Do Diabetic Patients with Acute Coronary Syndromes Have a Higher Threshold for Ischemic Pain?

Background: Data from over 4 decades have reported a higher incidence of silent infarction among patients with diabetes mellitus (DM), but recent publications have shown conflicting results regarding the correlation between DM and presence of pain in patients with acute coronary syndromes (ACS). Objective: Our primary objective was to analyze the association between DM and precordial pain at hospital arrival. Secondary analyses evaluated the association between hyperglycemia and precordial pain at presentation, and the subgroup of patients presenting within 6 hours of symptom onset. Methods: We analyzed a prospectively designed registry of 3,544 patients with ACS admitted to a Coronary Care Unit of a tertiary hospital. We developed multivariable models to adjust for potential confounders. Results: Patients with precordial pain were less likely to have DM (30.3%) than those without pain (34.0%; unadjusted p = 0.029), but this difference was not significant after multivariable adjustment, for the global population (p = 0.84), and for subset of patients that presented within 6 hours from symptom onset (p = 0.51). In contrast, precordial pain was more likely among patients with hyperglycemia (41.2% vs 37.0% without hyperglycemia, p = 0.035) in the overall population and also among those who presented within 6 hours (41.6% vs. 32.3%, p = 0.001). Adjusted models showed an independent association between hyperglycemia and pain at presentation, especially among patients who presented within 6 hours (OR = 1.41, p = 0.008). Conclusion: In this non-selected ACS population, there was no correlation between DM and hospital presentation without precordial pain. Moreover, hyperglycemia correlated significantly with pain at presentation, especially in the population that arrived within 6 hours from symptom onset.

Cholestasis in a murine experimental model: lesions include hepatocyte ischemic necrosis

OBJECTIVE: To establish a murine experimental model of bile duct obstruction that would enable controlled observations of the acute and subacute phases of cholestasis. METHODOLOGY: Adult male isogenic BALB/c mice underwent a bile duct ligation (22 animals) or a sham operation (10 animals). Fifteen days after surgery, or immediately after the animal's death, macroscopic findings were noted and histological study of the liver, biliary tree, and pancreas was performed (hematoxylin-eosin and Masson trichromic staining). RESULTS: Beginning 24 hours after surgery, all animals from the bile duct ligation group presented progressive generalized malaise. All animals presented jaundice in the parietal and visceral peritoneum, turgid and enlarged liver, and accentuated dilatation of gallbladder and common bile duct. Microscopic findings included marked dilatation and proliferation of bile ducts with accentuated collagen deposits, frequent areas of ischemic necrosis, hepatic microabscesses, and purulent cholangitis. Animals from the sham operation group presented no alterations. CONCLUSION: We established a murine experimental model of induced cholestasis, which made it possible to study acute and subacute tissue lesions. Our data suggests that in cholestasis, hepatic functional ischemia plays an important role in inducing hepatic lesions, and it also suggests that the infectious process is an important factor in morbidity and mortality.

Acute myocardial infarction in the Brazilian State of São Paulo. In-hospital deaths from 1979 to 1996 and hospital fatality from 1984 to 1998 in the public health system

OBJECTIVE: To determine the following parameters in the Brazilian State of São Paulo: 1) the percentage of deaths due to acute myocardial infarction (AMI) occurring in hospitals; 2) the percentage of deaths due to AMI occurring in public health system hospitals as compared with all in-hospital deaths due to AMI between 1979 and 1996; 3) the fatality due to AMI in public health system hospitals from 1984 to 1998. METHODS: Data were available on the Datasus Web site (the health information agency of the Brazilian Department of Health) that provided the following: a) number of deaths resulting from AMI in hospitals; b) number of deaths resulting from AMI in public health system hospitals; c) number of hospital admissions due to AMI in public health system hospitals. RESULTS: The percentage of in-hospital deaths due to AMI increased from 54.9 in 1979 to 68.6 in 1996. The percentage contribution of the public health system to total number of deaths due to AMI occurring in hospitals decreased from 22.9 in 1984 to 13.7 in 1996; fatality due to AMI occurring in public health system hospitals had an irregular evolution from 1984 to 1992 and showed a slight trend for increased frequency from 1993 to 1998. CONCLUSION: The percentage of in-hospital deaths due to AMI has been increasing. Deaths resulting from AMI in public health system hospitals have decreased when compared with the total number of deaths due to AMI in all hospitals. Fatality due to AMI in public health system hospitals did not decrease from 1992 to 1998.

Ischemic heart disease. Hospitalization, length of stay and expenses in Brazil from 1993 to 1997

OBJECTIVE: To identify characteristics of the hospitalizations due to ischemic heart disease (IHD) made by the Single Health System -- "Sistema Único de Saúde (SUS) in Brazil from 1993 to 1997. METHODS: The information used came from records of permissions for hospitalization due to IHD (diseases codified from 410 to 414 by the International Disease Classification -- 9th Revision) furnished by the data bank DATASUS. The material studied was classified according to age, sex and length of hospitalization of the patients, and expenses to the system for IHD. RESULTS: IHD represents 1.0% of total hospitalizations. Angina pectoris was the most frequent type, occurring in 53.3% of the cases, followed by acute myocardial infarct (26.6%). This later was more frequent in men and angina in women . The majority of patients with IHD stayed hospitalized from 5 to 8 days. In the years of 1997 the expenses due to hospital treatment for IHD reach to 0.01% of Brazil's Gross Internal Product. In the studied period (1993-1997), IHD was responsible by 1.0% of hospitalizations, however it was 3.3% of the expenses of SUS. CONCLUSION: IHD is an important cause of hospitalization by the SUS; it has a rather high cost, indicating the need for preventive measures aimed at reducing exposure to risk factors and to decrease the incidence of this group of diseases in the nation.

Effectiveness of primary angioplasty in the treatment of acute myocardial infarction. Analysis of in-hospital and late outcomes in 135 consecutive cases

OBJECTIVE: Evaluate early and late evolution of patients submitted to primary coronary angioplasty for acute myocardial infarction. METHODS: A prospective study of 135 patients with acute myocardial infarction submitted to primary transcutaneous coronary angioplasty (PTCA). Success was defined as TIMI 3 flow and residual lesion <50%. We performed statistical analyses by univariated, multivariated methods and survival analyze by Kaplan-Meier. RESULTS: PTCA success rate was 78% and early mortality 18,5%. Killip classes III and IV was associated to higher mortality, odds ratio 22.9 (95% CI: 5,7 to 91,8) and inversely related to age <75 years (OR = 0,93; 95% CI: 0.88 to 0.98). If we had chosen success flow as TIMI 2 and had excluded patients in Killip III/IV classes, success rate would be 86% and mortality 8%. The survival probability at the end or study, follow-up time 142 ± 114 days, was 80% and event free survival 35%. Greater survival was associated to stenting (OR = 0.09; 0.01 to 0.75) and univessel disease (OR = 0.21; 0.07 to 0.61). CONCLUSION: The success rate was lower and mortality was higher than randomized trials, however similar to that of non randomized studies. This demonstrated the efficacy of primary PTCA in our local conditions.

One-year follow-up after primary coronary intervention for acute myocardial infarction in diabetic patients: a substudy of the STENT PAMI trial

OBJECTIVE - This analysis was undertaken to determine the composite incidence of cumulative adverse events (death, reinfarction, disabling stroke, and target vessel revascularization) at the end of the first year after acute myocardial infarction, in diabetic patients who underwent coronary stenting or primary coronary balloon angioplasty. METHODS - From the STENT PAMI trial, we analyzed the 6-month angiographic and 1-year clinical outcomes of 135 diabetic (112, noninsulin dependent) patients who underwent the randomization process of the trial and compared them with 758 nondiabetic patients. RESULTS - Coronary stenting did not significantly reduce the primary composite clinical end point when compared with PTCA (20 vs. 30%, p=0.2). A significant benefit from stenting was observed in patients with noninsulin dependent diabetes, with a trend toward a lesser need for new revascularization procedures (10 vs. 21%, p<.001), with a significant reduction in the primary composite clinical end point at 1 year (12 vs. 28%, p=. 04). At 6 months, the restenosis rate were significantly reduced only in nondiabetic patients (18 vs. 33%, p<. 001). Diabetic patients had the same restenosis rate (38%) either with stenting or balloon PTCA. CONCLUSIONS - Coronary Stenting in diabetics noninsulin dependent offered a significant reduction in the composite incidence of major clinical adverse events compared with balloon PTCA.

Secular trends in a population with ischemic heart disease admitted to the Instituto do Coração in São Paulo

OBJECTIVE: To assess the clinical and demographic characteristics of a population with ischemic heart disease admitted in the final decades of the 20th century. METHODS: This study retrospectively assessed patients hospitalized with ischemic heart disease divided into the following 2 groups: acute group - 11.181 patients with acute myocardial infarction admitted from 1/1/82 to 12/31/94; and chronic group - 4.166 patients undergoing coronary artery bypass graft surgery from 1/1/84 to 12/31/94. RESULTS: In the acute group, an increase in the percentage of females (from 22.7% to 27.7%, P<0.001) and diabetic individuals (from 12.4% to 17.5%, P<0.001) was observed, as was an increase in age (from 57.4±11.5 to 59.9±12.1 years, P<0.05). In-hospital mortality was greater among females (27.8% and 15.7%, P=0.001), among diabetic individuals (24.2% and 17.8%, P=0.001), and among the elderly (60.9±15.2 and 57.7±11.8 years, P=0.0001). In the chronic group, an increase in the percentage of females (from 17.5% to 27.2%, P=0.001) was observed, as was an increase in age (from 56.3±8.6 to 60.5±9.6 years, P=0.0001). In-hospital mortality was greater among females (8.3% and 5.8%, P<0.05) and among the elderly (58.1±9.1 and 62.1±7.9 years, P=0.0001). CONCLUSION: The characteristics of the population studied with ischemic heart disease point towards a worse prognosis, due to the greater percentages of females, older patients, and diabetic patients, groups known to have greater in-hospital mortality.

Femoral versus Radial Access in Primary Angioplasty. Analysis of the ACCEPT Registry

Background:The radial access provides a lower risk of bleeding and vascular complications related to the puncture site in comparison to the femoral access. Recent studies have suggested a reduction in mortality associated with the radial access in patients with acute myocardial infarction undergoing percutaneous coronary intervention.Objective:To compare the occurrence of adverse cardiovascular ischemic and hemorrhagic events in patients undergoing primary angioplasty according to the type of arterial access route.Methods:From August 2010 to December 2011, 588 patients undergoing primary percutaneous coronary intervention during acute ST-segment elevation myocardial infarction were assessed; they were recruited from 47 centers participating in the ACCEPT registry. Patients were grouped and compared according to the arterial access used for the procedure.Results:The mean age was 61.8 years; 75% were males and 24% had diabetes mellitus. There was no difference between groups as regards the procedure success rate, as well as regards the occurrence of death, reinfarction, or stroke at six months of follow-up. Severe bleeding was reported in 1.1% of the sample analyzed, with no statistical difference related to the access used.Conclusions:The femoral and radial accesses are equally safe and effective for the performance of primary percutaneous coronary intervention. The low rate of cardiovascular events and of hemorrhagic complications reflects the quality of the participating centers and the operators expertise with the use of both techniques.

BNP was Associated with Ischemic Myocardial Scintigraphy and Death in Patients at Chest Pain Unit

Background:Recent studies have suggested that B-type Natriuretic Peptide (BNP) is an important predictor of ischemia and death in patients with suspected acute coronary syndrome. Increased levels of BNP are seen after episodes of myocardial ischemia and may be related to future adverse events.Objectives:To determine the prognostic value of BNP for major cardiac events and to evaluate its association with ischemic myocardial perfusion scintigraphy (MPS).Methods:This study included retrospectively 125 patients admitted to the chest pain unit between 2002 and 2006, who had their BNP levels measured on admission and underwent CPM for risk stratification. BNP values were compared with the results of the MPS. The chi-square test was used for qualitative variables and the Student t test, for quantitative variables. Survival curves were adjusted using the Kaplan-Meier method and analyzed by using Cox regression. The significance level was 5%.Results:The mean age was 63.9 ± 13.8 years, and the male sex represented 51.2% of the sample. Ischemia was found in 44% of the MPS. The mean BNP level was higher in patients with ischemia compared to patients with non-ischemic MPS (188.3 ± 208.7 versus 131.8 ± 88.6; p = 0.003). A BNP level greater than 80 pg/mL was the strongest predictor of ischemia on MPS (sensitivity = 60%, specificity = 70%, accuracy = 66%, PPV = 61%, NPV = 70%), and could predict medium-term mortality (RR = 7.29, 95% CI: 0.90-58.6; p = 0.045) independently of the presence of ischemia.Conclusions:BNP levels are associated with ischemic MPS findings and adverse prognosis in patients presenting with acute chest pain to the emergency room, thus, providing important prognostic information for an unfavorable clinical outcome.

Heart Failure with Preserved Left Ventricular Ejection Fraction in Patients with Acute Myocardial Infarction

AbstractBackground:The prevalence and clinical outcomes of heart failure with preserved left ventricular ejection fraction after acute myocardial infarction have not been well elucidated.Objective:To analyze the prevalence of heart failure with preserved left ventricular ejection fraction in acute myocardial infarction and its association with mortality.Methods:Patients with acute myocardial infarction (n = 1,474) were prospectively included. Patients without heart failure (Killip score = 1), with heart failure with preserved left ventricular ejection fraction (Killip score > 1 and left ventricle ejection fraction ≥ 50%), and with systolic dysfunction (Killip score > 1 and left ventricle ejection fraction < 50%) on admission were compared. The association between systolic dysfunction with preserved left ventricular ejection fraction and in-hospital mortality was tested in adjusted models.Results:Among the patients included, 1,256 (85.2%) were admitted without heart failure (72% men, 67 ± 15 years), 78 (5.3%) with heart failure with preserved left ventricular ejection fraction (59% men, 76 ± 14 years), and 140 (9.5%) with systolic dysfunction (69% men, 76 ± 14 years), with mortality rates of 4.3%, 17.9%, and 27.1%, respectively (p < 0.001). Logistic regression (adjusted for sex, age, troponin, diabetes, and body mass index) demonstrated that heart failure with preserved left ventricular ejection fraction (OR 2.91; 95% CI 1.35–6.27; p = 0.006) and systolic dysfunction (OR 5.38; 95% CI 3.10 to 9.32; p < 0.001) were associated with in-hospital mortality.Conclusion:One-third of patients with acute myocardial infarction admitted with heart failure had preserved left ventricular ejection fraction. Although this subgroup exhibited more favorable outcomes than those with systolic dysfunction, this condition presented a three-fold higher risk of death than the group without heart failure. Patients with acute myocardial infarction and heart failure with preserved left ventricular ejection fraction encounter elevated short-term risk and require special attention and monitoring during hospitalization.

Resilience in Patients with Ischemic Heart Disease

Background: Resilience is a psychosocial factor associated with clinical outcomes in chronic diseases. The relationship between this protective factor and certain diseases, such heart diseases, is still under-explored. Objective: The present study sought to investigate the frequency of resilience in individuals with ischemic heart disease. Method: This was a cross-sectional study with 133 patients of both genders, aged between 35 and 65 years, treated at Rio Grande do Sul Cardiology Institute - Cardiology University Foundation, with a diagnosis of ischemic heart disease during the study period. Sixty-seven patients had a history of acute myocardial infarction. The individuals were interviewed and evaluated by the Wagnild & Young resilience scale and a sociodemographic questionnaire. Results: Eighty-one percent of patients were classified as resilient according to the scale. Conclusion: In the sample studied, resilience was identified in high proportion among patients with ischemic heart disease.

When is the Best Time for the Second Antiplatelet Agent in Non-St Elevation Acute Coronary Syndrome?

Abstract Dual antiplatelet therapy is a well-established treatment in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), with class I of recommendation (level of evidence A) in current national and international guidelines. Nonetheless, these guidelines are not precise or consensual regarding the best time to start the second antiplatelet agent. The evidences are conflicting, and after more than a decade using clopidogrel in this scenario, benefits from the routine pretreatment, i.e. without knowing the coronary anatomy, with dual antiplatelet therapy remain uncertain. The recommendation for the upfront treatment with clopidogrel in NSTE-ACS is based on the reduction of non-fatal events in studies that used the conservative strategy with eventual invasive stratification, after many days of the acute event. This approach is different from the current management of these patients, considering the established benefits from the early invasive strategy, especially in moderate to high-risk patients. The only randomized study to date that specifically tested the pretreatment in NSTE-ACS in the context of early invasive strategy, used prasugrel, and it did not show any benefit in reducing ischemic events with pretreatment. On the contrary, its administration increased the risk of bleeding events. This study has brought the pretreatment again into discussion, and led to changes in recent guidelines of the American and European cardiology societies. In this paper, the authors review the main evidence of the pretreatment with dual antiplatelet therapy in NSTE-ACS.

First- Versus Second-Generation Drug-Eluting Stents in Acute Coronary Syndromes (Katowice-Zabrze Registry)

Abstract Background: There are sparse data on the performance of different types of drug-eluting stents (DES) in acute and real-life setting. Objective: The aim of the study was to compare the safety and efficacy of first- versus second-generation DES in patients with acute coronary syndromes (ACS). Methods: This all-comer registry enrolled consecutive patients diagnosed with ACS and treated with percutaneous coronary intervention with the implantation of first- or second-generation DES in one-year follow-up. The primary efficacy endpoint was defined as major adverse cardiac and cerebrovascular event (MACCE), a composite of all-cause death, nonfatal myocardial infarction, target-vessel revascularization and stroke. The primary safety outcome was definite stent thrombosis (ST) at one year. Results: From the total of 1916 patients enrolled into the registry, 1328 patients were diagnosed with ACS. Of them, 426 were treated with first- and 902 with second-generation DES. There was no significant difference in the incidence of MACCE between two types of DES at one year. The rate of acute and subacute ST was higher in first- vs. second-generation DES (1.6% vs. 0.1%, p < 0.001, and 1.2% vs. 0.2%, p = 0.025, respectively), but there was no difference regarding late ST (0.7% vs. 0.2%, respectively, p = 0.18) and gastrointestinal bleeding (2.1% vs. 1.1%, p = 0.21). In Cox regression, first-generation DES was an independent predictor for cumulative ST (HR 3.29 [1.30-8.31], p = 0.01). Conclusions: In an all-comer registry of ACS, the one-year rate of MACCE was comparable in groups treated with first- and second-generation DES. The use of first-generation DES was associated with higher rates of acute and subacute ST and was an independent predictor of cumulative ST.

Hepatic damage during acute pancreatitis in the rat

We studied the alterations in the metabolism of liver mitochondria in rats with acute pancreatitis. Male Wistar rats were allocated to a control group (group I) and to five other groups corresponding to 2, 4, 12, 24 and 48 h after the induction of acute pancreatitis by the injection of 5% sodium taurocholate into the pancreatic duct. Sham-operated animals were submitted to the same surgical steps except for the induction of acute pancreatitis. Mitochondrial oxidation and phosphorylation were measured polarographically by determining oxygen consumption without ADP (basal respiration, state 4) and in the presence of ADP (activated respiration, state 3). Serum amylase, transaminases (ALT and AST) and protein were also determined. Ascitic fluid, contents of amylase, trypsin and total protein were also determined and arterial blood pressure was measured in all groups. In ascitic fluid, trypsin and amylase increased reaching a maximum at 2 and 4 h, respectively. Serum amylase increased at 2 h reaching a maximum at 4 h. Serum transaminase levels increased at 12 and 24 h. After 2 h (and also 4 h) there was an increase in state 4 respiration (45.65 ± 1.79 vs 28.96 ± 1.50) and a decrease in respiration control rate (3.53 ± 0.09 vs 4.45 ± 0.08) and in the ADP/O ratio (1.77 ± 0.02 vs 1.91 ± 0.01) compared to controls (P<0.05). These results indicate a disruption of mitochondrial function, which recovered after 12 h. In the 48-h groups there was mitochondrial damage similar to that occurring in ischemic lesion. Beat-to-beat analysis (30 min) showed that arterial blood pressure remained normal up to 24 h (111 ± 3 mmHg) while a significant decrease occurred in the 48-h group (91 ± 4 mmHg). These data suggest biphasic damage in mitochondrial function in acute pancreatitis: an initial uncoupled phase, possibly secondary to enzyme activity, followed by a temporary recovery and then a late and final dysfunction, associated with arterial hypotension, possibly related to ischemic damage.

Contribution of CD4+ T cells to the early mechanisms of ischemia- reperfusion injury in a mouse model of acute renal failure

Renal ischemia-reperfusion (IR) injury is the major cause of acute renal failure in native and transplanted kidneys. Mononuclear leukocytes have been reported in renal tissue as part of the innate and adaptive responses triggered by IR. We investigated the participation of CD4+ T lymphocytes in the pathogenesis of renal IR injury. Male mice (C57BL/6, 8 to 12 weeks old) were submitted to 45 min of ischemia by renal pedicle clamping followed by reperfusion. We evaluated the role of CD4+ T cells using a monoclonal depleting antibody against CD4 (GK1.5, 50 µ, ip), and class II-major histocompatibility complex molecule knockout mice. Both CD4-depleted groups showed a marked improvement in renal function compared to the ischemic group, despite the fact that GK1.5 mAb treatment promoted a profound CD4 depletion (to less than 5% compared to normal controls) only within the first 24 h after IR. CD4-depleted groups presented a significant improvement in 5-day survival (84 vs 80 vs 39%; antibody treated, knockout mice and non-depleted groups, respectively) and also a significant reduction in the tubular necrosis area with an early tubular regeneration pattern. The peak of CD4-positive cell infiltration occurred on day 2, coinciding with the high expression of ßC mRNA and increased urea levels. CD4 depletion did not alter the CD11b infiltrate or the IFN-g and granzyme-B mRNA expression in renal tissue. These data indicate that a CD4+ subset of T lymphocytes may be implicated as key mediators of very early inflammatory responses after renal IR injury and that targeting CD4+ T lymphocytes may yield novel therapies.