Leo H.B. Baur

Detection and Quantification of Dysfunctional Myocardium by Magnetic Resonance Imaging A New Three-dimensional Method for Quantitative Wall-Thickening Analysis

BACKGROUND Regional left ventricular dysfunction is a major consequence of myocardial ischemia, and its extent determines long-term prognosis. Accurate and reproducible analysis of left ventricular dysfunction is therefore useful for risk stratification and patient management. METHODS AND RESULTS Short-axis cardiac cine magnetic resonance (MR) imaging was performed in 25 patients after anterior myocardial infarction at 21 +/- 2.1 days after the acute onset. The MR images were analyzed with the use of a dedicated analytical software package (MASS version 1.0), which includes a modified centerline method and a new three-dimensional analysis approach. A database of 48 healthy volunteers was constructed to objectively depict myocardial dysfunction in the patients; this database was compared with enzymatically determined infarct size. The mean (+/-SEM) quantity of dysfunctional myocardium and enzymatically calculated infarct size equaled 24.0 +/- 3.0 and 22.3 +/- 2.9 g, respectively (P = .69). Enzymatically determined infarct size correlated strongly with left ventricular dysfunction determined by cine MR imaging (y = 0.90x + .92. P < .0001). Segments related to the distribution of the left anterior descending coronary artery showed a significantly lower percentage wall thickening in patients than did corresponding segments of 48 normal subjects (46.0 +/- 8.22% versus 87.1 +/- mean SEM, respectively; P < .001). The mean (+/-SEM) end diastolic wall thickness of the infarcted segment did not differ from that of corresponding normal segments (7.4 +/- 0.33 versus 7.5 +/- 0.15 mm; P = .75). CONCLUSIONS We conclude that the use of three-dimensional quantitative analysis of cine MR images accurately quantities the extent of regional left ventricular dysfunction in the infarcted heart. This method of analysis may be useful in assessing the effect of interventional therapies.

Improved clinical outcome after invasive management of patients with recent myocardial infarction and proven myocardial viability: primary results of a randomized controlled trial (VIAMI-trial)

BackgroundPatients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia, especially when viability in the infarct-area is present. Therefore, an invasive strategy with PCI of the infarct-related coronary artery in patients with viability would reduce the occurrence of a composite end point of death, reinfarction, or unstable angina (UA).MethodsPatients admitted with an (sub)acute myocardial infarction, who were not treated by primary or rescue PCI, and who were stable during the first 48 hours after the acute event, were screened for the study. Eventually, we randomly assigned 216 patients with viability (demonstrated with low-dose dobutamine echocardiography) to an invasive or a conservative strategy. In the invasive strategy stenting of the infarct-related coronary artery was intended with abciximab as adjunct treatment. Seventy-five (75) patients without viability served as registry group. The primary endpoint was the composite of death from any cause, recurrent myocardial infarction (MI) and unstable angina at one year. As secondary endpoint the need for (repeat) revascularization procedures and anginal status were recorded.ResultsThe primary combined endpoint of death, recurrent MI and unstable angina was 7.5% (8/106) in the invasive group and 17.3% (19/110) in the conservative group (Hazard ratio 0.42; 95% confidence interval [CI] 0.18-0.96; p = 0.032). During follow up revascularization-procedures were performed in 6.6% (7/106) in the invasive group and 31.8% (35/110) in the conservative group (Hazard ratio 0.18; 95% CI 0.13-0.43; p < 0.0001). A low rate of recurrent ischemia was found in the non-viable group (5.4%) in comparison to the viable-conservative group (14.5%). (Hazard-ratio 0.35; 95% CI 0.17-1.00; p = 0.051).ConclusionWe demonstrated that after acute MI (treated with thrombolysis or without reperfusion therapy) patients with viability in the infarct-area benefit from a strategy of early in-hospital stenting of the infarct-related coronary artery. This treatment results in a long-term uneventful clinical course. The study confirmed the low risk of recurrent ischemia in patients without viability.Trial registrationClinicalTrials.gov: NCT00149591.

Circumstances of death in adult congenital heart disease

BACKGROUND Circumstances of death have been described for various cardiovascular diseases, but this study is the first for adults with congenital heart disease (CHD). METHODS Review of medical records and additional information from treating cardiologists and general practitioners, for circumstances of all deaths in a national registry of over 8000 adults with CHD. RESULTS Of 8595 patients, 231 (2.7%) patients died over 26,500 patient years. Main causes of death were progressive heart failure (26%) and sudden cardiac death (22%). Mortality was highest in the northern, most rural region of the country (p ≤ 0.05). Overall, death occurred out-of-hospital in approximately 35%, but more frequently in rural than in urban areas (55% versus 32%, p ≤ 0.05). Mortality was almost equally distributed throughout the seasons, although fall showed a slightly higher mortality rate. Cardiovascular death occurred suddenly in nearly 40%. Sudden cardiovascular death occurred in 8% during exercise, and most often out-of-hospital (62%). Of non-sudden cardiovascular deaths 18% had occurred out-of-hospital. CONCLUSION In adult patients with congenital heart disease, mortality shows substantial regional and subtle seasonal variation. Death usually occurs at rest; approximately 1 of 10 sudden cardiovascular deaths occur during exercise.

Heart failure admissions in adults with congenital heart disease; risk factors and prognosis

BACKGROUND Heart failure (HF) is a serious complication and often the cause of death in adults with congenital heart disease (CHD). Therefore, our aims were to determine the frequency of HF-admissions, and to assess risk factors of first HF-admission and of mortality after first HF-admission in adults with CHD. METHODS The Dutch CONCOR registry was linked to the Hospital Discharge Registry and National Mortality Registry to obtain data on HF-admissions and mortality. Risk factors for both HF-admission and mortality were assessed using Cox regression models. RESULTS Of 10,808 adult patients (49% male), 274 (2.5%) were admitted for HF during a median follow-up period of 21 years. The incidence of first HF-admission was 1.2 per 1000 patient-years, but the incidence of HF itself will be higher. Main defect, multiple defects, and surgical interventions in childhood were identified as independent risk factors of HF-admission. Patients admitted for HF had a five-fold higher risk of mortality than patients not admitted (hazard ratio (HR)=5.3; 95% confidence interval 4.2-6.9). One- and three-year mortality after first HF-admission were 24% and 35% respectively. Independent risk factors for three-year mortality after first HF-admission were male gender, pacemaker implantation, admission duration, non-cardiac medication use and high serum creatinine. CONCLUSIONS The incidence of HF-admission in adults with CHD is 1.2 per 1000 patient-years. Mortality risk is substantially increased after HF-admission, which emphasises the importance to identify patients at high risk of HF-admission. These patients might benefit from closer follow-up and earlier medical interventions. The presented risk factors may facilitate surveillance.

Assessment of left ventricular volume and mass by cine magnetic resonance imaging in patients with anterior myocardial infarction intra-observer and inter-observer variability on contour detection

Remodeling of the left ventricle after myocardial infarction can be documented by calculation of left ventricular volume and mass, using endocardial and epicardial tracings of multilevel multiphase short-axis cine magnetic resonance (MR) imaging series. We assessed left ventricular volume and mass from 8 slices and during 12 phases of the cardiac cycle in seven patients with an anterior wall myocardial infarction; one patient was studied twice, leaving eight MR examinations to be evaluated. Purpose of this study was to assess the intra-observer and interobserver variability of epicardial volume, endocardial volume, and left ventricular mass from contours manually traced by two independent observers. For the eight MR examinations, epicardial volume was found to be 292 ± 51 ml (mean ± SD) at end-diastole, which decreased to 237 ± 55 ml at end-systole. Endocardial volume was 141 ± 31 ml at end-diastole, which decreased to 79 ± 27 ml at end-systole. Left ventricular ejection fraction was 45 ± 8%. Mean left ventricular mass, when averaged over all patient studies and all phases, was 159 ± 30 g. Intra-observer and inter-observer variability were found to be 3.5% and 5.2% for endocardial volume, 2.0% and 2.5% for epicardial volume, and 3.6% and 3.6% for left ventricular mass, respectively. The contour analysis showed a statistically significant phase effect in the endocardial contour in the midventricular slices, which was resolved after establishing a more precise definition for the tracing of the endocardial border. In conclusion, left ventricular volume and mass in patients with an anterior wall myocardial infarction can be assessed with high reproducibility and relibility from manual contour tracings. A precise protocol for the definition of endocardial and epicardial contours is required to obtain reproducible and reliable results.

Combining salicylate and enalapril in patients with coronary artery disease and heart failure.

OBJECTIVE--To study the effects of adding a salicylate to the angiotensin converting enzyme inhibitor enalapril in patients with heart failure due to coronary artery disease. DESIGN--Double blind, crossover study for three days in hospital followed by an extended similar study outside hospital over two months of once daily enalapril plus salicylate and enalapril plus placebo. SETTING--Tertiary referral centre. PATIENTS--20 patients with heart failure due to myocardial infarction (New York Heart Association class II or III) and an ejection fraction less than 0.40. Twelve patients completed the two parts of the study. MAIN OUTCOME MEASURES--Blood pressure, plasma converting enzyme activity; plasma angiotensin II and noradrenaline concentrations; excretion of metabolites of renal and systemic prostanoids. RESULTS--The unloading effect of first and second dose of enalapril in the morning lasted only during the day; in the extended study it lasted 24 hours because of the drugs accumulation. Converting enzyme inhibitors attenuate the breakdown of bradykinin and therefore enhance prostaglandin E2 synthesis mediated by bradykinin. Evidence was found of such a prostaglandin E2 mediated contribution to ventricular unloading by enalapril, which was blocked by salicylate. The contribution, however, was small and variable, and salicylate addition had on average no significant de-unloading effect during the day. Unloading was abolished in only three of the 20 patients in the short term study and in one of the 12 in the extended study. At night, when other effects of enalapril on blood pressure had waned and the bradykinin induced effect persisted, salicylate significantly reduced the remaining small unloading effect. No effect was seen of salicylate addition on reversal of remodelling. Enalapril reduced angiotensin II induced synthesis of systemic and renal prostaglandin I2 and thromboxane A2, initially only during the day, but later also at night. It thereby masked suppression of thromboxane A2 synthesis by salicylate, which is the effect to which reinfarct prevention by salicylate is attributed. CONCLUSION--The risk is low that salicylate will substantially reduce the benefit of enalapril in patients with heart failure by de-unloading the ventricle. Like other effects induced by bradykinin significant de-unloading occurs in only a minority of the patients. In the presence of enalapril, however, salicylate will probably not be as effective as expected in reducing reinfarction risk, because enalapril already reduces thromboxane A2 synthesis effectively in patients with heart failure and no further reduction by salicylate was found.

Reproducibility of left ventricular size, shape and mass with echocardiography, magnetic resonance imaging and radionuclide angiography in patients with anterior wall infarction : A plea for core laboratories

After myocardial infarction, left ventricular volume and ejection fraction can be assessed by echocardiography, magnetic resonance imaging and radionuclide angiography to guide therapy and determine prognosis. Whether a measured parameter gives the same results irrespective of the method used and the observer who performs the analysis is only partly known. Intra-observer and inter-observer variability were determined for echo and magnetic resonance imaging. Left ventricular ejection fraction measured by these techniques was related to radionuclide angiograms performed in the same period. Intra-observer variability for both echo and MRI was low and in most instances below 5%. Inter-observer variability for the echo and MRI measurements were substantially higher than intra-observer variability. Comparison of the three imaging modalities revealed systematic differences. Therefore, in clinical studies, left ventricular volume and function parameters have to be measured with the same technique and by the same observer in qualified core laboratories.

Influence of angiotensin converting enzyme inhibition on pump function and cardiac contractility in patients with chronic congestive heart failure.

Eleven patients with coronary artery disease and chronic heart failure were studied before and three months after the angiotensin converting enzyme inhibitor enalapril was added to their frusemide medication. The following were measured: left ventricular pressure and volume with transient occlusion of the inferior vena cava, radionuclide angiography, and hormone concentrations in plasma. As in other reported studies, the clinical condition of the patients improved and their exercise tolerance increased moderately. Addition of enalapril reduced end diastolic and systolic pressure, reduced ventricular volume, and concomitantly increased the ejection fraction. The end systolic pressure-volume relation shifted to the left as it did in a similar animal study. In the animal study unloading by a vasodilator did not induce a leftward shift, so it can be inferred that in the present study unloading combined with a decrease in the angiotensin concentration was instrumental in remodelling the heart. Though unloading was expected to have a beneficial effect on the oxygen supply/demand ratio of the heart, the patients still showed the same drop in the ejection fraction during exercise as they did before treatment with enalapril, and early diastolic filling did not improve. Normally, regression of cardiac dilatation is only found if pump function improves; the present study showed that unloading in combination with angiotensin converting enzyme inhibition reshapes the ventricle without improving intrinsic pump function.

Detection of residual wall motion after sustained myocardial infarction by gated 99Tcm-tetrofosmin SPECT: a comparison with echocardiography.

The differentiation of residual viability from necrotic myocardium in patients with a previously sustained myocardial infarction is important in deciding indications for revascularization. Myocardial viability can be assessed by studying perfusion and regional wall motion. With gated single photon emission computed tomography (SPECT), it is possible to augment SPECT perfusion data with ventricular functional data both at a global and regional level. The aim of the study was to analyse the concordance between wall motion score derived by gated SPECT and echocardiography. Furthermore, the agreement between myocardial perfusion and left ventricular wall motion was analysed with both techniques. We studied a homogenous group of 25 consecutive patients with a previous myocardial infarction (MI) using both gated SPECT 99Tcm-tetrofosmin myocardial perfusion imaging and two-dimensional echocardiography. Echocardiography was performed within 2 weeks of the gated SPECT study. Both for gated SPECT and for echocardiography the left ventricle was divided into seven regions per patient. For comparison, the gated SPECT regions were matched to the echocardiographic regions, resulting in a total of 175 regions. Prevalence of abnormal wall motion (akinetic or dyskinetic) was 23% (39/171) for echocardiography and 21% (36/175) for gated SPECT (P = NS). There was a high agreement in wall motion score between echocardiography and gated SPECT of 80% (136/171). The agreement between myocardial perfusion and myocardial wall motion was 82% (143/175) for gated SPECT and 76% (130/171) for echocardiography (P = NS). Nineteen (34%) of the 56 regions with severely diminished or absent myocardial perfusion showed normal or hypokinetic wall motion both by gated SPECT and echocardiography suggesting residual myocardial viability in malperfused regions. Our results suggest that, gated SPECT imaging is a reliable tool for the assessment of regional wall motion in post myocardial infarction patients. Furthermore, in patients with a previous myocardial infarction gated SPECT imaging has the potential to detect preserved wall motion in regions with fixed perfusion defects, which might be indicative of residual myocardial viability.

Echocardiographic Parameters of the Freestyle Stentless Bioprosthesis in Aortic Position: The European Experience

The objective of this study was to determine normal Doppler and 2-dimensional characteristics of the Freestyle stentless aortic bioprosthesis. The Freestyle aortic bioprosthesis is a new type of aortic xenograft, and experience is limited. We therefore determined the normal range of echocardiographic and Doppler examinations of this valve. Three hundred thirty-nine consecutive patients with a Freestyle aortic bioprosthesis underwent an echocardiographic and Doppler examination according to a common protocol. Investigations were done within 4 weeks after operation, after 3 to 6 months, and after 1, 2, and 3 years. With a valve size from 19 to 27 mm, mean gradients decreased from 7.9 +/- 5.1 mm Hg at discharge to 5.5 +/- 3. 8 mm Hg after 3 to 6 months (P <.001). Thereafter, gradients remained stable. Effective orifice area 1 year after implantation was 1.59 +/- 0.58 cm(2) for the 21-mm valves, 1.92 +/- 0.74 cm(2) for the 23-mm valves, 2.03 +/- 0.64 cm(2) for the 25-mm valves, and 2.52 +/- 0.72 cm(2) for the 27-mm valves (P <.001). The performance index, the ratio of the measured effective orifice area in the patient divided by the effective orifice area measured in vitro, increased from 67% +/- 20% at discharge to 82% +/- 29% after 1, 2, and 3 years. Performance index was especially very high in the smaller-sized valves. After implantation with the subcoronary technique or root-inclusion technique, small cavities could be seen between the native aortic root and the Freestyle valve. Doppler values were evaluated for the Freestyle stentless porcine bioprostheses in the aortic root. Gradients appear to be close to those measured in native valves over a time period of 3 years.