Rolf P. Spielmann

Intramural Hemorrhage of the Thoracic Aorta Diagnostic and Therapeutic Implications

BACKGROUND Intramural hemorrhage (IMH) was recently identified at necropsy and anecdotally in vivo as a unique aortic syndrome (without entry and with no flap-like intraluminal component, such as overt aortic dissection). However, little is known about diagnosis, prognosis, and outcome of IMH. METHODS AND RESULTS Between 1983 and 1993, 360 patients from two medical centers with clinical indications of aortic dissection were prospectively evaluated; they presented to the emergency department a median of 3.5 hours after onset of back or chest pain or other suggestive symptoms. Among 195 patients with aortic syndromes, 25 patients (12.8%) were diagnosed to have IMH of the thoracic aorta with no evidence of a primary intimal tear, flap, or overt dissection by multiple noninvasive imaging modalities, including magnetic resonance imaging (n = 12), contrast-enhanced computed tomography (n = 14), and transesophageal echocardiography (n = 3) in random order. There were 16 men and 9 women with a median age of 56 +/- 13 years (range, 15 to 80 years). Arterial hypertension was present in the majority (84%), and Marfans syndrome was present in 3 patients (12%). IMH was diagnosed within 4 days of hospital admission (median, 2.5 hours). IMH involved the ascending aorta (type A) in 12 cases (48%), the aortic arch in 2 (8%), and the descending aorta (type B) in 11 cases (44%); imaging results were validated by crossmatching with intraoperative, pathomorphological, and/or angiographic findings. IMH was 8.5 +/- 5 cm in length and 2.0 +/- 1.2 cm in aortic wall thickness. Aortic regurgitation and pericardial and mediastinal effusion were present in 5 of 12 patients (42%) with type A IMH and 2 of 11 patients (18%) with type B IMH. IMH progression to overt dissection, rupture, and/or acute tamponade occurred in 8 of 25 patients (32%) within 24 to 72 hours, indicating the need for urgent intervention. The 30-day mortality rate of IMH afflicting the ascending aorta was 80% (4 of 5 cases) with medical treatment (sedation and blood pressure control) versus no mortality in 7 cases with early surgical repair (P < .01); after 1 year, 71.4% of surgically treated patients were alive versus 20% in the medical group (P < .05). IMH of the aortic arch resulted in an early mortality of 50% (1 of 2 patients) with medical treatment. In IMH confined to the descending thoracic aorta, survival with medical treatment was not different from surgical therapy; there was 1 early death among 6 patients with medical therapy and none out of 5 patients with surgery (P = NS). At 1-year follow-up, medical and surgical therapy groups had survival rates of 80% and 83%, respectively (P = NS). CONCLUSIONS IMH is associated with a clinical profile and prognosis similar to classic dissection and may be considered an ominous precursor of overt aortic dissection. Tomographic noninvasive imaging ensures rapid, nontraumatic diagnosis of IMH. The outcome of IMH of the ascending aorta appears favorable only with immediate surgical repair.

Iodine-123 meta-iodobenzylguanidine scintigraphy: A noninvasive method to demonstrate myocardial adrenergic nervous system disintegrity in patients with idiopathic dilated cardiomyopathy☆

Iodine-123 (I-123) meta-iodobenzylguanidine (MIBG) imaging was performed in 31 patients. Three patients were without cardiac disease and 28 had idiopathic dilated cardiomyopathy with various degrees of left ventricular dysfunction. The qualitatively assessed myocardial I-123 MIBG scintigrams and the myocardial versus mediastinal I-123 MIBG uptake ratio were related to I-123 MIBG activity and norepinephrine concentration determined from endomyocardial biopsy samples taken from the right side of the interventricular septum. Scintigrams and the MIBG uptake ratio were also related to plasma catecholamine concentrations, left ventricular ejection fraction and New York Heart Association functional class. Patients with distinct myocardial I-123 MIBG uptake (score 1) had a normal ejection fraction (58 +/- 16%). Patients with diffusely reduced uptake or scintigraphic defects (score 2) had a significantly lower ejection fraction (38 +/- 9%, p less than 0.05), whereas patients with shadowy or no visible myocardial uptake (score 3) had the lowest ejection fraction (23 +/- 6%, p less than 0.002 versus patients with score 2). The scintigraphically determined I-123 MIBG activity in the septal region correlated significantly with I-123 MIBG activity from the endomyocardial biopsy samples (r = 0.78, p less than 0.001, n = 9). The myocardial versus mediastinal I-123 MIBG activity ratio was significantly related to myocardial norepinephrine concentration (r = 0.63, n = 28) and to left ventricular ejection fraction (r = 0.74, n = 31). These data suggest that myocardial I-123 MIBG scintigraphy is a useful noninvasive method for the assessment of myocardial adrenergic nervous system disintegrity in patients with idiopathic dilated cardiomyopathy.

Diagnosis of thoracic aortic dissection. Magnetic resonance imaging versus transesophageal echocardiography.

BackgroundAortic dissection requires prompt and reliable diagnosis to reduce the high mortality. The purpose of this study was to assess the reliability of both ECG-triggered magnetic resonance imaging (MRI) and transesophageal two-dimensional echocardiography combined with color-coded Doppler flow imaging (TEE) for the diagnosis of thoracic aortic dissection and associated epiphenomena. Methods and ResultsFifty-three consecutive patients with clinically suspected aortic dissection were subjected to a dual noninvasive imaging protocol in random order; imaging results were compared and validated against the independent morphological “gold standard” of intraoperative findings (n=27), necropsy (n=7), and/or contrast angiography (n=53). No serious side effects were encountered with either imaging method. In contrast to a precursory screening transthoracic echogram, the sensitivities of both MRI and TEE were 100% for detecting a dissection of the thoracic aorta irrespective of its location. The specificity of TEE, however, was lower than the specificity of MRI for a dissection (TEE, 68.2% versus MRI, 100%; p<0.005), which resulted mainly from false-positive TEE findings confined to the ascending segment of the aorta (TEE, 78.8% versus MRI, 100%; p<0.01). In addition, MRI proved to be more sensitive than TEE in detecting the formation of thrombus in the false lumen of both the aortic arch (p<0.01) and the descending segment of the aorta (p<0.05). There were no discrepancies between the two imaging techniques in detecting the site of entry to a dissection, aortic regurgitation, or pericardial effusion. ConclusionsBoth MRI and TEE are atraumatic, safe, and highly sensitive methods to identify and classify acute and subacute dissections of the entire thoracic aorta. TEE, however, is associated with lower specificity for lesions in the ascending aorta. These results may still favor TEE as a semi-invasive diagnostic procedure after a precursory screening transthoracic echogram in suspected aortic dissection, but they establish Mil as an excellent method to avoid false-positive findings. Anatomic mapping by MRI may emerge as the most comprehensive approach and morphological standard to guide surgical interventions.

Syncope in hypertrophic cardiomyopathy: Multivariate analysis of prognostic determinants

Twenty-nine consecutive patients with symptomatic hypertrophic cardiomyopathy and a mean age of 44.8 +/- 12.2 years (range 21 to 63) underwent complex invasive and noninvasive testing to identify a risk profile for syncope. Clinical, morphologic, electrophysiologic and hemodynamic variables at rest and at a symptom-limited pacing rate were analyzed for a significant association with syncope. Exact stepwise logistic regression analysis identified three variables as significant independent predictors of syncope in hypertrophic cardiomyopathy: 1) age less than 30 years (beta = 4.803; p = 0.0007); 2) left ventricular end-diastolic volume index less than 60 ml/m2 (beta = 3.302; p = 0.006); and 3) nonsustained ventricular tachycardia on 72 h ambulatory electrocardiographic monitoring (beta = 2.5909; p = 0.03). The combined occurrence of all three variables had a sensitivity and specificity of 100% in identifying eight patients with syncopal events. Thus, the risk for syncope in hypertrophic cardiomyopathy is high in young patients with the combination of low left ventricular filling volume and episodes of nonsustained ventricular tachycardia. This finding might also explain the mechanism of syncope in hypertrophic cardiomyopathy as low input-low output failure induced by a sudden increase in heart rate in the presence of a low filling volume.

Comparison of conventional and transesophageal echocardiography with magnetic resonance imaging for anatomical mapping of thoracic aortic dissection: a dual noninvasive imaging study with anatomical and/or angiographic validation

Thirty-five consecutive patients with clinically suspected aortic dissection were subjected to a dual noninvasive imaging protocol using comprehensive echocardiography and ECG-triggered MRI with multi-slice spin echo and cine sequences in random order. The purpose of this dual imaging study was to compare the diagnostic accuracy of two-dimensional and color-coded Doppler echocardiography using the conventional transthoracic (TTE) and the transesophageal approach (TEE) with magnetic resonance imaging (MRI) for the exact morphologic evaluation and anatomical mapping of the thoracic aorta. The results of each diagnostic method were validated independently against the ‘gold standard’ of intraoperative findings (n=17), necropsy (n=4) or contrast angiography (n=22).Compared to conventional transthoracic echocardiography both TEE and MRI were more reliable in detecting aortic dissections (TTE vs TEE: p<0.02; TTE vs MRI: p<0.01) and associated epiphenomena. Moreover, the reliability of TTE decreased significantly from proximal to distal segments of the aorta, e.g. from the ascending segment to the arch (p<0.05) and to the descending aorta (p<0.005), whereas the sensitivities of both TEE and MRI were excellent irrespective of the site of dissection. With regard to epiphenomena such as thrombus formation and entry location, MRI emerged as the optimal method for detailed morphologic information in all segments of the aorta. No serious side effects were encountered with either method.Thus, in patients with suspected acute or subacute aortic dissections the echocardiographic assessment should include the transesophageal approach for significant improvement of the moderate sensitivity and specificity of TTE. Both TEE and MRI are non-traumatic, safe and diagnostically accurate to identify and classify acute and subacute dissections of the thoracic aorta irrespective of their location. MRI provides superb anatomical mapping of all type A and B dissections and more detailed information on the site of entry and thrombus formation than TEE. These features of TEE and MRI may render retrograde contrast angiography obsolete in the setting of thoracic aortic dissection and may encourage surgical interventions exclusively on the basis of noninvasive imaging.

Thallium-201/technetium-99m pyrophosphate overlap in patients with acute myocardial infarction after thrombolysis: Prediction of depressed wall motion despite thallium uptake

Intracoronary thallium-201/technetium-99m pyrophosphate planar scintigraphy was performed in 60 patients with acute myocardial infarction undergoing intracoronary thrombolysis to predict salvage of myocardium immediately after thrombolysis. In eight patients a significant overlap of new thallium uptake and technetium pyrophosphate accumulation was found after thrombolysis. Intravenous planar thallium scintigraphy revealed thallium uptake in the region of overlap in all patients; circumferential profile analysis showed no difference in the thallium scintigrams before and after technetium injections. Both findings indicate that overlap is not the result of scattering of technetium into the thallium window. Emission computed tomography revealed thallium/technetium pyrophosphate uptake in identical slices and regions. Regional wall motion in the area of overlap remained depressed in all patients, in contrast to patients with similar thallium uptake without overlap. These data suggest that thallium/technetium pyrophosphate overlap reflects the close proximity of viable and necrotic myocardial cells and predicts depressed wall motion after thrombolysis.

Comparison of the acute hemodynamic response to intravenous nisoldipine (bay k 5552) and intravenous nifedipine for left ventricular dysfunction secondary to myocardial infarction

Dihydropyridine calcium blocking drugs exert potentially dangerous negative inotropic action in selected patients with severe left ventricular dysfunction. In 10 patients peripheral and central hemodynamic effects of nisoldipine were intraindividually compared with nifedipine using a sequential crossover protocol. The drugs were titrated to a similar steady-state reduction of mean arterial pressure by 15 +/- 3% and 15 +/- 2% and systemic vascular resistance by 25 +/- 5% and 17 +/- 2%, respectively. The equi-effective dosage was 0.17 +/- 0.06 microgram/min/kg for nisoldipine and 0.58 +/- 0.1 microgram/min/kg for nifedipine. In contrast to nifedipine, administration of nisoldipine was associated with increases in cardiac index of 0.45 +/- 0.33 liters/min/m2 (p less than 0.05), stroke volume index of 3.91 +/- 3.0 ml/m2 (p less than 0.05) and left ventricular ejection fraction of 4.6 +/- 2.8% (p less than 0.05). Mean pulmonary capillary wedge pressure decreased with nisoldipine from 11.8 +/- 3.4 to 8.0 +/- 3.4 mm Hg (p less than 0.005) and mean pulmonary arterial pressure from 20.4 +/- 4.06 to 16.1 +/- 3.2 mm Hg (p less than 0.005); these variables were unaffected by nifedipine. Thus, intraindividual comparison revealed no cardiodepressive action of nisoldipine, whereas with nifedipine the conceptually beneficial effect of afterload reduction appears to be offset by intrinsic negative inotropic action. Due to higher vasospecificity and more effective unloading, nisoldipine appears to be superior to nifedipine in patients with left ventricular dysfunction secondary to ischemic heart disease.

Clinical use of ultrashort-lived radionuclide krypton-81m for noninvasive analysis of right ventricular performance in normal subjects and patients with right ventricular dysfunction

The ultrashort-lived radionuclide krypton-81m, eluted in 5% dextrose from a bedside rubidium-81m generator, was intravenously infused for rapid imaging of the right-sided heart chambers in the right anterior oblique projection adjusted for optimal right atrioventricular separation. Left-sided heart and lung background was minimized by rapid decay and efficient exhalation of krypton-81m, requiring no algorithm for background correction. A double region of interest method decreased the variability in the assessment of ejection fraction to 5%. In 10 normal subjects, 11 patients with pulmonary hypertension, 4 patients with right ventricular outflow tract obstruction and 4 patients with right ventricular infarction, right ventricular ejection fraction determined by krypton-81m equilibrium blood pool imaging ranged from 14 to 76%. The correlation between these values and those determined by cineangiography according to Simpsons rule was close: r = 0.93 for all data points (p less than 0.001), r = 0.92 for studies at rest (p less than 0.001) and r = 0.93 for exercise studies (p less than 0.001). Exercise-related changes in right ventricular function revealed a disturbed functional reserve with pulmonary hypertension and right ventricular infarction, whereas in compensated right ventricular outflow tract obstruction there was a physiologic increase in ejection fraction with exercise (p less than 0.001). Thus, equilibrium-gated right ventricular imaging using ultrashort-lived krypton-81m is a simple, accurate and reproducible method with potential for serial assessment of right ventricular ejection fraction in a variety of right ventricular anatomic and functional abnormalities, both at rest and during exercise. Advantages of this method include an extremely low radiation dose to patients and clear right atrioventricular separation without the need to correct for background activity.

Detection of human collateral circulation by vasodilation-thallium-201 tomography

Coronary arteriolar vasodilation may provoke redistribution of flow to collateral-dependent jeopardized myocardium. To assess the physiologic significance of collaterals, 80 consecutive post-infarction patients (age 58 +/- 8 years) underwent vasodilation-redistribution thallium-201 tomographic imaging after administration of 0.56 mg of intravenous dipyridamole/kg body weight. Circumferential profile analysis of thallium-201 uptake and redistribution in representative left ventricular tomograms provided quantitative assessment of transient and fixed defects and separation between periinfarctional and distant inducible hypoperfusion. Tomographic perfusion data were correlated to wall motion and collateral circulation between distinct anatomic perfusion territories. Patients were grouped according to presence (59%) or absence (41%) of angiographically visible collateral channels to jeopardized myocardium. In the presence of collaterals, distant reversible defects were larger than in absence of collaterals (p less than 0.05); the extent of combined periinfarctional and distant redistribution was also larger in collateralized patients (p less than 0.025), whereas the size of the persistent perfusion defect was similar in both groups. By prospective analysis the tomographic perfusion pattern of combined periinfarctional and distant redistribution revealed a sensitivity of 85% and a specificity of 78% for the detection of significant collateral circulation in this group of patients. Thus, using the exhausted flow reserve as a diagnostic tool, vasodilation-thallium-201 tomography has the potential to identify and quantitate collateralized myocardium in post-infarction patients and may guide diagnostic and therapeutic decision-making.

Development of Pulmonary Aneurysm in Primary Pulmonary Hypertension: A Case Report

Selected cases of severe primary pulmonary arterial hypertension and asso ciated pulmonary vascular disease have been related to the oral ingestion of aminorex fumarate, an anorexigen obviously responsible for an epidemic of primary pulmonary hypertension in Western Europe between 1967 and 1970. This report describes a fifteen year follow-up of a female patient with aminorex fumarate related pulmonary hypertension and the uncommon finding of the formation of an excessive fusiform pulmonary trunk aneurysm in the late stage of the disease process. The progressive clinical course was followed by serial chest x-ray films and repeat right heart catheterization. The diagnosis of a main stem pulmonary artery aneurysm was noninvasively established by two-dimen sional echocardiography and confirmed by contrast-enhanced computed tomo graphy and radionuclide blood pool imaging. The patient is alive, thus no histologic correlate of this entity is available at present.