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OBJECTIVES: In the present study, we aimed to deterimine the dose-related effects of ticagrelor, the first reversible inhibitor of the P2Y(12) receptor, found in smooth muscle cells as well as platelets, during neointimal hyperplasia in a rabbit carotid anastomosis model. METHODS: This study was an experimental, prospective, randomized controlled study including 20 New Zealand white female rabbits (6-months old; weighing 2300 +/- 300 g). Under general anaesthesia, the rabbits underwent transection of the right carotid artery and subsequent anastomosis of both ends. The study animals were divided into the following 4 groups: T1 (ticagrelor 5 mg/kg, orally, daily), T2 (ticagrelor 10 mg/kg, orally, daily), T3 (ticagrelor 20 mg/kg, orally, daily) and control (no ticagrelor treatment). The single oral doses were administered in phosphate-buffered saline. The control group received sterile phosphate-buffered saline (2 ml/kg/day, orally) for 3 weeks postoperatively. At the end of the study, the animals were killed, and the anastomosed segment of the right carotid artery and part of the left carotid artery were excised from each animal. Antibodies against transforming growth factor-beta were used in staining of arterial sections, which was followed by histomorphological and immunohistochemical studies. RESULTS: The median intimal thickness (2.0 +/- 0.14 m left vs 73.4 +/- 35.8 m anastomosed right arteries; P

We read with great interest the article by Song and co-workers [1]. We would like to congratulate the authors on their well-designed study with an important message that intraoperative hyperglycaemia >150 mg/dl and high glycaemic variability were independent risk factors of renal dysfunction after off-pump coronary artery bypass surgery, but would also like to add some comments. Intraoperative hyperglycaemia, which occurs frequently in cardiac surgical patients with and without diabetes, has been shown to be associated with increased morbidity and mortality. These patients are exposed to significant adverse consequences including surgical site infection, neurologic, renal, and cardiac complications as well as longer intensive care unit and hospital stay. In recent years, glycaemic control during coronary artery bypass surgery and all cardiac surgical procedures has been the focus of interest. However, an optimal value for glycaemic control has yet to be fully elucidated. Moreover, there are clear potential adverse consequences of tight glycaemic control such as hypoglycaemia [2]. In cardiac surgical patients, a number of observational studies have specifically investigated the effect of intraoperative glycaemic control on outcomes. These studies have suggested an association between greater glycaemic control and improved outcomes. While prospective randomized trials have been promising, the results have been less robust [2-4]. Successful glycaemic control requires a multidisciplinary approach, which includes representation from nursing, anesthesiology, pharmacy, surgery, and endocrinology. All studies have shown that maintaining serum glucose levels

In cardiovascular practice today, the axillary artery is one of the best alternative cannulation sites in acute type A aortic dissection [1]. It provides potential benefits such as antegrade perfusion of the aorta, low risk of false lumen perfusion in aortic dissection, and the possibility of antegrade cerebral perfusion during aortic arch repair. Indications of axillary cannulation also includes porcelain aorta, ascending aorta and aortic arch aneurysm, coronary artery disease associated with severely atherosclerotic ascending aorta, extracorporeal membrane oxygenation support, and complex redo cardiac surgery such as aortic regurgitation after previous ascending aortic replacement and pseudo-aneurysm after Bentall operation. We read with great interest the article by Fong and associates [2], regarding liberal use of axillary artery cannulation for cardiopulmonary bypass in aortic and complex cardiac surgical patients. We mostly agree with their considerations. However, we believe that some aspects of the article require further comment. Direct or graft-interposed axillary cannulation still remains a controversial issue among the cardiovascular surgeons. We routinely prefer direct right axillary cannulation in acute type A aortic dissections in our institute [3]. In our practice, there were no major complications related to this cannulation technique. In our opinion, direct axillary cannulation is not more traumatic, is less time-consuming, and less haemorrhagic during the operation than the graft interposition. Axillary cannulation is not always free from risk. Complications related to axillary cannulation are becoming associated with increased use of this technique [4]. These include ipsilateral brachial plexus injury resulting in hand weakness and numbness, axillary artery thrombosis, lymphocele requiring aspiration, vascular compromise, compartment syndrome involving the forearm, postoperative bleeding or local wound infection. Acute intraoperative aortic dissection due to the arterial cannulation into the axillary artery is a rare and devastating complication [5]. It is believed to be due to an intimal flap occurring during cannula insertion. As a strategy to prevent these complications, the arterial cannula should not be advanced too much during the right axillary cannulation. Forced cannulation should also be absolutely avoided. It may cause arterial injury or obstruct the right carotid artery. In our experience, a 20F or 22F flexible cannula was gently advanced 3-4 cm into the axillary artery. In strategic planning for arterial cannulation, transoesophageal echocardiography (TEE) guidance is useful to ensure correct placement of the cannula. An angiograhic, TEE or ultrasound examination plays an important role in preoperative evaluation including aortic branch vessels Axillary cannulation is an attractive and useful approach with an extended utilization, and may be safely used in aortic surgery and complex cardiac procedures including redo surgery. Conflict of interest: none declared.

We read with great interest the paper by Singh et al [1]. They described surgical treatment including proximal ligation and plication of the aneurysm with coronary artery bypass grafting in a series of 4 cases of coronary artery aneurysm (CAA) from a single centre. We would like to congratulate the authors for bringing such a rare entity to our attention. We would also like to add a short comment on this topic. Coronary artery dilatation is an exceptional and frequently unrecognized incidental finding in patients with coronary artery disease [2]. At present there is no uniform definition of this pathology. Coronary artery ectasia (CAE) and CAA are characterized by an abnormal dilatation of the coronary artery. They are used interchangeably for the condition. CAE may be classified into four types on basis of the extent of coronary artery involvement: Type I - diffuse ectasia of two or three vessels; Type II - diffuse ectasia in one vessel and localised disease (ie, aneurysm) in another; Type III - diffuse ectasia in one vessel only, and; Type IV - localised or segmental involvement (CAA) only [3]. This classification may have prognostic implications, with the worst outcomes in types I and II [2]. CAA may be classified in three different ways on the basis of the composition of the vessel wall (true aneurysms or pseudoaneurysms), the morphologic structure (saccular or fusiform aneurysms), and size (e.g., large or giant aneurysms) [2]. The various factors contributing to CAA formation include atherosclerosis, congenital malformations, Kawasaki disease, percutaneous coronary interventions, inflammatory arterial diseases (polyarteritis nodosa, systemic lupus erythematosus, Takayasu's arteritis), infectious causes (endocarditis, syphilis, candidosis, Lyme borreliosis), chest traumas, vasculitis (eg, Behcet disease), connective tissue disorders (Marfan's syndrome, Ehlers Danlos syndrome, scleroderma), primary cardiac lymphoma and primary hyperaldosteronism [2]. CAE is used to describe diffuse dilatation (>1.5 times the normal diameter) of the coronary arteries that involves 50% or more of the length of the vessel. However, CAA is defined as a localized dilatation that exceeds the diameter of normal adjacent coronary artery segments, or the diameter of the patient's largest coronary vessel by 1.5 times. Herein, coronary artery involment is less than 50% of the total length of the vessel [2]. A giant aneurysm is defined as one where the maximal vessel diameter exceeds 20 mm in adults or 8 mm in children. In adults, the reported diameter of giant CAAs varies from 50 to 150 mm. Giant CAAs are rare, with a reported prevalence of 0.02% [4]. Potential complications include rupture (subsequent cardiac tamponade), thrombosis, embolization, dissection, mechanical obstruction, and erosion into surrounding structures. In these patients, surgery should be considered as a means to avoid complications [5]. Conflict of interest: none declared

With the increasing age of the general population, the necessity for cardiac surgery in nonagenarians is also increasing, and this population shows a high incidence of degenerative calcific aortic stenosis (AS). Thus, cardiovascular surgeons are faced with the fact that an increasing number of very elderly patients are referred for aortic valve replacement (AVR). However, decision-making on nonagenarians is difficult due to the lack of clinical experience or evidence-based results upon which to develop optimal treatment alternatives. It should be based on careful assessment of the wishes of the patient and family, the relative medical risks and benefits, and the economic costs of the alternatives [1–3]. I read with great interest the article by Assmann and colleagues [4]. The authors have shared with us their results of 49 consecutive cardiac surgical operations in nonagenarians. They reported a remarkable postoperative morbidity and an overall in-hospital mortality of 10%, including 13% in the AVR subgroup. I fully agree with their conclusions regarding nonagenarians and would also like to add a brief comment on this topic. Owing to improvements in preoperative and postoperative care, AVR in selected nonagenarians may be performed with an acceptable mortality. Age itself should not be a contraindication to surgery or an indication for transcatheter aortic valve implantation (TAVI). The choice of therapeutic plan for those patients justifies a multidisciplinary approach. Today, approximately one-third of elderly patients with severe AS are not referred for surgery because of the high perioperative risk perceived by both patients and physicians. Recently, TAVI as an alternative modality to surgery has emerged in these high-risk patients. However, the safety and effectiveness of TAVI in nonagenarians has not been fully elucidated [5]. Furthermore, TAVI is associated with a higher incidence of major stroke, atrioventricular conduction system injury and major vascular complications. Although AVR in nonagenarians can be performed successfully in selected patients, increased mortality and morbidity rates, as well as prolonged length of stay, are associated with this age group [1, 2]. In the literature, reported morbidity rates are as high as 100%, and mortality is reported to range between 7% and 18% [1–3]. Edwards and Taylor [2] reported that in 35 nonagenarians who had undergone AVR, there was an apparent significantly higher risk of early mortality (17%) and morbidity (77%). The most recent study on nonagenarians by Easo et al. [3] showed an in-hospital mortality of 17.6% and a postoperative morbidity of 58%. In this age group, careful preoperative clinical evaluation combined with the use of risk scoring enables an adequate selection of low-risk patients who are suitable candidates for AVR, with excellent outcomes [3]. In recent years, economic considerations (scarce health care resources) and ethical factors have also come to play an important role in the decision-making regarding surgical AVR in nonagenarians. In summary, I think that by using appropriate selection criteria, AVR may be performed successfully in nonagenarians without prohibitive cost and with acceptable long-term survival and quality of life. It would therefore seem reasonable to operate on nonagenarians. Conflict of interest: none declared

Conventional aortic valve replacement (AVR) carries significant operative risks, especially in the elderly, high-risk patients with severe aortic valve stenosis including porcelain ascending aorta, complex left ventricular outflow tract obstruction, previous cardiac surgery (patent coronary grafts) or prior sternal infection, and previous radiation to the mediastinum. Transcatheter aortic valve implantation (TAVI) is an alternative therapeutic option in these complicated situations. Nevertheless, TAVI has some limitations in patients with severe aorto-iliac disease, small aortic annulus (

I read with great interest the paper by Smulter et al. [1]. The authors aimed at determining the incidence of and risk factors for postoperative delirium (POD), in older patients undergoing cardiac surgery. They reported an incidence of POD of 54.9% and confirmed many of the previously suggested risk factors. In their study, POD was strongly associated with an increased volume load during surgery. I would like to add some comment on this important topic. POD is a common and serious complication in elderly cardiac surgery patients. It is defined as an acute and fluctuating disturbance in consciousness, characterized by disorientation, a disturbed sleep-wake cycle, memory impairment, perceptual disturbances, and altered psychomotor activity [2,3]. POD is an important cause of prolonged hospital stay (economic burden), nursing home placement, and increased morbidity and mortality after cardiovascular surgery. In addition, it is associated with late death, hospital readmission, and reduced cognitive and functional recovery. The reported incidence of POD ranges from 30 to 73% depending on the diagnostic method used to define POD, study design, and type of cardiovascular procedure [2-a5]. The exact pathophysiology of POD is unknown. There are several potential mechanisms including perioperative cerebral hypoperfusion, alterations in the levels of neurotransmitters, systemic inflammation and physiologic stresses. This pathophysiologic complexity contributes to high incidence of POD [3,4]. Elderly cardiac surgery patients are at a particularly high risk for POD owing to the use of cardiopulmonary bypass, the presence of macro- or microemboli resulting from aortic and cardiac manipulation, the complexity and duration of surgical procedure, cerebral reperfusion injury, and large volume and pressure shifts [3]. The likelihood of developing POD increases proportionally with the number of existing risk factors [4]. Identification of risk factors for developing POD allows surgeons to implement interventions aimed at reducing the incidence of POD in these high risk patients. There are many patient (predisposing) and surgery (precipitating) risk factors related to POD. These risk factors include advanced age, pre-existing dementia, depression, functional impairment, cognitive impairment, hearing and visual impairment, alcohol abuse, smoking, decreased left ventricular ejection fraction, pre-existing pulmonary disease, hypertension, atrial fibrillation, laboratory abnormalities, cerebrovascular disease, decreased albumin level, lower hematocrit, postoperative hypotension and increased blood transfusion [2-5]. The most critical steps in management of POD are prevention and early recognition. Both prevention and treatment should focus on the minimization and/or elimination of predisposing and precipitating factors. There is currently no accepted preventive treatment for POD. Due to the multifactorial nature of POD, approaches which include strategies from multiple disciplines are the most effective in its prevention [5]. To prevent POD in high-risk patients, it should be focused on environmental modifications, psychoactive medication reduction, early mobilization, and prevention of complications [3]. Ten targeted domains to reduce delirium include (1) oxygen delivery to the brain, (2) fluid and electrolyte balance, (3) appropriate pain management, (4) decreased use of psychoactive medications, (5) optimization of bowel and bladder function, (6) nutritional support, (7) early mobilization, (8) prevention of postoperative complications, (9) appropriate environmental stimuli, and (10) treatment of delirium symptoms [5]. I think that recognition of early clinical signs and risk factors could be helpful for prevention and treatment, resulting in better outcomes. Conflict of interest: none declared

Functional tricuspid regurgitation (FTR) is a neglected and underestimated pathology. It occurs mostly from annular dilatation and right ventricular enlargement, which is frequent secondary to left-sided heart failure from myocardial or valvular causes, right ventricular volume and pressure overload, and dilatation of the cardiac chambers. Moderate-to-severe FTR should be corrected to improve short- and long-term outcomes in patients undergoing surgery for left-sided valvular diseases. Tricuspid annuloplasty is a safe and effective surgical option for FTR and seems to be associated with an improvement in both functional status and survival. I read with great interest the paper by Iida et al. [1]. They described a novel technique of adjustable annuloplasty for FTR employed in 11 patients. In their technique, an expanded polytetrafluoroethylene thread was passed inside the cover cloth of a flexible annuloplasty band. They tightened the thread with extracardiac control on beating heart under observation by transoesophageal echocardiography (TEE) after weaning off cardiopulmonary bypass (CPB). I would like to add a short comment on this annuloplasty technique. For the last four decades, various repair techniques have been described for the surgical correction of FTR with severe tricuspid annular dilatation. These broadly include ring annuloplasties (flexible and rigid prosthetic rings or three-dimensional rings, flexible prosthetic bands) and suture annuloplasties such as bicuspidization (Kay annuloplasty) or semicircular (De Vega annulopasty). Other approaches may include the edge-to-edge technique (Alfieri-type) or anterior tricuspid leaflet augmentation to increase leaflet coaptation and relief of tethered leaflets [2]. The selection of the appropriate repair is the most important issue in the management of FTR. Although ring annuloplasty seems to increase durability of valve repair, the De Vega annuloplasty modifications are still advocated because of their good results. To adjust the constriction of tricuspid annulus on the beating heart, after discontinuation of CPB, Alonso-Lej [3] described an adjustable modification of the De Vega annuloplasty. Herein, extracardiac control of suture annuloplasty was gained by taking both ends of the suture through the wall of the right atrium after weaning off CPB. The degree of tricuspid regurgitation now is evaluated solely with TEE rather than with digital palpation [3]. Adjustable segmental tricuspid annuloplasty is a new modified technique that tries to reduce the incidence of failure in the De Vega annuloplasty and adjusts and distributes the pursing forces in the more dilated area. Sarraj et al. [4] have used two separate sutures, and they have chosen the middle point between the anteroseptal commissure and posteroseptal commissure to perform the purse-string technique. These new modifications make the technique more selective in the remodelling of the tricuspid annulus. Choi et al. [5] described a modified technique of tricuspid ring annuloplasty to reduce postoperative residual regurgitation in patients with FTR; first, an adjustable segmental tricuspid annuloplasty is performed to obtain coaptation of the valve leaflets with two 5-0 monofilament annular sutures, and then a prosthetic ring of the same size as the competent valve area is implanted with continuous 3-0 poly㯲opylene sutures. Finally, I think that continued follow-up should be mandatory for confirming the effectiveness of these tricuspid annuloplasty techniques. Conflict of interest: none declared

The clinical spectrum of acute myocardial infarction (MI) may alter from ST elevation MI (STEMI) to non-ST elevation MI (NSTEMI) or unstable angina. It has commonly been suggested that early coronary artery bypass surgery (CABG) after acute MI may be associated with increased morbidity and mortality. However, advances in technology, surgical methods and myocardial protection techniques provide a chance for cardiovascular surgeon to achieve treatment of all these clinical scenarios [1]. We read with great interest the paper by Dayan and colleagues [2]. The authors have attempted to seek the answers to an important question: Does early CABG improve survival in NSTEMI? They concluded that CABG may be safely performed in patients with NSTEMI at any time after the first 6 h of MI in patients with cTnI

We read with great interest the article by Li et al. [1]. They performed a comprehensive literature search including 194 cases of intracardiac leiomyomatosis. We also would like to add some comments on misdiagnosis of this complicated pathology. Intravenous leiomyomatosis (IVL) is a rare neoplastic disease, which is characterized by intravenous growth of histologically benign, smooth muscle tumours arising from either a uterine myoma or from the wall of a uterine vessel [2, 3]. The tumour usually enters through the lumen of the iliac vein and extends upward to varying locations, including the inferior vena cava, adrenal and renal veins, right heart (intracardiac leiomyomatosis) and pulmonary artery. It is an insidious process and may lead to heart failure, pulmonary embolization, or even sudden cardiac death. Intracardiac extension may be easily misdiagnosed as either a primary cardiac tumour or a venous thrombus-in-transit. Misdiagnosis subsequently may lead to improper treatment [2, 4, 5]. Differential diagnosis of right-sided cardiac masses includes thrombi-in-transit, right atrial myxomas, vegetations on the tricuspid valve, primary caval leiomyosarcoma, intracardiac electrodes, and tumour thrombi from malignancies such as hepatocellular carcinoma, renal cell carcinoma, Wilms' tumour (in children), and others [3, 4]. IVL may be diagnosed by echocardiography, abdominal ultrasound, magnetic resonance imaging, enhanced chest and abdominal computed tomography, and venography. The diagnosis is confirmed intraoperatively or by postoperative histopathological examination [3, 5]. A thrombus-in-transit appears as an elongated mobile mass of venous cast giving a "popcorn" appearance within the right-sided cardiac chamber, whereas there are multiple points of attachment in the inferior vena cava and right-sided cardiac chambers in patients with IVL [8]. A correct diagnosis depends on a high index of suspicion. This pathology should be considered in young women with a right-sided cardiac mass and a pelvic mass or those who have previously undergone hysterectomy for uterus leiomyoma [2, 3, 5]. Finally, we think that IVL is an underdiagnosed pathology and a huge index of clinical doubt with the modern diagnostic imaging tools will lead to an increased number of reported cases in the future. Conflict of interest: none declared.

We read the article by Pagni et al. [1] with great interest. The authors have documented a case of aorto-right atrial fistulization after type A aortic dissection well. We think that the discussion should be primarily focused on fistulous complications of acute ascending aortic dissection, occurring after previous cardiac or aortic surgery. Acute dissection of the ascending aorta is a life-threatening pathology and may lead to serious complications. They include rupture to neighbouring structures, aortic insufficiency, haemothorax, haemopericardium, and occlusion of the major vessels originating from the aorta [2-5]. These complications may occur as the false lumen enlarges. Free rupture of aortic dissection into the pleural and pericardial spaces often results in sudden cardiovascular collapse and death. Fistulization to the cardiac chambers (right atrium, left atrium, and right ventricle) and the pulmonary artery is a rare and often fatal occurrence [2-5]. Fistulous complications can be explained by considering the anatomy of the aortic root. Aortopulmonary, aorta-right atrial, and aorta-right ventricular fistulas produce a left-to-right shunt and congestive heart failure. Pagni et al. [1] have reported a right-to-left shunt depending on the patent foramen ovale. Fistulous complications of aortic dissection may occur in any patient, especially in those with a history of previous cardiac or aortic surgery [2-5]. The incidence of fistulous formation tends to increase with redo surgery. Postoperative adhesions may play an important role in the pathogenetic mechanism of the fistula. In such patients, the dense adhesions probably restrain the free rupture and contribute to the fistulous occurrence. Undoubtedly, prompt diagnosis and early surgical repair of the dissection and fistula would provide for an excellent outcome. In such complicated situations, we think that one should use all the information and imaging techniques available to provide a timely diagnosis and treatment. Conflict of interest: none declared.