[Inflammatory cardiomyopathy and myocarditis]. / Inflammatorische Kardiomyopathie und Myokarditis.

We describe diagnosis, differential diagnosis, multimodality imaging and medical and invasive diagnostic treatment in patients with inflammatory cardiomyopathy and myocarditis under etiological considerations in reference to a landmark position paper of the Working Group Myocardial and Pericardial Diseases of the European Society of Cardiology together with recent developments in diagnosis and treatment. Diagnosis of the symptomatic patient is the assessment of etiology of inflammatory cardiomyopathy, followed by the clinical presentation, course, treatment option and prognosis. Viral myocarditis in its different facets can clearly be separated from autoreactive forms by histological and molecular methods in the endomyocardial biopsy, thus leading to an individualized targeted therapy beyond heart failure treatment.

[Diagnostics and therapy of pericarditis and pericardial effusion]. / Diagnostik und Therapie der Perikarditis und des Perikardergusses.

This article describes the diagnostics, differential diagnostics, multimodal imaging, medicinal and invasive diagnostic therapy of acute and chronic pericarditis, constrictive pericarditis, pericardial effusion and cardiac tamponade under etiological aspects and on the basis of the guidelines of the European Society of Cardiology (ESC). The starting point of the decision tree is the symptomatic patient with echocardiographic evidence of pericardial effusion. The principle feature of the diagnostics is the etiopathogenetic allocation of the pericardial disease which influences the clinical picture, course therapy and prognosis. Infectious pericarditis (e.g. viral, bacterial and tuberculous) is differentiated from sterile autoreactive pericarditis and from neoplastic pericardial effusion by the cytology of the effusion and immunohistological and molecular investigations of the pericardial and epicardial biopsies. Pericardioscopy plays an important role in the recognition of suspicious areas. In many cases intrapericardial administration of cisplatin for neoplastic pericardial effusion and instillation of triamcinolone for autoreactive pericarditis prevent recurrence just as a treatment of several months with colchicine.

Diabetic cardiomyopathy: ongoing controversies in 2012.

Diabetic cardiomyopathy is a controversial clinical entity that in its initial state is usually characterized by left ventricular diastolic dysfunction in patients with diabetes mellitus that cannot be explained by coronary artery disease, hypertension, or any other known cardiac disease. It was reported in up to 52-60% of well-controlled type-II diabetic subjects, but more recent studies, using standardized tissue Doppler criteria and more strict patient selection, revealed a much lower prevalence. The pathological substrate is myocardial damage, left ventricular hypertrophy, interstitial fibrosis, structural and functional changes of the small coronary vessels, metabolic disturbance, and autonomic cardiac neuropathy. Hyperglycemia causes myocardial necrosis and fibrosis, as well as the increase of myocardial free radicals and oxidants, which decrease nitric oxide levels, worsen the endothelial function, and induce myocardial inflammation. Insulin resistance with hyperinsulinemia and decreased insulin sensitivity may also contribute to the left ventricular hypertrophy. Clinical manifestations of diabetic cardiomyopathy may include dyspnea, arrhythmias, atypical chest pain, and dizziness. Currently, there is no specific treatment of diabetic cardiomyopathy that targets its pathophysiological substrate, but various therapeutic options are discussed that include improving diabetic control with both diet and drugs (metformin and thiazolidinediones), the use of ACE inhibitors, beta blockers, and calcium channel blockers. Daily physical activity and a reduction in body mass index may improve glucose homeostasis by reducing the glucose/insulin ratio and the increase of both insulin sensitivity and glucose oxidation by the skeletal and cardiac muscles.

[Diagnosis of pericardial cysts: significance of cardiac magnetic resonance and literature review].

Pericardial cysts are uncommon and caused by an incomplete coalescence of fetal lacunae forming the pericardium. The paper presents two cases of pericardial cyst and literature review. The first is a case of a female patient with progressive dispnoa and spherical mass located in the right cardiophrenic angle on a chest x-ray. A pericardial cyst with low signal intensity was noted on T1w, high signal intensity on T2w in TSE (turbo spin echo) sequence on magnetic resonance images (MRI) which was suggestive of serous content. The patient underwent pericardial puncture and was thereafter free of symptoms. Histologic study of the cyst confirmed hydatid cyst diagnosis. Another patient is with echocardiographic evidence of cystic formation which was confirmed on MRI, with high signal intensity on SSFP (steady state free precession) sequence. The cyst was without septa and without communication with pericardial space. Since there were no significant hemodynamic changes, the patient is on regular follow up.

Invasive techniques--from diagnosis to treatment.

Invasive diagnostic and therapeutic techniques are indispensable for the diagnosis and interventional treatment of coronary artery disease, valvular involvement and, in particular, if the specific components of the inflammatory or degenerative processes in rheumatic disease are to be identified in the different components of the heart. Although impairment of cardiac function and ischaemia can be suspected also by non-invasive techniques, coronary involvement needs the final proof by angiography. Endomyocardial or epicardial biopsy identifies the key players of autoreactivity: the infiltrating cells and the bound and circulating antibodies. Before corticoid treatment is started, a viral or microbial aetiology has to be excluded at the site of cardiac inflammation. This again can only be done by the analysis of cardiac tissue samples.

Cardiac imaging in rheumatic diseases.

The majority of the imaging techniques in cardiology could be applied in rheumatic diseases (RDs), such as echocardiography, single-photon emission computed tomography (SPECT), radionuclide ventriculography, angiography, cardiovascular MRI and CT. Inflammatory pericardial involvement is the most common cardiac manifestation in various forms of RD. Echocardiography is the gold standard for diagnosis of pericardial abnormalities, demonstrating location and amount of pericardial effusion. Cardiac MRI and CT can be used to assess the features of pericardial effusions and pericardial structures. In patients with valvular heart disease in RD, transoesophageal echocardiography is a superior method and offers reliable information about valve morphology, the severity of the disease and left ventricular (LV) function. In addition, cardiac MRI is a valuable tool for the evaluation of valvular stenosis and regurgitation severity. Myocardial involvement in RD is demonstrated by abnormalities in LV size and function, indicating myocardial inflammation. In these patients Doppler echocardiography and myocardial tissue imaging can provide essential diagnostic information. Both LV angiography and cardiac MRI can provide reliable information on LV size, function and mass. In patients with coronary disease associated with RD, LV ejection fraction and ventricular wall motion can be assessed by echocardiography, radionuclide ventriculography, gated SPECT and MRI. Three-dimensional (3D) echocardiography is considered superior to 2D echocardiographic techniques. Stress echocardiography is the most used method for detection of myocardial ischaemia. The only accurate visualization of the coronary arteries is by selective coronary arteriography, which remains the gold standard. Although new non-invasive techniques have been developed, including CT and MRI angiography, some limitations apply.

Cardiac arrhythmias and conduction disturbances in autoimmune rheumatic diseases.

Rhythm and conduction disturbances and sudden cardiac death (SCD) are important manifestations of cardiac involvement in autoimmune rheumatic diseases (ARDs). In patients with rheumatoid arthritis (RA), a major cause of SCD is atherosclerotic coronary artery disease, leading to acute coronary syndrome and ventricular arrhythmias. In systemic lupus erythematosus (SLE), sinus tachycardia, atrial fibrillation and atrial ectopic beats are the major cardiac arrhythmias. In some cases, sinus tachycardia may be the only manifestation of cardiac involvement. The most frequent cardiac rhythm disturbances in systemic sclerosis (SSc) are premature ventricular contractions (PVCs), often appearing as monomorphic, single PVCs, or rarely as bigeminy, trigeminy or pairs. Transient atrial fibrillation, flutter or paroxysmal supraventricular tachycardia are also described in 20-30% of SSc patients. Non-sustained ventricular tachycardia was described in 7-13%, while SCD is reported in 5-21% of unselected patients with SSc. The conduction disorders are more frequent in ARD than the cardiac arrhythmias. In RA, infiltration of the atrioventricular (AV) node can cause right bundle branch block in 35% of patients. AV block is rare in RA, and is usually complete. In SLE small vessel vasculitis, the infiltration of the sinus or AV nodes, or active myocarditis can lead to first-degree AV block in 34-70% of patients. In contrast to RA, conduction abnormalities may regress when the underlying disease is controlled. In neonatal lupus, 3% of infants whose mothers are antibody positive develop complete heart block. Conduction disturbances in SSc are due to fibrosis of sinoatrial node, presenting as abnormal ECG, bundle and fascicular blocks and occur in 25-75% of patients.

Intrapericardial treatment of autoreactive pericardial effusion with triamcinolone; the way to avoid side effects of systemic corticosteroid therapy.

AIMS: To evaluate efficacy and safety of intrapericardial treatment with the crystalloid corticosteroid triamcinolone in autoreactive pericardial effusion. METHODS AND RESULTS: Two hundred and sixty consecutive patients with pericarditis/myopericarditis underwent pericardiocentesis, pericardioscopy (Storz-AF1101B1), and epicardial biopsy with pericardial fluid and tissue analyses. By polymerase chain reaction for cardiotropic viruses/bacteria in pericardial effusion and epicardial biopsies as well as by immunohistochemistry and immunocytochemistry of epicardial and endomyocardial biopsies, 84/260 patients were classified as autoreactive pericarditis and underwent intrapericardial instillation of triamcinolone (group 1: 54 patients, 50% males, mean age 48.9 +/- 14.3 years, triamcinolone 600 mg x m(-2) x 24 h(-1); group 2: 30 patients, 46.7% males, mean age 52.5 +/- 12.7 years, triamcinolone 300 mg x m(-2) x 24 h(-1)). Intrapericardial administration of triamcinolone resulted in symptomatic improvement and prevented effusion recurrence in 92.6% vs 86.7% of the patients after 3 months and in 86.0% vs 82.1% after 1 year in groups 1 and 2, respectively (P>0.05). There were no treatment-related acute complications. During the follow-up, 29.6% of the patients developed transitory iatrogenic Cushing syndrome in group 1 in contrast to 13.3% in group 2 (P<0.05). Conclusion Intrapericardial treatment of autoreactive pericarditis with 300 mg x m(-2) x 24 h(-1) of triamcinolone prevented recurrence of symptoms and relapse of effusion as effectively as the 600 mg x m(-2) x 24 h(-1) regimen, but with significantly fewer side effects.

Neoplastic pericardial effusion. Efficacy and safety of intrapericardial treatment with cisplatin.

AIMS: To evaluate the clinical efficacy, safety, and long-term effect of intrapericardial treatment with cisplatin in large neoplastic pericardial effusions. METHODS AND RESULTS: Out of the registry of 260 patients undergoing pericardiocentesis, 42 patients with neoplastic pericardial effusion (69% males, mean age 58.8+/-13.2 years) were selected for treatment with cisplatin (single instillation of 30 mg.m(-2) x 24h(-1)) in addition to the tumour-specific systemic chemotherapy. All patients underwent clinical examination, echocardiography, pericardiocentesis, pericardioscopy, and epicardial biopsy. Pericardial effusion and biopsy analyses included biochemistry, cytology, serology, microbiology, histology, immunohistology, and PCR. The following malignancies were established: lung cancer, 52.4%; breast cancer, 19.0%; Hodgkin's disease, 4.8%; oesophageal cancer, 2.4%; mesothelioma, 2.4%; colon cancer, 4.8%; and undifferentiated cancer of unknown origin, 14.2%. Cisplatin appeared to prevent recurrence of pericardial effusion during the first 3 months of the follow-up in 92.8%, and after 6 months in 83.3% of the patients. Lung cancer patients had fewer effusion relapses at the 6 months follow-up (4.5%) than breast cancer patients (37.5%)(P<0.05). Myocardial ischemia occurred after 1/42 cisplatin instillations, but there were no other complications. CONCLUSION: Intrapericardial treatment with cisplatin appeared to successfully prevent recurrences of neoplastic pericardial effusion. The treatment was more successful in lung than in breast cancer patients.

Dipyridamole-atropine-induced myocardial infarction in a patient with patent epicardial coronary arteries.

BACKGROUND: The diagnostic accuracy of the physical and pharmacological stress echocardiography tests is higher than routine exercise electrocardiography. They have an acceptable safety profile and have been rarely associated with severe adverse effects. CASE REPORT: We present a case of acute anterior myocardial reinfarction immediately after exercise and pharmacological (dipyridamole-atropine) stress echocardiography testing 1 month after successful stent implantation in LAD. Our patient was a 43-year-old man with a history of heavy smoking and hypertension. Remarkably, the stress echocardiogram was non-diagnostic few hours before the infarction occurred. Angiography performed 4 months after the reinfarction revealed neither a culprit lesion nor stent thrombosis. CONCLUSION: Aggressive "last generation" pharmacological stress testing may provide optimal diagnostic accuracy, but as in our case, complications may occur, even after negative stress testing. To our knowledge, this is the first reported case of an acute myocardial infarction as a severe complication of stress testing, which developed in a patient after stent implantation.

Cardiac rhythm and conduction disturbances: what is the role of autoimmune mechanisms?

The immunopathogenesis of cardiac rhythm and conduction disorders has been underestimated. Therefore, the aim of this review is to analyze the current data and controversial issues in this area. The incidence of autoantibodies to human conducting tissue has been analyzed in sick sinus syndrome, bradyarrhythmia, and hypersensitive carotid sinus syndrome. Patients with anti-sinus node antibodies (ASNab) have a 10-fold higher risk of developing sick sinus syndrome, compared to age-matched controls. The risk of acquiring an atrioventricular block was up to 3-fold in patients with anti-atrioventricular node antibodies (AAVNab) in comparison to controls. The incidence of anti His antibodies (AHISab) was low both in patients and controls. Anti-cardiac Purkinje cell antibodies (ACPCab) seemed to be an epiphenomenon and not a pathogenetic marker of conduction disorders. In congenital heart block association with HLA-B27 and HLA-DR3 is a possible prerequisite in the pathophysiology of the disease, although transplacental passage of various antibodies and immune complexes is widely recognized. The main autoantibodies detected both in children with congenital heart block and their mothers are anti-Ro/SS-A and anti-La/SS-B antibodies. The cross-reactivity of laminin with anti-La antibodies could be important in the initiation of the autoimmune process. Autoantibodies against adrenoceptors and muscarinic cholinergic receptors of neonatal heart and human endogenous retrovirus-3 expressed in fetal cardiac tissue could also play a role in the pathogenesis of the congenital heart block. Of note, apoptosis could be one of the possible mechanisms of the progression of the congenital conduction disturbances to the complete heart block. In addition, evidence is compiling that cellular activation and cellular cytotoxicity specific for a given target tissue appears to be at least equally important in the pathogenesis of the disease as the humoral response. In conclusion, the immunopathogenesis of certain cardiac rhythm and conduction disorders is well established in sick sinus syndrome, congenital heart block, and connective tissue diseases. ASNab, AAVNab, anti-Ro/SS-A, and anti-La/SS-B antibodies can be regarded as diagnostic and prognostic markers.

Arrhythmias in acute pericarditis. An endomyocardial biopsy study.

It is still controversial whether the arrhythmias in acute pericarditis are of myocardial or pericardial origin. The aim of the present study was to investigate the occurrence of arrhythmias and conduction disorders in patients with acute pericarditis with no endomyocardial biopsy evidence of myocarditis (group 1: 40 patients, 65% males, mean age 45.6 +/- 15.7 years, mean heart rate [HR] 98.7 +/- 22.2 beats per minute) in comparison to endomyocardial biopsy proven acute myocarditis/perimyocarditis (group 2: 10 patients, 3/10 with perimyocarditis, 70% males, mean age 46.1 +/- 15.8 years, mean heart rate 76.7 +/- 33.1 beats per minute). At the initial assessment all patients underwent comprehensive clinical work-up including echocardiography, cardiac catheterization, and endomyocardial biopsy. In all patients biventricular endomyocardial biopsy was performed using standard femoral approach and Schikumed 7 F or 8 F bioptomes. Tissue samples were stained by H & E, v. Gieson and independently reviewed by two cardiac pathologists. In addition immunohistochemistry and immunocytochemistry were performed, and only patients fulfilling Dallas and World Heart Federation criteria were selected for group 2. Comparative analysis of electrocardiograms and 24-hour Holter recordings at initial presentation revealed in group 1 vs group 2 significantly less frequent paroxysmal supraventricular tachyarrhythmias (5% vs 40%), and ventricular fibrillation (0 vs 20%), in contrast to atrial fibrillation that occurred more often (20% vs 0) (all p < 0.05). Furthermore, in the group 2 one patient died due to VF and two patients underwent ICD implantation. Low voltage (40% vs 30%) and ST/T wave changes (47.5% vs 30%), as well as the incidence of the II degree AV block (5% vs 0) and complete AV block (2.5% vs 10%) were not significantly different between the groups. In conclusion, patients with pericarditis and no endomyocardial biopsy indications of myocarditis had significantly less often life threatening rhythm disorders in contrast to patients with endomyocardial biopsy proven acute myocarditis/perimyocarditis. On the contrary, incidence of transitory atrial fibrillation was higher in acute pericarditis, than in myocarditis.

Flexible percutaneous pericardioscopy: inherent drawbacks and recent advances.

Pericardioscopy enables endoscopic inspection and aimed biopsy of the parietal and visceral pericardium. To elucidate possible technical modifications contributing to the feasibility, diagnostic value and safety of the procedure, pericardioscopy with an Olympus HYF-1T flexible endoscope was performed in 32 patients (53.1% males, mean age 46.2 +/- 13.1 years) with pericardial effusions. In all patients, the initial step of the procedure was subxiphoid fluoroscopically controlled pericardiocentesis and drainage of the pericardial effusion. An Olympus FB-41ST biopsy forceps was applied for endoscopically guided pericardial biopsies. Standard sampling was used in 22/32 patients (3 to 6 samples/patient) and extensive sampling in 10/32 patients (18 to 20 samples/patient). In additional 12 patients pericardial biopsy was performed without pericardioscopy, under fluoroscopic control. Endoscopic visualization was clearly superior when pericardial effusion was partially replaced with 100 to 300 ml of air (29/32 procedures) in comparison to 3/32 procedures in which the pericardial effusion was replaced with warm normal saline (37 degrees C). In patients with hemorrhagic effusion (12/32), we either repeatedly injected and removed 100 to 150 ml volumes of normal saline (37 degrees C), or postponed pericardioscopy for 2 to 3 days of active drainage. The specificity of endoscopic findings is low and not decisive for the diagnosis. However, pericardioscopy is significantly contributing to the diagnostic value of pericardial biopsy, especially regarding establishing the new diagnosis and etiology of the pericardial disease. Sampling efficiency was also significantly higher for procedures using aimed pericardial biopsy with standard and extensive sampling compared to procedures performed under fluoroscopy: 86.2%, 87.3%, and 43.7%, respectively. No major complications directly related to the procedure were encountered. Minor complications included: short-run ventricular tachycardia (6.3%), pain at the sheath entry site (75%) and transient fever (37.5%). In conclusion, pericardioscopy with Olympus HYF-1T, after air instillation, is a technically complex, but safe procedure that enables excellent visualization and extensive pericardial sampling with improved diagnostic value of pericardial biopsies.

New directions in diagnosis and treatment of pericardial disease. A project of the Taskforce on Pericardial Disease of the World Heart Federation.

New directions in the diagnosis and treatment of pericardial diseases synthesize the achievements of modern imaging with molecular biology and immunology techniques. Comprehensive and systematic implementation of new techniques of pericardiocentesis, pericardial fluid analysis, pericardioscopy, epicardial and pericardial biopsy, as well the application of comprehensive molecular biology and immunology techniques for pericardial fluid and biopsy analyses have opened new windows to the pericardial diseases, permitting early specific diagnosis and creating foundations for etiologic treatment in many cases. In patients with recurrent pericarditis, resistant to conventional treatments, as well as in patients with neoplastic pericarditis an alternative intrapericardial treatment regimen was suggested by the Taskforce on Pericardial Diseases of the World Heart Federation. Intrapericardial application of medication avoids systemic side effects with increased local efficacy. The following protocols are proposed: CIRP (colchicine in recurrent pericarditis)--colchicine vs placebo in chronic/recurring pericarditis without pericardiocentesis; TRIPE (triamcinolone in pericardial effusion)--intrapericardial instillation of triamcinolone + 6 months colchicine vs pericardial puncture without instillation + 6 months colchicine; NEPIN (neoplastic effusion and pericardial instillation)--pericardiocentesis and drainage + intrapericardial instillation of cisplatin or thiotepa.

Intrapericardial treatment of autoreactive myocarditis with triamcinolon. Successful administration in patients with minimal pericardial effusion.

A major clinical drawback in the treatment of autoreactive pericarditis is its inherent feature to relapse. Intrapericardial treatment with triamcinolone was reported to be efficient in patients with large, symptomatic autoreactive pericardial effusions, avoiding side effects of systemic treatment as well as compliance problems. Intrapericardial treatment with 300 mg/m2 triamcinolone was for the first time performed in patients with autoreactive myopericarditis and minimal pericardial effusions (75 to 110 ml). After 12 months of follow-up both patients are asymptomatic and there were no further recurrences of pericardial effusion. Pericardiocentesis in these patients was performed with the application of the PerDUCER device, guided by pericardioscopy. This device has a hemispherical cavity at the top of the instrument connected with a vacuum-producing syringe. In this cavity the pericardium is captured by vacuum and tangentially punctured by the introducer needle. Pericardium that can be captured, must be up to 2 mm thin to fit into the hemispherical cavity. Pericardioscopy performed from the anterior mediastinum significantly contributed to the success of the procedures enabling visualization of the portions of the pericardium free of adipose tissue or adhesions, suitable for puncture with the PerDUCER. In conclusion, intrapericardial treatment of symptomatic autoreactive myopericarditis with minimal pericardial effusion was safely and efficiently performed in 2 patients. Pericardiocentesis was enabled by means of the PerDUCER device, facilitated by pericardioscopy.

Initial clinical experience with PerDUCER device: promising new tool in the diagnosis and treatment of pericardial disease.

BACKGROUND: The idea to enter the normal pericardial sac safely was unrealistic until recently. The development of a novel instrument (PerDUCER pericardial access device) for percutaneous access to the pericardium could potentially have a significant impact, not only on patients with pericardial diseases but even more, or primarily, on diagnosis and treatment of myocardial and coronary disease and arrhythmias. HYPOTHESIS: The overall objective of the present study was to evaluate the feasibility and safety of the percutaneous pericardial access with PerDUCER in patients with pericardial disease, and to analyze our initial experience with this new technique, with particular emphasis on sequential procedural steps. METHODS: The device was studied in five patients with pericardial disease (two men, mean age 50.4 years, range 30-68, four with normal body mass index). The procedure consists of two distinct techniques: (1) access to the mediastinal space, and (2) pericardial capture, puncture, and insertion of the guidewire. Access to the mediastinal space includes the introduction of a blunt cannula, a 0.038 guidewire, a dilator-introducer sheath set, and insertion of the PerDUCER device. Key points of the PerDUCER procedure are as follows: introduction of the blunt cannula without resistance, placement of the dilator-introducer sheath at the upper third of the heart, systolic movements of the PerDUCER device, successful vacuum and capture of pericardium, puncture and introduction of the intrapericardial guidewire. RESULTS: Access to the mediastinal space was accomplished in four of five patients, as were pericardial capture and probably puncture. However, despite numerous successful captures and probably punctures of pericardium, we were not able to confirm introduction of the intrapericardial guidewire into the pericardial cavity in any of our patients (0/5). The procedure was very well tolerated in all patients (5/5). No major complications developed during the procedure, bearing in mind that the intrapericardial placement of the guidewire was not achieved. Minor complications included pain at the dilator-introducer sheath entry site (5/5) and mild transient fever (2/5). CONCLUSIONS: According to the present experience, we believe that, with minor modifications, the PerDUCER device could be successfully implemented for pericardial entry in patients with pericardial disease. Further studies are needed to evaluate the feasibility and safety of this new instrument in patients with a normal pericardium. This could open a most exciting spectrum of possible implementations of the device in the future.