Marisa De Feo

Dose-dependent fetal complications of warfarin in pregnant women with mechanical heart valves

OBJECTIVES The purpose of this study was to assess the incidence of warfarin fetal complications and whether they are dose-dependent. BACKGROUND Gravid patients with mechanical heart valves require long-term anticoagulant therapy. Controversy exists concerning the appropriate treatment of these patients. METHODS Forty-three women on warfarin carrying out 58 pregnancies were studied. For each patient with full-term pregnancy a caesarian section was scheduled for the 38th week during brief warfarin discontinuation. Maternal and fetal complications were evaluated. Fetal complications were divided according to the warfarin dosage < or = 5 mg and > 5 mg necessary to keep an international normalized ratio (INR) of 2.5 to 3.5, and analyzed subsequently. RESULTS A total of 58 pregnancies were observed: 31 healthy babies (30 full term, 1 premature) and 27 fetal complications (22 spontaneous abortions, 2 warfarin embryopathies, 1 stillbirth, 1 ventricular septal defect, 1 growth retardation) were recorded. Two maternal valve thromboses occurred. No fetal or maternal bleeding was observed during caesarian sections or premature vaginal delivery. Patients whose warfarin doses during pregnancy were > 5 mg had 22 fetal complications, whereas those taking a dose < or = 5 mg had only five fetal complications (p = 0.0001). For an increase of the warfarin dose there was a substantially increased probability of fetal complications (p < 0.0001; p < 0.7316). CONCLUSIONS There is a close dependency between warfarin dosage and fetal complications. Patients on warfarin anticoagulation may be delivered by planned caesarian section at the 38th week while briefly interrupting anticoagulation.

Variables predicting adverse outcome in patients with deep sternal wound infection

BACKGROUND Mortality after deep sternal wound infection (DSWI) ranges between 5% and 47%. Variables predicting hospital mortality and prolonged hospital stay are still to be assessed. METHODS Among 13,420 patients who underwent cardiac surgery in our institution between 1979 and 1999, DSWI developed in 112 cases (0.8%). Multiple variables were recorded prospectively and analyzed retrospectively as predictors of hospital death and prolonged (>30 days) hospital stay. The analyzed variables were divided into three groups: (1) related to the patient, including demographic variables and preoperative conditions; (2) related to cardiac operation; and (3) related to infection. Predictive variables were assessed by univariate and multivariate logistic regression analysis. RESULTS Hospital mortality was 16.9%. The hospital stay of the 93 discharged patients ranged between 16 and 180 days (mean 31.3 +/- 15.2). Length of cardiac operation, length of stay in intensive care unit, interval between symptoms of DSWI and wound debridement were found to be the most significant predictors of bad outcome following DSWI. CONCLUSIONS In our study demographic variables and preoperative conditions did not affect the prognosis of DSWI. Lower mortality rate and shorter hospital stay could be achieved with earlier and aggressive treatment of DSWI.

Preoperative anemia in patients undergoing coronary artery bypass grafting predicts acute kidney injury

OBJECTIVES Recent authoritative studies suggested that low preoperative hemoglobin concentration may affect cardiac surgery outcomes. This study aimed, primarily, to investigate whether preoperative anemia is an independent determinant of adverse events after coronary artery bypass grafting and, secondarily, to evaluate the potential dose responsiveness between anemia severity and primary end points. METHODS This single-center prospective study investigated 1214 consecutive patients undergoing coronary artery bypass grafting between January 2004 and June 2007, collecting 100 variables per patient. In 1047 patients (median age 64 years, 18.8% female, 38.9% diabetic, 31.9% urgent/emergency, 15.3% with low preoperative left ventricular ejection fraction) who underwent on-pump procedures and received no preoperative transfusion, the prevalence of preoperative anemia (according to World Health Organization definition) and its unadjusted and adjusted relationships with in-hospital death, cardiac morbidity, and acute kidney injury (AKI-RIFLE [Risk, Injury, Failure, Loss, End-stage kidney disease] criteria) were obtained. RESULTS The prevalence of preoperative anemia was 28%. In-hospital death averaged 3.9%, cardiac morbidity 7.3%, and acute kidney injury 4%. Unadjusted odds ratios (Ors) for in-hospital death, cardiac morbidity, and acute kidney injury were 3.8 (95% confidence interval [CI] 2.0-7.3), 1.7 (95% CI 1.1-2.8), and 4.0 (95% CI 2.1-7.6), respectively. Adjusting for anemia in confounders proved an independent predictor of acute kidney injury (OR 2.06; 95% CI 1.14-3.70), whereas the cardiac morbidity and in-hospital mortality were independently predicted by kidney function. No dose-response relationship emerged between anemia severity and acute kidney injury. CONCLUSIONS Preoperative anemia is independently associated with acute kidney injury after coronary artery bypass grafting. Further studies are warranted to determine whether preoperative low hemoglobin concentration is a marker of severity of illness or a modifiable risk factor.

Recurrent infective endocarditis: a multivariate analysis of 21 years of experience

BACKGROUND To evaluate which variables predict recurrence of endocarditis after surgical treatment, we reviewed our 21-year experience. METHODS Between January 1979 and May 2000, 308 consecutive valve replacement procedures for infective endocarditis were performed in 271 patients. Univariate and multivariate time-related analyses were performed to retrospectively evaluate the role of the following variables in the development of recurrent postoperative endocarditis: gender, site of endocarditis, previous valve disease, drug abuse, diabetes, positive valve/blood cultures, sepsis, perivalvular involvement, previous embolic events, type of replacement device, and persistent postoperative fever. RESULTS Clinical and echocardiographic follow-up was 97.36% complete, mean follow-up time was 53.2+/-3.4 months. Recurrent endocarditis developed in 58 cases (22.5%). Variables predicting recurrence were prosthetic endocarditis (p = 0.00001), positive valve culture (p = 0.0039), and persistence of fever at the seventh postoperative day (p = 0.000001). CONCLUSIONS Correct protocols of antibiotic therapy guided by microbiology may reduce the incidence of recurrent endocarditis to allow for surgery on sterile tissues and to prevent prosthetic infection. Recurrence rate is not affected by the choice of valve substitute, but can be prevented by complete surgical debridement.

ROLE OF MYOFIBROBLASTS IN VASCULAR REMODELLING: FOCUS ON RESTENOSIS AND ANEURYSM

Myofibroblasts (MFs) are contractile cells deriving from a multiplicity of resident cells and/or circulating progenitors that are known to play a key role in wound healing. They were first discovered and analysed in the early 1970s in granulation tissue. Since their first identification, the role of MF and their mechanisms of differentiation have been highlighted in a number of diseases, including organ fibrosis and tumours, with particular attention devoted to the liver, kidney, and pulmonary fibrosis. The aim of this review is to summarize the current evidence for the role played by MFs in two frequent vascular diseases related to the remodelling of the vascular wall: the different forms of arterial restenosis and the most common forms of thoracic aortic aneurysm. The in-depth knowledge of the molecular pathways involved in MF differentiation, contraction, and survival/apoptosis could contribute to the identification of novel therapeutic strategies for anti-fibrotic and anti-remodelling therapy of vascular diseases in which these cells are involved.

Prosthesis-Patient Mismatch in the Elderly: Survival, Ventricular Mass Regression, and Quality of Life

BACKGROUND Evaluation of the impact of prosthesis-patient mismatch (PPM) on long-term outcome and quality of life (QOL) in elderly patients who underwent implantation of small size bileaflet prostheses for aortic stenosis. METHODS Between September 1988 and September 2006, 377 patients aged greater than 70 years underwent aortic valve replacement with a small size bileaflet prosthesis (17, 19, and 21 mm) in one Institution. The study populations survivors (345 patients) were divided into three groups according to the indexed effective orifice area (EOAI): Group A included patients with EOAI less than 0.60 cm(2)/m(2); group B included patients with EOAI ranging between 0.61 and 0.84 cm(2)/m(2); and group C included patients with EOAI 0.85 cm(2)/m(2) or greater. Cumulative and comparative analyses of long-term outcomes and of left ventricular mass regression were performed. The QOL was evaluated with the 36-Item Short Form Health Survey (SF-36) questionnaire. RESULTS Overall hospital mortality was 8.5% (32 patients). Group A included 33 patients (9.6%), group B 175 (50.7%), and group C 137 (39.7%). Actuarial survival was 88.8% +/- 0.016 at 1 year, 82.1% +/- 0.022 at 5 years, and 76.7% +/- 0.032 at 10 years. No difference emerged among the three groups. A significant reduction in left ventricular mass was observed in all groups and in all patient subsets of prosthetic size. The scores obtained in the SF-36 test were similar in the three groups and significantly higher than those of the general population (p < 0.001 in all domains). CONCLUSIONS Incidence of severe PPM is low after aortic valve replacement. Presence of severe or moderate PPM, did not influence long-term outcome, left ventricular mass regression and QOL in a population of septuagenarians.

Tissue Versus Mechanical Prostheses: Quality of Life in Octogenarians

BACKGROUND The aim of this study was to determine whether changes in prognosis and quality of life (QOL) after aortic valve replacement (AVR) in octogenarians differ depending on the choice of mechanical (MP) or tissue (BP) valves. METHODS Between July 1992 and September 2006, 160 consecutive octogenarians underwent AVR with (18.8%) or without concomitant coronary artery bypass grafting. At follow-up (mean 3.4 +/- 2.8 years, 552 patient-years, 98.3% complete), 121 were still alive and answered the Medical Outcomes Study Short-Form 36 Health Survey (SF-36) QOL questionnaire. RESULTS Group BP had 62 patients. Group MP had 98 patients. Preoperative risk factors were comparable except group BP was older. Global hospital mortality was 8.8%. There were 21 late deaths, 61.9% of which were not valve- or anticoagulation-related. A significant difference emerged in 1-, 3-, 5- and 8-year actuarial survival rates (BP: 86.4% +/- 0.04%, 76.9% +/- 0.06%, 58.1% +/- 0.1%, 46.5% +/- 0.14%, respectively, vs MP: 91.3% +/- 0.03%, 88.6% +/- 0.03%, 81.6% +/- 0.05%, 70% +/- 0.67%; p = 0.025) but not in terms of 8-year freedom from valve-related complications (82.6% +/- 0.1% vs 87% +/- 0.053%, p = 0.55). One anticoagulant-related hemorrhage occurred in group MP; one stroke occurred in group BP. Survivors had significant improvement in New York Heart Association functional class compared with preoperatively (1.1 vs 2.8, p < 0.001) Mean QOL scores were satisfactory and substantially comparable between the two groups; in seven domains, scores were higher than those of the age- and sex-matched general Italian population. CONCLUSIONS Long-term survival after AVR in selected octogenarians was similar to that of the general elderly population. The device type exerted no influence on QOL.

LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: Results from the “LOWERING-IT” Trial

BACKGROUND Moderate anticoagulation after mechanical heart valve replacement has been proposed to reduce the risk of bleeding related to lifelong anticoagulation. However, the efficacy of such reduced antithrombotic regimens is still unknown. The present prospective open-label, single-center, randomized controlled trial aimed to evaluate the safety and feasibility of reduced oral anticoagulation after isolated mechanical aortic valve replacement. METHODS Low-risk patients undergoing bileaflet mechanical aortic valve replacement were randomized to a low International normalized ratio (INR) target (1.5-2.5; LOW-INR group) or to the standard currently recommended INR (2.0-3.0; CONVENTIONAL-INR group) through daily coumarine oral therapy. No aspirin was added. Median follow-up was 5.6 years. The primary outcome was assessment of noninferiority of the low over the standard anticoagulation regimen on thromboembolic events. Secondary end point was the superiority of the reduced INR target strategy on bleeding events. RESULTS We analyzed 396 patients (197 in the LOW-INR group and 199 in the CONVENTIONAL-INR group). The mean of INR was 1.94 +/- 0.21 and 2.61 +/- 0.25 in the LOW-INR and CONVENTIONAL-INR groups, respectively (P < .001). One versus three thromboembolic events occurred in the LOW-INR and CONVENTIONAL-INR, respectively, meeting the noninferiority criterion (P = .62). Total hemorrhagic events occurred in 6 patients in the LOW-INR group and in 16 patients in the CONVENTIONAL-INR group (P = .04). CONCLUSIONS LOWERING-IT trial established that the proposed LOW-INR target is safe and feasible in low-risk patients after bileaflet aortic mechanical valve replacement. It results in similar thrombotic events and in a significant reduction of bleeding occurrence when compared to the conventional anticoagulation regimen.

Perioperative clinical predictors of atrial fibrillation occurrence following coronary artery surgery

OBJECTIVE Atrial fibrillation (AF) is the most frequently encountered arrhythmic complication associated with coronary surgery. The aim of this paper was then to identify the clinical predictors of post-CABG AF occurrence. METHODS 150 consecutive patients were included in this study and divided into two groups according to the absence (SR group, 104 male and 22 female, age 58.4+/-8.8 years) or presence (AF group, 23 male and 1 female, age 65.4+/-6.3 years) of post-CABG AF. Forty-seven perioperative variables were considered. RESULTS After univariate analysis, advanced age (SR vs. AF: 58.4+/-8.8 vs. 65.4+/-6.3, P < 0.001), an increased BMI (SR vs. AF: 26.1+/-2.7 vs. 27.4+/-2.5, P = 0.026), a prior history of paroxysmal AF (SR vs. AF: 3.2% vs. 16.7%, P = 0.028), left atrial enlargement (SR vs. AF: 21.1% vs. 70.8%, P < 0.001) and a more severe coronary artery disease (CAD) (SR vs. AF: no. of diseased vessels: 2.42+/-0.7 vs. 2.91+/-0.3, P = 0.001; three-vessel CAD (54.1% vs. 91.3%, P = 0.002) were the only factors that statistically differed between the groups. Multivariate logistic regression analysis identified left atrial enlargement (P < 0.0001), a prior history of paroxysmal AF (P = 0.007) and a more severe CAD (P = 0.0047) to be independent correlates for AF. CONCLUSIONS Post-CABG AF seems to require a well definite anatomical and electrical substrate that is generated by increased left atrial dimensions, a greater extension of coronary lesions and a possible electrical remodeling consequent to prior repetitive episodes of paroxysmal AF.

Mechanical Aortic Valve Replacement in Young Women Planning on Pregnancy : Maternal and Fetal Outcomes Under Low Oral Anticoagulation, a Pilot Observational Study on a Comprehensive Pre-Operative Counseling Protocol

OBJECTIVES This pilot prospective observational study aimed to evaluate the maternal and fetal outcomes of pregnancies under low-dose oral anticoagulation therapy after aortic mechanical replacement. BACKGROUND Need for valve replacement is still an issue for young women with native valve disease who are planning on future pregnancy. Choice of replacement device is a challenging clinical task. METHODS A comprehensive pre-operative counseling protocol to guide choice of replacement device was developed. The pre-operative anticoagulation trial to determine the warfarin daily dosage needed to reach target international normalized ratio (INR) represented the main stem of such protocol. Pregnancies on low-dose anticoagulation therapy (target INR: 1.5 to 2.5) were allowed in a highly selected subset of mechanical aortic valve recipients. RESULTS Twenty-two patients of 40 originally referred for native valve disease surgery requiring valve replacement, safely underwent the pre-operative anticoagulation challenge. No maternal or fetal complications were detected in 16 pregnancies under low oral anticoagulation. Patterns of warfarin daily dosage and induced INRs were characterized during pregnancy. CONCLUSIONS In this small sample observational study, a pre-operative anticoagulation therapy trial helped young women scheduled for valve replacement to acquire complete information as to the choice of prosthetic device. In selected third-generation mechanical aortic prosthesis recipients, low-dose anticoagulation therapy seems safe and feasible for both mother and fetus. Further studies are needed to validate this approach.