Is the diagnostic yield of myocardial stress perfusion MRI impaired by three-vessel coronary artery disease?

BACKGROUND: Three-vessel coronary artery disease (CAD) comes along with globally reduced myocardial perfusion potentially restricting the demarcation of regional hypoperfusion in stress perfusion cardiac magnetic resonance imaging (MRI). PURPOSE: To evaluate whether stress perfusion cardiac MRI is capable of detecting myocardial hypoperfusion in patients with 3-vessel CAD reliably. MATERIAL AND METHODS: Two hundred and five patients with symptoms of CAD were included. The examination protocol comprised imaging of myocardial perfusion at stress (0.14 mg/kg/min adenosine for 4 min) using a 2D saturation recovery gradient echo sequence after administration of gadobutrol (0.1 mmol/kg body weight). Perfusion sequences were assessed qualitatively by two experienced observers. Coronary angiography served as standard of reference. RESULTS: Sensitivity and specificity for hemodynamically relevant stenoses in patients with 0-, 1-, 2-, 3-vessel coronary artery disease were 100%/91%, 91%/73%, 90%/71%, 92%/64%; positive/negative predictive value, 67%/100%, 91%/73%, 83%/81%, 93%/58%; diagnostic accuracy, 93%/87%/83%/87%, respectively. The negative predictive value in patients with 3-vessel CAD was lower than in patients with 0- and 2-vessel CAD and the specificity lower than in patients with no CAD whereas the positive predictive value was higher than in patients with no CAD. The other proportions did not differ significantly between the groups. CONCLUSION: The diagnostic value of stress perfusion cardiac MRI in patients with 3-vessel CAD is comparable to results in patients with 1- or 2-vessel CAD. In the rare event that stress perfusion images do not depict regional hypoperfusion in patients with severe 3-vessel CAD, myocardial ischemia could be identified by reduced semi-quantitative perfusion parameters.

Mutation spectrum and prevalence of BRCA1 and BRCA2 genes in patients with familial and early-onset breast/ovarian cancer from Tunisia.

The contribution of BRCA1/BRCA2 mutations to hereditary breast cancer in the Tunisian population has not been accurately estimated. The purpose of our study was to estimate the incidence and spectrum of pathogenic mutations in BRCA1/2 genes in early onset and familial breast/ovarian cancer among Tunisian women. To identify predictive factors for BRCA1/2 mutations, we screened the entire coding sequences and intron/exon boundaries of BRCA1/BRCA2 genes in 48 patients by direct sequencing. Twelve pathogenic mutations were detected (25%); three in BRCA1 (c.211dupA in four families, c.5266dupC in three families and c.1504_1508delTTAAA in one family) and two novel mutations in BRCA2 (c.1313dupT in two families and c.7654dupT in two families). We also identified 23 different polymorphisms and unclassified variants. These results indicate that our population has a spectrum of recurrent BRCA mutations.

Is myocardial stress perfusion MR-imaging suitable to predict the long term clinical outcome after revascularization?

INTRODUCTION: Aim of our study was to evaluate, whether myocardial ischemia or myocardial infarction (MI) depicted by myocardial stress perfusion MR imaging (SP CMR) can predict the clinical outcome in patients with coronary artery disease (CAD). MATERIALS AND METHOD: 220 patients were included. Myocardial perfusion was assessed at stress and at rest, using a 2D saturation recovery gradient echo sequence (SR GRE) and myocardial viability by late gadolinium enhancement magnetic resonance images (LGE CMR). MR-images were assessed in regard of presence and extent of MI and ischemia. Patients were monitored for major adverse cardiac events (MACE) (monitoring period: 5-7 years). MACE were correlated with the initial results of SP CMR. RESULTS: Ischemia was found in 143 patients, MI in 107 patients. Number of MACE was in patients with normal SP CMR 0 (51 patients), with ischemia 21 (62 patients), with MI 14 (26 patients), with ischemia and MI 52 (81 patients). In all patients with severe MACE (MI, death) and in 63 of those with recurring symptoms LGE CMR revealed MI at baseline. CONCLUSION: Negative SP CMR indicates low risk for MACE. In patients with stress induced ischemia, MACE might occur even after myocardial revascularization. The presence of MI proved by LGE CMR is associated with a significantly increased risk for MACE.

Platelets and matrix metalloproteinases.

Matrix metalloproteinases (MMPs) and their inhibitors essentially contribute to a variety of pathophysiologies by modulating cell migration, tissue degradation and inflammation. Platelet-associated MMP activity appears to play a major role in these processes. First, platelets can concentrate leukocyte-derived MMP activity to sites of vascular injury by leukocyte recruitment. Second, platelets stimulate MMP production in e.g. leukocytes, endothelial cells, or tumour cells by direct receptor interaction or/and by paracrine pathways. Third, platelets synthesise and secrete a variety of MMPs including MMP-1, MMP-2, MMP-3, and MMP-14 (MT1-MMP), and potentially MMP-9 as well as the tissue inhibitors of metalloproteinase (TIMPs). This review focuses on platelet-derived and platelet-induced MMPs and their inhibitors.

[Cardiac magnetic resonance tomography in the diagnostics of restrictive and unclassified cardiopathies]. / Kardiale Magnetresonanztomographie in der Diagnostik der restriktiven und unklassifizierten Kardiomyopathien.

CLINICAL/METHODICAL ISSUE: Besides ischemic heart disease cardiomyopathies are common causes of heart failure and sudden cardiac death. STANDARD RADIOLOGICAL METHODS: The diagnostic spectrum in cardiomyopathies comprises non-invasive and invasive examination techniques. METHODICAL INNOVATIONS: The exact verification of certain cardiomyopathies necessitates knowledge of the latest classification of cardiomyopathies as well as dedicated examination protocols. PERFORMANCE: Modern imaging modalities, such as echocardiography and cardiac magnetic resonance imaging (MRI) have emerged as useful imaging tools in the investigation of patients suspected of having many different types of cardiomyopathies. ACHIEVEMENTS: Based on a better understanding of the underlying pathophysiology several diagnostic criteria have been defined using cardiac MRI. In particular there is an increasing importance of cardiac MRI in the description of patients with restrictive and unclassified cardiomyopathies. PRACTICAL RECOMMENDATIONS: Echocardiography still remains the modality of choice in the diagnostics of unclear left ventricular heart failure. Further diagnostic work-up should include cardiac MRI in case of any lack of clarity.

Atopaxar. A novel player in antiplatelet therapy?

Atopaxar, also known as E 5555 is a novel reversible protease-activated receptor-1 (PAR-1) thrombin receptor antagonist. To date, Atopaxar has been investigated in phase II trials with focus on safety and tolerability in patients with acute coronary syndromes or stable coronary artery disease on top of standard antiplatelet therapy. Atopaxar was generally well tolerated, however a rise in liver enzymes and prolongation of the QTcF interval were observed. The data suggest, that atopaxar administration may promote some minor bleeding complications, but does not seem to significantly increase the risk of major bleeding. Although not powered for efficacy, the currently available data suggest potential benefits in patients at high risk for recurrent ischemic events on top of standard antiplatelet therapy. In conclusion, more studies (e.g. phase III) are needed to evaluate efficacy and safety of atopaxar.

Expression of stromal-cell-derived factor-1 (SDF-1): a predictor of ischaemic stroke?

BACKGROUND AND PURPOSE: Platelet stromal-cell-derived factor-1 (SDF-1) plays a pivotal role in angiogenesis and the regeneration of ischaemic tissue through the regulation of haematopoietic progenitor cells and is upregulated at the sites of vascular injury and platelet activation. Thus, SDF-1 has recently been discussed as a predictor in ischaemic diseases such as acute myocardial infarction. However, no clinical data pertinent to the investigation of the platelet SDF-1 expression in patients with stroke are available. METHODS: We consecutively evaluated 196 patients who were admitted to the stroke unit with symptoms suspected for stroke. Surface expression of the platelet activation markers (P-selectin and GPIb) and the expression of platelet-bound SDF-1 were determined by two-colour whole blood flow cytometry. RESULTS: Patients with transient ischaemic attack (TIA) as well as with ischaemic stroke showed similar levels of SDF-1 expression on hospital admission compared with patients with non-ischaemic (NI) events and with 30 healthy controls (TIA (mean fluorescence intensity±SD): 31.5±18.2 vs. NI: 26.4±15.7; P=0.361; stroke: 28.7±19.8 vs. NI; P=0.943; control: 26.1±11.3; P>0.05 compared with all). Platelet SDF-1 expression showed a trend with the severity of stroke according to National Institute of Health Stroke Scale score (r=0.125; P=0.085), but significantly correlated with the peak levels of C-reactive protein (r=0.218; P=0.002) and with the levels of platelet activation (P-selectin: r=0.389; P=0.001). Multifactorial analysis of covariance revealed a significant influence on platelet SDF-1 expression by smoking (P=0.019). CONCLUSIONS: Platelet SDF-1 surface expression did not show any significant difference in patients with TIA and ischaemic stroke compared with patients with NI events. Thus, single biomarker evaluation of platelet SDF-1 surface expression is not helpful to predict ischaemic stroke.

Atopaxar.

Atopaxar, also known as E 5555 is a novel reversible protease-activated receptor-1 (PAR-1) thrombin receptor antagonist. To date, Atopaxar has been investigated in phase II trials with focus on safety and tolerability in patients with acute coronary syndromes or stable coronary artery disease on top of standard antiplatelet therapy. Atopaxar was generally well tolerated, however a rise in liver enzymes and prolongation of the QTcF interval were observed. The data suggest, that atopaxar administration may promote some minor bleeding complications, but does not seem to significantly increase the risk of major bleeding. Although not powered for efficacy, the currently available data suggest potential benefits in patients at high risk for recurrent ischemic events on top of standard antiplatelet therapy. In conclusion, more studies (e.g. phase III) are needed to evaluate efficacy and safety of atopaxar.

Successful bridge to recovery using a microaxial blood pump in a patient with electrical storm and cardiogenic shock.

A 59-year-old patient with dilated cardiomyopathy and incessant ventricular tachycardia leading to progressive cardiogenic shock is presented. Due to hemodynamic instability, high dose catecholamines were required in addition to the implantation of an intraaortic balloon pump (IABP), which, however, appeared to further augment the frequency and duration of ventricular tachycardias. The implantation of a microaxial blood pump allowed catecholamine administration to be terminated, thereby, ending this vicious circle of catecholamine-driven electrical storm. Within 5 days, the patient was hemodynamically stabilized and kidney and liver function recovered with the support of intensive antiarrhythmic therapy (amiodarone, mexiletine, sotalol). During a 24-month follow-up, the patient had no further ICD shocks and no rehospitalization was required for treatment of congestive heart failure.

[Recurrent pericardial effusion as first manifestation of Erdheim-Chester disease]. / Rezidivierender Perikarderguss als Erstmanifestation eines Morbus Erdheim-Chester.

HISTORY AND ADMISSION FINDINGS: A 65-year-old woman presented with reduced general condition and dyspnoea that was progressive over the last months. Clinical findings revealed an exophthalmus on the right, xanthelasm and mild peripheral oedema. Previously, a pericardiocentesis had been performed due to a large pericardial effusion. A previous CT scan showed a mass attached to the pericardium extending through the atrio-ventricular groove and a thickened aorta. In addition, a retroperitoneal fibrosis and an occlusion of both Aa. iliacae internae were found. INVESTIGATIONS: The ECG showed sinus rhythm. Laboratory findings demonstrated a microcytic anemia and a renal failure. Chest radiography showed a large cardiac silhouette, while the transthoracic echocardiography revealed a recurrent large pericardial effusion. A PET/CT scan of the chest and abdomen showed a tissue infiltration of the retroperitoneal structures, a mass surrounding the right coronary artery and the right orbita. Finally, a femur biopsy confirmed the diagnosis of Erdheim-Chester disease. DIAGNOSIS, TREATMENT AND COURSE: With the diagnosis Erdheim-Chester disease we started a high dose immunsuppressive therapy using glucocorticoids and interferon-a. Tumour size slightly decreased during the following 2 months, however the patient developed a severe urosepsis and died from multiorgan failure. CONCLUSIONS: We report a case of an Erdheim-Chester disease with cardiovascular involvement primarily diagnosed due to a recurrent large pericardial effusion. In case of cardial tumors with interatrial septum or coronary artery involvement together with cerebral manifestations, an Erdheim-Chester disease should be taken into account.

Expression of platelet glycoprotein VI is associated with transient ischemic attack and stroke.

BACKGROUND AND PURPOSE: Platelet collagen receptor glycoprotein VI (GPVI) contributes significantly to platelet adhesion and thrombus formation. We aimed to investigate GPVI in patients presenting with symptoms of acute cerebrovascular disease and to define GPVI as biomarker for acute stroke. METHODS: We consecutively evaluated 205 patients, who admitted the stroke unit with symptoms for stroke. Surface expression of the platelet activation markers (GPVI, CD62P, GPIb) was determined by two-color whole blood flow cytometry. RESULTS: Patients with transient ischemic attack (TIA) (n = 18; 8.8%) as well as with stroke (n = 133; 64.9%) showed a significantly enhanced GPVI expression (mean fluorescence intensity +/- SD) on admission compared to patients with non-ischemic (NI) events (n = 54; 26.3%) (TIA: 20.9 +/- 7.1 vs. NI: 16.2 +/- 3.9; P = 0.002; stroke: 20.4 +/- 5.7 vs. NI; P = 0.002). Neither CD62P nor GPIb surface expression showed a significant difference. Logistic regression analysis revealed that on admission GPVI was associated with stroke independent of conventional laboratory markers such as C-reactive protein, blood glucose, and creatine kinase. Using a receiver operating characteristic curve on GPVI, we have determined the cut off value of 18.2 for stroke. Thus, patients with enhanced GPVI expression levels (>or=18.2) had a 2.4-fold relative risk for stroke. Patients with elevated platelet GPVI expression level had a poorer clinical outcome in cumulative event-free survival for stroke, myocardial infarction, and cerebro-/cardiovascular death at 3-month follow-up (log rank; P = 0.045). CONCLUSIONS: These findings indicate that platelet GPVI surface expression is significantly enhanced in patients with TIA and stroke compared to patients with NI events. Determination of platelet-specific GPVI may be useful as an early biomarker for cerebral ischemia.

[Cardiac MRI in addition to MR angiography: a longitudinal study in vascular risk patients]. / Kardiale MRT als ergänzung zur MR-angiografie: eine longitudinale studie bei vaskulären risikopatienten.

PURPOSE: The aim of the study was to assess the feasibility and additional diagnostic information of cardiac MRI as a supplement to state-of-the-art MR angiography (MRA) in the case of vascular risk patients. Therefore, the prevalence of delayed myocardial enhancement (DE) was determined in patients suffering from peripheral artery disease (PAD) and a clinical follow-up was evaluated after 2 years. MATERIALS AND METHOD: 87 consecutive patients (ages 66 +/- 10 years, 67 males) with symptomatic peripheral arterial occlusive disease (n = 68) or abdominal aortic aneurysm (n = 19) were examined using delayed cardiac enhancement (DE) within the clinical indication of MRA at a 1.5T system. A follow-up examination was carried out two years later (24 months +/- 4 months) with regards to cardiac events (cardiac death, myocardial infarction or acute coronary syndrome, heart insufficiency, coronary revascularization). RESULTS: In total, 40 / 87 patients had myocardial infarctions shown in MRI (46 %). In 25 patients (29 %), the myocardial infarction was already known, while in 15 patients (17 %) an occult progressing infarction was diagnosed (38 % of the myocardial infarcts). Follow-up data was able to be obtained after 2 years for 82 patients. 15 patients had a major cardiac event during the follow-up period, and 10 (67 %) of them already showed DE in the MRI. In the group with occult progressing infarctions, cardiac events occurred in 40 % (6 / 15 patients, cardiac death n = 1, ischemia n = 4, heart insufficiency n = 1, bypass n = 1), in patients with known infarction in 17 % (4 / 23 patients, cardiac death n = 1, ischemia n = 3, bypass n = 2) and in 11 % of patients without myocardial scars (5 / 44 patients, cardiac death n = 1, ischemia n = 2, heart insufficiency n = 2). CONCLUSION: Cardiac MRI in combination with MRA was feasible and showed a high prevalence of known and unexpected myocardial infarctions. This was of prognostic relevance in the follow-up 2 years later. Therefore, this enables important additional information regarding to the risk stratification and eventually targeted therapy in risk patients with PAD.

UK registry of high-risk obstetric anaesthesia: report on neurological disease.

The UK registry of high-risk obstetric anaesthesia was set up in 1996 to collect reports of high-risk pregnancy, pool them into a central database and make them available to obstetric anaesthetists. This paper summarises the data relating to 102 patients with neurological disease who were reported to the registry between 1997 and 2002. The two most common conditions reported were spina bifida and multiple sclerosis. We describe the features and management of these and other cases.

[Acute thrombo-embolic elevated ST infarct in a patient with essential thrombocytosis]. / Akuter thrombembolischer ST-Hebungs-Infarkt bei einem Patienten mit essenzieller Thrombozytose.

A 48-year-old man presented with acute chest pain and a greatly increased platelet count. Emergency coronary angiographic revealed thrombotic occlusion of the right coronary artery. Coronary angioplasty and stenting were successfully combined with intracoronary abciximab administration. Due to inadequate postinterventional platelet inhibition an intensified dual antiplatelet therapy with acetylsalicylic acid (ASS) and clopidogrel was applied to prevent stent thrombosis. Due to the thrombo-embolic complication and a platelet count over 1 million/microl a cytoreductive treatment with hydroxyurea was initiated.

[MR stress perfusion for the detection of flow-limiting stenoses in symptomatic patients with known coronary artery disease and history of stent implantation]. / MR-Stressperfusion zur Vorhersage flusslimitierender Stenosen bei symptomatischen Patienten mit bekannter KHK nach Stentimplantation.

PURPOSE: The aim of the present study was to determine the correlation of myocardial perfusion MR imaging (MPMRI) and coronary angiography for the detection of flow-limiting stenosis in symptomatic patients with known coronary artery disease and a history of intervention. MATERIALS AND METHODS: MPMRI was performed in 51 symptomatic patients (44 male, 64.7 +/- 9.5 years) with known coronary artery disease and a history of stent implantation (between 5 years and 2 weeks prior to MRI). Malperfused myocardial regions were correlated with findings of coronary angiography. A stenosis of > 70% was regarded as hemodynamically significant. RESULTS: In MPMRI 37 patients (73%) showed a stress induced perfusion deficit. In 35 of these patients coronary angiography revealed a stenosis of > 70 %. A total of 38 patients (75%) showed stenoses of > 70%. MPMRI yielded a sensitivity of 92% with a specificity of 85 %. The positive predictive value was 95 % and negative predictive value was 79%. The assignment of malperfused segments to coronary artery territories was carried out according to the standardized myocardial model of the American Heart Association (sensitivity/specificity was 59/85% for RCA, 79/81% for LAD and 54/68 % for LCX). CONCLUSION: MPMRI is a suitable non-invasive method for detecting flow-limiting coronary artery stenoses in patients with a history of stent implantation.

Uncorrected total anomalous pulmonary venous drainage in pregnancy.

Total anomalous pulmonary venous drainage is a rare form of congenital heart disease. It usually presents in the neonatal period, although later presentation, including in adulthood, is known to occur. We could not find any accounts of adult survivors with the undiagnosed disease becoming pregnant. We describe the case of a 19-year-old Bengali primiparous woman who arrived in the UK at 27 weeks' gestation and needed an urgent caesarean section for intrauterine growth restriction at 34 weeks' gestation. Uncorrected congenital heart disease was diagnosed at this time although the exact nature of the pathology was not clear. She underwent an uncomplicated caesarean section using a combined spinal-epidural technique with invasive monitoring. Intrathecal 0.5% hyperbaric bupivacaine 0.7 mL and fentanyl 25 microg were sufficient for surgery. She remained cardiovascularly stable throughout the procedure and a female infant was successfully delivered. She underwent corrective cardiac surgery 14 months after delivery. To our knowledge, this is the first report of caesarean section in a patient with uncorrected total anomalous pulmonary venous drainage. In this case, regional anaesthesia was successfully used.

[Serious clinical course of myocarditis with "apical ballooning": first presentation of pathogenicity of HHV6 subtype A in myocarditis]. / Schwerer klinischer Verlauf einer Myokarditis mit "apical ballooning". Erstbeschreibung der Pathogenität von HHV6 Subtyp A bei Myokarditis.

We report of a 67 year-old female who has suffered a flu-like infection three days ago and presented with symptoms of acute coronary syndrome. Coronary heart disease could be excluded. The ventriculography showed a moderate reduced left ventricular function characterized by "apical ballooning". Endomyocardial biopsies and EDTA blood gave a direct proof of human herpes virus 6 subtype A. Histological and immunohistochemical analysis revealed a myocarditis with areas of interstitial macrophages and fibrosis. This case presents for the first time the cross-link of myocarditis with HHV6A infection and the appearance of "apical ballooning".