40 years on from the world’s first successful heart transplant the technique has been honed but supply remains an obstacle
On the 2nd of December 1967, South African surgeon, Christian Barnard, made history when he successfully transplanted the first heart, from a road traffic accident victim, Denise Duvall, into a patient, Louis Washkinsky.
The operation spurred an international sensation and was soon followed by other institutions across the globe. In 1968 the first transplant was conducted in the UK and since then almost 6,000 patients have reaped the benefits of the pioneering surgery.
A cardiomyopathy patient from Papworth Hospital (London, UK) who recently underwent the surgery said: “I have been literally given a new lease of life by my heart transplant and there is no amount of thanks that can really convey my appreciation and gratitude to my donor and their family.“
Due to medical advances in drugs and surgical techniques, heart transplant patients can expect to live for longer than ever before. However, the problem remains that the number of transplants that can be performed is tightly constrained by the shortage of donors. The average waiting time in the UK on the heart transplant list for an adult is 103 days, while it is 143 days for a child; unfortunately many people die while waiting.
UK Transplant’s Managing Director Chris Rudge said: “The heart is synonymous with kindness and when Dr Barnard showed that even this most symbolic of organs could be given by one person to another, it captured the public imagination. Over the years the operation has become more and more successful. With better drugs and improved techniques, survival rates are improving all the time. In fact the greatest obstacle we face in providing more transplants for the patients who need them is without a doubt the shortage of donated organs. I would encourage everyone who would like to pass on this generous gift of life to others to discuss their wishes with their families and join the NHS Organ Donor Register.”
You can find out more about organ donation by contacting the Organ Donor Line on 0845 60 60 400 or visiting www.uktransplant.org.uk.
Source: www.uktransplant.org.uk
INTENSIVE trial gets the go ahead
Trial: INTENSIVE
Patients (n): 900
Center: University at Buffalo
Drugs trialled: Insulin glargine and insulin glulisine
A 2-year clinical trial funded by sanofiaventis will investigate the cardioprotective properties of insulin. Led by Paresh Dandona from the University at Buffalo (NY, USA), the Intensive Insulin Therapy and Size of Infarct as a Validated Endpoint by Cardiac MRI (INTENSIVE) trial will involve 600 patients from 90 centers in the US and Latin America. Patients partaking in this trial will be treated with two forms of insulin – insulin glargine and insulin glulisine.
This trial, which is to determine whether insulin can limit heart-tissue damage during a heart attack, is based on a pilot trial published in 2004. In the pilot trial 32 patients received low-dose insulin and it was found that 48 h after a heart attack, levels of C-reactive protein and serum amyloid A, which are two critical markers of inflammation, were reduced by 40 and 50%, respectively. In addition, levels of three other inflammatory factors were also significantly reduced in patients who received insulin, compared with those who did not.
“The markers of myocardial damage that we measured were reduced significantly,” said Dandona, who was also involved in the pilot trial. “We are excited to learn more about the potential cardioprotective benefits we may discover with insulin. We think insulin will improve blood flow during a heart attack and help limit damage to heart tissue.”
One of the main reasons for the lack of success in this area to date is that any benefits of insulin were confounded by simultaneously increasing glucose levels, because patients were given too much glucose. Thus, in this trial the patients will be given relatively higher concentrations of insulin compared to glucose. In addition, the treatment will be tailored to those patients with diabetes who would benefit most – patients with glucose levels more than 140 mg/dl on admission and who have an anterior wall heart attack.
Co-principal investigator, Richard W Nesto explains: “This is the first largescale trial that will be conducted using this individually tailored treatment strategy in patients who are undergoing a coronary procedure (PCI) for their heart attack.”
Source: University at Buffalo: www.buffalo.edu
Advanced scanning technology becomes more widely available
A new 64-slice cardiac scan is introduced to the diagnostic armamentarium at St Mary’s Medical Center (CA, USA)
One of the most advanced coronary artery disease (CAD) diagnostic procedures available is now offered at the St. Mary’s Medical Center (SMMC) (CA, USA). The 64-slice scan captures highresolution, 3D images of heart anatomy, the coronary arteries and the surrounding chest cavity. This allows doctors to distinguish between calcified plaque and soft plaque that may be at risk of rupturing and causing heart attacks.
CAD is the leading cause of death in the USA. Approximately half a million Americans have a heart attack every year and almost half of the attacks are fatal.
Typically invasive coronary angiography, due to the nature of the procedure, is reserved for patients with advanced heart disease, that is, patients with greater than 70% blockage. Consequently, patients with less blockage are often left undiagnosed, although they may still be at high risk of heart attack.
The new technology is able to both identify patients with CAD, while reassuring those patients without CAD that they have a clean bill of health.
“The 64-slice CT scan is proving to be a powerful tool in the fight against coronary artery disease,” said Peter Teng, director of the Cardiac CT program at SMMC. “This gives us the ability to diagnose patients earlier and provide a high resolution image with accurate detail into the heart, chest cavity and arteries of most people.”
Source: www.stmarysmedicalcenter.org
The dangers of cigarette smoke & alcohol on the heart
Study shows that smoke inhalation cancels out beneficial health effects of moderate alcohol consumption
It seems to be common knowledge that one glass of red wine a day is good for the heart but it may not be this straightforward. A team of researchers from the University of Alabama at Birmingham (AL, USA) have discovered that any beneficial health effects of moderate alcohol consumption may be wiped out if combined with smoking or breathing in second-hand smoke.
Led by Scott Ballinger, the researchers discovered that mice exposed to smoky air and fed a liquid diet containing ethanol had a 4.7-fold increase in artery lesions, which is a major sign of advancing cardiovascular disease, compared with mice that breathed filtered air and had a normal diet.
In addition, mice solely exposed to smoky air had a 2.3-fold increase in artery lesions compared with mice that breathed filtered air, and mice fed the ethanol-only diet had a 3.5-fold increase in the lesions compared with mice fed a normal diet.
The study highlights an urgent need to investigate the negative biological impact of single or multiple risky behaviors, as well as the full effect of environmental hazards, such as second-hand smoke.
Ballinger stated: “our study shows that exposure to cigarette smoke when combined with alcohol consumption caused the greatest degree of cardiovascular disease development compared to either action or exposure alone.”
Another author of the study, Shannon Bailey, commented: “Because moderate alcohol consumption is commonly thought to be cardioprotective, these findings are important for smokers and nonsmokers alike in terms of what you should and should not do to protect their health.”
The team also examined other signs of advancing cardiovascular disease, such as DNA damage and oxidative stress in key heart tissue, and found that as with the artery lesions the combination of smoking and drinking nullified any potential heart benefit from drinking alcohol by itself.
Source: Cakir Y, Yang Z, Knight CA et al. Effect of alcohol and tobacco smoke on mtDNA damage and atherogenesis. Free Radic. Biol. Med. 43(9), 1279–1288 (2007).
One more reason to eat your greens
Nitrate found in green leafy vegetables, may limit heart attack damage
A study has found that the consumption of green leafy vegetables may minimize tissue damage that results from a heart attack. Researchers from the Albert Einstein College of Medicine of Yeshiva University (NY, USA) surmise it is the chemical nitrite that helps keep the heart healthy. Nitrite is found in green vegetables and this could be the reason for the apparent heart-healthy Mediterranean diet as people living in these countries consume far more of these vegetables than countries such as the UK and USA.
Study author David Lefer explains: “Recent studies show that administering nitrite to animals, either intravenously or orally, can greatly limit the damage caused by a heart attack and the stress to tissue that follows due to reperfusion– the return of blood to oxygen-starved heart muscle. We wondered if feeding animals much lower levels of nitrite and nitrate – equivalent to what people can readily obtain from their diets –could also provide protection from heart-attack injury.”
It was discovered in 1986 that nitric oxide, which can be produced by nitrite or nitrate, is made by cells lining healthy arteries and plays a key role in cardiovascular health by dilating arteries and helping blood flow. It is also known that damage to the artery lining impairs nitric oxide production and leads to cardiovascular disease.
During a heart attack, hearts actually have a back-up pathway for making nitric oxide. Once decreasing oxygen levels have been recognized, enzymes in the heart muscle convert stored nitrite into nitric acid, which helps to minimize tissue damage.
“This new appreciation of the health benefits of nitrite and nitrate is ironic,” says Lefer. “They’ve traditionally been regarded as toxic because they tend to form chemicals called nitrosamines, some of which are carcinogenic. But recent research has found no convincing evidence that nitrite and nitrate pose a cancer risk.”
“Our study suggests that building up nitrite stores in heart muscle could spell the difference between a mild heart attack and one that causes lasting heart damage or death. And since nitrite also accumulate in the brain, they could potentially help minimize the damage from strokes as well,” concludes Lefer.
Source: Bryan NS, Calvert JW, Elrod JW, Gundewar S, Ji SY, Lefer DJ. Dietary nitrite supplementation protects against myocardial ischemia-reperfusion injury. Proc. Natl Acad. Sci. USA DOI: 10.1073/pnas.0706579104 (2007).
FDA approval for Epic stented tissue valve with anticalcification technology
Device: Epic™ valve
Manufacturer: St Jude Medical Inc.
Indication: Replicates normal valve function and guards against tissue calcification
St Jude Medical Inc. (SJM) recently received US FDA approval of the Epic™ valve, its stented tissue valve with Linx™ anticalcification technology.
Mechanical heart valves are durable and should last a lifetime but require their recipient to take anticoagulants whereas bioprosthetic heart valves, composed of natural tissue, do not require anticoagulants but do not last as long.
Valve durability is a key consideration for physicians; the main complications that occur with bioprosthetic heart valves are tissue calcification and mechanical stress, so SJM have combined their Biocor™ valve design with an innovative anticalcification process.
Glutaraldehyde, calcium and phospholipids all play an important role in the calcification of bioprosthetic valves; Linx™ technology, developed and patented by Robert Levy, works to combat the calcification process and has been shown to be very effective in preventing leaflet calcification in sheep mitral valve replacement models.
The FDA have given the Epic Valve approval after a clinical study evaluating the safety and efficacy, as measured by hemodynamics and patient ability to perform everyday activities, as measured by the New York Heart Association (NYHA) functional classification system and adverse effects.
“Enhanced durability, combined with a design that facilitates the implant procedure, makes the Epic Valve an ideal prosthesis,” said Vibhu Kshettry, MD, director of Cardiac Surgery at the Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis (MN, USA), and a principal investigator in the Epic clinical study.
Source: www.sjm.com
New technology to model atherosclerosis
A new device has just been developed to model the behavior of human vascular cells used to aid potential drug screening
A collaborative team of researchers at the University of Virginia (VA, USA) have invented a device, which models the early signs of artherosclerosis that can be used to help the pharmaceutical industry identify and screen potential new drug compounds.
The HemoShear™ 2.0 device allows researchers to observe the behavior of human vascular cells under a variety of blood flow conditions that occur in the human body, in a model outside the body.
Artherosclerosis is a disease that causes narrowing and hardening of arterial blood vessels and can lead to heart attack or stroke. It occurs at locations in the arteries where blood flow is compromised, and the resulting shear-stress in the vessels causes detrimental changes to the endothelial cells that line the blood vessels and smooth muscle cells in the blood vessel walls.
Human endothelial cells and smooth muscle cells are plated on a synthetic elastic lamina, to mimic a real blood vessel wall, and different blood flow patterns, observed in the human circulation using MRI, were applied to the endothelial cells. This models the artheroprone and artheroprotective shear stresses that are seen in vivo and the cells mimic the early phases of the diseased artery.
Brian Wamhoff, assistant professor in the Department of Medicine (Cardiovascular Division) commented, “Research has been conducted wherein human cells are isolated to observe behavior patterns, but there are no available models that allow one to accurately study the intricate communication between endothelial cells and smooth muscle cells in a setting that mimics hemodynamic blood forces in the body.”
A provisional patent has been filed for HemoShear 2.0. The research that HemoShear 2.0 made possible was spearheaded by a biomedical engineering graduate student, Nicole Hastings, and has been accepted for publication in the American Journal of Physiology – Cell Physiology.
Source: www.virginia.edu
Low testosterone levels linked to increased cardiovascular risk in men
Latest study findings from the UK indicate a possible link between low testosterone levels in otherwise healthy men and an increased risk for cardiovascular and all-cause death
“The magnitude of the relationship of endogenous testosterone levels with cardiovascular disease (CVD) mortality was comparable in size – but independent of – the classical risk factors such as blood pressure and cholesterol,” noted lead author Kay-Tee Khaw of Addenbrooke’s Hospital (Cambridge, UK).
Khaw and colleagues conducted a nested case–control study of 11,606 men aged 40–79 years who were surveyed between 1993 and 1997 and followed- up in 2003. Testosterone levels were analyzed in men who were free from known CVD at the beginning of the study, of whom 825 subsequently died; 1489 were still alive at follow-up and served as controls.
Researchers found that mean testosterone levels were significantly lower in those men who died of any cause (CVD or cancer) compared with controls, at 15.6, 15.8 and 15.7 versus 16.7 nmol/l, respectively (p < 0.001). Furthermore, testosterone concentration was inversely related to all-cause mortality and CVD death. For example, men with testosterone levels in the highest quartile (19.6 nmol/l) had a 41% lower relative risk for all-cause mortality compared with those whose levels were in the lowest quartile (12.5 nmol/l).
Multivariable analysis using testosterone as a continuous variable revealed that, for every 6 nmol/l increase in serum testosterone, all-cause mortality decreased by 14% (OR = 0.86; p < 0.001). The effect size was similar for CVD death (OR = 0.83; p < 0.01), and changed little after adjustment for CV risk factors and sex hormone-binding globulin, or after the exclusion of deaths within 2 years.
Khaw speculated that testosterone supplementation could reduce CVD and all-cause mortality risk in men with low endogenous levels. However, he cautioned that long-term clinical trials are needed to investigate this, particularly in light of recent findings that estrogen and progestin replacement therapy increased the risk for stroke, thrombotic events and breast cancer in women.
If the findings are confirmed, testosterone could be considered an additional risk factor to help assess individual’s cardiovascular risk and guide preventive treatment.
Source: Khaw KT, Dowsett M, Folkerd E et al.: Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men. European Prospective Investigation Into Cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation 116(23), 2694–2701 (2007).