Márcio Jansen de Oliveira Figueiredo

Relationship of autonomic imbalance and circadian disruption with obesity and type 2 diabetes in resistant hypertensive patients

BackgroundHypertension, diabetes and obesity are not isolated findings, but a series of interacting interactive physiologic derangements. Taking into account genetic background and lifestyle behavior, AI (autonomic imbalance) could be a common root for RHTN (resistant hypertension) or RHTN plus type 2 diabetes (T2D) comorbidity development. Moreover, circadian disruption can lead to metabolic and vasomotor impairments such as obesity, insulin resistance and resistant hypertension. In order to better understand the triggered emergence of obesity and T2D comorbidity in resistant hypertension, we investigated the pattern of autonomic activity in the circadian rhythm in RHTN with and without type 2 diabetes (T2D), and its relationship with serum adiponectin concentration.MethodsTwenty five RHTN patients (15 non-T2D and 10 T2D, 15 males, 10 females; age range 34 to 70 years) were evaluated using the following parameters: BMI (body mass index), biochemical analysis, serum adiponectinemia, echocardiogram and ambulatory electrocardiograph heart rate variability (HRV) in time and frequency domains stratified into three periods: 24 hour, day time and night time.ResultsBoth groups demonstrated similar characteristics despite of the laboratory analysis concerning T2D like fasting glucose, HbA1c levels and hypertriglyceridemia. Both groups also revealed disruption of the circadian rhythm: inverted sympathetic and parasympathetic tones during day (parasympathetic > sympathetic tone) and night periods (sympathetic > parasympathetic tone). T2D group had increased BMI and serum triglyceride levels (mean 33.7 ± 4.0 vs 26.6 ± 3.7 kg/m2 - p = 0.00; 254.8 ± 226.4 vs 108.6 ± 48.7 mg/dL - p = 0.04), lower levels of adiponectin (6729.7 ± 3381.5 vs 10911.5 ± 5554.0 ng/mL - p = 0.04) and greater autonomic imbalance evaluated by HRV parameters in time domain compared to non-T2D RHTN patients. Total patients had HRV correlated positively with serum adiponectin (r = 0.37 [95% CI -0.04 - 1.00] p = 0.03), negatively with HbA1c levels (r = -0.58 [95% CI -1.00 - -0.3] p = 0.00) and also adiponectin correlated negatively with HbA1c levels (r = -0.40 [95% CI -1.00 - -0.07] p = 0.02).ConclusionType 2 diabetes comorbidity is associated with greater autonomic imbalance, lower adiponectin levels and greater BMI in RHTN patients. Similar circadian disruption was also found in both groups indicating the importance of lifestyle behavior in the genesis of RHTN.

Autonomic function in patients with functional dyspepsia assessed by 24-hour heart rate variability

The function of the autonomic nervous system was assessed in 23 patients with dysmotility-like functional dyspepsia and 12 healthy volunteers by analysis of 24-hr heart rate variability and a battery of five standardized sympathetic and parasympathetic cardiovascular reflex tests. Measures of heart rate variability were obtained by analysis of ambulatory electrocardiographic recordings using both the time and the frequency domain methods. The values of parameters reflecting vagal activity (HF, rMSSD) were significantly lower in patients with functional dyspepsia. Individual analysis of heart rate variability data identified at least one abnormal parameter of vagal function in seven (30.4%) patients, and in five of these the results of parasympathetic cardiovascular reflex tests were also abnormal. Our results suggest impaired efferent vagal function in a subgroup of patients with functional dyspepsia. This abnormality may play a role in the pathogenesis of the disease in these patients.

Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function

Summary Despite significant advances in our understanding of the biology determining systemic energy homeostasis, the treatment of obesity remains a medical challenge. Activation of AMP-activated protein kinase (AMPK) has been proposed as an attractive strategy for the treatment of obesity and its complications. AMPK is a conserved, ubiquitously expressed, heterotrimeric serine/threonine kinase whose short-term activation has multiple beneficial metabolic effects. Whether these translate into long-term benefits for obesity and its complications is unknown. Here, we observe that mice with chronic AMPK activation, resulting from mutation of the AMPK γ2 subunit, exhibit ghrelin signaling-dependent hyperphagia, obesity, and impaired pancreatic islet insulin secretion. Humans bearing the homologous mutation manifest a congruent phenotype. Our studies highlight that long-term AMPK activation throughout all tissues can have adverse metabolic consequences, with implications for pharmacological strategies seeking to chronically activate AMPK systemically to treat metabolic disease.

European Heart Rhythm Association (EHRA)/European Association of Cardiovascular Prevention and Rehabilitation (EACPR) position paper on how to prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) and Asia Pacific Heart Rhythm Society (APHRS)

EHRA Scientific Committee Task Force: Bulent Gorenek (chair)*, Antonio Pelliccia (co-chair), Emelia J. Benjamin, Giuseppe Boriani, Harry J. Crijns, Richard I. Fogel, Isabelle C. Van Gelder, Martin Halle, Gulmira Kudaiberdieva, Deirdre A. Lane, Torben Bjerregaard Larsen, Gregory Y. H. Lip, Maja-Lisa Løchen, Francisco Marin, Josef Niebauer, Prashanthan Sanders, Lale Tokgozoglu, Marc A. Vos and David R. Van Wagoner Document reviewers: Laurent Fauchier, Irina Savelieva, Andreas Goette, Stefan Agewall, Chern-En Chiang, Márcio Figueiredo, Martin Stiles, Timm Dickfeld, Kristen Patton, Massimo Piepoli, Ugo Corra, Pedro Manuel Marques-Vidal, Pompilio Faggiano, Jean-Paul Schmid and Ana Abreu Eskisehir Osmangazi University, Eskisehir, Turkey; Institute of Sport Medicine and Science, Rome, Italy; Framingham, MA, USA; University of Modena and Reggio Emilia, Modena Italy; Maastricht University Medical Centre, Maastricht, The Netherlands; St Vincent Medical Group, Indiana, USA; University Medical Center Groningen, Groningen, The Netherlands; Prevention and Sports Medicine, Technical University Munich, München, Germany; Adana, Turkey; University of Birmingham, Birmingham, UK; Aalborg University Hospital, Aalborg, Denmark; UiT The Arctic University of Norway, Tromso, Norway; Mary MacKillop Institute for Health Research, Centre for Research Excellence to Reduce Inequality in Heart Disease, Australian Catholic University, Melbourne, Australia; Hospital Universitario Virgen De La Arrixaca, Murcia, Spain; Paracelsus Medical University Salzburg, Salzburg, Austria; Royal Adelaide Hospital, Adelaide, South Australia;Hacettepe University, Ankara, Turkey; UMC Utrecht, Utrecht, The Netherlands; Cleveland Clinc Foundation, Cleveland, OH, USA; Centre Hospitalier Universitaire Trousseau, Tours, France; St George’s University of London, London, UK; St. Vincenz-Krankenhaus Gmbh Paderborn, Germany; Oslo University Hospital Ulleval, Ullevål, Norway; Taipei Veterans General Hospital, Taipei, Taiwan; State University of Campinas, San Paolo, Brazil; Waikato Hospital, Hamilton, New Zealand; Baltimore, MD, USA; University of Washington, Seattle, USA; Polichirurgico Hospital G. Da Saliceto, Romagna, Italy; Irccs Rehabilitation Medical Center, Veruno, Italy; University Hospital of Lausanne, Lausanne, Switzerland; Unita’ Operativa di Policardiografia, Brescia, Italy; Spital Tiefenau, Bern, Switzerland; and Hospital de Santa Marta, Lisboa, Portugal

Hypertension and cardiac arrhythmias: A consensus document from the European Heart Rhythm Association (EHRA) and ESC Council on Hypertension, endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS) and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE)

Hypertension is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease, stroke, peripheral artery disease and chronic renal insufficiency. Hypertensive heart disease can manifest as many cardiac arrhythmias, most commonly being atrial fibrillation (AF). Both supraventricular and ventricular arrhythmias may occur in hypertensive patients, especially in those with left ventricular hypertrophy (LVH) or HF. Also, some of the antihypertensive drugs commonly used to reduce blood pressure, such as thiazide diuretics, may result in electrolyte abnormalities (e.g. hypokalaemia, hypomagnesemia), further contributing to arrhythmias, whereas effective control of blood pressure may prevent the development of the arrhythmias such as AF. In recognizing this close relationship between hypertension and arrhythmias, the European Heart Rhythm Association (EHRA) and the European Society of Cardiology (ESC) Council on Hypertension convened a Task Force, with representation from the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE), with the remit to comprehensively review the available evidence to publish a joint consensus document on hypertension and cardiac arrhythmias, and to provide up-to-date consensus recommendations for use in clinical practice. The ultimate judgment regarding care of a particular patient must be made by the healthcare provider and the patient in light of all of the circumstances presented by that patient.

Investigation of Autonomic Function and Orocecal Transit Time in Patients With Nonalcoholic Cirrhosis and the Potential Influence of These Factors on Disease Outcome

Background The presence of autonomic dysfunction in nonalcoholic cirrhosis and its influence on intestinal transit and disease outcome still need clarification. Goals To investigate the function of the autonomic nervous system in patients with nonalcoholic cirrhosis and the possible associations among autonomic dysfunction, severity of liver disease, disturbed intestinal transit, and the development of complications during follow-up. Study Measurements of heart rate variability obtained by analysis of 24-hour ambulatory electrocardiographic recordings to assess autonomic function and lactulose breath hydrogen test to determine orocecal transit time were performed in 32 patients with nonalcoholic cirrhosis divided into Child A and B. Results Child B patients showed significantly lower values (P<0.05) of those parameters reflecting parasympathetic (high frequency, log-transformed high frequency, pNN50) and sympathetic function (low frequency, log-transformed low frequency) in comparison with controls and Child A patients. Orocecal transit time values were significantly (P=0.02) higher in Child B patients than in controls, but no relationship was found between delayed orocecal transit time and autonomic dysfunction. During follow-up, 42% of Child B patients developed encephalopathy. This complication was significantly associated with autonomic dysfunction. In addition, in the 4 patients who died the parameters reflecting parasympathetic function were significantly reduced in comparison with those of survivors. Conclusions Autonomic dysfunction and delayed intestinal transit are related to the severity of disease in nonalcoholic cirrhosis. Autonomic dysfunction seems to predispose cirrhotic patients to the development of encephalopathy and may be associated with a poor prognosis of these patients.

Hypertension and cardiac arrhythmias: executive summary of a consensus document from the European Heart Rhythm Association (EHRA) and ESC Council on Hypertension, endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE).

Hypertension (HTN) is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease (CAD), stroke, peripheral artery disease and chronic renal failure. Hypertensive heart disease can manifest as many types of cardiac arrhythmias, most commonly being atrial fibrillation (AF). Both supraventricular and ventricular arrhythmias may occur in HTN patients, especially in those with left ventricular hypertrophy (LVH), CAD, or HF. In addition, high doses of thiazide diuretics commonly used to treat HTN, may result in electrolyte abnormalities (e.g. hypokalaemia, hypomagnesaemia), contributing further to arrhythmias, while effective blood pressure control may prevent the development of the arrhythmias such as AF. In recognizing this close relationship between HTN and arrhythmias, the European Heart Rhythm Association (EHRA) and the European Society of Cardiology (ESC) Council on Hypertension convened a Task Force, with representation from the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE), with the remit of comprehensively reviewing the available evidence and publishing a joint consensus document on HTN and cardiac arrhythmias, and providing up-to-date consensus recommendations for use in clinical practice. The ultimate judgment on the care of a specific patient must be made by the healthcare provider and the patient in light of all individual factors presented. This is an executive summary of the full document co-published by EHRA in EP-Europace.

Rationale and design of the First Brazilian Cardiovascular Registry of Atrial Fibrillation: The RECALL study

BACKGROUND Atrial fibrillation (AF) is an important and growing public health problem worldwide, but data about its actual prevalence, therapeutic management, and clinical outcomes in middle- to low-income countries are scarce. DESIGN The First Brazilian Cardiovascular Registry of Atrial Fibrillation (the RECALL study) will assess demographic characteristics and evidence-based practice of a representative sample of patients with AF in Brazil. The prospective, multicenter registry has a planned sample size of around 5,000 patients at approximately 80 sites. Eligibility criteria include age >18 years and permanent, paroxysmal, or persistent AF documented by electrocardiogram, 24-hour Holter monitoring, or device interrogation. Patients will be followed up through 1 year after enrollment. Information on laboratory tests, echocardiographic data, medication use, and clinical outcomes will be obtained. Various aspects of the population will be described, including demographic characteristics; antithrombotic therapies; antiarrhythmic agents; level of control of international normalized ratio (by average time within the therapeutic range) among patients using vitamin K antagonists; rates of warfarin discontinuation; outcomes such as death, stroke, systemic embolism, and major bleeding within 1 year after enrollment in the study; and rates of electrical cardioversion, percutaneous ablation of AF, ablation of the atrioventricular junction, and pacemaker/cardioverter-defibrillator implantation. SUMMARY RECALL is the first prospective, multicenter registry of AF in Brazil. This study will provide important information about demographics, practice patterns, treatments, and associated outcomes in patients with AF. The results of this registry will also allow Brazilian data to be put in perspective with other AF registries across the world and provide opportunities to improve care of patients with AF in Brazil.

Conception and validation of a protocol for reuse of non-irrigated electrophysiology catheters in a Brazilian teaching hospital

PurposeSince the Brazilian current legislation permits the reuse of single-use devices under a validated processing protocol, the main purpose of our study was to develop and validate a method for reusing non-irrigated electrophysiology catheter (EC).MethodsManual and mechanical processing by ultrasonic washer was associated with the use of enzymatic solution and hydrogen peroxide with a final rinse with filtered water. Validation of the cleaning process, as well as catheter integrity, was done by observing the ECs in stereoscopic microscope at ×60 magnification, followed by HemoCheck-S® (HCS) test to monitor the presence of residual blood on their surfaces. Ethylene oxide (EO) was used for sterilization, and the final validations of the processing were performed by assays of sterility, pyrogenicity, and EO residuals. Lastly, a cost-minimization study was performed.ResultsCleaning process demonstrated absence of organic material detectable by HCS at the surfaces of the ECs. Assays for sterility were negative, and assays of EO residuals and endotoxins showed levels under established standards. The number of reuses was settled to a maximum of seven uses for the ECs with handle and ten uses for ECS without handle. The cost-minimization study showed an 84% savings, when considering seven reuses.ConclusionsProcessing of ECs was validated at all stages. Therefore, reuse of ECs under the conditions that we designed was considered safe for patients and cost-effective for our institution.

Cost-Effectiveness and Cost-Utility Analyses of Dabigatran Compared with Warfarin in Patients with Nonvalvular Atrial Fibrillation and Risk Factors for Stroke and Systemic Embolism within Brazilian Private and Public Health Care Systems Perspectives

OBJECTIVE To analyze the cost-effectiveness and cost-utility of dabigatran compared with warfarin in patients with nonvalvular atrial fibrillation with moderate to high risk of ischemic stroke or systemic embolism and eligible for treatment with anticoagulants. METHODS Markov-based economic analysis was performed to estimate treatment costs and outcomes. Epidemiological and efficacy data were determined after a critical revision of the medical literature. Unit costs were taken from Brazilian official databases. Only direct medical costs were covered. Costs and benefits were discounted at a rate of 5% per year. Outcomes were expressed as life-year (LY) and quality-adjusted life-year (QALY). RESULTS Dabigatran use is cost-effective in terms of LY and QALY considering a willingness-to-pay threshold of 3 times gross domestic product per capita of 2010 (Brazilian real 57,048/US