Systemic immune reactions to HMG-CoA reductase inhibitors. Report of 4 cases and review of the literature.

Four patients with systemic autoimmune disorders, 3 of a serious nature, presented to 1 cardiologist over a 20-month span. In 3 of these cases, an HMG-CoA reductase inhibitor was presumably etiologic, while in the fourth case, the HMG-CoA reductase inhibitor might have unmasked the disorder. It would be useful to determine the true frequency of this complication, particularly in older patients not included in most of the statin trials to date. It is well established that autoimmune phenomena and particularly the development of autoantibodies increase with age. The data presented in this report that the group of HMG-CoA reductase inhibitors could be a heretofore poorly recognized etiologic agent. This issue might be addressed by a case-control study looking at the prevalence of statin use in elderly patients with systemic autoimmune disorders and in controls. Until then, the authors advise caution in the use of this class of medications in patient subgroups for whom no clear-cut clinical benefit has yet been proven.

A method of dynamic analysis of iodine-123-metaiodobenzylguanidine scintigrams in cardiac mechanical overload hypertrophy and failure.

Cardiac sympathetic neuronal degeneration accompanies mechanical overload heart failure. We hypothesized that sympathetic nerve and myocyte failure share a common etiology and that 123I-metaiodobenzylguanidine (MIBG) might provide a precise method of detecting failure in chronic mechanical overload. Our aim was to develop a method for the dynamic analysis of 123I-MIBG scintigrams which could yield a quantitative index of myocardial sympathetic neuronal function in this condition. We performed serial 123I-MIBG scintigraphy in 33 volunteers, 10 orthotopic cardiac transplant recipients and 26 patients with chronic mechanical overload of the left ventricle. We constructed a compartmental model in which total heart activity represents the sum of cardiac sympathetic vesicular and cytosolic pools. Patients with antecedent mechanical overload heart failure or myocardial dysfunction had accelerated myocardial egress of tracer that we ascribed to a specific impairment in vesicular storage rather than to a more rapid turnover of an intact vesicular pool.

Pathophysiology of dynamic cardiomyoplasty: a clinico-pathological case study.

A 58-year-old man with end-stage ischemic cardiomyopathy underwent dynamic cardiomyoplasty. "On" and "off" studies with the cardiac assist device failed to show any significant hemodynamic changes despite improvement in functional status. The patient's late postoperative course was complicated by two episodes of acute pulmonary edema followed by cardiac arrest. These events were precipitated by ventricular tachycardia. The last episode led to myocardial infarction requiring diastolic counterpulsation and inotropic support. He died 4 1/2 months following the cardiomyoplasty. Postmortem findings revealed an anterior left ventricular infarct with aneurysm. There was fusion of skeletal muscle to the epicardium with minimal fibrosis and atrophy. The latissimus dorsi (LD) flap was viable, but myofibrillar ATPase stain revealed incomplete transformation. Several clinical observations have emerged from the early experience with dynamic cardiomyoplasty: (1) Important arrhythmias and cardiac arrest compromise the vascular supply and thus power of the muscular flap; (2) Resting ejection fraction does not correlate with exercise tolerance, therefore, other parameters must be sought to explain improved functional status; (3) Uniform muscle transformation in humans may be unpredictable with current clinical stimulation protocols. The conformation of LD to the epicardium underscores a potential remodeling phenomenon which may ultimately spare the diseased myocardium by altering its oxygen supply/demand ratio and thus the natural history.

Metaiodobenzylguanidine [131I] scintigraphy detects impaired myocardial sympathetic neuronal transport function of canine mechanical-overload heart failure.

In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine [131I] to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine [131I] and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4 hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/hour in normals), reflecting a disproportionately increased extraneuronal tracer pool. They also showed reduced late left ventricular and left atrial concentrations of tracer, consistent with a reduced intraneuronal tracer pool. By contrast, compensated hypertrophy dogs demonstrated a normal early mean left ventricular tracer efflux rate (16.4%/hour) and essentially normal late left ventricular and left atrial concentrations of tracer. Metaiodobenzylguanidine [131I] scintigraphic findings reflect the integrity of the cardiac sympathetic neuronal transport system in canine mechanical-overload heart failure. Metaiodobenzylguanidine [123I] scintigraphy should be explored as a means of early detection of mechanical-overload heart failure in patients.

Scintigraphic characterization of amyloid cardiomyopathy.

Amyloidosis is an important entity in the differential diagnosis of cardiac failure of undetermined etiology. In this case report, the typical pattern of combined systolic and diastolic impairment in amyloid cardiomyopathy was demonstrated by analysis of the cardiac blood pool study. In addition, the patient described had mild uptake of Ga-67 citrate, as well as the characteristically intense myocardial uptake of Tc-99m pyrophosphate. Scintigraphic assessment may be particularly helpful when the diagnosis of amyloidosis is being considered in a patient with unexplained cardiac failure.

Variations on calculating left-ventricular volume with the radionuclide count-based method.

Various methods for the calculation of left-ventricular volume by the count-based method utilizing red-blood-cell labeling with 99mTc and a parallel-hole collimator are evaluated. Attenuation correction, linked to an additional left posterior oblique view, is utilized for all 26 patients. We examine (1) two methods of calculating depth, (2) the use of a pair of attenuation coefficients, (3) the optimization of attenuation coefficients, and (4) the employment of an automated program for expansion of the region of interest. The standard error of the estimate (SEE) from the correlation of the radionuclide volumes with the contrast-angiography volumes, and the root-mean-square difference between the two volume sets at the minimum SEE are computed. It is found that optimizing a single linear attenuation coefficient assumed for attenuation correction best reduces the value of the SEE. The average of the optimum value from the end-diastolic data and that from the end-systolic data is 0.11 cm-1. This value agrees with the mean minus one standard deviation value determined independently from computed tomography scans (0.13-0.02 cm-1). It is also found that expansion of the region of interest beyond the second-derivative edge with an automated program, in order to correctly include more counts, does not lower the SEE as hoped. This result is in contrast to the results of others with different data and a manual method. Possible causes for the difference are given.

omega-123I-hexadecanoic acid metabolic probe of cardiomyopathy.

The utility of omega-123I-hexadecanoic acid myocardial scintigraphy as a metabolic probe of cardiomyopathies was investigated. Sixteen patients with a variety of cardiomyopathies and myopathies that involve cardiac muscle and ten volunteers were imaged in the postabsorptive state in a 40 degrees LAO projection after a standard dose of omega-123I-hexadecanoic acid. An elimination T1/2 was calculated from the left ventricular myocardial time-activity curve. An uptake index, corrected for chest wall attenuation, was also computed in 7 of 10 volunteers and 8 of 16 patients. Of the 16 patients, only 2 had distinctly abnormal omega-123I-hexadecanoic acid myocardial tracer kinetics. The first patient had a metabolic disorder of which carnitine deficiency was one component. The second patient had endocardial fibroelastosis, a process which has been linked to disorders which deprive the myocardium of oxygen and energy. Therefore, the cardiomyopathy may have been caused by some abnormality of cardiac metabolism other than carnitine deficiency. Although of limited utility in the overall cardiomyopathic population, omega-123I-hexadecanoic acid myocardial scintigraphy should be further investigated as a screening test for carnitine deficiency and related metabolic abnormalities in patients at risk.

Count-based left ventricular volume determination utilizing a left posterior oblique view for attenuation correction.

This study aimed to determine the inherent error of the left ventricular volume measurement from the gated equilibrium blood pool scintigram utilizing the count-based technique. The study population consisted of 26 patients who had undergone biplane contrast ventriculography. The patients were imaged with a parallel-hole collimator in the left anterior oblique position showing the septum to best advantage. A reference blood sample was counted and radionuclide volumes calculated without correction for attenuation. Attenuation corrected volumes were derived with the factor 1/e-mud, where d = distance from skin marker to center of the left ventricle in the orthogonal left posterior oblique view and mu = linear attenuation coefficient. A series of mu values from 0.08 to 0.15 cm-1 was evaluated. There was a trend toward improvement in the r value and lowering of the SEE with attenuation correction. The tightest 95% confidence limits achieved for an end-diastolic 150-ml ventricle were +/- 44 ml, and for an end-systolic 75-ml ventricle +/- 32 ml. In view of the magnitude of inherent error, the count-based volume measurement may be more suitable for group analyses and in cases in which an individual patient serves as his own control.

The effect of dobutamine on exercise performance in patients with symptomatic ischemic heart disease.

The effect of dobutamine on exercise performance was assessed in 20 patients with ischemic heart disease (CAD) and a positive stress test. These patients had a wide range of resting left ventricular ejection fraction (range 22% to 69%, mean 42%). Each patient entered a double-blind crossover study in which two identical exercise radionuclide ventriculograms were performed in patients on dobutamine, 5 micrograms/kg/min intravenously, or placebo. Dobutamine increased resting left ventricular ejection fraction. Although ejection fraction fell with dobutamine during submaximal exercise, it remained higher than with placebo. At peak exercise, ejection fraction fell to the same level on dobutamine as with placebo. Dobutamine diminished exercise time and time to ischemia while peak pressure-rate product was unchanged. Four of 20 patients developed complex ventricular premature beats, all while on dobutamine. Although useful when administered to resting patients with acute left ventricular failure, dobutamine's effects may be deleterious in exercising patients with chronic ischemic heart disease.

Selective right ventricular dysfunction after coronary artery bypass grafting.

Preoperative and postoperative right (RVEF) and left ventricular ejection fractions (LVEF) were studied by means of radionuclide techniques in 15 patients undergoing coronary bypass operations. Three of them, all with right coronary artery lesions, had postoperative depression of RVEF without concomitant decrease in LVEF. In contrast to those with left ventricular dysfunction, the patients with selective RVEF depression did not have significant elevation of myocardial injury index calculated from creatine kinase isoenzyme (CK-MB) curves.

Topography of preemptying ventricular segments in patients with Wolff-Parkinson-White syndrome using scintigraphic phase mapping and esophageal pacing.

We analyzed the sequence of ventricular emptying using the phase image in 10 patients with accessory pathways and in 15 normal subjects. In normal subjects, the earliest emptying occurred in ventricular septal, apical and left basal segments. Eight patients had manifest preexcitation; the earliest emptying occurred ectopically in the right ventricle in one of these patients and in the left ventricle in five. The remaining two patients had normal phase maps. Two patients had concealed left-sided pathways. Their phase maps showed earliest emptying in left basal segments. Six of the 10 patients underwent electrophysiologic mapping. There was complete agreement between phase and electrophysiologic maps. Transesophageal atrial pacing increased preexcitation in one patient, normalized the ECG in another and precipitated narrow QRS tachycardia in four patients. Phase maps then showed enlargement, reduction and loss of the ectopic earliest emptying segments, respectively. We conclude that this technique in conjunction with pacing is successful in lateralizing accessory pathways.

Evaluation of cardiac function in the presence of frequent ventricular premature beats.

Frequent ventricular ectopia in an otherwise healthy person is often benign. Nevertheless, for optimal patient management, serious underlying heart disease should be excluded. The authors illustrate the use of list-mode equilibrium blood-pool ventriculography for defining left ventricular function.

Impact of radionuclide techniques on evaluation of patients with ischemic heart disease.

Radiotracer studies of the heart have become clinically important in the last decade, especially for evaluation of patients with known or suspected ischemic heart disease. Radionuclide ventriculography provides quantitative measures of biventricular function and regional wall motion. Recent technical advances include the development of computer programs for analyzing diastolic function, parametric imaging methods such as "phase" analysis and methods for calculating absolute ventricular volumes. Thallium-201 scans provide maps of regional myocardial perfusion. Recent advances include development of computer programs to quantitate regional thallium-201 uptake and to calculate thallium-201 turnover rates and the development of tomographic imaging systems. Technetium-99m pyrophosphate localizes in irreversibly damaged myocardium and provides a method for diagnosing, localizing and sizing acute myocardial infarcts. Recent applications include tomographic imaging to improve image contrast and development of criteria to identify high risk patients after infarction. Two important trends affecting the application of all the radionuclide studies in clinical cardiologic practice are the increasing use of decision analysis for incorporating results of multiple tests into single diagnostic probability statements, and the use of diagnostic algorithms that include the radionuclide studies to optimize the cost effectiveness of evaluation of patients with ischemic heart disease.

Scintigraphic demonstration of ventriculo atrial conduction in the ventricular pacemaker syndrome.

A patient with the sick-sinus syndrome was evaluated because of symptomatic deterioration after insertion of a ventricular demand pacemaker. Clinical features of the ventricular pacemaker syndrome were recognized and confirmed by electrophysiological and hemodynamic studies. Phase analysis--a new technique for detecting patterns of cardiac emptying from gated cardiac blood-pool scintigrams--demonstrated a pattern consistent with 1:1 ventriculo-atrial conduction. Phase analysis of the gated cardiac blood-pool scintigram may be useful in the assessment of patients with ventricular demand pacemakers who complain of fatigue and effort intolerance.