[show abstract][hide abstract] ABSTRACT: Infections with cardiotrophic viruses and immune-mediated responses against the heart have been suggested to play a dominant role in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). Furthermore, immune-mediated inflammatory diseases (IMIDs) may result in DCM. It has not previously been assessed whether DCM patients with and without an IMID have different prevalences and quantities of cardiotrophic viruses in the heart. Therefore, we compared the profiles of cardiotrophic viruses in heart tissue of DCM patients with and without an IMID. Serum and myocardial tissue samples were obtained from 159 consecutive patients with DCM and 20 controls. Patients were subdivided into three groups, the first two based on the presence (n = 34) or absence (n = 125) of an IMID and the third being a control group. The parvovirus B19 virus genome was detected in equal quantities in the non-IMID DCM patients (100/125) and the control group (15/20) but in lower quantities in the IMID patients (21/34, P = 0.02). Both the non-IMID and IMID DCM patients demonstrated increased myocardial inflammation compared to controls: 12.5 ± 1.8 and 14.0 ± 3.2 CD45-positive inflammatory cells, respectively, versus 5.1 ± 0.7 for the controls (P < 0.05 for both). Importantly, significantly higher parvovirus B19 copy numbers could be amplified in non-IMID than in IMID patients (561 ± 97 versus 191 ± 92 copies/μg DNA, P < 0.001) and control subjects (103 ± 47 copies/μg DNA, P < 0.001). The present study shows decreased parvovirus B19 prevalence and copy numbers in hearts of DCM patients with an IMID compared to those without an IMID. These findings may suggest that DCM patients with an IMID have a different pathophysiologic mechanism from that which is present in the virus-induced form of DCM.
[show abstract][hide abstract] ABSTRACT: Despite recent advances in the management of patients with heart failure, morbidity and mortality rates remain high. Common causes of heart failure are ischaemic heart disease, uncontrolled hypertension and valvular disease. However, in up to 50 % of the cases its exact cause remains initially unknown; this condition is called idiopathic dilated cardiomyopathy (DCM). Improved diagnostic methods, most notably the advancements in molecular and immunohistological biopsy techniques and genetic research, have endorsed a new era in the diagnosis and classification of patients with idiopathic DCM. These insights have led to novel aetiology-based treatment strategies and improved outcome. The present article will briefly discuss all causes of DCM with a special focus on inflammatory- and virus-mediated forms of DCM.
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 05/2012; 20(7-8):332-5. · 1.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: For over 50 years, viral infection has been recognized as an important trigger of acute myocarditis, inflammatory dilated cardiomyopathy (DCM) and congestive heart failure. Nevertheless, viral heart disease remains challenging to diagnose and treat. Improved diagnostic methods for myocarditis have led to a better understanding of its pathophysiology. The recognition of virus-mediated damage, inflammation and autoimmune dysregulation in these patients highlights the importance of differentiating between virus-positive and virus-negative inflammatory DCM. These insights have led to the development of novel treatment strategies, including intravenous immunoglobulin and interferon therapy for virus-positive patients. This article will focus on the pathogenesis of viral myocarditis, especially parvovirus B19-induced, its progression to inflammatory DCM and future treatment strategies.
[show abstract][hide abstract] ABSTRACT: The frequent occurrence of ventricular tachycardia can create a serious problem in patients with an implantable cardioverter defibrillator. We assessed the long-term efficacy of catheter-based substrate modification using the voltage mapping technique of infarct-related ventricular tachycardia and recurrent device therapy.
The study population consisted of 27 consecutive patients (age 68 ± 8 years, 25 men, mean left ventricular ejection fraction 31 ± 9%) with an old myocardial infarction and multiple and/or hemodynamically not tolerated ventricular tachycardia necessitating repeated device therapy. A total of 31 substrate modification procedures were performed using the three-dimensional electroanatomical mapping system. Patients were followed up for a median of 23.5 (interquartile range 6.5-53.2) months before and 37.8 (interquartile range 11.7-71.8) months after ablation. Antiarrhythmic drugs were not changed after the procedure, and were stopped 6 to 9 months after the procedure in patients who did not show ventricular tachycardia recurrence.
Median ventricular tachycardias were 1.6 (interquartile range 0.7-6.7) per month before and 0.2 (interquartile range 0.00-1.3) per month after ablation (P = 0.006). Nine ventricular fibrillation episodes were registered in seven patients before and two after ablation (P = 0.025). Median antitachycardia pacing decreased from 1.6 (interquartile range 0.01-5.5) per month before to 0.18 (interquartile range 0.00-1.6) per month after ablation (P = 0.069). Median number of shocks decreased from 0.19 (interquartile range 0.04-0.81) per month before to 0.00 (interquartile range 0.00-0.09) per month after ablation (P = 0.001). One patient had a transient ischemic attack during the procedure, and another developed pericarditis. Nine patients died during follow-up, eight patients due to heart failure and one patient during valve surgery.
Catheter-based substrate modification using voltage mapping results in a long-lasting reduction of cardioverter defibrillator therapy in patients with multiple and/or hemodynamically not tolerated infarct-related ventricular tachyarrhythmia.
[show abstract][hide abstract] ABSTRACT: Small RNA molecules, called microRNAs, freely circulate in human plasma and correlate with varying pathologies. In this study, we explored their diagnostic potential in a selection of prevalent cardiovascular disorders.
MicroRNAs were isolated from plasmas from well-characterized patients with varying degrees of cardiac damage: (1) acute myocardial infarction, (2) viral myocarditis, (3) diastolic dysfunction, and (4) acute heart failure. Plasma levels of selected microRNAs, including heart-associated (miR-1, -133a, -208b, and -499), fibrosis-associated (miR-21 and miR-29b), and leukocyte-associated (miR-146, -155, and -223) candidates, were subsequently assessed using real-time polymerase chain reaction. Strikingly, in plasma from acute myocardial infarction patients, cardiac myocyte-associated miR-208b and -499 were highly elevated, 1600-fold (P<0.005) and 100-fold (P<0.0005), respectively, as compared with control subjects. Receiver operating characteristic curve analysis revealed an area under the curve of 0.94 (P<10(-10)) for miR-208b and 0.92 (P<10(-9)) for miR-499. Both microRNAs correlated with plasma troponin T, indicating release of microRNAs from injured cardiomyocytes. In viral myocarditis, we observed a milder but significant elevation of these microRNAs, 30-fold and 6-fold, respectively. Plasma levels of leukocyte-expressed microRNAs were not significantly increased in acute myocardial infarction or viral myocarditis patients, despite elevated white blood cell counts. In patients with acute heart failure, only miR-499 was significantly elevated (2-fold), whereas no significant changes in microRNAs studied could be observed in diastolic dysfunction. Remarkably, plasma microRNA levels were not affected by a wide range of clinical confounders, including age, sex, body mass index, kidney function, systolic blood pressure, and white blood cell count.
Cardiac damage initiates the detectable release of cardiomyocyte-specific microRNAs-208b and -499 into the circulation.
[show abstract][hide abstract] ABSTRACT: In chronic heart failure (CHF), reduced vagal activity correlates with increased mortality and acute decompensation. Experimentally, chronic vagus nerve stimulation (VNS) improved left ventricular (LV) function and survival; clinically, it is used for the treatment of drug-refractory epilepsy. We assessed safety and tolerability of chronic VNS in symptomatic CHF patients, using a novel implantable nerve stimulation system. The secondary goal was to obtain preliminary data on clinical efficacy.
This multi-centre, open-label phase II, two-staged study (8-patient feasibility phase plus 24-patient safety and tolerability phase) enrolled 32 New York Heart Association (NYHA) class II-IV patients [age 56 ± 11 years, LV ejection fraction (LVEF) 23 ± 8%]. Right cervical VNS with CardioFit (BioControl Medical) implantable system started 2-4 weeks after implant, slowly raising intensity; patients were followed 3 and 6 months thereafter with optional 1-year follow-up. Overall, 26 serious adverse events (SAEs) occurred in 13 of 32 patients (40.6%), including three deaths and two clearly device-related AEs (post-operative pulmonary oedema, need of surgical revision). Expected non-serious device-related AEs (cough, dysphonia, and stimulation-related pain) occurred early but were reduced and disappeared after stimulation intensity adjustment. There were significant improvements (P < 0.001) in NYHA class quality of life, 6-minute walk test (from 411 ± 76 to 471 ± 111 m), LVEF (from 22 ± 7 to 29 ± 8%), and LV systolic volumes (P = 0.02). These improvements were maintained at 1 year.
This open-label study shows that chronic VNS in CHF patients with severe systolic dysfunction may be safe and tolerable and may improve quality of life and LV function. A controlled clinical trial appears warranted.
European Heart Journal 10/2010; 32(7):847-55. · 14.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: Churg-Strauss syndrome (CSS) is a rare form of systemic vasculitis. Previous studies showing cardiac involvement in CSS patients were limited in the number of patients and were often based solely on clinical manifestations. The aim of the present study was to determine in detail the incidence of cardiac involvement in a large population of ambulatory CSS patients.
Thirty-two consecutive patients with CSS in remission (mean +/- SD duration of disease between diagnosis and enrollment 6.1 +/- 5.8 years, mean +/- SD age 61 +/- 10 years) who were previously unaware of cardiac involvement were compared with 32 randomly selected age- and sex-matched control subjects, using clinical evaluation, electrocardiography (EKG), echocardiography, and cardiac magnetic resonance imaging (MRI).
Detailed cardiac evaluation revealed a 62% prevalence of cardiac involvement in CSS patients compared with 3% in controls (P < 0.001), with clinical symptoms in 26% and 3%, respectively (P = 0.009), EKG abnormalities in 66% and 3%, respectively (P < 0.001), and echocardiographic defects in 50% and 3%, respectively (P < 0.001). Cardiac MRI detected cardiac manifestations in 62% of CSS patients. In the presence of cardiac MRI abnormalities, echocardiography could detect cardiac involvement with a sensitivity of 83% and a specificity of 80%. The absence of symptoms or EKG abnormalities did not exclude cardiac involvement, because abnormalities could still be detected in 38% of these patients at the time of echocardiography or cardiac MRI.
These results demonstrate a high incidence of cardiac involvement in CSS patients. Systematic cardiac evaluation including detailed imaging is required to properly identify CSS patients with cardiac involvement.
[show abstract][hide abstract] ABSTRACT: Parvovirus B19 (PVB19) persistence in the heart has been associated with progressive cardiac dysfunction and evolution to dilated cardiomyopathy. In the present study, we investigated whether immunomodulation with intravenous immunoglobulin (IVIg) in addition to conventional heart failure therapy is safe and achieves virus reduction. Such therapy might improve cardiac function in patients with chronic dilated cardiomyopathy (DCM) and a significant PVB19 viral load in the heart.
PVB19 viral load was studied in 25 post-mortem cardiac samples of patients with a normal heart. Then, 17 consecutive patients (mean age 53 +/-3 years) with DCM and symptomatic heart failure for >1 year with a PVB19 viral load in endomyocardial biopsies of >250 copies/microg DNA were treated with a high dose of IVIg (2 g/kg).
The post-mortem cardiac samples revealed a PVB19 presence in 80% with a mean load of 131 +/-40 copies/microg DNA. In the treated patients, IVIg resulted in a significant decrease of PVB19 viral load from 1,420 +/-216 to 619 +/-200 copies/microg DNA (P=0.004) and significantly improved the ejection fraction from 33 +/-3% 6 months before treatment and 34 +/-3% at baseline to 41 +/-3% 6 months (P=0.001) after IVIg therapy. The New York Heart Association classification significantly improved from 2.5 +/-0.1 at baseline to 2.1 +/-0.1 at follow-up (P=0.004). No therapy-related complications were noted.
The present pilot study demonstrates that IVIg significantly reduces viral load and improves cardiac function in patients with DCM related to increased PVB19 viral load in the heart.
[show abstract][hide abstract] ABSTRACT: Fulminant myocarditis is a rare inflammatory heart disease affecting relatively young adults. We describe a case of a 27-year-old male with acute onset severe heart failure. A rapid and accurate diagnostic approach suggested parvovirus B19 as the most probable cause for this fulminant viral myocarditis. Initial haemodynamic support, intensive immunosuppressive and antiviral therapy resulted in a complete recovery within 2 weeks. This case demonstrates the importance of a detailed diagnosis, allowing better classification of the underlying pathology and subsequent targeted treatment.
[show abstract][hide abstract] ABSTRACT: Dextrocardia with situs inversus is an uncommon congenital condition in which the major visceral organs are reversed. The clinical diagnosis and electrocardiographic localization of myocardial infarctions in these patients remain a great challenge. We report a case of a 64-year-old man known with dextrocardia and situs inversus totalis presenting with acute chest pain irradiating to the right arm. The admission and reversed "normalized" electrocardiogram are presented, allowing for correct diagnosis of an acute anteroseptal myocardial infarction. The present case emphasizes the importance of performing a reversed electrocardiogram in patients with dextrocardia.
Journal of electrocardiology 01/2009; 42(3):254-7. · 1.08 Impact Factor