Heart failure in patients is associated with downregulation of mitochondrial quality control genes.

BACKGROUND: Mitochondrial dysfunction is one of key factors causing heart failure. We performed a comprehensive analysis of expression of mitochondrial quality control (MQC) genes in heart failure. METHODS: Myocardial samples were obtained from patients with ischemic and dilated cardiomyopathy in a terminal stage of heart failure and donors without heart disease. Using quantitative real-time PCR, we analysed a total of 45 MQC genes belonging to mitochondrial biogenesis, fusion-fission balance, mitochondrial unfolded protein response (UPRmt), translocase of the inner membrane (TIM) and mitophagy. Protein expression was analysed by ELISA and immunohistochemistry. RESULTS: The following genes were downregulated in ischemic and dilated cardiomyopathy: COX1, NRF1, TFAM, SIRT1, MTOR, MFF, DNM1L, DDIT3, UBL5, HSPA9, HSPE1, YME1L, LONP1, SPG7, HTRA2, OMA1, TIMM23, TIMM17A, TIMM17B, TIMM44, PAM16, TIMM22, TIMM9, TIMM10, PINK1, PARK2, ROTH1, PARL, FUNDC1, BNIP3, BNIP3L, TPCN2, LAMP2, MAP1LC3A and BECN1. Moreover, MT-ATP8, MFN2, EIF2AK4 and ULK1 were downregulated in heart failure from dilated, but not ischemic cardiomyopathy. VDAC1 and JUN were only genes that exhibited significantly different expression between ischemic and dilated cardiomyopathy. Expression of PPARGC1, OPA1, JUN, CEBPB, EIF2A, HSPD1, TIMM50 and TPCN1 was not significantly different between control and any form of heart failure. TOMM20 and COX proteins were downregulated in ICM and DCM. CONCLUSIONS: Heart failure in patients with ischemic and dilated cardiomyopathy is associated with downregulation of large number of UPRmt, mitophagy, TIM and fusion-fission balance genes. This indicates multiple defects in MQC and represents one of potential mechanisms underlying mitochondrial dysfunction in patients with heart failure.

Bleeding risk assessment in patients undergoing elective cardiac surgery using ROTEM(®) platelet and Multiplate(®) impedance aggregometry.

Impaired platelet function is a major risk factor for peri-operative bleeding and transfusion. This prospective, observational study enrolled 101 consecutive patients undergoing elective cardiac surgery with cardiopulmonary bypass. Platelet function was assessed by two whole blood impedance aggregometers (ROTEM(®) platelet and Multiplate(®) ), using three different activators (arachidonic acid, adenosine diphosphate and thrombin receptor-activating peptide-6), at three peri-operative time points (before anaesthesia, after aortic declamping and 5-10 min after protamine administration). Platelet function was impaired over the time-course in all assays. Results after protamine administration demonstrated the best correlation with postoperative chest tube drainage. Patients with a chest tube drainage exceeding the 75th percentile of the entire study population, during the first 24 postoperative hours, were characterised to have excessive bleeding. Both devices provided similar predictability for postoperative chest tube drainage and red blood cell transfusion requirements. The latter was associated with the degree of platelet inhibition and the number of pathways inhibited determined respective cut-off values.

Management of heparin-induced thrombocytopenia with fondaparinux in a patient with left ventricular assist device.

Heparin-induced thrombocytopenia is an immune-mediated serious adverse effect of heparin therapy. It is a relatively frequent complication among patients with mechanical circulatory support. Herein, we present a patient with severe heart failure and sepsis who developed heparin-induced thrombocytopenia shortly after implantation of left ventricular assist device as a bridge to transplantation and who was successfully treated with fondaparinux.

Peptic ulcer disease in dyspeptic patients with ischemic heart disease: search and treat?

OBJECTIVE: The aim of this study was to determine the prevalence and risk factors for peptic ulcer disease (PUD) in dyspeptic patients with ischemic heart disease (IHD), and to assess whether the healing of PUD before coronary artery bypass grafting (CABG) could reduce the need for urgent postoperative endoscopy. PATIENTS AND METHODS: A series of 894 patients referred to Dubrava University Hospital in Zagreb for elective CABG during the period from May 1998 until April 2001 was prospectively analysed. Dyspepsia was assessed by a questionnaire, PUD by upper gastrointestinal endoscopy, and H. pylori status by histology/Giemsa staining and the rapid urease test. The need for urgent postoperative endoscopy (hematemesis and/or melena, sudden onset of anemia or unexplained epigastric pain) was compared between the prospective study group of 894 patients and a series of 463 patients referred for CABG to Dubrava University Hospital during the period from January 1997 until April 1998. RESULTS: Gastroduodenal dyspepsia predominated in 184 (20.6 %) patients, 142 (77.2 %) of them with Helicobacter (H.) pylori infection and 69 (37.5 %) with verified PUD. Univariate analysis indicated the increased risk of multiple PUD to be related to a previous diagnosis of PUD (OR 3.61, 95 % CI 1.32 - 9.82), H. pylori infection (OR 18.86, 95 % CI 2.31 - 153.98), use of aspirin (OR 5.70; 95 % CI 1.80 - 18.03) and left coronary artery occlusions (3.10, 95 % CI 1.00 - 9.59). Multivariate analysis pointed to H. pylori infection (OR 16.30, 95 % CI 1.57 - 168.53) and left coronary artery occlusions (OR 4.84, 95 % CI 1.05 - 22.30) as independent risk factors for multiple PUD. The OR for urgent postoperative endoscopy due to a major gastrointestinal event was 9.9 (95 % CI 2.2 - 45.1) and the OR for active peptic ulcer with stigmata of recent bleeding was 6.9 (95 % CI 1.4 - 33.1) in the group of patients with IHD who were not submitted to evaluation for dyspepsia prior to elective heart surgery. CONCLUSIONS: In areas with a high prevalence of H. pylori infection, endoscopy and a "search and treat" strategy for IHD patients with dyspepsia before elective cardiac surgery should significantly reduce the need for urgent postoperative endoscopy due to major gastrointestinal events.

Diagnostic accuracy of transesophageal echocardiography for detection of atrial masses.

The aim of this study was to assess the diagnostic accuracy of transthoracic (TTE) and transesophageal echocardiography (TEE) for the detection of atrial masses. The authors' own experiences with the use of TTE and TEE images in the assessment of atrial masses are reported. These masses included tumors, thrombi, and valvular vegetations. The study groups consisted of 14 consecutive patients (7 women an 7 men), age range 24-72 (mean age 56.6 < +13.4) years. Eleven patients had left atrial tumor, two patients had atrial thrombi, and one patient had vegetation in left atrium detected with TEE. Eight patients had left atrial myoma, two patients had right atrial myxoma, and one patient had right atrial leiomyosarcoma. There was no false negative and no false positive TEE diagnosis, yielding a 100% sensitivity and specificity of TEE in detecting atrial masses. TEE detected atrial masses in six (43%) patients, provided poor images in five (36%) patients, and failed to reveal atrial masses in three (21%) patients. The TEE diagnosis was confirmed by surgery and pathohistology in all patients. The ability of TEE to visualize both atria with great diagnostic accuracy makes it a very valuable procedure in the assessment of atrial masses.

Clinical and echocardiographic features of two large left atrial parietal thrombi.

A 62-year-old woman with severe mitral stenosis and two large parietal thrombi inside the left atrium is described. The patient was admitted to the hospital because of heart failure. Transthoracic and transesophageal echocardiography showed a severe calcific mitral stenosis and two large (56.9 and 46.2 mm in diameter) parietal thrombi inside the left atrium attached to the interatrial septum and associated with severe spontaneous echo contrast. This severe spontaneous echo contrast was detected in the left atrium and in the left atrial appendage. The patient was referred for cardiac surgery. The two large parietal thrombi were removed, and the valve was replaced with a Sorin-Bicarbon mitral valve prosthesis. Intraoperative transesophageal echocardiography after replacement of the mitral valve prosthesis and removal of the thrombotic mass showed absence of any spontaneous echo contrast in the left atrium and in the left atrial appendage. This report describes the diagnostic approach and successful surgical treatment of two very large parietal thrombi inside the left atrium associated with severe mitral stenosis and atrial fibrillation, which is a rare occurrence.

Cytomegalovirus disease as a possible etiologic factor for early atherosclerosis.

A group of 284 patients who underwent orthotopic heart transplantation between April 1986 to June 1991 and who were followed up for at least five years was analyzed in this paper. Patients were divided into three groups according to the presence or absence of cytomegalovirus infection or disease: patients without infection, patients with serologycaly proven infection and patients with cytomegalovirus disease. The analysis of survival was performed with respect to all major factors that influence survival: age and sex of a donor and a recipient, number of rejection episodes, perioperative ischemic time and pulmonary vascular resistence. A recipient's age was shown to be a significant factor. Patients who experienced at least one episode of cytomegalovirus disease had significantly worse long-term survival compared to those with the infection only or without the infection. That difference was caused by the increased incidence of coronary atherosclerosis, which caused deaths in patients with a previous episode of cytomegalovirus disease. A possible mechanism responsible for this phenomenon is discussed.

Minimally invasive coronary surgery--our experience.

Minimally invasive coronary artery surgery (MICS) has been defined as proceeding myocardial revascularization without cardiopulmonary bypass. Between January 1996 and August 1997, 19 patients (18 males, 1 female), aged 47-67 years (mean age 57.2 +/- 5.1 years), were operated on. All patients had single vessel coronary disease. In 11 (57.9%) patients, the operation was performed through median sternotomy, in 5 (26.3%) through left anterior small thoracotomy (the LAST procedure). In two (10.5%) patients, the operation began as a LAST, but conversion to median sternotomy was required due to lateroposition of the left anterior descending artery (LAD). In one (5.3%) patient, a minimal procedure was converted in to conventional cardiosurgical procedure with thrombendarterectomy and anastomosis of the left internal mammary artery (LIMA) to LAD. Anastomosis of LIMA to LAD was performed in 9 (47.4%) cases and of right internal mammary artery (RIMA) to right coronary artery (RCA) in four (21.1%) cases. In two (10.5%) cases, saphenous vein was used as a graft to RCA, and in four (21.1%) cases, to LAD. One (5.3%) patient died on the fourth postoperative day. One patient developed perioperative myocardial infarction, and one patient was reoperated on due to postoperative bleeding. Permanent pacemaker was implanted in one (5.3%) patient because of slow atrial fibrillation. The ischemic time was 8 to 25 minutes, and the whole procedure was completed in 90-175 minutes. Intensive care unit stay was up to 18 hours in 12 (63.2%) patients. The whole duration of hospitalization took from 7 to 14 days (mean 10.6 +/- 2.4 days). Minimally invasive coronary surgery is a safe and effective method in the surgical treatment of one-vessel coronary artery disease.

Penetrating cardiothoracic war wounds.

OBJECTIVE: Penetrating cardiothoracic war wounds are very common among war casualties. Those injuries require prompt and specific treatment in an aim to decrease mortality and late morbidity. There are a few controversies about the best modality of treatment for such injuries, and there are not many large series of such patients in recent literature. METHODS: We analysed a group of 259 patients with penetrating cardiothoracic war wounds admitted to our institutions between May 1991 and October 1992. RESULTS: There were 235 (90.7%) patients with thoracic wounds, 14 (5.4%) patients with cardiac, wounds and in 10 (3.7%) patients both heart and lungs were injured. The cause of injury was shrapnel in 174 patients (67%), bullets in 25 patients (9.7%), cluster bomb particles in 45 patients (17.3%) and other (blast etc.) in 15 patients (6%). Patients, 69, had concomitant injuries of various organs. The initial treatment in 164 operated patients was chest drainage in 76 (46.3%) patients, thoracotomy and suture of the lung in 71 (43.2%) patients, lobectomy in 12 (7.3%) patients and pneumonectomy in 5 (3%) patients. Complications include pleural empyema and/or lung abscess in 20 patients (8.4%), incomplete reexpansion of the lung in 10 patients (4.2%), osteomyelitis of the rib in 5 patients (2.1%) and bronchopleural fistula in 1 patient (0.4%). Secondary procedures were decortication in 12 patients, rib resection in 5 patients, lobectomy in 2 patients, pneumonectomy in 4 patients, reconstruction of the chest wall in 2 patients and closure of the bronchopleural fistula in 1 patient. The cardiac chamber involved was right ventricle in 12 patients, left ventricular in 6 patients, right atrium in 7 patients, left atrium in 3 patients, ascending aorta in 2 patients and 1 patient which involved descending aorta, right ventricle and coronary artery (left anterior descending) and inferior vena cava, respectively. The primary procedure was suture in 17 patients (in 10 patients with the additional suture of the lung), suture + extraction of the foreign body in 4 patients, 2 of them with cardiopulmonary bypass. Complications were pericardial effusion in 6 patients, arrhythmia in 2 patients, myocardial infraction in 1 patient and migration of the foreign body in 1 patient. Patients, 7, died, five of the group with concomitant injuries, two of thoracic and one of cardiac injuries (5, 1.2 and 4.2%, respectively). CONCLUSIONS: Penetrating cardiothoracic wounds are among the most serious injuries in war, either in combat or among civilians. In spite of their nature, they can be treated successfully with relatively low mortality and morbidity.

Peroxyacetic acid effect on the bacteriologic status of war wound.

In this study, the efficiency of peroxyacetic acid as a local antiseptic in war wound healing was investigated. Peroxyacetic acid was specially prepared for local application. The acidity was reduced from pH 2 to pH 5 using acetate buffer, the concentration was reduced to 0.2% and the use of sulfuric acid was avoided in the peroxyacetic acid preparation. Thirty-five patients with at least two similar wounds requiring daily dressing were included on a voluntary basis. Cranial wounds and wounds on the right side of the body were treated by peroxyacetic acid compresses, while other wounds were treated by the application of hypertonic NaCl solution. On day 12, the wounds treated by peroxyacetic acid (chi 2 = 52; df = 4, P < 0.001) were observed to be statistically significantly cleansed than the wounds treated conventionally. The use of peroxyacetic acid as a local antiseptic has not yet been described in the available literature. The possibilities and efficiency of peroxyacetic acid for this purpose, previously prepared for use in living tissue, are emphasized.

Adult respiratory distress syndrome.

In this article the authors present a case of successful treatment of a 54-year old male patient with non-insulin dependent diabetes mellitus (NIDDM) and triple-vessel coronary artery disease who underwent surgical myocardial revascularization and was reoperated on the same day because of excessive bleeding. The patient was given cca 5000 mL of whole blood and cca 3000 mL of blood derivatives. The first postoperative chest X-ray showed radiological signs of ARDS. The therapy was based upon authors' experience and was consisted of controlled mechanical ventilation (respiratory volume 12-15 mL/kg, 10-14 cycles/min, I/E ratio 1:2, FIO2 0.6, PEEP 2-5 cm H2O), daily bronchoscopies with bronchoaspiration, aggressive diuresis, negative fluid balance, specific antibiotic therapy, and last but not least, of prostaglandin E1 (PGE1) 0.5-20 micrograms/kg/min combined with dopamine inotropic support (2-5 micrograms/kg/h). Simple but careful clinical observation still remains a milestone for all therapeutic measures taken in ARDS patients.

The importance of glucose-insulin-potassium with cardiopulmonary bypass prior to cardioplegic arrest in open-heart surgery.

The benefit of a high dose glucose-insulin-potassium (33% glucose, 80 mmol KCl, 120 units of insulin - 1 mL/kg) (GIK) with cardiopulmonary bypass support (CPB) prior to cardioplegic arrest in open-heart surgery has been evaluated in this article. Twenty non-diabetic patients (PTS) were selected upon their preoperatively impaired left ventricular ejection fraction (LVEF < 45%) and were divided into two groups. Group 1 was given GIK and 20 minutes of CPB prior to cardioplegic arrest; Group 2 was the control group with no GIK and no CPB support. Hemodynamics was measured prior to surgery, 30 minutes after weaning from CPB, and 12 and 24 hours postoperatively. There were less rhythm disturbances and need for intraoperative defibrillation in Group 1 (2:10 pts VS 8:10 pts in the Group 2). There were significantly higher values of cardiac index (CI) in Group 1 30 minutes after weaning from CPB (2.5 +/- 0.28 VS 2.11 +/- 0.25: p < 0.01), while there was no significant difference in late postoperative course. Left ventricular stroke work index (LVSWI) in Group 2 was significantly higher 12 hours after the surgery (38.35 +/- 8.93 VS 29.76 +/- 8.17:p < 0.05). At 30 minutes and 24 hours postoperatively there was no significant difference, but clinical difference was observed, probably due to necessary inotropic stimulation in Group 2. There was neither clinical nor statistical difference in right ventricular stroke work index (RVSWI) throughout the whole measurement. The authors emphasise the importance of GIK with CPB in myocardial protection in patients undergoing open-heart surgery.

[Hemodynamic effects of amrinone, dobutamine and dopamine in the cardiac low output syndrome following open-heart surgery]. / Hemodinamski ucinak amrinona, dobutamina i dopamina u sindromu niskog minutnog volumena srca nakon kirurskog zahvata na otvorenom srcu.

Low heart stroke volume syndrome is clinically manifested with hypoperfusion of all body systems. Inotropic or mechanical support is applied. Acute heart failure is one of the most important complications after open heart surgery. Catecholamines have been up to non considered as a therapy of choice for the acute heart failure. Effectiveness of catecholamines could be limited with some side effects. Phosphodiesterase inhibitors promise a new therapeutic approach. PDE III primary act through phosphodiesterase inhibition which leads to a rise of aAPM levels. Thus they show positive inotropic and lusitropic effects, which could be monitored by occlusive pulmonary capillary pressure values. Amrinone is obviously superior to inotropic catecholamines.

Inotropic agents in the treatment of postoperative low cardiac output syndrome.

Two basic groups of inotropic drugs that are in the treatment of postcardiotomy low cardiac output syndrome (LCOS) are presented. The authors emphasize the advantages of phosphodiesterase inhibitors (PDE III) as compared to catecholamines.

Treatment of adult respiratory distress syndrome--our way.

From July 1991 to September 1992 the authors treated twenty-eight patients with proven adult respiratory distress syndrome (ARDS). In this paper five patients with ARDS accompanying septicaemia are presented. In this group of patients, elevated pulmonary artery pressure or pulmonary hypertension (PAH) could not have been caused by LV failure, as it was possible in remaining twenty-three patients with ARDS after open heart surgery, so the effect of prostaglandin E1 (PGE1) on pulmonary hypertension could be followed accurately. Moreover, ARDS after septicaemia carries the worst prognosis. All patients were admitted from other hospitals, they were intubated and mechanically ventilated. ARDS was diagnosed 4 to 7 days after the primary injury.

[Aortico-left ventricular tunnel]. / Aorto-lijevoventrikulski tunel.

The boy was first admitted to the Department of Pediatric Cardiology at the age of 4 1/2 because of cardiac murmur diagnosed on the third day of life. A diastolic murmur of a grade 4/6, left ventricular hypertrophy as well as left aortal and ventricular dilatation were discovered. The findings showed a tendency of increase with time, but the patient had no symptoms. X-ray in the long axis view revealed a defect within the upper part of the interventricular septum immediately below the aorta, and dilated right coronary sinus. An invasive diagnostic method was undertaken, as well. The operative procedure was done with a total cardio-pulmonary bypass and hypothermia (29 degrees C). A tunnel from the anterior aortal wall through the outflow tract of the right ventricle to the left side of the heart was established intraoperatively. The defect was solved by a "sandwich" technique (two patch technique). Postoperative period was uneventful. A Doppler echocardiogram demonstrated the normal hemodynamic status of the patient without the left-to-right or right-to-left shunt and aortal insufficiency.

[Direct communication of the pulmonary artery with the left atrium]. / Izravni spoj plucne arterije s lijevim atrijem.

A rare communication between the right pulmonary artery and the left atrium in a 3.5-year-old girl is described. Cyanosis of a central type and a continuous murmur over the heart were presenting symptoms. Echocardiography revealed only excessive pulsations of the pulmonary artery, while catheterization pointed to an abnormal aneurysmal communication between the right pulmonary artery and the left atrium. At this point the O2 saturation was at the level of the left atrium. The communication was clinically classified as a type IV according to Nelson. After an unsuccessful attempt through a right thoracotomy, the ligature of this fistula has been performed in the second attempt through a median sternotomy and under complete extracorporeal circulation. Clinical course and review of literature of this rare anomaly of the heart are being presented.