Safety of gadoversetamide in patients with acute and chronic myocardial infarction.

PURPOSE: To assess the safety data from two large, multicenter, phase 2 trials on the use of gadoversetamide (OptiMARK, Tyco Healthcare/Mallinckrodt, St. Louis, MO) as a contrast agent in delayed hyperenhancement magnetic resonance imaging (DE-MRI) in patients with acute and chronic myocardial infarction (MI). MATERIALS AND METHODS: The study population from both trials comprised 577 patients who were randomly assigned to one of four dose groups (0.05, 0.1, 0.2, or 0.3 mmol/kg) before undergoing DE-MRI. Safety evaluations included physical and electrocardiographic (ECG) examinations. Vital signs, laboratory values, adverse events (AE), and serious adverse events (SAE) were monitored before and after contrast administration. RESULTS: Of the 577 patients who received gadoversetamide, 124 (21.5%) reported a total of 164 AEs; most were mild (139 AEs; 84.8%) or moderate (25 AEs; 15.2%). ECG-related changes were the most frequent AE. Site investigators judged only eight AEs as likely related to gadoversetamide and only two of the eight as clinically relevant. Further evaluation suggested neither AE was related to gadoversetamide. Two SAEs were reported, but none was judged related to gadoversetamide by the site investigators. CONCLUSION: Gadoversetamide is safe for use in patients with acute or chronic MI up to a dose of 0.3 mmol/kg.

Comparison of SSFP and IR GRE techniques for measurement of total myocardial mass-influence of applied contrast dosage and implication for relative infarct size assessment.

OBJECTIVE: To compare total left ventricular mass assessment using steady state free precession (SSFP) and inversion recovery fast gradient echo (IR GRE) imaging and further to assess the influence of contrast dosage on mass by IR GRE and its implications on relative infarct size assessment with both methods. METHODS: Forty-three patients with first documented myocardial infarction and single vessel disease underwent measurement of total myocardial mass using SSFP technique and an IR GRE sequence. As part of a Phase 2 multi-center dose ranging study for infarct identification patients received 1 of 4 possible dosages (0.05, 0.1, 0.2 or 0.3 mmol/kg body weight) of the contrast agent gadoversetamide (OptiMARK, Tyco Healthcare Mallinckrodt, St. Louis, MO, USA). RESULTS: Left ventricular mass assessment using IR GRE resulted in a slightly greater detection of myocardial mass than from the SSFP images (160.1 and 156.4 g, respectively, p < 0.001). The overall good correlation of both methods (R2 = 0.97 for the total study group, p < 0.001) was further improved by using gadoversetamide at doses of 0.2 or 0.3 mmol/kg (R2= 0.99, p < 0.001), mainly as a result of a considerably higher blood-myocardial contrast-to-noise ratio (CNR) in the IR GRE images. Bland-Altman analysis in these subgroups showed very little scatter of the residuals over the mean (3.5 +/- 5.4 g and 1.3 +/- 6.9 g respectively, 95% confidence interval). The observed differences in total mass calculation, while statistically significant, were not correlated with clinically relevant differences in estimation of relative infarct size. CONCLUSION: Total LV mass calculations using SSFP and IR GRE techniques are interchangeable when using appropriate contrast media, such as gadoversetamide. Late gadolinium enhancement results in good blood myocardial CNR. Hence, for relative infarct size assessment either method for calculation of total myocardial mass can be used.

Cardiac involvement in limb-girdle muscular dystrophy 2I : conventional cardiac diagnostic and cardiovascular magnetic resonance.

BACKGROUND: The C826A mutation in the fukutin-related protein (FKRP) gene is typically associated with autosomal recessive limb-girdle muscular dystrophy 2I (LGMD2I) but oligosymptomatic phenotypes and patients with predominant cardiac involvement are also described. OBJECTIVE: To assess cardiac involvement in patients with LGMD2I. PATIENTS: Nine patients from 5 families (2 female, 7 male) homozygous for the 826C > A FKRP mutation were included. METHODS: Additional to conventional cardiac investigations (electrocardiography and echocardiography) the patients underwent cardiovascular magnetic resonance imaging (CMR). RESULTS/CONCLUSION: Cardiac involvement was detected by CMR in eight of nine patients (reduced left ventricular ejection fraction in 6, enlargement of left ventricular end-diastolic volume in 2 and left ventricular mass in 2) and in four patients by conventional cardiac diagnostic investigations. Two of the nine patients showed no muscle weakness or atrophy but suffered myalgias; both had cardiac manifestation of the disease. CMR is a sensitive method for detecting cardiac abnormalities in patients with LGMD2I and can be used for early detection of mild or subclinical cardiac involvement.

Volume measurement by CARTO compared with cardiac magnetic resonance.

AIMS: The CARTO electrophysiological mapping system has demonstrated accurate results for end-diastolic ventricular volumes in casts and animals. However, in humans, a comparison with cardiac magnetic resonance (CMR), the non-invasive gold standard for volumetric analysis, has not yet been performed. METHODS AND RESULTS: A total of 34 (29 male) heart failure patients (NYHA class III/IV) underwent an electrophysiological mapping procedure with the CARTO system in the left ventricle (LV) (n = 34) and right ventricle (RV) (n = 12) and CMR for RV and LV end-diastolic volume (RVEDV and LVEDV) measurements another day. Mean LVEDV was comparable between CMR and CARTO (328 +/- 95 and 320 +/- 92 mL, respectively; P = NS), whereas RV volumes measured by CARTO were larger (CMR 140 +/- 48 vs. CARTO 176 +/- 47 mL; P < 0.01). Overall, we found a good correlation between CMR and CARTO measurements for both chambers; however, the Bland-Altman analysis showed a non-interchangeability of these methods. Measurement differences were independent of chamber size, but significantly affected by the number of acquired mapping points. CONCLUSION: Although CMR and CARTO showed a good correlation in the measurement of RVEDV and LVEDV in a group of heart failure patients, the clinical interchangeability of the two methods may be questioned.

Comparison of the dual receptor endothelin antagonist enrasentan with enalapril in asymptomatic left ventricular systolic dysfunction: a cardiovascular magnetic resonance study.

OBJECTIVE: To compare the effect of the dual endothelin A/B receptor antagonist enrasentan with enalapril on left ventricular (LV) remodelling. METHODS: Multicentre, randomised, double blind, parallel group study of 72 asymptomatic patients with LV dysfunction. Patients received enrasentan (60-90 mg/day) or enalapril (10-20 mg/day). The primary end point was the change in LV end diastolic volume index (EDVI) after six months' treatment. RESULTS: LV EDVI increased with enrasentan but decreased with enalapril (3.9 (1.8) v -3.4 (1.4) ml/m2, p = 0.001). Enrasentan increased resting cardiac index compared with enalapril (0.11 (0.07) v -0.10 (0.07) l/m2, p = 0.04), as well as LV mass index (0.67 (1.6) v -3.6 (1.6) g/m2, p = 0.04). Other variables were comparable between groups. Enalapril lowered brain natriuretic peptide more than enrasentan (-19.3 (9.4) v -5.8 (6.9) pg/ml, p = 0.005). Noradrenaline (norepinephrine) (p = 0.02) increased more with enrasentan than with enalapril. Enrasentan was associated with more serious adverse events compared with enalapril (six (16.7%) patients v one (2.8%), p = 0.02); the rate of progression of heart failure did not differ. CONCLUSION: In asymptomatic patients with LV dysfunction, LV EDVI increased over six months with enrasentan compared with enalapril treatment, with adverse neurohormonal effects. This suggests that enrasentan at a dose of 60-90 mg/day over six months causes adverse ventricular remodelling despite an increase in the resting cardiac index.

Electrocardiographic characteristics in patients with nonrheumatic atrial fibrillation and their relation to echocardiographic parameters.

The aim of this study was to determine the relation between (1) ECG fibrillatory wave amplitude and left atrial diameter and left atrial appendage (LAA) flow velocity using different ECG recording techniques, and (2) ECG fibrillatory frequency and frequency of LAA contractions in patients with nonrheumatic AF. In 36 patients (22 men, 14 women, mean age 61 +/- 11 years) with persistent AF, ECG recordings were performed using a standard 12-lead EGG and an orthogonal EGG lead system using a high gain, high resolution ECG. AF was classified as coarse (fibrillatory amplitude > or = 1 mm) orfine (fibrillatory amplitude < 1 mm) in leads I, aVF, V1 and corresponding leads X, Y, and Z. Fibrillatory frequency from the ECG was determined by subtracting averaged QRST complexes and applying a Fourier analysis to the resulting signal. Doppler flow was obtained from LAA during transesophageal echocardiography and LAA emptying velocity was determined. Fourier analysis was also applied to the Doppler signal generating the frequency of LAA contractions. Coarse AF was observed in 0, 9, and 18 patients in leads I, aVF, and V, respectively. It was more often (P < 0.05) detected in corresponding leads X (n = 13), Y (n = 31), and Z (n = 23). Fine AF in lead X was associated with a reduced LAA velocity (33 +/- 16 cm/s in coarse AF vs 22 +/- 13 cm/s in fine AF, P = 0.05). There was neither a relation between AF coarseness in any other ECG lead and LAA flow velocity, left atrial diameter, or echo contrast. In 25 patients with an active LAA flow, the mean frequency of LAA contractions was 6.8 +/- 0.8 Hz. The corresponding mean frequency obtainedfrom the EGG was 6.7 +/- 0.7 Hz (r = 0.85, P < 0.001). The mean difference between these two measures was 0.04 Hz, and the 95% confidence limits were 0.90 and- 0.82 Hz using the Bland-Altman method. In conclusion, AF coarseness and its relation to LAA flow velocity depend on the ECG recording technique used. LAA contractions represent one mechanical correlate of the electrical fibrillatory activity in AF.

Left atrial appendage flow in nonrheumatic atrial fibrillation : relationship with pulmonary venous flow and ECG fibrillatory wave amplitude.

OBJECTIVE: This study was conducted (1) to examine the relationship between left atrial appendage (LAA) flow velocity and pulmonary venous flow (PVF) variables during nonrheumatic atrial fibrillation (AF), and (2) to determine whether a reduction in LAA flow is reflected by the fibrillatory wave amplitude on the surface ECG. BACKGROUND: Although LAA Doppler echocardiographic signals provide information regarding the velocity and direction of flow only for a localized narrow sample, systolic PVF represents in part the global left atrial function, mainly relaxation. Controversy exists about whether the amplitude of fibrillatory waves recorded on the surface ECG correlates with LAA flow velocity during AF. MEASUREMENTS AND RESULTS: Thirty-three patients (20 men, 13 women; mean [+/- SD] age, 61 +/- 11 years) with nonrheumatic AF undergoing transthoracic and transesophageal echocardiography were studied. A correlation between LAA flow velocity and systolic PVF variables (peak systolic velocity, R: = 0.450, p = 0.009; velocity-time integral of systolic flow, R = 0.491, p = 0.004; systolic fraction of PVF, R: = 0.627, p < 0.0001) was observed. Patients with a low LAA flow profile (< 25 cm/s) had a reduced systolic PVF. Longer AF duration and the occurrence of moderate mitral regurgitation were related to reduced LAA flow. AF was subdivided into coarse (peak-to-peak fibrillatory amplitude > or = 1 mm) or fine (< 1 mm) in standard ECG lead V1. There was no association between the coarseness of AF and the LAA flow profile. CONCLUSION: In patients with nonrheumatic AF, a reduction in LAA flow velocity correlates with a reduction in systolic PVF. These hemodynamic changes are not reflected by the ECG fibrillatory wave amplitude.

Improved cine cardiovascular magnetic resonance using Clariscan (NC100150 injection).

We evaluated the use of Clariscan 0.75, 2, and 5 mg Fe/kg body weight in six patients to determine optimal dosing for short repetition time cine imaging. Breathhold cine images were acquired in the vertical and horizontal long axes and the short axis. Blood-pool signal-to-noise ratio increased significantly in all planes (p < 0.01) but was least marked in the short axis. Myocardial signal-to-noise ratio increased by a lesser amount (p < 0.05). Myocardial to blood-pool signal-difference-to-noise ratio improved significantly in the long axes (p < 0.05) and was greatest at 2 mg Fe/kg body weight, but changes in the short axis were minor. With the 5-mg Fe/kg body weight dose, the response was reduced or reversed due to T2* effects. Visual assessment improved in all planes (p < 0.05) and was optimal at 2 mg Fe/kg body weight. In conclusion, Clariscan improves short repetition time cardiac breathhold cine imaging, particularly in the long axis planes, with an optimal dose of 2 mg Fe/kg body weight.

Quantification of right and left ventricular function by cardiovascular magnetic resonance.

Cardiac dysfunction is a major cause of cardiovascular morbidity and mortality. Accurate and reproducible assessment of cardiac function is essential for the diagnosis, the assessment of prognosis and evaluation of a patient's response to therapy. Cardiovascular Magnetic Resonance (CMR) provides a measure of global and regional function that is not only accurate and reproducible but is noninvasive, free of ionising radiation, and independent of the geometric assumptions and acoustic windows that limit echocardiography. With the advent of faster scanners, automated analysis, increasing availability and reducing costs, CMR is fast becoming a clinically tenable reference standard for the measurement of cardiac function.

Coronary artery imaging in grown up congenital heart disease: complementary role of magnetic resonance and x-ray coronary angiography.

BACKGROUND: There is a high incidence of anomalous coronary arteries in subjects with congenital heart disease. These abnormalities can be responsible for myocardial ischemia and sudden death or be damaged during surgical intervention. It can be difficult to define the proximal course of anomalous coronary arteries with the use of conventional x-ray coronary angiography. Magnetic resonance coronary angiography (MRCA) has been shown to be useful in the assessment of the 3-dimensional relationship between the coronary arteries and the great vessels in subjects with normal cardiac morphology but has not been used in patients with congenital heart disease. METHODS AND RESULTS: Twenty-five adults with various congenital heart abnormalities were studied. X-ray coronary angiography and respiratory-gated MRCA were performed in all subjects. Coronary artery origin and proximal course were assessed for each imaging modality by separate, blinded investigators. Images were then compared, and a consensus diagnosis was reached. With the consensus readings for both magnetic resonance and x-ray coronary angiography, it was possible to identify the origin and course of the proximal coronary arteries in all 25 subjects: 16 with coronary anomalies and 9 with normal coronary arteries. Respiratory-gated MRCA had an accuracy of 92%, a sensitivity of 88%, and a specificity of 100% for the detection of abnormal coronary arteries. The MRCA results were more likely to agree with the consensus for definition of the proximal course of the coronary arteries (P<0.02). CONCLUSIONS: For the assessment of anomalous coronary artery anatomy in patients with congenital heart disease, the use of the combination of MRCA with x-ray coronary angiography improves the definition of the proximal coronary artery course. MRCA provides correct spatial relationships, whereas x-ray angiography provides a view of the entire coronary length and its peripheral run-off. Furthermore, respiratory-gated MRCA can be performed without breath holding and with only limited subject cooperation.

Long-term results after surgery for acute mesenteric ischemia.

BACKGROUND: Acute mesenteric ischemia is associated with high mortality rates, and little is known about the long-term prognosis of patients after initially successful surgical intervention. METHODS: Ninety patients were treated by vascular reconstruction or bowel resection, or both, between 1972 and 1993. The overall mortality was 66%. The outcomes and rehabilitational statuses of those 31 patients who were discharged from the hospital were analyzed retrospectively. Anticoagulation consisted of vitamin K antagonists in patients with venous thrombosis and arterial embolism or inhibition of thrombocyte aggregation in patients with arterial thrombosis and nonocclusive mesenteric ischemia. RESULTS: In 31 patients discharged from the hospital venous thrombosis, arterial embolism, arterial thrombosis, and nonocclusive disease occurred in 19, 5, 5, and 2 patients, respectively. The 2- and 5-year survival rates were 70% and 50% and mainly related to cardiovascular comorbidity and malignant disease. Only one patient died after a recurrent attack of arterial mesenteric thrombosis. Twenty percent of the patients suffered from chronic short bowel syndrome after extensive bowel resection, but none required permanent parenteral nutrition. CONCLUSIONS: Under appropriate anticoagulation there is a remarkably low risk of recurrent mesenteric ischemia. The impaired life expectancy of long-surviving patients is mainly due to cardiovascular comorbidity and malignancies.

Results of portal thrombectomy and splanchnic thrombolysis for the surgical management of acute mesentericoportal thrombosis.

BACKGROUND: Acute venous mesenteric ischaemia is rare and there is no standard conservative or operative treatment. METHODS: The results of surgical treatment for acute mesentericoportal thrombosis were retrospectively analysed in 31 patients. The thrombotic occlusion affected the superior mesenteric vein in 19 patients, the portal vein in eight and both vessels in four. Surgical treatment comprised venous thrombectomy (nine patients), bowel resection (17), a combination of thrombectomy and bowel resection (two), distal splenorenal shunt (one) and simple laparotomy (two). RESULTS: When the mesentericoportal blood flow was restored, the mortality rate was lower, but not significantly so, than after bowel resection alone (two of nine versus seven of 17). In addition to thrombectomy, local thrombolysis with recombinant tissue plasminogen activator was performed in five patients via a catheter placed into a distal mesenteric vein and all survived. The overall hospital mortality rate was 11 (35 per cent) of 31. CONCLUSION: An active approach should be encouraged in patients with this condition employing thrombectomy in addition to bowel resection. Early results are encouraging and local thrombolysis warrants further study.

Acute mesenteric ischemia following cardiac surgery.

BACKGROUND: The results of surgical intervention for acute mesenteric ischemia following major cardiac surgery were analysed. EXPERIMENTAL DESIGN: Retrospective investigation. Setting. University Hospital of Hannover Medical School. PATIENTS: Eleven patients (five women and six men) amongst a total of 90 patients operated from 1972 to 1993 because of an acute splanchnic ischemia. This subgroup represented 12%. The causes of splanchnic ischemia were arterial embolism in 55% and nonocclusive disease in 45%. INTERVENTIONS: Surgical intervention comprised embolectomy in one patient (9%), bowel resection in 36% and exploratory laparotomy only in 55%. MEASURES: Hospital mortality, causes of death and long term survival were analysed. RESULTS: The inhospital mortality of the 11 patients was 91% and only one female patient with arterial embolism survived after bowel resection. In the 79 patients without previous cardiac surgery the postoperative mortality of mesenteric ischemia was significantly (p<0.001) lower with 62%. CONCLUSIONS: Following cardiac surgery mesenteric infarction is a rare complication with an incidence of 0.06% and the chance of survival is minimal. Whenever acute abdominal disease occurs after cardiac surgery, the differential diagnosis should include mesenteric ischemia. Only an immediate surgical intervention with revascularisation and/or removal of gangrenous bowel segments may eventually improve the patient's prognosis.

[Surgical therapy of acute mesenteric ischemia]. / Chirurgische Therapie akuter mesenterialer Ischämien.

Between 1972 and 1993 a total of 90 patients were operated on for acute mesenteric ischemia at Hanover Medical School, Department of Abdominal- and Transplantation Surgery. As causes of mesenteric ischemia, arterial embolism (23%), arterial thrombosis (30%), venous thrombosis (33%), and non-occlusive disease (14%) were differentiated. The overall hospital mortality was 66%. The hospital mortality after venous thrombosis was 37%, significantly lower than after arterial (79%) and functional (83%) types of mesenteric ischemia. Besides the pathogenesis of mesenteric infarction, a multivariate analysis revealed age and presence of peritonitis and intestinal perforation to be independent prognostic factors of hospital lethality. Patients with venous thrombosis had a mean age of 48 years and were significantly younger than the remaining patients who had an average age of over 60 years. Surgical procedures comprised solitary bowel resection (60%), isolated embolectomy and/or thrombectomy (10%), a combination of embolectomy/thrombectomy and bowel resection (4%), and exploratory laparotomy only (21%). Vascular reconstruction was associated with a significantly better survival rate than bowel resection only. While hospital mortality was dependent on the type of mesenteric ischemia, long-term survival after exclusion of hospital deaths proved independent of the original pathogenesis. Of the patients who survived the acute attack of mesenteric ischemia, 70% were alive 2 years later and 50% 5 years later. The survival probability of these patients was not determined by recurrence of mesenteric ischemia, but was mainly related to their cardiovascular comorbidity and a high incidence and prevalence of malignancies.