European Heart Journal (2014) 35, 2781–2788 doi:10.1093/eurheartj/ehu349
The 2014 European Society of Cardiology/ European Society of Anaesthesiology Guidelines on non-cardiac surgery: cardiovascular assessment and management have been published
Juhani Knuuti (photo Roni Lehti)
Steen Dalby Kristensen (photo Sam Rogers)
New guidelines on non-cardiac surgery: cardiovascular assessment and management have been produced by the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). The work by the Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the ESC and ESA forms a completely updated version of the guideline. The basic structure of the 2009 version has been retained because it was considered ‘excellent and very well liked with comprehensive summary of all major recommendations and stepwise approach at the end of the document’. However, there are also a number of important differences that have been introduced. In the latest document, the authors point out that the present Guidelines (GL) focus on the cardiovascular management of patients in whom heart disease is a potential source of complications during non-cardiac surgery. The risk of peri-operative complications depends on the condition of the patient before surgery, the
prevalence of comorbidities, and the urgency, magnitude, type, and duration of the surgical procedure. More specifically, cardiac complications can arise due to documented or asymptomatic ischaemic heart disease (IHD), left ventricular (LV) dysfunction, valvular heart disease (VHD), and arrhythmias, in patients who undergo surgical procedures that are associated with prolonged haemodynamic and cardiac stress. While seeking to address the magnitude of the problem in Europe, the Joint Task Force discovered that systematic data on the annual number and type of operations—and on patient outcomes—are only available at a national level in 23 European countries (41%), and in addition data definitions vary, as do data quantity and quality. In Europe, it is estimated that there are 19 million major procedures annually and while the majority of these procedures are performed in patients with minimal cardiovascular risk, 30% of patients undergo extensive surgical procedures in the presence of cardiovascular comorbidity; hence, 5.7 million procedures annually are performed in European patients who present with an increased risk of cardiovascular complications. Worldwide, non-cardiac surgery is associated with an average overall complication rate of 7 –11% and a mortality rate of 0.8 – 1.5%, depending on safety precautions. When applied to the population in the European Union member states, these figures translate into at least 167 000 cardiac complications annually due to non-cardiac surgical procedures, of which 19 000 are life-threatening. With this data in mind, the 2014 document has been updated with the following main differences:
(1) The GL recommends that a multi-disciplinary expert team should be considered for pre-operative evaluation of patients with a known or high risk of cardiac disease, who are undergoing high-risk non-cardiac surgery. (2) The surgical risk assessment, which depends on the planned procedure, has been completely updated. Furthermore, when alternative methods to the classical open surgery are considered, either through endovascular or less-invasive endoscopic procedures, the potential trade-offs between early benefits due to reduced morbidity and mid-long-term efficacy need to be taken into account. Accordingly, the GL recommends that patients should undergo pre-operative risk assessment independent of whether the surgery is by laparoscopy, or by an open surgical approach. 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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Co-chairs, Prof. Steen Dalby Kristensen and Juhani Knuuti, summarize the changes and updates with CardioPulse writer Mark Nicholls
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These Guidelines—intended for physicians and collaborators involved in the pre-operative, operative, and post-operative care of patients undergoing non-cardiac surgery—also identify important areas where there are gaps in knowledge and suggest, for example, that randomized clinical trials on beta-blockers and drugs such as statins are highly needed. The changing demographics across Europe within the next 20 years are also acknowledged with an ageing population having a major impact on peri-operative patient management. It is estimated
that elderly people require surgery four times as often as the rest of the population. The Joint Task Force states that the updated Guidelines have the potential to improve post-operative outcomes and highlight the existence of a clear opportunity for improving the quality of care in this high-risk group of patients. In addition to promoting an improvement in immediate peri-operative care, the guidelines will provide longterm advice. Mark Nicholls, [email protected]
How the new European Society of Cardiology/ European Society of Anaesthesiology Guidelines on non-cardiac surgery: cardiovascular assessment and management, are produced The two task force chairpersons present the process of bringing the Guidelines to completion During the last 16 months a Task Force established by the Guideline Committees of European Society of Cardiology (ESC) and European Society of Anaesthesiology (ESA) has been working on a new Guideline document on cardiovascular assessment and management of patients undergoing non-cardiac surgery.
The clinical scenario is common and the optimal management strategy for these patients is discussed by cardiologists, anaesthesiologists, surgeons, other doctors, and health personnel in our daily practice. The field is wide and complex and is evolving with many new developments. The ESC Board decided in December 2012 to
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(3) The patient risk assessment now includes not only the Lee score but also other validated risk scores such as NSQIP. The new version also has recommendations about the role of biomarkers (BNP and Troponins) for risk assessment. (4) The risk reduction section has also been completely updated. Most of the changes occurred in the beta-blocker section in which the main change is that pre-operative initiation of beta-blockers is not recommended in all patients but may be considered in patients scheduled for high-risk surgery and who have clinical risk factors, or who have known ischaemic heart disease or myocardial ischaemia. When initiated, the dose should be titrated. If the patient is already on beta-blocker therapy before surgery, its continuation is recommended. (5) The recommendation for the use of aspirin and P2Y12 inhibitors in patients undergoing non-cardiac surgery is updated. (6) With the availability of new oral anticoagulants, the guidelines now include recommendations on managing how patients undergoing non-cardiac surgery are treated with these drugs. (7) The recommendations on the timing of non-cardiac surgery in cardiac-stable/asymptomatic patients with previous revascularization are also updated by taking into account the new information about the safety margins after various revascularization procedures. As in theprevious GL, routine prophylactic myocardial revascularization before low- and intermediate-risk surgery in patients with proven IHD is not recommended but may be considered before high-risk surgery, depending on the extent of a stress-induced ischaemia. (8) The whole specific disease section has been completely updated and several new sections have been added. The section now covers numerous conditions that will have influence on the pre-operative evaluation such as chronic heart failure, arterial hypertension, VHD, arrhythmias, renal disease, carotid disease, peripheral artery disease, pulmonary artery hypertension, and pulmonary disease as well as congenital heart disease. (9) The peri-operative monitoring section has also been updated and expanded with the anaesthesia experts from ESA. The part now includes sections about intra-operative anaesthetic management, neuraxial techniques, peri-operative goal-directed therapy, risk stratification after surgery, early diagnosis of post-operative complications and post-operative pain management as well as specific recommendations about anaesthesia. (10) Naturally, these numerous changes have also resulted in major revisions of the summary table and the stepwise guidance sections at the end of the document. However, with these sections considered very useful for users, these revisions have been successfully managed. The stepwise approach, as well as one large table summarizing most of the recommendations, is included in the guideline document as well as in the pocket guideline.
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write a new Guideline on peri-operative care and established together with the ESA a new task force of experts co-chaired by Prof. Steen D. Kristensen, Aarhus, Denmark and Prof. Juhani Knuuti, Turku, Finland
Steen Dalby Kristensen (photo Sam Rogers)
Juhani Knuuti (photo Roni Lehti)
† How do we optimally evaluate pre- and peri-operative risk and what kind of impact it may have on patients undergoing noncardiac surgery? † New generation drug-eluting stents: should non-cardiac surgery be postponed and if so, for how long? † New and old anti-thrombotic drugs: what should we do if noncardiac surgery is needed? † When should we perform pre-operative revascularization? † How do we handle patients with valve disease, arrhythmia, heart failure, and other cardiac diseases? † What are the implications of co-morbidities such as diabetes, renal failure, and lung disease?
What is the optimal peri-operative medical treatment with, e.g. beta-blockers, statins, and ACE inhibitors/ARBs? The use of peri-operative beta-blocker treatment is complex and has received a lot of attention. As described in detail in a recent editorial by the editor-in-chief of the European Heart Journal (see this issue)1, the validity of some of the key publications in this field has been questioned and burning issues on dosing, type of compound and, in particular, which subgroups of patients will benefit are difficult to answer. Recent registry data show overall benefit of beta-blockers in some patients2,3 but to properly address the use of beta-blockers, conduction of new randomized studies are needed. Some colleagues and journalists have criticized the ESC and other leading scientific bodies for being too slow to react and change the Guidelines. However, as explained below, writing Guidelines is a lengthy
(Jose´ L. Zamorano) Once the development of an ESC Guideline is approved, the Committee for Practice Guidelines, chaired by Professor Jose´ L Zamorano from Madrid, prepares a list of potential writers to constitute the Task Force in charge of writing the guideline. From among the Task Force members, one or two Task Force chairpersons are chosen. The list of potential members of the Task Force is prepared in collaboration with ESC constituent bodies concerned, by the topic to be written. Eventually 15 – 25 experts are nominated for each Guideline Task Force, which is under the coordination of the chairpersons. The Task Force is primarily responsible for the scientific content of the Guideline. Once they have produced a final draft document, it will be reviewed by the Committee for Practice Guidelines members and external reviewers appointed by the Committee for Practice Guidelines in view of their knowledge in the field being discussed. Two Committee for Practice Guidelines members coordinate the review process. Comments from all reviewers are sent back to the Task Force chairpersons who have to address each and every one of them—it is not unusual that the number of comments exceeds one thousand. The revised version as well as the answers to all comments are sent back to the Committee for Practice Guidelines and the review process starts again until a final version is produced, usually after two to three review rounds. For the new ESC Guidelines on non-cardiac surgery .115 experts have been involved including 24 Task Force members, 26 members of the Committee for Practice Guidelines, 36 National Cardiac Society reviewers, 24 expert peer reviewers, and a number of ESC and ESA Board members. The document has been presented at the ESC
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The Guideline will cover the whole field from surgical risk assessment, pre-operative evaluation, and optimal perioperative management and also address relevant cardiology and anaesthesia issues in patients with specific cardiac diseases and common co-morbidities scheduled to undergo non-cardiac surgery. The goal is to provide optimal guidance in the clinical decision-making for patients undergoing non-cardiac surgery. Key areas with new recommendations based on scientific developments are as follows:
process and includes the comprehensive study of literature and evidence, as well as a multi-step review process, all of which are critical to the quality of the guidelines. Meanwhile, the ESC,AHA, and ACC decided in August 2013 to issue a common statement regarding temporary recommendations on the use of beta-blockers: ‘In the interim, our current joint position is that the initiation of beta blockers in patients who will undergo noncardiac surgery should not be considered routine, but should be considered carefully by each patient’s treating physician on a case-by-case basis’. http://www.escardio.org/about/press/press-releases/pr-13/ Pages/joint-statement-perioperative-guidelines.aspx. In that statement as well as earlier (March 2013) the ESC indicated that a new Guideline on non-cardiac surgery was in preparation. Our American colleagues from AHA/ACC are also in the process of writing a new Guideline on this topic. Guideline documents require meticulous preparation and their publication cannot be achieved in a rush for many reasons, the foremost being the safety of our patients.
2784 Annual Congress in Barcelona on 2 September this year and made available online in the European Heart Journal. The numerous comments from the reviewers have improved the quality of the document considerably. We would like to stress that although the beta-blocker section is important, numerically it only accounts for quite a small section in the whole document. Steen Kristensen MD DMSc, [email protected] Juhani Knuuti MD, [email protected]
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References 1. Lu¨scher TF, Gersh B, Landmesser Ulf, Ruschitzka F. Is the panic about beta-blockers in perioperative care justified? Eur Heart J 2014;35:2442 –2444. 2. London MJ, Hur K, Schwartz GG, Henderson WG. Association of perioperative beta blockade with mortality and cardiovascular morbidity following major noncardiac surgery. J Amer Med Ass 2013;16:1704 – 1713. 3. Andersson C, Merie C, Jorgensen M, Gislason GH, Torp-Pedersen C, Overgaard C, Kober L, Jensen PF, Hlatky MA. Association of b-blocker therapy with risks of adverse cardiovascular events and deaths in patients with ischemic heart disease undergoing noncardiac surgery a Danish nationwide cohort study. JAMA Intern Med 2014;174: 336 –344.
The ‘Ten Commandments’ of Noncardiac Surgery 2014 ESC/ESA Guidelines
(7)
(8)
(9)
(10)
information on safety margins after various revascularization procedures. As in previous GL, routine prophylactic myocardial revascularization before low- and intermediate-risk surgery in patients with proven IHD is not recommended but may be considered before high-risk surgery, depending on the extent of a stress-induced ischaemia. The entire section on specific diseases has been completely updated and several new sections have been added. The section now covers numerous conditions that will influence preoperative evaluation, i.e. chronic heart failure, arterial hypertension, valvular heart disease, arrhythmias, renal disease, carotid disease, peripheral artery disease, pulmonary artery hypertension, and pulmonary disease as well as congenital heart disease. The perioperative monitoring section has also been updated and expanded by the anaesthesia experts from European Society of Anaesthesiology. This section now includes parts on intra-operative anaesthetic management, neuraxial techniques, peri-operative goal-directed therapy, risk stratification after surgery, early diagnosis of post-operative complications, and post-operative pain management, as well as specific recommendations about the anaesthesia. Naturally, these numerous changes also led to major revisions of the summary table and step-by-step guidance sections at the end of the document. However, this section was considered very useful for users and these revisions were successfully managed. The recommendations for the step-by-step approach as well as one comprehensive table summarizing most of the recommendations are included in the guideline document as well is in the pocket guideline. Randomized clinical trials on the peri-operative use of bblockers and other drugs are highly needed. Steen D Kristensen MD, [email protected] Juhani Knuuti MD, [email protected]
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(1) A multidisciplinary expert team should be consulted for preoperative evaluation of patients with known or high risk of cardiac disease undergoing high-risk non-cardiac surgery. (2) The surgical risk assessment, which depends on the planned procedure, has been completely updated. Further, when alternative methods to the classical open surgery are considered, either through endovascular or less invasive endoscopic procedures, the potential trade-offs between early benefits due to reduced morbidity and mid-long-term efficacy must be considered. Accordingly, the Guidelines (GL) recommend that patients should undergo preoperative risk assessment independently of an open or laparoscopic surgical approach. (3) The patient risk assessment now includes not only the Lee score but also other validated risk scores such as NSQIP. The new version also has recommendations about the role of biomarkers (BNP and Troponins) for risk assessment. (4) The risk reduction section has also been completely updated. The key change is that preoperative initiation of b-blockers is not recommended in all patients but may be considered in patients scheduled for high-risk surgery and who have clinical risk factors, or, who have known ischaemic heart disease or myocardial ischaemia. When initiated, the dose should be titrated. If the patient has already had b-blocker therapy before surgery, continuation is recommended. (5) The recommendation for the use of aspirin and P2Y12 inhibitors for patients undergoing non-cardiac surgery has been updated. New oral anticoagulants are now available and recommendations on how to manage patients treated with these drugs undergoing non-cardiac surgery is described in a new section. (6) The recommendations for the timing of non-cardiac surgery in cardiac-stable/asymptomatic patients with previous revascularization has also been updated by considering new
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From evidence-based medicine to personalized medicine News from EuroPCR 2014 Results of the CENTURY II randomized, prospective trial (1123 patients) showed that the Ultimaster drug-eluting stent (Terumo) with a bioresorbable polymer was as safe and effective as the Xience stent (Abbott Vascular) with a permanent polymer. Finally, The SAPIEN 3 trial met its primary end-point of all-cause mortality of the valve-implant population at 30 days post-index procedure, generating promising results for this new generation of TAVI valves. More practical sessions also provided much interactivity with, for example, the learning sessions focusing on specific technical points during 90 min and the radial track that generated a lot of interest, but also with the young interventionist’s tracks that focused on ‘the essentials’ of different key interventional techniques. This year the peripheral programme was based on a new programme specifically oriented to the emerging needs of the interventional cardiology community. Finally, this year, the Ethica Award was presented to Adnan Kastrati. His work sums up the spirit of the course as he has succeeded, according to his peers, in obtaining a perfect synthesis between technical work in the cath lab and research with an emphasis on team work, demonstrated by the fact that he dedicated his award to his team.
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EuroPCR, the official annual meeting of the European Association of Percutaneous Cardiovascular Interventions (EAPCI), took place in Paris at the end of May on its twenty-fifth anniversary. This year, more than ever, the focus of the course was personalized medicine. This was reflected not only in the way the topics were addressed but also by the great interactivity that was generated by the .12 000 attendees. Discussion on personalized medicine started at the beginning of the Congress with the Great Debate that focused on the best strategies for STEMI patients. This produced a great deal of discussion, with contributions from all over the world on what should be the best reperfusion strategy according to local conditions. The personalized medicine concept continued to be prominent throughout the course: we all know that randomized trials are of utmost importance, but putting them into practice for treating an individual patient can sometimes be difficult. New sessions called ‘will this trial change my practice’, debated how to translate the results of recent large randomized trials, e.g. The ACCOAST trial or the TASTE trial, into personalized medicine for treating a given patient. The results of the SYMPLICITY-HTN-3 trial on renal denervation were also extensively debated during the Congress. In-depth discussions were continued on different topics in the intimate atmosphere of the ‘sharing centre’. The late-breaking trials allowed presentation of important clinical trials. The OCTAVIA trial assessed gender differences in the mechanisms of STEMI and vascular response to primary PCI with the current generation of drug-eluting stents. The clinical outcome at 30 days, 1 year and 2 years was identical with a key new finding, that erosion is more frequently a cause of STEMI than was anticipated.
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On the road to biological pacing and tissue repair Michael R. Rosen discussed the prospects and barriers at Cardiostim-EHRA Europace 2014 pacemaker lineages. On the positive side, many of the constructs have shown good catecholamine and acetylcholine responsiveness, and heart rate variability studies have shown a good autonomic response. Rates have ranged from 50 b.p.m. at rest to 100– 130 b.p.m. during excitement in large animal models. Issues have included the inability to deliver viral vector gene therapy that will persist (i.e. at the very least competitive with electronic pacemakers and, at best, lifelong), the inability to make hMSC delivery persist in situ for long intervals (efforts are underway to encapsulate them in nanofabrics to maintain them in place), and the need for immunosuppression with ESC delivery. Solving the issues at hand will be challenging, but the hope for a lifelong, autonomically responsive pacemaker should be realized. I will not venture an estimate of when this will occur: success will require time, imagination, and further technological development. Jennifer Taylor MPhil, [email protected]
Landmarks in the history of Cardiology V: the final story The era of devices in cardiology. With origins in the late nineteenth century, devices rapidly evolved from the late twentieth century to the present day. Since antiquity, medicine relied on technology in the form of scalpels, scissors, and probes. However, during the twentieth century, the collaboration among physicists, mathematicians, computer scientists, engineers, and physicians led to the invention of many devices for diagnosing and treating diseases. In the nineteenth century several experiments on the heart’s electrical activity were in motion, paving the way for the twentieth century discoveries. In 1841 Carlo Matteucci (1811–68) demonstrated that each heartbeat was associated with electrical activity1 and, 30 years later, the physicist Gabriel Lippmann (1845–1921) invented the capillary electrometer, an instrument that measured either small voltages or the interfacial tension between mercury and solutions (Figure 1). In 1877, the British physiologist Augustus-Desire´ Waller (1856– 1922) recorded the first single-lead electrocardiogram (ECG) (Figure 2), even if he did not realize its clinical importance: ‘I do not imagine that electrocardiography is likely to find any very extensive use in the hospital’.3,4 The major breakthrough in electrocardiography came in 1901 with the invention of the string galvanometer by the Nobel Laureate
physiologist Willem Einthoven (1860–1927). Einthoven detected recognizable waves, described several abnormal findings, and formulated the concept of ‘Einthoven’s triangle’.5 In 1911, Sir Thomas Lewis (1881–1954) in London assembled the first table model electrocardiograph6 and further improvements resulted in the widespread use of ECG in everyday clinical practice. When the young physicist Wilhelm-Conrad Roentgen (1845– 1923) discovered X-rays, he certainly could not have imagined the immense impact the technique would have in medicine. The same applies to the French physiologists, Claude Bernard (1813–78), Auguste Chauveau (1827–1917), and E´tienne-Jules Marey (1830– 1904) who attempted cardiac catheterization in animals.7 In 1929, the surgical resident Werner Forssmann (1904–79), trying to develop a therapeutic technique for the direct delivery of drugs to the heart, performed the first cardiac catheterization of a living person, on himself. Forssmann (Figure 3) inserted a 65 cm long, sterile, ureteric catheter into the antecubital vein of his left arm under local anaesthesia. He then walked to the X-ray room, where, under fluoroscopy, he advanced the catheter to the right atrium and he finally took the confirmatory X-ray documenting its positioning.8
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Biological pacing—a figment of the imagination 20 years ago—has become a reality, up to a point. It is a reality in the sense that we and others in the field have been able to identify the genes and cell types that can support pacemaker function, have demonstrated robust function in ‘pacemakers-in-a-dish’, and, as proof of concept pacemakers, having good function but limited longevity of function in small and large animal models. However, we have not reached near the point of human application. Approaches used have included viral vector delivery of genes to promote pacemaker function such as HCN2 or SkM1, delivery of the transcription factor TBX18 to turn subsets of mature myocardial cells into sinus node-like cells, human mesenchymal stem cell (hMSC) delivery of pacemaker genes, and human embryonic stem cells (hESCs) and induced pluripotent stem cells forced into
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Figure 2 Human ECG from Waller’s textFigure 1 Lipmann’s capillary electrom-
book An Introduction to Human Physiology, 1896.
eter, 1872.
In 1947, the pioneer cardiac surgeon Claude Beck (1894–1971) first successfully resuscitated a 14-year-old patient by internal cardiac massage and electrical defibrillation, which was followed in the 1960s by Paul Zoll’s (1911– 99) alternating current (AC) defibrillator, and B. Lown and J. Neuman’s DC defibrillator. In 1980 the cardiologist Michel Mirowski (1924–90) reported on the successful use of an implantable device that he invented in the 1970s, the automatic implantable cardioverter defibrillator.15 Along with electro-therapy, bio-electromagnetism developed. In 1871 F. Steiner first reported direct cardiac pacing in a dog anaesthetized with chloroform followed by Hugo von Ziemssen (1829 – 1902), who in 1882 applied this technique on a patient, Catharina Serafin, who had a large defect in the anterior left chest wall following resection of a tumour (Figures 4 and 5). The heart was covered by a thin skin layer on which Ziemssen placed electrodes.
Figure 4 Inge Edler and Hellmuth Hertz and their M-mode echocardiography machine.
Figure 5 Catharina Serafin on whom the first studies of electrical pacing were performed.
In 1932 Albert Hyman (1893–1972) developed the first artificial ˚ ke Senning pacemaker and in 1958 the Swedish cardiac surgeon A (1915–2000) implanted the first human cardiac pacemaker, which was developed by the engineer Rune Elmqvist (1906– 96).16
Where do we stand today? The fruitful collaboration between cardiology and bioengineering resulted in the development of a huge body of innovative technologies, such as: micro-transducers placed at the tip of catheters allowing intravascular imaging; wearable sensors/devices for continuous cardiovascular and haemodynamic monitoring; implantable devices for treating structural heart disease; catheters for electrical or chemical
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Years later, in 1941, Andre´ Cournand (1895–1988) and Dickinson Richards (1895–1973) measured cardiac output using a cardiac catheter and established cardiac catheterization as a diagnostic technique.9,10 For their discovery, Forssmann, Cournand, and Richards shared the 1956 Nobel Prize. In 1977, interventional cardiology went a step further, owing to Andreas Gru¨ntzig (1939–85), who performed the first percutaneous transluminal coronary angioplasty (PTCA) in a 37-year-old man with a stenosis of the proximal left anterior descending artery in Zurich.11 The technique evolved further to coronary atherectomy in 1986 and to coronary stenting in 1987. Concerning the evolution of ultrasound, in 1842 Christian Doppler (1803–53) discovered the phenomenon of frequency change of sound waves moving towards or away from a receiver; then in 1877, the Curie brothers discovered the piezo-electric effect. In clinical practice, the cardiologist Inge Edler (1911–2001) and the physicist Hellmuth Hertz (1920–90), launched in 1953, M-mode echocardiography, which they used in the pulse-echo technique for the detection of heart diseases. In the 1960s Claude Joyner (1925– 2006) and John Reid first noticed a contrast effect with the injection of saline and in the late 1970s, Jamil Tajik and Jim Seward, at the Mayo Clinic, used this technique to identify right to left shunts, and serious attempts to develop i.v. contrast agents (micro-bubbles) for ultrasound began.12 In the following years, echocardiography gained acceptance and applicability and new techniques developed such as two-dimensional transoesophageal Doppler echocardiography, contrast-enhanced harmonic ultrasonography, 3D and very recently 4D echocardiography, and intravascular ultrasound imaging. Almost 70 years ago, cardiac arrest meant death. A physician’s only choice was to open the chest and perform internal cardiac massage that could restart an inert heart but could not stop ventricular fibrillation. In 1899, the Swiss physiologists Jean-Louis Prevost (1838– 1927) and Frederic Battelli (1867– 1941) performed the first cardiac defibrillation in animals.13 They induced ventricular fibrillation by passing a 40 V current and reversed it with a stronger direct current (DC) of 240 –4800 V. Knowing the work of Prevost and Batelli, William Kouwenhoven (1886–1975), an electrical engineer at Johns Hopkins University, invented three different defibrillators (open-chest defibrillator, Hopkins AC, Mine Safety Portable) and developed cardiopulmonary resuscitation techniques.14
Figure 3 Nobel Prize winning physician Werner Forssmann MD.
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Marianna Karamanou MD PhD, Medical School, National and Kapodistrian University of Athens, Greece, [email protected] Theodore G. Papaioannou PhD, Biomedical Engineering Unit Hippokration Hospital, Medical School, National and Kapodistrian University of Athens, Greece George Androutsos MD PhD, Medical School, National and Kapodistrian University of Athens, Greece
References 1. Matteucci C. Me´moire sur l’e´lectricite´ animale. Annales de Chimie et de Physique 1834; 56:439–443.
2. Lippmann G. Relation entre les phe´nome`nes e´lectriques et capillaires. C. R. Se´ances Acad Sci Ser C 1873;76:1407 –1408. 3. Waller AD. A demonstration on man of electromotive changes accompanying the heart’s beat. J Physiol 1887;8:229 – 234. 4. Barker LF. Electrocardiography and phonocardiography: a collective review. Bull Johns Hopkins Hosp 1910;21:358 –389. 5. Snellen HA. Selected papers on electrocardiography of Willem Einthoven. Hague: Leiden, 1977. 6. Shapiro E. The first textbook of electrocardiography. Thomas Lewis: Clinical Electrocardiography. J Am Coll Cardiol 1983;1:1160 –1161. 7. Bounhoure JP. Histoire de la cardiologie. Des hommes, des de´couvertes, des techniques. Paris: Privat, 2004. 8. Forssmann W. Experiments on myself. Memoirs of a surgeon in Germany. New York: St Martin’s Press, 1974. 9. Cournand AF, Ranges HS. Catheterization of the right auricle in man. Proc Soc Exp Biol Med 1941;46:462 –466. 10. Richards DW. Cardiac output by the catheterization technique in various clinical conditions. Fed Proc 1945;4:215 –220. 11. Gruntzig AR, Senning A, Siegenthaler WE. Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty. N Engl J Med 1979;301:61 –68. 12. Karamanou M, Papaioannou TG, Stefanadis C, Androutsos G. Genesis of ultrasonic microbubbles: a quick historical overview. Curr Pharmaceut Design 2012;18: 2115 –2117. 13. Prevost JL, Batelli F. La mort par les de´charges e´lectriques. I. Conditions physiques. II. Me´canisme de la mort par des de´charges e´lectriques isole´es. J Physiol Pathol Gen 1899; 1:1085 –1129. 14. Kouwenhoven WB. The development of the defibrillator. Ann Intern Med 1969;71: 449 –458. 3. 15. Akselrod H, Kroll MW, Orlov MV. History of defibrillation. In Efimov IR, Kroll MW, Tchou PJ, eds. Cardiac Bioelectric Therapy: Mechanisms and Practical Implications. New York, NY: Springer, 2009. pp. 15 –38. 16. Geddes LA. Cardiac Pacing-Historical Highlights. In Bronzino JD ed. The Biomedical Engineering Handbook. 2nd edition. Boca Raton: CRC Press LLC, 2000. 17. Saltzman WM. Biomedical Engineering: Bridging Medicine and Technology. New York: Cambridge University Press, 2009. 18. Nichols M, Townsend N, Luengo-Fernandez R, Leal J, Gray A, Scarborough P, Rayner M. European Cardiovascular Disease Statistics 2012. European Heart Network, Brussels, European Society of Cardiology, Sophia Antipolis, 2012.
CardioPulse contact: Andros Tofield, Managing Editor. Email: [email protected]
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denervation; new artificial organs (left ventricular assist devices, total artificial heart, valves, stents, vascular grafts, pacemakers); and many others. Further discoveries beyond any imagination are about to occur in the near future due to the development of new biocompatible and biomimetic materials and the continuous progress in nanotechnology, bioinformatics, robotics, biomedical, and stem cell engineering.17 Inventions have stimulated and empowered the practice of cardiology but have also given rise to new dilemmas: profitable device industry, physicians’ financial relationships, bioethics in therapy, and death. Despite the numerous technological innovations and developments, recent epidemiological studies point out that cardiovascular events are increasing.18 This knowledge may question whether our efforts are in the right direction. In the fifth century BC, Hippocrates recognized that prevention is better than cure. Is it time to turn to better prevention strategies, with optimal nutrition and more physical activity?
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The 2014 European Society of Cardiology/ European Society of Anaesthesiology Guidelines on non-cardiac surgery: cardiovascular assessment and management have been published
Juhani Knuuti (photo Roni Lehti)
Steen Dalby Kristensen (photo Sam Rogers)
New guidelines on non-cardiac surgery: cardiovascular assessment and management have been produced by the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). The work by the Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the ESC and ESA forms a completely updated version of the guideline. The basic structure of the 2009 version has been retained because it was considered ‘excellent and very well liked with comprehensive summary of all major recommendations and stepwise approach at the end of the document’. However, there are also a number of important differences that have been introduced. In the latest document, the authors point out that the present Guidelines (GL) focus on the cardiovascular management of patients in whom heart disease is a potential source of complications during non-cardiac surgery. The risk of peri-operative complications depends on the condition of the patient before surgery, the
prevalence of comorbidities, and the urgency, magnitude, type, and duration of the surgical procedure. More specifically, cardiac complications can arise due to documented or asymptomatic ischaemic heart disease (IHD), left ventricular (LV) dysfunction, valvular heart disease (VHD), and arrhythmias, in patients who undergo surgical procedures that are associated with prolonged haemodynamic and cardiac stress. While seeking to address the magnitude of the problem in Europe, the Joint Task Force discovered that systematic data on the annual number and type of operations—and on patient outcomes—are only available at a national level in 23 European countries (41%), and in addition data definitions vary, as do data quantity and quality. In Europe, it is estimated that there are 19 million major procedures annually and while the majority of these procedures are performed in patients with minimal cardiovascular risk, 30% of patients undergo extensive surgical procedures in the presence of cardiovascular comorbidity; hence, 5.7 million procedures annually are performed in European patients who present with an increased risk of cardiovascular complications. Worldwide, non-cardiac surgery is associated with an average overall complication rate of 7 –11% and a mortality rate of 0.8 – 1.5%, depending on safety precautions. When applied to the population in the European Union member states, these figures translate into at least 167 000 cardiac complications annually due to non-cardiac surgical procedures, of which 19 000 are life-threatening. With this data in mind, the 2014 document has been updated with the following main differences:
(1) The GL recommends that a multi-disciplinary expert team should be considered for pre-operative evaluation of patients with a known or high risk of cardiac disease, who are undergoing high-risk non-cardiac surgery. (2) The surgical risk assessment, which depends on the planned procedure, has been completely updated. Furthermore, when alternative methods to the classical open surgery are considered, either through endovascular or less-invasive endoscopic procedures, the potential trade-offs between early benefits due to reduced morbidity and mid-long-term efficacy need to be taken into account. Accordingly, the GL recommends that patients should undergo pre-operative risk assessment independent of whether the surgery is by laparoscopy, or by an open surgical approach. 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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Co-chairs, Prof. Steen Dalby Kristensen and Juhani Knuuti, summarize the changes and updates with CardioPulse writer Mark Nicholls
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These Guidelines—intended for physicians and collaborators involved in the pre-operative, operative, and post-operative care of patients undergoing non-cardiac surgery—also identify important areas where there are gaps in knowledge and suggest, for example, that randomized clinical trials on beta-blockers and drugs such as statins are highly needed. The changing demographics across Europe within the next 20 years are also acknowledged with an ageing population having a major impact on peri-operative patient management. It is estimated
that elderly people require surgery four times as often as the rest of the population. The Joint Task Force states that the updated Guidelines have the potential to improve post-operative outcomes and highlight the existence of a clear opportunity for improving the quality of care in this high-risk group of patients. In addition to promoting an improvement in immediate peri-operative care, the guidelines will provide longterm advice. Mark Nicholls, [email protected]
How the new European Society of Cardiology/ European Society of Anaesthesiology Guidelines on non-cardiac surgery: cardiovascular assessment and management, are produced The two task force chairpersons present the process of bringing the Guidelines to completion During the last 16 months a Task Force established by the Guideline Committees of European Society of Cardiology (ESC) and European Society of Anaesthesiology (ESA) has been working on a new Guideline document on cardiovascular assessment and management of patients undergoing non-cardiac surgery.
The clinical scenario is common and the optimal management strategy for these patients is discussed by cardiologists, anaesthesiologists, surgeons, other doctors, and health personnel in our daily practice. The field is wide and complex and is evolving with many new developments. The ESC Board decided in December 2012 to
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(3) The patient risk assessment now includes not only the Lee score but also other validated risk scores such as NSQIP. The new version also has recommendations about the role of biomarkers (BNP and Troponins) for risk assessment. (4) The risk reduction section has also been completely updated. Most of the changes occurred in the beta-blocker section in which the main change is that pre-operative initiation of beta-blockers is not recommended in all patients but may be considered in patients scheduled for high-risk surgery and who have clinical risk factors, or who have known ischaemic heart disease or myocardial ischaemia. When initiated, the dose should be titrated. If the patient is already on beta-blocker therapy before surgery, its continuation is recommended. (5) The recommendation for the use of aspirin and P2Y12 inhibitors in patients undergoing non-cardiac surgery is updated. (6) With the availability of new oral anticoagulants, the guidelines now include recommendations on managing how patients undergoing non-cardiac surgery are treated with these drugs. (7) The recommendations on the timing of non-cardiac surgery in cardiac-stable/asymptomatic patients with previous revascularization are also updated by taking into account the new information about the safety margins after various revascularization procedures. As in theprevious GL, routine prophylactic myocardial revascularization before low- and intermediate-risk surgery in patients with proven IHD is not recommended but may be considered before high-risk surgery, depending on the extent of a stress-induced ischaemia. (8) The whole specific disease section has been completely updated and several new sections have been added. The section now covers numerous conditions that will have influence on the pre-operative evaluation such as chronic heart failure, arterial hypertension, VHD, arrhythmias, renal disease, carotid disease, peripheral artery disease, pulmonary artery hypertension, and pulmonary disease as well as congenital heart disease. (9) The peri-operative monitoring section has also been updated and expanded with the anaesthesia experts from ESA. The part now includes sections about intra-operative anaesthetic management, neuraxial techniques, peri-operative goal-directed therapy, risk stratification after surgery, early diagnosis of post-operative complications and post-operative pain management as well as specific recommendations about anaesthesia. (10) Naturally, these numerous changes have also resulted in major revisions of the summary table and the stepwise guidance sections at the end of the document. However, with these sections considered very useful for users, these revisions have been successfully managed. The stepwise approach, as well as one large table summarizing most of the recommendations, is included in the guideline document as well as in the pocket guideline.
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write a new Guideline on peri-operative care and established together with the ESA a new task force of experts co-chaired by Prof. Steen D. Kristensen, Aarhus, Denmark and Prof. Juhani Knuuti, Turku, Finland
Steen Dalby Kristensen (photo Sam Rogers)
Juhani Knuuti (photo Roni Lehti)
† How do we optimally evaluate pre- and peri-operative risk and what kind of impact it may have on patients undergoing noncardiac surgery? † New generation drug-eluting stents: should non-cardiac surgery be postponed and if so, for how long? † New and old anti-thrombotic drugs: what should we do if noncardiac surgery is needed? † When should we perform pre-operative revascularization? † How do we handle patients with valve disease, arrhythmia, heart failure, and other cardiac diseases? † What are the implications of co-morbidities such as diabetes, renal failure, and lung disease?
What is the optimal peri-operative medical treatment with, e.g. beta-blockers, statins, and ACE inhibitors/ARBs? The use of peri-operative beta-blocker treatment is complex and has received a lot of attention. As described in detail in a recent editorial by the editor-in-chief of the European Heart Journal (see this issue)1, the validity of some of the key publications in this field has been questioned and burning issues on dosing, type of compound and, in particular, which subgroups of patients will benefit are difficult to answer. Recent registry data show overall benefit of beta-blockers in some patients2,3 but to properly address the use of beta-blockers, conduction of new randomized studies are needed. Some colleagues and journalists have criticized the ESC and other leading scientific bodies for being too slow to react and change the Guidelines. However, as explained below, writing Guidelines is a lengthy
(Jose´ L. Zamorano) Once the development of an ESC Guideline is approved, the Committee for Practice Guidelines, chaired by Professor Jose´ L Zamorano from Madrid, prepares a list of potential writers to constitute the Task Force in charge of writing the guideline. From among the Task Force members, one or two Task Force chairpersons are chosen. The list of potential members of the Task Force is prepared in collaboration with ESC constituent bodies concerned, by the topic to be written. Eventually 15 – 25 experts are nominated for each Guideline Task Force, which is under the coordination of the chairpersons. The Task Force is primarily responsible for the scientific content of the Guideline. Once they have produced a final draft document, it will be reviewed by the Committee for Practice Guidelines members and external reviewers appointed by the Committee for Practice Guidelines in view of their knowledge in the field being discussed. Two Committee for Practice Guidelines members coordinate the review process. Comments from all reviewers are sent back to the Task Force chairpersons who have to address each and every one of them—it is not unusual that the number of comments exceeds one thousand. The revised version as well as the answers to all comments are sent back to the Committee for Practice Guidelines and the review process starts again until a final version is produced, usually after two to three review rounds. For the new ESC Guidelines on non-cardiac surgery .115 experts have been involved including 24 Task Force members, 26 members of the Committee for Practice Guidelines, 36 National Cardiac Society reviewers, 24 expert peer reviewers, and a number of ESC and ESA Board members. The document has been presented at the ESC
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The Guideline will cover the whole field from surgical risk assessment, pre-operative evaluation, and optimal perioperative management and also address relevant cardiology and anaesthesia issues in patients with specific cardiac diseases and common co-morbidities scheduled to undergo non-cardiac surgery. The goal is to provide optimal guidance in the clinical decision-making for patients undergoing non-cardiac surgery. Key areas with new recommendations based on scientific developments are as follows:
process and includes the comprehensive study of literature and evidence, as well as a multi-step review process, all of which are critical to the quality of the guidelines. Meanwhile, the ESC,AHA, and ACC decided in August 2013 to issue a common statement regarding temporary recommendations on the use of beta-blockers: ‘In the interim, our current joint position is that the initiation of beta blockers in patients who will undergo noncardiac surgery should not be considered routine, but should be considered carefully by each patient’s treating physician on a case-by-case basis’. http://www.escardio.org/about/press/press-releases/pr-13/ Pages/joint-statement-perioperative-guidelines.aspx. In that statement as well as earlier (March 2013) the ESC indicated that a new Guideline on non-cardiac surgery was in preparation. Our American colleagues from AHA/ACC are also in the process of writing a new Guideline on this topic. Guideline documents require meticulous preparation and their publication cannot be achieved in a rush for many reasons, the foremost being the safety of our patients.
2784 Annual Congress in Barcelona on 2 September this year and made available online in the European Heart Journal. The numerous comments from the reviewers have improved the quality of the document considerably. We would like to stress that although the beta-blocker section is important, numerically it only accounts for quite a small section in the whole document. Steen Kristensen MD DMSc, [email protected] Juhani Knuuti MD, [email protected]
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References 1. Lu¨scher TF, Gersh B, Landmesser Ulf, Ruschitzka F. Is the panic about beta-blockers in perioperative care justified? Eur Heart J 2014;35:2442 –2444. 2. London MJ, Hur K, Schwartz GG, Henderson WG. Association of perioperative beta blockade with mortality and cardiovascular morbidity following major noncardiac surgery. J Amer Med Ass 2013;16:1704 – 1713. 3. Andersson C, Merie C, Jorgensen M, Gislason GH, Torp-Pedersen C, Overgaard C, Kober L, Jensen PF, Hlatky MA. Association of b-blocker therapy with risks of adverse cardiovascular events and deaths in patients with ischemic heart disease undergoing noncardiac surgery a Danish nationwide cohort study. JAMA Intern Med 2014;174: 336 –344.
The ‘Ten Commandments’ of Noncardiac Surgery 2014 ESC/ESA Guidelines
(7)
(8)
(9)
(10)
information on safety margins after various revascularization procedures. As in previous GL, routine prophylactic myocardial revascularization before low- and intermediate-risk surgery in patients with proven IHD is not recommended but may be considered before high-risk surgery, depending on the extent of a stress-induced ischaemia. The entire section on specific diseases has been completely updated and several new sections have been added. The section now covers numerous conditions that will influence preoperative evaluation, i.e. chronic heart failure, arterial hypertension, valvular heart disease, arrhythmias, renal disease, carotid disease, peripheral artery disease, pulmonary artery hypertension, and pulmonary disease as well as congenital heart disease. The perioperative monitoring section has also been updated and expanded by the anaesthesia experts from European Society of Anaesthesiology. This section now includes parts on intra-operative anaesthetic management, neuraxial techniques, peri-operative goal-directed therapy, risk stratification after surgery, early diagnosis of post-operative complications, and post-operative pain management, as well as specific recommendations about the anaesthesia. Naturally, these numerous changes also led to major revisions of the summary table and step-by-step guidance sections at the end of the document. However, this section was considered very useful for users and these revisions were successfully managed. The recommendations for the step-by-step approach as well as one comprehensive table summarizing most of the recommendations are included in the guideline document as well is in the pocket guideline. Randomized clinical trials on the peri-operative use of bblockers and other drugs are highly needed. Steen D Kristensen MD, [email protected] Juhani Knuuti MD, [email protected]
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(1) A multidisciplinary expert team should be consulted for preoperative evaluation of patients with known or high risk of cardiac disease undergoing high-risk non-cardiac surgery. (2) The surgical risk assessment, which depends on the planned procedure, has been completely updated. Further, when alternative methods to the classical open surgery are considered, either through endovascular or less invasive endoscopic procedures, the potential trade-offs between early benefits due to reduced morbidity and mid-long-term efficacy must be considered. Accordingly, the Guidelines (GL) recommend that patients should undergo preoperative risk assessment independently of an open or laparoscopic surgical approach. (3) The patient risk assessment now includes not only the Lee score but also other validated risk scores such as NSQIP. The new version also has recommendations about the role of biomarkers (BNP and Troponins) for risk assessment. (4) The risk reduction section has also been completely updated. The key change is that preoperative initiation of b-blockers is not recommended in all patients but may be considered in patients scheduled for high-risk surgery and who have clinical risk factors, or, who have known ischaemic heart disease or myocardial ischaemia. When initiated, the dose should be titrated. If the patient has already had b-blocker therapy before surgery, continuation is recommended. (5) The recommendation for the use of aspirin and P2Y12 inhibitors for patients undergoing non-cardiac surgery has been updated. New oral anticoagulants are now available and recommendations on how to manage patients treated with these drugs undergoing non-cardiac surgery is described in a new section. (6) The recommendations for the timing of non-cardiac surgery in cardiac-stable/asymptomatic patients with previous revascularization has also been updated by considering new
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From evidence-based medicine to personalized medicine News from EuroPCR 2014 Results of the CENTURY II randomized, prospective trial (1123 patients) showed that the Ultimaster drug-eluting stent (Terumo) with a bioresorbable polymer was as safe and effective as the Xience stent (Abbott Vascular) with a permanent polymer. Finally, The SAPIEN 3 trial met its primary end-point of all-cause mortality of the valve-implant population at 30 days post-index procedure, generating promising results for this new generation of TAVI valves. More practical sessions also provided much interactivity with, for example, the learning sessions focusing on specific technical points during 90 min and the radial track that generated a lot of interest, but also with the young interventionist’s tracks that focused on ‘the essentials’ of different key interventional techniques. This year the peripheral programme was based on a new programme specifically oriented to the emerging needs of the interventional cardiology community. Finally, this year, the Ethica Award was presented to Adnan Kastrati. His work sums up the spirit of the course as he has succeeded, according to his peers, in obtaining a perfect synthesis between technical work in the cath lab and research with an emphasis on team work, demonstrated by the fact that he dedicated his award to his team.
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EuroPCR, the official annual meeting of the European Association of Percutaneous Cardiovascular Interventions (EAPCI), took place in Paris at the end of May on its twenty-fifth anniversary. This year, more than ever, the focus of the course was personalized medicine. This was reflected not only in the way the topics were addressed but also by the great interactivity that was generated by the .12 000 attendees. Discussion on personalized medicine started at the beginning of the Congress with the Great Debate that focused on the best strategies for STEMI patients. This produced a great deal of discussion, with contributions from all over the world on what should be the best reperfusion strategy according to local conditions. The personalized medicine concept continued to be prominent throughout the course: we all know that randomized trials are of utmost importance, but putting them into practice for treating an individual patient can sometimes be difficult. New sessions called ‘will this trial change my practice’, debated how to translate the results of recent large randomized trials, e.g. The ACCOAST trial or the TASTE trial, into personalized medicine for treating a given patient. The results of the SYMPLICITY-HTN-3 trial on renal denervation were also extensively debated during the Congress. In-depth discussions were continued on different topics in the intimate atmosphere of the ‘sharing centre’. The late-breaking trials allowed presentation of important clinical trials. The OCTAVIA trial assessed gender differences in the mechanisms of STEMI and vascular response to primary PCI with the current generation of drug-eluting stents. The clinical outcome at 30 days, 1 year and 2 years was identical with a key new finding, that erosion is more frequently a cause of STEMI than was anticipated.
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On the road to biological pacing and tissue repair Michael R. Rosen discussed the prospects and barriers at Cardiostim-EHRA Europace 2014 pacemaker lineages. On the positive side, many of the constructs have shown good catecholamine and acetylcholine responsiveness, and heart rate variability studies have shown a good autonomic response. Rates have ranged from 50 b.p.m. at rest to 100– 130 b.p.m. during excitement in large animal models. Issues have included the inability to deliver viral vector gene therapy that will persist (i.e. at the very least competitive with electronic pacemakers and, at best, lifelong), the inability to make hMSC delivery persist in situ for long intervals (efforts are underway to encapsulate them in nanofabrics to maintain them in place), and the need for immunosuppression with ESC delivery. Solving the issues at hand will be challenging, but the hope for a lifelong, autonomically responsive pacemaker should be realized. I will not venture an estimate of when this will occur: success will require time, imagination, and further technological development. Jennifer Taylor MPhil, [email protected]
Landmarks in the history of Cardiology V: the final story The era of devices in cardiology. With origins in the late nineteenth century, devices rapidly evolved from the late twentieth century to the present day. Since antiquity, medicine relied on technology in the form of scalpels, scissors, and probes. However, during the twentieth century, the collaboration among physicists, mathematicians, computer scientists, engineers, and physicians led to the invention of many devices for diagnosing and treating diseases. In the nineteenth century several experiments on the heart’s electrical activity were in motion, paving the way for the twentieth century discoveries. In 1841 Carlo Matteucci (1811–68) demonstrated that each heartbeat was associated with electrical activity1 and, 30 years later, the physicist Gabriel Lippmann (1845–1921) invented the capillary electrometer, an instrument that measured either small voltages or the interfacial tension between mercury and solutions (Figure 1). In 1877, the British physiologist Augustus-Desire´ Waller (1856– 1922) recorded the first single-lead electrocardiogram (ECG) (Figure 2), even if he did not realize its clinical importance: ‘I do not imagine that electrocardiography is likely to find any very extensive use in the hospital’.3,4 The major breakthrough in electrocardiography came in 1901 with the invention of the string galvanometer by the Nobel Laureate
physiologist Willem Einthoven (1860–1927). Einthoven detected recognizable waves, described several abnormal findings, and formulated the concept of ‘Einthoven’s triangle’.5 In 1911, Sir Thomas Lewis (1881–1954) in London assembled the first table model electrocardiograph6 and further improvements resulted in the widespread use of ECG in everyday clinical practice. When the young physicist Wilhelm-Conrad Roentgen (1845– 1923) discovered X-rays, he certainly could not have imagined the immense impact the technique would have in medicine. The same applies to the French physiologists, Claude Bernard (1813–78), Auguste Chauveau (1827–1917), and E´tienne-Jules Marey (1830– 1904) who attempted cardiac catheterization in animals.7 In 1929, the surgical resident Werner Forssmann (1904–79), trying to develop a therapeutic technique for the direct delivery of drugs to the heart, performed the first cardiac catheterization of a living person, on himself. Forssmann (Figure 3) inserted a 65 cm long, sterile, ureteric catheter into the antecubital vein of his left arm under local anaesthesia. He then walked to the X-ray room, where, under fluoroscopy, he advanced the catheter to the right atrium and he finally took the confirmatory X-ray documenting its positioning.8
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Biological pacing—a figment of the imagination 20 years ago—has become a reality, up to a point. It is a reality in the sense that we and others in the field have been able to identify the genes and cell types that can support pacemaker function, have demonstrated robust function in ‘pacemakers-in-a-dish’, and, as proof of concept pacemakers, having good function but limited longevity of function in small and large animal models. However, we have not reached near the point of human application. Approaches used have included viral vector delivery of genes to promote pacemaker function such as HCN2 or SkM1, delivery of the transcription factor TBX18 to turn subsets of mature myocardial cells into sinus node-like cells, human mesenchymal stem cell (hMSC) delivery of pacemaker genes, and human embryonic stem cells (hESCs) and induced pluripotent stem cells forced into
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Figure 2 Human ECG from Waller’s textFigure 1 Lipmann’s capillary electrom-
book An Introduction to Human Physiology, 1896.
eter, 1872.
In 1947, the pioneer cardiac surgeon Claude Beck (1894–1971) first successfully resuscitated a 14-year-old patient by internal cardiac massage and electrical defibrillation, which was followed in the 1960s by Paul Zoll’s (1911– 99) alternating current (AC) defibrillator, and B. Lown and J. Neuman’s DC defibrillator. In 1980 the cardiologist Michel Mirowski (1924–90) reported on the successful use of an implantable device that he invented in the 1970s, the automatic implantable cardioverter defibrillator.15 Along with electro-therapy, bio-electromagnetism developed. In 1871 F. Steiner first reported direct cardiac pacing in a dog anaesthetized with chloroform followed by Hugo von Ziemssen (1829 – 1902), who in 1882 applied this technique on a patient, Catharina Serafin, who had a large defect in the anterior left chest wall following resection of a tumour (Figures 4 and 5). The heart was covered by a thin skin layer on which Ziemssen placed electrodes.
Figure 4 Inge Edler and Hellmuth Hertz and their M-mode echocardiography machine.
Figure 5 Catharina Serafin on whom the first studies of electrical pacing were performed.
In 1932 Albert Hyman (1893–1972) developed the first artificial ˚ ke Senning pacemaker and in 1958 the Swedish cardiac surgeon A (1915–2000) implanted the first human cardiac pacemaker, which was developed by the engineer Rune Elmqvist (1906– 96).16
Where do we stand today? The fruitful collaboration between cardiology and bioengineering resulted in the development of a huge body of innovative technologies, such as: micro-transducers placed at the tip of catheters allowing intravascular imaging; wearable sensors/devices for continuous cardiovascular and haemodynamic monitoring; implantable devices for treating structural heart disease; catheters for electrical or chemical
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Years later, in 1941, Andre´ Cournand (1895–1988) and Dickinson Richards (1895–1973) measured cardiac output using a cardiac catheter and established cardiac catheterization as a diagnostic technique.9,10 For their discovery, Forssmann, Cournand, and Richards shared the 1956 Nobel Prize. In 1977, interventional cardiology went a step further, owing to Andreas Gru¨ntzig (1939–85), who performed the first percutaneous transluminal coronary angioplasty (PTCA) in a 37-year-old man with a stenosis of the proximal left anterior descending artery in Zurich.11 The technique evolved further to coronary atherectomy in 1986 and to coronary stenting in 1987. Concerning the evolution of ultrasound, in 1842 Christian Doppler (1803–53) discovered the phenomenon of frequency change of sound waves moving towards or away from a receiver; then in 1877, the Curie brothers discovered the piezo-electric effect. In clinical practice, the cardiologist Inge Edler (1911–2001) and the physicist Hellmuth Hertz (1920–90), launched in 1953, M-mode echocardiography, which they used in the pulse-echo technique for the detection of heart diseases. In the 1960s Claude Joyner (1925– 2006) and John Reid first noticed a contrast effect with the injection of saline and in the late 1970s, Jamil Tajik and Jim Seward, at the Mayo Clinic, used this technique to identify right to left shunts, and serious attempts to develop i.v. contrast agents (micro-bubbles) for ultrasound began.12 In the following years, echocardiography gained acceptance and applicability and new techniques developed such as two-dimensional transoesophageal Doppler echocardiography, contrast-enhanced harmonic ultrasonography, 3D and very recently 4D echocardiography, and intravascular ultrasound imaging. Almost 70 years ago, cardiac arrest meant death. A physician’s only choice was to open the chest and perform internal cardiac massage that could restart an inert heart but could not stop ventricular fibrillation. In 1899, the Swiss physiologists Jean-Louis Prevost (1838– 1927) and Frederic Battelli (1867– 1941) performed the first cardiac defibrillation in animals.13 They induced ventricular fibrillation by passing a 40 V current and reversed it with a stronger direct current (DC) of 240 –4800 V. Knowing the work of Prevost and Batelli, William Kouwenhoven (1886–1975), an electrical engineer at Johns Hopkins University, invented three different defibrillators (open-chest defibrillator, Hopkins AC, Mine Safety Portable) and developed cardiopulmonary resuscitation techniques.14
Figure 3 Nobel Prize winning physician Werner Forssmann MD.
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Marianna Karamanou MD PhD, Medical School, National and Kapodistrian University of Athens, Greece, [email protected] Theodore G. Papaioannou PhD, Biomedical Engineering Unit Hippokration Hospital, Medical School, National and Kapodistrian University of Athens, Greece George Androutsos MD PhD, Medical School, National and Kapodistrian University of Athens, Greece
References 1. Matteucci C. Me´moire sur l’e´lectricite´ animale. Annales de Chimie et de Physique 1834; 56:439–443.
2. Lippmann G. Relation entre les phe´nome`nes e´lectriques et capillaires. C. R. Se´ances Acad Sci Ser C 1873;76:1407 –1408. 3. Waller AD. A demonstration on man of electromotive changes accompanying the heart’s beat. J Physiol 1887;8:229 – 234. 4. Barker LF. Electrocardiography and phonocardiography: a collective review. Bull Johns Hopkins Hosp 1910;21:358 –389. 5. Snellen HA. Selected papers on electrocardiography of Willem Einthoven. Hague: Leiden, 1977. 6. Shapiro E. The first textbook of electrocardiography. Thomas Lewis: Clinical Electrocardiography. J Am Coll Cardiol 1983;1:1160 –1161. 7. Bounhoure JP. Histoire de la cardiologie. Des hommes, des de´couvertes, des techniques. Paris: Privat, 2004. 8. Forssmann W. Experiments on myself. Memoirs of a surgeon in Germany. New York: St Martin’s Press, 1974. 9. Cournand AF, Ranges HS. Catheterization of the right auricle in man. Proc Soc Exp Biol Med 1941;46:462 –466. 10. Richards DW. Cardiac output by the catheterization technique in various clinical conditions. Fed Proc 1945;4:215 –220. 11. Gruntzig AR, Senning A, Siegenthaler WE. Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty. N Engl J Med 1979;301:61 –68. 12. Karamanou M, Papaioannou TG, Stefanadis C, Androutsos G. Genesis of ultrasonic microbubbles: a quick historical overview. Curr Pharmaceut Design 2012;18: 2115 –2117. 13. Prevost JL, Batelli F. La mort par les de´charges e´lectriques. I. Conditions physiques. II. Me´canisme de la mort par des de´charges e´lectriques isole´es. J Physiol Pathol Gen 1899; 1:1085 –1129. 14. Kouwenhoven WB. The development of the defibrillator. Ann Intern Med 1969;71: 449 –458. 3. 15. Akselrod H, Kroll MW, Orlov MV. History of defibrillation. In Efimov IR, Kroll MW, Tchou PJ, eds. Cardiac Bioelectric Therapy: Mechanisms and Practical Implications. New York, NY: Springer, 2009. pp. 15 –38. 16. Geddes LA. Cardiac Pacing-Historical Highlights. In Bronzino JD ed. The Biomedical Engineering Handbook. 2nd edition. Boca Raton: CRC Press LLC, 2000. 17. Saltzman WM. Biomedical Engineering: Bridging Medicine and Technology. New York: Cambridge University Press, 2009. 18. Nichols M, Townsend N, Luengo-Fernandez R, Leal J, Gray A, Scarborough P, Rayner M. European Cardiovascular Disease Statistics 2012. European Heart Network, Brussels, European Society of Cardiology, Sophia Antipolis, 2012.
CardioPulse contact: Andros Tofield, Managing Editor. Email: [email protected]
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denervation; new artificial organs (left ventricular assist devices, total artificial heart, valves, stents, vascular grafts, pacemakers); and many others. Further discoveries beyond any imagination are about to occur in the near future due to the development of new biocompatible and biomimetic materials and the continuous progress in nanotechnology, bioinformatics, robotics, biomedical, and stem cell engineering.17 Inventions have stimulated and empowered the practice of cardiology but have also given rise to new dilemmas: profitable device industry, physicians’ financial relationships, bioethics in therapy, and death. Despite the numerous technological innovations and developments, recent epidemiological studies point out that cardiovascular events are increasing.18 This knowledge may question whether our efforts are in the right direction. In the fifth century BC, Hippocrates recognized that prevention is better than cure. Is it time to turn to better prevention strategies, with optimal nutrition and more physical activity?
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