Beta blockers and perioperative care: EHJ editorial addresses controversy

Since the end of 2011 when the scientific work of Professor Don Poldermans was first scrutinized there has been controversy in the medical world about the use of beta blockers in perioperative care.The recent publication — and retraction for proper peer reviewing and revision — in the European Heart Journal (EHJ) of a paper by Professors Cole and Francis from Imperial College, questioning whether beta blockers in perioperative care could lead to a mortality increase brought the topic back into the public eye.The EHJ has published an editorial today addressing these questions.In the editorial, Professors Thomas Lscher, Bernard Gersh, Ulf Landmesser and Frank Ruschitzka highlight, among other points, that jumping to conclusions may be particularly dangerous for both physicians and patients. In this respect, they pointed out that:The meta analysis is mainly driven by the POISE trial that used very high dosages of metoprolol immediately before surgery with further uptitration, which is not recommended by the ESC Guidelines Different dosing and starting time of betablockade before surgery may importantly determine outcome A registry published in 2013 in JAMA supports the use of perioperative blockade, at least in non-vascular surgery Until today, only one of Prof Poldermans’ manuscripts has been retracted, so the validity of his large beta blocker DECREASE trial published in the NEJM remains uncertain (3) A proper clinical trial is needed in order to assess whether the use of beta blockers starting at a low dose several days before surgery — as has been recommended by the ESC Guidelines of 2009 — might be beneficial or harmful The ESC Task Force led by Professors Steen Dalby Kristensen and Juhani Knuuti, is carefully revising all existing evidence and will present a new version of the ESC Guidelines on “Pre-operative Cardiac Risk Assessment and Perioperative Cardiac Management in Non-Cardiac Surgery” by this summer. These will try to answer two major issues: 1 Should beta blockers be continued in patients scheduled for surgery who are already on them? 2 Should beta blockers be started in patient undergoing surgery who have never received them previously? Whether beta blockers in perioperative care are protective, safe or harmful continues to be a subject of debate. The new ESC Guidelines will try to clarify some of the controversial issues. As stated jointly by ACC/AHA/ESC (4), in the meantime, the current position is that “the initiation of beta blockers in patients who will undergo non-cardiac surgery should not be considered routine, but should be considered carefully by each patient’s treating physician on a case-by-case basis.”Story Source:The above story is based on materials provided by European Society of Cardiology. Note: Materials may be edited for content and length.

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Heart attack patients return to work later, retire earlier if treatment is delayed

Oct. 12, 2013 — System delay in treating patients with ST-elevation myocardial infarction (STEMI) postpones their return to work and increases early retirement, according to research presented at the Acute Cardiac Care Congress 2013 by Kristina Laut, PhD student from Aarhus, Denmark.The Acute Cardiac Care Congress 2013 is the annual meeting of the Acute Cardiovascular Care Association (ACCA) of the European Society of Cardiology (ESC) and is held 12-14 October in Madrid, Spain.Ms Laut said: “System delay, which is time from emergency medical service call to reperfusion with primary angioplasty, has been associated with increased mortality and heart failure after STEMI. The 2012 ESC STEMI guidelines1 highlight system delay as a performance measure of quality of care.”She added: “Approximately 45% of patients admitted with STEMI are of working age but until now it was not known whether system delay impacts on timing of return to work and retirement. We decided to investigate this association because of the heavy burden to society with loss of production.”The study investigated whether system delay was associated with the duration of absence from work or time to retirement in STEMI patients treated with primary percutaneous coronary intervention (PPCI).This population-based cohort study included 4,061 patients under 67 years of age admitted with STEMI between 1 January 1999 and 1 December 2011 and treated with PPCI. The Danish National Register on Public Transfer Payments provided data on work outcomes. Only patients who were full- or part-time employed three weeks before their STEMI admission were included. Cut-off points of 4 and 8 years were used to ensure there were 10% of patients remaining for each of the analyses.After 4 years of follow up, 91% of the study population had returned to work. After 8 years of follow up, 29% had retired. After adjusting for confounding factors, system delay greater than 120 minutes was associated with postponed return to work (Sub Hazard Ratio=0.86; 95% Confidence Interval [CI]=0.81-0.92) and earlier retirement from work (Hazard Ratio=1.21; 95% CI=1.08-1.36).Ms Laut said: “We found that a large proportion of STEMI patients did return to the labour market within 4 years but 14% came back to work later because of a prolonged system delay. We also discovered that after 8 years, people with a long system delay had a 21% increase in retirement rate.”She added: “The association between increased system delay and reduced work resumption and earlier retirement exists but we need more studies to find out why. …

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Out-of-hospital cardiac arrest survival just 7 percent

Sep. 1, 2013 — Survival for out-of-hospital cardiac arrest is just 7%, according to research presented at ESC Congress 2013 by Professor Xavier Jouven and Dr Wulfran Bougouin from France.Professor Jouven said: “Sudden cardiac death (SCD) is an important public health problem, accounting for more than 400,000 deaths every year. The main cause is ventricular tachyarrhythmias which are often triggered by acute ischaemic events that can occur in persons with or without known heart disease. The survival rate from cardiac arrest has remained low over the last 40 years despite major investment and the epidemiology of SCD in Western Europe is unclear.” The Paris Sudden Death Expertise Centre (SDEC) Registry is a population based registry using multiple sources to collect every case of cardiac arrest in Greater Paris (population 6.6 million) according to the Utstein Style.1 Cases are continuously recorded (within hours of occurrence) and standardised follow-up is initiated on admission to the intensive care unit. Incidence, prognostic factors and outcomes are recorded.The results reported today reveal the 2 year experience of the SDEC Registry. From May 2011 to December 2012, 3,670 sudden cardiac arrests, with resuscitation attempted, occurred. Most cases occurred at home (72%) with bystanders in 81% of cases, performing cardiopulmonary resuscitation (CPR) in only 42% of cases. Among those cases only 34% of patients were admitted alive at hospital and 7% were discharged alive.Professor Jouven said: “The majority of sudden cardiac deaths occur outside hospital so specific programmes are needed in the community. Friends and relatives of people at risk of SCD should learn CPR and attend regular training to keep their skills up-to-date.” Therapeutic hypothermia and early coronary reperfusion were both significantly associated with survival (p<0.001) but these procedures were used in just 58% of patients admitted to hospital. Professor Jouven said: “These interventions markedly improve survival yet are given to just over half of patients. …

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Physical activity decreases sudden cardiac death risk in unfit men

Sep. 1, 2013 — Physical activity decreases the risk of sudden cardiac death in unfit men, reveals research presented at the ESC Congress today by Dr Jari Laukkanen and Dr Magnus Hagnas from Finland.Dr Laukkanen said: “Sudden cardiac death (SCD) accounts for approximately 50% of deaths from coronary heart disease. SCD typically occurs shortly after the onset of symptoms, leaving little time for effective medical interventions, and most cases occur outside hospital with few or no early warning signs. Finding ways to identify individuals at elevated risk of SCD would allow early interventions on risk factors to be implemented.” The current study investigated the impact of high leisure-time physical activity (LTPA) combined with cardiorespiratory fitness (CRF) on risk of SCD. It included 2,656 randomly selected men aged 42 to 60 years from the Kuopio Ischemic Heart Disease Risk Factor Study, a Finnish study of risk predictors for cardiovascular outcomes and SCD in the general population. Baseline cycle exercise test and risk factor assessment were performed in 1984-89. SCD was defined as death with cardiac origin within 24 hours after onset of symptoms.LTPA was assessed using a 12-month physical activity questionnaire. One third of subjects had low LTPA (energy consumption <191 kcal/day, equal to around 35 minutes of slow walking or 25 minutes of jogging for a 70 kg male). CRF was assessed with a maximal symptom limited cycle exercise test and peak oxygen uptake was calculated in metabolic equivalents (MET). One third of men had a low CRF (<7.9 METs).</p>For the analyses the study population was divided into 4 groups: 1) high CRF and high LTPA, 2) high CRF and low LTPA, 3) low CRF and high LTPA and 4) low CRF and low LTPA. …

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Multiple sclerosis drug shows promise for preventing heart failure

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New ‘biowire’ technology matures human heart by mimicking fetal heartrate

June 24, 2013 — A new method of maturing human heart cells that simulates the natural growth environment of heart cells while applying electrical pulses to mimic the heart rate of fetal humans has led researchers at the University of Toronto to an electrifying step forward for cardiac research.The discovery, announced this week in the scientific journal Nature Methods, offers cardiac researchers a fast and reliable method of creating mature human cardiac patches in a range of sizes.”You cannot obtain human cardiomyocytes (heart cells) from human patients,” explains Milica Radisic, Canada Research Chair in Functional Cardiovascular Tissue Engineering and Associate Professor at the Institute of Biomaterials & Biomedical Engineering (IBBME) and the Department of Chemical Engineering. Because human heart cells — integral for studying the efficacy of cardiac drugs, for instance — do not naturally proliferate in large numbers, to date researchers have been using heart cells derived from reprogrammed human induced pluripotent stem cells (hiPSC’s), which tend to be too immature to use effectively in research or transplantation.”The question is: if you want to test drugs or treat adult patients, do you want to use cells and look like and function like fetal cardiomyocytes?” asks Radisic, who was named a “Top Innovator Under 35” by MIT Technology Review and more recently was awarded the Order of Ontario and the Young Engineers of Canada 2012 Achievement Award. “Can we mature these cells to become more like adult cells?”In response to the challenge, Radisic and her team, which includes graduate student Jason Miklas and Dr. Sara Nunes, a scientist at the University Health Network (UHN) in Toronto, created a ‘biowire’. Stem-cells derived human cardiomyocytes are seeded along a silk suture typical to medical applications. The suture allows the cells to grow along its length, close to their natural growth pattern.Like a scene lifted from Frankenstein, the cells are then treated to cycles of electric pulses, like a mild version of a pacemaker, which have been show to stimulate the cells to increase in size, connect and beat like a real heart tissue.But the key to successfully and rapidly maturing the cells turns out to be the way the pulses are applied.Mimicking the conditions that occur naturally in cardiac biological development — in essence, simulating the way fetal heart rates escalates prior to birth, the team ramped up the rate at which the cells were being stimulated, from zero to 180 and 360 beats per minute.”We found that pushing the cells to their limits over the course of a week derived the best effect,” reports Radisic.Grown on sutures that can be sewn directly into a patient, the biowires are designed to be fully transplantable. The use of biodegradable sutures, important in surgical patches that will remain in the body, is also a viable option.Miklas argues that the research has practical implications for health care. “With this discovery we can reduce costs on the health care system by creating more accurate drug screening.”According to Nunes, the development takes cardiac research just one step closer to viable cardiac patches.”One of the greatest challenges of transplanting these patches is getting the cells to survive,” says Nunes, who is both a cardiac and a vascularization specialist, “and for that they need the blood vessels. Our next challenge is to put the vascularization together with cardiac cells.”Radisic, who calls the new method a “game changer,” points out just how far the field has come in a very short time.”In 2006 science saw the first derivation of induced pluripotent stem cells from mice,” she explains. “Now we can turn stem cells into cardiac cells and make relatively mature tissue from human samples, without ethical concerns.”

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Understanding the heart’s rhythm

June 11, 2013 — The heart’s regular rhythm is crucial to the delivery of oxygenated blood and nutrients to all the organs of the body. It is regulated by a bundle of cells called “the pacemaker,” which use electrical signals to set the pace of the heart. Dysfunction in this mechanism can lead to an irregular heartbeat, known as arrhythmia, and often necessitates the implantation of an artificial pacemaker.Previously, scientists found that many cases of inherited arrhythmias originating in the pacemaker could be attributed to functional defects in the channels responsible for the flow of sodium and calcium. Now Prof. Bernard Attali of Tel Aviv University’s Sackler Faculty of Medicine and his fellow researchers have discovered a previously unidentified potassium channel in the cardiac pacemaker which helps to regulate the heartbeat. He hypothesizes that some cases of unexplained arrhythmia could be traced back to irregularities in this channel.Developing therapies to target this potassium channel could be a significant step towards circumventing artificial pacemakers in favor of biological options, says Prof. Attali. This research has been reported in the journal PNAS.A cellular heart modelTo further investigate the workings of the biological pacemaker, Prof. Attali and his fellow researchers turned to embryonic stem cells isolated from human subjects. Once coaxed into differentiating into cardiac tissue, these cells began to beat automatically, like a small human heart.While observing and recording the cells’ electrical activity, researchers discovered the existence of a new channel in the pacemaker. …

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Cardiac MRI use reduces adverse events for patients with acute chest pain

June 10, 2013 — Wake Forest Baptist Medical Center doctors have found that using stress cardiac magnetic resonance (CMR) imaging in an Emergency Department observation unit to care for patients with acute chest pain is a win-win — for the patient and the institution.In a small, single-center clinical trial, Chadwick Miller, M.D., M.S., and colleagues found that evaluating older, more complex patients in the observation unit with stress cardiac MRI, as opposed to usual inpatient care, reduced hospital readmissions, coronary revascularization procedures and the need for additional cardiac testing.The observation unit is an area of the Emergency Department designed for short stays — longer than a typical ED visit, said Miller, but shorter than a hospital admission. Cardiac MRI is a type of heart testing that uses magnetic forces to capture pictures of the heart.”We were looking at the optimum way to evaluate people with chest pain and focusing on those patients who are generally older, have many risk factors for coronary disease or may have had prior health problems, basically the intermediate to higher risk population,” Miller said. “At most hospitals in the United States, after evaluation in the emergency department, these patients are admitted to the hospital to complete their care.”The study appears online this month ahead of print in the journal JACC: Cardiovascular Imaging.Miller, who serves as director of clinical research and executive vice-chair of Emergency Medicine at Wake Forest Baptist, said the study built on previous research findings that more complex patients managed in an observation unit with stress CMR testing experienced a reduction in care costs of about $2,100 per patient per year. For the new study, the researchers wanted to specifically look at three care events: coronary revascularization, hospital readmissions and additional heart testing.The researchers recruited 105 patients from Wake Forest Baptist’s Emergency Department, randomizing them to receive care either in the Observation Unit with CMR or in the hospital. The patients were followed for 90 days, after which the researchers found significant reductions in coronary revascularization procedures, fewer hospital readmissions and fewer recurrent cardiac testing episodes or the need for additional testing.”What’s exciting about this is not only can we reduce events that are important to patients, but we can reduce costs as well,” Miller said. “What we think is happening is that the cardiac MRI is more accurately selecting patients who will benefit the most from having invasive procedures done. It’s a win-win.”The single-center design of the study is a limitation, Miller said, and these findings need to be replicated across multiple centers to validate the findings.The study was funded by National Institutes of Health’s National Heart, Lung, and Blood Institute, grant 1 R21HL097131-01A1; 1 R01HL076438, NIH T-32 HL087730.

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Lifespan-extending drug given late in life reverses age-related heart disease in mice: Rapamycin

June 10, 2013 — Elderly mice suffering from age-related heart disease saw a significant improvement in cardiac function after being treated with the FDA-approved drug rapamycin for just three months. The research, led by a team of scientists at the Buck Institute for Research on Aging, shows how rapamycin impacts mammalian tissues, providing functional insights and possible benefits for a drug that has been shown to extend the lifespan of mice as much as 14 percent.There are implications for human health in the research appearing online in Aging Cell: heart disease is the leading cause of death in the U.S., claiming nearly 600,000 lives per year.Researchers at the Mayo Clinic are currently recruiting seniors with cardiac artery disease for a clinical trial involving low dose treatment with rapamycin.Rapamycin is an immunosuppressant drug which can be used to help prevent organ rejection after transplantation. It is also included in treatment regimens for some cancers. In this study, rapamycin was added to the diets of mice that were 24 months old — the human equivalent of 70 to 75 years of age. Similar to humans, the aged mice exhibited enlarged hearts, a general thickening of the heart wall and a reduced efficiency in the hearts ability to pump blood.The mice were examined with ultrasound echocardiography before and after the three-month treatment period — using metrics closely paralleling those used in humans. Buck Institute faculty Simon Melov, PhD, the senior author of the study, said age-related cardiac dysfunction was either slowed or reversed in the treated mice. “When we measured the efficiency of how the heart pumps blood, the treated mice showed a remarkable improvement from where they started. In contrast, the untreated mice saw a general decline in pumping efficiency at the end of the same three month period,” he said. “This study provides the first evidence that age-related heart dysfunction can be improved even in late life via appropriate drug treatment,” added Melov, who said the treated mice saw a reduction in heart size, reduced stress signaling in heart tissues and a reduction in inflammation.Buck researchers, utilizing genome analysis tools, uncovered suites of related genes which rapamycin modulates in the heart. “Rapamycin affected the expression of genes involved in calcium regulation, mitochondrial metabolism, hypertrophy and inflammation,” said Melov. …

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