Richard P. Cochran

Stress Variations in the Human Aortic Root and Valve: The Role of Anatomic Asymmetry

AbstractThe asymmetry of the aortic valve and aortic root may influence their biomechanics, yet was not considered in previous valve models. This study developed an anatomically representative model to evaluate the regional stresses of the valve within the root environment. A finite-element model was created from magnetic-resonance images of nine human valve–root specimens, carefully preserving their asymmetry. Regional thicknesses and anisotropic material properties were assigned to higher-order elastic shell elements representing the valve and root. After diastolic pressurization, peak principal stresses were evaluated for the right, left, and noncoronary leaflets and root walls. Valve stresses were highest in the noncoronary leaflet (538 kPa vs right 473 kPa vs left 410 kPa); peak stresses were located at the free margin and belly near the coaptation surfaces (averages 537 and 482 kPa for all leaflets, respectively). Right and noncoronary sinus stresses were 21% and 10% greater than the left sinus. In all sinuses, stresses near the annulus were higher than near the sinotubular junction. Stresses vary across the valve and root, likely due to their inherent morphologic asymmetry and stress sharing. These factors may influence bioprosthetic valve durability and the incidence of isolated sinus dilatation.

Perioperative Increases in Serum Creatinine Are Predictive of Increased 90-Day Mortality After Coronary Artery Bypass Graft Surgery

Background— Impaired renal function after coronary artery bypass graft (CABG) surgery is a key risk factor for in-hospital mortality. However, perioperative increases in serum creatinine and the association with mortality has not been well-studied. We assessed the hypothesis that perioperative increases in creatinine are associated with increased 90-day mortality. Methods and Results— We studied 1391 patients in northern New England undergoing CABG in 2001 and evaluated preoperative and postoperative creatinine. Patients with preoperative dialysis were excluded. Data were linked to the National Death Index to assess 90-day survival. Kaplan-Meier and log-rank techniques were used. Patients were stratified by percent increase in creatinine from baseline: <25%, 25% to 49%, 50% to 99%, ≥100%. We assessed 90-day survival and calculated adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for creatinine groups, adjusting for age and sex. Patients with the largest creatinine increases (50% to 99% or ≥100%) had significantly higher 90-day mortality compared with patients with a smaller increase (<50%; P<0.001). Adjusted HR and 95% CI confirmed patients in the higher 2 groups had an increased risk of mortality compared with the <25% (referent); however, the 25% to 49% group was not different from the referent: 1.80 (95% CI: 0.73 to 4.44), 6.57 (95% CI, 3.03 to 14.27), and 22.10 (95% CI, 11.25 to 43.39). Conclusions— Patients with large creatinine increases (≥50%) after CABG surgery have a higher 90-day mortality compared with patients with small increases. Efforts to identify patients with impaired renal function and to preserve renal function before cardiac surgery may yield benefits for patients in the future.

Multivariable Prediction of Renal Insufficiency Developing After Cardiac Surgery

Background— Renal insufficiency after coronary artery bypass graft (CABG) surgery is associated with increased short-term and long-term mortality. We hypothesized that preoperative patient characteristics could be used to predict the patient-specific risk of developing postoperative renal insufficiency. Methods and Results— Data were prospectively collected on 11 301 patients in northern New England who underwent isolated CABG surgery between 2001 and 2005. Based on National Kidney Foundation definitions, moderate renal insufficiency was defined as a GFR <60 mL/min/1.73m2 and severe renal insufficiency as a GFR <30. Patients with at least moderate renal insufficiency at baseline were eliminated from the analysis, leaving 8363 patients who became our study cohort. A prediction model was developed to identify variables that best predicted the risk of developing severe renal insufficiency using multiple logistic regression, and the predictive ability of the model quantified using a bootstrap validated C-Index (Area Under ROC) and Hosmer-Lemeshow statistic. Three percent of the patients with normal renal function before CABG surgery developed severe renal insufficiency (229/8363). In a multivariable model the preoperative patient characteristics most strongly associated with postoperative severe renal insufficiency included: age, gender, white blood cell count >12 000, prior CABG, congestive heart failure, peripheral vascular disease, diabetes, hypertension, and preoperative intraaortic balloon pump. The predictive model was significant with &khgr;2 150.8, probability value <0.0001. The model discriminated well, ROC 0.72 (95%CI: 0.68 to 0.75). The model was well calibrated according to the Hosmer-Lemeshow test. Conclusions— We developed a robust prediction rule to assist clinicians in identifying patients with normal, or near normal, preoperative renal function who are at high risk of developing severe renal insufficiency. Physicians may be able to take steps to limit this adverse outcome and its associated increase in morbidity and mortality.

Altered Collagen Concentration in Mitral Valve Leaflets: Biochemical and Finite Element Analysis

BACKGROUND Ischemic mitral regurgitation or ventricular wall motion abnormalities will alter the stress distribution in the mitral valve. We hypothesize that in response, the regional collagen concentration will be altered and will significantly impact the stress distribution in the mitral valve. METHODS Two sheep served as normal (sham) controls. Two other sheep had coronary ligation resulting in abnormal ventricular wall motion. Four sheep underwent ligation to infarct the posteromedial papillary muscle, resulting in ischemic regurgitation. After 4 or 8 weeks, the mitral valves were excised, and the anterior leaflet sections were subjected to an assay for collagen concentration. Next, in a finite element model, to simulate changes in collagen concentration, the tissue stiffness was increased by 20%, and then decreased by 20%. In another model, the thickness of the tissue was increased by 20%, and then combined with decreased tissue stiffness. Physiologic loading pressures were applied, and leaflet stress, chordal stress, and coaptation results were analyzed. RESULTS The average collagen concentration in the normal sheep leaflets was 59.2% (dry weight), 50.6% in the ischemic controls, and 45.8% in the papillary muscle infarct group. Collagen concentration was greatest at the midline and decreased toward the commissures. Increased tissue stiffness resulted in increased leaflet and chordal stresses, as well as reduced coaptation. Decreased stiffness resulted in the opposite. Increased tissue thickness reduced leaflet and chordal stresses, but also reduced coaptation. The combination of increased tissue thickness and decreased stiffness demonstrated the greatest reduction in leaflet and chordal stress, while maintaining normal leaflet coaptation. CONCLUSIONS The observed changes may demonstrate an early effort to compensate for increased leaflet stress. Microstructural alterations may demonstrate an early effort to compensate for altered physiologic loading to reduce stress and maintain coaptation. It is crucial in repairing or partially replacing thickened tissue that normal geometry and physiology be restored.

Mechanisms of aortic valve incompetence: finite element modeling of aortic root dilatation.

BACKGROUND Idiopathic root dilatation often results in dysfunction of an otherwise normal aortic valve. To examine the effect of root dilatation on leaflet stress, strain, and coaptation, we utilized a finite element model. METHODS The normal model incorporated the geometry, tissue thickness, stiffness, and collagen fiber alignment of normal human roots and valves. We evaluated four dilatation models in which diameters of the aortic root were dilated by 5%, 15%, 30%, and 50%. Regional stress and strain were evaluated and leaflet coaptation percent was calculated under diastolic pressure. RESULTS Root dilatation significantly increased regional leaflet stress and strain beyond that found in the normal model. Stress increases ranged from 57% to 399% and strain increases ranged from 39% to 189% in the 50% dilatation model. Leaflet stress and strain were disproportionately high at the attachment edge and coaptation area. Leaflet coaptation was decreased by 18% in the 50% root dilatation model. CONCLUSIONS Idiopathic root dilatation significantly increases leaflet stress and strain and reduces coaptation in an otherwise normal aortic valve. These alterations may affect valve-sparing aortic root replacement procedures.

Long-Term Survival of the Very Elderly Undergoing Aortic Valve Surgery

Background— Increasing numbers of the very elderly are undergoing aortic valve procedures. We describe the short- and long-term survivorship for this cohort. Methods and Results— We conducted a cohort study of 7584 consecutive patients undergoing open aortic valve surgery without (51.1%; AVR) or with (48.9%; AVR + CABG) concomitant coronary artery bypass graft surgery between November 10, 1987 through June 30, 2006. Patient records were linked to the Social Security Administration’s Death Master File. Survivorship was stratified by age and concomitant CABG surgery. During 39 835 person-years of follow-up, there were 2877 deaths. Among AVR, there were 3304 patients <80 years of age, 419 patients 80 to 84 years, and 156 patients ≥85 years (24 patients >90 years). Among AVR+CABG patients, there were 2890 patients <80 years of age, 577 patients 80 to 84 years, and 238 patients ≥85 years (22 patients >90 years). Median survivorship for patients undergoing isolated AVR was 11.5 years (<80 years), 6.8 years (80 to 84 years), 6.2 years (≥85 years); for patients undergoing AVR+CABG, median survivorship was 9.4 years (<80 years), 6.8 years (80 to 84 years), and 7.1 years (≥85 years). Among both procedures, adjusted survivorship was significantly different across strata of age (P<0.001). These findings are similar to life expectancy of the general population from actuarial tables: 80 to 84 years (7 years) and ≥85 years (5 years). Conclusions— Survivorship among octogenarians is favorable, with more than half the patients surviving more than 6 years after their surgery. Concomitant CABG surgery does not diminish median survivorship among patients >80 years of age.

Prospective Trial of Catheter Irrigation and Muscle Flaps for Sternal Wound Infection

BACKGROUND Sternal wound infection is a relatively rare but potentially devastating complication of open heart operations. The most common treatments after debridement are rewiring with antibiotic irrigation and muscle flaps. Here we present the results of a prospective trial to determine the appropriate roles of closed-chest catheter irrigation and muscle flap closure for sternotomy infection and to assess the effect of internal mammary artery bypass grafting on the outcome of each treatment modality. METHODS Between 1990 and 1994, 5,658 sternotomies were performed at the University of Washington Medical Center. Sternal dehiscence occurred in 43 patients, 25 of whom had infection (overall incidence, 0.44%). Because of the infrequency of this complication, a prospective, randomized trial was developed in which the initial approach to sternal dehiscence was rewiring and catheter irrigation. Muscle flaps were used as the primary treatment if the sternum could not be restabilized or as secondary treatment if catheter irrigation failed. Wound resolution, length of hospital stay, and complications were evaluated. RESULTS Sterile dehiscences were successfully closed with irrigation in 17 of 18 patients; the other patient required flap closure. Of the 25 patients with infection, 19 had irrigation and 6, closure with flaps primarily. In the group of infected patients, 17 of the 19 who received irrigation also had internal mammary artery bypass grafting. Irrigation failed in 15 (88.2%) of these 17 patients, and salvage was accomplished with muscle flap closure. All 6 patients with infection who were closed primarily with muscle flaps had a successful outcome. Hospitalization averaged 10.2 days when muscle flaps were used primarily and 14.3 additional days for unsuccessful irrigation. When irrigation was successful, the hospital stay averaged 11.2 days. CONCLUSIONS Catheter irrigation should be reserved for patients without infection or patients with infection but without internal mammary artery bypass grafts in whom dehiscence occurs less than 1 month after sternotomy. All others should have closure with muscle flaps.

Collagen synthesis is upregulated in mitral valves subjected to altered stress.

Mitral regurgitation (MR) and abnormal ventricular wall motion (AVWM) are two cardiac conditions that may increase mitral valve (MV) stresses. Theoretically, increased stress could induce damaging MV tissue alterations. These alterations may impair the preferred option of repair, and mandate replacement. It is hypothesized that MV collagen synthesis is upregulated in response to MR and AVWM. To test this hypothesis in a pilot study, an ischemic sheep model (n = 8) was employed. Four sheep underwent selective coronary artery ligation to infarct a papillary muscle, which resulted in MR. Two other sheep underwent similar coronary ligation to create AVWM. As controls, two sheep underwent sham surgery (no ligation), Sheep were killed 4 or 8 weeks post operatively and their MVs were sectioned. Sections were stained with an antibody (SP1.D8, University of lowa) to procollagen I (precursor to collagen I). The percent area of procollagen stain present was measured by image analysis (Optimas Corporation) and used as an indicator of collagen synthesis. Procollagen results indicated that MV collagen synthesis was upregulated by a factor of 1.8 in both the MR and AVWM groups versus controls. In addition, results showed greater upregulation in anterior leaflets compared with posterior leaflets in both infarct groups. These results indicate that MV collagen synthesis is upregulated in response to MR and AVWM.

Ambulatory intraaortic balloon pump use as bridge to heart transplant

BACKGROUND This study evaluates a modification of an ambulatory intraaortic balloon pump (IABP) technique used in patients with heart failure of ischemic origin for bridge to transplant. METHODS In this retrospective review we evaluated the ability to place the ambulatory IABP, any complications, time on device, and success in bridging to transplant on the ambulatory IABP device. In addition, the cost as compared to current ventricular assist devices was determined. RESULTS Between July 2000 and November 2001, 4 patients have been managed with ambulatory IABP in our combined University of Wisconsin and William S. Middleton Veterans Administration programs. All 4 patients had ischemia as their mode of heart failure, and each had a relative contraindication to standard ventricular assist device use. All 4 patients had ambulatory IABPs successfully placed through the left axillary artery without complication, and were able to ambulate early after ambulatory IABP placement, and increased their rehabilitation status before transplantation. Ambulatory IABP support ranged from 12 to 70 days. All 4 patients have been successfully transplanted and discharged from the hospital. Use of the ambulatory IABP support, even with multiple replacements, translated to 10- to 50-fold savings for each of the reported patients versus standard ventricular assist device use. CONCLUSIONS As a result of our initial experience, we believe that ambulatory IABP is an excellent mode of support in selected patients, and is cost-effective, as compared to conventional ventricular assist device therapy.

Perfluorocarbon emulsion in the cardiopulmonary bypass prime reduces neurologic injury

BACKGROUND Perfluorocarbon emulsion has proved beneficial in the prevention and amelioration of experimental air embolism. We examined whether the addition of perfluorocarbon to the prime solution could lead to a reduction in the incidence and severity of neurologic injury after the formation of a massive air embolism during cardiopulmonary bypass. METHODS Fourteen pigs underwent bypass in which either a crystalloid prime solution or a perfluorocarbon prime solution (10 mL/kg) was used. Ten minutes into bypass a bolus (5 mL/kg) of air or saline (control) was delivered via the carotid artery. The resulting cerebral infarcts were graded on the basis of the findings in triphenyltetrazolium chloride-stained cerebral sections. Colored microspheres were used to measure cerebral blood flow. Bitemporal electroencephalography was used to evaluate cerebral function. RESULTS Cerebral infarction was not found in the perfluorocarbon-air group (0 to 5 animals), as compared with its occurrence in 3 of the 5 animals in the crystalloid-air group. Cerebral blood flow was also maintained or increased in the perfluorocarbon-air group (p < 0.05), and the electroencephalogram total power showed less of a decrease and recovered more completely (p < 0.05) than it did in the crystalloid-air group. CONCLUSIONS The addition of perfluorocarbon emulsion to the cardiopulmonary bypass prime solution leads to a reduction in the incidence and severity of neurologic injury after the formation of a massive air embolism during bypass.