Effect of Vericiguat vs Placebo on Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The VITALITY-HFpEF Randomized Clinical Trial.

Importance: Patients with heart failure and preserved ejection fraction (HFpEF) are at high risk of mortality, hospitalizations, and reduced functional capacity and quality of life. Objective: To assess the efficacy of the oral soluble guanylate cyclase stimulator vericiguat on the physical limitation score (PLS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ). Design, Setting, and Participants: Phase 2b randomized, double-blind, placebo-controlled, multicenter trial of 789 patients with chronic HFpEF and left ventricular ejection fraction 45% or higher with New York Heart Association class II-III symptoms, within 6 months of a recent decompensation (HF hospitalization or intravenous diuretics for HF without hospitalization), and with elevated natriuretic peptides, enrolled at 167 sites in 21 countries from June 15, 2018, through March 27, 2019; follow-up was completed on November 4, 2019. Interventions: Patients were randomized to receive vericiguat, up-titrated to 15-mg (n = 264) or 10-mg (n = 263) daily oral dosages, compared with placebo (n = 262) and randomized 1:1:1. Main Outcomes and Measures: The primary outcome was change in the KCCQ PLS (range, 0-100; higher values indicate better functioning) after 24 weeks of treatment. The secondary outcome was 6-minute walking distance from baseline to 24 weeks. Results: Among 789 randomized patients, the mean age was 72.7 (SD, 9.4) years; 385 (49%) were female; mean EF was 56%; and median N-terminal pro-brain natriuretic peptide level was 1403 pg/mL; 761 (96.5%) completed the trial. The baseline and 24-week KCCQ PLS means for the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 60.0 and 68.3, 57.3 and 69.0, and 59.0 and 67.1, respectively, and the least-squares mean changes were 5.5, 6.4, and 6.9, respectively. The least-squares mean difference in scores between the 15-mg/d vericiguat and placebo groups was -1.5 (95% CI, -5.5 to 2.5; P = .47) and between the 10-mg/d vericiguat and placebo groups was -0.5 (95% CI, -4.6 to 3.5; P = .80). The baseline and 24-week 6-minute walking distance mean scores in the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 295.0 m and 311.8m , 292.1 m and 318.3 m, and 295.8 m and 311.4 m, and the least-squares mean changes were 5.0 m, 8.7 m, and 10.5 m, respectively. The least-squares mean difference between the 15-mg/d vericiguat and placebo groups was -5.5 m (95% CI, -19.7 m to 8.8 m; P = .45) and between the 10-mg/d vericiguat and placebo groups was -1.8 m (95% CI, -16.2 m to 12.6 m; P = .81), respectively. The proportions of patients who experienced symptomatic hypotension were 6.4% in the 15-mg/d vericiguat group, 4.2% in the 10-mg/d vericiguat group, and 3.4% in the placebo group; those with syncope were 1.5%, 0.8%, and 0.4%, respectively. Conclusions and Relevance: Among patients with HFpEF and recent decompensation, 24-week treatment with vericiguat at either 15-mg/d or 10-mg/d dosages compared with placebo did not improve the physical limitation score of the KCCQ. Trial Registration: ClinicalTrials.gov Identifier: NCT03547583.

Rationale and Design of the VITALITY-HFpEF Trial.

Background The VITALITY-HFpEF trial (Evaluate the Efficacy and Safety of the Oral sGC Stimulator Vericiguat to Improve Physical Functioning in Daily Living Activities of Patients With Heart Failure and Preserved Ejection Fraction) is designed to determine the efficacy and safety of a novel oral soluble guanylate cyclase stimulator, vericiguat, on quality of life and exercise tolerance in heart failure patients with preserved ejection fraction (HFpEF). Impaired physical functioning reduces the quality of life in patients with HFpEF. The primary goal of HF treatment along with improving survival is to improve function, reduce symptoms, and maximize quality of life. Abnormal cyclic guanosine monophosphate signaling may contribute to physical limitations in patients with HFpEF via central and peripheral mechanisms. Exploratory post hoc analyses from a prior trial showed that vericiguat can improve patient-relevant domains of the Kansas City Cardiomyopathy Questionnaire, especially the physical limitation score. Methods and Results VITALITY-HFpEF is a placebo-controlled, double-blind, multi-center, phase IIb trial of ≈735 patients, ≥45 years with HFpEF and ejection fraction ≥45% who will be randomized 1:1:1 to placebo, 10 mg, or 15 mg vericiguat. The primary end point is change in Kansas City Cardiomyopathy Questionnaire physical limitation score from baseline to week 24 and change in 6-minute walk test from baseline to week 24 is the secondary end point. Conclusions VITALITY-HFpEF is the first trial designed to assess the efficacy of vericiguat in patients with HFpEF using the Kansas City Cardiomyopathy Questionnaire physical limitation score as a novel primary end point. This study will also extend the prior dosing experience with vericiguat in HF by studying the safety and efficacy of a 15 mg dose. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT03547583.

Short time insulin treatment post burn improves elastic-collagen rearrangement and reepithelization.

Extensive burn may cause acute resistance to insulin, which accentuates hypermetabolism, impairs glucose metabolism, immune dysfunction and risks of sepsis. To minimize these effects, insulin is used as a treatment. The purpose was to analyze the collagen-elastic arrangement effects of insulin on the burned skin. Wistar rats were assigned in groups: control (C); control with insulin (C + I); scald burn injury (SBI); and SBI with insulin (SBI+ I). SBI were submitted to 45% total body surface area burn and the insulin-treated groups received insulin (5 UI/Kg/day) for 4 or 14 days (d). Insulin levels, glucose tolerance test and HOMA index were determined. The skin sections were analyzed for histophatological and morphoquantitative data. Histopathological findings showed increased reepithelization of SBI+ I and formation of a new muscle layer after 14 days. In the collagen-elastic arrangement, insulin for 4 days increased the volume fraction (Vv) of thin collagen and elastic fibers. After 14 days, independently of injury, insulin decreased the elastic fibers. Insulin was able to reverse damages in the collagen-elastic rearrangement and stimulate reepithelization after 4 days. Untreated scald-burned animals showed higher Vv of thick collagen after 4 days, while those treated had a higher Vv of thin collagen. The Vv of elastic fibers was increased in SBI+ I for 4 days. In conclusion, insulin treatment was able to stimulate reepithelization. It also reversed the damages to the collagen-elastic arrangement in the scald-burned group, improving the organization of thin collagen and increasing the Vv of elastic fibers in the injured group treated with insulin for a short time, that is, for 4 days.

Central and peripheral effects of physical exercise without weight reduction in obese and lean mice.

To investigate the central (hypothalamic) and peripheral effects of exercise without body weight change in diet-induced obesity (DIO). Twelve-week-old male C57Bl/6 mice received a control (C) or a high-fat diet (H). Half of them had free access to running wheels for 5 days/week for 10 weeks (CE) and HE, respectively). Hypothalamic expression of genes related to energy homeostasis, and leptin (Stat3 and p-Stat3) and insulin (Akt and p-Akt) signaling were evaluated. Glucose and leptin tolerance, peripheral insulin sensitivity, and plasma insulin, leptin and adiponectin were determined. Perigonadal and retroperitoneal fat depots were increased by diet but reduced by exercise despite lack of effect of exercise on body weight. Blood glucose during intraperitoneal glucose tolerance test (ipGTT) was higher and glucose decay during intraperitoneal insulin tolerance test (ipITT) was lower in H and HE compared with C and CE. Exercise increased liver p-Akt expression and reduced fast glycemia. High-fat diet increased plasma insulin and leptin. Exercise had no effect on insulin but decreased leptin and increased adiponectin. Leptin inhibited food intake in all groups. Hypothalamic total and p-Stat3 and Akt were similar amongst the groups despite higher plasma levels of leptin and insulin in H and HE mice. High-fat diet modulated gene expression favoring a positive energy balance. Exercise only marginally changed the gene expression. Exercise induced positive changes (decreased fast glycemia and fat depots; increased liver insulin signaling and adiponectin concentration) without weight loss. Thus, despite reducing body weight could bring additional benefits, the effects of exercise must not be overlooked when weight reduction is not achieved.

Riociguat in patients with chronic thromboembolic pulmonary hypertension: results from an early access study.

BACKGROUND: Following positive results from the Phase III CHEST-1 study in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), the Phase IIIb CTEPH early access study (EAS) was designed to assess the safety and tolerability of riociguat in real-world clinical practice, as well as to provide patients with early access to riociguat before launch. Riociguat is approved for the treatment of inoperable and persistent/recurrent CTEPH. METHODS: We performed an open-label, uncontrolled, single-arm, early access study in which 300 adult patients with inoperable or persistent/recurrent CTEPH received riociguat adjusted from 1 mg three times daily (tid) to a maximum of 2.5 mg tid. Patients switching from unsatisfactory prior pulmonary arterial hypertension (PAH)-targeted therapy (n = 84) underwent a washout period of at least 3 days before initiating riociguat. The primary aim was to assess the safety and tolerability of riociguat, with World Health Organization functional class and 6-min walking distance (6MWD) as exploratory efficacy endpoints. RESULTS: In total, 262 patients (87%) completed study treatment and entered the safety follow-up (median treatment duration 47 weeks). Adverse events were reported in 273 patients (91%). The most frequently reported serious adverse events were syncope (6%), right ventricular failure (3%), and pneumonia (2%). There were five deaths, none of which was considered related to study medication. The safety and tolerability of riociguat was similar in patients switched from other PAH-targeted therapies and those who were treatment naïve. In patients with data available, mean ± standard deviation 6MWD had increased by 33 ± 42 m at Week 12 with no clinically relevant differences between the switched and treatment-naïve subgroups. CONCLUSIONS: Riociguat was well tolerated in patients with CTEPH who were treatment naïve, and in those who were switched from other PAH-targeted therapies. No new safety signals were observed. TRIAL REGISTRATION: ClinicalTrials.org NCT01784562 . Registered February 4, 2013.

Spontaneous physical activity and mediators of energy homeostasis in the hypothalamus of mice from 4 to 10 months of age.

NEW FINDINGS: What is the central question of this study? Is the initial decline of spontaneous physical activity (SPA) in mice related to impaired insulin and leptin signalling or brain-derived neurotrophic factor expression in the hypothalamus? What is the main finding and its importance? We showed that SPA started to decline at an early stage, concomitantly with an impairment of hypothalamic leptin signalling. Consequently, energy expenditure decreased and glucose tolerance worsened. Our results demonstrate the need to counteract the initial decline in SPA to avoid metabolic impairments and indicate the possible involvement of central leptin in the reduction in SPA with age. The biological control of physical activity is poorly understood. Age decreases insulin, leptin and brain-derived neurotrophic factor (BDNF) signalling in the hypothalamus, and all have been shown to modulate spontaneous physical activity (SPA). We investigated the age at which SPA starts to decline and whether this is associated with the emergence of hypothalamic insulin and leptin resistance and reduced BDNF expression. Spontaneous physical activity (and other parameters of locomotion) and energy expenditure were determined monthly in mice from the 4th to the 10th month of age. Metabolic and hypothalamic analyses were performed in 4-, 6- and 10-month-old mice. Spontaneous physical activity, distance travelled and speed of locomotion started to decrease in 6-month-old mice. The reduction in SPA became more evident from 8 months of age. Energy expenditure decreased from the 8th month. Hypothalamic BDNF protein expression and insulin signalling did not change throughout the time span studied. Leptin signalling decreased at 6 and 10 months compared with 4 months. Also, compared with 4 months, 6- and 10-month-old mice were glucose intolerant. In conclusion, SPA begins to decline in parallel with reduced hypothalamic leptin signalling. Metabolic impairment also manifests as SPA decreases, highlighting the need to understand the regulation of SPA in order to combat its decline.

The effects of calorie-matched high-fat diet consumption on spontaneous physical activity and development of obesity.

AIMS: To characterize the effects of a calorie matched high-fat diet (HFD) on spontaneous physical activity (SPA), body weight, inflammatory status and expression of genes related to energy homeostasis in hypothalamus of mice. MAIN METHODS: C57Bl/6 mice (n=5 per group) were fed a control diet (16.5% calories from fat) - control group (C), or a calorie matched HFD (60% calories from fat). We evaluated, periodically, body weight and SPA by infrared beam sensors and, at the end of the 12th week, we verified blood glucose levels, fat pads weight, plasma insulin, TNF-α and IL-6 by ELISA and the hypothalamic expression of 84 genes related to energy homeostasis, by quantitative real-time PCR array. KEY FINDINGS: Isocaloric HFD reduced SPA already in the first 48h and SPA was kept lower in the HFD compared to C throughout. These changes resulted in an increase in body weight, adiposity, TNF-α and IL-6, blood glucose and hyperinsulinemia in the HFD group when compared to the C group. Expression of the Agrp, Bdnf, Adra2b and Pyy genes were altered in the hypothalamus of HFD-fed mice, highlighting the downregulation of Bdnf, key regulator of energy homeostasis. SIGNIFICANCE: Dietary macronutrient distribution plays an important part in energy homeostasis that goes beyond its energy content. Despite calorie-matched, the HFD led to increased body weight and adiposity due to decreased SPA, highlighting the key role of SPA on energy balance. The changes in hypothalamic gene expression seem to underlie the reduction in SPA caused by HFD.

Translational Science: How experimental research has contributed to the understanding of spontaneous Physical Activity and Energy Homeostasis

Abstract Spontaneous physical activity (SPA) consists of all daily living activities other than volitional exercise (e.g. sports and fitness-related activities). SPA is an important component of energy expenditure and may protect from overweight and obesity. Little is known about the biological regulation of SPA, but animal researchhas contributedsignificantly to expand our knowledge in this field. Studies in rodents have shown that SPA is influenced by nutrients and volitional exercise. High-fat diet seems to decrease SPA, which contributes to weigh gain. Volitional exercisemayalso reduce SPA, helping to explain the commonly reported low efficiency of exercise to cause weight loss, and highlighting the need to finda volume/intensity of exercise to maximize total daily energy expenditure. Animal studieshave also allowed for the identification of some brain areas and chemical mediatorsinvolved in SPA regulation. These discoveries could enable the development of new therapeutics aiming to enhance SPA.(AU)

Voluntary running decreases nonexercise activity in lean and diet-induced obese mice.

PURPOSE: Determine whether voluntary wheel running triggers compensatory changes in nonexercise activity in lean and high-fat diet fed mice. METHODS: C57Bl/6 mice received a control (C) or a high-fat diet (H) and half of them had free access to a running wheel 5days/week (CE and HE, respectively) for 10weeks. Energy intake, nonexercise activity (global activity, distance covered and average speed of displacement in the home cage) and energy expenditure (EE) were evaluated at weeks 5 and 10 during the 2days without the wheels. RESULTS: High-fat diet increased weight gain in H (110%) and HE (60%) groups compared to C and CE groups, respectively, with no effect of exercise. Wheel running increased energy intake (26% CE, 11% HE in week 5; 7% CE, 45% HE in week 10) and decreased distance covered (26% for both CE and HE in week 5; 35% CE and 13% HE in week 10) and average speed (35% CE and 13% HE in week 5; 45% CE and 18% HE in week 10) compared to the respective nonexercised groups. In week 10 there was an interaction between diet and exercise for global activity, which was reduced nearly 18% in CE, H, and HE groups compared to C. Access to a running wheel increased EE in week 5 (11% CE and 16% HE) but not in week 10, which is consistent with the period of highest running (number of turns: weeks 1-5 nearly 100%>weeks 6-10 for CE and HE groups). EE was reduced in H (19%) and HE (12%) groups compared to C and CE, in week 10. CONCLUSION: Voluntary running causes a compensatory decrease in nonexercise activity and an increase in energy intake, both contributing to the lack of effect of exercise on body mass.

Complicações cardíacas em cirurgia vascular / Cardiac complications in vascular surgery

CONTEXTO: Aproximadamente 60% dos pacientes portadores de doença arterial oclusiva crônica periférica têm doença coronariana grave, sendo que a principal causa de morte no pós-operatório de cirurgia vascular de grande porte é o infarto agudo do miocárdio. OBJETIVOS: Determinar a prevalência da doença coronariana em pacientes submetidos a cirurgia vascular eletiva de grande porte e sua relação com as complicações cardiológicas pós-operatórias. MÉTODOS: Foram analisados 200 pacientes submetidos a cirurgia vascular arterial eletiva: doença obstrutiva carotídea, aortoilíaca e femoropoplítea distal e doença aneurismática de aorta abdominal e de artérias ilíacas. Os pacientes constituíram três grupos: grupo I, sem doença coronariana; grupo II, com doença coronariana assintomática; e grupo III, com doença coronariana sintomática. As complicações cardiológicas consideradas foram infarto agudo do miocárdio fatal e não fatal, insuficiência cardíaca congestiva, choque cardiogênico, fibrilação atrial aguda e outras arritmias. RESULTADOS: Complicações cardíacas ocorreram em 11 pacientes (5,5%): três infartos agudos do miocárdio não fatais (1,5%) sempre em pacientes do grupo III. A complicação cardíaca mais frequente foi arritmia (exceto fibrilação atrial) ocorrida em cinco (2,5%) pacientes, sendo três do grupo II. A mortalidade precoce foi de nove pacientes (4,5%). Apenas uma morte foi decorrente de problema cardíaco: choque cardiogênico em paciente do grupo III. CONCLUSÕES: A doença coronariana não foi preditora de óbito nos pacientes submetidos a cirurgia vascular periférica de grande porte. A sobrevida dos pacientes com ou sem doença coronariana não mostrou diferenças estatísticas.

BACKGROUND: Approximately 60% of patients with chronic occlusive peripheral arterial disease have severe coronary disease and the principal cause of death during the postoperative period after major vascular surgery is acute myocardial infarction. OBJECTIVES: To determine the prevalence of coronary disease among patients scheduled for elective major vascular surgery and its relationship with postoperative cardiological complications. METHODS: A total of 200 patients who underwent elective vascular arterial surgery for obstructive carotid disease, aortoiliac and distal femoropopliteal disease and aneurysmal disease of the abdominal aorta and iliac arteries were analyzed. These patients were allocated to three groups: group I, free from coronary disease; group II, asymptomatic coronary disease; and group III, symptomatic coronary disease. The cardiological complications analyzed were fatal and nonfatal acute myocardial infarction, congestive heart failure, cardiogenic shock, acute atrial fibrillation and other arrhythmias. RESULTS: Cardiac complications occurred in 11 patients (5.5%): three nonfatal acute myocardial infarctions (1.5%), all in patients from group III. The most common cardiac complication was arrhythmia (excluding atrial fibrillation) in five (2.5%) patients, three from group II. Early mortality was nine patients (4.5%). Just one death was caused by a cardiac problem: cardiogenic shock in a patient from group III. CONCLUSIONS: Coronary disease was not predictive of death among patients who underwent major peripheral vascular surgery. There were no statistical differences in survival between patients with or without coronary disease.

Reduction in the length of stay with rivaroxaban as a single-drug regimen for the treatment of deep vein thrombosis and pulmonary embolism.

OBJECTIVE: The phase III EINSTEIN DVT and EINSTEIN PE trials demonstrated the potential of oral rivaroxaban for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). The length of initial hospitalization in patients presenting with either symptomatic DVT or PE was assessed using hospitalization records from these trials. METHODS: Analyses were carried out in the intention-to-treat population, using non-parametric and parametric statistical methods. RESULTS: Overall, 52% (1781/3434) of EINSTEIN DVT patients and 90% (4328/4821) of EINSTEIN PE patients were admitted to hospital. The proportion of hospitalized patients with a length of stay of five or fewer days receiving rivaroxaban was 54% compared with 31% for enoxaparin/vitamin K antagonist (VKA) in patients with DVT. For patients with PE, the corresponding values were 45% and 33%. Stays of 6-10 days were observed in 29% of rivaroxaban-treated patients compared with 45% of enoxaparin/VKA-treated patients for DVT. For patients with PE, these values were 39% and 46% in the rivaroxaban and enoxaparin/VKA groups, respectively. Overall, length of stay was significantly shorter in the rivaroxaban group, compared with the enoxaparin/VKA group across all analyses performed (p < 0.0001). Across regions, the observed admission rates and length of stay duration varied greatly: Asia had the longest overall hospitalization rates, whereas the lowest rates were reported in North America, Australia and New Zealand. Nevertheless, a consistent trend was observed: length of hospital stay in patients with DVT or PE receiving rivaroxaban was shorter than, or at least similar to, patients receiving enoxaparin/VKA. CONCLUSION: A single-drug regimen with rivaroxaban may reduce the burden on healthcare systems and patients, and provides effective and well tolerated treatment. The studies shared an open-label design that allowed comparison of initial hospitalization, but limitations include the well monitored clinical trial setting in which decisions on admission and discharge could vary from real-world management.

Alisquireno: uma nova opção terapêutica na Cardiomiopatia Hipertrófica / Aliskiren: a new therapeutic option in Hypertrophic Cardiomyopathy

Caso clínico de Cardiomiopatia Hipertrófica (CMH), que após a introdução do alisquireno, houve regressão da massa do Ventrículo Esquerdo (VE) com remodelamento do VE à custa do aumento da cavidade do VE, associado à diminuição da espessura de suas paredes, com manutenção da função do VE. Também ocorreu desaparecimento do gradiente intraventricular de repouso, e durante o estresse esse gradiente deixou de ser significativo. A análise do Eletrocardiograma (ECG) evidenciou melhora do padrão de repolarização ventricular. De sorte que o paciente foi liberado para realizar atividade física não competitiva e gradual.

Clinical case of Hypertrophic Cardiomyopathy (HCM) that after the introduction of aliskiren, there was regression of the Left Ventricle (LV) mass with LV remodeling at the expense of increased LV cavity, associated with decreased thickness of its walls, with maintenance of LV function. There was also disappearance of the intraventricular gradient at rest and during stress, this gradient was no longer significant. The Eletrocardiogram (EKG) analysis showed improvement in ventricular repolarization pattern. So that the patient was released for non-competitive and gradual physical activity.

A sazonalidade do tromboembolismo venoso no clima subtropical de São Paulo / Seasonal variation of venous thromboembolism in the subtropical climate of São Paulo, Brazil

CONTEXTO: Os fatores desencadeantes da doença tromboembólica venosa vêm sendo cada vez melhor identificados. Causas externas podem influir na sua ocorrência, e algum destaque tem sido dado a fatores climáticos. Nada se sabe quanto a essa interferência em nossa latitude. OBJETIVOS: Analisar se há diferença na incidência do tromboembolismo venoso de acordo com as estações do ano, num hospital da cidade de São Paulo, Brasil, cujo clima é categorizado como subtropical. MÉTODOS: Foi realizado trabalho retrospectivo de levantamento de dados a partir de prontuários de pacientes cujo diagnóstico de internação ou óbito foi de trombose venosa profunda ou tromboembolismo pulmonar, no período de janeiro de 1996 a outubro de 2003, no Hospital da Beneficência Portuguesa de São Paulo. Para comparação e estudo, os casos foram agrupados em trimestres (primeiro trimestre = janeiro, fevereiro e março; segundo trimestre = abril, maio e junho; terceiro trimestre = julho, agosto e setembro; e quarto trimestre = outubro, novembro e dezembro) e conforme sua ocorrência nos chamados meses quentes e frios, de acordo com a média de temperatura mensal (meses quentes = outubro a abril; meses frios = maio a setembro). RESULTADOS: Foram encontrados 955 casos de tromboembolismo venoso no período analisado. Foi utilizado o teste ANOVA para análise, que não revelou diferença estatisticamente significativa na incidência do tromboembolismo venoso de acordo com os trimestres. Quando analisados separadamente, também não se evidenciou significância estatística em relação ao tromboembolismo pulmonar e à trombose venosa profunda. Quando comparados os meses quentes e frios, observou-se aumento da incidência de trombose venosa profunda nos meses quentes (p < 0,05, teste de Mann-Whitney). CONCLUSÃO: O tromboembolismo venoso é uma doença que não tem uma relação bem estabelecida com as variações climáticas. A influência da temperatura ambiental na coagulabilidade ainda precisa ser ...

BACKGROUND: The triggering factors of venous thromboembolic disease have been increasingly clarified. External causes may influence its occurrence, and some climactic factors have stood out. Nothing is known about such interference in our latitude. OBJECTIVES: To determine whether there are seasonal variations in venous thromboembolism in a hospital-based population in São Paulo, Brazil, which has subtropical climate. METHODS: Medical records of patients admitted to Hospital da Beneficência Portuguesa de São Paulo with the diagnosis of deep venous thrombosis or pulmonary thromboembolism were reviewed from January 1996 to October 2003. Cases were grouped in trimesters (first trimester = January, February and March; second trimester = April, May and June; third trimester = July, August and September; fourth trimester = October, November and December). They were also grouped as to warm and cold months, according to mean temperature (warm months = October through April; cold months = May through September). RESULTS: A total of 955 cases of venous thromboembolism were found during the study period. The ANOVA test was used for statistical analysis, showing no significant difference in the occurrence of venous thromboembolism considering the four trimesters. Separate analysis of deep venous thrombosis and pulmonary embolism incidence showed no differences either. Comparing warm and cold months, there was an increased incidence of deep venous thrombosis during warm months (p < 0.05, Mann-Whitney test). CONCLUSION: Venous thromboembolism is not clearly related to climatic variations. The influence of climate and temperature on blood coagulability is poorly understood and needs to be further studied.

[Prospective study of early and late morbidity and mortality in the abdominal aortic aneurysm surgical repair]. / Estudo prospectivo da morbi-mortalidade precoce e tardia da cirurgia do aneurisma da aorta abdominal.

OBJECTIVE: To prospectively assess early and late morbidity and mortality of patients undergoing elective surgical repair of abdominal infrarenal aortic aneurysms and to determine the independent predictors of cardiac events. METHODS: For 6 consecutive years, this study analyzed 130 patients, who underwent routine standardized preoperative assessment always with the same clinical, surgical, and anesthesia teams. RESULTS: In-hospital mortality was 3.1% (4 patients), and the major cause of death was mesenteric ischemia, which occurred in 3 patients. Forty-eight (37%) nonsurgical complications occurred as follows: 8.5% were cardiac complications and 28.5% were noncardiac complications. The most common complications were the pulmonary ones, which occurred in 14 (10.8%) patients. Survivals in the first, third, and sixth postoperative years were 95%, 87%, and 76%, respectively. The variables that significantly correlated with morbidity and mortality were clinical predictors, mean age of 70.5 years, and presence of heart failure and chronic renal failure. No predictor of late morbidity and mortality was identified. CONCLUSION: Although this is considered a highly complex surgery, mortality is low, the cardiac complications are not very significant, and the patients have a good long-term evolution.

Estudo prospectivo da morbi-mortalidade precoce e tardia da cirurgia do aneurisma da aorta abdominal / Prospective study of early and late morbidity and mortality in the abdominal aortic aneurysm surgical repair

OBJETIVO: Avaliar, prospectivamente, a morbidade e mortalidade precoce e tardia de pacientes submetidos a correção cirúrgica eletiva de aneurisma de aorta abdominal infra-renal e determinar os preditores independentes de eventos cardiológicos. MÉTODOS: Estudados 130 pacientes durante seis anos consecutivos, submetidos a rotina de avaliação pré-operatória padronizada e cirúrgica, sempre pela mesma equipe clínica, cirúrgica e anestesiológica. RESULTADOS: A mortalidade hospitalar foi de 3,1 por cento (4 pacientes), sendo a principal causa de óbito isquemia mesentérica, ocorrida em três pacientes. Houve 48 (37 por cento) complicações não-operatórias, 8,5 por cento consistiram em complicações cardíacas e 28,5 por cento em complicações não cardíacas. As complicações pulmonares foram as mais comuns, ocorridas em 14 (10,8 por cento) pacientes. A sobrevida no 1°, 3° e 6° ano pós-operatório foi, respectivamente, de 95 por cento, 87 por cento e 76 por cento. As variáveis que se correlacionaram significativamente com a morbimortalidade foram preditor clínico, idade média de 70,5 anos, presença de insuficiência cardíaca e insuficiência renal crônica. Não foi identificado nenhum preditor de morbimortalidade tardia. CONCLUSÃO: Apesar de ser uma cirurgia considerada de alta complexidade, a mortalidade é baixa, as complicações cardíacas são de pequena monta e os pacientes apresentam boa evolução a longo prazo.

Acute reduction of ventricular volume decreases QT interval dispersion in elderly subjects with and without heart failure.

To evaluate the effects of acute reduction in ventricular volume (VV) on QT interval dispersion (QTd), 14 men with heart failure (HF; 74.5 +/- 2 yr of age) and 11 healthy male control subjects (68 +/- 2 yr of age) were studied. For 15 min, lower body negative pressure (LBNP) was applied at -15 and -40 mmHg to reduce venous return. At baseline and during LBNP application, QTd was measured with an 87-lead, body-surface-mapping device; chamber volumes were assessed by radioisotope ventriculography; blood pressure (BP) and heart rate (HR) were continuously monitored; and blood samples were obtained for assessment of norepinephrine (Nor) levels. At -15 mmHg, LNBP application induced a significant decrease in VV but did not change BP and HR in both groups. In addition, Nor levels increased significantly (P < or = 0.05) in the control group (from 286.7 +/- 31.5 to 388.8 +/- 41.2 pg/ml) and in HF patients (from 405.8 +/- 56 to 477.6 +/- 47 pg/ml), and QTd was significantly (P < or = 0.05) decreased in the control group (57.2 +/- 3.8 vs. 49.1 +/- 3.4 ms) and in HF patients (67.8 +/- 6 vs. 63.7 +/- 5.9 ms). No additional decreases in VV or QTd were produced by -40 mmHg LNBP, but Nor levels did increase in both groups and reach 475.5 +/- 34 and 586.5 +/- 60 pg/ml (P < 0.05) in the control and HF groups, respectively; BP did not change, but HR also increased in both groups. In conclusion, an acute LBNP-induced reduction in VV caused a decrease in the QTd of elderly men regardless of the existence of HF. Because increased sympathetic activity with more intense LBNP was not accompanied by additional changes in QTd, altered QTd may be better related to changes in VV than to autonomic nervous system activity.