Zoltán Szabolcs

Minimal invasive coronary sinus lead reposition technique for the treatment of phrenic nerve stimulation

AIMS Phrenic nerve stimulation (PNS), which is often intolerable for the patient, is a known complication of resynchronization therapy. We describe a new, minimal invasive method for treating PNS. METHODS AND RESULTS Untreatable PNS was found in nine cardiac resynchronization therapy patients with distal coronary sinus (CS) lead position 6 +/- 6 (0.5-17) months after the implantation. Ablation catheter and Amplatz Left 2 type guiding catheter were introduced into the right atrium via the right femoral vein. Coronary sinus was cannulated with the Amplatz catheter, and on a normal guide wire, a coronary stent was introduced beside the lead into the side branch in seven cases or a bigger stent into the CS in two patients. The ablation catheter was looped around the CS lead in the atrium with bent tip and was drawn backward together with the CS electrode. New lead positions were evaluated with electrophysiological measurements, and the suitable position was stabilized with inflation of the stent. Pericardial effusion was not detected on post-operative echocardiography. After repositioning, suitable pacing parameters were registered (threshold: 1.6 +/- 1.1 V; 0.5 ms, impedance: 565 +/- 62 ohm). Phrenic nerve stimulation was not found with 7.5 V; 1.5 ms pacing. During follow-up (7.7 +/- 4.6 months), stable pacing threshold and impedance values were measured; transient and reprogrammable PNS was present in only one patient. CONCLUSION Coronary sinus electrode reposition using the femoral approach seems to be a safe and effective procedure, which means smaller burden for the patients compared with the established reposition operation. The technique can be used successfully if the CS lead is in a distal position.

The role of transforming growth factor-beta in Marfan syndrome

The starting point, in Marfan syndrome (MFS) appears to be the mutation of fibrillin-1 gene whose deconstructed protein product cannot bind transforming growth factor beta (TGF-b), leading to an increased TGF-b tissue level. The aim of this review is to review the already known features of the cellular signal transduction downstream to TGF-b and its impact on the tissue homeostasis of microfibrils, and elastic fibers. We also investigate current data on the extracellular regulation of TGF-b level including mechanotransduction and the feedback cycles of integrin-dependent and independent activation of the latent TGF-b complex. Together these factors, by the destruction of the connective tissue fibers, may play an important role in the development of the diverse cardiac and extracardiac manifestations of MFS and many of them could be a target of conservative treatment. We present currently investigated drugs for the treatment of the syndrome, and explore possible avenues of research into pathogenesis of MFS in order to improve understanding of the disease.

Shortening the Second Phase Duration of Biphasic Shocks: Effects of Class III Antiarrhythmic Drugs on Defibrillation Efficacy in Humans

Optimizing the Second Phase of Biphasic Shocks. Introduction: The specific waveform providing optimal defibrillation threshold (DFT) is unknown. We compared the defibrillation efficacy of biphasic pulses with second phases (P2) of 2 and 5 msec in a randomized prospective clinical study.

Characterization of pericardial and plasma ghrelin levels in patients with ischemic and non-ischemic heart disease

Ghrelin is an endocrine regulatory peptide with multiple functions including cardioprotective effects. It is produced in various tissues among others in the myocardium. Pericardial fluid has been proven to be a biologically active compartment of the heart that communicates with the myocardial interstitium. Thus, pericardial level of certain agents may reflect their concentration in the myocardium well. In our study we measured acylated (active) and total (acylated and non-acylated) pericardial and plasma ghrelin levels of patients with ischemic and non-ischemic heart disease. Pericardial fluid and plasma samples were obtained from patients with coronary artery disease (ISCH, n=54) or valvular heart disease (VHD, n=41) undergoing cardiac surgery. Acylated pericardial ghrelin concentrations were found to be significantly higher in patients with ischemic heart disease (ISCH vs. VHD, 32±3 vs. 16±2pg/ml, p<0.01), whereas plasma levels of the peptide showed no difference between patient groups. Pericardial-to-plasma ratio, an index abolishing systemic effects on local ghrelin level was also significantly higher in ISCH group for both acylated and total ghrelin. Plasma total ghrelin showed negative correlation to BMI, plasma insulin and insulin resistance index HOMA-A. Pericardial acylated and total ghrelin concentrations were negatively correlated with posterior wall thickness (R=-0.31, p<0.05 and R=-0.35, p<0.01, respectively). Plasma insulin concentration and HOMA-A showed significant negative correlation with pericardial ghrelin levels. In conclusion, increased pericardial active ghrelin content and higher pericardial-to-plasma ghrelin ratio were found in ischemic heart disease as compared to non-ischemic patients suggesting an increased ghrelin production of the chronically ischemic myocardium. According to our results, pericardial ghrelin content is negatively influenced by left ventricular hypertrophy and insulin resistance.

Efficacy of the non-adenosine analogue A1 adenosine receptor agonist (BR-4935) on cardiovascular function after cardiopulmonary bypass

BACKGROUND We tested the hypothesis that pharmacological preconditioning with a newly developed, potent non-adenosine analogue A1AdoR agonist (BR-4935) improves biventricular cardiac and endothelial function after cardiopulmonary bypass. METHODS Twelve anesthetized dogs underwent cardiopulmonary bypass. Dogs were divided into two groups: group 1 (n = 6) received saline vehicle, group 2 (n = 6) received BR-4935 before cardiopulmonary bypass. Biventricular hemodynamic variables were measured using a combined pressure-volume conductance catheter. Coronary blood flow, ATP content, malondialdehyde and myeloperoxidase levels and vasodilatative responses to acetylcholine and sodium nitroprusside were also determined. RESULTS Administration of the A1AdoR agonist led to a significantly better recovery of left and right ventricular systolic function after 60 minutes of reperfusion. Although the vasodilatative response to sodium nitroprusside was similar in both groups, acetylcholine resulted in a significantly greater increase in coronary blood flow in the BR-4935 group. In addition, the ATP content was significantly higher in the same group. Furthermore, malondialdehyde and myeloperoxidase levels significantly decreased in the A1AdoR group. CONCLUSION Pharmacological preconditioning with a new, potent non-adenosine analogue A1AdoR agonist improves biventricular function recovery and endothelial function after hypothermic cardiac arrest.

Connections between apolipoprotein E genotypes and the development of cardiovascular diseases

Elevated plasma lipid level is one of the main risk factors for cardiovascular diseases, which are considered to be primary causes of death. Apolipoprotein E plays a part in the lipid transport in the blood, thus polimophisms of that affect the lipid composition of the plasma. The three most common alleles of apolipoprotein E are e2, e3, e4. Out of the two non-wild type alleles, the e2 and e4, the latter was shown to play a role in the development of cardiovascular diseases and Alzheimers disease. Some studies mention the e2/e2 homozygote genotype as one of the causes of hyperlipoproteinemia type III. Besides lipid metabolism, apolipoprotein E also influences the manifestation of cardiovascular diseases through other biochemical pathways, therefore it is essential to explore the molecular background of these metabolic pathways.

Fetuin-A serum levels in patients with aortic aneurysms of Marfan syndrome and atherosclerosis.

Eur J Clin Invest 2011; 41 (2): 176–182

Heterotopic abdominal rat heart transplantation as a model to investigate volume dependency of myocardial remodeling

Abstract Heterotopic abdominal rat heart transplantation has been extensively used to investigate ischemic-reperfusion injury, immunological consequences during heart transplantations and also to study remodeling of the myocardium due to volume unloading. We provide a unique review on the latter and present a summary of the experimental studies on rat heart transplantation to illustrate changes that occur to the myocardium due to volume unloading. We divided the literature based on whether normal or failing rat heart models were used. This analysis may provide a basis to understand the physiological effects of mechanical circulatory support therapy.

Cytomegalovirus Immunoglobulin After Thoracic Transplantation: An Overview.

Abstract Cytomegalovirus (CMV) is a highly complex pathogen which, despite modern prophylactic regimens, continues to affect a high proportion of thoracic organ transplant recipients. The symptomatic manifestations of CMV infection are compounded by adverse indirect effects induced by the multiple immunomodulatory actions of CMV. These include a higher risk of acute rejection, cardiac allograft vasculopathy after heart transplantation, and potentially bronchiolitis obliterans syndrome in lung transplant recipients, with a greater propensity for opportunistic secondary infections. Prophylaxis for CMV using antiviral agents (typically oral valganciclovir or intravenous ganciclovir) is now almost universal, at least in high-risk transplants (D+/R−). Even with extended prophylactic regimens, however, challenges remain. The CMV events can still occur despite antiviral prophylaxis, including late-onset infection or recurrent disease, and patients with ganciclovir-resistant CMV infection or who are intolerant to antiviral therapy require alternative strategies. The CMV immunoglobulin (CMVIG) and antiviral agents have complementary modes of action. High-titer CMVIG preparations provide passive CMV-specific immunity but also exert complex immunomodulatory properties which augment the antiviral effect of antiviral agents and offer the potential to suppress the indirect effects of CMV infection. This supplement discusses the available data concerning the immunological and clinical effects of CMVIG after heart or lung transplantation.

Acute Type A Aortic Dissection Complicated by Aortic Stent Graft Collapse

A 57-year-old man complaining of chest pain presented with signs of lower limb ischemia 1 year after implantation of a stent graft at the aortoiliac bifurcation. A computed tomography scan revealed the presence of a type A aortic dissection and complete collapse of the stent graft by bulging of the false lumen. The patient underwent emergency surgical reconstruction of the aortic root and arch, which allowed reexpansion of the previously collapsed stent graft. Stenting of residual stenoses distal to the stent graft and of an occluded left renal artery was also successful.