PubMed HealthSearch

Biomedical subjects

J Ivanov

Publications and source records attributed to J Ivanov.

At least 19 recordsLinked to original sources

Operative risks and long-term results of operation for left ventricular aneurysm.

A review of 336 consecutive patients who underwent repair of left ventricular aneurysm from 1978 to 1989 disclosed that partial resection of the aneurysm and conventional closure of the ventriculotomy was performed in 281 patients, inverted T closure in 17, and endocardial patch in 38. These two latter techniques were developed in an attempt to restore normal left ventricular geometry. The operative mortality was 6.8% (23 patients). A stepwise logistic regression analysis of various preopeative clinical, hemodynamic, and angiographic variables revealed that left ventricular ejection fraction of 0.20 or less, age greater than 60 years, previous myocardial revascularization, lack of angina, and New York Heart Association functional class IV were independent predictors of operative mortality. The technique of repair was not a predictor of outcome, but when patients with poor left ventricular function were analyzed separately, the operative mortality was reduced from 12.5% to 6.5% when newer techniques were employed. Patients were followed up during a mean of 6.3 years. There have been 51 late deaths, 45 cardiac. Cox regression analysis indicated that poor left ventricular function and left main coronary artery stenosis were the only two predictors of late mortality. The actuarial survival at 10 years was 63% +/- 4%. Most patients (88%) are in New York Heart Association class I or II. These data indicate excellent long-term results after repair of left ventricular aneurysm. Newer techniques of repair are valuable in patients with poor left ventricular function.

Actuarial Analysis

Alternative techniques of cardioplegia.

BACKGROUND: Although normothermic cardioplegia has been used with acceptable clinical results, no studies have previously been performed to determine the metabolic consequences of these various techniques of myocardial protection. Therefore, we have performed a randomized clinical trial to assess the effects of three cardioplegic techniques on myocardial metabolic recovery. METHODS AND RESULTS: Seventy-four patients undergoing coronary artery bypass graft surgery were randomized to receive normothermic antegrade blood cardioplegia (n = 25), normothermic retrograde blood cardioplegia (n = 23), or intermittent cold antegrade blood cardioplegia (n = 26). Myocardial oxygen consumption and lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during the operation, and cardiac creatine kinase isoenzyme (CK-MB) release was assessed after surgery. Warm antegrade cardioplegia maximized myocardial oxygen consumption during cardioplegic delivery. Postoperative CK-MB release was less after warm antegrade cardioplegia, but the difference was not statistically significant. Warm retrograde cardioplegia resulted in the greatest degree of anaerobic lactate production but did not increase morbidity and mortality. Perioperative myocardial infarctions and postoperative low-output syndrome were most common after cold cardioplegia, but this trend was not statistically significant. During warm antegrade cardioplegia, adenosine triphosphate (ATP) was metabolized to diffusible precursors, which were washed out during cardioplegic infusion. Warm retrograde cardioplegia produced a breakdown of ATP to inosine and hypoxanthine, small molecules that accumulated during the cross-clamp period and were not washed out, perhaps because of inadequate perfusion with retrograde delivery. During cold cardioplegia, ATP was dephosphorylated, and adenosine diphosphate, adenosine monophosphate, and adenosine accumulated. These compounds were not regenerated to ATP but were not washed out of myocytes because they are large anionic molecules. CONCLUSIONS: Intermittent cold cardioplegia inhibited mitochondrial function but prevented the degradation of adenine nucleotides. Warm antegrade cardioplegia had the greatest myocardial oxygen consumption, and warm retrograde cardioplegia had the greatest anaerobic lactate production. There were no differences in clinical outcomes between cardioplegic groups.

Adenosine Triphosphate

Coronary artery bypass grafting in patients with poor ventricular function. Cardiovascular Surgeons of the University of Toronto.

Although patients with severe ventricular dysfunction have improved long-term survival times after coronary bypass procedures, operative morbidity and mortality rates remain high. This study was designed to identify the contemporary risk factors for isolated coronary artery bypass grafting in this high-risk subgroup. Between January 1982 and December 1990, a total of 12,471 patients underwent isolated coronary artery bypass grafting. The 9445 patients with preoperative ejection fractions greater than 40% had a lower operative mortality rate (2.3%) than that of the 2539 patients with ejection fractions between 20% and 40% (4.8%) and that of the 487 patients with ejection fractions less than 20% (9.8%; p less than 0.001). However, patients with ejection fractions of less than 20% were demographically distinct from those with higher ejection fractions. This group was older, with fewer women, a higher frequency of left main stenosis, and more frequent requirement of urgent operation for unstable angina. The risk factors for operative death also varied with preoperative ejection fraction. The traditionally accepted risk factors--urgency of operation, left main coronary artery stenosis, reoperation, sex, and age--were predictive of risk of operative death for patients with ejection fractions greater than 40%. The risk of operative death for patients with ejection fractions between 20% and 40% was predicted by urgency of operation, reoperation, sex, myocardial protection, and age. The only predictor of risk of operative death for patients with ejection fractions less than 20% was urgency of operation. Patients undergoing isolated coronary artery bypass grafting who have severe ventricular dysfunction are therefore a highly selected, high-risk subgroup of patients who risk depends on the urgency of operation. Strategies to improve the results in these patients should be focused on patient selection, improvement of myocardial protection, and more aggressive preoperative treatment of myocardial ischemia.

Age Factors

The effect of warm heart surgery on postoperative bleeding.

The effects of normothermic systemic perfusion (35 degrees to 37 degrees C; n = 73) were compared with those of moderately hypothermic systemic perfusion (25 degrees to 29 degrees C; n = 73) with respect to blood loss, transfusion requirements, and platelet levels in 146 patients undergoing isolated, primary coronary artery bypass grafting. In addition, most patients were given an antifibrinolytic medication during operation as follows: tranexamic acid (10 gm intravenously; n = 63), epsilon-aminocaproic acid (15 gm intravenously; n = 63), or no drug as a control. (n = 20). Normothermic patients tended to bleed less at 24 hours (warm, 864 +/- 42 ml and cold, 918 +/- 68 ml), but these differences were not statistically significant. Patients receiving either tranexamic acid or epsilon-aminocaproic acid, regardless of perfusion temperature, bled less after 6, 12, and 24 hours than did cold control patients (p less than 0.05). Warm control patients also bled less than did cold control patients after 6 or 12 hours (p less than 0.05), and neither drug further reduced blood loss in these patients. Circulating platelet levels were better preserved in patients receiving either tranexamic acid or epsilon-aminocaproic acid and in patients with warm perfusion and no drug than in cold control patients. Normothermic systemic perfusion, tranexamic acid, and epsilon-aminocaproic acid each reduced postoperative blood loss and preserved platelets.

Aminocaproic Acid

Survival and valve failure after aortic valve replacement.

A prospective evaluation of 412 consecutive patients undergoing isolated aortic valve replacement between January 1982 and December 1985 was performed in an attempt to identify the determinants of survival and valve failure. A variety of valves were inserted to permit a prospective evaluation of alternative valves including: Björk-Shiley mechanical (n = 37), Ionescu-Shiley pericardial (n = 261), Hancock pericardial (n = 78), and Carpentier-Edwards porcine (n = 36). Thirteen patients died in the hospital (3.2%) and 47 patients died in the follow-up period producing an actuarial survival of 81% +/- 3% at 48 months. Survival was independently predicted by advancing age, preoperative New York Heart Association functional class, and the presence of endocarditis (p less than 0.05 by Cox regression analysis). The majority of patients were symptomatically improved (New York Heart Association class I or II: 21% preoperative, 88% postoperative). Freedom from structural valve dysfunction, prosthetic valve endocarditis, and reoperation for valve-related complications were 95% +/- 2%, 95% +/- 2%, and 92% +/- 2% at 48 months, respectively. These valve-related complications occurred more frequently in younger patients and in those with a Hancock pericardial valve (freedom from structural valve dysfunction, 89% +/- 5%; prosthetic valve endocarditis, 84% +/- 9%; reoperation, 78% +/- 10%; p less than 0.05 by Cox regression). Freedom from thromboembolism was 88% +/- 2% at 48 months; it was significantly lower in patients with a preoperative thromboembolic event and was not influenced by the type of prosthesis inserted. Freedom from anticoagulant-related hemorrhage was 85% +/- 8% at 48 months and was not influenced by any preoperative factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve

Current risk of coronary bypass for unstable angina.

The risk associated with surgical revascularization for unstable angina is critically dependent upon the clinical presentation of the patient. For this study, between January 1982 and December 1987, clinical, angiographic, operative and hospital outcome data were collected prospectively for 6539 patients undergoing surgery for unstable angina. Urgent surgery was performed in 1523 patients (23.3%), while 5016 (76.7%) underwent semielective revascularization. The mean age was 58.9 +/- 9.2 years and 805 patients (12.3%) were aged 70 years or above. The male:female ratio was 3.6:1. Depressed left ventricular function (left ventricular ejection fraction less than 40%) was present in 27.2% of the population. Preoperative myocardial infarction (within 30 days of surgery) had occurred in 588 patients (9.0%). Operative mortality was 4.6% (301 deaths). Stepwise logistic regression analysis was performed to determine the independent predictors of operative mortality. The following variables were selected in descending order: urgent surgery (P less than 0.001), coronary reoperation (P less than 0.001), depressed left ventricular (P less than 0.001), female gender (P less than 0.001), increasing age (P less than 0.001), left main stenosis (P = 0.002), and preoperative myocardial infarction (P less than 0.001). Predicted operative mortality varied between 0.5 +/- 0.3% and 82.6 +/- 12.7%. The most important determinant for patients with a preoperative myocardial infarction was left ventricular dysfunction, whereas urgent surgery for unstable angina was the most important risk variable in those without preoperative necrosis.

Adult

Recent preoperative myocardial infarction increases the risk of surgery for unstable angina.

Patients with postinfarction angina undergoing surgery for unstable angina face an increased risk of operative mortality. Between January 1982 and December 1987, clinical, angiographic, and operative data was collected prospectively in 588 unstable patients with a prior myocardial infarction within 30 days of surgery (MI) and 5951 unstable patients without preoperative damage (NONMI). MI patients were characterized as being older (age greater than or equal to 70 years: MI, 19.7%; NONMI, 11.6%; p less than 0.001) and having more left ventricular dysfunction (left ventricular ejection fraction less than 40%: MI, 34.8%; NONMI, 26.4%; p less than 0.001). Semi-elective surgery was performed in 82.0% of NONMI patients while 76.9% of MI patients underwent urgent surgery. Operative mortality was increased in MI patients (MI, 11.1%; NONMI, 4.0%; p less than 0.001) which was related to the extent of preoperative MI (non-Q wave, 8.3%; Q wave, 17.5%; p less than 0.001). Stepwise logistic regression analysis identified preoperative MI as an independent risk variable of operative mortality for unstable angina. Separate multivariate analyses were performed to identify the independent predictors for MI and NONMI patients. The multivariate predictors of operative death for MI patients were left ventricular dysfunction, reoperative coronary surgery, nonuse of the internal mammary, age, transmural MI (relative risk 2.11 vs non-Q wave infarction) and left main stenosis. For NONMI patients, the independent variables were urgent operation, left ventricular dysfunction, reoperation, female gender, left main stenosis, and age. The results of this study indicate that recent preoperative MI adversely influences the surgical results in patients with unstable angina. Alternative treatment strategies are warranted for high risk patients, particularly those with transmural MIs and impaired ventricular function.

Adult

Thoracic aortic surgery.

Between 1982 and 1989, 119 patients had repair of thoracic aortic pathology. Thirty-seven had repair of ascending aortic aneurysms, with an 11% hospital mortality. Forty-one patients had urgent repair of acute type A aortic dissections, with a 32% hospital mortality. The independent predictors of mortality were the use of crystalloid cardioplegia, aortic dissection, and the use of an intraluminal prosthesis or the inclusion surgical technique. Better grafts and the resection technique has reduced mortality since 1986. Seventeen patients had their primary pathology in the aortic arch, with a 47% hospital mortality. The urgency of the procedure and crystalloid cardioplegia predicted an unsuccessful outcome. Seventeen patients had descending aortic aneurysms repaired, with an 18% mortality. The urgency of surgery was the predictor of mortality. Seven patients had a descending thoracic aortic disruption repaired, with one death (14%). Better graft materials, surgical techniques, and methods of myocardial protection have contributed to the improved results of thoracic aortic surgery in recent years.

Aortic Dissection

Optimal delivery of blood cardioplegia.

A prospective randomized controlled trial was performed to determine optimal flow rates and hemoglobin concentrations for continuous normothermic blood cardioplegia and to compare warm heart surgery with standard intermittent cold blood cardioplegia. Thirty-five patients received intermittent cold blood cardioplegia, low hemoglobin low flow, low hemoglobin high flow, high hemoglobin low flow, or high hemoglobin high flow warm blood cardioplegia (seven patients per group: low hemoglobin, 50 g/l; high hemoglobin, 80 g/l; low flow, less than 80 ml/min; high flow, greater than 80 ml/min). Hypothermia resulted in a significantly greater accumulation of ADP and AMP during cross clamp, consistent with impaired mitochondrial function. Low hemoglobin low flow warm blood cardioplegia increased myocardial oxygen consumption and coronary sinus blood flow after cross clamp release, and also decreased lactate consumption. Postoperative myocardial performance and diastolic compliance were reduced in low hemoglobin low flow warm patients, and diastolic compliance was increased with high hemoglobin high flow warm blood cardioplegia when compared with cold patients. In this study, continuous normothermic cardioplegia was safe when delivered at 80 ml/min or greater, with a hemoglobin concentration of at least 80 g/l, affording myocardial metabolic and functional recovery comparable to that found after intermittent cold blood cardioplegia.

Blood

Determinants of survival and valve failure after mitral valve replacement.

A prospective evaluation of 333 consecutive patients undergoing isolated mitral valve replacement between 1982 and 1985 was performed to identify the predictors of survival and valve failure. Follow-up between 2 and 6 years postoperatively (mean, 32 +/- 17 months) was 98% complete. Four prostheses were inserted to permit a prospective evaluation of alternative valves: Björk-Shiley mechanical (n = 118), Ionescu-Shiley pericardial (n = 146), Carpentier-Edwards porcine (n = 38), and Hancock pericardial (n = 31). Hospital mortality was 6%, and actuarial survival at 5 years was 74% +/- 5%. Multivariate Cox regression analysis identified advancing age (less than 40 years, 88% +/- 7%; greater than 70 years, 50% +/- 14%) and poor left ventricular function (ejection fraction less than 0.20, 62% +/- 17%; ejection fraction greater than 0.60, 80% +/- 7%) as independent predictors of postoperative survival. Freedom from structural valve dysfunction, prosthetic valve endocarditis, reoperation, and valve-related mortality and morbidity were 86% +/- 4%, 91% +/- 4%, 81% +/- 4%, and 72% +/- 5%, respectively, at 5 years. The actuarial incidence of valve failure was inordinately high with the Hancock pericardial valve (p less than 0.05). Freedom from thromboembolic events (78% +/- 8% at 5 years) was significantly lower in patients with poor ventricular function (ejection fraction (less than 0.20, 54% +/- 20%; ejection fraction greater than 0.60, 73% +/- 11%; p less than 0.05). Survival after mitral valve replacement was determined by age and left ventricular function. Premature failure of the Hancock pericardial valve resulted in an unacceptable rate of valve-related complications.

Adult

Dipyridamole for coronary artery bypass surgery.

A randomized trial to compare the effects of oral and intravenous dipyridamole was conducted in 58 patients undergoing coronary artery bypass graft (CABG) surgery. Preoperative oral administration of dipyridamole resulted in lower plasma drug concentrations in the early postoperative period than perioperative intravenous administration. Postoperative platelet counts were highest in the patients receiving intravenous dipyridamole, intermediate in those receiving oral dipyridamole and lowest in the control group. Postoperative blood loss was significantly reduced with both oral and intravenous dipyridamole. A second randomized trial was conducted in an additional 40 patients undergoing CABG surgery to evaluate the effects of dipyridamole on myocardial platelet and leukocyte deposition and the cardiac release of thromboxane. Twenty patients received intravenous dipyridamole perioperatively. Autologous platelets and leukocytes were labeled with 111In and 99mTc respectively and were infused before release of the crossclamp. Myocardial biopsies were obtained after aortic declamping and indicated that platelets and leukocytes were deposited in the myocardium during reperfusion. Dipyridamole reduced both platelet and leukocyte deposition. Cardiac release of thromboxane B2 occurred in the early postoperative period and was reduced by dipyridamole. In conclusion, dipyridamole preserved platelets and reduced postoperative bleeding and blood product transfusions in patients undergoing CABG surgery. Dipyridamole also reduced cardiac platelet deposition and thromboxane release and may reduce perioperative ischemic injury.

Administration, Oral

Clinical and Doppler echocardiographic evaluation of bioprosthetic valve failure after 10 years.

Four hundred thirteen consecutive patients underwent valve replacement with a bioprosthesis between 1976 and 1982. Aortic valve replacement was performed in 240 patients, mitral valve replacement in 132 patients, and multiple valve replacement in 41. The Carpentier-Edwards porcine (n = 336), Angell-Shiley porcine (n = 23), Hancock porcine (n = 11), and the Ionescu-Shiley pericardial valves (n = 43) were inserted. Follow-up between 5 and 12 years postoperatively was 98% complete. Freedom from structural valve deterioration was 72 +/- 7%, 59 +/- 9%, and 59 +/- 9%, respectively, after aortic, mitral, and double valve replacement. The risk of structural valve deterioration and reoperation for valve-related complications was significantly increased with the Ionescu-Shiley pericardial prosthesis. The risk for reoperation was inversely related to patient age. Postoperative Doppler echocardiographic studies in 87% of available patients revealed a subgroup of asymptomatic patients with evidence of structural valve deterioration. These patients (n = 61) had significantly reduced prosthetic valve areas (aortic less than 1 cm2, mitral less than 1.7 cm2), elevated resting transvalvular gradients (aortic greater than 40 mm Hg), or moderate-to-severe regurgitation. In summary, postoperative Doppler echocardiographic examination identified asymptomatic patients with structural valve dysfunction. These patients must be followed up carefully to determine the optimal timing of reoperation.

Aortic Valve

Right ventricular function and metabolism.

Right ventricular protection may be limited with current methods of cardioplegic delivery. Sensitive measurements of right and left ventricular function and metabolism were made in 30 patients undergoing elective coronary artery bypass surgery with cold cardioplegic arrest. Myocardial adenine nucleotide concentrations decreased with cardioplegia and reperfusion in both the right and left ventricles despite adequate levels of precursors, suggesting perioperative mitochondrial dysfunction. Postoperatively, right and left ventricular pressures were measured with micromanometer catheters and volumes were measured by nuclear ventriculography. Right and left ventricular systolic elastance was calculated by the isochronic method and by the end-systolic method. Both methods provided sensitive indexes of end-systolic elastance. This study demonstrated that right ventricular function and metabolism can be evaluated by methods analogous to methods used in the left ventricle. These results suggest that right ventricular functional and metabolic recovery are delayed despite apparently adequate myocardial protection. Sensitive measurements may permit improved assessment of alternative methods of right ventricular protection.

Adenine Nucleotides

Delayed myocardial metabolic recovery after blood cardioplegia.

Previous studies have demonstrated that both myocardial metabolism and ventricular function were depressed after blood cardioplegic arrest for elective coronary artery bypass grafting. To evaluate the etiology of this metabolic defect, we measured the levels of adenine nucleotides and their precursors in 29 patients undergoing elective coronary revascularization. Myocardial biopsy specimens were obtained at 37 degrees C before cardioplegic arrest, immediately after 74 +/- 4 minutes of cardioplegic arrest, and after 30 minutes of reperfusion. Biopsy specimens were analyzed for levels of adenine nucleotides and their precursors by high-performance liquid chromatography. Adenosine triphosphate concentrations decreased with cardioplegic arrest and with reperfusion. Adenosine monophosphate concentrations increased after cardioplegic arrest and remained nearly twice the initial values after reperfusion. The ratio of adenosine monophosphate to adenosine triphosphate doubled after reperfusion, suggesting defective conversion of adenosine monophosphate to adenosine triphosphate. Levels of adenine nucleotide degradation products (adenosine, inosine, and hypoxanthine) increased after cardioplegia and decreased with reperfusion, suggesting a washout of soluble precursors. This study suggests that improvements in myocardial protection should attempt to stimulate mitochondrial energy production and preserve adenine nucleotide precursors.

Adenosine Diphosphate

Survival and bioprosthetic valve failure. Ten-year follow-up.

Between 1976 and 1982, 413 consecutive patients underwent valvular replacement with a bioprosthesis. Aortic valve replacement was performed in 240 patients, mitral valve replacement in 132, and multiple-valve replacement in 41. Four prostheses were employed: Carpentier-Edwards porcine (n = 336), Angel-Shiley porcine (n = 23), Hancock porcine (n = 11), and Ionescu-Shiley pericardial (n = 43). Follow-up was conducted between 5 and 12 years postoperatively and was 98% complete. Survival was 65 +/- 4% at 10 years and was independently influenced by advancing age, poor ventricular function, male sex, concomitant coronary artery bypass surgery, and valvular type. The risk of structural valvular dysfunction, reoperation, and any valve-related mortality and morbidity was significantly increased with the Ionescu-Shiley pericardial prosthesis. Long-term survival after valvular replacement was influenced by patient- and valve-related factors. The Ionescu-Shiley pericardial valve had an unusually high incidence of premature failure.

Adult

The changing pattern of coronary artery bypass surgery.

Recent advances in interventional cardiology have altered the profile of patients referred for coronary artery bypass surgery. In recent years, the proportion of high-risk patients has increased dramatically. To evaluate the impact of the changing pattern of surgical patients, we prospectively followed up 7,334 patients who had coronary artery bypass surgery between 1982 and 1986. Multivariate analysis identified the following risk factors for operative mortality: urgency of surgery, left ventricular ejection fraction, age, female sex, previous bypass surgery, and left main coronary artery stenosis. Perioperative mortality has remained stable despite an increasing incidence of high-risk patients. However, perioperative morbidity has increased, due to the large number of high-risk patients. A multivariate analysis was performed by year to identify temporal trends in risk factors. Urgency of surgery, age, and previous bypass surgery have become more significant predictors of mortality with respect to time, whereas female sex, left ventricular ejection fraction, and left main coronary artery stenosis have become less significant determinants of mortality. Our results demonstrate the critical dependence of mortality and morbidity rates on the case mix, and further improvements in the results of coronary artery bypass surgery will require better strategies for the increasing number of high-risk patients.

Age Factors

Valvular surgery in the elderly.

In previous studies from this university, advanced age was identified as an independent predictor of operative mortality for valvular surgery. Therefore, between January 1982 and December 1986, early results were compared in 469 patients greater than 70 years old (Old; 74.0 +/- 3.4 years, mean +/- SD) and in 2,040 patients less than 70 years old (Young; 53.7 +/- 12.1 years). Patients underwent single- or multiple-valve repair or replacement with or without concomitant coronary artery bypass surgery. Data consisting of 31 clinical and angiographic variables were collected prospectively and were analyzed by univariate and multivariate statistics. Old patients were characterized by having more frequent left ventricular dysfunction (left ventricular ejection fraction less than 40%: Old, 33.5%; Young, 22.4%; p less than 0.001), coronary artery disease (Old, 54.5%; Young, 24.2%; p less than 0.001), and urgent surgery (Old, 15.6%; Young, 11.8%; p = 0.02). Aortic valve procedures (Old, 59.7%; Young, 40.1%; p less than 0.001) and concomitant coronary artery bypass surgery (Old, 46.4%; Young, 20.3%; p less than 0.001) were performed more commonly in the Old patient. Operative mortality occurred in 10.0% of Old patients compared with 5.6% of Young patients (p less than 0.001), and major morbidity (low-output syndrome, perioperative myocardial infarction, intra-aortic balloon pump counterpulsation, and stroke) occurred significantly more frequently (p less than 0.001) in the Old. Stepwise logistic regression identified that urgent operation (p = 0.002), mitral or double-valve surgery (p = 0.004), coronary artery disease especially when not treated by bypass surgery (p = 0.02), female gender (p = 0.02), and left ventricular dysfunction (p = 0.05) independently predicted operative death in the Old population. The significant predictors of mortality in the Young patient were urgent operation (p less than 0.001), New York Heart Association class IV (p less than 0.001), associated tricuspid valve disease (p = 0.002), decreased left ventricular function (p = 0.01), valvular re-replacement (p = 0.02), and increasing age (p = 0.03). The predicted probability of operative mortality in Old patients ranged between 0.9 +/- 0.5% and 76 +/- 16%. Elderly patients in good risk categories should be offered surgical intervention for correction of valvular lesions. Alternative therapy may be indicated in patients with multiple risk factors.

Age Factors