Causes of death and cardiovascular complications in adolescents and adults with congenitally malformed hearts: an autopsy study of 102 cases

Objectives: To identify the causes of death and main cardiovascular complications in adolescents and adults with congenitally malformed hearts. Design: Retrospective review of 102 necropsy reports from a tertiary centre obtained over a period of 19 years. Methods: The diagnosis, the operated or non-operated state of the main defect, the cause of death, and main complications were related to the age and gender. Other clinically relevant conditions, and identifiable sequels of previous diseases, were also noted. Results: The ages ranged from 15 to 69 years, with a mean of 31.1 and a median of 28 years, with no difference detected according to the gender. Of the patients, two-thirds had been submitted to at least one cardiac surgery. The mean age of death was significantly higher in non-operated patients (p = 0.003). The most prevalent cause of death in the whole group was related to recent surgery, found in one-third. From them, two-fifths corresponded to reoperations. Among the others, cardiac failure was the main terminal cause in another third, and the second cause was pulmonary thromboembolism in just over one-fifth, presenting a significant association with histopathological signs of pulmonary hypertension (p = 0.011). Infection was the cause of death in 7.8% of the patients, all previously operated. Acute infective endocarditis was present or was the indication for the recent surgery in one-tenth of the patients, this cohort having a mean age of 27.8 years. There was a statistically significant association between the occurrence of endocarditis and defects causing low pulmonary blood flow (p = 0.043). Conclusions: Data derived from necropsies of adults with congenital heart defects can help the multidisciplinary team refine both their diagnosis and treatment.

Azithromycin does not prevent six-month myointimal proliferation but attenuates the transient systemic inflammation occurring after coronary stenting

Stent implantation produces a systemic increase of inflammatory markers that correlates with Chlamydophila pneumoniae infection in atherosclerotic plaque. We performed a clinical intervention study to investigate the effect of antibiotic treatment on 6-month follow-up angiographic minimal luminal diameter after stenting. Ninety patients were randomly assigned to oral azithromycin or placebo in a double-blinded and randomized fashion. Medication was initiated 2 weeks before a pre-scheduled stenting procedure and maintained 12 weeks thereafter. Angiographic outcomes were evaluated by a six-month follow-up angiography and laboratorial parameters were accessed by blood sampling 2 weeks before stenting, within the first 24 h after procedure and additional samples after four weeks and 6 months. Minimal luminal diameter (1.76 +/- A 0.56 mm Vs. 1.70 +/- A 0.86 mm; P = 0.7), restenosis rate, diameter stenosis, late loss, and binary restenosis rates were comparable in placebo and azithromycin group in the 6 months follow-up. Serum levels of C-reactive protein presented a three fold significant increase in the control group one day after stenting but did not change in the azithromycin group (8.5 [3.0;16.4] Vs. 2.9 [1.7;6.6]-median [25;75 percentile] P < 0.01). Azithromycin does not improve late angiographic outcomes but attenuates the elevation of C-reactive protein levels after stenting, indicating an anti-inflammatory effect.

Risk factors for Chagas` disease reactivation after heart transplantation

Background: Chagas` disease is the illness caused by the protozoan Trypanosoma cruzi and it is still endemic in Latin America. Heart transplantation is a therapeutic option for patients with end-stage Chagas` cardiomyopathy. Nevertheless, reactivation may occur after transplantation, leading to higher morbidity and graft dysfunction. This study aimed to identify risk factors for Chagas` disease reactivation episodes. Methods: This investigation is a retrospective cohort study of all Chagas` disease heart transplant recipients from September 1985 through September 2004. Clinical, microbiologic and histopathologic data were reviewed. Statistical analysis was performed with SPSS (version 13) software. Results: Sixty-four (21.9%) patients with chronic Chagas` disease underwent heart transplantation during the study period. Seventeen patients (26.5%) had at least one episode of Chagas` disease reactivation, and univariate analysis identified number of rejection episodes (p = 0.013) and development of neoplasms (p = 0.040) as factors associated with Chagas` disease reactivation episodes. Multivariate analysis showed that number of rejection episodes (hazard ratio = 1.31; 95% confidence interval [CI]: 1.06 to 1.62; p = 0.011), neoplasms (hazard ratio = 5.07; 95% CI: 1.49 to 17.20; p = 0.009) and use of mycophenolate mofetil (hazard ratio = 3.14; 95% CI: 1.00 to 9.84; p = 0.049) are independent determinants for reactivation after transplantation. Age (p = 0.88), male gender (p = 0.15), presence of rejection (p = 0.17), cytomegalovirus infection (p = 0.79) and mortality after hospital discharge (p = 0.15) showed no statistically significant difference. Conclusions: Our data suggest that events resulting in greater immunosuppression status contribute to Chagas` disease reactivation episodes after heart transplantation and should alert physicians to make an early diagnosis and perform pre-emptive therapy. Although reactivation led to a high rate of morbidity, a low mortality risk was observed.

Gene expression profile of residual breast cancer after doxorubicin and cyclophosphamide neoadjuvant chemotherapy

In breast cancer patients, primary chemotherapy is associated with the same survival benefits as adjuvant chemotherapy. Residual tumors represent a clinical challenge, Lis they may be resistant to additional cycles of the same drugs. Our aim was to identify differential transcripts expressed in residual tumors, after neoadjuvant chemotherapy, that might be related with tumor resistance. Hence, 16 patients with paired tumor samples, collected before and after treatment (4 cycles doxorubicin/cyclophosphamide, AC) had their gene expression evaluated on cDNA microarray slides containing 4,608 genes. Three hundred and eighty-nine genes were differentially expressed (paired Student`s t-test, pFDR<0.01) between pre- and post-chemotherapy samples and among the regulated functions were the JNK cascade and cell death. Unsupervised hierarchical clustering identified one branch comprising exclusively, eight pre-chemotherapy samples and another branch, including the former correspondent eight post-chemotherapy samples and other 16 paired pre/post-chemotherapy samples. No differences in clinical and tumor parameters could explain this clustering. Another group of I I patients with paired samples had expression of selected genes determined by real-time RT-PCR and CTGF and DUSP1 were confirmed more expressed in post- as compared to pre-chemotherapy samples. After neoadjuvant chemotherapy some residual samples may retain their molecular signature while others present significant changes in their gene expression, probably induced by the treatment. CTGF and DUSP1 overexpression in residual samples may be a reflection of resistance to further administration of AC regimen.

Long-Term Follow-Up After Successful Transjugular Intrahepatic Portosystemic Shunt Placement in a Pediatric Patient with Budd-Chiari Syndrome

Orthotopic liver transplantation is the standard of care in patients with Budd-Chiari syndrome (BCS), and transjugular intrahepatic portosystemic shunt (TIPS) has become an important adjunct procedure while the patient is waiting for a liver. No long-term follow up of TIPS in BCS patients has been published in children. We report successful 10-year follow-up of a child with BCS and iatrogenic TIPS dysfunction caused by oral contraceptive use.

Evaluating Causes of Death in Familial Adenomatous Polyposis

Background Familial adenomatous polyposis is a genetic syndrome associated with an increased risk of colorectal cancer (CRC) and different extracolonic manifestations Goals The goal of this study is to evaluate the frequency of death causes Material and Methods Charts from 97 patients treated from 1977 to 2008 were reviewed Retrieved data and family information allowed us to classify causes of death in those related to CCR to other malignancies or other causes Results There were analyzed data from 46 men (47 4%) and 51 women (52 6%) with an average age of 35 1 years (14 to 82) At diagnosis, 57 patients (58 7%) already had CRC-associated polyposis There were performed 93 colectomies, one internal diversion, and one partial resection Two patients were not operated on Results from 19 deceased patients (19 5%) were analyzed CRC, other tumors (desmoid tumors, lymphoma, and gastric cancer), and other causes (complication of duodenal cancer surgery, complication after ileorectal anastomosis (IRA), and coronary disease) were responsible for 12 (63 1%), four (21 1%), and three (15 8%) of all deaths, respectively Death from CRC occurred in the context of either systemic, rectal, or pouch recurrence Desmoid disease was the second cause of death (10 5% of all causes), leading to a fatal outcome 22% of all patients who developed DT during the study period Upper digestive carcinomas were responsible for other two death cases Conclusions (1) CRC is still the most prevalent cause of death, (2) even after curative resections, CRC can cause death through rectal or pouch malignization, (3) long-term survival was also strongly related to the development of extracolonic neoplasia, especially desmoid tumors and gastroduodenal carcinoma, (4) our results raise the need for local improvement in familiar screening and help us to define follow-up strategies and patient-information standards

Early keratocyte apoptosis after epithelial scrape injury in the human cornea

Animal studies in mice, rats, rabbits, pigs and hens demonstrated that anterior keratocytes undergo programmed cell death or apoptosis after corneal epithelial injury. Many other wound healing changes subsequently follow the keratocyte apoptosis response. This study evaluated early keratocyte apoptosis after corneal epithelial scrape injury in human eyes scheduled for enucleation for malignancy. Two eyes had corneal epithelial scrape 1 h prior to the enucleation and another eye served as a control and had no corneal scrape prior to enucleation. One additional eye was enucleated, washed with balanced salt solution, and then had the corneal epithelium scraped 1 h prior to processing for analysis. Apoptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and confirmed by transmission electron microscopy (TEM). Anterior keratocyte apoptosis was detected in the three corneas that had epithelial scrape injury, but not in the control unwounded cornea. This study confirmed that keratocyte apoptosis is also an early response to corneal epithelial injury in humans and showed that tears are not essential for keratocyte apoptosis to occur in response to epithelial injury. (C) 2009 Elsevier Ltd. All rights reserved.

Gender-Specific Differences in Fetal Cardiac Troponin T in Pregnancies Complicated by Placental Insufficiency

Background: Placental insufficiency and fetal growth restriction may lead to fetal hypoxia and acidemia, which result in fetal cardiac injury. Objective: The goal of this study was to compare the levels of fetal cardiac troponin T (cTnT) at birth and fetal Doppler parameters according to fetal gender in pregnancies complicated by placental insufficiency before 34 weeks` gestation. Methods: Between March 2007 and November 2010, singleton pregnancies with placental insufficiency characterized by abnormal umbilical artery Doppler results were prospectively studied. All the patients delivered by cesarean section, and Doppler examinations were performed up to 48 hours before birth. Immediately after delivery, umbilical artery blood samples were obtained for fetal cTnT measurements. Results: Fifty high-risk pregnant women met the study criteria. The study groups were as follows: group 1 consisted of 23 male fetuses (46%) and group 2 consisted of 27 female fetuses (54%). cTnT levels were significantly higher in the group of male fetuses (median, 0.14; range, 0.01-0.85) compared with the group of female fetuses (median, 0.05; range, 0.01-0.27) (P = 0.039). In the group of male fetuses, Doppler results of the ductus venosus assessment revealed values of pulsatility index for veins >= 1.0 in 15 male fetuses (65.2%) and 9 female fetuses (33.3%) (P = 0.032). Conclusions: Fetal gender was associated with cTnT level at birth in pregnancies complicated by placental insufficiency before 34 weeks` gestation, although the Doppler findings did not support gender differences. The fetal cardiac compromise and cardiac injury may be influenced by fetal gender, suggesting differences in the cardiovascular response to fetal hypoxia. (Gend Med. 2011;8:202-208) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.

Red Blood Cell Transfusions are Independently Associated with Intra-Hospital Mortality in Very Low Birth Weight Preterm Infants

Objective To test the hypothesis that red blood cell (RBC) transfusions in preterm infants are associated with increased intra-hospital mortality. Study design Variables associated with death were studied with Cox regression analysis in a prospective cohort of preterm infants with birth weight <1500 g in the Brazilian Network on Neonatal Research. Intra-hospital death and death after 28 days of life were analyzed as dependent variables. Independent variables were infant demographic and clinical characteristics and RBC transfusions. Results Of 1077 infants, 574 (53.3%) received at least one RBC transfusion during the hospital stay. The mean number of transfusions per infant was 3.3 +/- 3.4, with 2.1 +/- 2.1 in the first 28 days of life. Intra-hospital death occurred in 299 neonates (27.8%), and 60 infants (5.6%) died after 28 days of life. After adjusting for confounders, the relative risk of death during hospital stay was 1.49 in infants who received at least one RBC transfusion in the first 28 days of life, compared with infants who did not receive a transfusion. The risk of death after 28 days of life was 1.89 times higher in infants who received more than two RBC transfusions during their hospital stay, compared with infants who received one or two transfusions. Conclusion Transfusion was associated with increased death, and transfusion guidelines should consider risks and benefits of transfusion. (J Pediatr 2011; 159: 371-6).

Influence of coronary artery disease assessment and treatment in the incidence of cardiac events in renal transplant recipients

Background: The best strategy for pre-transplant investigation and treatment of coronary artery disease (CAD) is controversial. Methods: We evaluated 167 renal transplant recipients before transplantation to determine the incidence of cardiac events and death. We performed clinical evaluations and myocardial scans in all patients and coronary angiography in select patients. Results: Asymptomatic patients with normal myocardial scans (n = 57) had significantly fewer cardiac events (log-rank = 0.0002) and deaths (log-rank = 0.0005) than did patients with abnormal scans but no angiographic evidence of CAD (n = 76) and individuals with CAD (n = 34) documented angiographically. CAD increased the probability of events (HR = 2.27, % CI 1.007-5.11; p = 0.04). The incidence of cardiac events (log-rank = 0.349) and deaths (log-rank = 0.588) was similar among patients treated medically (n = 23) or by intervention (n = 11). Conclusion: Asymptomatic patients with normal myocardial scans had a better cardiac prognosis than did patients with or without CAD and positive for myocardial ischemia. Patients with altered scan and CAD had the poorer outcome. Guideline-oriented medical treatment is safe and yields results comparable to coronary intervention in renal transplant patients with CAD. The data do not support pre-emptive myocardial revascularization for renal transplant candidates.

Myocardial Perfusion Imaging Is a Strong Predictor of Death in Women

OBJECTIVES We sought to assess the prognostic value and risk classification improvement using contemporary single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) to predict all-cause mortality. BACKGROUND Myocardial perfusion is a strong estimator of prognosis. Evidence published to date has not established the added prognostic value of SPECT-MPI nor defined an approach to detect improve classification of risk in women from a developing nation. METHODS A total of 2,225 women referred for SPECT-MPI were followed by a mean period of 3.7 +/- 1.4 years. SPECT-MPI results were classified as abnormal on the presence of any perfusion defect. Abnormal scans were further classified as with mild/moderate reversible, severe reversible, partial reversible, or fixed perfusion defects. Risk estimates for incident mortality were categorized as <1%/year, 1% to 2%/year, and >2%/year using Cox proportional hazard models. Risk-adjusted models incorporated clinical risk factors, left ventricular ejection fraction (LVEF), and perfusion variables. RESULTS All-cause death occurred in 139 patients. SPECT-MPI significantly risk stratified the population; patients with abnormal scans had significantly higher death rates compared with patients with normal scans, 13.1% versus 4.0%, respectively (p < 0.001). Cox analysis demonstrated that after adjusting for clinical risk factors and LVEF, SPECT-MPI improved the model discrimination (integrated discrimination index = 0.009; p = 0.02), added significant incremental prognostic information (global chi-square increased from 87.7 to 127.1; p < 0.0001), and improved risk prediction (net reclassification improvement = 0.12; p = 0.005). CONCLUSIONS SPECT-MPI added significant incremental prognostic information to clinical and left ventricular functional variables while enhancing the ability to classify this Brazilian female population into low-and high-risk categories of all-cause mortality. (J Am Coll Cardiol Img 2011;4:880-8) (C) 2011 by the American College of Cardiology Foundation

Recovery of Renal Function in Heart Transplantation Patients After Conversion From a Calcineurin Inhibitor-Based Therapy to Sirolimus

Background. Renal failure is the most important comorbidity in patients with heart transplantation, it is associated with increased mortality. The major cause of renal dysfunction is the toxic effects of calcineurin inhibitors (CNI). Sirolimus, a proliferation signal inhibitor, is an imunossupressant recently introduced in cardiac transplantation. Its nonnephrotoxic properties make it an attractive immunosuppressive agent for patients with renal dysfunction. In this study, we evaluated the improvement in renal function after switching the CNI to sirolimus among patients with new-onset kidney dysfunction after heart transplantation. Methods. The study included orthotopic cardiac transplant (OHT) patients who required discontinuation of CNI due to worsening renal function (creatinine clearance <50 mL/min). We excluded subjects who had another indication for initiation of sirolimus, that is, rejection, malignancy, or allograft vasculopathy. The patients were followed for 6 months. The creatinine clearance (CrCl) was estimated according to the Cockcroft-Gault equation using the baseline weight and the serum creatinine at the time of introduction of sirolimus and 6 months there after. Nine patients were included, 7 (78%) were males and the overall mean age was 60.1 +/- 12.3 years and time since transplantation 8.7 +/- 6.1 years. The allograft was beyond 1 year in all patients. There was a significant improvement in the serum creatinine (2.98 +/- 0.9 to 1.69 +/- 0.5 mg/dL, P = .01) and CrCl (24.9 +/- 6.5 to 45.7 +/- 17.2 mL/min, P = .005) at 6 months follow-up. Conclusion. The replacement of CNI by sirolimus for imunosuppressive therapy for patients with renal failure after OHT was associated with a significant improvement in renal function after 6 months.

The Aging Process of the Heart: Obesity Is the Main Risk Factor for Left Atrial Enlargement During Aging The MONICA/KORA (Monitoring of Trends and Determinations in Cardiovascular Disease/Cooperative Research in the Region of Augsburg) Study

Objectives This prospective study evaluated the association of obesity and hypertension with left atrial (LA) volume over 10 years. Background Although left atrial enlargement (LAE) is an independent risk factor for atrial fibrillation, stroke, and death, little information is available about determinants of LA size in the general population. Methods Participants (1,212 men and women, age 25 to 74 years) originated from a sex-and age-stratified random sample of German residents of the Augsburg area (MONICA S3). Left atrial volume was determined by standardized echocardiography at baseline and again after 10 years. Left atrial volume was indexed to body height (iLA). Left atrial enlargement was defined as iLA >= 35.7 and >= 33.7 ml/m in men and women, respectively. Results At baseline, the prevalence of LAE was 9.8%. Both obesity and hypertension were independent predictors of LAE, obesity (odds ratio [OR]: 2.4; p < 0.001) being numerically stronger than hypertension (OR: 2.2; p < 0.001). Adjusted mean values for iLA were significantly lower in normal-weight hypertensive patients (25.4 ml/m) than in obese normotensive individuals (27.3 ml/m; p = 0.016). The highest iLA was found in the obese hypertensive subgroup (30.0 ml/m; p < 0.001 vs. all other groups). This group also presented with the highest increase in iLA (+6.0 ml/m) and the highest incidence (31.6%) of LAE upon follow-up. Conclusions In the general population, obesity appears to be the most important risk factor for LAE. Given the increasing prevalence of obesity, early interventions, especially in young obese individuals, are essential to prevent premature onset of cardiac remodeling at the atrial level. (J Am Coll Cardiol 2009; 54: 1982-9) (C) 2009 by the American College of Cardiology Foundation

Effect of Femtosecond Laser Energy Level on Corneal Stromal Cell Death and Inflammation

PURPOSE: To analyze the effects of variations in femtosecond laser energy level on corneal stromal cell death. and inflammatory cell influx following flap creation in a rabbit model. METHODS: Eighteen rabbits were stratified in three different groups according to level of energy applied for flap creation (six animals per group). Three different energy levels were chosen for both the lamellar and side cut; 2.7 mu J (high energy), 1.6 mu J (intermediate energy), and 0.5 mu J (low energy) with a 60 kHz, model II, femtosecond laser (IntraLase). The opposite eye of each rabbit served as a control. At the 24-hour time point after surgery, all rabbits were euthanized and the comeoscleral rims were analyzed for the levels of cell death and inflammatory cell influx with the terminal uridine deoxynucleotidyl transferase dUTP-nick end labeling (TUNEL) assay and immunocytochemistry for monocyte marker CD11b, respectively. RESULTS: The high energy group (31.9 +/- 7.1 [standard error of mean (SEM) 2.9]) had significantly more TUNEL positive cells in the central flap compared to the intermediate (22.2 +/- 1.9 [SEM 0.8], P=.004), low (17.9 +/- 4.0 [SEM 1.6], P <= .001), and control eye (0.06 +/- 0.02 [SEM 0.009], P <= .001) groups. The intermediate and low energy groups also had significantly more TUNEL positive cells than the control groups (P <= .001). The difference between the intermediate and low energy levels was not significant (P=.56). The mean for CD11b-positive cells/400x field at the flap edge was 26.1 +/- 29.3 (SEM 11.9), 5.8 +/- 4.1 (SEM 1.6), 1.6 +/- 4.1 (SEM 1.6), and 0.005 +/- 0.01 (SEM 0.005) for high energy, intermediate energy, low energy, and control groups, respectively. Only the intermediate energy group showed statistically more inflammatory cells than control eyes (P = .015), most likely due to variability between eyes. CONCLUSIONS: Higher energy levels trigger greater cell death when the femtosecond laser is used to create corneal flaps: Greater corneal inflammatory cell infiltration is observed with higher femtosecond laser energy levels. [J Refract Surg. 2009;25:869-874.] doi:10.3928/1081597X-20090917-08

Prevention of Venous Thrombosis by Warfarin after Permanent Transvenous Leads Implantation in High-Risk Patients

Background: The incidence of venous lesions following transvenous cardiac device implantation is high. Previous implantation of temporary leads ipsilateral to the permanent devices, and a depressed left ventricular ejection fraction have been associated with an increased risk of venous lesions, though the effects of preventive strategies remain controversial. This randomized trial examined the effects of warfarin in the prevention of these complications in high-risk patients. Method: Between February 2004 and September 2007, we studied 101 adults who underwent a first cardiac device implantation, and who had a left ventricular ejection fraction <= 0.40, or a temporary pacing system ipsilateral to the permanent implant, or both. After device implantation, the patients were randomly assigned to warfarin to a target international normalized ratio of 2.0-3.5, or to placebo. Clinical and laboratory evaluations were performed regularly up to 6 months postimplant. Venous lesions were detected at 6 months by digital subtraction venography. Results: Venous obstructions of various degrees were observed in 46 of the 92 patients (50.0%) who underwent venography. The frequency of venous obstructions was 60.4% in the placebo, versus 38.6% in the warfarin group (P = 0.018), corresponding to an absolute risk reduction of 22% (relative risk = 0.63; 95% confidence interval = 0.013-0.42). Conclusions: Warfarin prophylaxis lowered the frequency of venous lesions after transvenous devices implantation in high-risk patients. (PACE 2009; 32:S247-S251)