Sudden Cardiac Death in Brazil: Study Based on Physicians' Perceptions of the Public Health Care System

Background: There are no available statistical data about sudden cardiac death in Brazil. Therefore, this study has been conducted to evaluate the incidence of sudden cardiac death in our population and its implications. Methods: The research methodology was based on Thurstone's Law of Comparative Judgment, whose premise is that the more an A stimulus differs from a B stimulus, the greater will be the number of people who will perceive this difference. This technique allows an estimation of actual occurrences from subjective perceptions, when compared to official statistics. Data were collected through telephone interviews conducted with Primary and Secondary Care physicians of the Public Health Service in the Metropolitan Area of Sao Paulo (MASP). Results: In the period from October 19, 2009, to October 28, 2009, 196 interviews were conducted. The incidence of 21,270 cases of sudden cardiac death per year was estimated by linear regression analysis of the physicians responses and data from the Mortality Information System of the Brazilian Ministry of Health, with the following correlation and determination coefficients: r = 0.98 and r2= 0.95 (95% confidence interval 0.81.0, P < 0.05). The lack of waiting list for specialized care and socioadministrative problems were considered the main barriers to tertiary care access. Conclusions: The incidence of sudden cardiac death in the MASP is high, and it was estimated as being higher than all other causes of deaths; the extrapolation technique based on the physicians perceptions was validated; and the most important bureaucratic barriers to patient referral to tertiary care have been identified. (PACE 2012; 35:13261331)

Chronic Stress Improves the Myocardial Function without Altering L-type Ca+2 Channel Activity in Rats

Background: Chronic stress is associated with cardiac remodeling; however the mechanisms have yet to be clarified. Objective: The purpose of this study was test the hypothesis that chronic stress promotes cardiac dysfunction associated to L-type calcium Ca2+ channel activity depression. Methods: Thirty-day-old male Wistar rats (70 - 100 g) were distributed into two groups: control (C) and chronic stress (St). The stress was consistently maintained at immobilization during 15 weeks, 5 times per week, 1h per day. The cardiac function was evaluated by left ventricular performance through echocardiography and by ventricular isolated papillary muscle. The myocardial papillary muscle activity was assessed at baseline conditions and with inotropic maneuvers such as: post-rest contraction and increases in extracellular Ca2+ concentration, in presence or absence of specific blockers L-type calcium channels. Results: The stress was characterized for adrenal glands hypertrophy, increase of systemic corticosterone level and arterial hypertension. The chronic stress provided left ventricular hypertrophy. The left ventricular and baseline myocardial function did not change with chronic stress. However, it improved the response of the papillary muscle in relation to positive inotropic stimulation. This function improvement was not associated with the L-type Ca2+ channel. Conclusion: Chronic stress produced cardiac hypertrophy; however, in the study of papillary muscle, the positive inotropic maneuvers potentiated cardiac function in stressed rats, without involvement of L-type Ca2+ channel. Thus, the responsible mechanisms remain unclear with respect to Ca2+ influx alterations. (Arq Bras Cardiol 2012;99(4):907-914)

Global and Regional Ventricular Repolarization Study by Body Surface Potential Mapping in Patients with Left Bundle-Branch Block and Heart Failure Undergoing Cardiac Resynchronization Therapy

Background: The controversial effects promoted by cardiac resynchronization therapy (CRT) on the ventricular repolarization (VR) have motivated VR evaluation by body surface potential mapping (BSPM) in CRT patients. Methods: Fifty-two CRT patients, mean age 58.8 +/- 12.3 years, 31 male, LVEF 27.5 +/- 9.2, NYHA III-IV heart failure with QRS181.5 +/- 14.2 ms, underwent 87-lead BSPM in sinus rhythm (BASELINE) and biventricular pacing (BIV). Measurements of mean and corrected QT intervals and dispersion, mean and corrected T peak end intervals and their dispersion, and JT intervals characterized global and regional (RV, Intermediate, and LV regions) ventricular repolarization response. Results: Global QTm (P < 0.001) and QTcm (P < 0.05) were decreased in BIV; QTm was similar across regions in both modes (P = ns); QTcm values were lower in RV/LV than in Intermediate region in BASELINE and BIV (P < 0.001); only RV/Septum showed a significant difference (P < 0.01) in the BIV mode. QTD values both of BASELINE (P < 0.01) and BIV (P < 0.001) were greater in the Intermediate than in the LV region. CRT effect significantly reduced global/regional QTm and QTcm values. QTD was globally decreased in RV/LV (Intermediate: P = ns). BIV mode significantly reduced global T peak end mean and corrected intervals and their dispersion. JT values were not significant. Conclusions: Ventricular repolarization parameters QTm, QTcm, and QTD global/regional values, as assessed by BSPM, were reduced in patients under CRT with severe HF and LBBB. Greater recovery impairment in the Intermediate region was detected by the smaller variation of its dispersion.

Applying the National Institute for Clinical Excellence criteria to patients treated with the Genous (TM) Bio-engineered R stent (TM): a sub-study of the e-HEALING (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth) worldwide registry

The National Institute for Clinical Excellence (NICE) guidelines recommend the use of bare-metal stents (BMS) in non-complex lesions with a low risk of restenosis (diameter a parts per thousand yen3 mm and lesion length a parts per thousand currency sign15 mm) and the use of drug-eluting stents (DES) in more complex lesions with a high risk of restenosis (diameter < 3.0 mm or lesion length > 15 mm). However, the guidelines were created based on studies evaluating BMS and DES only. We performed an analysis of patients undergoing non-urgent percutaneous coronary intervention with the novel endothelial cell capturing stent (ECS). The ECS is coated with CD34(+) antibodies that attract circulating endothelial progenitor cells to the stent surface, thereby accelerating the endothelialization of the stented area. We analyzed all patients enrolled in the worldwide e-HEALING registry that met the NICE criteria for either low-risk or high-risk lesions and were treated with a parts per thousand yen1 ECS. The main study outcome was target vessel failure (TVF) at 12-month follow-up, defined as the composite of cardiac death or MI and target vessel revascularization (TVR). A total of 4,241 patients were assessed in the current analysis. At 12-month follow-up, TVF occurred in 7.0% of the patients with low-risk lesions and in 8.8% of the patients with high-risk lesions (p = 0.045). When evaluating the diabetic patients versus the non-diabetic patients per risk group, no significant differences were found in TVF, MI or TVR in either risk group. The ECS shows good clinical outcomes in lesions carrying either a high or a low risk of restenosis according to the NICE guidelines with comparable rates of cardiac death, myocardial infarction, and stent thrombosis. The TVF rate with ECS was slightly higher in patients with high-risk lesions, driven by higher clinically driven TLR. The risk of restenosis with ECS in patients carrying high-risk lesions needs to be carefully considered relative to other risks associated with DES. Furthermore, the presence of diabetes mellitus did not influence the incidence of TVF in either risk group.

Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and a History of Stroke or Transient Ischemic Attack

Background-Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages. Methods and Results-We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively). Conclusions-Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality.

Dyslipidemia: evidence of efficacy of the pharmacological and non-pharmacological treatment in the elderly

The clinical decision to control risk factors for cardiovascular disease (CVD) in the elderly takes the followings into consideration: (1) the elderly life expectancy; (2) the elderly biological age and functional capacity; (3) the role of cardiovascular disease in the elderly group; (4) the prevalence of risk factors in the elderly; and (5) The effectiveness of treatment of risk factors in the elderly. A large number of studies showed the efficacy of secondary and primary prevention of dyslipidemia in the elderly. However, the only trial that included patients over 80 years was the Heart Protection Study (HPS). Statins are considered the first line therapy for lowering low-density lipoprotein cholesterol (LDL-C). Because lifestyle changes are very difficult to achieve, doctors in general tend to prescribe many drugs to control cardiovascular risk factors. However, healthy food consumption remains a cornerstone in primary and secondary cardiovascular prevention and should be implemented by everyone.

Low-dose Enalapril Reduces Angiotensin II and Attenuates Diabetic-induced Cardiac and Autonomic Dysfunctions

Activation of renin-angiotensin system has been linked to cardiovascular and autonomic dysfunctions in diabetes. Experiments were performed to investigate the effects of angiotensin-converting enzyme inhibitor (ACEI), enalapril, on cardiac and autonomic functions in diabetic rats. Diabetes was induced by streptozotocin (50 mg/kg), and rats were treated with enalapril (1 mg.kg(-1).d(-1)). After 30 days, evaluations were performed in control, diabetic, and enalapril-treated groups. Cardiac function was evaluated by echocardiography and through cannulation of the left ventricle (at baseline and in response to volume overload). Heart rate and systolic blood pressure variabilities were evaluated in the time and frequency domains. Streptozotocin rats had left ventricular systolic and diastolic dysfunctions, expressed by reduced ejection fraction and increased isovolumic relaxation time. The ACEI prevented these changes, improved diastolic cardiac responses to volume overload and total power of heart rate variability, reduced the ACE1 activity and protein expression and cardiac angiotensin (Ang) II levels, and increased angiotensin-converting enzyme 2 activity, despite unchanged blood pressure. Correlations were obtained between Ang II content with systolic and diastolic functions and heart rate variability. These findings provide evidence that the low-dose ACEI prevents autonomic and cardiac dysfunctions induced by diabetes without changing blood pressure and associated with reduced cardiac Ang II and increased angiotensin-converting enzyme 2 activity.

Plasma Pro-B-Type Natriuretic Peptide Testing as a Screening Method for Hypertrophic Cardiomyopathy

Background: Clinical multistage risk assessment associated with electrocardiogram (ECG) and NT-proBNP may be a feasible strategy to screen hypertrophic cardiomyopathy (HCM). We investigated the effectiveness of a screening based on ECG and NT-proBNP in first-degree relatives of patients with HCM. Methods and Results: A total of 106 first-degree relatives were included. All individuals were evaluated by echocardiography, ECG, NT-proBNP, and molecular screening (available for 65 individuals). From the 106 individuals, 36 (34%) had diagnosis confirmed by echocardiography. Using echocardiography as the gold standard, ECG criteria had a sensitivity of 0.71, 0.42, and 0.52 for the Romhilt-Estes, Sokolow-Lyon, and Cornell criteria, respectively. Mean values of NT-ProBNP were higher in affected as compared with nonaffected relatives (26.1 vs. 1290.5, P < .001). The AUC of NT-proBNP was 0.98. Using a cutoff value of 70 pg/mL, we observed a sensitivity of 0.92 and specificity of 0.96. Using molecular genetics as the gold standard, ECG criteria had a sensitivity of 0.67, 0.37, and 0.42 for the Romhilt-Estes, Sokolow-Lyon, and Cornell criteria, respectively. Using a cutoff value of 70 pg/mL, we observed a sensitivity of 0.83 and specificity of 0.98. Conclusion: Values of NT-proBNP above 70 pg/mL can be used to effectively select high-risk first-degree relatives for HCM screening. (J Cardiac Fail 2012;18:564-568)

ST Elevation Myocardial Infarction in the elderly

Acute coronary syndromes (ACS) are the leading causes of death in the elderly. The suspicion and diagnosis of ACS in this age group is more difficult, since typical angina is less frequent. The morbidity and mortality is greater in older age patients presenting ACS. Despite the higher prevalence and greater risk, elderly patients are underrepresented in major clinical trials from which evidence based recommendations are formulated. The authors describe, in this article, the challenges in the diagnosis and management of ST elevation myocardial infarction in the elderly, and discuss the available evidence.

Biventricular structural and functional responses to aortic constriction in a rabbit model of chronic right ventricular pressure overload

Objectives: Chronic right ventricular (RV) pressure overload results in pathologic RV hypertrophy and diminished RV function. Although aortic constriction has been shown to improve systolic function in acute RV failure, its effect on RV responses to chronic pressure overload is unknown. Methods: Adjustable vascular banding devices were placed on the main pulmonary artery and descending aorta. In 5 animals (sham group), neither band was inflated. In 9 animals (PAB group), only the pulmonary arterial band was inflated, with adjustments on a weekly basis to generate systemic or suprasystemic RV pressure at 28 days. In 9 animals, both pulmonary arterial and aortic devices were inflated (PAB+AO group), the pulmonary arterial band as for the PAB group and the aortic band adjusted to increase proximal systolic blood pressure by approximately 20 mm Hg. Effects on the functional performance were assessed 5 weeks after surgery by conductance catheters, followed by histologic and molecular assessment. Results: Contractile performance was significantly improved in the PAB+AO group versus the PAB group for both ventricles. Relative to sham-operated animals, both banding groups showed significant differences in myocardial histologic and molecular responses. Relative to the PAB group, the PAB+AO group showed significantly decreased RV cardiomyocyte diameter, decreased RV collagen content, and reduced RV expression of endothelin receptor type B, matrix metalloproteinase 9, and transforming growth factor beta genes. Conclusions: Aortic constriction in an experimental model of chronic RV pressure overload not only resulted in improved biventricular systolic function but also improved myocardial remodeling. These data suggest that chronically increased left ventricular afterload leads to a more physiologically hypertrophic response in the pressure-overloaded RV. (J Thorac Cardiovasc Surg 2012;144:1494-501)

Inspiratory Muscle Training Reduces Sympathetic Nervous Activity and Improves Inspiratory Muscle Weakness and Quality of Life in Patients With Chronic Heart Failure A CLINICAL TRIAL

PURPOSE: To evaluate the effect of inspiratory muscle training (IMT) on cardiac autonomic modulation and on peripheral nerve sympathetic activity in patients with chronic heart failure (CHF). METHODS: Functional capacity, low-frequency (LF) and high-frequency (HF) components of heart rate variability, muscle sympathetic nerve activity inferred by microneurography, and quality of life were determined in 27 patients with CHF who had been sequentially allocated to 1 of 2 groups: (1) control group (with no intervention) and (2) IMT group. Inspiratory muscle training consisted of respiratory exercises, with inspiratory threshold loading of seven 30-minute sessions per week for a period of 12 weeks, with a monthly increase of 30% in maximal inspiratory pressure (PImax) at rest. Multivariate analysis was applied to detect differences between baseline and followup period. RESULTS: Inspiratory muscle training significantly increased PImax (59.2 +/- 4.9 vs 87.5 +/- 6.5 cmH(2)O, P = .001) and peak oxygen uptake (14.4 +/- 0.7 vs 18.9 +/- 0.8 mL.kg(-1).min(-1), P = .002); decreased the peak ventilation (V. E) +/- carbon dioxide production (V-CO2) ratio (35.8 +/- 0.8 vs 32.5 +/- 0.4, P = .001) and the (V) over dotE +/-(V) over dotCO(2) slope (37.3 +/- 1.1 vs 31.3 +/- 1.1, P = .004); increased the HF component (49.3 +/- 4.1 vs 58.4 +/- 4.2 normalized units, P = .004) and decreased the LF component (50.7 +/- 4.1 vs 41.6 +/- 4.2 normalized units, P = .001) of heart rate variability; decreased muscle sympathetic nerve activity (37.1 +/- 3 vs 29.5 +/- 2.3 bursts per minute, P = .001); and improved quality of life. No significant changes were observed in the control group. CONCLUSION: Home-based IMT represents an important strategy to improve cardiac and peripheral autonomic controls, functional capacity, and quality of life in patients with CHF.

Estudo do Padrão Respiratório e Movimento Toracoabdominal em Valvopatia Mitral

FUNDAMENTO: pacientes com valvopatia mitral podem evoluir com congestão pulmonar, que aumenta o trabalho dos músculos respiratórios; essa sobrecarga pode alterar o padrão respiratório com predomínio do deslocamento torácico ou presença de movimentos paradoxais. OBJETIVO: a) estudar o padrão respiratório e movimento toracoabdominal (MTA) em pacientes com doença mitral b) estudar o efeito do posicionamento nos parâmetros respiratórios c) correlacionar hipertensão pulmonar com presença de incoordenação do MTA. MÉTODOS: o padrão respiratório e o MTA de pacientes com doença mitral foram avaliados por pletismografia respiratória por indutância, nas posições dorsal e sentada, durante dois minutos de respiração tranquila. Analisou-se volume corrente (Vc) e tempos respiratórios e as variáveis do MTA. RESULTADOS: de 65 pacientes incluídos, 10 foram retirados, 29 participaram do grupo estenose mitral e 26 do grupo insuficiência mitral. O Vc, a ventilação pulmonar e o fluxo inspiratório médio aumentaram significantemente na posição sentada, sem diferenças entre os grupos. O MTA manteve-se coordenado entre os grupos e as posições; no entanto, cinco pacientes na posição dorsal apresentaram incoordenação (três no grupo estenose mitral; dois no grupo insuficiência mitral) com correlação significante com valores de pressão de artéria pulmonar (r = 0,992, p = 0,007). CONCLUSÃO: o padrão respiratório e o MTA não apresentam diferenças entre pacientes com estenose ou insuficiência mitral. A posição sentada aumenta o Vc sem alterar os tempos respiratórios. A presença de incoordenação toracoabdominal na posição dorsal esteve associação à hipertensão pulmonar.

Birth weight, current body mass index, and insulin sensitivity and secretion in young adults in two Latin American populations

Background and aims: Although studies have shown association of birth weight (BW) and adult body mass index (BMI) with insulin sensitivity in adults, there is limited evidence that BW is associated with insulin secretion. We assessed the associations between BW and current BMI with insulin sensitivity and secretion in young Latin American adults. Methods and results: Two birth cohorts, one from Ribeirao Preto, Brazil, based on 1984 participants aged 23-25 years, and another from Limache, Chile, based on 965 participants aged 22-28 years were studied. Weight and height at birth, and current fasting plasma glucose and insulin levels were measured. Insulin sensitivity (HOMA%S) and secretion (HOMA%beta) were estimated using the Homeostatic Model Assessment (HOMA2). Multiple linear regression analyses were carried out to test the associations between BW and adult BMI z-scores on log HOMA%S and log HOMA%beta. BW z-score was associated with HOMA%S in the two populations and HOMA%beta in Ribeirao Preto when adult BMI z-score was included in the model. BW z-score was associated with decreasing insulin secretion even without adjusting for adult BMI, but only in Ribeirao Preto. BMI z-score was associated with low HOMA%S and high HOMA%beta. No interactions between BW and BMI z-scores on insulin sensitivity were shown. Conclusions: This study supports the finding that BW may affect insulin sensitivity and secretion in young adults. The effect size of BW on insulin status is small in comparison to current BMI. (C) 2010 Elsevier B.V. All rights reserved.

RHYTHM-AF: design of an international registry on cardioversion of atrial fibrillation and characteristics of participating centers

Background: Atrial fibrillation is a serious public health problem posing a considerable burden to not only patients, but the healthcare environment due to high rates of morbidity, mortality, and medical resource utilization. There are limited data on the variation in treatment practice patterns across different countries, healthcare settings and the associated health outcomes. Methods/design: RHYTHM-AF was a prospective observational multinational study of management of recent onset atrial fibrillation patients considered for cardioversion designed to collect data on international treatment patterns and short term outcomes related to cardioversion. We present data collected in 10 countries between May 2010 and June 2011. Enrollment was ongoing in Italy and Brazil at the time of data analysis. Data were collected at the time of atrial fibrillation episode in all countries (Australia, Brazil, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom), and cumulative follow-up data were collected at day 60 (+/- 10) in all but Spain. Information on center characteristics, enrollment data, patient demographics, detail of atrial fibrillation episode, medical history, diagnostic procedures, acute treatment of atrial fibrillation, discharge information and the follow-up data on major events and rehospitalizations up to day 60 were collected. Discussion: A total of 3940 patients were enrolled from 175 acute care centers. 70.5% of the centers were either academic (44%) or teaching (26%) hospitals with an overall median capacity of 510 beds. The sites were mostly specialized with anticoagulation clinics (65.9%), heart failure (75.1%) and hypertension clinics (60.1%) available. The RHYTHM-AF registry will provide insight into regional variability of antiarrhythmic and antithrombotic treatment of atrial fibrillation, the appropriateness of such treatments with respect to outcomes, and their cost-efficacy. Observations will help inform strategies to improve cardiovascular outcomes in patients with atrial fibrillation.

Identification of epsilon PKC Targets During Cardiac Ischemic Injury

Background: Epsilon-protein kinase C (epsilon PKC) protects the heart from ischemic injury. However, the mechanism(s) of epsilon PKC cardioprotection is still unclear. Identification of the epsilon PKC targets may aid in elucidating the epsilon PKC-mediated cardioprotective mechanisms. Previous studies, using epsilon PKC transgenic mice and difference in gel electrophoresis, identified proteins involved in glucose metabolism, the expression of which was modified by epsilon PKC. Those studies were accompanied by metabolomic analysis, suggesting that increased glucose oxidation may be responsible for the cardioprotective effect of epsilon PKC. Whether these epsilon PKC-mediated alterations were because of differences in protein expression or phosphorylation was not determined. Methods and Results: In the present study, we used an epsilon PKC -specific activator peptide, psi epsilon RACK, combined with phosphoproteomics, to find epsilon PKC targets, and identified that the proteins whose phosphorylation was altered by selective activation of epsilon PKC were mostly mitochondrial proteins. Analysis of the mitochondrial phosphoproteome led to the identification of 55 spots, corresponding to 37 individual proteins, exclusively phosphorylated, in the presence of psi epsilon RACK. The majority of the proteins identified were involved in glucose and lipid metabolism, components of the respiratory chain as well as mitochondrial heat shock proteins. Conclusions: The protective effect of epsilon PKC during ischemia involves phosphorylation of several mitochondrial proteins involved in glucose and lipid metabolism and oxidative phosphorylation. Regulation of these metabolic pathways by epsilon PKC phosphorylation may lead to epsilon PKC-mediated cardioprotection induced by psi epsilon RACK. (Circ J 2012; 76: 1476-1485)