Roman Przybylski

Advanced glycation end product accumulation in the cardiomyocytes of heart failure patients with and without diabetes.

BACKGROUND Non-enzymatic coupling of protein and lipid cellular structures with glucose leading to the formation of advanced glycation end products (AGE) plays a role in aging and the development of diabetic complications, but its contribution to myocardial pathology is unclear. We aimed to assess the role of heart failure on AGE formation in patients with or without diabetes mellitus type 2 (DM2). MATERIAL/METHODS Heart tissue specimens from 136 patients undergoing transplantation were grouped as follows: 14 cases of ischemic cardiomyopathy (ICM) and DM2, 8 cases of dilated cardiomyopathy (DCM) and DM2, 67 cases of ICM without DM2, and 47 cases of DCM without DM2. Fourteen heart samples were from the autopsies of patients with DM2 without heart disease, and 20 heart samples were from organ donors in whom the heart was wasted. AGE deposits were localized immunohistochemically counted using a semiquantitative scale and characterized by their staining pattern. RESULTS Positive staining was present in all samples from both cardiomyopathy groups with DM2, in 71% of healthy hearts from the DM2 subjects, in 51% of ICM non-diabetic hearts, and in 38% of DCM non-diabetic hearts, and in only 15% of the organ donors. Mixed-diffuse and granular AGE patterns were characteristic for DM2, while a diffuse pattern was more frequently observed in heart failure patients without diabetes. The semiquantitative results supported increased AGE accumulation in patients with DM2 and/or cardiomyopathy. CONCLUSIONS The amount of AGE in cardiomyocytes increases significantly in both diabetes and heart failure, with a staining pattern typical for each condition.

Transcatheter Closure of Postinfarction Ventricular Septal Defects Using Amplatzer Devices

We carried out transcatheter procedures to close postinfarction ventricular septal defects (PIVSDs) in 19 patients: two had recanalization after surgical closure, and 17 had a primary PIVSD. In three of the latter patients, who had acute PIVSDs, the procedure was carried out in the first 3 weeks after infarction; in the 13 patients with subacute PIVSD, it was carried out 3.5-12 weeks after infarction. There was another procedure in one patient with chronic PIVSD. In total, 22 procedures were completed: 17 using an Amplatzer atrial septal occluder, two using an Amplatzer postinfarction ventricular septal defect occluder, and two using an Amplatzer muscular ventricular septal defect occluder. The procedure was successful in 14 patients: in 11 with subacute PIVSD, one with chronic PIVSD, and two with postsurgical PIVSD. Transcatheter closure of PIVSDs using an Amplatzer atrial septal occluder is probably the treatment of choice in patients undergoing surgery more than 3.5 weeks after myocardial infarction and in those with recanalization after previous surgical closure.

Surgical wound-healing complications in heart transplant recipients treated with rapamycin

The aim of this retrospective analysis was to assess the influence of rapamycin (RAPA) used perioperatively on surgical complications in heart transplant recipients. The study group consisted of 28 heart transplant recipients (26M/2F, 49.2±11 years) receiving 15 mg of RAPA before operation, 10 mg of RAPA on the first postoperative day (POD) and 5 mg daily (n=20) thereafter, or 5 mg daily starting on POD 2 (n=8), until the introduction of cyclosporine‐A. A matched historical control group was composed of 28 patients (26M/2F, 49.7±9 years) receiving cyclosporine‐A from POD 1. We compared a number of surgical complications and reinterventions among groups. Statistical significance was assessed using the chi‐square test and the Mann–Whitney U‐test. There were 16 (57%) patients in the study group vs. six (21%) in the control group requiring reintervention (p=0.014). Pericardial tamponade decompression was performed in seven (25%) vs. zero patients, and sternum refixation in seven (25%) vs. zero patients (p=0.015). None of the wounds was infected. The overall drainage volume was 4,213±5,996 vs. 1,911±1,728 mL (p=NS). The frequencies of biopsy‐proven rejection and infection were comparable, except lower cytomegalovirus infection rates in the study group: three (11%) vs. 11 (39%) for the control group (p=0.023). The use of RAPA in the perioperative period of heart transplantation increases the risk of surgical wound‐healing complications.

Cierre percutáneo de comunicaciones interventriculares postinfarto mediante los dispositivos de Amplatzer

Se intento el cierre percutaneo de la comunicacion interventricular postinfarto (CIVPI) en 19 pacientes: 2 con recanalizacion tras el cierre quirurgico y 17 con CIVPI primaria. En estos ultimos, el procedimiento se realizo en 3 pacientes con CIVPI aguda dentro de las primeras 3 semanas postinfarto, en 13 con CIVPI subaguda 3,5-12 semanas postinfarto y en uno con CIVPI cronica. Se llevaron a cabo 22 intervenciones mediante la utilizacion de 17 oclusores Amplatzer auriculares, 2 ventriculares postinfarto y 2 ventriculares musculares. El procedimiento fue satisfactorio en 14 pacientes: 11 con CIVPI subaguda, uno con CIVPI cronica y 2 posquirurgicos. El cierre percutaneo de CIVPI con el Amplatzer Atrial Occlusor es probablemente el tratamiento de eleccion en pacientes con mas de 3,5 semanas despues del infarto de miocardio y en casos con recanalizacion tras el cierre quirurgico.

Advanced glycation end-products in myocardium-supported vessels: Effects of heart failure and diabetes mellitus

BACKGROUND Disturbed glucose metabolism, particularly in diabetes, is an important but not the sole factor leading to advanced glycation end-product (AGE) formation. The AGE amount and its distribution in cardiopathic myocardial tissues in the presence or absence of diabetes are not well documented. The aim of this study was to assess AGE deposition in unaffected myocardial vessels in heart failure patients with and without diabetes mellitus type 2 (DM2) undergoing transplantation. METHODS The following groups were established: 14 hearts harvested from subjects with ischemic cardiopathy and DM2; 8 hearts from subjects with dilated cardiopathy with DM2; 67 hearts from subjects with ischemic cardiopathy; 47 hearts from subjects with dilated cardiopathy; and 14 hearts from autopsy cases with diagnosed DM2. A control group consisted of 20 heart donors. AGE localization was determined immunohistochemically in tissue sections. A semi-quantitative scale was used to assess reaction intensity in arteries, arterioles, capillaries, venules and veins. RESULTS Both types of cardiomyopathy increased AGE accumulation in intramyocardial veins more than in arteries. The presence of DM2 significantly increased AGE in arterioles and capillaries, especially when coexisting with cardiomyopathy. The type of cardiopathy did not influence the pattern of AGE accumulation in myocardial vessels. CONCLUSION Both chronic heart failure and DM2 intensified AGE pathology and changed the susceptibility of myocardial vasculature to glycation. However, chronic heart failure increases AGE deposition mostly in veins, whereas DM2 predisposes arterioles to AGE accumulation.

Persistent mild lesions in coronary angiography predict poor long-term survival of heart transplant recipients

BACKGROUND Even though coronary angiography (CAG) underestimates coronary allograft vasculopathy (CAV) development, especially in the distal parts of arteries, it remains a frame of reference for International Society for Heart and Lung Transplantation (ISHLT) CAV classification. A retrospective analysis was performed to assess the prognostic value of CAG findings. METHODS Among 310 orthotopic heart transplantation (OHT) recipients with at least 2 CAGs at 2-year intervals, we identified 197 (146 men and 41 women; 55 ± 13 years) without lesions (Group 0), 27 (15 men and 12 women; 58 ± 8 years) in whom mild changes remained in consecutive CAGs (Group 1), 28 (24 men and 4 women; 58 ± 10 years) in whom mild lesions decreased in consecutive CAGs (Group 1REG), and 58 (53 men and 5 women; 56 ± 10 years) in whom the stenosis criteria of ISHLT CAV 2 or 3 were covered (Group 2). We compared survival and other clinical variables among the groups. RESULTS The average follow-up was 10 ± 4 years. Forty-one (21%) deaths occurred in Group 0, 15 (56%) in Group 1 (p = 0.002), 9(31%) in Group 1REG (p = NS), and 26 (46%) in Group 2 (p = 0.004, chi-square test). Time free from all-cause death was significantly shorter in Group 1 (T1/2 = 8 years) than in Group 0 (T1/2 = 15.5 years; p = 0.00072, log-rank test). Time free from cardiovascular death was significantly shorter in Groups 1 and 2, as was time free from CAV-related death in Groups 1, 1REG, and 2. Multivariate analysis, using a Cox proportional hazards model, revealed that Group 1 inclusion criterion of CAG findings is an independent predictor of all-cause death, cardiovascular death, and CAV-related death. CONCLUSIONS Persistent mild coronary lesions, observed in consecutive CAG, predicted shorter survival of OHT recipients.

Cytomegalovirus Infection Does Not Accelerate Microvasculopathy Development in Heart Transplant Recipients

BACKGROUND Clinical studies with intravascular ultrasound have suggested that even subclinical cytomegalovirus (CMV) infections increase intimal hyperplasia in transplanted heart coronary arteries after 1 year. The potential influence of CMV on microvasculopathy development is not known. The Aim of our study was to compare the occurrence of microvasulopathy in endomyocardial biopsies (EMBs) of heart transplant recipients with versus without CMV infection. MATERIALS AND METHODS We performed a case-controlled, retrospective study of 58 subjects diagnosed with CMV infection by the presence of pp65 antigen. The 49 men and 91 women of overall age 49 +/- 8 years showed ischemic cardiomyopathy in 52%. We matched a control cohort of 58 subjects without CMV disease. Microvasculopathy was assessed using 4-degree grading system developed by Hiemann et al for elective EMBs performed at 1 and 12 months after transplantation. RESULTS Significant acute rejection episodes were observed among 22% versus 21% of 1-month EMBs, and 3% versus 5% of 12-month EMBs for CMV(+) versus control group subjects respectively. The commonest microvasculopathy was nonstenotic thickening (grade B) 60% versus 59% (35 versus 34 patients) among 1-month EMBs; and 50% versus 60% (29 vs 35 patients) among 12-month EMBs, respectively. Progression of microvasculopathy score between 1- and 12-month EMB was observed in 40% versus 41% of subjects, and regression occurred in 22% versus 21%, respectively. None of differences was significant. CONCLUSION Our data do not support the thesis that CMV infection promotes microvasculopathy development among heart transplant recipients.

The influence of heparin resistance on postoperative complications in patients undergoing coronary surgery

Summary Background Heparin resistance is relatively frequent in patients undergoing coronary surgery. We aimed to assess the impact of heparin resistance on the outcome of patients undergoing coronary surgery with cardiopulmonary bypass (CABG). Three definitions of heparin resistance were adopted. Material/Methods We performed a retrospective review of 756 consecutive patients undergoing isolated CABG. All anaesthesia records were reviewed manually. Heparin resistance was recognized if: ACT was less than 400 seconds after 300 U/kg heparin (local criteria), ACT was less than 480 seconds after 400 U/kg or more heparin (stringent criteria), or if heparin sensitivity index was lower than 1.3. Postoperative assessment included perioperative morbidity and mortality. A multiple logistic regression model was used to investigate the influence of all demographic, preoperative and surgical variables, as well as heparin resistance (variably defined) on hospital mortality and postoperative complications. Results Heparin sensitivity index, local criteria and stringent criteria identified 64.8%, 12.0% and 4.3% heparin resistant patients, respectively. Heparin-resistant patients more frequently had preoperative heparin administration, unstable course of coronary artery disease, and higher coronary symptoms scoring. Severe form of heparin resistance (expressed by the ACT less than 480 seconds after 400 U/kg heparin) was an independent predictor of death (OR 4.92; CI 1.11–21.89). Conclusions Mild forms of heparin resistance are relatively frequent and are not associated with increased morbidity and mortality. The isolation of severe heparin resistance as an independent predictor of death in our large cohort of coronary patients suggests that this phenomenon should be given more attention in future studies.

Awake Heart Valve Surgery in a Patient With Severe Pulmonary Disease

Cardiac operations may be performed in a conscious, spontaneously breathing patient, but it is difficult to justify an awake technique in patients undergoing coronary artery procedures with low operative risk. We describe an elderly patient with severe chronic obstructive pulmonary disease in whom general anesthesia was contraindicated. A valve procedure was performed under thoracic epidural anesthesia alone, thus avoiding intubation and mechanical ventilation. The patient had an uneventful postoperative course and excellent recovery.

Symetis Acurate Transapical Aortic Valve: the initial experience with a second generation of transcatheter aortic valve replacement device

BACKGROUND Transcatheter aortic valve replacement (TAVR) has proven to be a valuable alternative to conventional surgical aortic valve replacement in high risk and surgically in operable patients who suffer from severe symptomatic aortic stenosis. However, a significant number of complications, associated with both the learning curve and device specificity, have required attention and subsequent improvement. The Symetis transapical TAVR system is a self-positioning bioprosthesis composed of a non-coronary leaflet of surgical quality porcine tissue valve sewn into a self-expanding nitinol stent that iscovered with a PET-skirt. METHODS From June to September 2013 six patients have been operated on severe aortic stenosis using the new TAVR device. All patients have undergone critical assessment of a local Heart Team and have been disqualified from conventional AVR. Five were woman. Mean age was 82.3 ± 2.0 (mean LogEuroScore 23.9 ± 14.3). Four patients suffered from coronary artery disease - two had history of previous percutaneous coronary intervention with intracoronary stents, while the next two had history of coronary artery bypass grafting. Diabetes was frequent (n = 3) as well as chronic obstructive pulmonary disease (n = 4). Carotid artery disease was encountered in three patients similarly to atrial fibrillation. Mean left ventricular ejection fraction (LVEF) was 51.5 ± 11.8%, but one patient had suffered from low-flow-low-gradient aortic stenosis with LVEF of 29%. RESULTS The procedure was carried out successfully in all six cases. Two patients have received the valve sized L, three - M and one - S. Mean procedure time was 180 ± 19 min, mean cine 7.2 ± 1.2 min. Mean X-ray dose 930 ± 439 mGy, while mean volume of contrast given was 135 ± 61 mL. In all patients but one perivalvular leak (PVL) was not present. One patient had trace of PVL. Also, good LVEF was noted in all patients. Similar findings were obtained 30 days post procedure. No strokes, transient ischaemic attack or other cerebrovascular incidents were observed. CONCLUSIONS This brief clinical communication reports the first Polish experience with the second generation of TAVR device - the Symetis Acurate Transapical Aortic Valve. While it lacks large patient population and longer follow-up, it reveals that TAVR procedure can be performed safely, with minimal X-ray exposure time and contrast given and successfully - with almost nonexistent PVL and no cerebrovascular incidents or heart rhythm disturbances. Heart Team approach is vital, and transapical access should not be treated inferiorly, but rather as an equally appealing TAVR option.