Sex-Linked Differences in Cardiac Atrophy After Mechanical Unloading Induced by Heterotopic Heart Transplantation.

No information is available about sex-related differences in unloading-induced cardiac atrophy. We aimed to compare the course of unloading-induced cardiac atrophy in intact (without gonadectomy) male and female rats, and in animals after gonadectomy, to obtain insight into the influence of sex hormones on this process. Heterotopic heart transplantation (HT((x)) was used as a model for heart unloading. Cardiac atrophy was assessed as the weight ratio of heterotopically transplanted heart weight (HW) to the native HW on days 7 and 14 after HTx in intact male and female rats. In separate experimental groups, gonadectomy was performed in male and female recipient animals 28 days before HT(x) and the course of cardiac atrophy was again evaluated on days 7 and 14 after HT(x). In intact male rats, HT(x) resulted in significantly greater decreases in whole HW when compared to intact female rats. The dynamics of the left ventricle (LV) and right ventricle (RV) atrophy after HT(x) was quite similar to that of whole hearts. Gonadectomy did not have any significant effect on the decreases in whole HW, LV, and RV weights, with similar results in male and female rats. Our results show that the development of unloading-induced cardiac atrophy is substantially reduced in female rats when compared to male rats. Since gonadectomy did not alter the course of cardiac atrophy after HTx, similarly in both male and female rats, we conclude that sex-linked differences in the development of unloading-induced cardiac atrophy are not caused by the activity of sex hormones.

Effects of Acute Pump Speed Changes on Cerebral Hemodynamics in Patients With an Implantable Continuous-Flow Left Ventricular Assist Devices.

Mechanical circulatory support (MCS) with an implantable left ventricular assist device (LVAD) is an established therapeutic option for advanced heart failure. Most of the currently used LVADs generate a continuous stream of blood that decreases arterial pulse pressure. This study investigated whether a change of the pulse pressure during different pump speed settings would affect cerebral autoregulation and thereby affect cerebral blood flow (CBF). The study included 21 haemodynamically stable outpatients with a continuous-flow LVAD (HeartMate II, Abbott, USA) implanted a median of 6 months before the study (interquartile range 3 to 14 months). Arterial blood pressure (measured by finger plethysmography) was recorded simultaneously with CBF (measured by transcranial Doppler ultrasound) during baseline pump speed (8900 rpm [IQR 8800; 9200]) and during minimum and maximum tolerated pump speeds (8000 rpm [IQR 8000; 8200] and 9800 rpm [IQR 9800; 10 000]). An increase in LVAD pump speed by 800 rpm [IQR 800; 1000] from the baseline lead to a significant decrease in arterial pulse pressure and cerebral blood flow pulsatility (relative change ?24% and ?32%, both p < 0.01), but it did not affect mean arterial pressure and mean CBF velocity (relative change 1% and ?1.7%, p = 0.1 and 0.7). In stable patients with a continuous-flow LVAD, changes of pump speed settings within a clinically used range did not impair static cerebral autoregulation and cerebral blood flow.

Sex-dependent effect of perinatal hypoxia on cardiac tolerance to oxygen deprivation in adults.

Epidemiological studies have demonstrated a relationship between the adverse influence of perinatal development and increased risk of ischemic heart disease in adults. From negative factors to which the fetus is subjected, the most important is hypoxia. The fetus may experience hypoxic stress under different conditions, including pregnancy at high altitude, pregnancy with anemia, placental insufficiency, and heart, lung, and kidney disease. One of the most common insults during the early stages of postnatal development is hypoxemia due to congenital cyanotic heart defects. Experimental studies have demonstrated a link between early hypoxia and increased risk of ischemia/reperfusion injury (I/R) in adults. Furthermore, it has been observed that late myocardial effects of chronic hypoxia, experienced in early life, may be sex-dependent. Unlike in males, perinatal hypoxia significantly increased cardiac tolerance to acute I/R injury in adult females, expressed as decreased infarct size and lower incidence of ischemic arrhythmias. It was suggested that early hypoxia may result in sex-dependent programming of specific genes in the offspring with the consequence of increased cardiac susceptibility to I/R injury in adult males. These results would have important clinical implications, since cardiac sensitivity to oxygen deprivation in adult patients may be significantly influenced by perinatal hypoxia in a sex-dependent manner.

Increased Number of Mast Cells in Epicardial Adipose Tissue of Cardiac Surgery Patients With Coronary Artery Disease.

Chronic inflammation of adipose tissue is associated with the pathogenesis of cardiovascular diseases. Mast cells represent an important component of the innate defense system of the organism. In our work, we quantified mast cell number in epicardial adipose tissue (EAT), subcutaneous adipose tissue (SAT), and right atrial myocardium (RA) in patients undergoing open heart surgery (n=57). Bioptic samples of EAT (n=44), SAT (n=42) and RA (n=17) were fixed by 4 % paraformaldehyde and embedded into paraffin. An anti-mast cell tryptase antibody was used for immunohistochemical detection and quantification of mast cells. We also demonstrated immunohistochemically the expression of CD117 and chymase markers. In EAT of patients with coronary artery disease (CAD), higher incidence of mast cells has been found compared to patients without CAD (3.7±2.6 vs. 2.1±1.2 cells/mm(2)). In SAT and RA, there was no difference in the number of mast cells in CAD and non-CAD patients. Mast cells in SAT, EAT and RA expressed CD117 and chymase. An increased incidence of mast cells in EAT of CAD patients may indicate the specific role of these inflammatory cells in relation to EAT and coronary arteries affected by atherosclerosis.

Intraventricular placement of a spring expander does not attenuate cardiac atrophy of the healthy heart induced by unloading via heterotopic heart transplantation.

An important complication of the prolonged left ventricle assist device support in patients with heart failure is unloading-induced cardiac atrophy which proved resistant to various treatments. Heterotopic heart transplantation (HTx) is the usual experimental model to study this process. We showed previously that implantation of the newly designed intraventricular spring expander can attenuate the atrophy when examined after HTx in the failing heart (derived from animals with established heart failure). The present study aimed to examine if enhanced isovolumic loading achieved by implantation of the expander would attenuate cardiac post-HTx atrophy also in the healthy heart. Cardiac atrophy was assessed as the ratio of the transplanted-to-native heart weight (HW) and its degree was determined on days 7, 14, 21 and 28 after HTx. The transplantation resulted in 32±3, 46±2, 48±3 and 46±3 % HW loss when measured at the four time points; implantation of the expander had no significant effect on these decreases. We conclude that enhanced isovolumic loading achieved by intraventricular implantation of the expander does not attenuate the development of cardiac atrophy after HTx in the healthy heart. This indicates that such an approach does not represent a useful therapeutic measure to attenuate the development of unloading-induced cardiac atrophy.

Effects of increased myocardial tissue concentration of myristic, palmitic and palmitoleic acids on the course of cardiac atrophy of the failing heart unloaded by heterotopic transplantation.

The present experiments were performed to evaluate if increased heart tissue concentration of fatty acids, specifically myristic, palmitic and palmitoleic acids that are believed to promote physiological heart growth, can attenuate the progression of unloading-induced cardiac atrophy in rats with healthy and failing hearts. Heterotopic abdominal heart transplantation (HT(x)) was used as a model for heart unloading. Cardiac atrophy was assessed from the ratio of the native- to-transplanted heart weight (HW). The degree of cardiac atrophy after HT(x) was determined on days 7, 14, 21 and 28 after HT(x) in recipients of either healthy or failing hearts. HT(x) of healthy hearts resulted in 23+/-3, 46+/-3, 48+/-4 and 46+/-4 % HW loss at the four time-points. HT(x) of the failing heart resulted in even greater HW losses, of 46+/-4, 58+/-3, 66+/-2 and 68+/-4 %, respectively (P<0.05). Activation of "fetal gene cardiac program" (e.g. beta myosin heavy chain gene expression) and "genes reflecting cardiac remodeling" (e.g. atrial natriuretic peptide gene expression) after HT(x) was greater in failing than in healthy hearts (P<0.05 each time). Exposure to isocaloric high sugar diet caused significant increases in fatty acid concentrations in healthy and in failing hearts. However, these increases were not associated with any change in the course of cardiac atrophy, similarly in healthy and post-HT(x) failing hearts. We conclude that increasing heart tissue concentrations of the fatty acids allegedly involved in heart growth does not attenuate the unloading-induced cardiac atrophy.

Sensitivity to perioperative ischemia/reperfusion injury in male and female donor myocardium.

Many functions of the cardiovascular apparatus are affected by gender. The aim of our study was find out whether markers of cell death present in the donor myocardium differ in male and female hearts. The study involved 81 patients undergoing heart transplantation from September 2010 to January 2013. Patients were divided into two groups: male allograft (n=49), and female allograft (n=32). Two types of myocardial cell death were analyzed. High-sensitive cardiac troponin T as a necrosis marker and protein bcl-2, caspase 3 and TUNEL as apoptosis markers were measured. We observed a significantly higher level of high-sensitive cardiac troponin T after correcting for predicted ventricular mass in female donors before transplantation as well as in the female allograft group after transplantation throughout the monitored period (P=0.011). There were no differences in apoptosis markers (bcl-2, caspase 3, TUNEL) between male and female hearts before transplantation. Both genders showed a significant increase of TUNEL-positive myocytes one week after transplantation without differences between the groups. Moreover, there were no differences in caspase 3 and bcl-2 expression between the two groups. Our results demonstrated the presence of necrotic and apoptotic cell death in human heart allografts. High-sensitive cardiac troponin T adjusted for predicted ventricular mass as a marker of myocardial necrosis was higher in female donors, and this gender difference was even more pronounced after transplantation.

Circulating microparticles as a predictor of vascular properties in patients on mechanical circulatory support; hype or hope?

Microparticles are small circulating vesicles originating from circulatory system and vascular wall cells released during their activation or damage. They possess different roles in regulation of endothelial function, inflammation, thrombosis, angiogenesis, and in general, cellular stress. Microparticles are the subject of intensive research in pulmonary hypertension, atherosclerotic disease, and heart failure. Another recently emerging role is the evaluation of the status of vasculature in end-stage heart failure patients treated with implantable ventricular assist devices. In patients implanted as destination therapy, assessment of the long-term effect of currently used continuous-flow left ventricular assist devices (LVADs) on vasculature might be of critical importance. However, unique continuous flow pattern generated by LVADs makes it difficult to assess reliably the vascular function with most currently used methods, based mainly on ultrasound detection of changes of arterial dilatation during pulsatile flow. In this respect, the measurement of circulating microparticles as a marker of vascular status may help to elucidate both short- and long-term effects of LVADs on the vascular system. Because data regarding this topic are very limited, this review is focused on the advantages and caveats of the circulating microparticles as markers of vascular function in patients on continuous-flow LVADs.

Biomarkers of cellular apoptosis and necrosis in donor myocardium are not predictive of primary graft dysfunction.

Primary graft dysfunction (PGD) is a life-threatening complication among heart transplant recipients and a major cause of early mortality. Although the pathogenesis of PGD is still unclear, ischemia/reperfusion injury has been identified as a predominant factor. Both necrosis and apoptosis contribute to the loss of cardiomyocytes during ischemia/reperfusion injury, and this loss of cells can ultimately lead to PGD. The aim of our prospective study was to find out whether cell death, necrosis and apoptosis markers present in the donor myocardium can predict PGD. The prospective study involved 64 consecutive patients who underwent orthotopic heart transplantation at our institute between September 2010 and January 2013. High-sensitive cardiac troponin T (hs-cTnT) as a marker of minor myocardial necrosis was detected from arterial blood samples before the donor's pericardium was opened. Apoptosis (caspase-3, active + pro-caspase-3, bcl-2, TUNEL) was assessed from bioptic samples taken from the right ventricle prior graft harvesting. In our study, 14 % of transplant recipients developed PGD classified according to the standardized definition proposed by the ISHLT Working Group. We did not find differences between the groups in regard to hs-cTnT serum levels. The mean hs-cTnT value for the PGD group was 57.4+/-22.9 ng/l, compared to 68.4+/-10.8 ng/l in the group without PGD. The presence and severity of apoptosis in grafted hearts did not differ between grafts without PGD and hearts that subsequently developed PGD. In conclusion, our findings did not demonstrate any association between measured myocardial cell death, necrosis or apoptosis markers in donor myocardium and PGD in allograft recipients. More detailed investigations of cell death signaling pathways in transplanted hearts are required.

Endothelial dysfunction expressed as endothelial microparticles in patients with end-stage heart failure.

Left ventricular assist devices (LVAD), currently used in treatment of terminal heart failure, are working on principle of rotary pump, which generates continuous blood flow. Non-pulsatile flow is supposed to expose endothelial cells to high stress and potential damage. Therefore, we investigated longitudinal changes in concentration of circulating endothelial microparticles (EMP) as a possible marker of endothelial damage before and after implantation of LVAD. Study population comprised 30 patients with end-stage heart failure indicated for implantation of the Heart Mate II LVAD. Concentrations of microparticles were measured as nanomoles per liter relative to phosphatidylserine before and 3 months after implantation. At 3 months after implantation we observed significant decrease in concentration of EMP [5.89 (95 % CI 4.31-8.03) vs. 3.69 (95 % CI 2.70-5.03), p=0.03] in the whole group; there was no difference observed between patients with ischemic etiology of heart failure (n=18) and with heart failure of non-ischemic etiology (n=12). In addition, heart failure etiology had no effect on the rate of EMP concentration decrease with time. These results indicate possibility that LVAD do not cause vascular damage 3 months after implantation. Whether these results suggest improvement of vascular wall function and of endothelium is to be proved in long-term studies.

Ventricular assist devices in heart failure: how to support the heart but prevent atrophy?

Ventricular assist devices (VAD) have recently established themselves as an irreplaceable therapeutic modality of terminal heart failure. Because of the worldwide shortage of donors, ventricular assist devices play a key role in modern heart failure therapy. Some clinical data have revealed the possibility of cardiac recovery during VAD application. On the other hand, both clinical and experimental studies indicate the risk of the cardiac atrophy development, especially after prolonged mechanical unloading. Little is known about the specific mechanisms governing the unloading-induced cardiac atrophy and about the exact ultrastructural changes in cardiomyocytes, and even less is known about the ways in which possible therapeutical interventions may affect heart atrophy. One aim of this review was to present important aspects of the development of VAD-related cardiac atrophy in humans and we also review the most significant observations linking clinical data and those derived from studies using experimental models. The focus of this article was to review current methods applied to alleviate cardiac atrophy which follows mechanical unloading of the heart. Out of many pharmacological agents studied, only the selective beta2 agonist clenbuterol has been proved to have a significantly beneficial effect on unloading-induced atrophy. Mechanical means of atrophy alleviation also seem to be effective and promising.

Cardiac surgery increases serum concentrations of adipocyte fatty acid-binding protein and its mRNA expression in circulating monocytes but not in adipose tissue.

Adipocyte fatty acid binding protein (A-FABP) is a novel adipokine involved in the regulation of lipid and glucose metabolism and inflammation. To evaluate its potential role in the development of postoperative hyperglycemia and insulin resistance we assessed A-FABP serum concentrations and mRNA expression in skeletal and myocardial muscle, subcutaneous and epicardial adipose tissue and peripheral monocytes in 11 diabetic and 20 age- and sex-matched non-diabetic patients undergoing elective cardiac surgery. Baseline serum A-FABP did not differ between the groups (31.1+/-5.1 vs. 25.9+/-4.6 ng/ml, p=0.175). Cardiac surgery markedly increased serum A-FABP in both groups with a rapid peak at the end of surgery followed by a gradual decrease to baseline values during the next 48 h with no significant difference between the groups at any timepoint. These trends were analogous to postoperative excursions of plasma glucose, insulin and selected proinflammatory markers. Cardiac surgery increased A-FABP mRNA expression in peripheral monocytes, while no effect was observed in adipose tissue or muscle. Our data suggest that circulating A-FABP might be involved in the development of acute perioperative stress response, insulin resistance and hyperglycemia of critically ill irrespectively of the presence of diabetes mellitus.

[Abdominal complications in patients with implanted mechanical cardiac support]. / Abdominální komplikace u pacientu po implantaci mechanické srdecní podpory.

Patients with implanted mechanical cardiac support are exposed to the risk of various complications in the early postoperative period. Although thromboembolic and bleeding events occur most frequently in these patients, we cannot disregard other complications that can have a significant impact on the further development of the implanted patients condition. These include abdominal complications. Literature data show clearly that mortality in implanted patients who developed an abdominal complication is significantly higher than that in patients without postoperative abdominal complications.

Comparison of the effects of ketamine-dexmedetomidine and sevoflurane-sufentanil anesthesia on cardiac biomarkers after cardiac surgery: an observational study.

Inhalational anesthetics have demonstrated cardioprotective effects against myocardial ischemia-reperfusion injury. Clinical studies in cardiac surgery have supported these findings, although not with the consistency demonstrated in experimental studies. Recent investigations have questioned the advantages of inhalational over intravenous anesthetics with respect to cardiac protection. Ketamine has been shown to be comparable with sufentanil, and has even demonstrated anti-inflammatory properties. Dexmedetomidine has been established as a sedative/anesthetic drug with analgesic properties, and has also demonstrated myocardial protective effects. In this retrospective observational study, the influence of ketamine-dexmedetomidine-based anesthesia (KET-DEX group; n=17) on the release of cardiac biomarkers was compared with that of sevoflurane-sufentanil-based anesthesia (SEVO group; n=21) in patients undergoing elective coronary artery bypass grafting. Compared with the SEVO group, the KET-DEX group exhibited significantly reduced cardiac troponin I (2.22+/-1.73 vs. 3.63+/-2.37 microg/l; P=0.02) and myocardial fraction of creatine kinase (CK-MB) levels (12.4+/-10.4 vs. 20.3+/-11.2 microg/l; P=0.01) on the morning of the first postoperative day. Furthermore, cardiac troponin I release, evaluated as the area under the curve, was significantly reduced in the KET-DEX group (32.1+/-20.1 vs. 50.6+/-23.2; P=0.01). These results demonstrate the cardioprotective effects of ketamine-dexmedetomidine anesthesia compared with those of sevoflurane-sufentanil anesthesia.

Heart transplantations at the Heart Center IKEM, Prague, Czech Republic.

The heart transplant program at the Institute for Clinical and Experimental Medicine in Prague was established on January 31, 1984. Through November 2012, 881 orthotopic cardiac transplantations have been performed, with an annual rate of about 40 procedures. Current legislation concerning solid organ transplantations in the Czech Republic is described. Like other centers, we have noticed an increasing age of donors, and, reflecting the shortage of grafts, we have expanded our selection criteria for heart transplantation. The advent of a mechanical circulatory support program at our center in April 2003 has given us another valuable tool in the management of chronic heart failure patients. Currently, around half of our patients are transplanted from mechanical support. Nonischemic etiology of heart failure is a leading cause of transplantation at our center, followed by ischemic cardiomyopathy, valvular heart lesions, and adult congenital heart diseases. Our current immunosupression protocol, including induction therapy, is outlined in detail and survival rates, as well as most common complications and our treatment strategies, are also discussed.

Suppression of ischemic and reperfusion ventricular arrhythmias by inhalational anesthetic-induced preconditioning in the rat heart.

Inhalational anesthetic-induced preconditioning (APC) has been shown to reduce infarct size and attenuate contractile dysfunction caused by myocardial ischemia. Only a few studies have reported the effects of APC on arrhythmias during myocardial ischemia-reperfusion injury, focusing exclusively on reperfusion. Accordingly, the aim of the present study was to examine the influence of APC on ventricular arrhythmias evoked by regional no-flow ischemia. APC was induced in adult male Wistar rats by 12-min exposures to two different concentrations (0.5 and 1.0 MAC) of isoflurane followed by 30-min wash-out periods. Ventricular arrhythmias were assessed in the isolated perfused hearts during a 45-min regional ischemia and a subsequent 15-min reperfusion. Myocardial infarct size was determined after an additional 45 min of reperfusion. The incidence, severity and duration of ventricular arrhythmias during ischemia were markedly reduced by APC. The higher concentration of isoflurane had a larger effect on the incidence of ventricular fibrillation than the lower concentration. The incidence of ventricular tachycardia and reversible ventricular fibrillation during reperfusion was also significantly reduced by APC; the same was true for myocardial infarct size. In conclusion, we have shown that preconditioning with isoflurane confers profound protection against myocardial ischemia- and reperfusion-induced arrhythmias and lethal myocardial injury.

Is severe pulmonary hypertension a contraindication for orthotopic heart transplantation? Not any more.

Pulmonary hypertension (PH) unresponsive to pharmacological intervention is considered a contraindication for orthotopic heart transplantation (OHTX) due to risk of postoperative right-heart failure. In this prospective study, we describe our experience with a treatment strategy of improving severe PH in heart transplant candidates by means of ventricular assist device (VAD) implantation and subsequent OHTX. In 11 heart transplantation candidates with severe PH unresponsive to pharmacological intervention we implanted VAD with the aim of achieving PH to values acceptable for OHTX. In all patients we observed significant drop in pulmonary pressures, PVR and TPG (p < 0.001 for all) 3 months after VAD implantation to values sufficient to allow OHTX. Seven patients underwent transplantation (mean duration of support 216 days) while none of patients suffered right-side heart failure in postoperative period. Two patients died after transplantation and five patients are living in very good condition with a mean duration of 286 days after OHTX. In our opinion, severe PH is not a contraindication for orthotopic heart transplantation any more.

Increased circulating and epicardial adipose tissue mRNA expression of fibroblast growth factor-21 after cardiac surgery: possible role in postoperative inflammatory response and insulin resistance.

We studied the changes in serum fibroblast growth factor-21 (FGF-21) concentrations, its mRNA, and protein expression in skeletal muscle and adipose tissue of 15 patients undergoing cardiac surgery. Blood samples were obtained: prior to initiation of anesthesia, prior to the start of extracorporeal circulation, upon completion of the surgery, and 6, 24, 48, and 96 hours after the end of the surgery. Tissue sampling was performed at the start and end of surgery. The mean baseline serum FGF-21 concentration was 63.1 (43.03-113.95) pg/ml and it increased during surgery with peak 6 hours after its end [385.5 (274.55-761.65) pg/ml, p < 0.001], and returned to baseline value [41.4 (29.15-142.83) pg/ml] 96 hours after the end of the surgery. Serum glucose, insulin, CRP, IL-6, IL-8, MCP-1, and TNF-alpha concentrations significantly increased during the surgery. Baseline FGF-21 mRNA expression in skeletal muscle was higher than in both adipose tissue depots and it was not affected by the surgery. Epicardial fat FGF-21 mRNA increased after surgery. Muscle FGF-21 mRNA positively correlated with blood glucose levels at the end of the surgery. Our data suggest a possible role of FGF-21 in the regulation of glucose metabolism and insulin sensitivity in surgery-related stress.

[Technique of implantation and experience with temporary mechanical cardiac support in right ventricular failure]. / Technika implantace a zkusenosti s docasnou mechanickou srdecní podporou pri selhání pravé komory.

AIM: Severe right heart failure remains unfrequent but fatal complication of cardiac surgical procedures. Implantation of temporary right ventricular assist device may be life-saving procedure in various situations of right heart failure as: heart transplantation, LVAD therapy and post-cardiotomy failure. The aim of the study is an introduction of the implantation technique and retrospective review of current experience with the method. MATERIAL AND METHODS: Since January 2007 isolated right ventricular assist device Levitronix CentriMag has been implanted in 16 patients. Patients were divided into 3 groups: post transplantation (post-Tx), post LVAD implantation (post-LVAD) and other cardiac procedures (OCP). Success rate of weaning from RVAD, 30-days mortality and major complications has been assessed. OUTCOMES: Distribution of implants in groups was: post-Tx 5 pts (31%), post-LVAD 6 pts (38%) and 5 in OCP group (31%). The mean support time was 12 days. Off-pump implantation was achieved in 9 pts. The device was successfully weaned in 13 (81%) patients. 30-days mortality occurred in 1 case only. CONCLUSION: Presented outcomes are encouraging for broader acceptance of the therapy. Excellent success rate has been reached in post-Tx and post-LVAD. This study emphasises decesive role of proactive approach in early indication of RVAD implantation for achieving satisfactory results.

[Outcomes of combined mitral valve repair surgery and aortic valve replacement in IKEM Praha]. / Výsledky kombinované plastiky mitrální a náhrady aortální chlopne v IKEM Praha.

AIM OF THE STUDY: We retrospectively analyzed long-term outcome of concomitant mitral valve repair and aortic valve replacement. METHODS: From 1996 to 2009 we performed mitral valve plasty with aortic valve replacement in 50 patients. Clinical and echocardiographic data were obtained from computer database and hospital records. Missing data were obtained through mailed questionnaire. We evaluated hospital mortality, long-term survival, thromboembolic and hemorrhagic complications and TR of 3+ on follow up echocardiography. RESULTS: Four patients who had previously undergone aortic valve surgery were excluded from the study. Aortic valve pathology was stenosis in 21 patients, regurgitation in 20 and 4 patients presented with mixed aortic disease. The etiology of mitral regurgitation was rheumatic in 6, non-rheumatic in 31 and infective in 6 patients. Aortic valve was replaced with mechanical prosthesis in 22 (mean age 59) and tissue prosthesis in 24 (mean age 71) patients. Additional surgical procedure was performed in 26 patients. Follow-up was 94% complete, with a mean duration of 51 months. Hospital mortality was 13%. Two and five year survival was 79% and 64% respectively. We noted one case of retroperitoneal hemorrhage and one stroke. We recorded 9 (19.6%) patients with residual TR of more than 3+ grade on follow up echocardiography. Out of 9 patients with residual TR, 3 were operated for rheumatic and 6 for non-rheumatic mitral valve disease. One patients underwent successful mitral valve replacement with mechanical prosthesis, 3 died and 5 are treated expectantly. CONCLUSION: We conclude that concomitant mitral valve repair with aortic valve replacement has high hospital mortality, excellent long-term survival and low complication rate. The durability of mitral valve repair in patients with rheumatic mitral valve disease is limited and replacement, rather that repair should be considered in this patient group.