One thousand Carpentier-Edwards pericardial valves in the aortic position: what has changed in the past 20 years, and what are the effects on hospital complications?

BACKGROUND AND AIM OF THE STUDY: Over the past 20 years, both the typical age and co-morbidity of patients referred for aortic valve replacement (AVR) have increased. In order to assess the effect of these changes on hospital complications, an evaluation was conducted of patient characteristics within this time period. METHODS: This retrospective study included 1,000 consecutive patients who underwent AVR with a pericardial valve. Concomitant coronary artery bypass grafting (CABG) was performed in 610 cases. Among 25 preoperative and five perioperative factors, and eight hospital complications, the changes in incidence that occurred during the periods 1986-1991, 1992-1996, 1997-2001, and 2002-2006, were investigated. Predictive factors for non-cardiac hospital complications required further exploration, as these were the only complications to increase significantly with time; however, this type of complication is less lethal. RESULTS: Significant increases were identified in age, and in the incidence of non-cardiac co-morbidity, previous CABG and preoperative congestive heart failure (p mostly <0.0001). Among hospital complications, only non-cardiac problems showed a significant increase. The independent predictors included previous CABG (p = 0.004), concomitant CABG (p = 0.006), renal impairment (p = 0.008), conduction defects (p = 0.010), previous pacemaker implantation (p = 0.014), chronic obstructive lung disease (p = 0.015), and concomitant carotid artery surgery (p = 0.032). CONCLUSION: During the past 20 years, patients referred for AVR have become older and have more co-morbidity. However, the incidence only of non-cardiac hospital complications was increased. Previous and concomitant surgery, as well as non-cardiac co-morbidity, are important predictors that must be taken into account at referral, but should not contraindicate AVR.

Endogenous inhibitors of hypertrophy in concentric versus eccentric hypertrophy.

Left ventricular (LV) hypertrophy (LVH) is an adaptive response to hemodynamic overload, but also contributes to the pathogenesis of heart failure. LVH can be concentric (cLVH) but subsequent dilatation and progression to eccentric hypertrophy (eLVH) may lead to global pump failure. Recently, several endogenous molecular inhibitors of hypertrophy have been identified. Using real-time PCR, we compared the myocardial mRNA expression of these inhibitors in pressure-overload induced cLVH (severe aortic stenosis) and in volume overload-induced eLVH (severe mitral regurgitation) in patients, and during the progression from cLVH to eLVH in pressure overload in rat. Each of these genes showed a unique temporal expression profile. Strikingly, except for SOCS-3, changes in gene expression of these negative regulators in rat cLVH and eLVH vs sham were recapitulated in human cLVH and eLVH. In particular, VDUP-1 and MCIP-1 were high in cLVH but expression levels were normal in eLVH, both in rat and human. These data indicate that during the progression of LVH, both in pressure and volume overload, expression levels of endogenous inhibitors of hypertrophy are modified and that these changes may have pathophysiological significance. In particular, MCIP-1 (the endogenous calcineurin inhibitor) and VDUP-1 (the endogenous inhibitor of thioredoxin) are potential molecular switches in the progression of LV hypertrophy.

Histological evaluation of autophagic cell death in calcified aortic valve stenosis.

BACKGROUND AND AIM OF THE STUDY: Calcification in aortic valves is the most common valvular lesion in western populations. This event is correlated with cellular degeneration in the valvular cusps, although there is no exact evidence how these cells die: this requires further exploration. METHODS: Twelve human severely calcified aortic valves obtained during cardiac surgery were studied by semi-quantitative analysis, and results compared with data from 12 human control aortic valves obtained during autopsy. Tissue analysis was by hematoxylin and eosin and Alcian blue staining. Detection of neurons was by immunohistochemical staining of PGP9.5 and neurofilament. In order to detect autophagy, an immunohistochemical staining for ubiquitin was used. The TUNEL technique was used to detect apoptosis. Co-localization of Alizarin red with ubiquitin labeling was performed on non-decalcified aortic valves. RESULTS: Hematoxylin and eosin staining showed moderate to severe mineralization in 10 of 12 patients in the surgical group, but in only one of 12 in the autopsy group. No significant observations were made with regard to PGP9.5 and neurofilament staining. Moderate to severe ubiquitin labeling was found initially in the majority of the surgical resection group (9/12) compared to a minority in the autopsy group (1/12). TUNEL-positive labeling was very rare and found mostly at the endothelial layer of the valvular cusps. CONCLUSION: Immunohistochemical methods showed the main cell death mechanism involved in the calcification of aortic leaflets to be autophagy rather than apoptosis. These findings suggest that autophagic cell death might play a role in the release of matrix vesicles in early degenerative aortic valves, thereby attracting inflammatory cells, and this could eventually lead to mineralization.

Risk factors for congestive heart failure after aortic valve replacement with a Carpentier-Edwards pericardial prosthesis in the elderly.

BACKGROUND AND AIM OF THE STUDY: Congestive heart failure (CHF) after aortic valve replacement (AVR) is an important cause of morbidity. The study aim was to identify preoperative risk factors for CHF. METHODS: A total of 500 consecutive patients (271 males, 229 females; median age 73 years; range: 71-77 years) was investigated retrospectively. The AVR was performed using a Carpentier-Edwards pericardial valve, and a total of 348 additional procedures (313 coronary artery bypass grafts; CABG) was carried out. The outcome studied was CHF, during both hospital stay and long-term follow up. Univariate and multivariate statistical analyses were used to investigate 15 risk factors. RESULTS: During the hospital stay, 13 patients developed CHF, with four fatalities. Significant risk factors for CHF included urgent operation (p = 0.031), preoperative atrial fibrillation (AF) (p = 0.031) and NYHA functional class IV (p = 0.05). A logistic regression analysis revealed need for urgent operation (p = 0.034) as the sole factor. During long-term follow up, 43 patients developed CHF, with seven fatalities. Univariate analysis identified seven risk factors with significant effect: valve size <19 mm (p = 0.004), preoperative conduction defects (p = 0.007), chronic postoperative AF (p = 0.013), cross-clamp time >75 min (p = 0.032), NYHA class IV (p = 0.041), coronary artery disease (CAD) (p = 0.043) and additional CABG (p = 0.050). Multivariate analysis identified three risk factors: preoperative conduction defects (p = 0.004), postoperative AF (p = 0.005) and CAD (p = 0.037) CONCLUSION: Morbidity due to CHF after AVR could be minimized with correct treatment of AF and of conduction defects. Patient age, valve size, cross-clamp time and preoperative severity or symptoms were not independent risk factors. Moreover, small native aortic valve rings should not necessarily be enlarged, the cross-clamp time should be kept to a minimum, and surgery should not be delayed when symptoms have developed.

Risk factors and survival after aortic valve replacement in octogenarians.

BACKGROUND AND AIM OF THE STUDY: The study aim was to determine if aortic valve replacement in octogenarians is still rewarding. METHODS: Between 1986 and 2000, 500 patients received a Carpentier-Edwards pericardial valve in the aortic position. Of these patients, 348 also underwent coronary artery bypass grafting (CABG). Sixty patients were aged > or =80 years. A retrospective follow up totaled 2,022 patient-years. A Cox multivariate regression analysis included 17 preoperative potential risk factors: age >80 years; gender; carcinoma; chronic obstructive pulmonary disease; renal failure; stroke; arterial hypertension; carotid artery disease; myocardial infarction; coronary artery disease; conduction defects; atrial fibrillation; medically treated endocarditis; severity of symptoms; urgent operation; left ventricular function; and need for digitalis. RESULTS: For hospital mortality, independent predictors were urgent surgery (Risk Ratio 10.2, 95% CI 2.5-42.0, p = 0.001); age over 80 (RR 4.5, CI 1.3-14.9; p = 0.015); need for digitalis (RR 3.8, CI 1.3-10.6, p = 0.010); male gender (RR 3.7, CI 1.1-12.4; p = 0.035); and myocardial infarction (RR 3.1, CI 1.0-9.4, p = 0.051). For long-term mortality, independent predictors. were urgent surgery (RR 4.5, CI 1.6-12.6; p = 0.004), age >80 (RR 2.5, CI 1.4-4.5, p = 0.002); myocardial infarction (RR 2.1, CI 1.3-3.4; p = 0.003); carcinoma (RR 2.0; CI 1.1-3.7; p = 0.021); and digitalis use (RR 1.8; CI 1.2-2.7; p = 0.004). Univariate analysis revealed that age >80 years (38.6% versus 77.0%), need for urgent operation (0% versus 75.1%), need for digitalis (69.4% versus 76.3%) and myocardial infarction (57.1% versus 76.4%) had a significant effect on five-year survival. CONCLUSION: For hospital mortality and long-term mortality, a need for urgent surgery was the most determining factor. Age >80 years was the second most important factor, but previous myocardial infarction and need for digitalis were almost equally important. Aortic valve replacement in octogenarians is still rewarding, as five-year survival is 38.6%. Thus, surgery in these patients should not be postponed.

Effect of prior malignancy on survival after cardiac surgery.

BACKGROUND: The number of patients with a previously treated tumor, needing cardiac surgery is increasing. Whether this operation in these patients is justified is determined by the long-term outcome. METHODS: Of 8620 patients referred for cardiac surgery, 205 had a documented malignant tumor. The time interval between the occurrence of the tumor and the cardiac surgery was recorded. These patients were matched with 205 patients without a tumor according to age, gender, comorbidity and type of cardiac surgery. The patients were followed retrospectively. A chi(2) Kaplan Meier and Cox' regression analysis were performed. RESULTS: During follow-up, 95.8% of the patients were traced (2794 patient years). Univariate analysis showed that 5- and 10-year survival was better in patients without a malignant tumor in the history (0.91 +/- 0.02 versus 0.72 +/- 0.03 and 0.73 +/- 0.04 versus 0.40 +/- 0.05; p < 0.0001). For shorter time intervals, mortality for all causes and mortality due to the tumor increase significantly (p < 0.0001). Multivariate analysis identified 4 independent variables: a malignant tumor in the history (p < 0.001), chronic obstructive pulmonary disease (p = 0.003), age (p = 0.001), and impaired left ventricular function (p = 0.035) CONCLUSIONS: A malignant tumor in the history is the most prognostic factor after cardiac surgery, but the operation is still rewarding. Fatal progression of the tumor is seen if the time interval between the occurrence of the malignant tumor and cardiac surgery is short. Other unfavorable factors are decreased left ventricular function, chronic obstructive pulmonary disease and high age.