Validity of Ultrasound for the Diagnosis of Arterial Thoracic Outlet Syndrome.

Objective: Thoracic outlet syndrome (TOS) is a rare disorder mostly seen in younger individuals. Although patient wellbeing is relevantly impaired, it often takes a long time before the diagnosis is made. Digital subtraction angiography (DSA) is routinely used despite its radiation exposure, which is a major concern in this young patient population. Moreover, DSA offers limited opportunities for functional assessment. By contrast, ultrasonography is widely accessible without causing radiation exposure and allows for flexible functional assessment. The main goal of the study was to investigate whether ultrasound (US) was a viable alternative to DSA in diagnosing arterial TOS (aTOS). Methods: Patients, referred to a tertiary centre for evaluation of suspected TOS, were recruited into the study. DSA was routinely performed with the patient's arms both in the raised (abducted) and neutral (adducted) position. Two vascular surgeons and two radiologists assessed the resulting images for the presence of aTOS. Additionally, two examiners performed US according to a standardised protocol. The reference for presence of aTOS was the DSA based interdisciplinary vascular conference consensus. Inter-rater agreement and latent class analysis (LCA) were performed between assessors and diagnostic methods. Results: Fifty one consecutive patients (two thirds female) aged 39.3 ± 13.0 years were included within 11 months. US agreement was excellent at 0.94 (0.841-0.980), DSA agreement for vascular surgeons was good at 0.779 (0.479-1.000), whereas it was moderate at 0.546 (0.046-1.000) for radiologists. Results suggest that DSA is untenable as the gold standard for aTOS diagnosis. In LCA, US was shown to be a reliable diagnostic tool for the detection of aTOS. Conclusion: US examination is a valid test for the detection of haemodynamically relevant compression of arteries in the diagnostic work up of aTOS using a standardised protocol. The role of DSA as the gold standard should be reviewed and needs to be reconsidered.

Patients' Perspective on Termination of Pacemaker Therapy-A Cross-Sectional Anonymous Survey among Patients Carrying a Pacemaker in Germany.

OBJECTIVE: To determine the opinions of patients regarding the withdrawal of pacemaker therapy. PARTICIPANTS AND METHODS: A cross-sectional anonymous questionnaire was administered to patients visiting an outpatient cardiologic clinic for routine follow-up visits of pacemaker therapy or patients carrying a pacemaker admitted to a hospital between 2021 and 2022. RESULTS: Three-hundred and forty patients answered the questionnaire. A total of 56% of the participants were male. The mean age was 81 years. The majority of respondents were very comfortable with their PM and felt well informed, with one exception: more than half of respondents were missing information on withdrawal of pacemaker therapy. Almost two-thirds wanted to decide for themselves if their pacemaker therapy was withdrawn regardless of whether they were ill or healthy. Almost 60% of patients would like the pacemaker to be turned off when dying. Women expressed this wish significantly more often than men. CONCLUSION: Our survey shows that patients prefer to be informed on issues regarding the withdrawal of pacemakers as early as preimplantation. Also, patients would like to be involved in decisions that have to be made at the end of life, including decisions on withdrawal. Offers of conversations about this important issue should include information on special features of the patient's pacemaker, e.g., the absence or presence of pacemaker dependency. Knowledge about the pacemaker's functionality may prevent distress among individuals nearing their end of life when, for example, under the false impression that timely deactivation may allow for a more peaceful death.

Feasibility and safety of automated CO2 angiography in peripheral arterial interventions.

ABSTRACT: Carbon dioxide (CO2) gas is an established alternative to iodine contrast during angiography in patients with risk of postcontrast acute kidney injury and in those with history of iodine contrast allergy. Different CO2 delivery systems during angiography are reported in literature, with automated delivery system being the latest. The aim of this study is to evaluate the safety, efficacy, and learning curve of an automated CO2 injection system with controlled pressures in peripheral arterial interventions and also to study the patients' tolerance to the system.From January 2018 to October 2019 peripheral arterial interventions were performed in 40 patients (median age-78 years, interquartile range: 69-84 years) using an automated CO2 injection system with customized protocols, with conventional iodine contrast agent used only as a bailout option. The pain and tolerance during the CO2 angiography were evaluated with a visual analog scale at the end of each procedure. The amount of CO2, iodine contrast used, and radiation dose area product for the interventions were also systematically recorded for all procedures. These values were statistically compared in 2 groups, viz first 20 patients where a learning curve was expected vs the rest 20 patients.All procedures were successfully completed without complications. All patients tolerated the CO2 angiography with a median total pain score of 3 (interquartile range: 3-4), with no statistical difference between the groups (P = .529). The 2 groups were statistically comparable in terms of comorbidities and the type of procedures performed (P = .807). The amount of iodine contrast agent used (24.60 ±â€Š6.44 ml vs 32.70 ±â€Š8.70 ml, P = .006) and the radiation dose area product associated were significantly lower in the second group (2160.74 ±â€Š1181.52 µGym2 vs 1531.62 ±â€Š536.47 µGym2, P = .043).Automated CO2 angiography is technically feasible and safe for peripheral arterial interventions and is well tolerated by the patients. With the interventionalist becoming familiar with the technique, better diagnostic accuracy could be obtained using lower volumes of conventional iodine contrast agents and reduction of the radiation dose involved.

Factor VII Activating Protease Expression in Human Platelets and Accumulation in Symptomatic Carotid Plaque.

Background Factor VII activating protease (FSAP) is of interest as a marker for vascular inflammation and plaque destabilization. The aim of this study was to analyze the expression profile of FSAP in endarterectomy specimens that were taken from patients with asymptomatic and symptomatic carotid atherosclerotic plaques and to compare them with circulating FSAP levels. Methods and Results Plasma FSAP concentration, activity, and mRNA expression were measured in endarterectomy specimens and in monocytes and platelets. Plaque and plasma FSAP levels were higher in symptomatic patients (n=10) than in asymptomatic patients (n=14). Stronger FSAP immunostaining was observed in advanced symptomatic lesions, in intraplaque hemorrhage-related structures, and in lipid-rich areas within the necrotic core. FSAP was also colocalized with monocytes and macrophages (CD11b/CD68-positive cells) and platelets (CD41-positive cells) of the plaques. Moreover, human platelets expressed FSAP in vitro, at both the mRNA and protein levels. Expression is stimulated by thrombin receptor-activating peptide and ADP and reduced by acetylsalicylic acid. Conclusions Plasma FSAP levels were significantly increased in patients with symptomatic carotid stenosis and thus may be involved in plaque development This plaque-associated FSAP may be produced by platelets or macrophages or may be taken up from the circulation. To establish FSAP's utility as a circulating or plaque biomarker in patients with symptomatic carotid atherosclerotic plaques, further studies are needed.

[Maurice Raynaud (1834-1881) and the Mystery of "Raynaud's Phanomenon"]. / Maurice Raynaud (1834­1881) und das Mysterium "Raynaud-Phänomen".

Maurice Raynaud first described color changes and symptoms of the fingers due to cold-induced vasospasm and restricted blood flow in his medical school thesis in 1862. Raynaud's phenomenon is common and exists as an uncomplicated primary Raynaud phenomenon and a Raynaud phenomenon secondary to underlying diseases and medication. Mechanisms contributing to altered vasoconstrictor activity are endothelial and not-endothelial. Cold-induced vasospasm is probably a thermoregulatory problem and effects are mediated by sympathetic activity and selective stimulation of alpha2c-adrenoreceptors.

Combined treatment of subacute and acute synthetic and venous bypass-graft occlusions with percutaneous mechanical thrombectomy and thrombolysis.

INTRODUCTION: Percutaneous mechanical thrombectomy (PMT) is a third choice of treatment for acute arterial occlusions, in addition to thrombolysis and surgical thrombectomy. The aim of this retrospective study was to compare the combined treatment of PMT and local thrombolysis with thrombolysis therapy alone. MATERIALS AND METHODS: Sixty-nine patients with acute (<14 days [n = 35]) or subacute (14-42 days [n = 34]) femoropopliteal bypass occlusions were treated with PMT combined with thrombolysis. Seventy-two patients with acute [n=40] or subacute [n = 32] femoropopliteal bypass occlusions were treated with thrombolysis alone. The thrombolysis in myocardial infarction (TIMI) classification was used to assess the bypass occlusion. Local thrombolysis time and dosage, reopening time, time in the intensive care unit, necessary surgical re-interventions, and clinical outcome were compared between the 2 groups. RESULTS: The TIMI scores were significantly higher in the PMT plus thrombolysis group than in the thrombolysis group (acute occlusions 1188 versus 935, p<0.001; subacute occlusions 935 versus 605, p<0.001). The total urokinase dosage, the total hours of thrombolysis, time in the intensive care unit, and total hospital stay in the acute PMT plus thrombolysis group were significantly lesser than those in the thrombolysis group. After 24h of treatment, the ankle-brachial index improved in all groups (p<0.001): in the acute and subacute PMT plus thrombolysis group to 0.63 ± 0.14 and 0.43 ± 0.08, respectively; and in the acute and subacute thrombolysis group to 0.51 ± 0.11 and 0.41 ± 0.04, respectively. CONCLUSIONS: PMT combined with thrombolysis is a safe and very effective therapy for acute and subacute femoropopliteal bypass occlusions compared to treatment with thrombolysis alone.

Heat shock protein expression and change of cytochrome c oxidase activity: presence of two phylogenic old systems to protect tissues in ischemia and reperfusion.

Induction of heat shock proteins (hsp) has been shown to protect cells from ischemia by providing transient tolerance against myocardial injury and improving postischemic functional recovery. Attenuation of ATP depletion and earlier restoration of ATP content on reperfusion are thought to play a role in this scenario. Hsp induction is accompanied by altered enzyme activity of the respiratory chain, the major generator of ATP under physiological conditions. This report addresses the question whether processing and final assembly of the active holoenzyme cytochrome c oxidase (CcO, complex IV), member of the respiratory chain, is compromised under hypoxic conditions unless protected by stress proteins. Special focus is laid on function of the enzyme's subunits and importance of cellular energy availability and maintenance.

Direct measurement of myocardial oxygen tension and high energy phosphate content under varying ventilatory conditions in rabbits.

Effective myocardial oxygen supply should not be compromised during cardiac surgery as it is essential to avoid circulatory and cardiac dysfunction. Local measurement of myocardial oxygen partial pressure (pO2) was therefore introduced into the operative monitoring of myocardial ischemia. The aim of the present study was to assess whether myocardial oxygen partial pressure correlates with the content of high energy phosphates (HEPs). Seven male rabbits were examined in parallel with measurement of myocardial pO2 by an implanted Clark electrode and 31phosphorus-NMR spectroscopy. The ventilatory management established hyperoxygenation followed by systemic hypoxia with hypercapnia for 20 min. Additionally, analysis of end-expiratory gas composition in combination with blood gas analysis was performed simultaneously, and hemodynamic parameter was recorded. Under hypoxic conditions the cardiovascular system was severely compromised, whereas the myocardial pO2 was only moderately impaired (pO2M 45.0+/-16.0 mm Hg). Immediately before cardiac arrest, low values of arterial and venous pO2 were found (17.6+/-6.0 and 12.9+/-6.1 mm Hg). In contrast to near normal myocardial pO2, HEP content in the myocardium was considerably reduced and inorganic phosphorus was increased. Artificial ventilation leading to systemic hypoxia and eventually circulatory arrest resulted in almost normal myocardial pO2 but severely compromised HEP content. This somewhat unexpected finding requires further clarification, but is in accordance with findings reported previously where regulatory mechanisms have been shown to play a role in the pathophysiology of severe hypoxic conditions such as those for cellular oxygen delivery and demand, P/O coupling and finally control of HEP production facilitating the interaction between respiratory chain and myoglobin oxygen transport.

HLA-DQB1* polymorphism and associations with dilated cardiomyopathy, inflammatory dilated cardiomyopathy and myocarditis.

To date, only weak associations have been reported between idiopathic dilated cardiomyopathy (DCM) and certain HLA class II alleles. Associations between HLA class II alleles and specific causes of DCM, especially myocarditis, have as yet not been systematically investigated. Typing of HLA DQB1* allele was performed using a sequence-specific primer-polymerase chain reaction technique in 22 unrelated patients with idiopathic DCM, 19 patients with myocarditis and normal left ventricular function, and 16 patients with myocarditis and impaired left ventricular function (i.e. inflammatory DCM). Controls comprised 44 patients without (inflammatory) cardiac disease and a population control. A significant association was found for presence of HLA DQB1*0303 with myocarditis without cardiac dysfunction. Weaker associations were seen for presence of HLA DQB1*0301 and absence of HLA DQB1*06 with inflammatory DCM. Additionally, allelic combination DQB1*02-DQB1*03 may be able to distinguish idiopathic from inflammatory DCM, and HLA DQB1*02 myocarditis with cardiac dysfunction from myocarditis without, if results are confirmed by larger prospective studies.

HSPA1B polymorphism in familial forms of inflammatory dilated cardiomyopathy.

Mutations in genes encoding cytoskeletal proteins participate in the pathogenesis of familial dilated cardiomyopathy (fDCM). Additional factors including inflammatory reactions are believed to play a role in deterioration of left-ventricular function. An association of inflammatory fDCM with the HSPA1B 1267 A-->G polymorphism was identified. Since the HSPA1B 1267 A-->G polymorphism has been associated with autoimmune disorders, this finding might point to a pathogenetic role of (auto-) immune phenomena in distinct forms of familial DCM. HSPA1B 1267 A-->G is part of an extended DR3 haplotype explaining the strong association between both alleles. Recombinant haplotype mapping including neighboring genes might aid in identification and classification of susceptibility genes which in turn can point to the not yet identified causative agent.

Familial inflammatory dilated cardiomyopathy.

BACKGROUND: Systematic family screening has recently identified dilated cardiomyopathy as an inherited disorder in up to 30% of cases. Mutations in genes encoding proteins responsible for myocardial architecture have been identified, but additional pathophysiological mechanisms including inflammatory reactions have been proposed. AIMS: Identification and characterization of familial DCM, where at least one affected family member fulfils the criteria for inflammatory DCM may lead to a better understanding of the aetiology and pathogenesis of (inflammatory) DCM. METHODS AND RESULTS: Ten families were examined. In six families, clinical characteristics and mode of inheritance were compatible with pure fDCM, fDCM with conduction defect and autosomal recessive fDCM. In four families, (auto-)immune features were diagnosed in affected and non-affected family members. CONCLUSIONS: Familial DCM with an inflammatory component was identified as a specific subgroup of familial DCM. In most cases, the inflammatory process seems to modify, i.e. aggravate, the "classic, cytoskeletopathic" familial DCM, but in some, especially when taking clinical and genetic aspects into account, inflammatory (auto-)immune features can be addressed as the leading pathogenetic principle. Further elucidation of these families may provide a better insight into pathophysiologic processes and may aid in the development of specific therapeutic strategies.

[Women and autoimmune diseases with cardiovascular manifestations]. / Frauen und Autoimmunerkrankungen mit vaskulärer und (peri)kardialer Beteiligung.

Women's greater susceptibility to autoimmune diseases has been recognized for more than 100 years. And although the basic immune response (including a more vigorous immune response and increased antibody production) has been known to differ between men and women, conclusive pathophysiological explanations for this phenomenon are still lacking. Experimental work done in animal models have revealed a profound influence of sex hormones on the susceptibility to autoimmune diseases and on clinical disease via direct and indirect signaling pathways. Apart from sex hormones additional factors seem to participate in the pathogenesis of autoimmune diseases, which remain to be elucidated ("so far, you cannot explain autoimmunity [only] with estrogen" [lockshin]).

Inflammatory dilated cardiomyopathy (DCMI).

Cardiomyopathies are heart muscle diseases, which have been defined by their central hemodynamics and macropathology and divided in five major forms: dilated (DCM), hypertrophic (HCM), restrictive (RCM), right ventricular (RVCM), and nonclassifiable cardiomyopathies (NCCM). Furthermore, the most recent WHO/WHF definition also comprises, among the specific cardiomyopathies, inflammatory cardiomyopathy as a distinct entity, defined as myocarditis in association with cardiac dysfunction. Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy were recognized. Viral cardiomyopathy has been defined as viral persistence in a dilated heart. It may be accompanied by myocardial inflammation and then termed inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (< 14 lymphocytes and macrophages/mm(2)), the term viral cardiomyopathy or viral persistence in DCM should be applied according to the WHF Task Force recommendations. Within the German heart failure net it is the authors' working hypothesis, that DCM shares genetic risk factors with other diseases of presumed autoimmune etiology and, therefore, the same multiple genes in combination with environmental factors lead to numerous different autoimmune diseases including DCM. Therefore, the authors' primary goal is to acquire epidemiologic data of patients with DCM regarding an infectious and inflammatory etiology of the disease. Circumstantial evidence points to a major role of viral myocarditis in the etiology of DCM. The common presence of viral genetic material in the myocardium of patients with DCM provides the most compelling evidence, but proof of causality is still lacking. In addition, autoimmune reactions have been described in many studies, indicating them as an important etiologic factor. Nevertheless, data on the proportion of patients, in whom both mechanisms play a role are still missing.A pivotal role for autoimmunity in a substantial proportion of patients with DCM is supported by the presence of organ-specific autoantibodies, inflammatory infiltrates and pro-inflammatory cytotoxic cytokines. Furthermore, familial occurrence of DCM has been described in about 20-30% of cases, with the presence of autoantibodies and abnormal cytokine profiles in first-degree relatives with asymptomatic left ventricular enlargement. This suggests the involvement of a disrupted humoral and cellular immunity early in the development of the disease. A similar pattern of humoral and cellular immune dysregulation has been described in other autoimmune diseases. There is considerable evidence that genetic factors play an important role in the pathogenesis of DCM, either as contributors to the susceptibility to environmental factors or as determinants of functional and structural changes that characterize the phenotypic expression of the disease.Yet, it is not known whether the susceptibility to immunologically mediated myocardial damage reflects the presence of genetic risk factors shared by other autoimmune diseases. Preliminary investigations suggest, that this is the case, because the frequency of autoimmune disorders other than DCM was higher in first-degree relatives of the subjects with DCM including juvenile diabetes, rheumatoid arthritis, thyroiditis, psoriasis, and asthma. The nature of the genetic risk is undetermined and probably involves genes in the major histocompatibility (MHC) locus as well as other susceptibility loci. Therefore, the authors started their investigation with the search for MHC class 2 DQ polymorphisms in the peripheral blood of patients with DCM in parallel to the search for new interesting susceptibility loci by the use of the microarray analysis regarding genes responsible for inflammatory and autoimmune diseases. By this approach a new insight in the familial clustering of other autoimmune diseases in patients with DCM and in genetic predisposition can be expected.

Detection of anti-hsp70 immunoglobulin G antibodies indicates better outcome in coronary artery bypass grafting patients suffering from severe preoperative angina.

BACKGROUND: Recent findings indicate that molecular chaperones actively participate in myocardial cytoprotection. Moreover, ischemic tolerance can be induced in humans by brief ischemic events. Therefore, we investigated patients with severe angina attacks before coronary artery bypass grafting. We focused on appearance of anti-hsp70 antibodies as an immunologic response to heat shock protein induction by ischemia followed up by hemodynamic measurements perioperatively. We correlated these clinical findings with the presence of antibodies against hsp70 and the antioxidative capacity of patients' sera. METHODS: Thirty-five consecutive patients with coronary artery disease scheduled for coronary artery bypass grafting were included. Seventeen patients had severe angina, and 18 patients suffered from chronic stable angina preoperatively. In the patients' sera, antibodies against hsp70 were detected by enzyme-linked immunosorbent assay, and antioxidative capacity was detected using the chromogen assay. Cardiac output and pulmonary capillary wedge pressure were measured using a thermodilution catheter. We also evaluated C-reactive protein and creatine kinase MB isoenzyme, and performed a conventional leukocyte count. RESULTS: The sera of the 17 patients with severe angina attacks before surgery contained antibodies against hsp70 and a low antioxidative capacity. The interval between a severe angina attack and anti-hsp70 antibody titer are inversely correlated. These patients had better cardiac output and lower pulmonary capillary wedge pressure values after surgery. CONCLUSIONS: Severe angina before cardiac surgery coincided with an improved outcome as measured by hemodynamic variables as compared with chronic stable angina. This finding correlated significantly with a low antioxidative capacity and the presence of antibodies against hsp70. These pathophysiologic mechanisms might therefore play a role in myocardial protection.

[Noninvasive methods in the diagnosis of macro- and microangiopathy of peripherial and carotid arteries]. / Nichtinvasive diagnostische Methoden der Makro- und Mikroangiopathie der peripheren Gefässe und Karotiden.

PURPOSE: Indications and diagnostic value of the most important noninvasive procedures for the diagnosis of peripheral arterial disease and diseases of the supraaortic arteries are reviewed in this article with particular emphasis on cardiologic questions. PERIPHERAL ARTERIAL DISEASE: As compared to coronary artery disease, peripheral arterial disease has long been addressed as being negligible in number and importance, a view that had to be reassessed in recent years. The prevalence of claudication and critical leg ischemia has increased. Earlier diagnosis and specific therapeutic regimens will be able to prevent or at least slow progression of the disease and, thereby, major amputation. The patient's history and physical examination in addition to measurement of the ankle-brachial index (ABI; determined by dividing the systolic pressure measured by Doppler ultrasonography of the A. dorsalis pedis or A. tibialis posterior by that of the A. brachialis) usually allows for the diagnosis of peripheral arterial disease (ABI < 0.9). If in doubt (ABI > 0.9, but presence of typical claudication), a treadmill test or additional tests such as pressure-pulse recording (mechanical oscillography), toe pressure measurements, or duplex ultrasonography should be performed. When peripheral arterial disease has been diagnosed, duplex ultrasonography or treadmill testing aids in planning additional diagnostic procedures and the adequate therapeutic regimen. Transcutaneous oxymetry is of prognostic value in assessing the tendency of wound healing in distal limb ulceration and can distinguish between critical limb ischemia and complicated claudication. Thermography is used to document functional and organic peripheral arterial occlusions and capillaroscopy to directly view nail fold capillaries in order to distinguish between primary and secondary Raynaud's phenomenon. Noninvasive radiologic techniques in the diagnosis of peripheral arterial disease are also discussed in this journal. SUPRAAORTIC ARTERIES: Noninvasive diagnostic procedures in assessing disease of the supraaortic arteries include history-taking, physical examination, continuous-wave-(cw-)Doppler and color-coded ultrasonography. Cw-Doppler ultrasonography is still widely used and sufficient in diagnosing moderate to severe stenosis or occlusion of the carotid artery. B-mode and color-coded ultrasonography has several advantages over cw-Doppler ultrasonography through direct visualization of the vascular membrane, perivascular structures, and intravascular blood flow. Carotid stenosis < 50% and plaque morphology can be assessed, inflammatory processes, aneurysms, and dissections diagnosed. Increase in intima-media thickness and echolucent plaques are associated with cerebral ischemic events and can be diagnosed via duplex sonography. These findings have great implications in the consultation of patients with atherogenic risk factors.

Prevalence of the parvovirus B19 genome in endomyocardial biopsy specimens.

Although enteroviruses have long been considered the most common cause of inflammatory heart muscle diseases, parvovirus B19 (PVB19) is emerging as a new and important candidate for myocarditis and dilated cardiomyopathy with inflammation (DCMi) and without inflammation (DCM). We investigated left ventricular endomyocardial biopsy specimens from 110 patients with suspected inflammatory heart disease for the presence of PVB19, Coxsackie virus (CVB), and adenovirus (Ad2) genome by polymerase chain reaction. Diagnosis of myocarditis (36 patients), DCM (18 patients), DCMi (13 patients), and perimyocarditis (12 patients) was made by immunohistochemical and histopathological investigation of endomyocardial biopsy specimens. A control group consisting of patients with arterial hypertension was also investigated. Prevalence of the PVB19 genome in endomyocardial biopsy specimens was highest in patients with DCMi (3 of 13) and patients with myocarditis (7 of 36); in patients with DCM and perimyocarditis, prevalence was 3 of 13 and 2 of 12, respectively. In patients with resolved myocarditis, no PVB19 DNA was detected; in patients with no inflammation and controls, prevalence was only 4% and 7%, respectively. CVB-RNA was detected in endomyocardial biopsy specimens from 3 of 37 patients with myocarditis; Ad2-DNA was found in 1 patient with DCM and 1 patient with perimyocarditis. These findings suggest an association of the PVB19 genome in endomyocardial biopsy specimens of adults with the development of DCM, DCMi, and chronic myocarditis more frequently than previously expected. PVB19 should therefore be recognized as a potential cardiotropic pathogen in patients of all ages.

Human viral cardiomyopathy.

Viral infection of the heart is relatively common, usually asymptomatic and has a spontaneous and complete resolution. It can, however, in rare cases, lead to substantial cardiac damage, development of viral cardiomyopathy and congestive heart failure. Viral cardiomyopathy is defined as viral persistence in a dilated heart. It may be accompanied by myocardial inflammation and then termed inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (<14 lymphocytes and macrophages/mm ) the term viral cardiomyopathy or viral persistence in dilated cardiomyopathy should be applied. The diagnosis of myocarditis and viral cardiomyopathy can be made only by endomyocardial biopsy, implementing the WHO/WHF criteria, and PCR techniques for identification of viral genome. The most frequent cardiotropic viruses detected by endomyocardial biopsy are Parvo B19, enteroviruses, adenoviruses, cytomegalovirus, and less frequently Epstein-Barr virus, and influenza virus.

Pathophysiology of cardiac inflammation: molecular mechanisms.

BACKGROUND: Inflammatory processes induced by rival infection are believed to be one of the major pathogenetic mechanisms in inflammatory dilated cardiomyopathy. Although the reason for progression to myocardial failure is not fully understood, postulated mechanisms include persistent viral infection alone or in combination with autoimmune processes. PATHOPHYSIOLOGY: Murine models of myocarditis have provided insight into the mechanisms by which autoimmune responses to cardiac antigens, probably in response to viral infection of the myocardium, arise and cause tissue pathology. Organ-specificity, cross-reactivity between microbial agents and cardiac tissue, and induction of tolerance to self-antigen are issues still at stake. In addition, cytokines mediate activation and effector phase of innate and specific immunity, which are both important in controlling viral infection. The innate immune response not only has an important protective function but also serves to initiate and regulate subsequent specific immune responses. In man, on the one hand specific T cells and antibodies against different cardiac tissue components have been demonstrated in myocardium and sera of patients with inflammatory cardiomyopathy, and on the other hand viral genome has been identified in endomyocardial biopsies due to the rapid development of new molecular biological techniques such as polymerase chain reaction (PCR), southern blot analysis and in-situ hybridization. But it is still a mater of debate whether virus infection itself, the ensuing immune response, or both, contribute to the deterioration of left ventricular function. CONCLUSION: Taking these mechanisms into account, screening for viral genome by PCR and detection of inflammatory infiltrates by immunohistochemistry are considered crucial for the establishment of a definite diagnosis thereby allowing for the initiation of specific therapeutic strategies.