Hans Hermann Hilger

Feasibility of high-dose dipyridamole-magnetic resonance imaging for detection of coronary artery disease and comparison with coronary angiography

To assess the feasibility, safety and usefulness of gradient-echo magnetic resonance imaging (MRI) combined with pharmacologic stress testing for the detection of coronary artery disease, 23 patients without previous myocardial infarction but with significant stenosis (greater than 70% diameter stenosis) of greater than or equal to 1 major coronary artery were selected for dipyridamole-MRI stress testing. Each patient underwent MRI at rest, and high-dose dipyridamole-MRI (0.75 mg/kg over 10 minutes) of corresponding basal and midventricular short-axis tomograms. Additionally, these patients performed symptom-limited exercise stress tests. All short-axis tomograms were evaluated on a standardized segmental basis by grading each segment as normal, hypokinetic, akinetic or dyskinetic. Dipyridamole-MRI was considered pathologic if segmental wall motion deteriorated by greater than or equal to 1 grade after dipyridamole. For comparison with coronary angiography, segmental wall motion gradings were related to the respective coronary artery territories in the short-axis plane. Pathologic dipyridamole-MRI was obtained in 18 of 23 (78%) patients. For 1- and 2-vessel diseases, sensitivity was 69 and 90%, respectively. Exercise stress tests were pathologic in 14 of 23 (66%) patients. For 1- and 2-vessel diseases, sensitivity of exercise stress test was 58% (7 of 12 patients) and 77% (7 of 9), respectively. Sensitivity/specificity of dipyridamole-MRI for the localization of the stenosed coronary artery was 78/100% for left anterior descending, 73/100% for left circumflex, and 88/87% for right coronary artery stenoses. It is concluded that dipyridamole-MRI is a feasible nonexercise-dependent test for detection and localization of functionally significant coronary artery disease.

Chronic myocardial infarction: Assessment of morphology, function, and perfusion by gradient echo magnetic resonance imaging and 99mTc-methoxyisobutyl-isonitrile SPECT

To assess the ability of magnetic resonance imaging (MRI) to identify the anatomic and functional abnormalities associated with completely scarred myocardium, 20 patients with chronic transmural myocardial infarction confirmed by electrocardiography and cineventriculography were examined by gradient echo MRI. Myocardial perfusion at rest was assessed in corresponding transverse sections using 99mTc-methoxyisobutyl-isonitrile single-photon emission computed tomography (MIBI-SPECT). MRI scar was defined as diastolic wall thickness (DWT) 2.5 SD below corresponding normal values or systolic wall thickening (delta WT) less than or equal to 1 mm. For MIBI-SPECT images, scar was defined as a MIBI uptake less than 2.5 SD below normal values. By MIBI-SPECT, 152 segments contained normal tissue and 88 contained scarred myocardium. In 226 of 240 (94%) segments, MRI gradings by DWT and MIBI-SPECT gradings were identical. DWT by MRI was higher in normal than in scarred MIBI-SPECT segments (10 +/- 1 versus 4 +/- 2 mm, p less than 0.001). In 230 of 240 (96%) segments, MRI gradings by delta WT and MIBI-SPECT gradings were identical. Segments graded normal by MIBI-SPECT showed higher delta WT by MRI than scar segments (5 +/- 1 versus 0.3 +/- 1 mm, p less than 0.001). MIBI-SPECT perfusion defect size and regions with reduced DWT on MRI tomograms correlated well (r = 0.85). This study indicates that myocardial regions fulfilling electrocardiographic and ventriculographic criteria for transmural myocardial scar are clearly depicted by regional diastolic wall thinning and delta WT less than or equal to 1 mm on gradient echo MR images.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a twenty-four-hour milrinone infusion in patients with severe heart failure and cardiogenic shock as a function of the hemodynamic initial condition

The systemic and pulmonary arterial hemodynamics of 40 patients with severe congestive heart failure were determined during a 24-hour infusion of milrinone (0.5 micrograms/kg/min) after a loading dose of 50 micrograms/kg. A subgroup (n = 18) with severe cardiac pump dysfunction and three patients in cardiogenic shock were analyzed separately; their hemodynamic response was compared with that of the total group (n = 40). After 15 minutes of intravenous therapy with milrinone, the total group (n = 40) showed an increase of 65% in cardiac index; in the subgroup (n = 18) cardiac index increased by 94% after 15 minutes and by 106% after 30 minutes. Likewise, pulmonary capillary wedge pressure decreased after 30 minutes in both the total group (n = 40) and the subgroup (n = 18). The heart rate showed an overall tendency to decrease. The systolic blood pressure tended upward and remained statistically unchanged in the total group, whereas in the subgroup in which pressure was initially low, there was an increase in the systolic pressure after 1 hour and a further increase after 24 hours. Mean arterial pressure also rose in this subgroup. The early improvement in all measured hemodynamic parameters was sustained throughout the 24-hour infusion period. Development of tolerance was not observed, nor were any clinically symptomatic side effects or symptomatic arrhythmias. Thus intravenous milrinone is a safe medication for the rapid and prolonged improvement in hemodynamics, specifically in patients with severely restricted cardiac pumping function.

Phosphodiesterase III inhibition or adrenoreceptor stimulation: Milrinone as an alternative to dobutamine in the treatment of severe heart failure

High levels of endogenous plasma catecholamines in patients with severe congestive heart failure induce a down-regulation of the myocardial beta-adrenoreceptors and thus cause adrenoreceptor agonists, such as dobutamine, to be less effective in the treatment of these patients. Phosphodiesterase III inhibitors work independent of adrenoreceptor activity and plasma catecholamine levels; thus these agents are likely to be more effective in the treatment of severe heart failure. The present study compares both the initial and late hemodynamic effects of dobutamine and milrinone during sequentially administered 24-hour infusions. Twenty patients with severe heart failure (New York Heart Association class III, n = 4; New York Heart Association class IV, n = 16) were investigated. Dobutamine could be administered at the prescribed maximum dose of 15 micrograms/kg/min for 24 hours in only 15 of 20 patients. In three patients the dose was reduced or dobutamine infusion completely stopped because of a drug-related increase in heart rate greater than 140 beats/min. Another 2 of 20 patients showed no hemodynamic improvement over 3 hours at the maximum dose of 15 micrograms/kg/min. Dobutamine administration was also discontinued in these patients on account of the existing unfavorable hemodynamic condition, and therapy with intravenous milrinone was started. All 20 patients responded to milrinone without side effects, although comparison of the hemodynamic effects during a 24-hour infusion was possible in only 15 patients. The 15 patients studied over both observation periods experienced an increase in heart rate from 88.8 to 105.6 beats/min (+ 1 hour; p less than or equal to 0.001) when receiving dobutamine but had no increase with milrinone. Stroke volume increased during dobutamine infusion from 19.3 to 28.9 ml/m2 (+49.6%) after 1 hour and then fell continuously to 25.2 ml/m2 after 12 hours; during milrinone therapy, stroke volume increased from 18.8 to 31.2 ml/m2 (+66%; p less than or equal to 0.001) and remained at this level until the end of the infusion (30.2 ml/m2). Pulmonary capillary wedge pressure (PCWP) decreased (p less than or equal to 0.001) immediately during milrinone therapy from 26.5 to 16.2 mm Hg after 30 minutes and stabilized at 20.1 mm Hg after 24 hours. During dobutamine infusion PCWP showed a delayed decrease from 27.8 to 19.0 mm Hg after 6 hours and subsequently rose to 22.7 mm Hg after 24 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac involvement during and after malaria

SummaryIn 22 patients without a previous history of cardiac disease, we prospectively evaluated cardiac involvement during acute malaria and 9±5 months after recovery using non-invasive methods including resting electrocardiogram (ECG) and two-dimensional (2D) echocardiography. During the acute phase ECG abnormalities were common (5/22); pericardial effusion was found in 2 patients and global left ventricular hypokinesia in 1 patient infected with Plasmodium falciparum. At a follow-up of 19 patients, the resting ECG and echocardiography were normal or had normalized in all patients. The results of our study suggest that persistent cardiac damage following malarial infection seems to be rare; however, further trials in a larger patient population are needed to confirm our findings.

Regurgitant flow in cardiac valve prostheses: diagnostic value of gradient echo nuclear magnetic resonance imaging in reference to transesophageal two-dimensional color Doppler echocardiography.

Gradient echo nuclear magnetic resonance (NMR) imaging and transesophageal two-dimensional color Doppler echocardiography are flow-sensitive techniques that have been used in the diagnosis and grading of valvular regurgitation. To define the diagnostic value of gradient echo NMR imaging in the detection of regurgitant flow in cardiac valve prostheses and the differentiation of physiologic leakage flow from pathologic transvalvular or paravalvular leakage flow, 47 patients with 55 valve prostheses were examined. Color Doppler transesophageal echocardiography was used for comparison. Surgical confirmation of findings was obtained in 11 patients with 13 valve prostheses. Gradient echo NMR imaging showed regurgitant flow in 37 of 43 valves with a jet seen on transesophageal echocardiography and it detected physiologic leakage flow in 4 additional valves. There was 96% agreement between the two methods in distinguishing between physiologic and pathologic leakage flow. The methods differed on jet origin of pathologic leakage flow in six prostheses. The degree of regurgitation was graded by both NMR imaging and transesophageal echocardiography, according to the area of the regurgitant jet visualized; gradings were identical for 75% of valve prostheses. Quantification of jet length and area showed a good correlation between the two methods (r = 0.85 and r = 0.91, respectively). Gradient echo NMR imaging is a useful noninvasive technique for the detection, localization and estimation of regurgitant flow in cardiac valve prostheses. However, because transesophageal echocardiography is less time-consuming and less expensive, gradient echo NMR imaging is unlikely to displace transesophageal echocardiography and should be used only in the occasional patient who cannot be adequately imaged by echocardiography.

Noninvasive detection of intracardiac tumors by ultrasound and computed tomography

Nine patients presenting with intracardiac masses were examined by ultrasound (US) and computed tomography (CT). Of these, 6 patients with atrial myxomas were diagnosed primarily by US, with the movement of the pedunculated tumors well visualized by this technique. The myxomas and the three solid tumors were demonstrated by CT as contrast defects following the intravenous administration of contrast medium. Two solid intraventricular tumors, however, were overlooked by US.In the detection of solid tumors CT is considered superior to US, owing to its better geometric resolution. Generally solid tumors require heart catheterization to obtain information about the blood supply. Visualization of atrial myxomas by CT and US, in contrast, should be followed by immediate operation without additional invasive procedures.

Which role will ultrasound have with regard to NMR images

Comparison of MRI and echocardiography is informative: both are noninvasive imaging methods and both provide tomographic sections without radiation. A further similarity is that visualization of a regurgitant jet emanating from insufficient valves depends on acceleration and turbulence of blood flow.

Evaluation of the Cardiopulmonary Exercise Tolerance in Patients with Coronary Artery Disease (CAD) and Chronic Heart Failure (CHF)

The O2-uptake at the anaerobic threshold ( (dot V) O2 AT), as detected by gas exchange measurements during an incremental exercise test on a semi-supine bicycle, is an objective parameter for the estimation of cardiopulmonary exercise capacity. It was used to assess the severity of cardiopulmonary and cardiovasculary diseases in patients with coronary heart disease (CAD, N = 22, mean age 54.05 ± 7.88 years) and chronic heart failure (CHF, n = 15, mean age 57.73 ± 12.61 years). According to (dot V) O2 AT, we found a high distinction between the subjective and the objective evaluation of exercise capacity, using the Weber- and the NYHA-classes. The NYHA-classes provide insufficient criteria for exercise capacity (i.e. 14 CAD-patients NYHA II were individually assigned to very different Weber-classes: 2/14 Weber A, 2/14 Weber B, 4/14 Weber C, 5/14 Weber D, 1/14 Weber E). Our investigations showed that the O2-uptake of every pedaled watt (Δ (dot V) O2/ΔWR) should be a parameter to estimate the exercise capacity, but seems to be very insufficient in patients with severe heart failure and low values of maximum work rate (WR). Oscillations of the respiratory variables during rest, exercise, and recovery were reported in 4/22 CAD-patients (18.2%) and in 9/15 CHF-patients (60%). A constant value for O2-pulse, the O2-uptake of every heart beat ( (dot V) O2/HR), was reached in 10/ 22 CAD-patients (45.5%) and in 8/15 CHF-patients (53.3%). The computerized ergospirometry is a feasible, secure, accurate, and well-tolerated method to objectively evaluate the functional disability of patients with CAD of CHF. The present study offers new insights in the evaluation of critically ill patients using non-invasive procedures.

Cardiopulmonary Exercise Testing in the Diagnosis of HIV-Infected Patients

Pulmonary complications are a major cause of morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS). Full-blown pneumocystis carinii pneumonia (PCP) with fever, cough, dyspnea, interstitial infiltrates in the x-ray, and low oxygen tension in the arterial blood gas analysis is easy to diagnose. In contrast, early diagnosis of PCP is difficult, because x-ray of the chest and arterial oxygen tension are often normal and respiratory symptoms are unspecific. Early treatment of pulmonary complications improves prognosis of the HIV-infected patients, therefore functional screening tests for early recognition are needed. Exercise blood gas analysis (Ex.-BGA) has been proven to be a highly sensitive marker of approaching interstitial pneumonia [1]. Cardiopulmonary exercise testing (CPX) measures pulmonary gas exchange and is a modern computerized version of spiroergometry, used to test cardiopulmonary limitations to exercise. Little is known about CPX in the diagnosis of HIV-associated pulmonary complications. It was therefore the aim of our study to investigate the diagnostic value of CPX for early diagnosis of pulmonary complications in HIV-infected patients.