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Background: Transcatheter aortic valve replacement (TAVR) was developed for inoperable patients with severe aortic stenosis. However, despite TAVR advancements, some patients remain untreated due to complex comorbidities, necessitating less-invasive approaches. Non-invasive ultrasound therapy (NIUT), a new treatment modality, has the potential to address this treatment gap, delivering short ultrasound pulses that create cavitation bubble clouds, aimed at softening embedded calcification in stiffened valve tissue. Methods: In the prospective Valvosoft® Serbian first-in-human study, we assessed the safety and efficacy of NIUT and its impact on aortic valve hemodynamics, on the left ventricle, and on systemic inflammation in patients with severe symptomatic aortic stenosis not eligible for TAVR or surgery. Results: Ten patients were included. Significant improvements were observed in hemodynamic parameters from baseline to one month, including a 39% increase in the aortic valve area (from 0.5 cm2 to 0.7 cm2, p = 0.001) and a 23% decrease in the mean transvalvular gradient (from 54 mmHg to 38 mmHg, p = 0.01). Additionally, left ventricular global longitudinal strain significantly rose, while global wasted work significantly declined at one month. A dose-response relationship was observed between treatment parameters (peak acoustic power, intensity spatial-peak pulse-average, and mean acoustic energy) and hemodynamic outcomes. NIUT was safely applied, with no clinically relevant changes in high-sensitivity troponin T or C-reactive protein and with a numerical, but not statistically significant, reduction in brain natriuretic peptide (from 471 pg/mL at baseline to 251 pg/mL at one month). Conclusions: This first-in-human study demonstrates that NIUT is safe and confers statistically significant hemodynamic benefits both on the valve and ventricle.

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Background: The aim of our study was to evaluate the degree of genetic homozygosity in cardiac surgical patients with postoperative acute kidney injury (AKI), compared to the subgroup without postoperative AKI, as well as to evaluate antropomorpho-genetic variability in cardiac surgical patients with regard to the presence and severity degree of AKI. Materials and methods: The prospective cohort study included an analysis of 138 eligible coronary artery disease (CAD) surgical patients that were screened consecutively. The tested group was divided into three subgroups according to RIFLE criteria: Subgroup NoAKI (N = 91), risk (N = 31), and injury (N = 16). All individuals were evaluated for the presence of 19 observable recessive human traits (ORHT) as a marker of chromosomal homozygosity and variability. Results: Comparing subgroups NoAKI and risk, four ORHTs were significantly more frequent in the risk subgroup. Comparing subgroups NoAKI and injury, nine ORHTs were significantly more frequent in the injury subgroup; while comparing the injury subgroup and risk, five ORHTs were significantly more frequent in injury than in the risk subgroup. Results also showed a significant increase in the mean value of ORHTs for the injury subgroup compared to NoAKI subgroup (p = 0.039). Variability decreased proportionally to the increase in the severity of AKI (V NoAKI = 32.81%, V Risk = 30.92%, and V Injury = 28.62%). Conclusion: Our findings pointed to the higher degree of recessive homozygosity and decreased variability in AKI patients vs. NoAKI individuals, thus presumably facilitating the development and severity degree expression of AKI in patients after cardiac surgery.

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BACKGROUND: Heart failure is the most frequent cause of pulmonary artery hypertension (PAH) and its severity may predict the development of heart failure (HF) and is known to be a prognostic factor of poor outcome after heart transplant (HTx). The aim of this study was to investigate the impact of preoperative PAH related to left-sided HF on long-term survival after HTx and to identify the hemodynamic parameters of PAH that predict survival after HTx. METHODS: A prospective observational trial was performed, and it included 44 patients subjected to heart transplantation. Patients were divided into two groups: The first one with the preoperative diagnosis of PAH and the second one without the PAH diagnosed prior to the HTx. The two groups were compared for baseline characteristics, operative characteristics, survival, and hemodynamic parameters obtained by right heart catheterization. Survival was analyzed using Kaplan Meyer analysis, and Cox regression analysis was performed to determine independent predictors of survival. RESULTS: The median follow-up time was 637.4 days (1-2028 days). The median survival within the group of patients with preoperative PAH was 1144 days (95% CI 662.884-1625.116) and 1918.920 days (95% CI 1594.577-2243.263) within the group of patients without PAH (P = .023), HR 0.279 (95% [CI]: 0.086-0.910; P = .034. The 30-day mortality in patients within PAH group was significantly higher, six versus two patients in the non PAH group (χ2 = 5.103, P < .05), while the long-term outcome after this period did not differ between the groups. Patients with preoperative PAH had significantly higher values of MPAP, PCWP, TPG and PVRI, while CO and CI did not differ between the two groups. Mean PVRI was 359.1 ± 97.3 dyn·s·cm-5 in the group with preoperative PAH and 232.2 ± 22.75 dyn·s·cm-5 in the group without PAH, P < .001. TPG values were 11.95 ± 5.08 mmHg in the PAH group while patients without PAH had mean values of 5.16 ± 1.97 mmHg, P < .001. Cox regression analysis was done for the aforementioned parameters. Hazard ratio for worse survival after HTx for elevated values of PVRI was 1.006 (95% [CI]: 1.001-1.012; P = .018) TPG had a hazard ratio of 1.172 (95% [CI]: 1.032-1.233; P = .015). CONCLUSION: Pulmonary artery hypertension is an independent risk factor for higher 30-day mortality after HTx, while it does not affect the long-term outcome. Hemodynamic parameters obtained by right heart catheterization in heart transplant candidates could predict postoperative outcome. PVRI and TPG have been identified as independent predictors of higher 30-day postoperative mortality.

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INTRODUCTION: While the survival rates for patients with end-stage heart failure have dramatically improved with newer generations of left ventricular assist devices, LVAD-specific infections are important cause of morbidity, mortality, and hospital readmissions in these patients. METHODS: We performed a retrospective analysis of all driveline infections in patients who had undergone LVAD implantation at a single cardiosurgical center. Between June 2013 and March 2017, 51 patients underwent implantation of LVAD. Among these, 12 received Heart Ware LVAD,34 Heart Mate II LVAD, and 5 Heart Mate III LVAD. The end goal for LVAD therapy was destination therapy in three patients and bridge-to-transplantation in 48 patients. RESULTS: One month, six months, and one-year survival rates were 90%, 85%, and 81%, respectively. Five patients developed driveline infections. Median time from LVAD implantation to driveline infections was 126 days. One of these patients underwent heart transplantation. Two patients were treated with antibiotics and surgical driveline repositioning with extensive debridement of the wound. Two patients with a chronic infection were treated conservatively with regular wound cleaning. CONCLUSION: Driveline infections remain a serious therapeutic challenge. With the development of surgical techniques and new devices, it is possible to reduce morbidity and increase survival rate in patients with implanted LVAD. KEY WORDS: Driveline, Infections, LVAD.

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BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) frequently occurs in patients assessed as low-risk for developing CSA-AKI. Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1) and lactate are promising biomarkers of CSA-AKI but have not yet been explored in low-risk patients. AIM: To evaluate urinary NGAL (uNGAL), KIM-1 and lactate as biomarkers of CSA-AKI in patients with low-risk for developing CSA-AKI. METHODS: This prospective, observational study included 100 adult elective cardiac surgery patients assessed as low-risk for developing CSA-AKI. UNGAL, KIM-1 and lactate were measured preoperatively, at the end of cardiopulmonary bypass (CPB) and 3, 12, 24 and 48 h later. RESULTS: Fifteen patients developed CSA-AKI. Patients with CSA-AKI had significantly higher lactate but similar uNGAL and KIM-1 levels compared to patients without CSA-AKI. Unlike uNGAL and KIM-1, postoperative lactate was good biomarker of CSA-AKI with the highest odds ratio (OR) 2.7 [1.4-4.9] 24 h after CPB. Peak lactate concentration ≥ 4 mmol/L carried dramatically higher risk for developing CSA-AKI (OR 6.3 [1.9-20.5]). CONCLUSIONS: Unlike uNGAL and KIM-1, postoperative lactate was significant independent predictor of CSA-AKI with the highest odds ratio 24 h after CPB.

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BACKGROUND: The aim of our study was to evaluate the degree of genetic homozygosity in the group of patients with coronary artery disease (CAD), as well as to evaluate morphogenetic variability in CAD patients regarding the presence of investigated risk factors (RF) compared to a control sample of individuals. Additionally, we aimed to evaluate the distribution of ABO blood type frequencies between tested samples of individuals. METHODS: This study analyzed individual phenotype and morphogenetic variability of 17 homozygously-recessive characteristics (HRC), by using HRC test in a sample of 148 individuals in CAD patients group and 156 individuals in the control group. The following RF were analyzed: hypertension, diabetes mellitus, hyperlipidemia, and smoking. RESULTS: The mean value of HRC in CAD patients is significantly higher, while variability decreases compared to the control sample (CAD patients: 4.24 ± 1.59, control sample: 3.75 ± 1.69; VCAD-patients = 37.50%, VC = 45.07%). There is a significant difference in individual variations of 17 HRC between control sample and CAD patients (χ² = 169.144; p < 0.01), which points out to different variability for tested genes. Mean values of HRC significantly differed in CAD patients in regard to the number of RF present. A blood type (OR = 1.75) is significant predictor for CAD, while O blood type (OR = 0.43) was significantly associated with controls. CONCLUSION: There is a higher degree of recessive homozygosity in CAD patients versus individuals in the control sample, and the presence of significant variations in the degree of recessive homozygosity as the number of tested RF increases.

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We analyzed morphogenetic variability and degree of genetic homozygosity in male and female individuals with coronary artery disease (CAD) versus unaffected controls. We have tested 235 CAD patients; 109 were diagnosed also with diabetes mellitus (DM) and 126 with hypertension (HTN). We additionally evaluated 152 healthy individuals without manifested CAD. For the evaluation of the degree of recessive homozygosity, we have performed the homozygously recessive characteristics (HRC) test and tested 19 HRCs. In controls, the frequency of HRC for males was 2.88 ± 1.89, while for females, it was 3.65 ± 1.60. In the CAD group, the frequency of HRC for males was 4.21 ± 1.47, while for females, it was 4.73 ± 1.60. There is significant difference in HRC frequencies between controls and CAD separately for males (p < 0.001) and females (p < 0.001). The same applies between controls and CAD with DM (males: p < 0.001 and females: p = 0.004), and controls and CAD with HTN (males: p < 0.001 and females: p < 0.001). There is no significant difference in HRC frequencies between the group of CAD with DM and the group of CAD with HTN (males: p = 0.952 and females: p = 0.529). Our findings point to the increased degree of recessive homozygosity and decreased variability in both genders of CAD patients versus controls, indicating the potential genetic predisposition for CAD.

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BACKGROUND: Alcaptonuria, a rare metabolic disorder (1:250 000), is usually presented with symptoms such as arthropathies of weight bearing joints. CASE REPORT: In this case, a 65 year old woman was admitted to our hospital with severe aortic stenosis and no other symptoms that would suggest the existance of Alcaptonuria. Intraoperative findings of black discoloration of the affected valve and ascending aorta, pointed towards the diagnosis of cardiac ochronosis, what was then confirmed by a PH examination. CONCLUSION: This case suggests that although alcaptonuria is a slow progressive disease with cardiac ochronosis as a predictable late complication, it can nevertheless be a first sign. In that case the attention should be brought to the surely affected lumbar spine and weight bearing joints, and other connective tissue. KEY WORDS: Alcaptonuria, Aortic valve, Cardiac ochronosis, Surgery.

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INTRODUCTION: Myxomas arising from the right ventricle are extremely rare. CASE REPORT: We presented a 71-year-old patient with worsening symptoms of the exertional dyspnea and atypical chest pains lasting 6 months. A transthoracic and transesophageal echocardiogram revealed a large, 2.6 x 2.2 cm, ovoid, well-circumscribed, echogenic mass in the right ventricle outflow tract attached by small pedicle, partly obstructing the right ventricular outflow tract and protruding through the pulmonic valve during systole. The tumor was completely removed with the stalk and 5 mm of the surrounding tissue. The histopathological findings confirmed the diagnosis of myxoma. CONCLUSION: This case illustrates the usefulness of echocardiography both in diagnosis of patients with atypical symptoms without family history and associated syndromes (like Carney's complex), and in surgical approach planning. It also stresses the importance of surgical excision of tumor as soon as possible following the diagnosis to prevent the complications such are: valvular obstruction, pulmonary embolization and syncopes.

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BACKGROUND: The symptoms of myxoma are atypical, vary greatly, and may mimic numerous conditions. Our aim was to investigate the correlation of localization, size, and consistency of myxoma with its treatment and prognosis. METHODS: Over a span of 30 years, 74 consecutive patients (24 men, mean age 46.7 years) were surgically treated for echocardiography-diagnosed myxomas at our center. RESULTS: Left atrial myxomas were more frequent (89.19%), with the racemous form being predominantly left-sided and having no difference in tumor size regardless of localization. Three patients were asymptomatic; and those who were symptomatic, symptoms appeared 2 to 36 months (mean 13.60 ± 7.52) before diagnosis. Nonspecific symptoms and signs were present in 91.98% of patients, whereas specific symptoms and signs were present in 74.32%. More often, patients with myxomas >5 cm in diameter were symptomatic. Embolic events occurred in 15 patients (9 cerebral, 4 pulmonary, 2 peripheral), more frequently in right atrial myxomas of >5 cm diameter. All patients were surgically treated on diagnoses, with no intraoperative mortality or recurrences. CONCLUSIONS: Symptoms in our cardiac myxoma patients were more pronounced when the myxomas were left-sided, racemous, and over 5 cm in diameter. Even in asymptomatic patients, a high index of suspicion assured timely diagnosis and management.

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Atrial fibrillation occurs as a frequent complication after cardiac interventions. It can be found in 5% of all surgical patients, and it is far more common in cardiac (10% - 65% of patients) than in non-cardiac procedures. In a number of patients it remains asymptomatic, but may be accompanied by very severe symptoms of hypotension, heart failure, syncope, systemic or pulmonary embolism, perioperative myocardial infarction, cerebrovascular insult and increased operative mortality. Patients whose postoperative course is complicated by atrial fibrillation require longer hospitalization. Possible predisposing factors of this arrhythmia are numerous and are associated with surgery, extensive coronary heart disease and revascularization, and preoperative diseases. According to the recommendations of the European Society of Cardiology orally applied beta-blocker, amiodarone and sotalol can be used for prophylaxis of atrial fibrillation. Following the recommendations, treatment of postoperative atrial fibrillation should include beta-blockers, amiodarone, and in patients with heart failure and left ventricular dysfunction, digoxin. Due to the increased risk of stroke, an anticoagulant protection is necessary. Many studies have been conducted with results supporting the prophylactic use of amiodarone and beta-blockers, while the treatment with new agents such as magnesium, statins, omega-3 fatty acids and inhibitors of the renin-angiotensin-aldosterone system is still being investigated.

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INTRODUCTION: Heart injuries can be classified as penetrating and non-penetrating (blunt). Penetrating wounds are usually caused by stabbing with a piercing object, weapon or projectiles--missiles. The right atrium is damaged in most cases, because of its anatomical position--making the most of the anterior side of the heart. Morbidity caused by stabbing injuries to the heart is 20%-30%, while piercing wounds cause 30%-60% of deaths. CASE REPORT: . A 28-year-old patient was admitted to our clinic with acute ischemia of the extremities. Angiography revealed a bullet in the right common femoral artery, occluding it. The patient denied having any piercing or shooting wound to his leg, but he said that four years before he had been shot to his chest. Echocardiography revealed an atrial septal defect of secondary type. An event reconstruction revealed that, four years after shooting, the bullet was displaced from the heart to the right common femoral artery. CONCLUSION: This case report is unique because of the rare type of injury, time that passed from the injury, the way bullet entered the artery (via atrial septal defect) and especially the success of both surgical procedures (embolectomy and repair of atrial septal defect).

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INTRODUCTION: Endocarditis is the most common cardiovascular manifestation of brucellosis with high mortality rate. Brucella is less accesable to antibiotic (but not for all) and relapse can occur after a various period of clinical latency. CASE REPORT: A 55-year-old farmer was diagnozed with acute systemic Brucella infection in May 2008 and treated with antibiotic therapy in regional hospital for two months and for three months after discharge. He began to feel myalgia, arthralgia, malaise, shortness of breath, abdominal pain, vomiting, diarrhoea and lost weight eight months after initial symptoms occured. Because symptoms progressed he was admitted to our hospital in February 2009. Based on a combination of epidemiological, clinical data (on admission he was catchetic, adynamic, dyspneic, hypotensive 80/50 mmHg, fever up to 39.5 degrees C), positive serological Wright test for brucellosis (1 : 5,120), and echocardiographic examination findings, the diagnosis of very severe relapse of brucellosis with mitral valve endocarditis, complicated with perforation of anterior mitral leaflet, severe mitral regurgitation and pulmonary hypertension was established. He was treated with a combined triple antibiotic therapy (vancomycin, ciprofloxacin and gentamicin, and swiched to regimen with doxycycline, gentamicin and imipenem, replacing gentamicin by rifampicin) for 4 weeks and for the next 2 weeks was receiving trimetoprime/sulfamethoxazole and rifampicin. The patients' condition was improved and he was operated. The diagnosis of infective endocarditis was confirmed intraoperatively. Mitral valve replacement was performed, and combined triple antibiotic treatment (amikacin + ciprofloxacin + cefazolin, for 2 weeks and cephazolin + doxycycline + rifampicin, for 2 weeks) was continued, following with two antibiotics (doxycycline + rifampicin) for 5 months. The patient completely recovered without any signs of infection 30 months postoperatively. CONCLUSION: A combined antibiotic therapy and surgery reduce complications and mortality associated with Brucella endocarditis and improve quality of patients' life.

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INTRODUCTION: False aneurysms of the ascending aorta represent a rare but potentially fatal complication of cardiac surgical procedures. Predisposing factors are aortic dissection, infection, connective tissue disorders, chronic hypertension, aortic calcifications and aortotomy dehiscence. At the beginning they are usually asymptomatic, but later various symptoms arise as a consequence of vital structures compression. Potential risk of rupture rises with time and pseudoaneurysm enlargement. From surgical point of view treatment of such cases represents a unique challenge because of the great danger of inadvertent opening of the aneurysm during resternotomy. CASE OUTLINE: A 58-year-old female patient underwent aortic valve replacement due to severe aortic stenosis in 2004. Operation and postoperative recovery were uneventful.Three years later she started complaining about chest pain. On chest X-ray there was upper mediastinal widening. CT scan showed a pseudoaneurysm of the ascending aorta located in front of the right atrium and right ventricle, which was subsequently verified by angiography. During redo operation the pseudoaneurysm was successfully resected and aorta closed with separate ethybond sutures with pledgets. CONCLUSION: Postoperative pseudoaneurysms of the ascending aorta mostly arise from the suture lines. The most useful diagnostic procedures are contrast CT scan, echocardiography, angiography and MRI. Surgical intervention is absolutely indicated. The institution of cardiopulmonary bypass by alternative ways before chest opening is strongly recommended.

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INTRODUCTION: The subset of patients most likely to benefit from off-pump coronary artery bypass grafting (OPCABG) remains a controversial issue, but the technique has been proposed to decrease postoperative mortality and morbidity. Coronary artery bypass grafting (CABG) with a cardiopulmonary bypass carries a significant risk for patients with severe left ventricular (LV) dysfunction. OBJECTIVE: The objective of this study was to compare off-pump to on-pump CABG in patients with ejection fraction (EF) lower than 30%. METHODS: Prospective randomized study was carried out between June 2004 and March 2006 at the Institute for Cardiovascular Diseases of the Clinical Centre of Serbia. Sixty prospectively randomized high-risk patients divided into two groups to undergo off-pump or on-pump CABG. All recruited patients had left ventricular ejection fraction lower than 30%. RESULTS: Thirty patients averaging 59.2 years of age underwent 2.30 grafts on pump, and another 30 averaging 59.6 years of age underwent 2.03 grafts off pump. OPCABG patients exhibited a significantly less release of TnI (average 0.71 micro/L) than on-pump patients (3.00 micro/L). Inotropic requirements were less in the off-pump group. The patients undergoing OPCABG received fewer units of blood and had shorter postoperative length of stay in intensive care unit and hospital stay. There was no significant difference in hospital mortality and complication rate. CONCLUSION: The present study suggests that off-pump CABG in patients with poor LV function when compared with conventional CABG achieved similar number of grafts per patient, similar in-hospital outcomes, shorter length of stay, reduced transfusion requirement, and less myocardial injury.

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In patients with valvular heart disease planned for any type of surgery preoperative evaluation and preparation are especially important for a successfull outcome of the surgery. Preoperative preparation and intraoperative treatment of patients with valvular heart disease are different de-Spending on the type of valvular disease: aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation or mitral valve prolapse. In this paper we have outlined the criteria for evaluating the severity of valvular disease, given that the risk in surgery is proportional to the degree of valvular disease. Also, given that the risk in surgery is also directly proportional to the type and extent of non cardiac surgery, it will be presented recommendations for intraoperative monitoring, with the purpose of evaluating patient's hemodynamic state, as well as recommendations for perioperative treatment of hypotension, tachycardia, and other hemodynamic disturbances. In the paper we will separately discuss bacterial endocarditis profilaxys which can occur after the surgery of patients with valvular disease. Since the patients with valvular disease, and especially the ones with implanted prosthetic valve or heart arrhythmia, are usually on oral anticoagulation therapy, it will be given recommendations for treatment of patients on oral anticoagulation therapy as part of preoperative preparations.

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Patients with vascular diseases mainly caused by atherosclerosis, that are undergoing nonvascular surgery, often have co-existing conditions which affect their cardiovascular system. Cardiovascular complications are among the most common perioperative complications including respiratory complications and infections. These include coronary disease, hypertension, heart insufficiency, pulmonary hypertension, and renovascular hypertension, among others. Preoperative preparation must include the use of beta-blocker therapy, antihypertensive, antithrombotic and antilipogenic therapy. Electrocardiogram (ECG) and trans-thoracic echocardiography are the minimum preoperative diagnostic evaluations that should be performed, because complications may arise even in patients without prior cardiovascular symptomatology. Venous diseases are the most common contemporary diseases affecting people of all age groups and races. Invasive-diagnostic-therapeutic procedures may cause lesions of venous endothelium, hence perioperative prevention of deep vein thrombosis (DVT) with the use of heparin or low-molecular -weight heparin (LMWH) should be undertaken.

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In the current article, 3 cases of aortic aneurysm and dissection in pregnant patients with Marfan's syndrome are reported. It is well known that pregnancy is a risk factor for the development of aortic aneurysm and dissection in women with Marfan's syndrome since it is shown that dissection can develop both before and after labor. Marfan patients with an aortic root diameter greater than 4 cm should undergo preconceptual counseling for surgical aortic repair before pregnancy. Pregnant Marfan patients with an aortic aneurysm should be closely and continuously evaluated by multidisciplinary specialists in order to prevent possible aortic dissection that could be fatal for both the mother and the fetus.

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INTRODUCTION: Treatment of ischemic mitral regurgitation in patients that require revascularization of myocardium is still debatable. OBJECTIVE: The aim of this study was to compare three surgical approaches: valve repair and revascularization; valve replacement and revascularization, and revascularization alone. METHODS: In 2006 and 2007 at the Institute for Cardiovascular Diseases, Clinical Centre of Serbia, Belgrade, 1,040 patients with coronary disease underwent surgery. Forty-three patients (4.3%) had also mitral insufficiency 3-4+. The patients were examined clinically, echocardiographically and haemodynamically. In group I there were 14 (32.3%) patients, in group II 16 (37.2%) patients and in group III 3 (30.5%) patients. Ninety-three per cent of patients were classified as New York Heart Association (NYHA) class III and IV, and three (7%) patients had congestive heart weakness with ejection fraction < or =30%. The decision as to surgical procedure was made by the surgeon. Postoperatively, patients were checked clinically and echocardiographically after 3, 6 and 12 months. The follow-up period was approximately 15 months (8-20). RESULTS: Hospital mortality for the whole group was 6.9% (3 patients). In group I mortality was 14.2% (2 patients), in group II 6.25% and in group III there was no mortality. Long term results, up to 15 months, showed 100% survival in groups I and II, and in group III one patient died (7.7%). CONCLUSION: Short term results upto 30 days were best in group III, but longer term results were better in groups I and II.

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