Afternoon heart surgery– better outcomes for patients

Outcomes for open heart surgery could potentially be improved by moving surgery to the afternoon, rather than in the morning, according to a study published in The Lancet.

A recent study identifies a link between a person’s circadian clock and their risk of heart damage and major cardiac events after heart surgery. It suggests that moving surgery to the afternoon, rather than in the morning results in better outcomes for the patient.

The study – “Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erb antagonism: a single-centre propensitymatched cohort study and a randomised study” – also provides early insights into the mechanism behind this link, identifying nearly 300 genes linking the circadian clock – the internal body clock that controls when people sleep, eat and wake up – to heart damage.

Following open heart surgery, some patients may develop heart damage impacting on the heart’s ability to pump blood, resulting in poor outcomes including onset of heart failure and a heightened risk of death.

Previous research has suggested that cardiovascular events, such as myocardial infarction, that happen in the morning may be associated with a higher risk of damage, compared to afternoon events, but reasons have remained unclear.

The study consisted of four parts: an observational study looking at the association between time of day of surgery and outcomes; a randomised controlled trial to investigate whether there was a causal link between time of day of surgery and outcomes; a human tissue analysis to identify genes involved in the circadian effect on heart surgery; and a mouse model further investigating the biological mechanism and a potential therapeutic approach.

“Currently, there are few other surgical options to reduce the risk of post-surgery heart damage, meaning new techniques to protect patients are needed,” says author Professor David Montaigne, University of Lille, France. “Our study found that postsurgery heart damage is more common among people who have heart surgery in the morning, compared to the afternoon. Our findings suggest this is because part of the biological mechanism behind the damage is affected by a person’s circadian clock and the underlying genes that control it. As a result, moving heart surgery to the afternoon may help to reduce a person’s risk of heart damage after surgery.”

In the observational study, which ran from January 2009 to December 2015, researchers tracked the medical records of 596 people who had heart valve replacement surgery (half had surgery in the morning, half in the afternoon) for 500 days to monitor for any major cardiac events such as a heart attack, heart failure or died from heart disease.

People who had surgery in the afternoon had a 50% lower risk of a major cardiac event, compared to people who had surgery in the morning (28/298 [9.4%] compared to 54/298 [18.1%]) – this could equate to one major event being avoided for every 11 patients who have afternoon surgery.

In the randomised controlled trial, which took place from January 2016 to February 2017, 88 patients were randomly scheduled for heart valve replacement surgery in the morning or afternoon (half had morning surgery and the other half had afternoon surgery) and their health was monitored until they left hospital.

There were no deaths in either group and the average time in hospital was 12 days. However, patients who had afternoon surgery had lower levels of heart tissue damage after surgery, compared to morning surgery patients.

To understand why there were these differences in outcomes for morning and afternoon surgery, the researchers tested 30 heart tissue samples from a sub-group of patients from the randomised controlled trial (14 from the morning surgery group, and 16 from the afternoon surgery group). In laboratory tests on the tissue, they found that the afternoon surgery samples more quickly regained their ability to contract when put in conditions that replicated the heart refilling with blood.

A genetic analysis of these samples also showed that 287 genes linked to the circadian clock were more active in the afternoon surgery samples, compared to the morning surgery samples. This suggests that the heart is subject to the body’s circadian clock, and the surgical outcomes reflect the heart’s poorer ability to repair in the morning than in the afternoon.

To further understand the mechanism, the researchers deleted and replaced the relevant genes in a mouse to study how this affected the sleep-to-wake transition. They also provided a proof of concept for future drug development by demonstrating the cardio-protective activities of a drug targeting the nuclear receptor and clock protein Rev-erba. Developing drugs which modulate these genes could help protect the heart during surgery. However, they note that the mechanism will require further confirmation in humans.

The authors note that the study will need to be replicated in larger trials to fully understand the association between the circadian clock and damage after heart surgery, and to confirm their findings. They also note that the research needs to be replicated in high-risk patients with diabetes and kidney failure, as they are at higher risk of heart disease and poor outcomes, and were not included in this study.

Writing in a linked Comment, Professor Michel Ovize, Hôpital Louis Pradel, France, says: “In addition to the central clock located in the CNS, each organ and cell type has its own internal (peripheral) clock. Geneexpression analysis – mainly performed in rodents but also in human beings – has shown a rhythmic expression of clock genes in the heart... Whether or not clock genes modulate cell death directly and whether they affect ischaemia injury or reperfusion injury remain to be established. Nevertheless, the authors have clearly shown that circadian rhythm is of clinical importance in aortic valve replacement surgery. Beyond the fact that it brings a new effect-modifying factor into the complexity of ischaemiareperfusion injury clinical trial design and interpretation, the study by Montaigne and colleagues might already have some practical implications. Even before we have drugs available to regulate the circadian clock, one might propose that high-risk patients should preferentially be operated on in the afternoon.”

• doi: 10.1016/S0140-6736(17)32132-3

Researchers produce 3D data to show cardiac conduction system

A pioneering new study is set to help surgeons repair hearts without damaging precious tissue.

A team of scientists from Liverpool John Moores University (LJMU), The University of Manchester, Aarhus University and Newcastle University, have developed a way of producing 3D data to show the cardiac conduction system – the special cells that enable hearts to beat – in unprecedented detail. The findings were published in Scientifi c Reports.

The new data in this study gives them a much more accurate framework than previously available for computer models of the heartbeat and should improve the ability to make sense of abnormal heart rhythms like atrial fi brillation. The data reveals exactly where the cardiac conduction system is in a normal heart. For example, it shows just how close it runs to the aortic valve.

Professor Jonathan Jarvis who is based at the LJMU School of Sport and Exercise Sciences explained: “The 3D data makes it much easier to understand the complex relationships between the cardiac conduction system and the rest of the heart. We also use the data to make 3D printed models that are really useful in our discussions with heart doctors, other researchers and patients with heart problems.

“New strategies to repair or replace the aortic valve must therefore make sure that they do not damage or compress this precious tissue. In future work we will be able to see where the cardiac conduction system runs in hearts that have not formed properly. This will help the surgeons who repair such hearts to design operations that have the least risk of damaging the cardiac conduction system.”

Co-author Dr Halina Dobrzynski, who is based in The University of Manchester’s Cardiovascular Division, has been working on the anatomy of the cardiac conduction system for 20 years. She says: “This is just the beginning. The British Heart Foundation is supporting my group to visualise this system in 3D from aged and failing hearts. With my research assistant Andrew Atkinson and working with Professor Jonathan Jarvis, Robert Stephenson and others, we will produce families of data from aged and failing hearts in 3D.”

How does this work? Soaking post-mortem samples in a solution of iodine, means soft tissue such as the heart can absorb X-rays and become visible.

With X-ray scanners, scientists can make detailed 3D images. In the best images, they can even see the boundaries between single heart cells, and detect in which direction they are arranged. Within the heart, there is a special network called the cardiac conduction system that generates and distributes a wave of electrical activity stimulating the heart muscle to contract. This system makes sure that the various parts of the heart contract regularly and in a coordinated way, a bit like a team of rowers in a boat race. If the system is damaged, and one part of the heart contracts out of time with the rest, then the heart does not pump so effi ciently.

This research was carried out in collaboration with the Visible Heart Laboratory, University of Minnesota, Minneapolis, US; National Institute of Legal Medicine, Bucharest, Romania and Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand

The paper, ‘High resolution 3-Dimensional imaging of the human cardiac conduction system from microanatomy to mathematical modelling,’ was published in Scientifi c Reports.

• doi:10.1038/s41598-017-07694-8


Cardiac surgeons at Cleveland Clinic Abu Dhabi perform complex valve-replacement procedure

Physicians at Cleveland Clinic Abu Dhabi have successfully performed a rare and complex operation on an Emirati national patient to replace two heart valves that were destroyed by cancer.

The tumour originated in the stomach, spread to the liver and released chemicals that destroyed two rightside heart valves – the tricuspid and pulmonary valves.

A multidisciplinary team worked to treat the tumour and its complications, as well as replacing the heart valves of the patient using an openchest procedure.

The patient, a retired Emirati national, had visited a number of hospitals for tests before the tumour was detected at Cleveland Clinic Abu Dhabi.

After receiving a correct diagnosis at Cleveland Clinic Abu Dhabi, the patient, who had previously always travelled abroad for medical treatment, flew to Singapore for a second opinion.

Staff at the hospital in Singapore confi rmed the diagnosis and advised him to return to Cleveland Clinic Abu Dhabi to have his cancer treatment and valvereplacement surgery.

Dr Rakesh Suri, Acting CEO and Chief of Thoracic and Cardiovascular Surgery at Cleveland Clinic Abu Dhabi, explained: “Complex surgeries to replace the damaged valves in cardiac carcinoid syndrome can only be performed in a few places in the world, because the management of such patients can be challenging and risky. Cleveland Clinic Abu Dhabi has brought the highest level of expertise to the region to provide advanced treatment options for patients and to deliver superior outcomes in cases such as this one.”

In the case of the patient, he quickly returned to his normal daily life and now continues to visit Cleveland Clinic Abu Dhabi for check-ups and rehabilitation.

“Although it was major surgery, my experience felt as minor and as painless as having my teeth cleaned at the dentist,” said the patient. “Everyone performed their roles to the highest degree and I now recommend Cleveland Clinic Abu Dhabi over and above overseas treatment to my friends and family.”


Historic day as physicians perform UAE ’s first full heart transplant

Performing the historic heart surgery: Dr Johannes Bonatti, Chief of the Heart & Vascular Institute (center, with dark glasses); Dr Rakesh Suri, Acting CEO of Cleveland Clinic Abu Dhabi and Dr Stefan Sanger, Clinical Associate (left, back to camera); with Dr Jehad Al Ramahi, Clinical Associate, and other caregivers from Cleveland Clinic Abu Dhabi.

Physicians at Cleveland Clinic Abu Dhabi have successfully completing the United Arab Emirates’ first full heart transplant.

The pioneering surgery, which took place on 5 December, was performed by a four-person surgical team that included Dr Rakesh Suri, Acting CEO of Cleveland Clinic Abu Dhabi; Dr Johannes Bonatti, Chief of the Heart & Vascular Institute; Dr Stefan Sanger, Clinical Associate; and Dr Jehad Al Ramahi, Clinical Associate – all of Cleveland Clinic Abu Dhabi.

The patient, a 38-year-old Emirati man, had been suffering from end-stage heart failure and was managed by the Heart Failure and Transplant Program for almost six months. He was placed on ClevelandClinic Abu Dhabi’s transplant waiting list shortly after the UAE Government’s decree earlier this year that allows deceased donor transplants.

On the same night, Dr Bashir Sankari, the Chief of the Surgical Subspecialties Institute at Cleveland Clinic Abu Dhabi, performed a kidney transplant from the same donor, providing vital surgery for another patient on the hospital’s transplant list.

Sheikh Abdullah bin Mohammed Al Hamed, Chairman of the Health Authority, said: “What we have accomplished today is a historic accomplishment. The passing of the law regulating the transfer and transplantation of organs earlier this year has made a significant impact on enabling such sophisticated operations in the country.”

Waleed Al Mokarrab Al Muhairi, Chairman of Cleveland Clinic Abu Dhabi, Mubadala Deputy Group CEO, and Chief Executive Officer, Alternative Investments & Infrastructure, said: “We established Cleveland Clinic Abu Dhabi to provide the people of the UAE with the highest standards of care; to stimulate medical innovation; and to invest in the development of Emirati healthcare professionals. This remarkable series of operations delivered on all three objectives, and marked an important medical first for our hospital and our nation.”

Dr Ali Al Obaidli, Chair of the National Transplant Committee, said: “This operation marks the culmination of years of planning and preparation to ensure that the UAE has a comprehensive framework for transplant surgery. Working together, we have ensured that we have the surgical expertise and advanced treatments in place to support a full transplant program, in parallel with necessary regulatory changes.”

Dr Suri said: “It is a signifi cant achievement for Cleveland Clinic Abu Dhabi and our transplant team, who have accomplished a historic medical milestone in the UAE. This operation underlines the incredible social impact that our transplant services are having – thanks to one donor, we have transformed the lives of multiple patients and their families.

“The UAE has taken important strides in introducing new legislation to support transplant operations in 2017, and we are very proud that Cleveland Clinic Abu Dhabi is the first and only multi-organ transplant facility in the country. After two years of sophisticated training and preparation, our team was fully prepared to undertake and excel in performing this innovative series of operations,” he added. Demonstrating the remarkable benefi ts that organ donation can offer, teams from another medical facility in the UAE and from the Kingdom of Saudi Arabia were also involved in the transplants. The donor’s second kidney went to a paediatric patient at Sheikh Khalifa Medical City in Abu Dhabi, while a team from the Saudi Center for Organ Transplantation (SCOT) was present for the surgery.

The operation received strong support from the UAE National Organ Transplant Committee, who were heavily involved in the preparations for the transplant. “This was a demonstration of Cleveland Clinic Abu Dhabi’s multidisciplinary excellence at every level,” said Dr Bonatti.

“The donor heart started beating immediately after implantation and the heart patient was taken to the intensive care unit after six hours in the operating room.”

Cleveland Clinic Abu Dhabi has worked closely with Cleveland Clinic in the United States and Mubadala in establishing its organ transplant program. The ClevelandClinic Transplant Center in the US is a world leader in organ transplantation, and the team in Abu Dhabi has benefi tted signifi cantly from sharing best practice and new innovations with their colleagues in the US.

Dr Feras Bader, the Director of Cleveland Clinic Abu Dhabi’s Heart Failure and Transplant Program, said: “I was called about the donor 48 hours before the transplant surgery. It was the same day that the world was celebrating the 50th anniversary of the world’s first heart transplant in 1967, and also the day the UAE was celebrating its 46th National Day. It’s a remarkable coincidence and one that shows the incredible progress this nation has made.”

Dr Bader said the 24-member multidisciplinary Heart Failure and Transplant team had been preparing for its fi rst heart transplant for the past two years, including attending extensive education sessions and simulating the transplant process and surgery on multiple occasions. For Emirati national Dr Jehad Al Ramahi, the opportunity to be part of the fi rst UAE heart transplant team was a career-defi ning experience. Cleveland Clinic Abu Dhabi is committed to supporting the growth and development of UAE national physicians, as part of its efforts to help build a sustainable healthcare sector.

Percutaneous coronary intervention is well-justifi ed treatment option for severe coronary artery disease

The treatment of left main coronary artery disease by percutaneous coronary intervention is associated with a smaller risk of severe cardiovascular events than coronary artery bypass grafting in the weeks following surgery. A meta-analysis of several trials and nearly 5,000 patients revealed no differences in mortality between the two treatments. The finding is signifi cant when it comes to selecting the form of treatment: percutaneous coronary intervention is less burdensome on the patient, as it does not require long-term hospitalisation and enables rapid return to work.

The prognosis of left main coronary artery disease is worse than in any other form of coronary artery disease. The treatment options include percutaneous coronary intervention and coronary artery bypass grafting. In European and American treatment guidelines, coronary artery bypass grafting is generally regarded as the fi rst-line treatment for severe left main coronary artery disease. However, some studies have suggested that percutaneous coronary intervention with drug-releasing stent implantation would also be a recommendable course of treatment in the severe form of the disease, but the evidence has been inconsistent.

A new study by investigators from the University of Eastern Finland and Oulu University Hospital compared percutaneous coronary intervention with drugreleasing stent implantation and coronary artery bypass grafting in the treatment of left main coronary artery disease. The authors pooled evidence from six comparable, randomised, controlled trials involving 4,700 people.

The researchers analysed all available randomized studies among patients who had undergone percutaneous coronary intervention or coronary artery bypass grafting, comparing their risk of all-cause mortality, major adverse cardiac and cerebrovascular events, and other cardiovascular events at time points of 30 days, one year and three years after surgery. There were no differences between the treatments as regards the risk of death, or cardiac or cerebrovascular events. Percutaneous coronary intervention patients needed repetitive interventions more often over the years.

According to the researchers, the fi ndings suggest that percutaneous coronary intervention with drug-releasing stent implantation should be more frequently considered as a treatment option for patients suffering from left main coronary artery disease. There are no differences in mortality between patients of percutaneous coronary intervention and patients undergoing coronary artery bypass grafting, and as percutaneous coronary intervention is less burdensome on the patient both from the viewpoint of quality of life and functional capacity, it is an option worth considering.

The results of the meta-analysis were published in Open Heart.

• doi: 10.1136/openhrt-2017-000638


Proteome of the human heart mapped for the first time

A healthy heart beats about two billion times during a lifetime – thanks to the interplay of more than 10,000 proteins. Researchers from the Max Planck Institute of Biochemistry (MPIB) and the German Heart Centre at the Technical University of Munich (TUM) have now determined which and how many individual proteins are present in each type of cell that occurs in the heart. In doing so, they compiled the first atlas of the healthy human heart, known as the cardiac proteome. The atlas will make it easier to identify differences between healthy and diseased hearts.

Proteins are the molecular machines of cells, in which they perform a range of functions. They are produced by the cells based on blueprints stored in their DNA. Changes occurring at the DNA or protein level can lead to disorders. For such changes to be recognized as underlying causes of heart disease, it is important to know precisely which proteins are present in the healthy heart and in what quantities.

Protein map of the heart
The first such protein atlas of the heart was recently published in Nature Communications by a research team from Munich. The scientists determined the protein profile of cells in all the regions of the heart, such as heart valves, cardiac chambers and major blood vessels. In addition, they investigated the protein composition in three different cell types of the heart: cardiac fibroblasts, smooth muscle cells and endothelial cells. In this way, the researchers were able to map the distribution of proteins in the various regions of the heart. Using mass spectrometry, they identified nearly 11,000 different proteins throughout the heart.

Previous studies had focused for the most part only on individual cell types, or they used tissue from diseased hearts.

“This approach has two problems,” says Sophia Doll of the MPIB and lead author of the study. “First, the results did not give a full picture of the heart across all its regions and tissues; and second, comparative data on healthy hearts were often missing. Our study has eliminated both problems. Now the data can be used as a reference for future studies.

“Looking at the protein atlas of the human heart, you can see that all healthy hearts work in a very similar manner. We measured similar protein compositions in all the regions with few differences between them,” says Doll. “We were also surprised to find that the right and left halves of the heart are similar, despite having quite different functions: the right half pumps oxygen-poor blood to the lungs, while the left half pumps oxygen-rich blood from the lungs to the body.

Sick vs healthy: identifying differences
In the next step, the team wanted to test whether the data from healthy hearts could serve as a control for detecting changes in diseased hearts. They compared their values with the cardiac proteomes of patients with atrial fibrillation, a very common rhythm disorder of the heart. The results indeed provided initial clues as to the cause of the disease. The tissue of the diseased hearts was most different in proteins responsible for supplying energy to the cells.

The comparison provided yet another interesting finding: Although the proteins involved in energy metabolism were changed in all the patients, those changes differed between individuals.

“These findings show us how important personalized medicine is. Although all the patients had very similar symptoms, we see from the data that a different molecular dysfunction was responsible in each case. We need to learn to recognize and treat such individual differences - especially in cardiac medicine,” says Adjunct Teaching Professor Dr Markus Krane, Deputy Director of the Department of Cardiovascular Surgery of the German Heart Centre Munich at TUM.

Nearly 11,000 proteins in less than two days
Together with his colleagues at the Department of Cardiovascular Surgery (Director: Professor Rüdiger Lange), Markus Krane has collected more than 150 tissue samplesfrom over 60 cardiac operations and forensic samples. Using elaborate cell culture methods, they were able to extract the various cell types from them. This large amount of cardiac material was a crucial factor for studying the individual heart regions so precisely. Professor Matthias Mann, director of the Department of Proteomics and Signal Transduction at the MPIB, and his team carried out extensive mass spectrometric measurements. Thanks to advances in mass spectrometry and sample processing, the researchers are lighting the way towards personalized medicine.

The team at MPIB attaches great importance to precise, repeatable and fast analytical methods. They have improved the measuring technique to the extent that an entire heart region can now be determined in less than two days - twice as fast as before. This is crucial, especially for potential use on patients.

• The data will be available in the public database MaxQB • doi: 10.1038/s41467-017-01747-2

Dubai-based cardiologist pioneers new procedure

Successful first commercial CoreValve Evolut PRO implant in MEACAT Region

Mediclinic City Hospital has announced the success of the first CoreValve Evolut PRO (*) implant in the Middle East, Africa, Central Asia and Turkey (MEACAT); making the United Arab Emirates the birthplace of yet again another technological breakthrough in the field of medicine in the region.

The procedure was performed by leading Consultant Interventional Cardiologist Dr Talib Majwal in Dubai Healthcare City. Dr Majwal successfully completed the percutaneous coronary interventional procedure where he executed it by inserting an advanced transcatheter aortic valve replacement using femoral access.

The pioneering minimally invasive procedure was conducted using the CoreValve Evolut PRO, the newest transcatheter aortic valve replacement (TAVR) system by global medical technology developer Medtronic. The selfexpanding device is intended to treat patients with severe aortic stenosis who are considered at high or extreme risk for open-heart surgery.

The Evolut PRO System offers unique value design and advanced sealing technology to enhance valve sealing performance and in turn addresses the occurrence of blood leaking through the sides of the valve. Preventing leakage in turn leads to preserving patients’ heart muscles for an extended period of time.

The Evolut PRO technology is proven to allow for faster recovery of patients as well as cause fewer complications compared to other technologies. The pioneering procedure in Dubai by Dr Majwal, took place on 23 November 2017, where the female patient was admitted, treated and discharged in a total of 48 hours.

Dr Majwal said: “Given the heavily calcified annulus of the patient, the valve was deployed without pre or post dilatation, which reflects a sufficient radial force at the inflow portion of the valve.”

The Evolut PRO is designed with an outer biocompatible pericardial tissue wrap that adds surface area contact between the valve and the native aortic annulus and hence allows it to improve valve-sealing performance in order to address the occurrence of blood leaking through the sides of the valve. The valve used in this pioneering surgery also features various clinical advantages including a self-expanding nitinol frame that helps achieve excellent hemodynamic performance and the ability to position and deploy the Evolut PRO device with greater control.

Dr Majwal stated: “The PVL (Para Valvular Leakage) was trivial given this much of annular calcification which confirms the functionality of the externally added pericardial wrap.”

In line with the manufacturing company Medtronic’s mission of contributing to human welfare, the Evolut PRO is clinically proven to lead to an improvement in the quality of life of patients, allowing patients to finally return to their daily activities, partake in sports, travel and engage in various activities that they were previously unable to engage in due to their medical condition.

Dr Majwal added: “In this procedure the valve was deployed without rapid pacing, presenting hope for patients with reduced ejection fraction.”

The procedure by Dr Majwal, a first of its kind in the MEACAT region, is considered a milestone in the evolution of minimally invasive cardiology solutions and acts as a future indicator of the role of advancement in medical technology in alleviating pain, restoring health, and improving the overall quality of life of patients in the region.

* CoreValve™ and Evolut™ are trademarks of Medtronic.



Date of upload: 15th Jan 2018

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