In spite of a relatively short history, the use of implantable cardioverter defibrillators (ICDs) has been growing by leaps and bounds. For clinicians, an ICD offers a direct means to avoid sudden cardiac death. Other reasons for the popularity of ICDs include advances in technology, above all miniaturization. More recently, new implantation methodologies such as subcutaneous ICD promise a further boost to their use. The working of ICDs are also easy to explain to patients. There is, nevertheless, one major challenge which ICDs have to still address: limitations to battery life.

Primary and secondary prevention
The principle behind an ICD is relatively straightforward, and covers two broad types of prevention: primary and secondary.
Primary prevention, which accounts for the bulk of ICD implants, refers to patients who have not yet suffered life-threatening arrhythmia.
Secondary prevention concerns survivors of cardiac arrest secondary to ventricular fibrillation or sustained tachycardia (together known as a tachyarrhythmia). Although the user group is smaller, secondary prevention makes the strongest case for an ICD.

Differentiating ventricular tachycardia and ventricular fibrillation
After implantation, the ICD continuously monitors cardiac rhythm and detects abnormalities. ICDs are programmed to recognize and differentiate between ventricular tachycardia (VT) and ventricular fibrillation (VF), after which they deliver therapy in the form of a low- or high-energy electric shock or programmable overdrive pacing to restore sinus rhythm – in the case of ventricular tachycardia, to break the tachycardia before it progresses to fibrillation. Overdrive or anti-tachycardia pacing (ATP) is effective only against VT, not ventricular fibrillation.

Defibrillation now almost 70 years old
The first defibrillation of a human heart dates to 1947, when Claude Beck, an American surgeon at Western University in Ohio, sought to revive a 14-year-old boy whose pulse had stopped during wound closure, following cardiothoracic surgery. Cardiac massage was attempted for 45 minutes, but failed to restart the heart. Ventricular fibrillation was confirmed by ECG. Beck saw no other choice but to deliver a single electric shock. This did not work. However, along with intracardiac administration of procaine hydrochloride, a second shock restored sinus rhythm. Beck’s success led to worldwide acceptance of defibrillation. However, his alternating current (AC) device (subsequently commercialised by RAND Development Corporation) was capable of defibrillating only exposed hearts.

Merging defibrillation and cardioversion
On its part, the pioneering of cardioversion (and the coining of this term) is credited to Bernard Lown, a physician at the Peter Bent Brigham Hospital in Boston. Lown merged defibrillation and cardioversion, and coupled these to portability. In 1959, he successfully applied transthoracic AC shock via a defibrillator to a patient with recurrent bouts of ventricular tachycardia (VT), who had failed to respond to intravenous procainamide. This was the first termination of an arrhythmia other than VF.
Two years later, Lown joined a young electrical engineer called Barouh Berkovitz, who had been researching a relatively safer direct current (DC) defibrillator – based on earlier work in the Soviet Union and Czechoslovakia.
Together, Lown and Berkovits pioneered the concept of synchronizing delivery of an electric shock with the QRS complex sensed by ECG, and a monophasic waveform for shock delivery during a rhythm other than VF. Their work led to launch of the first DC cardioverter-defibrillator in patients.

The implantable ICD device: parallel pathways
The Lown-Berkovits effort was confined to external devices. The concept of an implantable, automated cardiac defibrillator dates to work by Michel Mirowski at Israel’s Tel Hashomer Hospital in the mid-1960s. Mirowski moved to the US in 1968, where he joined forces with Morton Mower, a cardiologist at Sinai Hospital in Baltimore. The two tested a prototype automated defibrillator on dogs.
As often happens in science, another researcher had also been approaching the challenge on a parallel path. In 1970, Dr. John Schuder from the University of Missouri successfully tested an implanted cardiac defibrillator, again in a dog. Schuder also developed the low-energy, high voltage, biphasic waveforms which paved the way for current ICD therapy.
The first human ICD, however, was credited to Mirowski and Mower, along with Dr. Stephen Heiman, owner of a medical technology business called Medrac. In 1980, a defibrillator based on their design was implanted in a patient at Johns Hopkins University, followed shortly afterwards by a model incorporating a cardioverter. The ICD obtained approval from the US Food and Drug Administration (FDA) in 1985.

From thoracotomy to transvenous implantation
The first generation of ICDs were implanted via a thoracotomy, using defibrillator patches applied to the pericardium or epicardium, and connected by transvenous and subcutaneous leads to the device, which was contained in a pocket in the abdominal wall.
ICDs have since become smaller and lighter (thicknesses below 13 mm and weights of 70-75 grams). They are typically implanted transvenously with the device placed, like a pacemaker, in the left pectoral region. Defibrillation is achieved via intravascular coil or spring electrodes.

ICDs versus pharmacotherapy
Over the past two decades, clinical trials have demonstrated the benefits of ICDs compared to antiarrhythmic drugs (AADs). Three randomized trials, known as AVID (Antiarrhythmic versus Implantable Devices), the Canadian Implantable Defibrillator (CIDS) study, and Cardiac Arrest Study Hamburg (CASH), were initiated between the late 1980s and early 1990s in the US, Canada and Europe, respectively.
In 2000, a meta-analysis of the three studies was published in European Heart Journal.’ This found that ICDs reduced the relative risk of recurrent sudden cardiac death by 50% and death from any cause by 28%.

Use after myocardial infarction, quality of life issues
Follow-on initiatives looked at other issues. The Multicenter Automatic Defibrillator Implantation Trial (MADDIT) found that ICD benefited patients with reduced left ventricular function after myocardial infarction (MI). In 2005, the Sudden Cardiac Death in Heart Failure trial (SCD-HeFT) established that ICD reduced all-cause death risk in heart failure patients by 23% as compared to a placebo and absolute mortality by 7.2% after five years.
Quality-of-life (QoL) issues have also assisted acceptance of ICDs. In 2009, psychologists and cardiologists at universities in North Carolina and Florida concluded that QoL in ICD patients was at least equal to, or better than, that of AAD users.

Guidelines on ICD use – differences between US and Europe
Professional bodies have established guidelines on the use of ICDs and routinely provide updates. In the US, these originate from the American College of Cardiology, American Heart Association and the Heart Failure Society of America, and in Europe from the European Society of Cardiology.
Although there are many areas of agreement, some differences exist between the US guideline and the European Society of Cardiology. One difference is that in the US guideline, cardiac resynchronization therapy (CRT) is recommended in New York Heart Association (NYHA) class I patients who have LVEF ≤30%, have ischemic heart disease, are in sinus rhythm, and have a left bundle branch block (LBBB) with a QRS duration ≥150 ms. There is no similar recommendation in the European Society of Cardiology document.

The European Society of Cardiology recommendations include patients with QRS duration <120 ms. The US does not recommend CRT for any functional class or ejection fraction with QRS durations <120 ms. ICD and magnetic resonance
The biggest driver of ICD use in recent years, however, may consist of compatibility with magnetic resonance (MR) imaging. Like other metallic objects, ICDs have been contraindicated for MR. This is however set to change, after the first MR-compatible ICD (Medtronic’s Evera SureScan) received FDA approval in September 2016.
The relevance of MR was researched in significant depth by a team at Pittsburgh’s Allegheny General Hospital, led by Dr. Robert Biederman, medical director of its Cardiovascular MRI Center. The study covered patients in three implantable cardiac device case groups, namely cardiovascular, musculoskeletal and neurology.
The findings were conclusive. In 92-100% of cardiac and musculoskeletal, and 88% of neurology cases, MR exam provided value for the final diagnosis. In 18% of neurology cases, the MR exam altered the diagnosis entirely. In the bulk of cases, said Dr. Biederman, the information could not be obtained with cardiac catheterization, echo or nuclear. In addition, patients were saved from a biopsy of the heart muscle, with all its attendant risks.

The launch of leadless, subcutaneous ICDs
Meanwhile, other factors too are driving development of ICDs. One of the biggest shortcomings of ICDs is the need to run an electric lead through blood vessels. These are susceptible to breakages.
In 2012, Boston Scientific received FDA approval for the world’s first leadless, subcutaneous ICD (S-ICD). Rather than leads, the device uses a pulse generator and electrode beneath the skin with a shocking coil implanted under the left arm. A second-generation S-ICD system, branded Emblem, was approved in 2015.
Nevertheless, S-ICDs have drawbacks. Lacking a lead in sufficient contact with the heart, they cannot pace patients out of bad heart rhythms. S-ICDs are also not MR compatible.

The challenge of battery life
Many experts believe that the principal challenge facing ICDs is battery life. According to the Mayo Clinic, batteries in an ICD ‘can last up to seven years.’ It recommends monitoring battery status every 3-6 months during routine checkups, and states when the battery is ‘nearly out of power,’ the old shock generator needs to be ‘replaced with a new one during a minor outpatient procedure.’
Nevertheless, there has recently been some attention about the risk of the latter. In 2014, a research team led by Daniel B. Kramer of Harvard Medical School studied 111,826 patients in the US National Cardiovascular Data Registry (NCDR) who had end-of-battery life ICD generator replacements. They found more than 40% of patients died within five years of ICD generator replacement, and almost 10% within a year. The authors, however, emphasized that atrial fibrillation, heart failure, and left ventricular ejection fraction were independently associated with poorer survival as were noncardiac co-morbidities (chronic lung disease, cerebrovascular disease, diabetes and kidney conditions). What was needed, they concluded, would be a non-ICD control group.
A recent article in the British Medical Journal’ (BMJ) suggests that battery life needs to be extended to 25 years or more to avoid the risks associated with replacement. The author, Dr. John Dean, a cardiologist at Royal Devon and Exeter Hospital in the UK, points out that 1-5% of battery replacements also carry infection risk for patients.

The future: patient needs and superior waveforms
Ultimately, it is patient needs which will drive the next wave in ICD development. While the medical devices industry has focused on device miniaturization, longer battery life is also clearly a priority. Indeed, a 2004 study in Pacing and Clinical Electrophysiology’ found 90% of ICD patients saying they would trade off smaller ICDs for longer-lasting models.
ICD manufacturers are also looking at developing more sophisticated cardioversion/defibrillation waveforms in order to reduce the threshold of defibrillation, and thereby reduce pain and discomfort.

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Due to the increased number of monitored parameters available today and the need to reduce healthcare costs, algorithms must both be more sensitive and prevent more false alarms than in the past. Cardiac Care Units are always so busy that the large number of false alarms generated every day by monitoring systems can become a serious issue for healthcare personnel. This large number of false alarms induces so-called Alarm Fatigue’: in a nutshell, healthcare professionals, tired of wasting time in silencing false alarms, not only lose trust in their monitoring system, but tend to ignore possibly real alarms.

Mortara VERITAS^TM covers a large variety of diagnostic fields: from automatic resting ECG interpretation, to ambulatory Holter monitoring, to real-time algorithms specifically designed for bedside monitors and central stations, largely employed in Coronary Care and Intensive Care Units. Integrated in all Mortara product lines, VERITAS is constantly updated with new features and improved specificity and sensitivity.

Having obtained levels of sensitivity and specificity in line with major manufacturers is not enough to fight Alarm Fatigue. That is why much attention and investment have been devoted to reducing false alarm rates without affecting sensitivity. The updated VERITAS Arrhythmia algorithm defines a new standard in Alarm Fatigue management: up to 60percent less false alarms for lethal arrhythmias when compared to the most common algorithms available on the market, resulting in vast improvement of reliability of the systems on which it is installed.

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Medical tourism refers to people who travel overseas for obtaining treatment. In the past, it referred to (wealthy/privileged) patients from developing countries who visited medical centres in industrialized countries to get treatment not available at home.
However, the situation has since reversed, in certain cases dramatically. Medical tourism now typically refers to patients from industrialized countries who travel to poorer countries for lower priced, or more quickly available (and in some cases, superior) treatment. Top medical tourist destinations in this respect include India and Thailand as well as Costa Rica, Mexico and the Gulf.

Medical tourism and health tourism
Some studies do not consider medical tourism to include cosmetic and wellness tourism – with dental treatment also viewed as a cosmetic procedure. This, larger group is often referred to as health tourism.
Market revenues for a major medical tourism destination, Thailand, include a relatively large number of cosmetic surgery procedures. This segment also includes a multitude of places in south America, with the industry’s maturity fed by bustling local demand. For example, according to the Sociedad Boliviana de Cirugia Plastica y Reconstructiva’, over 70percent of middle and upper class women in the country have had plastic surgery.

India leads in higher-end procedures
Conversely, at the other end, if only surgical procedures for overseas patients are included, India leads the global medical tourism market.
Consultants McKinsey estimated 180,000 medical tourists were treated at Indian facilities in 2004 (up from 10,000 just five years earlier). Arrivals have since been rising sharply and are estimated to have reached 250,000 in 2012, contributing 3 billion USD in revenues. This is effectively about 30percent of the global market, estimated for the year at 10.5 billion USD by Transparency Market Research.
India has proven to be a preferred destination for US and UK patients, in particular, because of the use of English in most professional interactions, as well as the fact that both countries have a large number of Indian-origin physicians. Indeed, the US government’s top medic, the Surgeon General, is Vivek Hallegere Murthy, a 40-year old Indian.
India stands out as an interesting destination in another respect. Its massive generic drugs industry provides post-operative medicinal treatment at prices well below the West.

Market drivers: cost, waiting times, accreditation
Key factors driving medical tourism from the West to developing countries include the high cost of healthcare and increasing waiting times for certain procedures. Insurance in several countries often does not cover 100percent of the costs of common age-related requirements such as a knee or hip replacement, or limits the choice of the prosthetics, or the surgeon and facility.
Accreditation of top hospitals in medical tourism destinations has also fuelled demand. The oldest international accrediting body is Accreditation Canada, which has accredited hospitals in about a dozen countries.
The best known accreditation group, however, is Joint Commission International (JCI) in the US. JCI was set up in 1994 to provide international clients education and consulting services, and several international hospitals now see accreditation as a way to attract American patients. JCI is an independent private, not-for-profit organization that seeks to develop nationally and internationally recognized procedures to help improve patient care and safety. It advises hospitals to meet standards for patient care and then accredits hospitals meeting the standards.
A British scheme, QHA Trent Accreditation, is an active independent holistic accreditation scheme. Another is GCR.org, which monitors success metrics and standards of almost 500,000 medical clinics worldwide.
These schemes vary in quality, size and cost to hospitals making use of them.
Increasingly, hospitals are looking towards dual international accreditation, perhaps having both JCI to cover potential US clientele, and Accreditation Canada or QHA Trent for Canadian and British patients.

Indian price advantage boosted by quality, innovations
Practically all surgery procedures performed in medical tourism destinations cost a fraction of what they do in industrialized countries. For example, while a liver transplant in the US costs about 300,000 USD ( Euro 280,000), the figure in India is 50,000 USD ( Euro 47,000). Open heart surgery in India costs between 3,000 ( Euro 2,800) and 10,000 USD ( Euro 9,400), compared to 70,000 USD ( Euro 65,500) in the UK and 150,000 USD ( Euro 140,000) in the US.
Such figures acquire added value when one reviews the conclusions of a Harvard Business School (HBS) study in November 2013, comparing data on angioplasty in the US versus India. The study found that one in 200 US angioplasty patients required emergency surgery, with half of them dying, while only two of 40,000 angioplasty patients at India’s CARE Hospitals required emergency surgery, with just one death in the OR since the hospital’s inception in 1997.
The HBS study also studied other Indian hospitals and interventions, finding them to be on par or better than their US counterparts – for example, Apollo Hospitals with knee, coronary and prostate surgery as well as for infections related to the operating theatre and catheters, Narayana for coronary artery bypass procedures, Deccan for peritoneal dialysis and Aravind for ophthalmology.
The HBS review noted India was not simply an improver but an innovator too, for example Indian doctors pioneered the beating-heart method of surgery, where they operate without shutting patients’ hearts down via a heart-lung machine, leading to fewer complications, shorter hospital stays and quicker recovery.

New segment of intra-Third World medical tourism
While much attention remains on Western medical tourists, one of the fastest growing market segments consists of patients within the Third World, who travel to more advanced developing countries. India again is at the top of the list. In early Dec 2016 / Jan 2017, for instance, it was announced that Iman Abdulati, a 36-year old woman weighing half a tonne, was to be flown to India from her home in Egypt for bariatric surgery.
Such cases have drawn considerable attention for other, political reasons.
Pakistani patients with severe conditions requiring top-notch treatment are a routine media fixture in India. For example, in September 2016, Pakistan’s Express Tribune’ featured the case of Abdul Basit, an 11-year old boy who had been suffering from the rare condition known as Crigler-Najjar syndrome and went for a liver transplant to India. Two years previously, after complications, the wife of former Afghan President Hamid Karzai gave birth to a girl at Fortis Hospital in New Delhi.
In August 2016, The Diplomat’ reported India had emerged as one of the fastest growing global healthcare destinations, particularly for patients from conflict countries like Afghanistan, Iraq, Yemen, Sudan, the Democratic Republic of Congo (DRC), and Somalia, attracting close to 400,000 foreign patients a year, half from war-ravaged countries.
The selection of India as preferred medical tourism destination is being officially sanctioned. In 2004, BBC News’ reported that ‘India was chosen as the place’ for sending sick patients from Tanzania unable to be treated at home, after the Tanzanian government ‘did a comparative analysis of health facilities in South Africa, India and western European countries.’ In 2007, Companion Global Healthcare teamed up with hospitals in India (as well as Thailand and Singapore).

China lags India due to egalitarian healthcare model
Due to a variety of reasons, the other Asian behemoth, China, has a much less mature medical tourism sector. WHO figures show hospital bed densities far lower in India, at just 9 per 10,000 people (making a total of roughly 1 million beds) compared to 42 in China (about 5 million). However, the higher share of private beds in India (40percent against 6.5percent in China) means that India has slightly more private beds – about 400,000, against China’s 325,000.

More than anything, India’s lead over China in medical tourism symbolises its top-down approach to healthcare, in contrast to China’s bottom-up one which first aims at providing top quality healthcare to local Chinese. As a result, China does not provide good healthcare for its middle and upper class. For Britain’s Guardian’, poor rural Chinese were curiously’ better off than their city cousins.’ The Guardian’ contrasted this with India, where ‘many city-based healthcare facilities are excellent….’ This higher-end focus provides India with more medical tourists than China.

Hospital budgets: the sky’s the limit
There are now at least a dozen major private hospital groups in India. Leading groups (with 20-50 facilities, and 2,500-8,000 beds) include Apollo, Max Healthcare, Fortis, Escorts Healthcare, Wockhardt and the Manipal Group. Many of the above (as well as newcomers from cash-rich Indian conglomerates such as Reliance, the Hindujas, Sahara and ITC) are also pursuing the new concept of Medicities, involving suburban developments dedicated wholly to integrated hospital facilities.
The procurement budget of such groups is not insignificant. Apollo’s annual spending on medical equipment, for example, has been close to 200 million USD in recent years. Such budgets allows cash-rich Indian hospitals to procure state-of-the-art equipment – from Da Vinci robots and stereotactic laser surgery to wide-bore 3T Silent Scan MRIs.
Nevertheless, as far as spending is concerned, Indian hospital groups face several challenges in the coming years, especially from the cash-flush Gulf.

US hospitals lead Gulf partnerships
US hospitals are at the forefront of partnerships in the Gulf. One of the key reasons was the difficulty for medical tourists from the region to obtain US visas after 9/11, according to the American Hospital Association.
Key US partners of Gulf hospitals include Johns Hopkins Medicine, which has an agreement since 2006 to partner the General Health Authority for Health Services in the UAE. It also manages the 400-plus bed Tawam Hospital in Abu Dhabi and an affiliated centre offering state-of-the-art molecular imaging services. Johns Hopkins also has alliances with King Khaled Eye Specialist Hospital in Saudi Arabia.
Another example is the Cleveland Clinic, which is affiliated with the International Medical Centre in Jeddah, Saudi Arabia, and is a strategic partner at the 360-bed, multi-specialty Cleveland Clinic Abu Dhabi Hospital in the UAE.
Elsewhere in the UAE, Methodist International manages the operations of Burj Dubai Medical Centre as well as clinics in Dubai, while Partners Harvard Medical International is a key strategic collaborator with Dubai Healthcare City (which explicitly seeks to attract foreign medical tourists).

Education and training focus in Gulf
Many of these alliances are increasing their focus on education and training. For example, the Partners-Dubai Healthcare City has added a high profile unit called Harvard Medical School Dubai Center Institute for Postgraduate Education and Research, while in 2014 Johns Hopkins signed a partnership with oil major Aramco to provide medical education and training in Saudi Arabia.
Qatar, too, has sought US partners. The Weill Cornell Medical College was in fact one of the earliest ventures, established in 2001 as a partnership between Cornell University and the Qatar Foundation for Education, Science and Community Development. It aims to provide medical education and cutting-edge research.
Ironically, the focus on training might hit a traditional source of physicians in the Gulf especially hard, namely Indians who would be replaced by skilled locals.

4D cardiac imaging, which generates a three-dimensional motion picture of a beating’ heart, offers cardiologists a revolutionary new tool. Indeed, the ability to acquire images across all phases of a heartbeat cycle is the only way to meaningfully visualizing morphological anomalies and make an authentic assessment of cardiac function.
Traditionally, ultrasound has been a preferred modality for 4D cardiac imaging. However, 4D cardiac MRI (known formally as cardiovascular’ MRI) has been gaining ground. Coupled with MRA (magnetic resonance angiography), it enables cardiologists to view images of the heart, major blood vessels and blood flow.

The novelty of 4D
4D cardiac imaging is a recent technique. Its novelty is best illustrated by an editorial in The Journal of the American College of Cardiology’. The editorial, published as recently as 2009, observed the role of ‘2- and 3-dimensional coronary mapping’ in high-resolution digital imaging.
Major imaging vendors now offer real-time 3D/4D imaging products – across all modalities, PET/CT, MRI and ultrasound. However, the bulk of 4D applications so far have involved ultrasound – especially for cardiac imaging. This may be changing, with increased attention, above all, to MRI.

Ultrasound’s longer legacy
One reason for ultrasound’s pole position in 4D consists of a longer legacy. In the early 1980s, researchers from Duke University in the US reported that though MRI was faster, ultrasound offered the closest achievement of ‘3D real-time acquisition,’ or what is now called 4D.
Technical standardization bodies also moved quickly to endorse and drive the take-up of 4D ultrasound. In 2008, the DICOM (Digital Imaging and Communications in Medicine) initiative approved Supplement 43 which addressed the exchange of real time 3D ultrasound datasets between different vendors. In 2011, IHE (Integrating the Health Enterprise) published a White Paper on 3D/4D imaging workflow.

Early adoption of 4D ultrasound by cardiologists
On their part, cardiologists were enthusiastic early adopters of 3D (and later 4D) ultrasound. The IHE’s White Paper mentioned above was written by its Cardiology Technical Committee. Another factor strongly favouring ultrasound was mobility, since small ultrasound devices could be transported to the patient.
During this period, competing imaging modalities seemed to stand little chance as far as cardiology was concerned.
Computerized tomography (CT) was dismissed since it required cardiologists to use complex post-processing techniques in order to visualize the bearing heart. Cardiac magnetic resonance imaging (MRI) was considered relatively expensive, with limited availability and requiring specialized training.

GE’s cSound: industry seizes the ultrasound opportunity
Industry was quick to seize the ultrasound opportunity. In 2015, healthcare technology giant GE released new software for its ultrasound machines called cSound. cSound-equipped machines intelligently process data being returned by an ultrasound signal, analysing almost 5 gigabytes of data every second, and then filtering it on a pixel-by-pixel basis via algorithms which produced real-time 4D views. This allowed cardiologists to observe how blood swirls around clots in arteries, measure blood leakage around the valves and assess damage. cSound reinforced GE’s presence at the cutting edge of ultrasound, reinforcing a technique patented by the company in the early 2000s and known as Spatial Temporal Image Correlation (STIC). STIC allowed for the quick capture of a full fetal heart cycle beating in real-time.

4D PET/CT and MRI turn to diagnostic oncology
Proponents of 4D PET (positron emission tomography)/CT and MRI were however not sitting by idly. Rather than cardiology, they turned their attention to other specialities, above all oncology where 4D offered huge potential in diagnostics.
4D PET, for example, seemed unmatched in characterizing solitary pulmonary nodules, while 4D CT offered a revolutionary approach in oncology – such as gating tumours and determining treatment margins. On its part, 4D MRI demonstrated a superiority to CT in soft-tissue imaging and in cases where radiation exposure was a concern.

From 4D to 5D imaging
As of now, the focus in diagnostics is to combine the anatomical with functional or molecular imaging, in order to make precise assessments of biological and metabolic pathways. Key modalities include PET with radio-labelled tracers for molecular imaging, and MRI using molecular markers for functional imaging. The molecular/functional enhancement is often referred to as 5D, and to its proponents, offers hope in increasing the specificity and sensibility of diagnostics.
At some stage in the future, it is inevitable that cardiologists will see the virtues of 5D imaging for diagnostics.

The challenge from multi-detector ultrasound scanners
Meanwhile, cardiac ultrasound faces competition in certain applications from other imaging modalities.
In recent years, multi-detector CT scanners seem to offer considerable promise, particularly for non-invasive detection of coronary artery disease and higher flexibility for analysis and visualization of individual vessels. These images, nevertheless, continue to require special processing and rendering tools for assessment of segmental narrowing or occlusions.

The growing promise of 4D cardiac MRI
Rather than CT, cardiac (or cardiovascular) MRI in 4D seems to have rapidly become the principal technology paradigm challenger to ultrasound.
Cardiac MRI scanners do not use open’ magnets which face serious limitations in the case of moving objects – such as a beating heart. The magnet strengths most widely used for cardiac MRI are 1.5T and 3T – although the latter, in some conditions, require software to cancel artifacts. Higher strength magnets are, however, the technology of choice in studying conditions such as aortic construction.
What is also a key advantage of cardiac MRI compared to CT is its lack of ionizing radiation, high spatial resolution and the ability to provide a functional cardiac assessment in one scan.

The technique of 4D cardiac MRI is closely based on traditional MRI. However, it is optimized for use in the cardiovascular system in real time, principally via ECG gating and rapid imaging sequences. This results in acquisition of images at each stage of a sequence of cardiac cycles, and functional assessment of the heart. Blood, in such sequences (technically known as balanced steady state free precession or bSSFP), appears bright due to contrast with blood flow. As a result, 4D cardiac MRI makes it possible to discriminate in a relatively easy fashion between the myocardium and blood.

With and without contrast agents
Cardiac MRI typically uses several approaches to make a comprehensive assessment of the heart and cardiovascular system. Some of the most promising applications include the ability to visualize heart muscle fat or scar in high resolution without the need for a contrast agent. This is based on a technique called spin echo’, which shows blood as black, and identifies myocardium abnormalities through differences in intrinsic contrast.

On the other hand, contrast agents like gadolinium-DTPA can be used for applications such as infarct imaging – where healthy heart muscle appears dark, and infarction areas show in bright white. Contrast agents in cardiac MRI have also proven their worth for treatment of coronary artery narrowing, which starves the heart muscle of oxygen. The contrast agent reveals any transient perfusion defects from artery constriction. Knowing about the presence of such a defect assists in guiding interventional procedures.

Image quality, superior access to anatomical structures
Cardiac MRI provides images of superior quality, accuracy and versatility, alongside access to anatomical structures which are tough to achieve with ultrasound. Examples of these include congenital heart anomalies as well as anatomical changes after surgical interventions.
The latest generation of MRI scanners allow for acquiring high-resolution isotropic data with detailed anatomical information and identical resolution in all three dimensions. Frontier areas of research for 4D MRI include qualitative and quantitative flow pattern analysis in mice with aortic constriction.

Detecting hemodynamic alterations with 4D MRI
At present, one of the most promising cardiac applications for 4D MRI consists of the detection of haemodynamic alterations. The incorporation of pharmacological stress procedures allows for enhanced detection of alterations in heart function during stress-induced ischemia.
In April 2014, a team at Northwestern University reported that 4D flow MRI would help better understand altered hemodynamics in patients with cardiovascular diseases and improve patient management and monitoring of therapeutic response. Their study, published in Cardiovascular Diagnosis and Therapy’, noted that these hemodynamic insights could also lead to new risk stratification metrics in patients and impact upon individualized treatment decisions in order to optimize patient outcomes.

Diagnostics and prognosis of heart events
Cardiac MRI is also being seen as a diagnostic tool to predict heart events. In May 2016, a study led by John P. Greenwood from the University of Leeds in Britain noted that it was ‘a better prognosticator of risk for serious cardiovascular events than SPECT, regardless of a person’s risk factors, angiography results, or initial treatment, and that it would be a powerful tool for ‘the diagnosis and management of patients with suspected coronary heart disease.’ The serious events, assessed over a 5-year period, included death, myocardial infarction/acute coronary syndrome, unscheduled coronary revascularization, or hospitalization for stroke, transient ischemic attack, heart failure, or arrhythmia.
The study was based on a multi-parametric cardiovascular MRI protocol, and performed on a 1.5T MRI scanner and published in the Annals of Internal Medicine’. It was formally known as the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease (CE-MARC), and billed as ‘the largest prospective comparison of cardiovascular MRI and nuclear myocardial perfusion imaging (MPI) with SPECT’ with X-ray angiography used as the reference standard.

Genotoxicity poses calls for caution
There have, nevertheless, been some calls for caution due to the chance of genotoxic effects of cardiac MRI scanning.
In October 2011, a study by researchers at Seoul National University in South Korea, assessed high-field intensity 3T clinical MRI scans in cultured human lymphocytes in vitro and ‘observed a significant increase in the frequency of single-strand DNA breaks following exposure to a 3T MRI.’
In June 2013, another study on cardiac MRI in European Heart Journal’ reported similar conclusions, this time in vivo. The study, by researchers from University Hospital Zurich, prospectively enrolled 20 patients, and found a ‘significant increase in median numbers of DNA DSBs in lymphocytes induced by routine 1.5T’ MR scanners. The study also made a recommendation, urging cardiac MRI to ‘be used with caution and that similar restrictions may apply as for X-ray-based and nuclear imaging techniques in order to avoid unnecessary damage of DNA integrity with potential carcinogenic effect.’

Finns call for further studies
Nevertheless, there has been no study so far on the genotoxic effects of MRI compared with those of CT scans. In addition, cardiac MRI risk research has been based entirely on cell level experiments with no conclusive and definitive evidence of actual cancer risk. This is in direct contrast to the link between ionizing radiation and cancer risk.
MRI is therefore still considered by its proponents as the safest alternative.
Indeed, weeks after the University Hospital Zurich study, Finnish researchers published a riposte, again in the European Heart Journal”, arguing that the ‘cellular mechanism’ of how cardiac MRI induced DNA damage was unknown ‘and may be different from that of radiation.’ They concluded that it was ‘obvious that further larger studies are warranted before any restrictions’ were imposed on the use of cardiac MRI.