The HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes was released by the Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA) and Asia Pacific Heart Rhythm Society (APHRS).
“The complexity and prevalence of inherited cardiovascular diseases is growing, thereby creating a greater demand for the proper diagnosis and management of patients with these conditions,” said HRS Chairperson Dr Silvia G Priori (Fondazione Salvatore Maugeri, Department of Molecular Medicine, University of Pavia, Pavia, Italy). “Clinicians and other healthcare professionals from around the world have come together to address this concern which is top of mind for our field,” she added.
The consensus statement provides recommendations from an international writing group, based on literature review and their own clinical experience. The consensus statement is aimed at all healthcare professionals who manage the care of individuals who have survived cardiac arrest at a young age, family members of individuals who have died suddenly at a young age with a negative autopsy, patients in whom the diagnosis of an inherited arrhythmia is clinically possible, or young patients with unexplained syncope.
The statement provides the diagnostic risk stratification and management of patients, among others, affected by long QT Syndrome (LQTS) and Brugada Syndrome (BrS). The statement also includes a consensus of recommendations on the diagnosis, risk stratification, and management of the following arrhythmic diseases and unexplained causes of sudden death/cardiac arrest:
* Catecholaminergic polymorphic ventricular tachycardia (CPVT)
* Short QT syndrome (SQTS)
* Early repolarisation (ER)
* Progressive cardiac conduction disease (PCCD)
* Unexplained cardiac arrest including idiopathic ventricular fibrillation (VF), sudden unexplained death syndrome (SUDS), and sudden unexplained death in infancy (SUDI).
“This document is a great advancement for electrophysiology because it provides one, comprehensive and uniform recommendation on all rare arrhythmia syndromes,” said EHRA Chairperson Dr Arthur Wilde (University of Amsterdam, Amsterdam, Netherlands). “As new data emerges and our understanding of the role of genetics improves, collaboration like this will help ensure the best quality of care is delivered,” he added.
An additional primary recommendation from the expert consensus writing committee is that patients and first-degree relatives with a diagnosed or suspected inherited cardiovascular disease should be evaluated in a dedicated clinic with appropriately trained clinical staff and the resources to provide support to the patient and family members.
The document will be published simultaneously in HeartRhythm and in EP Europace in autumn 2013.
Because amiodarone is fat-soluble and degrades very slowly, large amounts can accumulate in soft tissues after a long-term prescription. Previous studies have shown that amiodarone might increase the risk of certain cancers, but no large-scale study has looked at the issue.
Researchers led by Dr Vincent Yi-Fong Su (Taipei Veterans General Hospital, Taiwan) studied 6,418 individuals taking the drug, following them for an average of 2.57 years. A total of 280 participants developed cancer.
Patients who were male or who received high cumulative daily doses of amiodarone within the first year had an increased risk of developing cancer. Those with both factors were 46% more likely to develop cancer than those with neither factor. After taking age, sex, and illnesses into account, individuals taking a high amount of amiodarone had nearly twice the risk of developing cancer as those taking a low amount of the drug.
“We suggest that cancer events should be routinely reported in future amiodarone trials, and further observational research is necessary,” said Dr Su. “Also, when prescribing amiodarone, doctors need to keep in mind that this medication may increase cancer risk.”
Speaking to theheart.org, another expert cautions that while we should pay attention to the findings of this study, “we need to take it with a grain of salt.” Dr James Marshall (Roswell Park Cancer Institute, Buffalo, NY), who wasn’t involved in the analysis, pointed out that it has a number of limitations.
It is based on the use of standard incidence ratios (SIR)s, he noted, which compare the number of observed cancer cases with the “expected” number of cases within a population or geographic area.
“There was only a 12% increase for the whole group, and that is a small increase,” Marshall said. “If this were a pristine study, it might mean something, but they are using standard incidence ratios, and those are notoriously difficult to interpret.”
The use of the cumulative defined daily dose is a little cleaner, he said. “They can then compare high exposure and low exposure.”
Marshall also noted that while the authors did adjust for age, gender, and comorbidities, they did not look at potential risk factors such as smoking, environmental exposure, family history of malignancy, alcohol use, and obesity.
“We do want to make note of these results,” he said, “And not just toss the data out. But I don’t think cardiologists are going to change treatment based on this one study alone. We need to be careful about coming to conclusions until we see some confirmation of this in other studies.”
1. Su VY, Hu Y-W, Chou K-T, et al. Amiodarone and the risk of cancer: a nationwide population-based study. Cancer 2013;119:1699–705. http://dx.doi.org/10.1002/cncr.27881
After considering meta-analyses and the latest clinical trials on different types of meditation, the report stated that while TM is recommended to lower blood pressure, there is not enough scientific evidence to recommend other meditation or relaxation techniques.
The authors of the report assessed three categories of alternative approaches: behavioural therapies such as meditation, non-invasive procedures or devices, and exercise-based regimens. The report did not review diets or dietary supplements.
Meta-analyses referenced in the report found that TM practice lowers blood pressure on average 5 mmHg systolic and 3 mmHg diastolic. Although this is by some accounts modest, Dr Schneider pointed out that for millions of people with high blood pressure, this reduction may help to bring them into a more normal range or prevent the need for hypertension medication with attendant side effects and costs. Clinical trials have shown that lower blood pressure through TM practice is associated with significantly lower rates of death, heart attack, and stroke.
The report also recognised that TM is generally considered safe and without harmful side effects. As an additional advantage, the statement noted that many of the reviewed alternative therapies, such as meditation, may provide a range of health or psychological benefits beyond blood pressure lowering or cardiovascular risk reduction.
The report concluded that, “It is the consensus of the writing group that it is reasonable for all individuals with blood pressure levels >120/80 mm Hg to consider trials of alternative approaches as adjuvant methods to help lower blood pressure when clinically appropriate.”
“We are gratified that our research demonstrating the efficacy of TM on blood pressure is being recognised and hope that this consensus will result in its wider use in clinical practice,” said Professor C. Noel Bairey Merz, (Cedars Sinai Medical Center, Los Angeles, California, USA), principal investigator for a National Institutes of Health sponsored clinical trial on TM and cardiovascular health.
“This is an important breakthrough in the evolution of medical practice, since it is the first time that the TM technique has been recognised and recommended for consideration by a national medical organisation that provides professional practice guidelines to physicians, health care payers, and policymakers,” said Dr Robert Schneider, director of the Institute for Natural Medicine and Prevention. Dr Schneider has been the principal investigator for several research studies on the TM technique and cardiovascular disease. “This type of guideline statement has been what health insurance companies have been requesting for many years,” he added.
1. Brook RD, Appel LJ, Rubenfire M, et al. Beyond medications and diet: alternative approaches to lowering blood pressure: a scientific statement from the American Heart Association. Hypertension 2013;61. http://dx.doi.org/10.1161/HYP.0b013e318293645f
The aims of the RecordAF (REgistry on Cardiac Rhythm DisORDers Assessing the Control of Atrial Fibrillation) study were to identify risk factors for AF progression and the effects of management approaches.
Researchers assessed AF progression at 12 months in the US cohort. AF progression was defined as a change of AF to a more sustained form (either paroxysmal becoming persistent or permanent, or persistent becoming permanent).
The US cohort included 955 patients, with mean age of 68.9 years; 56.8% were men and 88.8% were white. At entry, 59.6% of patients were selected for rate-control and 40.4% for rhythm-control therapy. At 12 months, the management strategy was unchanged for 68.2% of the patients in the rate- and 77.7% of the patients in the rhythm-control groups.
Overall, AF progression had occurred in 18.6% of patients at 12 months. The progression rate was significantly greater in the rate-control (27.6%) than in the rhythm-control (5.8%) group (p<0.001). Progression to permanent AF occurred in 16.4% of patients. In addition to a rate-control strategy, older age, AF rhythm at entry, persistent AF at baseline, and a history of stroke or transient ischaemic attack independently predicted AF progression.
Rate control was associated with AF progression, with a propensity score adjusted odds ratio of 2.67 (p<0.001). The authors conclude that although rate control was the preferred USA treatment, it was associated with more AF progression than rhythm control.
1. Zhang Y-Y, Qiu C, Davis PJ, Jhaveri M, Prystowsky EN, MD Kowey P, Weintraub WS. Predictors of progression of recently diagnosed atrial fibrillation in REgistry on Cardiac Rhythm DisORDers Assessing the Control of Atrial Fibrillation (RecordAF) – United States Cohort. Am J Cardiol 2013. http://dx.doi.org/10.1016/j.amjcard.2013.02.056
The “heart patch” developed by biomedical engineers at Duke University (Durham, North Carolina, USA), using pluripotent human embryonic stem cells, conducts electricity at roughly the same speed as natural heart cells, and ‘squeezes’ appropriately. Earlier attempts to create functional heart patches have largely been unable to overcome those obstacles, say the authors.
“The structural and functional properties of these 3-D tissue patches surpass all previous reports for engineered human heart muscle,” said Dr Nenad Bursac, associate professor of biomedical engineering at Duke’s Pratt School of Engineering. “This is the closest man-made approximation of native human heart tissue to date.”
“In past studies, human stem cell-derived cardiomyocytes were not able to both rapidly conduct electrical activity and strongly contract as well as normal cardiomyocytes,” Dr Bursac said. “Through optimisation of a three-dimensional environment for cell growth, we were able to ‘push’ cardiomyocytes to reach unprecedented levels of electrical and mechanical maturation.”
The rate of functional maturation is an important element for the patch to become practical, said Dr Bursca – while it takes about nine months for a neonatal functioning heart to develop in a developing human embryo, advancing the functional properties of these bioengineered patches took little more than a month. “Currently, it would take us about five to six weeks starting from pluripotent stem cells to grow a highly functional heart patch,” he said, adding that as technology advances, the time should shorten.
“When someone has a heart attack, a portion of the heart muscle dies,” Dr Bursac said. “Our goal would be to implant a patch of new and functional heart tissue at the site of the injury as rapidly after heart attack as possible. Using a patient’s own cells to generate pluripotent stem cells would add further advantage in that there would likely be no immune system reaction, since the cells in the patch would be recognised by the body as self.”
In addition to a possible therapy for patients with heart disease, Dr Bursac said that engineered heart tissues could also be used to effectively screen new drugs or therapies: “Tests or trials of new drugs can be expensive and time-consuming. Instead of, or along with testing drugs on animals, the ability to test on actual, functioning human tissue may be more predictive of the drugs’ effects and help determine which drugs should go on to further studies.”
The current experiments were conducted on one human pluripotent stem cell line. Dr Bursac and his colleagues have reproduced their findings on two other cell lines and are testing additional lines. They are also planning to move to larger animal models to learn how the patch would become functionally integrated with its host and how the patch establishes connections with the circulatory system.
Speaking to BJC Arrhythmia Watch, Dr Bursac said: “In terms of adopting this technology to routine clinical practice, I would anticipate that it will take another 10 years of careful tests before this approach would reach clinics. At the current stage, the technology can be utilised for drug development and toxicology studies, but getting to clinical practice will require careful demonstration of safety and efficacy in large animal models.”
“The hope is that potential functional benefits of such a tissue engineering approach will offset risks that open heart surgery (currently the only mode of patch delivery) may incur. A stepping stone in this process will be the use of pluripotent stem cell-derived cardiomyocytes (as cell injections rather than a patch) in clinical trials, which is something that I could envision happen in the next five years,” he added.
1. Zhang D, Shadrin IY, Lamb J, Xian HQ, Snodgrass HR, Bursac N. Tissue-engineered cardiac patch for advanced functional maturation of human ESC-derived cardiomyocytes. Biomaterials 2013;34:5813–20. http://dx.doi.org/10.1016/j.biomaterials.2013.04.026
Investigators followed 3,302 premenopausal women between the ages of 42–52 for 11 years, who were enrolled in the Study of Women’s Health across the Nation (SWAN). Researchers compared CVD risk factors in women prior to and following elective hysterectomy with or without ovary removal to the risk factors prior to and following final menstrual period in women who underwent natural menopause.
They found that several CVD risk factor changes differed prior to and following hysterectomy, compared to changes prior to and following a natural menopause, but those changes did not suggest an increased CVD risk following hysterectomy, independent of body mass index, which did increase after hysterectomy with removal of ovaries. These effects were similar in all ethnic groups in the study.
“Middle-aged women who are considering hysterectomy should be encouraged because our results suggest that increased levels of cardiovascular risk factors are not any more likely after hysterectomy relative to after natural menopause,” said lead author Professor Karen A Matthews, (University of Pittsburgh, Pennsylvania, USA).
Professor Matthews said it is unclear why this study’s findings differed from other studies exploring hysterectomy and cardiovascular risk, but likely factors include the age of participants since hysterectomy that occurs earlier in life may present more cardiovascular risk. Also, earlier studies included women who had hysterectomy for any reason, whereas the SWAN study excluded women who had hysterectomy because of cancers, she added.
“This study will prove very reassuring to women who have undergone hysterectomy,” said American College of Cardiology CardioSmart Chief Medical Expert Dr JoAnne Foody. “As with anything, if a woman is concerned about her risk for heart disease she should discuss this with her health care provider.”
1. Matthews KA, Gibson CJ, El Khoudary SR, Thurston RC. Changes in cardiovascular risk factors by hysterectomy status with and without oophorectomy: study of women’s health across the nation. J Am Coll Cardiol 2013. http://dx.doi.org/10.1016/j.jacc.2013.04.042
The clinical study was conducted at the Radboud University Nijmegen Medical Centre (Nijmegen, the Netherlands) between September and November 2012, involving 39 patients with a body mass index (BMI) range of 20–37. During the study, two coronary angiography scans of the same patient were compared: for the first scan conventional interventional X-ray technology was used, while for the second scan new technology (AlluraClarity system with ClarityIQ technology, Philips) was used.
Six independent interventional cardiologists from across Europe (Italy, France, Germany, the Netherlands and Sweden) then evaluated the image quality of these scans, and concluded that compared to conventional X-ray technology, the new technology provided equivalent image quality at 50% less X-ray dose.
“We have extensively explored and tested this new technology at our cardiac center”, said co-author Professor N Reifart. “It now enables us to perform most diagnostic angiographies with at least 50% lower radiation levels, equivalent to less than 1 mSv, with similar image quality as in the past”.
Additional studies on the new technology in the fields of neuroradiology and electrophysiology are ongoing, with results expected later this year.
Speaking at a meeting organised by 2020health, a “grass-roots, health and technology policy Think Tank,” at the Microsoft offices in London recently, Mr Burnham described how the NHS is paid by those who “go through the door,” know as an “episodic tariff,” and thereby the hospital has become the “default setting”.
In fact what we need is to create the reverse, where the home becomes the default, he said. While, at present, the social side of care is outside of the healthcare system, “We need to look towards the wider determinants of health” where the physical, mental and social needs of patients are integrated, “that’s the nub of it” in Mr Burnhams view.
“There should be a decisive switch towards prevention,” he went on, utilising new technologies such as telehealth – the delivery of health-related services and information via telecommunications technologies. This, an extension of telemedicine, encompasses preventative, promotive and curative aspects of health. It may be as simple as using the phone to communicate with patients, to more sophisticated transmission of medical images and health informatics.
Mr Burnham described the fear of isolation and neglect in old age now commonplace, as the need of more social and medical care in the elderly increases – something we “cannot allow to happen,” he said.
We need to “triage” the older more at risk individuals in the community and stop the drift towards hospital. This requires a re-think from first principles and demands an integration of care, away from the present very narrow medical perspective. “We need to exploit technology to help” and this “can’t come a moment too soon,” Mr Burnham concluded.
“Our love affair with technology seems to extend into every area of our lives but health,” in the view of Julia Manning, Chief Executive of 2020health. This raises a number of questions on how we can engage both professionals and patients towards participation in such new initiatives.
Researchers led by Drs Lia Crotti (University of Pavia, Italy) and Michael J Ackerman (Mayo Clinic, Rochester, USA) conducted a study to determine the spectrum and prevalence of mutations in the three most common LQTS-susceptible genes (KCNQ1, KCNH2, and SCN5A) for a group of unexplained foetal death cases. In this case series, retrospective postmortem genetic testing was conducted on a sample of 91 unexplained intrauterine foetal deaths that were collected from 2006–2012 (average estimated gestational age at foetal death, 26.3 weeks; 51 females, 40 males).
More than 1,300 ostensibly healthy individuals served as controls. In addition, publicly available exome databases were assessed for the general population frequency of identified genetic variants.
Excluding two very common genetic variants, the researchers identified 14 genetic variants in 18 intrauterine foetal deaths (19.8%) of 91 including three of 30 late abortion or miscarriages (10%) and 15 of 61 stillbirths (24.6%). “Three variants found in three intrauterine foetal death cases (3.3%) of 91 were considered putative pathogenic mutations based on their absence in more than 1,000 ethnically similar controls, a heterozygote frequency below the prevalence of LQTS in the general population (0.05%) as determined by analysis of more than 10,000 publicly available exomes, and an abnormal functional electrophysiological profile.”
In addition, five intrauterine foetal deaths hosted SCN5A rare non-synonymous genetic variants (a polymorphism that results in a change in the amino acid sequence of a protein) that conferred in vitro electrophysiological characteristics consistent with potentially pro-arrhythmic phenotypes.
Overall, genetic variants leading to dysfunctional LQTS-associated ion channels in vitro were discovered in 8 cases (8.8%).
Postmortem evaluations fail to identify a cause of death in approximately 25–40% of foetal deaths, according to the authors. However, “LQTS has been shown to be a major determinant in young sudden death individuals for which an autopsy was performed but had remained inconclusive and a determinant for as much as 10% of sudden infant death syndrome (SIDS),” they add, speculating that long QT syndrome may also contribute to sudden unexpected foetal mortality.
“To our knowledge, this represents the first demonstration of such findings. This preliminary evidence suggests LQTS is one plausible cause of intrauterine fetal death; supports the previously proposed mechanistic link between some cases of intrauterine fetal death, SIDS, and LQTS; and provides precedence for further large-scale investigations into the extent and role of cardiac channelopathies in stillbirth,” the authors conclude.
In an accompanying editorial2, Dr Alan Guttmacher (National Institutes of Health, Bethesda, USA) and colleagues say:”Understanding the etiology of stillbirth is essential not just for crafting effective prevention strategies but also for providing families and clinicians with counseling information and the opportunity for a greater sense of closure”.
“Recent efforts to fully characterize stillbirths have provided a foundation for identifying the causal factors and include novel technologies to evaluate the genomic alterations in stillbirth. The findings of Crotti and colleagues add another piece to solving this puzzle. If confirmed in well-characterized cohorts and amplified by broader genomic approaches, such work may provide an explanation for many cases of late miscarriage and stillbirth previously labeled as ‘unknown,’” they conclude.
1. Crotti L, Tester DJ, White WM, et al. Long QT syndrome–associated mutations in intrauterine fetal death. J Am Med Assoc 2013;309:1473–82. http://dx.doi.org/10.1001/jama.2013.3219
2. Guttmacher AE, Spong CY, Willinger M. Long QT syndrome susceptibility mutations and pregnancy loss another piece of a still unfinished puzzle? J Am Med Assoc 2013;309:1525–6. http://dx.doi.org/10.1001/jama.2013.3373
The toolkit recommends the use of NEWS – the National Early Warning Score, launched by the RCP in 2012 – to rapidly identify patients who are severely ill or at risk of sudden deterioration. The sickest of these patients should be transferred to the hospital’s intensive care unit or high dependency unit.
The RCP is concerned about those patients identified as requiring an intensity of monitoring and care greater than that available on a standard medical ward. More enhanced care beds (level 1 beds), with higher nurse to patient ratios, should be available on acute medical units. In addition, hospitals should designate enhanced care beds on selected medical wards that manage acutely ill patients.
Recommendations for assessment:
Recommendations – right patient, right bed:
Lead author Dr Rhid Dowdle said: “One of the major drivers for this toolkit was the identification of shortcomings in the care of seriously unwell medical patients by the National Confidential Enquiry into Patient Outcome and Death (NCEPOD). I hope the recommendations we have made will, if implemented, improve the care of this vulnerable group of patients.”
Dr Mark Temple, RCP acute care fellow and toolkit series lead, said: “The early recognition of the patient who is deteriorating or at risk of deterioration, provides the best opportunity to intervene rapidly and effectively. Acute care toolkit 6 focuses on the use of the National Early Warning Score (NEWS) to detect changes in the severity of a patient’s illness and links this to a series of actions by nurses and doctors to escalate care. The toolkit deals with best practice in the management of acutely ill patients throughout the hospital and is fundamental to improving patient outcomes and saving lives.”
Dr Chris Roseveare, Society for Acute Medicine president said: “I am delighted that we are able to launch this key document at the Society for Acute Medicine spring conference this week. Ensuring that seriously unwell patients receive prompt, safe care should be a top priority for all staff working on the acute medical unit. The toolkit highlights the importance of early recognition, followed by rapid, senior review for this high risk group of patients; this will be a key message from the three speakers at our opening symposium today.
“It is crucial to ensure that such patients are managed in the most appropriate ward setting, by staff with the skills to provide this care. Many acute medical units already provide such facilities, and the next generation of acute medicine consultants will all undergo a formal period of critical care training to ensure that these skills are embedded into the AMU team,” he added.
Download the toolkit at http://www.rcplondon.ac.uk/resources/acute-care-toolkit-6-medical-patient-risk