European Heart Journal (2014) 35, 2849–2854 doi:10.1093/eurheartj/ehu375
The 2014 ESC Guidelines on the Diagnosis and Management of Hypertrophic Cardiomyopathy have been published Chairman of the European Society of Cardiology Taskforce Prof. Perry Elliott, MD, FRCP, FESC, University College London and Lead for Inherited Cardiovascular Disease services, The Heart Hospital, UCLH, summarizes the changes and updates 1. Recognition of the diverse range of conditions that can cause HCM For the first time, we provide guidance on a clinically focused approach to the diagnosis of genetic and acquired causes of HCM. This is based on careful history-taking including analysis of family pedigrees and a cardiomyopathy-centred interpretation of commonly used diagnostic tools, such as electrocardiography and cardiac imaging. 2. Genetic testing We provide a clinically focused approach to the request for and interpretation of genetic tests. The role of expert counselling before and after genetic analysis is strongly emphasized and we provide clear guidance on the management of family members in different clinical scenarios based on the results of genetic testing. Most importantly, we advise consideration of genetic testing whenever it has implications for the screening of relatives. 3. Management of left ventricular outflow tract obstruction This is a common feature of HCM that can be treated with drugs or invasive therapies such as surgery and alcohol septal ablation. For the first time, we present a systematic approach to the assessment of left ventricular outflow tract obstruction that can be used to tailor therapies to the characteristics of individual patients. 4. Prevention of sudden cardiac death While the risk of sudden death is low for most patients with HCM, a small number are prone to life-threatening ventricular arrhythmias. One of the most important innovations in this guideline is the promotion of a new risk calculator (HCMRisk-SCD) that uses simple clinical measures to estimate the 5-year risk of sudden cardiac death. This estimate is then used to stratify patients into high-, intermediate-, and low-risk categories that can be used to guide the use of ICDs. These recommendations for sudden death prevention are likely to spark considerable interest and debate as they provide advice based on real estimates of risk rather than relative risks as in all previous guidelines. This will bring into focus the balance between clinical efficacy on the one hand and the potential risks and costs of therapy to individual patients and health-care economies on the other. 5. Management of heart failure Treatment of heart failure in patients with HCM is challenging and, unlike other diseases that cause heart failure, is unsupported by
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected].
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New Guidelines on the Diagnosis and Management of Hypertrophic Cardiomyopathy have been heralded as a significant step forwards in helping health-care professionals raise the standard of care for patients with the condition. Produced by the European Society of Cardiology taskforce on the diagnosis and management of hypertrophic cardiomyopathy (HCM), the emphasis is on improving diagnostic accuracy and delivering a more patient-centred approach to clinical management of HCM. The last ESC Guideline on HCM was published in 2003 as a joint consensus document with the American College of Cardiology [European Heart Journal (2003) 24, 1965–1991]. Chairman of the ESC taskforce, Prof. Perry Elliott points out that HCM is a relatively common disease that affects 1 in 500 of the population. It also affects people of all ages and is an important cause of premature death and morbidity. ‘Remarkably for such a common disease’, he said. ‘There have been very few randomized trials of therapy in people with HCM since that time, but a large body of basic and observational clinical studies has increased knowledge on the aetiology of the disease as well as its natural history’. ‘In this new version of the guideline, these data have informed a major change in the approach to the diagnosis of HCM that involves a deliberate search for specific genetic and non-genetic forms of the disease. In addition, there is greater emphasis on a systematic approach to defining the mechanisms of symptoms in order to target therapies more effectively’. ‘Two important innovations are, the adoption of an individualized approach to the estimation of sudden death risk that can be used to guide implantable cardioverter defibrillator (ICD) therapy and the provision of detailed advice to women with HCM on reproductive and pregnancy related issues’. The 2014 guidelines balance an ideal of best practice with the realities of health care provision. Prof. Elliott acknowledges that the recommendations will prove challenging in some countries, in particular the advice to consider early referral to multidisciplinary teams with expertise in the diagnosis and management of HCM, but the aim is to raise the general standard of care for all patients wherever they live. Prof. Elliott outlined the key changes and updates as follows:
2850 randomized clinical trials. Nevertheless, we provide a simple guide to physicians that can be used to tailor drug and device therapy. 6. Pregnancy and contraception We provide detailed and tailored advice to the assessment and management of women with HCM. Specifically, we provide guidance on pre-pregnancy assessment, the management of labour and detailed recommendations for contraception, sterilization, and termination. 7. Management of children For the first time, we provide advice on children in key sections on diagnosis and treatment. 8. Advice to patients Also included for the first time is the provision of guidance on practical everyday issues that affect the lives of patients with HCM
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and can be used by any health-care professional or patient support organization. Prof. Elliott concludes: ‘It is our collective hope that these guidelines will raise the standard of care for patients of all ages by improving the accuracy of diagnosis and through the use of a rationale, patientcentred approach to clinical management’. ‘Obvious gaps in evidence remain, but we believe that the guidelines provide a framework for future research and innovations in patient care’.
(1) Clinicians should consider referral of patients to multidisciplinary teams with expertise in the diagnosis, genetics, risk stratification, and management of heart muscle disease. (2) A clinically focused approach to the diagnosis of genetic and acquired causes of HCM based on careful history including analysis of family pedigrees and a cardiomyopathy-centred interpretation of commonly used diagnostic tools such as electrocardiography and cardiac imaging should be adopted. (3) Genetic counselling is recommended in all patients with unequivocal HCM when it cannot be explained solely by a non-genetic cause. (4) When a definite causative genetic mutation is identified in a patient, his or her first-degree relatives should first be genetically tested, and then clinically evaluated if they are found to carry the same mutation. (5) Exercise stress echocardiography is recommended in symptomatic patients with an LVOT gradient ,50 mmHg at rest. (6) When a gradient is detected in the left ventricular cavity, obstruction caused by subaortic membranes, structural mitral valve leaflet abnormalities, and mid-cavity obstruction should be systematically excluded. (7) Use of a new risk calculator (HCMRisk-SCD) is recommended to guide the use of implantable cardioverter defibrillators. (8) Patients with HCM and paroxysmal, persistent, or permanent atrial fibrillation should receive treatment with vitamin K antagonists and life-long therapy with oral anticoagulants is recommended, even when sinus rhythm is restored. (9) Patients in sinus rhythm with left atrial diameter ≥45 mm should undergo 6 –12 monthly 48-h ambulatory ECG monitoring to detect AF. (10) Most women with HCM tolerate pregnancy well but require expert advice before conception and throughout pregnancy.
EuroPCR 2014, Hypertension and Heart Failure Track take-home messages This year’s EuroPCR 2014 Hypertension and Heart Failure Track in Paris included presentation of live cases and discussion of new data, how-to and hotline sessions, as well as scientific poster and oral abstract sessions. Furthermore, dedicated sessions for practical training with hands-on anatomical models using different renal denervation systems have been very well attended. Altogether, .60 sessions discussed the topic around and about renal denervation. The ‘Interventions for Hypertension and Heart Failure Track′ started with an overview and update session entitled ‘All You
Need to Know About Renal Denervation’. The objectives of that session were to obtain a comprehensive update, to identify the current evidence base and existing guidelines, and to recognize the open questions that need to be addressed in the near future. The take-home messages stressed by the chairman Roland Schmieder (Germany) were ‘The sympathetic nervous system is more complex than we might have initially thought, and adequate patient selection and experienced operators are crucial to obtaining
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The ‘Ten Commandments’ of the ESC Hypertrophic Cardiomyopathy Guidelines
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variability’. It was reported that in the vast majority of patients in Symplicity HTN-3 (up to 70%) radiofrequency ablations were performed in a non-circumferential manner, which contradicts current clinical treatment recommendations. Interestingly, the delivery of ablations in four quadrants of the renal artery was consistently associated with more pronounced reductions in office, home, and ambulatory blood pressure. Furthermore, increasing reductions in systolic BP were associated with increasing numbers of ablations and complete four-quadrant ablation (Kandzari D, EuroPCR 2014). Thereafter, the Hypertension and Heart Failure Track continued in the main arena with a live demonstration of renal denervation in a patient with resistant hypertension as part of the EnlighHTN study from the Institut Cardiovasculaire Paris Sud Massy performed by Hakim Benamer and his team. Finally, the participants were introduced to device-based approaches targeting ventricular reshaping and cavity reduction. At the same time the therapeutic potential of sympatho-modulation in affecting end-organ damage and cardiovascular comorbidities was highlighted in a session entitled: ‘Catheter-based renal denervation - Treating across the cardiovascular continuum’, where some of the current 30 studies investigating the potential role of renal denervation in patients with metabolic syndrome, atrial fibrillation, and chronic heart failure were discussed. In summary, the sessions about and around Hypertension and Heart Failure were very well attended and the interest in renal denervation is still huge. This year’s EuroPCR was the first international meeting after the publication of Symplicity HTN-3 and provided a forum to discuss all the available data with the right critical spirit. The programme was focused on the science of renal denervation and what the next steps are, and illuminated the need for new and refined technologies to help monitor successful ablation of renal sympathetic nerve fibres intra-procedurally and to help identify patients with sympathetic overactivity. One thing was very clear at the end of the meeting: research efforts in that area of interventional medicine would and should continue. S.E. and F.M. are supported by Deutsche Hochdruckliga and Deutsche Gesellschaft fu¨r Kardiologie. F.M. has received research grants, speaker honorarium, and/or consultancy fees from Medtronic/Ardian, St Jude Medical, Cordis, and Recor.
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good results’. At the end of the day, data from the Symplicity HTN-3 trial and the Global Symplicity Registry were discussed. After an introduction and overview of resistant hypertension by Michael Bo¨hm (Germany), Manesh Patel (USA), one of the US investigators of Symplicity HTN-3, explained the results of the study and provided some subgroup analyses. Even though no subgroup met the statistical significance for treatment interaction, a seemingly greater blood pressure effect could be detected in non-African Americans. The outcome of Symplicity HTN-3 was contrary to the results of the previously published Symplicity HTN-1 and HTN-2 studies, which led to a very interactive discussion about potential reasons for the differences. In the multivariate analyses of predictors of response to renal denervation, only office systolic blood pressure ≥180 mmHg reached statistical significance. The second day of the track started in a room specifically designed to stimulate interaction between facilitators and participants, where different CE-marked devices for renal denervation have been discussed with the support of different educational tools, such as, Live-in-a-Boxw cases. This session aimed to exchange experiences derived from daily practice, addressed specific technical features that interventionists need to know in order to correctly use the various devices, and critically discussed the available clinical data. Parallel to this the participants had the opportunity to follow a session about revascularization in patients with ischaemic heart failure. These sessions were followed by an update on the results of the REDUCE-HTN, EnligHTN, ACHIEVE, REALISE, RAPID, and SYMPLICITY Spyral studies. The programme continued with two cardiovascular innovation pipeline sessions dedicated to new techniques for modulation of the sympathetic nervous system. One session discussed new approaches to target sympathetic nerve fibres in the kidney and other target structures. Another very interesting session focused on pre-clinical findings of different renal denervation techniques and catheter systems and these pre-clinical data were put into a clinical perspective. Renu Virmani concluded the session with a review of histopathological images of pig renal artery treated with the different renal denervation systems. The third day started with a comprehensive ‘State-of-the-Art’ lecture about percutaneous mitral valve repair with Mitraclip in heart failure [Chairmen: Jozef Bartunek (Belgium) and Olaf Franzen (Germany]. The Mitraclip procedure itself was a lively discussion with the use of a Live-in-a-Boxw case. A parallel hot-line session on resistant hypertension presented new data of the EnligHTN trial by Stephen Worthley (Australia), Global Symplicity Registry by Felix Mahfoud (Germany), Symplicity HTN-3 by David Kandzari (USA), ACHIEVE by Jost Daemen (The Netherlands), and REDUCE-HTN by Joachim Schofer (USA). David Kandzari concluded his presentation by stating that ‘prespecified and post-hoc analyses of Symplicity HTN-3 have identified potentially confounding factors, including antihypertensive medication use changes, differences in study populations and procedural
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Tales from another career: Douglas W. Losordo MD American cardiologist Douglas W. Losordo, MD, FACC, FAHA recently took up the post of chief medical officer with NeoStem, Inc., a company engaged in the development of cell-based therapeutics. He talks to Judy Ozkan about his experiences. were others who were very sceptical and remain sceptical. Literature searches will show that there are quite a few people devoted to working against the data, but my lab focus has always been on patients. It wasn’t just a co-incidence that my research laboratory was located adjacent to, or attached to a hospital in the days before term ‘translational medicine’ even existed. What we were doing was looking at patients conditions and saying ‘let’s try to figure something out in the lab that will help patients’. We would always start out with a proven concept study and a pre-clinical model and work backwards to the patient′ . Over the course of his career, he has been professor of medicine at Tufts University School of Medicine and chief of cardiovascular research at St Elizabeth’s Medical Centre in Boston. He is an adjunct professor of medicine at Northwestern University in Chicago, IL, USA. He views his career trajectory from academia to industry as a logical transition. ‘Although the process of conceiving ideas and then testing them in the lab is very rewarding in itself, I eventually came to feel like a spectator at drug development, as the ultimate goal is to turn your idea into a fully-approved therapy. It seemed to me there was a space for a scientific, clinical expert to help guide the final stage of drug development and see therapies approved and used in patients. Industry was the only place I felt able to achieve that goal. It was a natural extension of my ambitions and also gave me the opportunity of having a much wider impact on a larger number of patients by contributing to the development of new therapies. I have also broadened out my role into other areas aside from cardiology such as diabetes, asthma and renal therapy’. NeoStem, Inc., with its patient-based approach and emphasis on finding therapies for cardiovascular diseases fitted in with Losordo’s background. For him there was no compromise in the transition; his ultimate goal is to develop therapies to treat patients and the important point for a public company is to ‘do well by doing good’. He joined the company at a pivotal point in its development and in his first year has seen the company’s one ongoing novel programme now expanded to four. For the future, the team is looking at starting a heart programme potentially in Europe in the near future. Losordo foresees the ability of physicians to reverse chronic diseases within the next few years and points to the outcome of ongoing trials as being potential catalysts of the next paradigm shift that will see the definitive development of therapies targeting
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The son of a New York City police officer and a nurse, Losordo’s childhood ambition was to become a doctor. He studied biology and philosophy at the University of Vermont and then medicine in Boston at Tufts Medical School. He chose cardiology through a combination of instinct, ‘gravitational pull’, and the perception that it offered interesting opportunities for innovation. He developed acumen for research alongside his medical training in response to unanswered questions, but it was not until he crossed paths with gene therapy pioneer, the late Jeff Isner in the early 1980s that he was able to get involved in a careerdefining field of work. Following a lecture by Isner, Losordo was sufficiently intrigued to request an appointment to talk about possible collaboration. Isner cancelled two successive appointments at short notice and Losordo was forced to return a third time during which Isner accepted his proposal. Isner later revealed the cancelled appointments were a ruse to test prospective researchers’ enthusiasm. Although Isner went on to become famous for his pioneering work on gene therapy, when Losordo joined his lab, the use of lasers in cardiovascular medicine was the theme of the day. However, everything changed when Isner decided to focus on the emerging area of molecular biology and the lasers disappeared overnight. The team spent the next decade working on different approaches to gene therapy and ways to treat cardiovascular disease as well as running some of the first clinical trials of gene therapy to treat patients with advanced cardiovascular disease. In the mid-1990s one of Isner’s post-graduates discovered an adult progenitor cell with the capability of contributing to the repair of blood vessels. Losordo described this as a paradigm shift which prompted the team to switch their focus from gene therapy to cell therapy in the face of compelling evidence. ‘The reason it was compelling was that we were trying to figure out which was the right gene to over express. We picked out what we thought was a pre-programmed repair cell that would go into the target tissue orchestrating the process of tissue repair. We didn’t have to figure out how it would do this, because nature had already done that and we were just amplifying a natural method of tissue repair whereby you are collecting, concentrating and deploying cells to damaged tissues’. ‘This was controversial; there were people who accepted, embraced and began working on similar areas right away and there
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individual diseases. He is in no doubt that he is in the right place to apply his skills and knowledge. ‘I feel very lucky to have gone through this transition because we will have the real opportunity to leverage and expand our current knowledge. Medicine is going to be very exciting for the next few decades as we figure out more and more ways to leverage the natural biology of our bodies to do things to repair damage that exists’.
D.W.L. is a paid employee of NeoStem, Inc.
The Kyrgyz Society of Cardiologists and Structure of Cardiology Services in Kyrgyzstan
Figure 1 The causes of mortality in the population of the Kyrgyz Republic from Republican Medical Information Centre (RMIC), 2011.
1991. In 1991 the mortality index caused by CVD was 261 (9 deaths per 100 000 population); in 2011 this index was 326, a rise of 24%. Moreover, among the younger population (age 30 –39 years) this increase was even more dramatic: from 40.5% per 100 000 persons in 1991 to 58.6% per 100 000 persons in 2011.3 The dramatic increase in mortality after 1991 was connected with the disintegration of the USSR. The change in economic relations between Kyrgyzstan and the USSR resulted in a considerable reduction in health-care finances and a consequent deterioration of the quality of medical service. The health-care reform with its focus on family medicine and the loss of specialist medical staff led to a significant reduction in cardiologists and cardiological brigades for urgent cardiac care in the Republic. However, since 2006, with the implementation of programmes controlling CVD and increased financial resources for health care, the mortality from CVDs has been stabilized4,5 and, to some extent, there appears to be a trend of a reduction in deaths due to CVD in the Republic. At the same time, there still exist a number of unsolved problems. Among them is the shortage of qualified specialists in the field of cardiology. According to statistical data, there are 268 cardiologists in the Republic (0.5 per 100 000 population) most of whom work in the capital of Kyrgyzstan, while in some regions, there are ,1 cardiologist, only 0.1 –0.2, per 100 000 people. Cardiology specialists mainly work in hospitals providing secondary and tertiary care. This results
Figure 2 The aetiology of mortality in Kyrgyzstan, caused by cardiovascular disease.
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The establishment of the Kyrgyz Society of Cardiologists (KSC) was dictated by the unfavourable situation of cardiovascular diseases (CVDs) in the Republic. The main causes of mortality, morbidity, and disability in Kyrgyzstan are CVDs,1 occupying first place and accounting for half (50.1%) of all mortality cases in 2011(Figure 1). According to data issued by the Regional Bureau of WHO in 2010, Kyrgyzstan, in accordance with the standardized mortality rate, occupies the first place in the Eurasian region for stroke, at 198.8 cases per 100 000 people, and its mortality rate from CHD places it in fourth position, after the Ukraine, Russia, and Moldova. The main causes (.90%) of death from CVDs in the population are coronary heart disease, cerebrovascular disease, and hypertension (Figure 2). The majority of people who die from these three causes (77.0%) are able-bodied persons. According to the statistical data of 2011, the primary cause of disability among adults is CVD, which at 19.6% is considerably higher than the disability caused by any other single disease.2 Such an unfavourable situation of mortality due to CVD is partly connected with the high prevalence of CVD risk factors, mainly arterial hypertension, hypercholesterolaemia, hyperglycaemia, low physical activity, overweight, and obesity. Analysis of mortality due to CVD shows a progressive increase compared with the data of
2854 in the primary health care of patients with cardiovascular pathology being provided by family doctors. Therefore, the main priorities of the KSC together with the Ministry of Health, National Centre of Cardiology and Internal Diseases, are the development and coordination of programmes for the control of CVD and improving the qualifications and knowledge of medical personnel in CVDs and related fields. There is also active work conducted among the population of the Republic promoting a healthy lifestyle and improving the level of education for primary and secondary prevention of CVD.
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References 1. Ministry of Public Health and the Republican Medical Information Centre (RMIC). Health of population and the activity of the institutions of healthcare of the Kyrgyz Republic in 2011/ Collection (of articles) Bishkek, 2012,356. 2. The statement of the government of the Kyrgyz Republic. On the strategy of development of healthcare in the Kyrgyz Republic up to 2020. 42. 3. Kadyralieva RB, Dzumagulova AC. The state and perspectives of development of cardiological service in Kyrgyzstan. Arch Intern Med 2013;28–34 (a special issue). 4. www.hpac.kg (no. 44,45). 5. The Ministry of Healthcare. Report Valuation of the realization of the National program of the reform of healthcare of the Kyrgyz Republic ‘Manas taalimi’, Bishkek, 2011, p. 127
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CardioPulse contact: Andros Tofield, Managing Editor. Email: [email protected]
The 2014 ESC Guidelines on the Diagnosis and Management of Hypertrophic Cardiomyopathy have been published Chairman of the European Society of Cardiology Taskforce Prof. Perry Elliott, MD, FRCP, FESC, University College London and Lead for Inherited Cardiovascular Disease services, The Heart Hospital, UCLH, summarizes the changes and updates 1. Recognition of the diverse range of conditions that can cause HCM For the first time, we provide guidance on a clinically focused approach to the diagnosis of genetic and acquired causes of HCM. This is based on careful history-taking including analysis of family pedigrees and a cardiomyopathy-centred interpretation of commonly used diagnostic tools, such as electrocardiography and cardiac imaging. 2. Genetic testing We provide a clinically focused approach to the request for and interpretation of genetic tests. The role of expert counselling before and after genetic analysis is strongly emphasized and we provide clear guidance on the management of family members in different clinical scenarios based on the results of genetic testing. Most importantly, we advise consideration of genetic testing whenever it has implications for the screening of relatives. 3. Management of left ventricular outflow tract obstruction This is a common feature of HCM that can be treated with drugs or invasive therapies such as surgery and alcohol septal ablation. For the first time, we present a systematic approach to the assessment of left ventricular outflow tract obstruction that can be used to tailor therapies to the characteristics of individual patients. 4. Prevention of sudden cardiac death While the risk of sudden death is low for most patients with HCM, a small number are prone to life-threatening ventricular arrhythmias. One of the most important innovations in this guideline is the promotion of a new risk calculator (HCMRisk-SCD) that uses simple clinical measures to estimate the 5-year risk of sudden cardiac death. This estimate is then used to stratify patients into high-, intermediate-, and low-risk categories that can be used to guide the use of ICDs. These recommendations for sudden death prevention are likely to spark considerable interest and debate as they provide advice based on real estimates of risk rather than relative risks as in all previous guidelines. This will bring into focus the balance between clinical efficacy on the one hand and the potential risks and costs of therapy to individual patients and health-care economies on the other. 5. Management of heart failure Treatment of heart failure in patients with HCM is challenging and, unlike other diseases that cause heart failure, is unsupported by
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected].
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on March 23, 2016
New Guidelines on the Diagnosis and Management of Hypertrophic Cardiomyopathy have been heralded as a significant step forwards in helping health-care professionals raise the standard of care for patients with the condition. Produced by the European Society of Cardiology taskforce on the diagnosis and management of hypertrophic cardiomyopathy (HCM), the emphasis is on improving diagnostic accuracy and delivering a more patient-centred approach to clinical management of HCM. The last ESC Guideline on HCM was published in 2003 as a joint consensus document with the American College of Cardiology [European Heart Journal (2003) 24, 1965–1991]. Chairman of the ESC taskforce, Prof. Perry Elliott points out that HCM is a relatively common disease that affects 1 in 500 of the population. It also affects people of all ages and is an important cause of premature death and morbidity. ‘Remarkably for such a common disease’, he said. ‘There have been very few randomized trials of therapy in people with HCM since that time, but a large body of basic and observational clinical studies has increased knowledge on the aetiology of the disease as well as its natural history’. ‘In this new version of the guideline, these data have informed a major change in the approach to the diagnosis of HCM that involves a deliberate search for specific genetic and non-genetic forms of the disease. In addition, there is greater emphasis on a systematic approach to defining the mechanisms of symptoms in order to target therapies more effectively’. ‘Two important innovations are, the adoption of an individualized approach to the estimation of sudden death risk that can be used to guide implantable cardioverter defibrillator (ICD) therapy and the provision of detailed advice to women with HCM on reproductive and pregnancy related issues’. The 2014 guidelines balance an ideal of best practice with the realities of health care provision. Prof. Elliott acknowledges that the recommendations will prove challenging in some countries, in particular the advice to consider early referral to multidisciplinary teams with expertise in the diagnosis and management of HCM, but the aim is to raise the general standard of care for all patients wherever they live. Prof. Elliott outlined the key changes and updates as follows:
2850 randomized clinical trials. Nevertheless, we provide a simple guide to physicians that can be used to tailor drug and device therapy. 6. Pregnancy and contraception We provide detailed and tailored advice to the assessment and management of women with HCM. Specifically, we provide guidance on pre-pregnancy assessment, the management of labour and detailed recommendations for contraception, sterilization, and termination. 7. Management of children For the first time, we provide advice on children in key sections on diagnosis and treatment. 8. Advice to patients Also included for the first time is the provision of guidance on practical everyday issues that affect the lives of patients with HCM
CardioPulse
and can be used by any health-care professional or patient support organization. Prof. Elliott concludes: ‘It is our collective hope that these guidelines will raise the standard of care for patients of all ages by improving the accuracy of diagnosis and through the use of a rationale, patientcentred approach to clinical management’. ‘Obvious gaps in evidence remain, but we believe that the guidelines provide a framework for future research and innovations in patient care’.
(1) Clinicians should consider referral of patients to multidisciplinary teams with expertise in the diagnosis, genetics, risk stratification, and management of heart muscle disease. (2) A clinically focused approach to the diagnosis of genetic and acquired causes of HCM based on careful history including analysis of family pedigrees and a cardiomyopathy-centred interpretation of commonly used diagnostic tools such as electrocardiography and cardiac imaging should be adopted. (3) Genetic counselling is recommended in all patients with unequivocal HCM when it cannot be explained solely by a non-genetic cause. (4) When a definite causative genetic mutation is identified in a patient, his or her first-degree relatives should first be genetically tested, and then clinically evaluated if they are found to carry the same mutation. (5) Exercise stress echocardiography is recommended in symptomatic patients with an LVOT gradient ,50 mmHg at rest. (6) When a gradient is detected in the left ventricular cavity, obstruction caused by subaortic membranes, structural mitral valve leaflet abnormalities, and mid-cavity obstruction should be systematically excluded. (7) Use of a new risk calculator (HCMRisk-SCD) is recommended to guide the use of implantable cardioverter defibrillators. (8) Patients with HCM and paroxysmal, persistent, or permanent atrial fibrillation should receive treatment with vitamin K antagonists and life-long therapy with oral anticoagulants is recommended, even when sinus rhythm is restored. (9) Patients in sinus rhythm with left atrial diameter ≥45 mm should undergo 6 –12 monthly 48-h ambulatory ECG monitoring to detect AF. (10) Most women with HCM tolerate pregnancy well but require expert advice before conception and throughout pregnancy.
EuroPCR 2014, Hypertension and Heart Failure Track take-home messages This year’s EuroPCR 2014 Hypertension and Heart Failure Track in Paris included presentation of live cases and discussion of new data, how-to and hotline sessions, as well as scientific poster and oral abstract sessions. Furthermore, dedicated sessions for practical training with hands-on anatomical models using different renal denervation systems have been very well attended. Altogether, .60 sessions discussed the topic around and about renal denervation. The ‘Interventions for Hypertension and Heart Failure Track′ started with an overview and update session entitled ‘All You
Need to Know About Renal Denervation’. The objectives of that session were to obtain a comprehensive update, to identify the current evidence base and existing guidelines, and to recognize the open questions that need to be addressed in the near future. The take-home messages stressed by the chairman Roland Schmieder (Germany) were ‘The sympathetic nervous system is more complex than we might have initially thought, and adequate patient selection and experienced operators are crucial to obtaining
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on March 23, 2016
The ‘Ten Commandments’ of the ESC Hypertrophic Cardiomyopathy Guidelines
CardioPulse
variability’. It was reported that in the vast majority of patients in Symplicity HTN-3 (up to 70%) radiofrequency ablations were performed in a non-circumferential manner, which contradicts current clinical treatment recommendations. Interestingly, the delivery of ablations in four quadrants of the renal artery was consistently associated with more pronounced reductions in office, home, and ambulatory blood pressure. Furthermore, increasing reductions in systolic BP were associated with increasing numbers of ablations and complete four-quadrant ablation (Kandzari D, EuroPCR 2014). Thereafter, the Hypertension and Heart Failure Track continued in the main arena with a live demonstration of renal denervation in a patient with resistant hypertension as part of the EnlighHTN study from the Institut Cardiovasculaire Paris Sud Massy performed by Hakim Benamer and his team. Finally, the participants were introduced to device-based approaches targeting ventricular reshaping and cavity reduction. At the same time the therapeutic potential of sympatho-modulation in affecting end-organ damage and cardiovascular comorbidities was highlighted in a session entitled: ‘Catheter-based renal denervation - Treating across the cardiovascular continuum’, where some of the current 30 studies investigating the potential role of renal denervation in patients with metabolic syndrome, atrial fibrillation, and chronic heart failure were discussed. In summary, the sessions about and around Hypertension and Heart Failure were very well attended and the interest in renal denervation is still huge. This year’s EuroPCR was the first international meeting after the publication of Symplicity HTN-3 and provided a forum to discuss all the available data with the right critical spirit. The programme was focused on the science of renal denervation and what the next steps are, and illuminated the need for new and refined technologies to help monitor successful ablation of renal sympathetic nerve fibres intra-procedurally and to help identify patients with sympathetic overactivity. One thing was very clear at the end of the meeting: research efforts in that area of interventional medicine would and should continue. S.E. and F.M. are supported by Deutsche Hochdruckliga and Deutsche Gesellschaft fu¨r Kardiologie. F.M. has received research grants, speaker honorarium, and/or consultancy fees from Medtronic/Ardian, St Jude Medical, Cordis, and Recor.
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good results’. At the end of the day, data from the Symplicity HTN-3 trial and the Global Symplicity Registry were discussed. After an introduction and overview of resistant hypertension by Michael Bo¨hm (Germany), Manesh Patel (USA), one of the US investigators of Symplicity HTN-3, explained the results of the study and provided some subgroup analyses. Even though no subgroup met the statistical significance for treatment interaction, a seemingly greater blood pressure effect could be detected in non-African Americans. The outcome of Symplicity HTN-3 was contrary to the results of the previously published Symplicity HTN-1 and HTN-2 studies, which led to a very interactive discussion about potential reasons for the differences. In the multivariate analyses of predictors of response to renal denervation, only office systolic blood pressure ≥180 mmHg reached statistical significance. The second day of the track started in a room specifically designed to stimulate interaction between facilitators and participants, where different CE-marked devices for renal denervation have been discussed with the support of different educational tools, such as, Live-in-a-Boxw cases. This session aimed to exchange experiences derived from daily practice, addressed specific technical features that interventionists need to know in order to correctly use the various devices, and critically discussed the available clinical data. Parallel to this the participants had the opportunity to follow a session about revascularization in patients with ischaemic heart failure. These sessions were followed by an update on the results of the REDUCE-HTN, EnligHTN, ACHIEVE, REALISE, RAPID, and SYMPLICITY Spyral studies. The programme continued with two cardiovascular innovation pipeline sessions dedicated to new techniques for modulation of the sympathetic nervous system. One session discussed new approaches to target sympathetic nerve fibres in the kidney and other target structures. Another very interesting session focused on pre-clinical findings of different renal denervation techniques and catheter systems and these pre-clinical data were put into a clinical perspective. Renu Virmani concluded the session with a review of histopathological images of pig renal artery treated with the different renal denervation systems. The third day started with a comprehensive ‘State-of-the-Art’ lecture about percutaneous mitral valve repair with Mitraclip in heart failure [Chairmen: Jozef Bartunek (Belgium) and Olaf Franzen (Germany]. The Mitraclip procedure itself was a lively discussion with the use of a Live-in-a-Boxw case. A parallel hot-line session on resistant hypertension presented new data of the EnligHTN trial by Stephen Worthley (Australia), Global Symplicity Registry by Felix Mahfoud (Germany), Symplicity HTN-3 by David Kandzari (USA), ACHIEVE by Jost Daemen (The Netherlands), and REDUCE-HTN by Joachim Schofer (USA). David Kandzari concluded his presentation by stating that ‘prespecified and post-hoc analyses of Symplicity HTN-3 have identified potentially confounding factors, including antihypertensive medication use changes, differences in study populations and procedural
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Tales from another career: Douglas W. Losordo MD American cardiologist Douglas W. Losordo, MD, FACC, FAHA recently took up the post of chief medical officer with NeoStem, Inc., a company engaged in the development of cell-based therapeutics. He talks to Judy Ozkan about his experiences. were others who were very sceptical and remain sceptical. Literature searches will show that there are quite a few people devoted to working against the data, but my lab focus has always been on patients. It wasn’t just a co-incidence that my research laboratory was located adjacent to, or attached to a hospital in the days before term ‘translational medicine’ even existed. What we were doing was looking at patients conditions and saying ‘let’s try to figure something out in the lab that will help patients’. We would always start out with a proven concept study and a pre-clinical model and work backwards to the patient′ . Over the course of his career, he has been professor of medicine at Tufts University School of Medicine and chief of cardiovascular research at St Elizabeth’s Medical Centre in Boston. He is an adjunct professor of medicine at Northwestern University in Chicago, IL, USA. He views his career trajectory from academia to industry as a logical transition. ‘Although the process of conceiving ideas and then testing them in the lab is very rewarding in itself, I eventually came to feel like a spectator at drug development, as the ultimate goal is to turn your idea into a fully-approved therapy. It seemed to me there was a space for a scientific, clinical expert to help guide the final stage of drug development and see therapies approved and used in patients. Industry was the only place I felt able to achieve that goal. It was a natural extension of my ambitions and also gave me the opportunity of having a much wider impact on a larger number of patients by contributing to the development of new therapies. I have also broadened out my role into other areas aside from cardiology such as diabetes, asthma and renal therapy’. NeoStem, Inc., with its patient-based approach and emphasis on finding therapies for cardiovascular diseases fitted in with Losordo’s background. For him there was no compromise in the transition; his ultimate goal is to develop therapies to treat patients and the important point for a public company is to ‘do well by doing good’. He joined the company at a pivotal point in its development and in his first year has seen the company’s one ongoing novel programme now expanded to four. For the future, the team is looking at starting a heart programme potentially in Europe in the near future. Losordo foresees the ability of physicians to reverse chronic diseases within the next few years and points to the outcome of ongoing trials as being potential catalysts of the next paradigm shift that will see the definitive development of therapies targeting
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The son of a New York City police officer and a nurse, Losordo’s childhood ambition was to become a doctor. He studied biology and philosophy at the University of Vermont and then medicine in Boston at Tufts Medical School. He chose cardiology through a combination of instinct, ‘gravitational pull’, and the perception that it offered interesting opportunities for innovation. He developed acumen for research alongside his medical training in response to unanswered questions, but it was not until he crossed paths with gene therapy pioneer, the late Jeff Isner in the early 1980s that he was able to get involved in a careerdefining field of work. Following a lecture by Isner, Losordo was sufficiently intrigued to request an appointment to talk about possible collaboration. Isner cancelled two successive appointments at short notice and Losordo was forced to return a third time during which Isner accepted his proposal. Isner later revealed the cancelled appointments were a ruse to test prospective researchers’ enthusiasm. Although Isner went on to become famous for his pioneering work on gene therapy, when Losordo joined his lab, the use of lasers in cardiovascular medicine was the theme of the day. However, everything changed when Isner decided to focus on the emerging area of molecular biology and the lasers disappeared overnight. The team spent the next decade working on different approaches to gene therapy and ways to treat cardiovascular disease as well as running some of the first clinical trials of gene therapy to treat patients with advanced cardiovascular disease. In the mid-1990s one of Isner’s post-graduates discovered an adult progenitor cell with the capability of contributing to the repair of blood vessels. Losordo described this as a paradigm shift which prompted the team to switch their focus from gene therapy to cell therapy in the face of compelling evidence. ‘The reason it was compelling was that we were trying to figure out which was the right gene to over express. We picked out what we thought was a pre-programmed repair cell that would go into the target tissue orchestrating the process of tissue repair. We didn’t have to figure out how it would do this, because nature had already done that and we were just amplifying a natural method of tissue repair whereby you are collecting, concentrating and deploying cells to damaged tissues’. ‘This was controversial; there were people who accepted, embraced and began working on similar areas right away and there
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individual diseases. He is in no doubt that he is in the right place to apply his skills and knowledge. ‘I feel very lucky to have gone through this transition because we will have the real opportunity to leverage and expand our current knowledge. Medicine is going to be very exciting for the next few decades as we figure out more and more ways to leverage the natural biology of our bodies to do things to repair damage that exists’.
D.W.L. is a paid employee of NeoStem, Inc.
The Kyrgyz Society of Cardiologists and Structure of Cardiology Services in Kyrgyzstan
Figure 1 The causes of mortality in the population of the Kyrgyz Republic from Republican Medical Information Centre (RMIC), 2011.
1991. In 1991 the mortality index caused by CVD was 261 (9 deaths per 100 000 population); in 2011 this index was 326, a rise of 24%. Moreover, among the younger population (age 30 –39 years) this increase was even more dramatic: from 40.5% per 100 000 persons in 1991 to 58.6% per 100 000 persons in 2011.3 The dramatic increase in mortality after 1991 was connected with the disintegration of the USSR. The change in economic relations between Kyrgyzstan and the USSR resulted in a considerable reduction in health-care finances and a consequent deterioration of the quality of medical service. The health-care reform with its focus on family medicine and the loss of specialist medical staff led to a significant reduction in cardiologists and cardiological brigades for urgent cardiac care in the Republic. However, since 2006, with the implementation of programmes controlling CVD and increased financial resources for health care, the mortality from CVDs has been stabilized4,5 and, to some extent, there appears to be a trend of a reduction in deaths due to CVD in the Republic. At the same time, there still exist a number of unsolved problems. Among them is the shortage of qualified specialists in the field of cardiology. According to statistical data, there are 268 cardiologists in the Republic (0.5 per 100 000 population) most of whom work in the capital of Kyrgyzstan, while in some regions, there are ,1 cardiologist, only 0.1 –0.2, per 100 000 people. Cardiology specialists mainly work in hospitals providing secondary and tertiary care. This results
Figure 2 The aetiology of mortality in Kyrgyzstan, caused by cardiovascular disease.
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The establishment of the Kyrgyz Society of Cardiologists (KSC) was dictated by the unfavourable situation of cardiovascular diseases (CVDs) in the Republic. The main causes of mortality, morbidity, and disability in Kyrgyzstan are CVDs,1 occupying first place and accounting for half (50.1%) of all mortality cases in 2011(Figure 1). According to data issued by the Regional Bureau of WHO in 2010, Kyrgyzstan, in accordance with the standardized mortality rate, occupies the first place in the Eurasian region for stroke, at 198.8 cases per 100 000 people, and its mortality rate from CHD places it in fourth position, after the Ukraine, Russia, and Moldova. The main causes (.90%) of death from CVDs in the population are coronary heart disease, cerebrovascular disease, and hypertension (Figure 2). The majority of people who die from these three causes (77.0%) are able-bodied persons. According to the statistical data of 2011, the primary cause of disability among adults is CVD, which at 19.6% is considerably higher than the disability caused by any other single disease.2 Such an unfavourable situation of mortality due to CVD is partly connected with the high prevalence of CVD risk factors, mainly arterial hypertension, hypercholesterolaemia, hyperglycaemia, low physical activity, overweight, and obesity. Analysis of mortality due to CVD shows a progressive increase compared with the data of
2854 in the primary health care of patients with cardiovascular pathology being provided by family doctors. Therefore, the main priorities of the KSC together with the Ministry of Health, National Centre of Cardiology and Internal Diseases, are the development and coordination of programmes for the control of CVD and improving the qualifications and knowledge of medical personnel in CVDs and related fields. There is also active work conducted among the population of the Republic promoting a healthy lifestyle and improving the level of education for primary and secondary prevention of CVD.
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References 1. Ministry of Public Health and the Republican Medical Information Centre (RMIC). Health of population and the activity of the institutions of healthcare of the Kyrgyz Republic in 2011/ Collection (of articles) Bishkek, 2012,356. 2. The statement of the government of the Kyrgyz Republic. On the strategy of development of healthcare in the Kyrgyz Republic up to 2020. 42. 3. Kadyralieva RB, Dzumagulova AC. The state and perspectives of development of cardiological service in Kyrgyzstan. Arch Intern Med 2013;28–34 (a special issue). 4. www.hpac.kg (no. 44,45). 5. The Ministry of Healthcare. Report Valuation of the realization of the National program of the reform of healthcare of the Kyrgyz Republic ‘Manas taalimi’, Bishkek, 2011, p. 127
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CardioPulse contact: Andros Tofield, Managing Editor. Email: [email protected]
