Isolated right ventricular infarction presenting with anterior ST-segment elevation: a case for careful assessment of right ventricular branch occlusion.

We describe the case of a 61-year-old man who presented with chest pain and ST-segment elevation in the anterior precordial leads (V1-V5) due to proximal occlusion of the right ventricular branch of a codominant right coronary artery. Primary coronary angioplasty and stenting of this branch was performed resulting in resolution of the chest pain and ST-segment elevation. Our description illustrates a case of isolated right ventricular infarction as an uncommon but important differential diagnosis of anterior ST-segment elevation. In addition, it highlights the value of careful review of the angiographic images in this context, as the culprit lesion may be a right ventricular branch occlusion. To the best of our knowledge, this is the first reported case of primary percutaneous coronary intervention treatment of a right ventricular branch occlusion causing isolated acute right ventricular myocardial infarction and anterior ST-segment elevation.

Anterior STEMI complicating acute aortic syndrome: mechanistic insight and bridge to surgery with intravascular ultrasound-guided primary PCI.

Stanford type A acute aortic syndromes (AAS) can be complicated with acute coronary closure and ST segment elevation myocardial infarction (STEMI) leading to significant additional morbidity and mortality. The recommended treatment for type A AAS is emergency cardiac surgery. We present the case of a patient with intramural haematoma involving the ascending and descending aorta complicated with anterior wall STEMI after CT imaging. Coronary angiography and intravascular ultrasonography (IVUS) revealed the dissection spiralling into the media of the left main stem (LMS) and left anterior descending (LAD) coronary artery. In the setting of acute vessel closure and ongoing myocardial ischaemia primary percutaneous coronary intervention (PCI) was performed to the LMS, LAD and second diagonal branch prior to successful emergency cardiac surgery with an aortic-arch interposition graft. Emergency IVUS-guided stenting to relieve acute coronary occlusion in the context of aortic dissection can be performed in selected cases to safely bridge the patient for cardiac surgery.

A case of the crossed coronaries.

Coronary artery anomalies are rare; however, can be a potential cause of significant morbidity and even mortality. Crossed left anterior descending and left circumflex arteries is a rare finding, and therefore the significance of this finding is not well understood. CT coronary angiography is an excellent non-invasive modality which enables the diagnosis of such abnormalities, and it is likely that with the increased use of CT coronary angiography in cardiology, other similar cases will be diagnosed.

Proton pump inhibitors in patients treated with aspirin and clopidogrel after acute coronary syndrome.

INTRODUCTION: Clopidogrel is an antiplatelet agent converted to its active metabolite by cytochrome P-450 isoenzymes. Numerous drugs are known to inhibit P-450 isoenzymes, including proton pump inhibitors (PPIs), which are often associated with aspirin and clopidogrel to prevent adverse gastrointestinal effects. In vitro studies first showed that PPIs reduced the antiplatelet effect of clopidogrel, while recent clinical studies have raised concerns that the addition of a PPI to clopidogrel in acute coronary syndrome (ACS) patients could actually increase the risk of recurrent cardiovascular events. OBJECTIVE: The aim of this study was to evaluate whether the prescription of a PPI conferred a worse prognosis in patients discharged with aspirin and clopidogrel treatment after ACS. METHODS: A total of 876 patients admitted with ACS and discharged with aspirin and clopidogrel, with a planned duration of at least six months, from January 2004 to March 2008, were reviewed. Patients were classified in two groups according to whether or not a PPI was prescribed at discharge. The PPIs considered were those mainly metabolized by cytochrome P-450 2C19. We excluded patients with insufficient information available on either prescription or clinical records that could allow clearly confirm or exclude exposure to a PPI. Primary end points were six-month all-cause mortality and the composite of death, myocardial infarction and unstable angina at six months. RESULTS: Of the 802 patients considered for further analysis, 274 (34.2%) individuals were medicated with a PPI in addition to dual antiplatelet therapy. Patients taking PPIs were older, more often had renal insufficiency and less often had a history of coronary revascularization and smoking. They more often presented with Killip class >I and lower hemoglobin concentration on admission. There were no significant differences between the two groups in terms of medical treatment (during hospital stay and at discharge) or invasive procedures. By multivariate analysis, independent and positive predictors of PPI prescription were older age and lower hemoglobin concentration on admission. Patients taking PPIs had a slightly higher prevalence of six-month mortality (6.5% vs. 3.9%) and of the composite end point (12.9% vs. 9.2%), although without statistical significance. By multivariate analysis including potential confounding variables, the prescription of a PPI on top of aspirin and clopidogrel was still n ot associated with a worse prognosis. CONCLUSIONS: In the present study, PPI precription in addition to aspirin and clopidogrel after ACS was not associated with a worse six-month prognosis.

Predictors of pre-hospital delay in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Early reperfusion therapy in ST-elevation myocardial infarction (STEMI) correlates with its success. The aim of our study was to characterize patients admitted with a diagnosis of STEMI with longer prehospital delay and to analyze its impact on the choice of treatment and on in-hospital prognosis. METHODS: We performed a retrospective cohort study of 797 patients consecutively admitted with a diagnosis of STEMI from January 2002 to December 2007. The cutoff for longer pre-hospital delay was defined as three hours. We analyzed demographic, clinical and echocardiographic data and determined the predictors of pre-hospital delay of > or = 3 h. RESULTS: Of the 797 patients, 77% were male and mean age was 62 +/- 13.64 years. Patients with longer pre-hospital delay were older (p < 0.001), with a higher proportion of female (p = 0.001), hypertensive (p = 0.002), diabetic (p < 0.001), and surgically revascularized patients (p = 0.007), and those with symptom onset between 10 pm and 8 am (p = 0.001). The group with shorter pre-hospital delay included more men (p = 0.001), patients with prior myocardial infarction (p = 0.025) and smokers (p = 0.009). Independent predictors of pre-hospital delay of 3 h included female gender (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.03-2.16), diabetes (OR 1.78, 95% CI 1.23-2.56), systemic arterial hypertension (OR 1.41, 95% CI 1.04-1.93), and symptom onset between 10 pm and 8 am (OR 1.76, 95% CI 1.31-2.38). Independent predictors of pre-hospital delay of > or = 3 h included male gender (OR 0.67, 95% CI 0.46-0.97) and prior myocardial infarction (OR 0.48, 95% CI 0.27-0.84). Reperfusion therapy was performed in 72%, 52% and 12% of patients with pre-hospital delay of <3 h, 3-12 h and >12 h, respectively (p for trend <0.001). Patients with longer delay more often had severely reduced left ventricular ejection fraction (LVEF) (p = 0.004). A non-significant trend was observed towards increased in-hospital mortality with longer delay (8.3% vs. 6.6%, p for trend = 0.342). CONCLUSIONS: A significant proportion of patients continue to have long pre-hospital delay. Female patients and those with diabetes, systemic arterial hypertension and symptom onset between 10 pm and 8 am made up the majority of this group. Longer pre-hospital delay was associated with a lower probability of being treated with reperfusion therapy, a higher frequency of severely depressed LVEF and a non-significant increase in in-hospital mortality. It is essential to develop mechanisms to reduce pre-hospital delay.

Echocardiographic assessment of a cardiac lymphoma: beyond two-dimensional imaging.

Lymphoma is usually recognized as the third most frequent metastatic malignancy involving the heart. In recent years, the incidence of cardiac lymphoma has increased, mainly because of HIV-infected patients. We present a case of secondary cardiac lymphoma in an HIV patient presenting with heart failure. Transthoracic echocardiography showed increased left ventricular (LV) wall thickness and an extensive mass in the right cavities with involvement of the tricuspid annulus (Figure 1). Doppler tissue imaging (DTI) showed reduced systolic and diastolic velocities at mitral and tricuspid annulus, compatible with systolic and diastolic myocardial dysfunction, likely owing to infiltration. After 2 weeks of chemotherapy, repeated exam showed significant reduction of the tumour mass and of the LV wall thickness, as well as normalized systolic and diastolic velocities at mitral and tricuspid annulus, as assessed by DTI. Use of transthoracic echocardiography, mostly two-dimensional imaging, has been described for several years for the diagnosis of cardiac involvement as well as for the assessment of tumour regression in response to chemotherapy. The present case report highlights the potential utility of other echocardiographic modalities, particularly DTI, for the assessment of cardiac lymphoma but also for monitoring the tumour response to adequate therapy.

Association between red blood cell distribution width and outcomes at six months in patients with acute coronary syndromes.

BACKGROUND: Higher values of red ceildistribution width (RDW) may be associated with adverse outcomes in patients with heart failure and in those with stable coronary artery disease. We assessed the hypothesis that higher RDW values are associated with adverse cardiovascular outcomes in patients with acute coronary syndromes (ACS). METHODS: We studied 1796 patients with ACS admitted to a coronary care unit. We analyzed clinical and laboratory characteristics, management, and outcomes of patients according to tertiles of baseline RDW. The primary outcome was death or myocardial infarction (MI) during six-month follow-up. RESULTS: Patients with higher RDW values tended to be older, were more likely to be female and have a history of MI, and more often had renal dysfunction, anemia, and Killip class >I on admission (p < 0.05). Higher RDW values were associated with increased 6-month mortality (tertile 1: 8.2%; tertile 2: 10.9%; tertile 3: 15.5%; p = 0.001 for trend) and increased 6-month death/MI rates (tertile 1, 13.0%; tertile 2, 17.2%; tertile 3, 22.9%; p < 0.0001 for trend). An association between higher RDW and increased 6-month death/MI rates was found in patients with non-ST-elevation ACS (10.5% vs. 15.3% vs. 22.7%; p < 0.001 for trend), with a tendency in patients admitted with ST-elevation MI (15.1% vs. 19.1% vs. 23.1%; p = 0.053 for trend). After adjustment for baseline characteristics and treatment, higher RDW values remained independently associated with the study's primary composite outcome but not with all-cause death. Using the first tertile of RDW as reference, the adjusted odds ratio (OR) for 6-month death/MI among patients in the highest RDW tertile was 1.43 (95% confidence interval [CI], 1.00-2.05; p = 0.049). Using RDW as a continuous variable, the adjusted OR for 6-month death/MI was 1.16 (95% CI, 1.03-1.30; p = 0.017) per 1% increase in RDW. CONCLUSIONS: RDW is an easily determined predictor of outcome after ACS. We found a graded independent association between higher RDW values and adverse outcomes in patients with ACS.

Prognostic impact of hemoglobin drop during hospital stay in patients with acute coronary syndromes.

INTRODUCTION: Bleeding is currently the most common non-cardiac complication of therapy in patients with acute coronary syndromes (ACS), and may itself be associated with adverse outcomes. The aim of this study was to determine the effect of hemoglobin drop during hospital stay on outcome among patients with ACS. METHODS: Using Cox proportional-hazards modeling, we examined the association between hemoglobin drop and death or myocardial infarction (MI) at 6 months in 1172 patients admitted with ACS to an intensive cardiac care unit. Patients were stratified according to quartiles of hemoglobin drop: Q1, < or = 0.8 g/dL; Q2, 0.9-1.5 g/dL; Q3, 1.6-2.3 g/dL; Q4, > or = 2.4 g/dL. We also identified independent predictors of increased hemoglobin drop (> or =2.4 g/dL) using multivariate logistic regression analysis. RESULTS: Median nadir hemoglobin concentration was 1.5 g/dL lower (IQR 0.8-2.3) compared with baseline hemoglobin (p < 0.0001). Independent predictors of increased hemoglobin drop included older Sage, renal dysfunction, lower weight, and use of thrombolytic therapy, glycoprotein IIb/IIIa inhibitors, nitrates, and percutaneous coronary intervention. Higher levels of hemoglobin drop were associated with increased rates of 6-month mortality (8.0% vs. 9.4% vs. 9.6% vs. 15.7%; p for trend = 0.014) and 6-month death/ MI (12.4% vs. 17.0% vs. 17.2% vs. 22.1%; p for trend = 0.021). Using Q1 as reference group, the adjusted hazard ratio (HR) for 6-month mortality and 6-month death/MI among patients in the highest quartile of hemoglobin drop was 1.83 (95% confidence interval [CI] 1.08-3.11; p = 0.026) and 1.60 (95% CI 1.04-2.44; p = 0.031) respectively. Considered as a continuous variable, the adjusted HR for 6-month mortality was 1.16 (95% CI 1.01-1.32; p = 0.030) per 1 g/dL increase in hemoglobin drop. CONCLUSIONS: A decrease in hemoglobin frequently occurs during hospitalization for ACS and is independently associated with adverse outcomes.

Non-ST elevation acute coronary syndrome: QRS duration and long-term prognosis.

BACKGROUND: Recent studies have demonstrated that QRS duration (QRSd) is associated with poor prognosis in heart failure and ST-elevation myocardial infarction. Less is known about the prognostic importance of QRSd in patients with non-ST elevation acute coronary syndrome (non-ST ACS). AIM: To determine if admission QRSd is associated with 1-year mortality in non-ST ACS. METHODS: We studied 539 patients (aged 65.52 +/- 12.47 years, 69.9% male) admitted to the coronary unit with non-ST ACS. QRSd was measured on the admission electrocardiogram. RESULTS: Mean QRSd was 94.29 +/- 18.3 ms. One-year mortality was 13.4%. QRSd showed a good correlation with 1-year mortality and its best cut-off was 92 ms. Patients with QRSd > or = 92 ms were older, more frequently male and with prior history of coronary heart disease. On admission they presented more often in Killip class > 1, and had a higher incidence of heart failure and left ventricular systolic dysfunction. They less often underwent coronary angiography. One-year mortality was higher in patients with QRSd > or = 92 ms. After adjusting for baseline characteristics and treatment, QRSd > or = 92 ms remained an independent predictor of 1-year mortality (adjusted OR=3.87; 95% CI 1.74-8.44). CONCLUSION: In this non-ST ACS population, QRSd was an independent predictor of 1-year mortality after the event.

Coexistence of coronary cameral fistulae and cor triatriatum sinister in an elderly patient.

Coronary cameral fistulae are unusual congenital or acquired anomalous communications between an epicardial coronary artery and a cardiac chamber. There are no reported cases of the association of coronary cameral fistulae and cor triatriatum, a rare congenital cardiac anomaly in which a fibromuscular membrane divides the left atrium into two chambers. We report the case of an 82-year-old man presenting with recurrent anterior chest pain. Echocardiographic examination identified non-obstructive cor triatriatum, mitral valve prolapse resulting in significant mitral regurgitation, dilated coronary arteries, and established the entry site of coronary artery fistulae at the apex of the left ventricle (Figure 1). Coronary angiography confirmed the existence of a plexiform fistula between the left anterior descending coronary artery and the left ventricle. Tetrofosmine scintigraphy revealed the presence of stress-induced ischaemia in the apex. To our knowledge, we report the oldest person with coronary cameral fistulae presenting with angina only at this stage, and the interesting case of the coexistence of two, although unconnected, congenital conditions in an elderly patient. In addition, this report highlights the important role of transthoracic and transoesophageal echocardiography to the characterization of these unusual anomalies, and the complementary information offered by three-dimensional transthoracic echocardiography.

Impact of atrial fibrillation in acute coronary syndromes.

INTRODUCTION: Atrial fibrillation (AF) is a relatively common arrhythmia in the context of acute coronary syndromes (ACS). However, the impact of AF on these patients' survival is not well established. The present study aimed to estimate the prevalence of AF in ACS patients and to evaluate its impact on in-hospital and six-month post-event mortality, from any cause. METHODS: This was a retrospective cohort study that included 1183 patients admitted consecutively to a Coronary Care Unit with ACS. Demographic and clinical data and information from various complementary exams were collected and occurrence of AF during the first 48 hours of hospitalization was analyzed. Six-month follow-up was achieved in 95.9% of the patients. Logistic regression statistical analysis was used to identify independent predictors of in-hospital and six-month post-event mortality. RESULTS: AF was diagnosed in 140 patients (11.8%); these patients were older (73.89 +/- 8.69 vs. 63.20 +/- 12.73 years; p<0.0001) and less likely to be male (60.0% vs. 74.1%; p=0.001), and had a lower prevalence of dyslipidemia (32.9% vs. 44.1%; p=0.001) and smoking (10.0% vs. 25.9%; p<0.0001). Fewer patients with AF underwent reperfusion therapy (19.3% vs. 29.7%; p=0.006), beta-blocker therapy (72.1% vs. 85.7%; p<0.0001), and cardiac catheterization (48.2% vs. 62.9%; p=0.001) or percutaneous coronary intervention (14.3% vs. 23.4%; p=0.01). These patients more frequently developed heart failure (54.3% vs. 28.5%; p<0.0001) and more often presented left ventricular dysfunction (69.3% vs. 57.2%; p=0.002). In patients presenting AF, there were significant increases in in-hospital (12.1% vs. 4.2%; p<0.0001) and six-month mortality (27.2% vs. 8.2%. p<0.0001). In multivariate analysis, AF remained an independent marker of in-hospital (OR 1.95; 95% CI 1.03-3.69; p=0.03) and six-month mortality (OR 2.89; 95% CI 1.67-5.00; p=0.0001), as was age >75 years, severe left ventricular dysfunction and heart failure. The performance of coronary angiography correlated with improved prognosis. CONCLUSIONS: AF in the context of ACS is an independent predictor of increased in-hospital and six-month mortality. These findings should be taken into consideration in the management and treatment of such patients.

Prognostic impact of moderate renal dysfunction in acute coronary syndromes.

INTRODUCTION: End-stage renal disease is associated with high cardiovascular mortality. The prognostic importance of milder degrees of renal impairment in patients who have had an acute coronary syndrome (ACS) is less well defined. The purpose of this study was to evaluate the impact of baseline renal dysfunction assessed by estimated glomerular filtration rate (GFR) on mortality in patients admitted with an ACS. METHODS: We studied all patients with an ACS consecutively admitted to an Intensive Cardiac Care Unit over 18 months. The GFR was estimated by means of the four-component Modification of Diet in Renal Disease study equation. Patients were grouped according to their estimated GFR (less than 45.0; 45.0 to 59.9; 60.0 to 74.9; and at least 75.0 ml/min/1.73 m2). Primary outcome was death from any cause. RESULTS: The mean age of the 589 study patients was 64.1 years, 73.7% were male, and 49.2% had an ACS with ST-segment elevation. Arterial hypertension, diabetes mellitus, prior myocardial infarction, and Killip class > I were incrementally more common across increasing renal dysfunction strata (p < 0.01). The use of reperfusion therapy, beta-blockers, and coronary angioplasty was lower in groups with reduced estimated GFR (p < 0.001). Overall six-month mortality was 13.6%. Using the group with an estimated GFR of at least 75.0 ml/min/1.73 m2 as the reference group yielded odds ratios for six-month mortality that increased with the degree of renal impairment. After adjusting for baseline characteristics, impaired renal funtion remained associated with increased mortality. The multivariable-adjusted odds ratio for six-month mortality in patients with mild renal impairment (GFR 60.0 to 74.9 ml/min/1.73 m2) was 2.71 (95% confidence interval [CI] 1.09 to 6.69), compared with 7.53 (95% CI, 3.21 to 17.71) and 8.10 (95% CI, 3.18 to 20.60) in patients with moderate and more severe renal dysfunction, respectively. CONCLUSIONS: Baseline renal dysfunction, as assessed by estimated GFR, is a potent and easily identifiable determinant of outcome after an ACS. Even mild levels of renal impairment are independently associated with increased mortality after an ACS.

Thrombosed aneurysm of the left sinus of Valsalva.

The authors present the case of a 57-year-old asymptomatic woman, in whom a large left coronary sinus of Valsalva aneurysm was incidentally diagnosed on a routine echocardiogram in 1998. The case was initially presented to cardiac surgery consultants, and since there were no signs of rupture and the patient was asymptomatic, it was decided to keep her in close clinical and echocardiographic follow-up. Eight years later, and with no clinical manifestation in the meantime, a transesophageal echocardiogram (TEE) showed that the aneurysm was filled with swirling spontaneous echo contrast ("smoke") overlying a thrombus, which was not detected by transthoracic echocardiography. The patient then underwent surgical treatment with aortic root and aortic valve replacement and coronary reimplantation, with an excellent result. Although the need for early surgical intervention in patients with ruptured sinus of Valsalva aneurysms is well established, the optimal management of an asymptomatic, unruptured aneurysm is less clear, due to the absence of a precise natural history. The follow-up of our patient clearly demonstrated that it is mandatory to assess unruptured sinus of Valsalva aneurysms by TEE, particularly to exclude thrombotic complications. Such complications are one of the possible paths of the natural history of unruptured sinus of Valsalva aneurysms, and support the indication for early surgical treatment to avoid future complications.

Cardiovascular toxicity of cocaine of iatrogenic origin. Case report.

The use of cocaine as an illicit drug is associated with various cardiovascular events. In recent decades, because of growing levels of consumption, there has been an increasing incidence of these complications. At the same time, cocaine is also widely used as a local anesthetic, mainly in nasal surgery. Its application in this context is controversial due to the potential associated adverse effects. The authors report the case of a 29-year-old patient, with no known cardiovascular risk factors, admitted for elective nasal surgery, under general anesthesia combined with topical application of cocaine. During surgery the patient developed hemodynamic instability in the context of ventricular arrhythmias, after which she presented evolving electrocardiographic changes and increased levels of myocardial necrosis markers, diagnostic of non-ST-segment elevation acute coronary syndrome. The authors review the cardiovascular complications associated with cocaine use and the underlying pathophysiologic mechanisms and discuss the role of cocaine as a topical anesthetic.

Heart failure after acute coronary syndrome: identify to treat better!

INTRODUCTION: The development of heart failure (HF) following acute coronary syndromes (ACS) significantly worsens short- and long-term prognosis. The present study aimed to identify clinical characteristics, detectable at admission for ACS, that could predict HF development during hospitalization, and to evaluate its impact on in-hospital mortality. METHODS: This was a retrospective cohort study that included 601 patients consecutively admitted with ACS. Demographic, clinical and laboratory data at admission were collected and HF was defined as maximum Killip class II or III. Logistic regression analysis was performed to identify independent predictors of HF and, additionally, in-hospital death. RESULTS: 29.3% of the population developed HF, mostly older patients (69.52+/-11.9 years vs. 61.81+/-12.4 years, p<0.0001), women, hypertensive, diabetic and non-smokers. On admission, this subgroup of patients presented with higher heart rate and glycemia, and lower glomerular filtration rate (eGFR) and hemoglobin. The percentage of patients with left ventricular systolic dysfunction (LVSD) was significantly higher in the group of patients with HF (74.4% versus 48.7%, p<0.0001); however, no significant differences were found in the type of ACS or its location. In the present study, we found that patients with HF were stratified less invasively (less likely to undergo cardiac catheterization or percutaneous coronary intervention). The development of HF was associated with longer hospitalization and higher in-hospital mortality (7.4% versus 2.1%, p=0.004) on univariate analysis, but not on multivariate analysis. On multivariate analysis, only age (OR=1.04; 95% CI 1.02-1.06), diabetes mellitus (OR=1.77; 95% CI 1.05-2.96), glycemia (OR=1.05; 95% CI 1.01-1.08), eGFR <60 ml/min/1.73m2 (OR=2.90, 95% CI 1.73- 4.84), heart rate (OR=1.03, 95% CI 1.02-1.04) and LVSD (OR=2.48, 95% CI 1.59-3.85) were independent predictors of HF. CONCLUSIONS: HF is a frequent complication in ACS and is associated with higher in-hospital mortality. Identifying risk of HF development on admission, through easily acquired clinical characteristics (older age, diabetes and/or elevated glycemia, renal failure and higher heart rate), will certainly influence immediate therapeutic choices and permit an individualized approach to each patient.

Admission glycemia: a predictor of death after acute coronary syndrome in non-diabetic patients?

BACKGROUND: Previous studies have demonstrated that acute phase hyperglycemia is associated with increased in-hospital mortality in diabetic patients admitted with acute coronary syndrome (ACS), but this has not been clearly demonstrated in non-diabetic patients. The present study was designed to determine whether admission hyperglycemia (AG) is an independent predictor of in-hospital and six-month mortality after ACS in non-diabetic patients. METHODS: This was a retrospective cohort study of 426 non-diabetic patients consecutively admitted with ACS. The patients were stratified into quartile groups according to AG, which was also analyzed as a continuous variable. Vital status was obtained at six-month follow-up in 96.8% of the patients surviving hospitalization. Logistic regression analysis was used to identify independent predictors of in-hospital and six-month death. RESULTS: Of the 426 patients included in the study (age 62.6 years+/-13.1, 77% male), 22 (5.4%) patients died during hospitalization and 20 (5.2% of the patients surviving hospitalization) within six months of ACS. Mean AG was 134.89 mg/dl+/-51.95. The higher the AG, the more probable was presentation with ST-segment elevation ACS (STEMI), anterior STEMI, higher heart rate, Killip class higher than one (KK >1), higher serum creatinine and greater risk of in-hospital and six-month death. In multivariate analysis, only age (OR=1.10; 95% CI 1.04-1.17), STEMI (OR=3.02; 95% CI 1.07-8.50), AG (OR=1.073; 95% CI 1.004-1.146), serum creatinine (OR=1.10; 95% CI 1.009-1.204) and KK >1 on admission (OR=4.65; 95% CI 1.59-13.52) were independently associated with in-hospital death. Age (OR=1.07; 95% CI 1.03-1.12), serum creatinine (OR=1.09; 95% CI 1.01-1.18) and in-hospital development of heart failure (OR=2.34; 95% CI 1.07-5.10) were independently associated with higher risk of death within six months of ACS. CONCLUSIONS: AG is an independent predictive factor of in-hospital death after ACS in non-diabetic patients. Although it did not show an independent association with higher risk of six-month death, AG appears to contribute to it, since the risk is greater the higher the AG. Its predictive value may have been blunted by the insufficient power of the sample and/or by the time interval between acquisition of AG and the evaluated endpoint.

Intragenic deletion of CDH1 as the inactivating mechanism of the wild-type allele in an HDGC tumour.

Mutations in CDH1, encoding E-cadherin, are the underlying genetic defect in approximately one-third of the hereditary diffuse gastric cancer (HDGC) families described so far. Tumours arising in these families show abnormal or absence of E-cadherin expression, following the model of tumour suppressor gene inactivation. A single study has been reported showing inactivation of the CDH1 wild-type allele in tumour cells from HDGC families either by promoter methylation or by somatic mutation. In order to find the genetic alteration responsible for the presence of diffuse gastric cancers in four members of a Caucasian family, we have screened the coding sequence of CDH1 for germline mutations and searched for the second inactivating hit in the tumour samples. In this family, we have found a germline splice-site mutation in all members affected by gastric cancer and, in one tumour, a somatic deletion affecting at least exon 8 of CDH1. Our results show that a CDH1 intragenic deletion is the second hit inactivating the wild-type allele, in one of the tumours in this family.

E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients.

Approximately 30% of all hereditary diffuse gastric cancer (HDGC) families carry CDH1 germline mutations. The other two thirds remain genetically unexplained and are probably caused by alterations in other genes. Using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP)/sequencing, we screened 32 Portuguese families with a history of gastric cancer and 23 patients with early onset gastric cancer for CDH1 germline mutations. In probands negative for CDH1 mutations, we screened genes involved in hereditary cancer syndromes in which gastric cancer may be one of the component tumours, namely p53 (Li-Fraumeni Syndrome) and hMLH1 and hMSH2 (HNPCC). We also screened in these patients for mutations in Caspase-10, a gene inactivated in sporadic gastric cancer, and SMAD4, a gene whose inactivation in mice is associated with signet-ring cell carcinoma of the stomach. One of the families fulfilling the HDGC criteria harboured a CDH1 germline mutation, and one of the families with incomplete criteria harboured a p53 germline mutation. No mutations were identified in hMLH1 and hMSH2, and only sequence variants were found in SMAD4 and Caspase-10. The present work reports for the first time CDH1 germline mutations in Portuguese gastric cancer families, and highlights the need for p53 mutation screening in families lacking CDH1 germline mutations, in a country with one of the highest incidences of gastric cancer in the world. No evidence was found for a role of germline mutations in SMAD4 and Caspase-10 in families lacking CDH1 mutations.

Patterns of beta-catenin expression in gastric carcinoma: clinicopathological relevance and mutation analysis.

Studies on the expression of beta-catenin (beta-ct) in gastric carcinoma have provided conflicting results, and the role played by beta-ct mutations in gastric carcinogenesis remains unclear. In an attempt to clarify the aforementioned issues we undertook the retrospective study of 157 gastric carcinomas by using immunohistochemistry and molecular genetics. Reduced/absent membranous beta-ct expression was significantly associated with isolated-cell/diffuse histotype both in "pure" diffuse gastric carcinomas and in the isolated-cell/diffuse component of mixed carcinomas. Cytoplasmic and/or nuclear beta-ct expression was particularly prevalent in mixed carcinomas and was significantly associated with lymphatic vessel invasion and lymph node metastases. beta-ct mutations were not detected in any case. We conclude that the pattern of beta-ct expression is closely related to gastric carcinoma histotype. The activation of Wnt/beta-ct pathway is associated with mixed gastric carcinoma and with features of clinical aggressiveness; the mechanism(s) underlying this pathway in gastric carcinoma are not due to beta-ct mutations and remain to be elucidated.