**5. Factors affecting long-term outcome after AVR**

	- **◦** Older age
	- **◦** Male sex

**Bleeding event** – Formerly classified as anti-coagulant hemorrhage, a bleeding event is an episode of major internal or external bleeding that causes death, hospitalization, and perma‐ nent injury or requires transfusion. This definition applies to all patients, irrespective of anticoagulation status. *Mechanical valves* are durability but anticoagulation is key of long-term success. International Normalized Ratio (INR) is the standard to which anticoagulation levels should be targeted. Level of INR should be individual for each person. Complications occur during fluctuations in the INR and less during steady-state levels, be they high or low.[30,31] When levels of INR increase, bleeding episodes become more common, and when levels of INR decrease thromboembolic episodes become more common. Some studies showed that around 40 % of the bleeding episodes occurred in the first year after surgery, when levels of INR are more likely to fluctuate. Many studies suggested that in the early postoperative period slowly raise the level of INR to therapeutic levels is needed, to prevent bleeding events. [21,32,33] According to ACC and ACH after mechanical AVR, the goal of antithrombotic therapy is usually to achieve an INR of 2.5 to 3.5 for the first 3 months after surgery and 2.0 to 3.0 beyond that time. At that level of anticoagulation, the risk of significant hemorrhage appears to be 1% to 2% per year.7 Low-dose aspirin is also indicated in addition to warfarin to result in a lower incidence of thromboembolic event, with a low possibility for bleeding.[34] Older patients are at higher risk for thromboembolic event because of the greater number of risk factors that accumulate with aging.[30] Anticoagulation-related hemorrhage (ARH) is the most common valve-related event. More often it will occur during fluctuations in INR, which happens most often early after valve replacement.[21,22] The most common places for ARH are gastrointestinal tract and central nervous system.[21] Acceptable ARH rates range from 1.0 to 2.5% per patient-year in long term reports.[21,22,25,35] It is very dangerous complication, because mortality more often occurs in relation to bleeding events than in relation to throm‐

**Operative mortality** – Operative mortality is defined as all-cause mortality within 30 days of operation. According to the Society of Thoracic Surgeons mortality for isolated AVR is 4.3% and for AVR with concomitant coronary artery disease is 8%.[36] Many factors have been associated with an increased risk of operative mortality in isolated AVR. Some of these risk factors are age, female gender, diabetes, renal failure, and emergency status, previous operation, advanced preoperative NYHA class, lower cardiac index, concomitant coronary artery bypass grafting and longer aortic crossclamp and cardiopulmonary bypass time respectively.[37] In the absence of major comorbidities and preserved ejection fraction, isolated

Several studies have evaluated independent risk factors for operative mortality after AVR. Five variables predictive of increased mortality risk after AVR are common to each of these analyses: preoperative renal failure, urgency of AVR, preoperative heart failure, presence of CAD or recent MI, and redo cardiac operation. Other factors independently associated with operative mortality from the individual studies include preoperative atrial fibrillation, active endocarditis, preoperative stroke, advanced age, lower body surface area, multiple valve

AVR can be performed with an expected mortality of less than 2%.[38]

boembolic events.[21]

370 Calcific Aortic Valve Disease

procedures, and hypertension. [39, 40]

	- **◦** Longer cardiopulmonary bypass time
	- **◦** Previous myocardial infarction
	- **◦** Left ventricular structure and functional abnormality
	- **◦** Previous aortic valve surgery
	- **◦** Coronary artery disease (CAD)

Older patients have a lot of comorbiditis and they are at higher risk for valve-related events. Atrial fibrillation is one of the risk factor for thromboembolism, because of that INR levels must be higher (INR 2.5 to 3.5) than regular.[30,34] The majority of patients undergoing AVR have other cardiac lesions, most commonly CAD, and more complex pathology has been associated with increased risk. Combined myocardial revascularization and AVR increases cross-clamp time and has the potential to increase perioperative myocardial infarction and early postoperative mortality compared with patients undergoing isolated AVR.7 In addition to severity of CAD and AS, the multivariate factors for late postoperative mortality include low ejection fraction, severity of LV dysfunction, age greater than 70 years (especially in women), and presence of NYHA functional class IV symptoms.[36]
