Simultaneous Aortic and Mitral Valve Replacement in Octogenarians: A Viable Option?

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1 Simultaneous Aortic and Mitral Valve Replacement in Octogenarians: A Viable Option? Ariane Maleszka, MD,* Georg Kleikamp, MD, PhD,* Armin Zittermann, PhD, Maria R. G. Serrano, MD, and Reiner Koerfer, MD, PhD Department of Thoracic and Cardiovascular Surgery, Heart and Diabetes Center North-Rhine Westfalia, University Hospital of Ruhr University Bochum, Bad Oeynhausen, Germany Background. Few reliable data are available on clinical outcome of octogenarians undergoing simultaneous aortic and mitral valve replacement. Methods. We performed a retrospective analysis of 55 patients aged 80 years and over with double valve replacement who were operated on at our institution between 2001 and Thirty-day mortality and 1-year survival were assessed. Results. For most of the patients, stenosis was the cause of aortic valve surgery, whereas regurgitation was the cause of mitral valve replacement in the majority of patients. In one third of the patients, cardiac surgery had to be performed on an urgent/emergency basis. A large number of patients had concomitant diagnoses such as atrial fibrillation (73%), coronary artery disease (44%), renal insufficiency (29%), chronic obstructive pulmonary disease (20%), and diabetes mellitus (15%). In total, 16 patients (29%) died during follow-up. Survival rates at 30 days and 1 year were 91% and 71%, respectively. As determined by multivariable logistic regression analysis, Karnofsky performance status (hazard ratio: per % increase; 95% confidence interval: to 0.996; p 0.043) and bypass time (hazard ratio: per min; 95% confidence interval: to 1.120; p 0.028) were independent predictors of 30-day mortality. Beside these factors, additional independent predictors of 1-year mortality were preoperative stroke and postoperative intestinal failure (p and 0.003, respectively). Conclusions. Our data demonstrate that, for selected octogenarians, double valve replacement can be performed with acceptable outcome. A better performance status of the patients at the time of cardiac surgery will probably improve 1-year survival. (Ann Thorac Surg 2008;86:1804 8) 2008 by The Society of Thoracic Surgeons Accepted for publication July 29, *Drs Maleszka and Kleikamp contributed equally to this work. Address correspondence to Dr Maleszka, Department of Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, University Hospital of Ruhr University Bochum, Georgstrabe 11, Bad Oeynhausen, 32545, Germany; amaleszka@hdz-nrw.de. The number of open heart procedures in octogenarians has increased steadily in the last 2 decades. The average life expectancy for the population of the industrialized countries has risen considerably over the last 50 years and is expected to increase further in the future [1]. This development leads also to a significant increase of degenerative valvular disease in this age group [2]. Although previous studies have demonstrated a higher risk for octogenarians undergoing heart surgery compared with younger patient groups [3 4], recent studies have shown that isolated aortic valve replacement in selected octogenarians can be performed with acceptable hospital and midterm mortality [5]. For multivalvular disease, it is reported in the literature that the overall operative risk of simultaneous aortic and mitral valve replacement lies between 4% and 13% and is, therefore, much higher than the risk of either aortic valve replacement or mitral valve replacement alone [6 8]. Recent reports suggest an even higher perioperative risk for octogenarians undergoing simultaneous aortic and mitral valve replacement [9, 10]. However, reliable data are scarce. Therefore, it is the aim of this study to determine whether simultaneous aortic and mitral valve replacement is a viable therapeutical option for multivalvular disease in this age group. Material and Methods Patients Between January 2001 and December 2005, 499 consecutive patients underwent double valve replacement at our institution. From the clinical database, we identified 55 patients aged 80 years and older who underwent aortic and mitral valve replacement alone or in combination with other procedures: tricuspid anuloplasty, coronary artery bypass graft surgery, and enlargement of the aortic anulus. All patients included in this study had mitral valve disease not amenable to mitral valve repair mostly because of extensive calcification or destruction of the mitral apparatus. Patients with aortic valve replacement and mitral valve repair were excluded from this study. All patients had preoperative coronary angiography and echocardiography or cardiac catheterization, or both, to assess hemodynamic data. All coronary lesions of at least 50% were considered for bypass surgery. Forty-two patients were admitted to our heart center for cardiac surgery from other clinics, whereas 13 patients were 2008 by The Society of Thoracic Surgeons /08/$34.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg MALESZKA ET AL 2008;86: DOUBLE VALVE REPLACEMENT IN OCTOGENARIANS 1805 ambulatory. The choice of prosthetic valve was based on the patient s preference. However, all but 1 patient with atrial fibrillation wished implantation of a bioprosthetic instead of mechanical valves, as most of these patients wanted to avoid the lifelong strict oral anticoagulation regimen to prevent thromboembolic events of aortic and mitral valve prostheses. Postoperative antithrombotic treatment with intravenous unfractionated heparin was started for all patients in the intensive care unit. On the first postoperative day, oral anticoagulation therapy was started with phenprocoumon with a target international normalized ratio (INR) of 2.8 to 3.5 until discharge. Thereafter, patients checked INR values with their cardiologists. For bioprostheses, oral anticoagulation therapy was discontinued after 12 weeks postoperatively when other indications (eg, atrial fibrillation) for anticoagulation were absent. The Ruhr University Ethics Committee, Bochum, Germany, approved the study, and the need for individual informed consent was waived. Data Collection and Definitions Preoperative, perioperative, and postoperative data were collected and entered into a computerized database. The 30-day mortality was registered. Variables for the shortterm follow-up were demographic, preoperative and postoperative hemodynamic data, timing and comorbidities, surgical procedure, postoperative bleeding, and neurologic, renal, abdominal, and pulmonary complications. Renal dysfunction preoperatively and postoperatively was defined as a serum creatinine level greater than 2.0 mg/dl. Neurologic events were defined as the occurrence of a transient ischemic attack (fully reversible symptoms of short duration) or a stroke (central neurologic deficit persisting for more than 72 hours). Pulmonary complication was defined as prolonged mechanical ventilation (longer than 24 hours). Intestinal failure comprised clinical ileus and ileus with abnormal permeability diagnosed clinically, by ultrasonography or roentgenographic imaging, or both, leading to conservative or operative therapy. Low cardiac output was considered when cardiac index was below 1.8 L min 1 m 2.We calculated the logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) [11] for all patients. In addition, we assessed the Karnofsky performance status [12] preoperatively and postoperatively. In May 2007, the surviving patients, their relatives, and their cardiologists or general practitioners were interviewed by telephone to assess 1-year survival and morbidities retrospectively. According to published guideline for reporting mortality after cardiac valve interventions [13], we classified causes of death as allcause mortality, valve-related mortality, sudden unexpected death, and cardiac death. Surgical Procedure Valve replacements and concomitant procedures were performed using standard extracorporal circulation and median sternotomy, cold crystalloid cardioplegia (Bretschneider), and mild systemic hypothermia (30 to 32 C). For coronary artery bypass graft surgery, the left internal mammary artery and saphenous vein grafts were used. Tricuspid anuloplasty was performed as a modification of the De Vega technique in all cases. Table 1. Characteristics of the Study Group Variable Number Percent Sex Males Female Age group years years 8 15 Body mass index 20 kg/m kg/m kg/m Cardiac surgery Aortic valve replacement Mitral valve replacement Tricuspid valve anuloplasty Coronary artery bypass grafting Patch plasty of aortic annulus 4 7 Previous thoracic surgery 7 13 Concomitant diagnosis Coronary artery disease Previous myocardial infarction 3 6 Tricuspid valve regurgitation Diabetes mellitus 8 15 Atrial fibrillation Stroke 3 6 Renal insufficiency (serum creatinine mg/dl) Chronic obstructive pulmonary disease Urgent/emergency operation Indication for aortic valve replacement Stenosis Regurgitation 8 15 Combined Indication for mitral valve replacement Stenosis 9 16 Regurgitation Combined 7 13 Left ventricular ejection fraction 55% % 55% % 5 9 Karnofsky performance status 50% % EuroSCORE (logistic) EuroSCORE European System for Cardiac Operative Risk Evaluation.

3 1806 MALESZKA ET AL Ann Thorac Surg DOUBLE VALVE REPLACEMENT IN OCTOGENARIANS 2008;86: Statistical Analysis We report categorical variables using the number (n) and percent of observations. Continuous variables are expressed as mean and standard deviation or median and interquartile range (IQR) when appropriate. The Mann- Whitney U test was used for comparative evaluations of continuous variables. All p values less than 0.05 were considered statistically significant. Survival rates were calculated with the Kaplan-Meier product-limit estimator. We also tested associations of risk factors to 30-day mortality and 1-year mortality. Risk factors were first tested in a univariate logistic regression model (30-day mortality) and a univariate Cox regression model (1-year mortality). As only preoperative and intraoperative risk factors are relevant for operative death, the following variables were tested in the univariate model for 30-day mortality: age, sex, body mass index, diabetes mellitus, logistic EuroSCORE, Karnofsky performance status, atrial fibrillation, stroke, myocardial infarction, renal insufficiency, coronary artery disease, patchplasty, redo, concomitant coronary artery bypass graft surgery, chronic obstructive pulmonary disease, and urgent/ emergency operation. To assess predictors of 1-year mortality, we also included postoperative complications such as renal failure, gastrointestinal failure, respiratory failure, neurologic complications, low cardiac output syndrome, and rethoracotomy in the univariate model. Because the number of variables that can be included for multivariable testing is limited and depends on the number of events [14], we retained only variables with a p value less than 0.01 in the univariable analysis for multivariable proportional hazard analysis. We used the software SPSS, version 14 (Chicago, Illinois), to perform the analyses. Results Table 2. Postoperative Complications of the Study Groups Postoperative Complications Number Percent Renal failure a Gastrointestinal failure 7 13 Rethoracotomy 5 9 Neurologic events 4 7 Respiratory failure Low cardiac output syndrome Thirty-day mortality 5 9 a Rise of serum creatinine 1.0 mg/dl or more. Fig 1. Probability of survival among octogenarians with double valve replacement. Dotted lines indicate 95% confidence intervals. Characteristics of the study group are presented in Table 1. In most of the patients, stenosis was the cause of aortic valve surgery, whereas regurgitation was the cause of mitral valve replacement in the majority of patients. In one third of the patients, cardiac surgery had to be performed on an urgent/emergency basis. A large number of patients had concomitant diagnoses such as atrial fibrillation (73%), coronary artery disease (44%), renal insufficiency (29%), chronic obstructive pulmonary disease (20%), and diabetes mellitus (15%). Only a relatively small percentage of patients (29%) were overweight (body mass index 25 kg/m 2 ). As indicated by Karnofsky performance status, the vast majority of patients (n 39) required considerable assistance and frequent medical care. No active endocarditis was found; histologic examinations of resected valves showed degenerative disease and healed endocarditis in most cases. Eight patients (15%) had one-vessel disease, 7 (13%) had two-vessel disease, and 9 (16%) had three-vessel disease. Fifty-four bioprostheses (34 porcine and 20 pericardial prostheses) and 1 mechanical bileaflet prostheses were implanted in aortic position; for the mitral position, 54 porcine bioprostheses and 1 bileaflet mechanical prosthesis were chosen. In the aortic position, 1 19-mm prosthesis (2%), and mm (29%), mm (44%), mm (20%), and 3 27-mm prostheses (5%) were implanted. In mitral position, 1 25-mm prosthesis (2%), and mm (51%), mm (34%), and 7 31-mm (13%) prostheses were implanted. Clamping time and bypass time were minutes and minutes, respectively. During follow-up, no bleeding event or valve endocarditis occurred. No reintervention was necessary. Neurologic events occurred in 4 patients: a stroke in 2 patients, 1 of whom died in postoperative month 11, and transient ischemic attack in 2 patients. The frequency of other postoperative complications is presented in Table 2. The survival curve is illustrated in Figure 1. Thirty-day and 1-year survival were 91% (95% confidence interval: 83% to 99%) and 71% (95% confidence interval: 61% to 85%), respectively. Thus, all-cause mortality was 29% (16 patients) during follow-up. Of these 16 patients, 5 (9%) died during the first 30 days. Early mortality was caused by an abdominal thrombembolic event leading to peritonitis and sepsis in 1 patient, by congestive heart failure in 2 patients, and by multiorgan system failure in 2 other patients. During the 1-year follow-up, 1 additional death was caused by a thrombembolic event and 4 other deaths were cardiac related. According to guidelines for reporting mortality after cardiac valve interventions, 2 of the 16

4 Ann Thorac Surg MALESZKA ET AL 2008;86: DOUBLE VALVE REPLACEMENT IN OCTOGENARIANS 1807 Table 3. Predictors of 1-Year Mortality in Patients With Double Valve Replacement Univariate Multivariate Variable HR 95% CI HR 95% CI p Value Stroke, preoperatively (yes) Karnofsky performance status (percent) Logistic EuroSCORE (per unit) Bypass time (per min) Respiratory failure, postoperatively (yes) Intestinal failure, postoperatively (yes) Low cardiac output syndrome, postoperatively (yes) Hazard ratio (HR) from Cox regression analysis. Variables with p less than 0.01 on univariate analysis are shown in Table and included in the multivariate model (see Methods for all tested variables). CI confidence interval; EuroSCORE European System for Cardiac Operative Risk Evaluation. deaths during 1-year follow-up were valve related and 8 deaths were cardiac related. Of the 16 patients who died, 8 have had concomitant surgical procedures such as coronary artery bypass graft, patchplasty of the aortic anulus, and tricuspid anuloplasty, whereas the 8 other patients underwent valve replacement only. No structural valve deterioration or valve thrombosis occurred during the follow-up time. For the entire group, Karnofsky performance status increased nonsignificantly from a median preoperative value of 50% (IQR, 40% to 60%) to 70% (IQR, 0% to 90%) postoperatively (p 0.237). For the survivors, however, the median value increased from 50% (50% to 60%) to 80% (70% to 90%; p 0.001). In 3 of the 40 patients with preoperative atrial fibrillation, cardiac arrhythmia disappeared after valve replacement. The univariate logistic regression analysis revealed that preoperative Karnofsky performance status and bypass time were predictors of 30-day survival. Both variables remained independent predictors of 30-day mortality in the multivariable logistic regression analysis (Karnofsky performance status, hazard ratio: per percent increase; 95% CI: to 0.996, p 0.043; bypass time, hazard ratio: per minute; 95% CI: to 1.120, p 0.028). As determined by univariate Cox regression analysis, preoperative stroke, the logistic EuroSCORE, Karnofsky performance status, bypass time, postoperative respiratory failure, intestinal failure, and low cardiac output syndrome were predictors of 1-year mortality. As determined by multivariable analysis, however, only preoperative stroke, preoperative Karnofsky score, bypass time, and postoperative intestinal failure remained independent predictors of 1-year mortality (Table 3). Comment Our study has investigated the clinical outcome of octogenarians with multivalvular disease undergoing double valve replacement. All patients included in this study had mitral valve disease not amenable to mitral valve repair, mostly because of extensive calcification or destruction of the mitral apparatus. Our study demonstrates that double valve replacement results in an acceptable 1-year survival in this age group. Preoperative variables such as Karnofsky performance status as well as perioperative variables such as bypass time were independent predictors of 30-day and 1-year mortality. It was a surprising finding that bypass time and intestinal failure were independent risk factors of 1-year survival, whereas preoperative left ventricular dysfunction was not. Kuwaki and coworkers [15] have identified preoperative ventricular dysfunction as the main predictor of survival in a group of 123 patients aged 53.8 years undergoing double valve replacement. We only may speculate that in our series the reason for the lack of left ventricular dysfunction as risk factor is due to the relatively small number of patients and a strong selection bias leading to a homogeneous group of patients. The bypass time, after the more complex surgical procedure of double valve replacement compared to isolated aortic valve replacement, may underline the important role of sufficient myocardial protection in this context. This finding underlines the need to prevent organ dysfunction, especially in this patient group. Recent studies of octogenarians undergoing aortic valve replacement alone showed that the valve replacement on an urgent or emergency basis was an independent predictor of mortality, reflecting the failing heart during decompensation [16 18]. In our series, procedures were performed on urgent or emergency basis in one third of the patients. However, this classification did not predict mortality in our study cohort. Nevertheless, we cannot rule out that an urgent/emergency operation has influenced outcome indirectly by leading to longer bypass times. It may also be that other factors may reflect clinical status more appropriately than classification of cardiac surgery as elective, urgent, or emergent does. This assumption is in line with the finding that the preoperatively assessed Karnofsky performance status and the presence of stroke were independent predictors of mortality. Earlier investigations of octogenarians with aortic valve replacement alone have shown that patients with concomitant coronary artery disease had more often left ventricular dysfunction after myocardial infarction, lead-

5 1808 MALESZKA ET AL Ann Thorac Surg DOUBLE VALVE REPLACEMENT IN OCTOGENARIANS 2008;86: ing to a worse midterm and long-term outcome than patients with isolated aortic valve disease [1, 19 21]. Moreover, in an earlier series of 170 patients aged 50.5 years, concomitant tricuspid valve and aortocoronary bypass surgery were related to poorer survival rates after double valve replacement [8]. However, our data do not confirm the assumption that those factors are important independent risk factors for survival in cardiac surgery patients. Of the 16 patients who died within the first postoperative year, roughly 50% had concomitant surgical procedures such as tricuspid valve and aortocoronary bypass surgery or patchplasty of the aortic anulus. In Germany, the mean life expectancy of an 82-yearold woman is 7.5 years, and for an 82-year-old man, it is 6.3 years [22]. These data indicate that clinical outcome was acceptable in the present study cohort with double valve replacement. The postoperative improvements in Karnofsky performance status for the survivors of our study demonstrate that double valve replacement not only added years to life but also reduced functional impairment in these patients. Nevertheless, it is also obvious from our data that 1-year mortality should be reduced. Our study has some limitations. Firstly, this investigation has the general limitations of a retrospective study. Secondly, the study group included different types of bioprostheses (porcine and pericardial) and even one pair of bileaflet mechanical valves. That may have influenced study results independent of age and surgery procedure. Thirdly, the cardiologists referring the patients may have executed some form of bias. Patients considered too ill may have been denied referral to a surgical institution altogether. Finally, the number of variables in the multivariable analyses was limited owing to statistical restrictions. The use of more covariates may sometimes come to opposite conclusions [23]. From the clinical point of view, however, it is likely that preoperative functional impairment (as indicated by Karnofsky performance status) and unexpected perioperative and postoperative complications can significantly influence 1-year survival. In summary, our data demonstrate that double valve replacement for selected patients aged 80 years and older can be performed with an acceptable outcome. Therefore, octogenarians should not be denied complex valvular surgery because of their age alone. A better performance status of the patients at the time of cardiac surgery would probably improve 1-year mortality. References 1. Craver JM, Puskas JD, Weintraub WW, et al. 601 Octogenarians undergoing cardiac surgery: outcome and comparison with younger age groups. Ann Thorac Surg 1999;67: Horstkotte D, Loogen F. The natural history of aortic valve stenosis. 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