István Hartyánszky

Risks and Predictors of Blood Transfusion in Pediatric Patients Undergoing Open Heart Operations

BACKGROUND Blood transfusion in adults is associated with increased mortality and morbidity after cardiac operations. The aim of this study was to identify the main predictors of blood transfusion and explore the relationship between blood transfusion and adverse outcomes in a pediatric population. METHODS We retrospectively analyzed a prospectively collected database (January 2002 to December 2003) of 657 consecutive pediatric patients undergoing open heart procedures in a tertiary pediatric cardiac center. Risk models were calculated for each blood product and for the total amount of blood transfused during the operation and in the first 24 hours. Postoperative adverse events were investigated after propensity score adjustment. RESULTS During the postoperative period, 30 patients (4.6%) died, 80 (12.2%) sustained nonvascular pulmonary complications, and 113 (17.2%) had infection. The risk model for the total amount of blood transfusion included weight, preoperative creatinine clearance, preoperative mechanical ventilation, duration of operation and cross-clamp, surgeon, delayed chest closure, inotropic dose, and nitric oxide administration. Univariate analyses demonstrated significant associations between blood transfusion and occurrence of every complication except of neurologic events. After adjustment for propensity score and disease severity, the total amount of blood transfusion was independently associated with an increased risk for infections (odds ratio, 1.01; 95% confidence interval, 1.002 to 1.02; p = 0.01). Transfusion of platelets was associated with lower incidence of nonvascular pulmonary complications (odds ratio, 0.89; 95% confidence interval, 0.79 to 0.99; p = 0.049). CONCLUSIONS The amount of blood transfusion is independently associated with infections but not with mortality.

Locally different role of atrial natriuretic peptide (ANP) in the pericardial fluid.

Pericardial fluid (PF) contains several vasoactive agents in higher concentrations than venous plasma (VP). However, with human atrial natriuretic peptide (ANP) controversial data have been reported in earlier studies performed on a limited number of patients (less than 20). The present study was designed to characterize the ANP levels in human PF and cardiac tissues, and to ascertain whether myocardial ischemic state is a major factor in determining ANP production of the human heart. In a total of 316 consecutive patients undergoing open heart surgery ANP levels in VP, PF, atrial and ventricular tissues were measured by radioimmunoassay and analyzed by high-performance liquid chromatography (HPLC). The data are presented as median and 25th-75th percentiles. Our results showed ANP concentration [ANP] of PF significantly exceeded that of VP and [ANP] in the atrial tissue was significantly higher than in the ventricular tissue (p < 0.001). In patients without myocardial ischemia (valvular heart disease) [ANP] in the PF was 258.3 (189.9-342.5) pg/ml, in the VP 28.4 (11.7-57.6) pg/ml and 151.7 (78.4-447.6) ng/mg in the atrial, 0.4 (0.2-1.6) ng/mg in the ventricular tissue. The corresponding values for patients with coronary artery disease were 208.1 (153.8-318.9) pg/ml in the PF, 19.8 (9.4-27.9) pg/ml in the VP, 129.6 (66.5-455.0) ng/mg in the atrial and 1.0 (0.1-1.8) ng/mg in the ventricular tissue. The ventricular tissue levels correlated to the atrial tissue levels (r = 0.317; p < 0.05). Great difference (p < 0.001) was found in the atrial tissue levels between females [414.6 (119.7-734.4) ng/mg] and males [105.4 (65.3-204.2) ng/mg]. In HPLC analysis the majority of the pericardial fluid and tissue ir-ANP coeluted with human ANP [99-126]. In conclusion, [ANP] in PF of cardiosurgical patients is higher by an order of magnitude than in VP. Intrapericardial ANP may reflect the peptide concentration in the myocardial interstitium and may represent a paracrine regulatory mechanism, which seems independent of ANP-induced putative antiischemic influences.

Plasma nociceptin/orphanin FQ levels are lower in patients with chronic ischemic cardiovascular diseases--A pilot study.

BACKGROUND Clinical studies are limited regarding the role of human nociceptin/orphanin FQ (N/OFQ) in ischemic cardiovascular diseases, which are still the number one cause of death in the developed world. The aim of our study was to measure the plasma levels of N/OFQ in patients with chronic ischemic cardiovascular diseases in a pilot study. METHODS AND RESULTS Our study population consisted of 22 patients presenting symptoms of stable angina pectoris (SAP): 12 severe Canadian Cardiovascular Society (CCS) III-IV functional class, and 10 with milder SAP (CCS II-III). 12 patients were also enrolled with chronic peripheral artery disease (9 with intermittent claudication; 3 with rest pain and gangrene). Patients were asked to avoid any exertion or given analgetics for their rest pain. Patients had no episodes of chest or limb pain in 1week before their fasting blood samples were taken and N/OFQ plasma levels were measured by radioimmunoassay. 14 healthy subjects without any cardiac risk factors served as a control group. CONCLUSIONS N/OFQ levels were significantly lower in patient groups with severe vs. milder chronic angina (p<0.05) and vs. control subjects (p<0.01). Patients suffering from peripheral artery disease had also a lower plasma N/OFQ levels than in healthy controls (p<0.01). Our findings show that chronic ischemic conditions of atherosclerotic origin are associated with significantly lower plasma N/OFQ levels.

Total Aortic Arch Replacement: Superior Ventriculo-Arterial Coupling with Decellularized Allografts Compared with Conventional Prostheses

Background To date, no experimental or clinical study provides detailed analysis of vascular impedance changes after total aortic arch replacement. This study investigated ventriculoarterial coupling and vascular impedance after replacement of the aortic arch with conventional prostheses vs. decellularized allografts. Methods After preparing decellularized aortic arch allografts, their mechanical, histological and biochemical properties were evaluated and compared to native aortic arches and conventional prostheses in vitro. In open-chest dogs, total aortic arch replacement was performed with conventional prostheses and compared to decellularized allografts (n = 5/group). Aortic flow and pressure were recorded continuously, left ventricular pressure-volume relations were measured by using a pressure-conductance catheter. From the hemodynamic variables end-systolic elastance (Ees), arterial elastance (Ea) and ventriculoarterial coupling were calculated. Characteristic impedance (Z) was assessed by Fourier analysis. Results While Ees did not differ between the groups and over time (4.1±1.19 vs. 4.58±1.39 mmHg/mL and 3.21±0.97 vs. 3.96±1.16 mmHg/mL), Ea showed a higher increase in the prosthesis group (4.01±0.67 vs. 6.18±0.20 mmHg/mL, P<0.05) in comparison to decellularized allografts (5.03±0.35 vs. 5.99±1.09 mmHg/mL). This led to impaired ventriculoarterial coupling in the prosthesis group, while it remained unchanged in the allograft group (62.5±50.9 vs. 3.9±23.4%). Z showed a strong increasing tendency in the prosthesis group and it was markedly higher after replacement when compared to decellularized allografts (44.6±8.3dyn·sec·cm−5 vs. 32.4±2.0dyn·sec·cm−5, P<0.05). Conclusions Total aortic arch replacement leads to contractility-afterload mismatch by means of increased impedance and invert ventriculoarterial coupling ratio after implantation of conventional prostheses. Implantation of decellularized allografts preserves vascular impedance thereby improving ventriculoarterial mechanoenergetics after aortic arch replacement.

No mutation but high mRNA expression of Coxsackie-Adenovirus Receptor was observed in both dilated and ischemic cardiomyopathy

The most common causes of acute myocarditis and the possible consequence of dilated cardiomyopathy are virus infections. The receptor of the two most common viruses connected to these myocardial diseases was identified as Coxsackie-Adenovirus Receptor. The purpose of this study was to assess Coxsackie-Adenovirus Receptor mRNA expression in the myocardium and search for mutations in the Coxsackie-Adenovirus Receptor gene to compare dilated, inflammatory and ischemic cardiomyopathy with control group. All the myocardial samples were obtained from 35 explanted hearts during heart transplantation, than DNA and RNA were isolated from the muscle samples. cDNA was generated from RNA using reverse transcription, and real-time PCR was performed with relative quantification by β-actin gene as endogenous control. Using DNA extracted from the myocardial samples, we sequenced all the seven exons of the Coxsackie-Adenovirus Receptor gene. Coxsackie-Adenovirus Receptor mRNA expression was higher in both ischemic and dilated cardiomyopathy groups than in inflammatory cardiomyopathy and healthy control groups. Sequencing of CAR gene showed no sign of mutation. Therefore, the sequences result of CAR exons did not show any mutation or polymorphism, that explains a determinant role of CAR in dilated or ischemic CM. Our results suggest that high mRNA expression of Coxsackie-Adenovirus Receptor may support its role in regeneration of the damaged myocardium rather than having any role in viral mediated heart disease.

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.

External subcommissural annuloplasty to prevent regurgitation in the pulmonary autograft

In pediatric patients, the further growth potential is a major advantage in using the pulmonary autograft (Ross procedure). The authors describe a modified annuloplasty technique that appears to prevent the development of undesirable aortic regurgitation associated with root enlargement while not affecting overall tissue growth in the autograft.

The Role of Viral Infections in the Development of Dilated Cardiomyopathy

Enteroviruses (EVs) are the most frequent pathogens in myocarditis and in the subsequently developing dilated cardiomyopathy as well. Furthermore, persistence of other viruses might play a pathogenic role in the evolution from myocarditis to dilated cardiomyopathy. Explanted heart of 28 patients, who underwent heart transplantation were screened for EV, AdV3 and HHV6 sequences in order to assess the incidence of cardiac viral infection that may be implicated in the pathogenesis of cardiomyopathy, and estimate viral distribution in the myocardium. Viral sequences were extracted from five different regions of the hearts. Nested PCR was used to amplify conservative regions of AdV3, HHV6 and EVs. Histological examination was performed on routinely processed myocardial samples. AdV3 was verified in one fourth of the patients. ADV3 and HHV6 sequences coexisted in one case with inflammatory cardiomyopathy. Some patients had more than one positive area of their heart. AdV3 positive right ventricular samples were double in amount compared to the left ones. None of the patients had positive result for EV. This is the first occasion to identify AdV3 (a mainly respiratory infective virus) sequence in explanted hearts of cardiomyopathy patients. Though the clinical importance of our results is still unclear, AdV3 could be a new member of the viral group with possible pathogenic effect on the myocardium. Regional distribution of viral sequence location confirmed that the right ventricular wall as a biopsy sampling site might be adequate for endomyocardial biopsy pro diagnostic purposes.

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.

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.