inferoseptal myocardial infarction: another cause of precordial ST-segment depression in transmural inferior wall myocardial infarction?

Electrocardiographic ST-segment depression in the anterior precordial leads is a frequent observation during the initial hospital phase of acute transmural inferior myocardial infarction (MI), but is of uncertain significance. No available clinical studies have examined the prevalence of inferoseptal necrosis complicating inferior MI. Therefore, the clinical course, electrocardiographic features, radionuclide angiograms and cardiac enzyme changes in 57 patients with transmural inferior MI who did not have prior anterior or concomitant "true posterior" MI, associated anterior or posterolateral asynergy by radionuclide ventriculography, or left or right bundle branch block were reviewed retrospectively. Patients were categorized according to the presence (group A) or absence (group B) of precordial ST-segment depression and according to the presence (group I) or absence (group II) of radionuclide septal wall motion abnormalities. There were no significant differences in global left ventricular ejection fraction (group A, 49 +/- 8, group B, 52 +/- 41; group I, 51 +/- 7, group II, 51 +/- 6), right ventricular ejection fraction (group A, 45 +/- 9, group B, 42 +/- 7; group I, 43 +/- 8, group II, 41 +/- 8), or clinical outcome in the hospital. However, chi-square analysis revealed a significant (p less than 0.05) association between the presence or absence of septal asynergy and the presence or absence of precordial ST depression. In addition, average peak creatine kinase elevation (group I, 761 +/- 164 IU; group II, 698 +/- 178 IU) attained marginal significance by paired t test (p = 0.06). Precordial ST-segment depression during transmural inferior MI is frequently associated with septal asynergy by gated radionuclide angiography (15 of 26 patients, 58%).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular asynergy in electrocardiographic "posterior" myocardial infarction.

P2 300 selected patients, scalar electrocardiograms and contemporaneous radionuclide angiograms were analyzed retrospectively to assess the association between prominent right precordial R waves (duration greater than or equal to 0.04 second, R greater than or equal to S in lead V1 or V2), traditionally considered diagnostic of "posterior" infarction, and asynergy in various left ventricular segments. Mathematical methods for analysis of association between nonparametric variables clearly demonstrated that prominent right precordial R waves were strongly associated with asynergy of the basal lateral left ventricular wall, although asynergy of adjacent inferior and lateral segments was common. With the exclusion of right ventricular hypertrophy and bundle branch block, a prominent R wave in lead V1 exhibited a high specificity (greater than to 99%), a high positive predictive value (91%) and a low sensitivity (36%) for diagnosing basal lateral myocardial infarction. A prominent R wave in lead V2 exhibited a higher sensitivity (61%), a somewhat lower specificity (95%) and a significantly lower positive predictive value (76%). A newly developed criterion for such infarction--a prominent R wave in lead V2 and a Q wave inferior infarction--had intermediate characteristics and may be more clinically useful. The most common reasons for the decreased sensitivities of all three criteria were left ventricular hypertrophy or associated anterior myocardial infarction. These data demonstrate that prominent right precordial R waves are clinically useful in identifying inferior and lateral wall infarctions that involve the basal lateral left ventricular segment. Confusion results primarily from inappropriate use of the electrocardiographic term "posterior" for such infarctions.

Unstable angina with episodic ST segment elevation and minimal creatine kinase release culminating in extensive, recurrent infarction.

The syndrome of episodic angina at rest, recurrent ST segment elevation (mean = 9 mV) and nontransmural infarction characterized by minimal serum creatine kinase (CK) (mean 243 IU; upper normal limit 132 IU) was studied in 15 patients who presented with these findings. All were initially managed with intensive nitrate and beta-receptor blocker therapy. Eleven patients underwent intraaortic balloon counterpulsation for refractory angina and 13 underwent cardiac catheterization. High grade (greater than or equal to 90%) stenosis of the proximal left anterior descending coronary artery was demonstrated in 11 patients, and coronary spasm without significant, fixed occlusive disease was noted in 2 patients. Urgent aortocoronary bypass surgery was performed in seven patients with recurrent pain or electrocardiographic injury, or both, unresponsive to maximal medical therapy. The initial mean ST segment elevation and CK elevation for this group was 10 mV and 232 IU, respectively. No surgical patient developed recurrent infarction; there was one late death after reoperation. Eight patients whose condition stabilized initially on medical therapy did not undergo urgent surgery. However, five subsequently developed large transmural anterior reinfarction despite intensive medical therapy, and three died from pump failure. These patients on medical therapy did not differ from the surgical group in magnitude of ST segment elevation or increase in serum CK. Their initial mean ST segment elevation and CK elevation were 8 mV and 254 IU, respectively (difference not significant). Thus, repetitive episodes of rest angina with marked anterior wall ST segment elevation and mild CK elevations may define a subset of patients who appear to progress rapidly from minimal nontransmural necrosis to massive transmural infarction. Prompt recognition of this syndrome, followed by cardiac catheterization and urgent aortocoronary bypass surgery, may prevent extensive cardiac muscle loss.

Calculation of the left ventricular ejection fraction by gated radionuclide angiography without direct background correction.

The mathematical characteristics of the cardiac background were studied in 50 patients who underwent both gated radionuclide angiography and cardiac catheterization. The background-corrected ejection fraction (BCEF) was calculated in the standard manner using an operator-defined periventricular background region. The "uncorrected" ejection fraction (UEF) was calculated from the uncorrected left ventricular time-activity curve and compared to both the BCEF and the angiographic ejection fraction (AEF), UEF exhibited remarkable linear correlation with both BCEF and AEF. The empirically determined linear regression equation, AEF = 2.18 (UEF) + 0.13, allowed calculation of a radionuclide ejection fraction corresponding to angiographic methods without direct background correction. When measurement of the left ventricular ejection fraction using this linear regression method was tested prospectively in 25 catheterized patients, the radionuclide regression ejection fraction showed excellent linear correlation with AEF (r = 0.85) and minimal inter-observer variability.

Hemodynamic correlates of right ventricular ejection fraction measured with gated radionuclide angiography.

Right ventricular function was studied in 60 patients with equilibrium gated radionuclide angiography. The mean (+/- standard deviation) right ventricular ejection fraction in 20 normal subjects was 53 +/- 6 percent, a value in agreement with previous data from both radionuclide and contrast angiographic studies. This value was similar (55 +/- 7 percent) in 11 patients with coronary artery disease but normal left ventricular function. Radionuclide measurements of right ventricular ejection fraction were correlated with right heart hemodynamics. There was a significant negative linear correlation between right ventricular ejection fraction and mean pulmonary arterial pressure (r = -0.82) and between right ventricular ejection fraction and right ventricular end-diastolic pressure (4 = -0.67). Furthermore, patients with elevated right ventricular end-diastolic pressure and mean pulmonary arterial pressure had a more severely depressed ejection fraction than did those with an elevated mean pulmonary arterial pressure alone. Thus, an abnormal value for right ventricular ejection fraction by gated radionuclide angiography in the absence of primary right ventricular volume overload suggests abnormal right heart pressures, whereas a normal value excludes severe pulmonary arterial hypertension or an elevated right ventricular end-diastolic pressure.

Measurement of normal left atrial function with gated radionuclide angiography.

A method is described for measuring relative left atrial volume changes with gated radionuclide angiography, using an approximate computer-generated functional image to locate the atrial region of interest. M mode echocardiographic measurements of left atrial and left ventricular distances from the chest wall allowed calculation of a correction factor for the differential attenuation of atrial and ventricular photons. Background-corrected left atrial time-activity curves obtained from normal subjects exhibited excellent temporal resolution and were used to identify and quantitate the reservoir and contractile phases of left atrial volume change. In 20 normal subjects, the mean (+/- standard deviation) value for left atrial fractional emptying was 0.39 +/- 0.07. Expressed as fractions of the left ventricular stroke volume, mean values of the specific phases of atrial volume change were (1) reservoir volume 0.25 +/- 0.09, (2) contractile volume 0.29 +/- 0.10, and (3) conduit volume 0.46 +/- 0.12.

Exercise-induced coronary spasm with S-T segment depression and normal coronary arteriography.

The unique association of both exercise-induced coronary arterial spasm and S-T segment depression with normal findings on selective coronary arteriography is described. The patient had a prior history of typical effort angina that had recently progressed to angina at rest. Despite the change in anginal pattern, the electrocardiogram disclosed S-T segment depression that was consistent with subendocardial ischemia, during both exercise testing and spontaneous chest pain. Exercise thallium-201 scintigraphy demonstrated the presence of large perfusion defects of the anterior and septal walls of the left ventricle. Coronary arteriographic findings, in the absence of symptoms, were entirely normal. Severe localized, reversible coronary spasm of the proximal left anterior descending coronary artery was subsequently demonstrated during spontaneous angina, isometric arm exercise and after the administration of ergonovine maleate. After treatment with isosorbide dinitrate and nifedipine, the patient had no further chest pain or electrocardiographic changes, and a repeated thallium-201 stress test revealed normal findings and greatly improved exercise tolerance.

Measurement of the ventricular stroke volume ratio by gated radionuclide angiography.

The ventricular stroke volume ratio or VSVR (left/right) was measured by gated radionuclide angiography in 33 normal subjects, using a 30 degree caudal slant-hole collimator and computer-generated functional images to aid in definition of the right ventricle. The mean ratio was found to be 1.06 +/- 0.05, compared to the normal value of 1.00. Comparative studies indicated that definition of the right ventricle based on the end-diastolic frame alone or standard collimation without caudal angulation commonly causes overestimation of the VSVR and considerably greater variance between measurements. Such errors are the result of inadequate atrioventricular separation and/or underestimation of the right-ventricular region.

Tricuspid valve replacement for cardiogenic shock after acute right ventricular infarction.

A 66-year-old man had an acute inferior wall myocardial infarction complicated by hypotension, high-grade atrioventricular block, and distended neck veins, suggesting associated right ventricular infarction. He failed to respond to volume loading, intra-aortic balloon counterpulsation, and pharmacologic afterload reduction. Cardiac catheterization five days after the infarction disclosed severe tricuspid regurgitation and a hemodynamic pattern resembling pericardial constriction. Emergency tricuspid valve replacement was dramatically successful.

Gated radionuclide angiographic evaluation of valve regurgitation.

Gated radionuclide angiography is a new noninvasive technique that can be used to calculate the ratio of left and right ventricular stroke volumes. This stroke volume ratio, which must be unity in normal subjects, increases in patients with aortic or mitral regurgitation in direct proportion to the degree of left ventricular volume overload, provided no shunts or regurgitant right heart lesions are present. In 22 patients with aortic or mitral regurgitation there was excellent correlation between the stroke volume ratio determined with gated radionuclide angiography and with standard quantitative catheterization methods (r = 0.79). Measurement of valve regurgitation with this radionuclide method also correlated well with data obtained from semiquantitative aortic root or left ventricular cineangiography (r = 0.72). Twenty-one of the 22 patients with valve regurgitation had an abnormally elevated stroke volume ratio, thereby suggesting that gated radionuclide angtiography may be useful in detecting or excluding hemodynamically significant valve regurgitation.