Nico Abegunewardene

Influence of Contrast Agent Dose and Image Acquisition Timing on the Quantitative Determination of Nonviable Myocardial Tissue Using Delayed Contrast‐Enhanced Magnetic Resonance Imaging

BACKGROUND Delayed contrast-enhanced magnetic resonance imaging (ceMRI) has been shown to identify areas of irreversible myocardial injury due to infarction (MI) with high spatial resolution, allowing precise quantification of nonviable (hyperenhanced) myocardium. The aim of our study was to investigate the size of nonviable myocardium quantitatively as a function of time post-contrast when inversion time is held constant in patients post-myocardial infarction using two contrast agent (CA) doses. METHODS Nine patients with chronic MI underwent two MR scans on a 1.5 Tesla system. Contrast-enhanced MRI data in two short-axis (SA) slices were continuously acquired until 40 minutes after CA injection [gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), 0.1 mmol/kg body weight = single dose] interrupted only for a complete stack of SA slices encompassing the entire left ventricle (LV) between minutes 20 and 28. Left ventricular mass showing hyperenhancement was determined. The measurement was repeated on the subsequent day with double dose CA (0.2 mmol/kg body weight). Differences of signal intensities for hyperenhanced, nonhyperenhanced myocardium, and LV cavity were calculated. RESULTS Total mass of hyperenhancement from a complete SA stack acquired between minutes 20 and 28 was lower for single dose CA [9.0% vs. 14.2% for single and double dose, respectively (p = 0.03)]. Ten to 18 minutes after CA injection, there was no significant difference between the two doses and to an internal reference for both single and double dose. For single dose the image contrast between hyperenhancement and LV cavity was superior (minutes 10 to 16, p < 0.05) but inferior between hyperenhanced and nonhyperenhanced myocardium (minutes 6 to 16, p < 0.05). CONCLUSION Myocardial infarct size measurements are a function of time postcontrast when inversion time is held constant regardless of the contrast agent dose. These data underscore the fact that a standardized imaging protocol that defines how the appropriate inversion time should be selected is needed for comparison of results obtained at various cMR sites.

Effects of selective If-channel inhibition with ivabradine on hemodynamics in a patient with restrictive cardiomyopathy

Heart-rate reduction is a major goal in treatment of patients with coronary artery disease (CAD) and chronic congestive heart failure [1, 2], and an elevated resting pulse robustly correlates with decreased survival in these patients [3]. Therefore, heart rate reduction down to 55–60 bpm is recommended in the current guidelines for the treatment of CAD of the American Heart Association [4] and of the European Society of Cardiology [5] alike. The selective If-channel inhibitor ivabradine represents a novel pharmaceutical to achieve this goal [6]. In an experimental trial in a rodent model of heart failure, ivabradine was demonstrated to increase stroke volume, improve LV-function, and beneficially influence myocardial remodeling [7]. Whether the use of this drug is beneficial in patients with established systolic chronic heart failure, is currently under investigation in the SHIFT trial [8]. The treatment of restrictive cardiomyopathy, e.g., due to cardiac amyloidosis, however, differs substantially from that of patients with systolic heart failure due to ischemic heart disease or idopathic dilated cardiomyopathy. Special attention must be payed to fluid balance, and blood pressure lowering drugs must be administered carefully due to the development of profound hypotension; in addition, the usefulness of betablockers in patients with sinus rhythm has not been tested in cardiac amyloidosis [9]. So far, there are also no data about the effects of ivabradine in patients with cardiac amyloidosis, and data are lacking, if a heart rate reduction per se can improve hemodynamics, outcomes, or quality-of-life in patients with restrictive cardiomyopathy. We here report on a 78-year old male who was admitted to our emergency room with symptoms of decompensated congestive heart failure (pulmonary congestion, massive peripheral edema, pleural effusion), hypotension, and acute on chronic renal failure (creatinine 2.08 mg/dl, urea-N 83 mg/dl). Brain natriuretic peptide levels exceeded 5,000 pg/ml. The initial ECG showed a left axis, sinus rhythm, tachycardia of 110 bpm, and a Sokolow-LyonIndex of 3.5 mV. It is noteworthy that the patient had no history of arterial hypertension. A therapy with furosemide i.v. was initiated to recompensate the patient. This kind of therapy was not successful and the patient could not get rid of the massive peripheral edema, and we could not reduce the body weight. Echocardiography revealed the picture of a restrictive cardiomyopathy (see Fig. 1). Cardiac MRI showed diffuse hyperenhancement typical for amyloidois. Cardiac catheterization revealed a cardiac index (CI) of 1.2 l/min/m, a dip-plateau-phenomenon, and a tachycardia of 90–100 bpm. The coronary arteries were free of significant stenosis. Histological examination of a right-ventricular biopsy revealed a positive Kongo-red-staining proving the diagnosis cardiac amyloidosis, which was secondary to monoclonal gammopathy type lambda. Due to severe hypotension, diuretic resistance to high doses of furosemide and a marked tachycardia at rest was noted. Due to the low blood pressure, treatment with betablockers was not possible. The poor clinical state of the patient did not allow an aggressive treatment of the amyloidosis, e.g., using alkylating agents like melphalan. Slowing down the heart rate in patients with restrictive cardiomyopathy via use of digoxin and betareceptor P. Wenzel (&) N. Abegunewardene T. Munzel Universitatsmedizin der Johannes-Gutenberg-Universitat Mainz, II. Medizinische Klinik—Kardiologie, Angiologie und Internistische Intensivmedizin, Langenbeckstr. 1, 55131 Mainz, Germany e-mail: wenzelp@uni-mainz.de

Quantification of resting myocardial blood flow in a pig model of acute ischemia based on first-pass MRI

Qualitative and semiquantitative contrast‐enhanced (CE) dynamic perfusion MRI techniques are established as noninvasive diagnostic means of assessing coronary artery disease. However, to date quantification of myocardial blood flow (MBF) has not reached the same acceptance as MBF quantification with nuclear techniques. To validate quantification of MBF at rest using the extracellular contrast agent (CA) Gd‐DTPA, we performed an animal study in a pig model of acute myocardial ischemia. We quantified MBF from MRI data with a mathematical model (MMID4) of the underlying vasculature. These MBF results were subsequently compared with the results from fluorescent microspheres. The study showed a correlation of r = 0.66 between MBF estimates obtained with MRI and those obtained with fluorescent microspheres. The correlation for ischemic and nonischemic myocardium was r = 0.86 and r = 0.47, respectively. In conclusion, quantification of resting MBF using MMID4 is a valid method under conditions of acute myocardial ischemia. Magn Reson Med 53:1223–1227, 2005.

Tako-Tsubo syndrome: dying of a broken heart?

AimThe aim of the article is to review the etiology, pathology and epidemiology of a disease entity named Tako-Tsubo syndrome, receiving this name according to the picture obtained during ventriculography resembling a Japanese octopus trap. The Tako-Tsubo syndrome is a diagnosis encountered in patients with acute coronary syndrome and, therefore, is important to consider.MethodsThe literature search was performed in the MEDLINE database to identify the relevant topics. The references reported were used to complete the literature search.ResultsThe Tako-Tsubo syndrome is rising in incidence and makes up a relevant part of patients with acute coronary syndrome. The prevalence is described to be 0.6–2.5%. Especially, older women in the postmenopause with emotional stress are affected. The clinical changes and ECG alterations resemble the same characteristics like in acute coronary syndrome; however, the coronary arteries often show no impaired blood flow or only marginal changes. The reason for this syndrome is allocated to stress reactions with increased levels of stress hormones. As well, some patients develop contraction abnormalities like in Tako-Tsubo syndrome during intracranial bleeding, pheochromocytoma, seizures, infectious causes and sepsis, showing that not only emotional stress is responsible for the manifestation of this disease.ConclusionThe prevalence of Tako-Tsubo syndrome is about 2%, therefore this syndrome has to be considered in patients with acute coronary syndrome. Despite the life-threatening complications during the acute phase, a complete regression of the contraction abnormality is often reported.

Late improvement of regional wall motion after the subacute phase of myocardial infarction treated by acute PTCA in a 6-month follow-up.

BACKGROUND The aim of this follow-up study was to investigate the late effects of acute coronary angioplasty (PTCA) on regional wall motion after the subacute phase of myocardial infarction (MI). METHODS AND RESULTS Seventeen patients were investigated initially at a median of 11 days and again at 6 months after acute PTCA for myocardial infarction (< 8 hours after onset of symptoms) by cardiac magnetic resonance imaging. Corresponding short-axis slices encompassing the left ventricle (LV) were acquired using a standard cine MR for regional wall motion analysis and using delayed contrast enhanced magnetic resonance imaging (ceMRI) for infarct size quantification. The infarct size was similar in the subacute phase and the 6 month follow-up (20.8 and 21.9%, respectively; n.s.). Regional wall motion improved significantly in the area of hyperenhancement [percentage wall thickening (PWT) 21.9% and 37.9%, p < 0.05] in contrast to remote normal myocardium (46.4% and 38.4%; n.s.). Regional wall motion was significantly poorer in transmural compared with nontransmural MI in the subacute stage, and a late improvement could only be observed in transmural MI. CONCLUSION Transmural areas of hyperenhancement displayed significant late long-term improvement of regional wall motion after acute PTCA, possibly related to prolonged stunning compared with nontransmural areas.

Diagnostic value of routine clinical parameters in acute myocardial infarction: a comparison to delayed contrast enhanced magnetic resonance imaging

Aims: Contrast enhanced magnetic resonance imaging (ceMRI) has been shown to reliably identify irreversible myocardial injury. The aim of this study was to compare the findings on ceMRI with routine clinical markers of myocardial injury in patients with acute myocardial infarction (MI). Methods and results: Twenty-four patients with acute MI were investigated at 1.5 T. The global myocardial function was analysed with a standard cine MR protocol and a stack of short axis slices encompassing the entire left ventricle. Corresponding short axis slices were acquired for delayed ceMRI 15–20 min after the administration of 0.2 mmol gadolinium–DTPA/kg body weight. Mass of hyperenhancement and peak creatine kinase release (peak CK) was determined for each patient. The presenting 12-lead ECG was analysed for ST-elevation on admission and later development of Q-waves. Mass of hyperenhancement correlated moderately well to peak CK (r = 0.65, p < 0.01) and endsystolic volume index (r = 0.55, p < 0.01). Mass of hyperenhancement was inversely correlated to ejection fraction (r = −0.50, p = 0.02). Neither the presence of ST elevation on the admission ECG nor the later development of Q-waves did relate to the transmural extent of hyperenhancement and to the mass of hyperenhancement. Conclusion: Mass of hyperenhancement significantly correlates to global myocardial function and to peak CK. However, there is no relationship between the findings in ceMRI and 12-lead ECG abnormalities on admission suggesting an advantage of ceMRI in defining transmural extent and depicting small areas of necrosis.

Area at Risk and Viability after Myocardial Ischemia and Reperfusion Can Be Determined by Contrast-Enhanced Cardiac Magnetic Resonance Imaging

Background/Aims: Clinical differentiation between infarcted and viable myocardium in the ischemic area at risk is controversial. We investigated the potential of contrast-enhanced cardiac magnetic resonance imaging (ceCMRI) in determining the area at risk 24 h after ischemia. Methods: Myocardial ischemia was induced by percutaneous coronary intervention of the left anterior descending coronary artery in pigs. Coronary occlusion time was 30 min in group A, which caused little myocardial infarction and 45 min in group B, which led to irreversible damage. 24 h after reperfusion ceCMRI was performed at 2 and 15 min after administration of gadolinium-diethylenetriamine pentaacetic acid. The area at risk was determined by intravenous injection of Evans blue and myocardial viability by triphenyltetrazolium-chloride staining. Results: The signal-intense areas at 2 and 15 min after contrast administration matched the area at risk in groups A and B. Nonviable myocardium in group A was overestimated (14–15%) while good agreement was present in group B. Conclusion: The area at risk of reperfused ischemic myocardium can be determined by ceCMRI 24 h after coronary recanalization. This type of information might have relevant clinical implications in the treatment and stratification of patients with acute coronary syndrome in particular after surgical interventions.

Resistance of the Internal Mammary Artery to Restenosis : A Histomorphologic Study of Various Porcine Arteries

Background/Aims: Restenosis after percutaneous transluminal angioplasty (PTA) of the internal mammary artery (IMA) grafts is much less pronounced than in other arteries and venous grafts. The aim of the study was to test whether various arteries respond differently to dilatation. Methods: PTA of the IMA, carotid, renal and circumflex coronary (RCx) arteries was performed in 9 pigs (balloon to artery ratio of 1:1.5). After 8 weeks, angiography was repeated and vessels prepared for histological analysis. Immunohistochemical staining was done to examine proliferative activity (Ki67) and to identify the vasa vasorum of the adventitia (F VIII-RA). Results: The intima-media ratio after PTA was lowest in the IMA (0.06), followed by the carotid (0.27) and renal arteries (0.49) and the RCx (0.69). Proliferation of the intima was seen at 287° of the vessel circumference in the RCx, at 286° in the renal and at 166° in the carotid artery. No proliferative activity was seen in the IMA. The intima-adventitia ratio was lower in the IMA than in the RCx and renal arteries (p < 0.05). Conclusion: Intima proliferation after PTA varies between the different vessels, with best results seen in the IMA. There are differences in remodeling after PTA between muscular, muscular/elastic and elastic arteries.

Critical single proximal left arterial descending coronary artery stenosis to mimic chronic myocardial ischemia: a new model induced by minimal invasive technology.

Background/Aims: The present report examines a new pig model for progressive induction of high-grade stenosis, for the study of chronic myocardial ischemia and the dynamics of collateral vessel growth. Methods: Thirty-nine Landrace pigs were instrumented with a novel experimental stent (GVD stent) in the left anterior descending coronary artery. Eight animals underwent transthoracic echocardiography at rest and under low-dose dobutamine. Seven animals were examined by nuclear PET and SPECT analysis. Epi-, mid- and endocardial fibrosis and the numbers of arterial vessels were examined by histology. Results: Functional analysis showed a significant decrease in global left ventricular ejection fraction (24.5 ± 1.6%) 3 weeks after implantation. There was a trend to increased left ventricular ejection fraction after low-dose dobutamine stress (36.0 ± 6.6%) and a significant improvement of the impaired regional anterior wall motion. PET and SPECT imaging documented chronic hibernation. Myocardial fibrosis increased significantly in the ischemic area with a gradient from epi- to endocardial. The number of arterial vessels in the ischemic area increased and coronary angiography showed abundant collateral vessels of Rentrop class 1. Conclusion: The presented experimental model mimics the clinical situation of chronic myocardial ischemia secondary to 1-vessel coronary disease.

Low IL-10/TNFα ratio in patients with coronary artery disease and reduced left ventricular ejection fraction with a poor prognosis after 10 years.

Monocytes and dendritic cells (DC) produce tumour necrosis factor (TNF)α during inflammatory processes, but secrete interleukin (IL)-10 simultaneously in order to balance the pro-inflammation. In the present study, we investigated the expression of TNFα and IL-10 by monocytes and DC in patients with a poor cardiovascular prognosis after 10 years. Peripheral blood monocytes were isolated from 30 patients with coronary artery disease (CAD) with stable angina pectoris (SAP), or with an acute coronary syndrome (ACS). Monocytes were differentiated over 7 days to DC. Intracellular accumulation of TNFα and IL-10 in monocytes and DC was analysed by flow cytometry and correlated with the heart function, total and cardiovascular (CV) mortality, as well as with cardiovascular event rate over 10 years. We observed a decreased left ventricular function (LV-EF) for both SAP and ACS patients (p < 0.01), as well as a reduced IL-10/TNFα ratio for monocytes (p = 0.01) and DC (p < 0.01) for both patient groups in comparison to age-matched control group. Only the IL-10/TNFα ratio for monocytes correlated with LV-EF (r = 0.4302; p < 0.01). Patients with a low LV-EF as well as patients with a low IL-10/TNFα ratio showed an increased cardiovascular mortality over 10 years (both p < 0.05). The IL-10/TNFα ratio is decreased in patients with low ejection fraction and poor prognosis. The reduced heart function correlates with an increased proinflammatory state (low monocytic IL-10/TNFα ratio) in patients with CAD. This observed imbalance of IL-10 and TNFα in monocytes might explain pathophysiological processes in atherosclerosis and heart failure.