Influence of ischemic preconditioning in myocardial protection in patients undergoing myocardial revascularization with intermittent crossclamping of the aorta. Analysis of ions and blood gases

OBJECTIVE: To test the hypothesis that short periods of ischemia may increase the myocardial protection obtained with intermittent crossclamping of the aorta. METHODS: In the control group (18 patients), surgery was performed with systemic hypothermia at 32ºC and intermittent crossclamping of the aorta. Extracorporeal circulation was used. In the preconditioning group (17 patients), 2 crossclampings of the aorta lasting 3min each were added prior to the intermittent crossclamping of the conventional technique with an interval of 2min of reperfusion between them. Blood samples for analyses of pH, pCO2, pO2, sodium, potassium, calcium, and magnesium were obtained from the coronary sinus at the beginning of extracorporeal circulation (time 1), at the end of the first anastomosis (time 2), and at the end of extracorporeal circulation (time 3). RESULTS: No difference was observed in the results of the 2 groups, except for a variation in the ionic values in the different times of blood withdrawal; sodium values, however, remained stable. All patients had a good clinical outcome. CONCLUSION: The results of intermittent crossclamping of the aorta with moderate hypothermia were not altered by the use of ischemic preconditioning.

Acute Myocardial Infarction: The First Manifestation of Ischemic Heart Disease and Relation to Risk Factors

OBJECTIVE: To assess the association between cardiovascular risk factors and acute myocardial infarction as the first manifestation of ischemic heart disease, correlating them with coronary angiographic findings. METHODS: We carried out a cross-sectional study of 104 patients with previous acute myocardial infarction, who were divided into 2 groups according to the presence or absence of angina prior to acute myocardial infarction. We assessed the presence of angina preceding acute myocardial infarction and risk factors, such as age >55 years, male sex, smoking, systemic arterial hypertension, lipid profile, diabetes mellitus, obesity, sedentary lifestyle, and familial history of ischemic heart disease. On coronary angiography, the severity of coronary heart disease and presence of left ventricular hypertrophy were assessed. RESULTS: Of the 104 patients studied, 72.1% were males, 90.4% were white, 73.1% were older than 55 years, and 53.8% were hypertensive. Acute myocardial infarction was the first manifestation of ischemic heart disease in 49% of the patients. The associated risk factors were systemic arterial hypertension (RR=0.19; 95% CI=0.06-0.59; P=0.04) and left ventricular hypertrophy (RR=0.27; 95% CI=0,.8-0.88; P=0.03). The remaining risk factors were not statistically significant. CONCLUSION: Prevalence of acute myocardial infarction as the first manifestation of ischemic heart disease is high, approximately 50%. Hypertensive individuals more frequently have symptoms preceding acute myocardial infarction, probably due to ventricular hypertrophy associated with high blood pressure levels.

Experimental Model of Gene Transfection in Healthy Canine Myocardium: Perspectives of Gene Therapy for Ischemic Heart Disease

OBJECTIVE: To assess the transfection of the gene that encodes green fluorescent protein (GFP) through direct intramyocardial injection. METHODS: The pREGFP plasmid vector was used. The EGFP gene was inserted downstream from the constitutive promoter of the Rous sarcoma virus. Five male dogs were used (mean weight 13.5 kg), in which 0.5 mL of saline solution (n=1) or 0.5 mL of plasmid solution containing 0.5 µg of pREGFP/dog (n=4) were injected into the myocardium of the left ventricular lateral wall. The dogs were euthanized 1 week later, and cardiac biopsies were obtained. RESULTS: Fluorescence microscopy showed differences between the cells transfected and not transfected with pREGFP plasmid. Mild fluorescence was observed in the cardiac fibers that received saline solution; however, the myocardial cells transfected with pREGFP had overt EGFP expression. CONCLUSION: Transfection with the EGFP gene in healthy canine myocardium was effective. The reproduction of this efficacy using vascular endothelial growth factor (VEGF) instead of EGFP aims at developing gene therapy for ischemic heart disease.

Trends of the Risk of Death due to Circulatory, Cerebrovascular, and Ischemic Heart Diseases in 11 Brazilian Capitals from 1980 to 1998

OBJECTIVE: To assess the trends of the risk of death due to circulatory (CD), cerebrovascular (CVD), and ischemic heart diseases (IHD) in 11 Brazilian capitals from 1980 to 1998. METHODS: Data on mortality due to CD, CVD and IHD were obtained from the Brazilian Health Ministry, and the population estimates were calculated by interpolation with the Lagrange method based on census data from 1980 and 1991 and the population count of 1996. The trends were analyzed with the multiple linear regression method. RESULTS: CD showed a trend towards a decrease in most capitals, except for Brasília, where a mild increase was observed. The cities of Porto Alegre, Curitiba, Rio de Janeiro, Cuiabá, Goiânia, Belém, and Manaus showed a decrease in the risk of death due to CVD and IHD, while the city of Brasília showed an increase in CVD and IHD. The city of São Paulo showed a mild increase in IHD for individuals of both sexes aged 30 to 39 years and for females aged 40 to 59 years. In the cities of Recife and Salvador, a reduction in CD was observed for all ages and both sexes. In the city of Recife, however, an increase in IHD was observed at younger ages (30 to 49 years), and this trend decreased until a mild reduction (-4%) was observed in males ³ 70 years. CONCLUSION: In general, a reduction in the risk of death due to CD and an increase in IHD were observed, mainly in the cities of Recife and Brasília.

Malignant hypertension and hypertensive encephalopathy in primary aldosteronism caused by adrenal adenoma

Two cases are reported as follows: 1) 1 female patient with accelerated-malignant hypertension secondary to an aldosterone-producing adrenal adenoma; and 2) 1 female patient with adrenal adenoma, severe hypertension, and hypertensive encephalopathy. This association is a rare clinical finding, and malignant hypertension may modify the hormonal characteristic of primary aldosteronism, making its diagnosis more difficult. The diagnosis of primary aldosteronism should be considered in patients with malignant hypertension or hypertensive encephalopathy if persistent hypokalemia occurs. Identification of primary aldosteronism is of paramount importance for the patient's evolution, because the surgical treatment makes the prognosis more favorable.

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.

Mortality by Heart Failure and Ischemic Heart Disease in Brazil from 1996 to 2011

Background:Circulatory system diseases are the first cause of death in Brazil.Objective:To analyze the evolution of mortality caused by heart failure, by ischemic heart diseases and by ill-defined causes, as well as their possible relations, in Brazil and in the geoeconomic regions of the country (North, Northeast, Center-West, South and Southeast), from 1996 to 2011.Methods:Data were obtained from DATASUS and death declaration records with codes I20 and I24 for acute ischemic diseases, I25 for chronic ischemic diseases, and I50 for heart failure, and codes in chapter XIII for ill-defined causes, according to geoeconomic regions of Brazil, from 1996 to 2011.Results:Mortality rates due to heart failure declined in Brazil and its regions, except for the North and the Northeast. Mortality rates due to acute ischemic heart diseases increased in the North and Northeast regions, especially from 2005 on; they remained stable in the Center-West region; and decreased in the South and in the Southeast. Mortality due to chronic ischemic heart diseases decreased in Brazil and in the Center-West, South and Southeast regions, and had little variation in the North and in the Northeast. The highest mortality rates due to ill-defined causes occurred in the Northeast until 2005.Conclusions:Mortality due to heart failure is decreasing in Brazil and in all of its geoeconomic regions. The temporal evolution of mortality caused by ischemic heart diseases was similar to that of heart failure. The decreasing number of deaths due to ill-defined causes may represent the improvement in the quality of information about mortality in Brazil. The evolution of acute ischemic heart diseases ranged according to regions, being possibly confused with the differential evolution of ill-defined causes.

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.

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.

Effects of Ischemic Postconditioning on the Hemodynamic Parameters and Heart Nitric Oxide Levels of Hypothyroid Rats

Background: Ischemic postconditioning (IPost) is a method of protecting the heart against ischemia-reperfusion (IR) injury. However, the effectiveness of IPost in cases of ischemic heart disease accompanied by co-morbidities such as hypothyroidism remains unclear. Objective: The aim of this study was to determine the effect of IPost on myocardial IR injury in hypothyroid male rats. Methods: Propylthiouracil in drinking water (500 mg/L) was administered to male rats for 21 days to induce hypothyroidism. The hearts from control and hypothyroid rats were perfused in a Langendorff apparatus and exposed to 30 min of global ischemia, followed by 120 min of reperfusion. IPost was induced immediately following ischemia. Results: Hypothyroidism and IPost significantly improved the left ventricular developed pressure (LVDP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) during reperfusion in control rats (p < 0.05). However, IPost had no add-on effect on the recovery of LVDP and ±dp/dt in hypothyroid rats. Furthermore, hypothyroidism significantly decreased the basal NO metabolite (NOx) levels of the serum (72.5 ± 4.2 vs. 102.8 ± 3.7 μmol/L; p < 0.05) and heart (7.9 ± 1.6 vs. 18.8 ± 3.2 μmol/L; p < 0.05). Heart NOx concentration in the hypothyroid groups did not change after IR and IPost, whereas these were significantly (p < 0.05) higher and lower after IR and IPost, respectively, in the control groups. Conclusion: Hypothyroidism protects the heart from IR injury, which may be due to a decrease in basal nitric oxide (NO) levels in the serum and heart and a decrease in NO after IR. IPost did not decrease the NO level and did not provide further cardioprotection in the hypothyroid group.

Left Atrial Volume Determinants in Patients with Non-Ischemic Dilated Cardiomyopathy

Background:Left atrial volume (LAV) is a predictor of prognosis in patients with heart failure.Objective:We aimed to evaluate the determinants of LAV in patients with dilated cardiomyopathy (DCM).Methods:Ninety patients with DCM and left ventricular (LV) ejection fraction ≤ 0.50 were included. LAV was measured with real-time three-dimensional echocardiography (eco3D). The variables evaluated were heart rate, systolic blood pressure, LV end-diastolic volume and end-systolic volume and ejection fraction (eco3D), mitral inflow E wave, tissue Doppler e´ wave, E/e´ ratio, intraventricular dyssynchrony, 3D dyssynchrony index and mitral regurgitation vena contracta. Pearson´s coefficient was used to identify the correlation of the LAV with the assessed variables. A multiple linear regression model was developed that included LAV as the dependent variable and the variables correlated with it as the predictive variables.Results:Mean age was 52 ± 11 years-old, LV ejection fraction: 31.5 ± 8.0% (16-50%) and LAV: 39.2±15.7 ml/m2. The variables that correlated with the LAV were LV end-diastolic volume (r = 0.38; p < 0.01), LV end-systolic volume (r = 0.43; p < 0.001), LV ejection fraction (r = -0.36; p < 0.01), E wave (r = 0.50; p < 0.01), E/e´ ratio (r = 0.51; p < 0.01) and mitral regurgitation (r = 0.53; p < 0.01). A multivariate analysis identified the E/e´ ratio (p = 0.02) and mitral regurgitation (p = 0.02) as the only independent variables associated with LAV increase.Conclusion:The LAV is independently determined by LV filling pressures (E/e´ ratio) and mitral regurgitation in DCM.

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.

PFO closure vs. medical therapy in cryptogenic stroke or transient ischemic attack: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: This study aims to assess whether patent foramen ovale (PFO) closure is superior to medical therapy in preventing recurrence of cryptogenic ischemic stroke or transient ischemic attack (TIA). METHODS: We searched PubMed for randomized trials which compared PFO closure with medical therapy in cryptogenic stroke/TIA using the items: "stroke or cerebrovascular accident or TIA" and "patent foramen ovale or paradoxical embolism" and "trial or study". RESULTS: Among 650 potentially eligible articles, 3 were included including 2303 patients. There was no statistically significant difference between PFO-closure and medical therapy in ischemic stroke recurrence (1.91% vs. 2.94% respectively, OR: 0.64, 95%CI: 0.37-1.10), TIA (2.08% vs. 2.42% respectively, OR: 0.87, 95%CI: 0.50-1.51) and death (0.60% vs. 0.86% respectively, OR: 0.71, 95%CI: 0.28-1.82). In subgroup analysis, there was significant reduction of ischemic strokes in the AMPLATZER PFO Occluder arm vs. medical therapy (1.4% vs. 3.04% respectively, OR: 0.46, 95%CI: 0.21-0.98, relative-risk-reduction: 53.2%, absolute-risk-reduction: 1.6%, number-needed-to-treat: 61.8) but not in the STARFlex device (2.7% vs. 2.8% with medical therapy, OR: 0.93, 95%CI: 0.45-2.11). Compared to medical therapy, the number of patients with new-onset atrial fibrillation (AF) was similar in the AMPLATZER PFO Occluder arm (0.72% vs. 1.28% respectively, OR: 1.81, 95%CI: 0.60-5.42) but higher in the STARFlex device (0.64% vs. 5.14% respectively, OR: 8.30, 95%CI: 2.47-27.84). CONCLUSIONS: This meta-analysis does not support PFO closure for secondary prevention with unselected devices in cryptogenic stroke/TIA. In subgroup analysis, selected closure devices may be superior to medical therapy without increasing the risk of new-onset AF, however. This observation should be confirmed in further trials using inclusion criteria for patients with high likelihood of PFO-related stroke recurrence.

Thrombolysis in ischemic stroke without arterial occlusion at presentation.

BACKGROUND AND PURPOSE: None of the randomized trials of intravenous tissue-type plasminogen activator reported vascular imaging acquired before thrombolysis. Efficacy of tissue-type plasminogen activator in stroke without arterial occlusion on vascular imaging remains unknown and speculative. METHODS: We performed a retrospective, multicenter study to collect data of patients who presented to participating centers during a 5-year period with ischemic stroke diagnosed by clinical examination and MRI and with imaging evidence of no vascular occlusion. These patients were divided into 2 groups: those who received thrombolytic therapy and those who did not. Primary outcome measure of the study was excellent clinical outcome defined as modified Rankin Scale of 0 to 1 at 90 days from stroke onset. Secondary outcome measures were good clinical outcome (modified Rankin Scale, 0-2) and perfect outcome (modified Rankin Scale, 0). Safety outcome measures were incidence of symptomatic intracerebral hemorrhage and poor outcome (modified Rankin Scale, 4-6). RESULTS: A total of 256 patients met study criteria, 103 with thrombolysis and 153 without. Logistic regression analysis showed that patients who received thrombolysis had more frequent excellent outcomes with odds ratio of 3.79 (P<0.01). Symptomatic intracerebral hemorrhage was more frequent in thrombolysis group (4.9 versus 0.7%; P=0.04). Thrombolysis led to more frequent excellent outcome in nonlacunar group with odds ratio 4.90 (P<0.01) and more frequent perfect outcome in lacunar group with odds ratio 8.25 (P<0.01). CONCLUSIONS: This study provides crucial data that patients with ischemic stroke who do not have visible arterial occlusion at presentation may benefit from thrombolysis.

Phosphodiesterase-5 inhibition mimics intermittent reoxygenation and improves cardioprotection in the hypoxic myocardium.

Although chronic hypoxia is a claimed myocardial risk factor reducing tolerance to ischemia/reperfusion (I/R), intermittent reoxygenation has beneficial effects and enhances heart tolerance to I/R. AIM OF THE STUDY: To test the hypothesis that, by mimicking intermittent reoxygenation, selective inhibition of phosphodiesterase-5 activity improves ischemia tolerance during hypoxia. Adult male Sprague-Dawley rats were exposed to hypoxia for 15 days (10% O₂) and treated with placebo, sildenafil (1.4 mg/kg/day, i. p.), intermittent reoxygenation (1 h/day exposure to room air) or both. Controls were normoxic hearts. To assess tolerance to I/R all hearts were subjected to 30-min regional ischemia by left anterior descending coronary artery ligation followed by 3 h-reperfusion. Whereas hypoxia depressed tolerance to I/R, both sildenafil and intermittent reoxygenation reduced the infarct size without exhibiting cumulative effects. The changes in myocardial cGMP, apoptosis (DNA fragmentation), caspase-3 activity (alternative marker for cardiomyocyte apoptosis), eNOS phosphorylation and Akt activity paralleled the changes in cardioprotection. However, the level of plasma nitrates and nitrites was higher in the sildenafil+intermittent reoxygenation than sildenafil and intermittent reoxygenation groups, whereas total eNOS and Akt proteins were unchanged throughout. CONCLUSIONS: Sildenafil administration has the potential to mimic the cardioprotective effects led by intermittent reoxygenation, thereby opening the possibility to treat patients unable to be reoxygenated through a pharmacological modulation of NO-dependent mechanisms.