E. E. van der Wall

Pulmonary regurgitation in the late postoperative follow-up of tetralogy of Fallot. Volumetric quantitation by nuclear magnetic resonance velocity mapping.

BackgroundPulmonary regurgitation frequently occurs after surgical correction of tetralogy of Fallot. To date, reliable quantitation of pulmonary regurgitation has not been possible, and therefore the clinical significance of pulmonary regurgitation is controversial. Nuclear magnetic resonance (NMR) velocity mapping allows accurate measurement of volumetric flow. The feasibility and accuracy of NMR velocity mapping to quantify pulmonary regurgitation volumes are studied in patients after Fallot repair. Methods and ResultsIn 18 patients (mean age, 16.5±6.5 years), late (12.6±5.2 years) after Fallot surgery, forward and regurgitant volume flow was measured in the main pulmonary artery with NMR velocity mapping. To validate the measurements of pulmonary forward flow, right ventricular stroke volume was used as an internal reference standard. Pulmonary regurgitation volumes were compared with the differences between the corresponding right and left ventricular stroke volumes. Ventricular volumes were measured with a multisection gradient echo NMR method. In addition, the relation between pulmonary regurgitation and right ventricular volumes was studied. Measurements of pulmonary regurgitation volume with NMR velocity mapping closely corresponded with the tomographically determined volumes (r=.93). Forward pulmonary volume flow was neariy identical to right ventricular stroke volume (r=.98). Pulmonary regurgitation volume was significantly correlated with end-diastolic volume (r=.82, P<.0005), end-systolic volume (r=.63, P<.01), and stroke volume (r=.89, P<.0005) of the right ventricle but not with right ventricular ejection fraction (r= −.41, P=NS). ConclusionsNMR velocity mapping is an accurate method for the noninvasive, volumetric quantification of pulmonary regurgitation after surgical correction of tetralogy of Fallot.

Magnetic resonance imaging during dobutamine stress for detection and localization of coronary artery disease. Quantitative wall motion analysis using a modification of the centerline method.

Quantitative measurement of wall motion is essential to assess objectively the functional significance of coronary artery disease. We developed a quantitative wall thickening analysis on stress magnetic resonance images. This study was designed to assess the clinical value of magnetic resonance imaging (MRI) during dobutamine stress for detection and localization of myocardial ischemia in patients with suspected coronary artery disease. Methods and ResultsThirty-nine consecutive patients with clinically suspected coronary artery disease referred for coronary arteriography and 10 normal volunteers underwent gradient- echo MRI at rest and during peak dobutamine stress (infusion rate, 20 μg· kg−1· min−2). MRI was performed in the short-axis plane at four adjacent levels. Display in a cine loop provided a qualitative impression of regional wall motion (cine MRI). A modification of the centerline method was applied for quantitative wall motion analysis by means of calculation of percent systolic wall thickening. Short-axis cine MRI images were analyzed at 100 equally spaced chords constructed perpendicular to a centerline drawn midway between the end-diastolic and end-systolic contours. Dobutamine MRI was considered positive for coronary artery disease if the percent systolic wall thickening of more than four adjacent chords was < 2 SD below the mean values obtained from the normal volunteers. The overall sensitivity of dobutamine MRI for the detection of significant coronary artery disease (diameter stenosis ≥ 50%) was 91% (30 of 33), specificity was 80% (5 of 6), and accuracy was 90% (35 of 39). The sensitivity for identifying one-vessel disease was 88% (15 of 17), for twovessel disease 91% (10 of 11), and for three-vessel disease 100% (5 of 5). The sensitivity for detection of individual coronary artery lesions was 75% for the left anterior descending coronary artery, 87% for the right coronary artery, and 63% for the left circumflex coronary artery. ConclusionsDobutamine MRI clearly identifies wall motion abnormalities by quantitative analysis using a modification of the centerline method. Dobutamine MRI is an accurate method for detection and localization of myocardial ischemia and may emerge as a new noninvasive approach for evaluation of patients with known or suspected coronary artery disease.

Lesional Overexpression of Matrix Metalloproteinase-9 Promotes Intraplaque Hemorrhage in Advanced Lesions But Not at Earlier Stages of Atherogenesis

Background—Matrix metalloproteinase-9 (MMP-9) is involved in atherosclerosis and elevated MMP-9 activity has been found in unstable plaques, suggesting a crucial role in plaque rupture. This study aims to assess the effect of MMP-9 on plaque stability in apolipoprotein E-deficient mice at different stages of plaque progression. Methods and Results—Atherosclerotic lesions were elicited in carotid arteries by perivascular collar placement. MMP-9 overexpression in intermediate or advanced plaques was effected by intraluminal incubation with an adenovirus (Ad.MMP-9). A subset was coincubated with Ad.TIMP-1. Mock virus served as a control. Plaques were analyzed histologically. In intermediate lesions, MMP-9 overexpression induced outward remodeling, as shown by a 30% increase in media size (p=0.03). In both intermediate and advanced lesions, prevalence of vulnerable plaque morphology tended to be increased. Half of MMP-9–treated lesions displayed intraplaque hemorrhage, whereas in controls and the Ad.MMP-9/Ad.TIMP-1 group this was 8% and 16%, respectively (p=0.007). Colocalization with neovessels may point to neo-angiogenesis as a source for intraplaque hemorrhage. Conclusion—These data show a differential effect of MMP-9 at various stages of plaque progression and suggest that lesion-targeted MMP-9 inhibition might be a valuable therapeutic modality in stabilizing advanced plaques, but not at earlier stages of lesion progression.

Increased brain and atrial natriuretic peptides in patients with chronic right ventricular pressure overload: correlation between plasma neurohormones and right ventricular dysfunction

OBJECTIVE To evaluate the role of plasma neurohormones in the diagnosis of asymptomatic or minimally symptomatic right ventricular dysfunction. SETTING Tertiary cardiovascular referral centre. METHODS Plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations were measured in 21 asymptomatic or minimally symptomatic patients with chronic right ventricular pressure overload caused by congenital heart disease, and in seven healthy volunteers. Right ventricular ejection fraction was determined using magnetic resonance imaging. RESULTS Right ventricular ejection fraction in the volunteers was higher than in the patients (69.0 (8.2)% v 58.0(12.0)%, respectively; p < 0.006). Left ventricular ejection fraction was 72.3(7.8)% in volunteers and 68.1(11.0)% in patients (NS). There was a significant difference between patients and volunteers in the plasma concentrations of BNP (5.3 (3.5) v 2.3 (1.7) pmol/l, respectively; p < 0.009) and ANP (7.3 (4.5)v 3.6 (1.4) pmol/l; p < 0.05). In both patients and volunteers, mean plasma ANP was higher than mean plasma BNP. Right ventricular ejection fraction was inversely correlated with BNP and ANP (respectively, r = 0.65; p < 0.0002 and r = 0.61; p < 0.002). There was no correlation between left ventricular ejection fraction and BNP (r = 0.2; NS) or ANP (r = 0.52; NS). Similarly, no correlation was shown between the level of right ventricular systolic pressure and either plasma BNP (r = 0.20) or plasma ANP (r = 0.07). CONCLUSIONS There was a significant inverse correlation between right ventricular ejection fraction and the plasma neurohormones BNP and ANP in asymptomatic or minimally symptomatic patients with right ventricular pressure overload and congenital heart disease. Monitoring changes in BNP and ANP may provide quantitative follow up of right ventricular dysfunction in these patients.

Assessing right ventricular function: the role of echocardiography and complementary technologies

The physiological importance of the right ventricle (RV) has been underestimated; the RV was considered mainly as a conduit whereas its contractile performance was thought to be haemodynamically unimportant.1 However, its essential contribution to normal cardiac pump function is well established with the primary RV functions being: RV function may be impaired either by primary right sided heart disease, or secondary to left sided cardiomyopathy or valvar heart disease.2 In addition, it should be considered that RV dysfunction may affect left ventricular (LV) function, not only by limiting LV preload, but also by adverse systolic and diastolic interaction via the intraventricular septum and the pericardium (ventricular interdependence). Moreover, RV function has been shown to be a major determinant of clinical outcome3–9 and consequently should be considered during clinical management and treatment.10 Thus, the need for diagnosis of RV dysfunction is evident. In practice, clinicians largely rely on non-invasive imaging methods for assessment of RV function. Two dimensional echocardiography is the mainstay for analysis of RV function, but recently alternative techniques have been proposed, including tissue Doppler imaging (TDI) techniques,11 three dimensional echocardiography,12 magnetic resonance imaging (MRI), and even invasive assessment of pressure–volume loops.13–17 An overview of these imaging modalities for assessment of RV function is provided in the current manuscript. Due to its widespread availability, echocardiography is used as the first line imaging modality for assessment of RV size and RV function. The quantitative assessment of RV size and function is often difficult, because of the complex anatomy. Nevertheless, when used …

Prevalence of coronary artery disease and plaque morphology assessed by multi-slice computed tomography coronary angiography and calcium scoring in asymptomatic patients with type 2 diabetes

Objective: The purpose of the study was to evaluate the prevalence of CAD as well as plaque morphology in asymptomatic patients with type 2 diabetes using multi-slice computed tomography (MSCT). In addition, the relation between calcium score and MSCT findings was explored. Design: In 70 patients, coronary calcium scoring and non-invasive coronary angiography were performed. Angiograms showing atherosclerosis were further classified as obstructive (⩾50% luminal narrowing) CAD or not. Plaque type (non-calcified, mixed and calcified) was determined. Finally, the relation between calcium score and MSCT findings was explored. Results: A calcium score <10 was observed in 31 (44%) patients. A calcium score of 10–100 was observed in 14 (20%) patients while a score of 101–400 or >400 was identified in 12 (17%) and 13 (19%) patients respectively. Non-invasive coronary angiography showed CAD in 56 (80%) patients. 322 coronary segments with plaque were identified, of which 132 (41%) contained non-calcified plaques, 65 (20%) mixed plaques and 125 (39%) calcified plaques. The percentage of patients with obstructive CAD paralleled increasing calcium score. The presence of CAD was noted in 17 (55%) patients with no or minimal calcium (score <10). Conclusions: MSCT angiography detected a high prevalence of CAD in asymptomatic patients with type 2 diabetes. A relatively high proportion of plaques were non-calcified (41%). Importantly, a calcium score <10 did not exclude CAD in these patients. MSCT might be a useful technique to identify CAD in asymptomatic patients with type 2 diabetes with incremental value over calcium scoring.

Survival and complication free survival in Marfan’s syndrome: implications of current guidelines

OBJECTIVE To evaluate survival and complication free survival in patients with Marfan’s syndrome and to assess the possible influence of recently revised guidelines for prophylactic aortic root replacement in these patients. METHODS 130 patients who had been attending one institution over 14 years were evaluated. Kaplan–Meier analysis was performed in 125 patients who did not present with aortic root dissection as the first sign of Marfan’s syndrome, with the end points: death, aortic root dissection, and prophylactic aortic root replacement after diagnosis. In the patients developing aortic root dissection, current guidelines for prophylactic aortic root replacement were retrospectively applied to investigate the number of dissections that could theoretically have been prevented. The guidelines were: (1) aortic root diameter ⩾ 55 mm, (2) positive family history of aortic dissections and aortic root diameter ⩾ 50 mm, and (3) aortic root growth ⩾ 2 mm/year. Outcomes following emergency surgery (15 patients) and prophylactic surgery of the aortic root (30 patients) were compared. RESULTS Five and 10 year survival after diagnosis was 95% and 88%, and the five and 10 year complication free survival was 78% and 66%, respectively. Thirteen patients developed dissection, 30 underwent prophylactic repair, and 82 had an uncomplicated course. Eleven dissections could theoretically have been prevented by application of the current guidelines. Five year survival following emergency and prophylactic repair of the aortic root was 51%, and 97%, respectively. CONCLUSIONS Survival in the Marfan’s syndrome in the past 14 years seems satisfactory; with application of current guidelines, it has probably even improved. However, because of the high fatality rate in Marfan patients developing aortic root dissection, more extensive screening for Marfan’s syndrome and a search for additional risk factors are desirable.

Diagnostic significance of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in thrombolytic treatment for acute myocardial infarction: its potential in assessing reperfusion.

The diagnostic value of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in patients treated by thrombolysis for acute myocardial infarction was assessed in 27 consecutive patients who had a first acute myocardial infarction (14 anterior, 13 inferior) and who underwent thrombolytic treatment and coronary arteriography within 4 hours of the onset of symptoms. Magnetic resonance imaging was performed 93 hours (range 15-241) after the onset of symptoms. A Philips Gyroscan (0.5 T) was used, and spin echo measurements (echo time 30 ms) were made before and 20 minutes after intravenous injection of 0.1 mmol/kg gadolinium-DTPA. In all patients contrast enhancement of the infarcted areas was seen after Gd-DTPA. The signal intensities of the infarcted and normal values were used to calculate the intensity ratios. Mean (SD) intensity ratios after Gd-DTPA were significantly increased (1.15 (0.17) v 1.52 (0.29). Intensity ratios were higher in the 17 patients who underwent magnetic resonance imaging more than 72 hours after the onset of symptoms than in the 10 who underwent magnetic resonance imaging earlier, the difference being significantly greater after administration of Gd-DTPA (1.38 (0.12) v 1.61 (0.34). When patients were classified according to the site and size of the infarcted areas, or to reperfusion (n = 19) versus non-reperfusion (n = 8), the intensity ratios both before and after Gd-DTPA did not show significant differences. Magnetic resonance imaging with Gd-DTPA improved the identification of acutely infarcted areas, but with current techniques did not identify patients in whom thrombolytic treatment was successful.

Prophylactic ciprofloxacin for catheter-associated urinary-tract infection

Patients receiving antibiotics during bladder drainage have a lower incidence of urinary-tract infections compared with similar patients not on antibiotics. However, antibiotic prophylaxis in patients with a urinary catheter is opposed because of the fear of inducing resistant bacterial strains. We have done a double-blind, placebo-controlled trial of prophylactic ciprofloxacin in selected groups of surgical patients who had postoperative bladder drainage scheduled to last for 3 to 14 days. Patients were randomly assigned to receive placebo (n = 61), 250 mg ciprofloxacin per day (n = 59), or 500 mg ciprofloxacin twice daily (n = 64) from postoperative day 2 until catheter removal. 75% of placebo patients were bacteriuric at catheter removal compared with 16% of ciprofloxacin-treated patients (relative risk [RR] [95% CI] 4.7 [3.0-7.4]). The prevalence of pyuria among placebo patients increased from 11% to 42% while the catheter was in place; by contrast, the rate of pyuria was 11% or less in patients receiving ciprofloxacin (RR 4.0 [2.1-7.3]). 20% of placebo patients had symptomatic urinary-tract infections, including 3 with septicaemia, compared with 5% of the ciprofloxacin groups (RR 4.0 [1.6-10.2]). Bacteria isolated from urines of placebo patients at catheter removal were mostly species of enterobacteriaceae (37%), staphylococci (26%), and Enterococcus faecalis (20%), whereas species isolated from urines of ciprofloxacin patients were virtually all gram-positive. Ciprofloxacin-resistant mutants of normally sensitive gram-negative bacteria were not observed. Ciprofloxacin prophylaxis is effective and safe in the prevention of catheter-associated urinary tract infection and related morbidity in selected groups of patients requiring 3 to 14 days of bladder drainage.

Differences in plaque composition and distribution in stable coronary artery disease versus acute coronary syndromes; non‐invasive evaluation with multi‐slice computed tomography

Background: Plaque composition rather than degree of luminal narrowing may be predictive of acute coronary syndromes (ACS). The purpose of the study was to compare plaque composition and distribution with multi‐slice computed tomography (MSCT) between patients presenting with either stable coronary artery disease (CAD) or ACS. Methods: MSCT was performed in 22 and 24 patients presenting with ACS or stable CAD, respectively. Coronary lesions were classified as calcified, non‐calcified or mixed while signal intensity (SI) was measured. Results: In patients with stable CAD, the majority of lesions were calcified (89%). In patients with ACS, less calcifications were observed with a greater proportion of non‐calcified (18%) or mixed (36%) lesions (P<0.001). Accordingly, mean SI of plaques was significantly less in ACS (320±201 HU versus 620±256 HU in stable CAD, P<0.001). Dividing lesions in the ACS group according to culprit versus non‐culprit vessel location resulted in no significant difference in average SI between these two groups while still lower as compared to stable CAD (P<0.001). Conclusions: In patients with ACS, significantly less calcifications were present as compared to stable CAD. Moreover, even in non‐culprit vessels, multiple non‐calcified plaques were detected, indicating diffuse rather than focal atherosclerosis in ACS.