Wood Street Clinic Blog

Here you will find a selection of RSS feeds and blog entries

Asymptomatic cardiovascular disease is prevalent and occurs earlier in adult survivors of childhood cancer

For adult survivors of childhood cancer, cardiovascular disease presents at an earlier age, is associated with substantial morbidity, and is often asymptomatic. According to researchers, the type and frequency of screening that should be used in this group is not clear. The study is published in Annals of Internal Medicine.

The number of adult survivors of childhood or adolescent cancer is projected to surpass 500,000 by 2020. Historically, the leading cause of death has been cancer recurrence. However, late effects of therapy have become the leading cause of death 30 years after diagnosis, and deaths are frequently attributed to premature cardiovascular disease. Utilizing data from the St. Jude Lifetime Cohort Study, researchers systematically assessed cardiac outcomes among survivors of childhood cancer.

The data showed evidence of cardiomyopathies, conduction or rhythm abnormalities and coronary artery and valvular diseases in substantial numbers of adult survivors of childhood cancer who were exposed to cardiotoxic therapies. Many of the patients were younger and asymptomatic, suggesting that prospective studies to assess the potential value of screening for cardiac abnormalities in adult survivors of childhood cancer are needed.

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There is a need to recognize heart attack symptoms more quickly

Patients are putting their own heart health at risk by taking too long to recognize the symptoms of a heart attack and not seeking immediate treatment, according to a study published in the journal of the American College of Cardiology, JACC: Cardiovascular Interventions.
[man and woman with doctor]
The shorter the time from onset to treatment, the better the outlook.

Door-to-balloon time is the time from when a heart attack patient arrives in the emergency room until percutaneous coronary intervention is performed to restore blood flow.

ST-segment elevation myocardial infarction (STEMI) is "a severe heart attack caused by a prolonged period of blocked blood supply that affects a large area of the heart," according to the American Heart Association.

American College of Cardiology/American Heart Association (ACC/AHA) guidelines state that hospitals treating STEMI patients with emergency percutaneous coronary intervention should do so within 90 minutes or less of reaching the hospital.

The ACC launched the Door-to-Balloon (D2B) Alliance in 2006 to reduce the time to which STEMI patients receive percutaneous coronary intervention in US hospitals, and hospitals have made progress in doing so.

In about 90% of percutaneous coronary intervention cases, blood flow is restored in the surface of the heart, but in about 1 in 3 patients, blood flow is not restored to the heart muscle.

Researchers in this study compared the impact on heart muscle function of the time from onset until treatment with time from door-to-balloon, in other words, between arrival at the emergency department until treatment.

The team reviewed the records of 2,056 patients in the multi-center Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial; they compared patients with symptom onset-to-balloon time in three categories: 2 hours and less, between 2-4 hours, more than 4 hours.

Patients who received treatment with a balloon angioplasty to restore blood flow to the heart after 2-4 hours or longer from the onset of symptoms were less likely to have blood flow fully restored to the heart and more likely to die within 3 years than patients treated more quickly.

Study author Dr. Roxana Mehran, who is director of interventional cardiovascular research and clinical trials at the Zena and Michael A. Weiner Cardiovascular Institute at Mount Sinai School of Medicine in New York City, says:

"The decrease in median door-to-balloon time in recent years has not resulted in a reduction in mortality in STEMI patients. This study highlights the need to reconsider the role of door-to-balloon as a performance metric and examine the utility of a broader metric of systems delay such as first medical contact to balloon time as well as total ischemic time."

In an accompanying editorial, Dr. Michael A. Kutcher, of Wake Forest Baptist Medical Center, said the door-to-balloon metric and systems in place are extremely valuable and should continue.

However, he points out the need for physicians to look at associated metrics, such as the signs and symptoms of the onset of ischemia or loss of blood flow.

Dr. Kutcher believes that the reduced door-to-balloon time has not been matched by a significant improvement in mortality and morbidity because microvascular damage can still occur with shorter door-to-balloon time; this can increase the risk of death.

He says that patients with longer door-to-balloon time are a high-risk group and should be treated accordingly with assertive strategies. He wants the interventional cardiology community to continue to educate the public and health care providers regarding the importance of prompt action.

Medical News Today recently reported that women who experience a heart attack continue to be at risk of illness and death in the long term.

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Treatment time lags for heart attack patients with prior bypass graft surgery

Heart attack patients who had previously undergone coronary artery bypass graft surgery were less likely than other heart attack patients, including those with prior angioplasty, to be treated within the 90-minute recommended "door-to-balloon time," according to a study published today in JACC: Cardiovascular Interventions.

Door-to-balloon time refers to the time from a patient's arrival at the hospital to treatment to restore blood flow to the heart with angioplasty and a stent.

Using data from the National Cardiovascular Data Registry CathPCI Registry linked with the ACTION Registry-GWTG, researchers examined records of 15,628 heart attack patients treated at 297 U.S. hospitals between June 2009 and September 2011. Of that group, 6 percent had a history of previous coronary artery bypass graft surgery, 19 percent had previous angioplasty, and 75 percent had no prior history of procedures.

Heart attack patients with prior revascularization through surgery were older, with an average age of 66, than those with prior angioplasty, average age 60, or without any previous interventions, average age 59; and they were more likely to have other medical conditions, including high blood pressure, high cholesterol, and diabetes.

Results showed that 76 percent of patients with prior revascularization via open heart surgery were treated within the recommended 90-minute door-to-balloon time compared to 88.5 percent of patients with prior angioplasty and 88 percent of patients with no previous interventions. Door-to-balloon time was achieved in 90 percent of patients with a prior history of angioplasty with a stent when the new lesion was located in the previous stent and in 87.3 percent of patients if the lesion was in a non-stented area. For patients with a prior history of bypass graft surgery, 75.9 percent had their angioplasty done within 90 minutes when the new lesion was in the graft site, as did 77 percent when the lesion was located in a new vessel.

Overall, 88.3 percent of patients in the prior surgery group had successful procedures compared with 93.4 percent of patients who had a prior angioplasty and 94.4 percent of patients with no prior interventions. After adjusting for clinical and procedural differences, the study found no significant differences in in-hospital mortality, major adverse events, and major bleeding among the three groups.

Luis Gruberg, M.D., FACC, the study's lead author and professor of medicine at Stony Brook University in New York said patients with a history of prior coronary artery bypass surgery have more complex anatomy and more comorbidities, and therefore have a more prolonged door-to-balloon time compared to the other groups in the study. "Nonetheless, every effort should be made to improve timeliness in patients with a history of previous coronary artery bypass surgery," Gruberg said.

In an accompanying editorial, John S. Douglas Jr., M.D., professor of medicine at the Emory University School of Medicine in Atlanta, said the delay in door-to-balloon time for prior bypass graft patients has important implications for salvaging the heart muscle. According to Douglas, because door-to-catheterization lab and catheterization lab-to-balloon times were not provided, it's not clear where the delay occurred. "Increased awareness of 'time is muscle,'" Douglas said, "may lead to shortened door-to-cath lab times and timely performance" for the more difficult patients.

Douglas said the study "should be interpreted as a 'call to action' with the goal of earliest possible treatment in all heart attack patients, including those who have had prior coronary artery bypass graft surgery."

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Limes: Health Benefits, Nutritional Information

Limes are a citrus fruit often used to accent flavors in foods and are a common ingredient in Mexican, Vietnamese and Thai cuisine. They are grown year-round in tropical climates and are usually smaller and less sour than lemons.

The Tahitian lime, also called the Persian lime, is the variety most commonly used in cooking. Key limes are smaller, rounder and more acidic than Tahitian limes and are used in the classic dessert Key Lime pie.

It is a misconception that key limes are grown in Key West, FL. They are primarily grown in subtropical climates such as Mexico, India and Egypt.1

This MNT Knowledge Center feature is part of a collection of articles on the health benefits of popular foods. It provides a nutritional breakdown of limes and an in-depth look at its possible health benefits, how to incorporate more limes into your diet and any potential health risks of consuming limes.

Nutritional breakdown of limes According to the US Department of Agriculture National Nutrient Database, the juice of one lime (approximately 44 grams) contains 11 calories, 4 grams of carbohydrate (including 1 gram of sugar and 0 grams of fiber) and 0 grams of protein as well as 22% of the daily recommended amount of vitamin C. One teaspoon of lime zest (approximately 1 gram) contains 1 calorie and 4% of recommended vitamin C. Possible benefits of consuming limes Limes.
Limes are rich in vitamin C and have antibacterial and antifungal properties.

Consuming fruits and vegetables of all kinds has long been associated with a reduced risk of many lifestyle-related health conditions.

Many studies have suggested that increasing consumption of plant foods like limes decreases the risk of obesity, diabetes, heart disease and overall mortality while promoting a healthy complexion and hair, increased energy and overall lower weight.

Vitamin C has been shown to reduce all-cause mortality.2 Limes are a very concentrated source of vitamin C, a well-known antioxidant.

Heart health

In a study published by the ARYA Atherosclerosis journal, lime juice and peel was shown to decrease fatty streaks found in coronary arteries, which are indicators of plaque buildup and subsequently cardiovascular disease.3 A different study showed that low vitamin C levels are associated with increased risk of stroke.4

Antimicrobial activity

Lime juice has antibacterial and antifungal properties.5 A study published by Tropical Medicine & International Health showed that lime juice inhibited the growth of Vibrio cholerae specifically.6

Asthma prevention

The risks for developing asthma are lower in people who consume a high amount of certain nutrients. One of these nutrients is vitamin C, found in many fruits and vegetables including limes.

Increasing iron absorption

Iron deficiency is one of the most common nutrient deficiencies in developed countries and a leading cause of anemia. Pairing foods that are high in vitamin C with foods that are iron-rich will maximize the body's ability to absorb iron. For example, squeeze fresh lime juice onto a salad with spinach and chickpeas (both a good source of iron).

Boosting the immune system

Foods that are high in vitamin C and other antioxidants can help the immune system battle germs that cause a cold or flu. Maintaining a healthy diet high in fruits and vegetables is especially important during the winter months when physical activity levels tend to drop.

Healthy skin

Vitamin C, when eaten in its natural form (in fresh produce as opposed to supplement form), can help to fight skin damage caused by the sun and pollution, reduce wrinkles and improve overall skin texture. Adequate intake of vitamin C (the juice of one lime provides 22% of daily needs) is also needed for the building and maintenance of collagen that provides structure to skin and hair.

Lowering risk of stroke

According to the American Heart Association, eating higher amounts of citrus fruits may lower ischemic stroke risk for women. In one study, participants who ate the highest amounts of citrus had a 19% lower risk of ischemic stroke than those who consumed the least.7

How to incorporate more limes into your diet Chopped limes added to a jar of water.
Make a quick, refreshing drink by adding some limes to water. Quick tips: Top any white fish with thinly sliced limes Combine lime juice with oil and any seasoning for a quick dressing Squeeze lime juice into water or tea Top entrees with lime zest or use zest in marinades. Start with this citrus rub. Or, try these healthy and delicious recipes developed by registered dietitians: Cilantro-lime tuna patties
Edamame, black bean and corn quesadillas
Homemade salsa
Asian slaw. Potential health risks of consuming limes Wash the peels of limes even if you are not planning on using the peel. Bacteria from the peel can be transferred inside the fruit by the knife in cutting. If zesting the lime, use organic limes if possible. It is the total diet or overall eating pattern that is most important in disease prevention and achieving good health. It is better to eat a diet with variety than to concentrate on individual foods as the key to good health.
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Lower BP targets to help those at risk of cardiovascular events

Anyone at high risk of a cardiovascular event should be offered blood pressure-lowering drugs, regardless of their blood pressure at the start of treatment, says research published in The Lancet.
[taking BP]
People with low BP but at risk of cardiovascular disease could benefit from BP treatment.

High blood pressure (BP) is the leading cause of heart disease and stroke. It affects more than 1 billion individuals worldwide and kills 9.4 million people every year.

The benefits of treating high BP with BP-lowering medications are well established.

But uncertainty remains about whether to treat those who currently have low BP but are at risk of cardiovascular events, and which drugs to use.

The UK's National Institute for Health and Care Excellence (NICE) and the European Society of Hypertension have recently moved blood pressure targets from 130/85 mmHg to 140/90 mmHg, and for the elderly to even higher targets of 150/90 mmHg.

The authors of the present study call for an urgent revision of these and other current blood pressure-lowering guidelines.

They also recommend a shift from rigid blood pressure targets to individualized risk-based targets, even when blood pressure is below 130 mmHg before treatment.

Prof. Kazem Rahimi, from The George Institute for Global Health at the University of Oxford in the UK, and colleagues analyzed the findings of 123 large-scale randomized trials comparing different blood pressure targets for over 600,000 people from January 1966-July 2015.

They found that treatment with any of the main classes of blood pressure-lowering drugs significantly reduced the risk of major cardiovascular events, stroke, heart failure and death, proportional to the extent to which blood pressure was lowered.

Overall, every 10 mmHg reduction in systolic blood pressure reduced the risks of major cardiovascular disease (CVD) events and heart disease by about 20%, of stroke and heart failure by about 25% and the risk of death from any cause by 13%.

The reductions were similar across a wide range of high-risk patients, including those with a history of CVD, heart failure, diabetes and kidney disease, regardless of whether their blood pressure was already low (less than 130 mmHg) to begin with.

The five major drug classes examined were found to be equally effective at protecting against cardiovascular events, but some classes were more effective than others for specific outcomes; for example, calcium channel blockers seemed better for stroke, and diuretics were better for heart failure prevention.

Prof. Rahimi says:

"Our findings clearly show that treating blood pressure to a lower level than currently recommended could greatly reduce the incidence of cardiovascular disease and potentially save millions of lives if the treatment was widely implemented."

He argues that results provide strong support for reducing systolic blood pressure to less than 130 mmHg, and recommends offering blood pressure-lowering drugs to all patients at high risk of a heart attack or stroke, for whatever reason.

In a linked comment, Prof. Stephane Laurent, from the University Paris Descartes, in Paris, France, says that since lowering BP seems safe and beneficial to patients, it could be applied to high-risk patients, especially now that uncontrolled hypertension is a worldwide problem.

Medical News Today recently reported on research showing that men who take alpha blockers run a higher risk of stroke.

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Unsynching the heartbeat a bit each day halts worsening heart failure

Short daily exposure to 'asynchrony' using a pacemaker may jump-start a suite of recovery mechanisms, experiments suggest.

Johns Hopkins has demonstrated in animals that applying a pacemaker's mild electrical shocks to push the heart in and out of normal synchronized contraction for part of each day may be an effective way to slow down the progression of heart failure, a disorder that afflicts millions of Americans.

After PITA
After PITA therapy, the damage to the heart's force-generating elements, myofilaments, are repaired.
Credit: Jonathan Kirk

In the study published online in the Dec. 23 issue of Science Translational Medicine, the researchers say recent experiments in dogs show that the therapy, called Pacemaker Induced Transient Asynchrony, or PITA, reverses cellular damage to the heart's response to hormones, like adrenaline, and fixes the damage to the motor proteins in the heart muscle that generate force. Essentially, the therapy uses a pacemaker over several hours to alternately "zap" a region of heart muscle with electrical shocks so it beats out of synch, and then reverses this so the heart beats again in synchrony for the rest of the day.

"It's the process of going back and forth that is important. In a way, we've attached a light-switch timer to a pacemaker -- like the automatic timers used in homes to turn lights on and off -- but here it flips the pacemaker between synchronous and out-of-synch states each day," says David Kass, M.D., a professor of medicine and biomedical engineering at the Johns Hopkins University School of Medicine. "We're very excited about prospects for this therapy because if further research confirms its effectiveness and safety, it's relatively easy to implement. The pacemaker hardware already exists, and with some software upgrades, we may have a treatment that would benefit many, many people."

According to Kass, congestive heart failure, marked by enlargement and weakness of the heart muscle, affects tens of millions of people worldwide and remains a leading cause of hospitalization and death. In approximately 25 percent of patients, the disease is worsened by so-called dyssynchronous contraction resulting from delays in electrical activation between the two sides of the heart.

"For heart failure patients who develop dyssynchrony, the heart ends up out of tune, like a car with a broken timing belt," says Kass. A decade ago, his team pioneered cardiac resynchronization therapy, which uses a pacemaker to deliver electric pulses to both sides of the heart so it's retuned, or synchronized. Over the years, they discovered that resynchronization therapy also improves the heart's tissue, including changes in the way that calcium flows through heart muscle cells, the way that receptors on the heart respond to hormones, like adrenaline, and the way that the heart's force-generating fibers performed. "We discovered that this wasn't just tuning the engine -- the engine itself wasn't the same anymore," says Kass. "At a very basic level, the molecular processes that control heart contraction had improved."

These observations led Kass and his colleagues to develop PITA and begin their latest animal experiments. They would ultimately be aimed at the 75 percent of heart failure patients who do not have dyssynchrony and so are not eligible for a resynchronizing pacemaker.

In the new experiments with dogs, the researchers first induced heart failure in the animals -- 10 received PITA, and 13 served as heart failure controls -- by delivering atrial pacing, or small electrical pulses to the right atrium of the heart, 200 times per minute, 24 hours a day for four weeks. After four weeks, the PITA treatment group received six hours of electrical pulses per day to the right ventricle at the same 200-times-per-minute rate and then atrial pacing for the remaining 18 hours of the day. The control group received an additional four weeks of continuous atrial pacing. An additional eight dogs received no atrial pacing at all and were kept as controls.

The investigators found that, relative to the heart failure control group, four weeks of PITA treatment reduced progressive enlargement of the heart, boosted its response to adrenaline stimulation by 38 percent, reversed dysfunction and structural damage of motor proteins that occurred in about 40 percent of the heart failure group, and increased the force-generating ability of the muscle also by about 40 percent. There were no apparent adverse side effects from PITA.

"We liken PITA to immunization, where you're given just a bit of a bug to help you mount a robust immune response that protects you against a more serious infection. Too much dyssynchrony exposure is also bad for the heart; we knew that, but here we show that a little bit each day can stimulate beneficial effects," says Kass.

Kass speculates that the ideal patient for PITA, if further research affirms its value, would be one with heart failure who has normal synchronous heart contractions and is a candidate for an internal defibrillator; this covers about 75 percent of heart failure patients. A defibrillator is an insurance policy that is only helpful if you have a lethal arrhythmia, but by itself, it does not change heart function or symptoms. Used in conjunction with PITA, though, the defibrillator has the potential to improve symptoms now as well. PITA was not compared to any drug therapies in this animal study, and long-term risks remain to be determined.

Additional authors on the study include Khalid Chakir, Richard Tunin, Iraklis Pozios, Theodore Abraham and Jennifer Van Eyk of Johns Hopkins Medicine; Jonathan Kirk and Pieter de Tombe of Loyola University; Kyoung Hwan Lee and Roger Craig of the University of Massachusetts Medical School; Edward Karst and Taraneh Farazi of St. Jude Medical; Ronald Holewinski of Cedars-Sinai Medical Center; and Gianluigi Pironti and Howard Rockman of Duke University.

The study was funded by grants from the National Heart, Lung, and Blood Institute (P01-HL077180, T32-HL007227, P01-HL059408, NHLBI-HV-10-05(2), P01-HL75443); Abraham and Virginia Weiss and Michael and Janet Huff Endowments; the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR034711); the Department of Health and Human Services (HHSN268201000032C); the American Heart Association (14SDG20380148); and the Burroughs Wellcome Fund.

Kass, who has a patent pending for PITA in accordance with Johns Hopkins University policies, says clinical trials with PITA could begin in 2017 in selected patients.

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HMH, Hardin County EMS, 911 partner to provide life-saving app

Beginning today, Hardin Memorial Health (HMH), Hardin County Emergency Medical Services (EMS) and Hardin County 911 are making a new life-saving smartphone app available in the market place. The app, called PulsePoint, is integrated in the county's 911 system and alerts CPR-trained bystanders in the immediate vicinity of a cardiac emergency, so they can get to the scene and start CPR in the critical minutes before EMS teams arrive.

The three partners came together today at the Hardin County Government Building to announce the availability of the app. Hardin County is the second community in the state to make this app available - Erlanger, Kentucky was the first.

"We are thrilled to partner with Hardin County EMS and Hardin County 911 to bring this life-saving tool to Hardin County," said Sharon Wright, HMH Chief Nursing Officer.

Wright added that every day, 1,000 people experience Sudden Cardiac Arrest (SCA), the leading cause of death in our country.

Director of Hardin County EMS John Malcomson said that number typically increases over the holidays.

"There couldn't be a better time to roll this out," Malcomson said.

The American Heart Association estimates that effective bystander CPR, provided immediately after sudden cardiac arrest, can double or triple a person's chance of survival, but only about one quarter of SCA victims receive bystander CPR.

"We want to change that," Malcomson said. "Minutes matter when it comes to savings lives, especially the life of someone experiencing a cardiac emergency. This app can make a difference in a life or death situation."

Malcomson shared the real-life story of Rodney Druen, who attended the announcement. Druen went into cardiac arrest at his home in Sonora. His neighbor, a volunteer firefighter, administered CPR until EMS arrived.

"I wouldn't be standing here today if it weren't for my neighbor, Brad, and the excellent care I received from Hardin County EMS and Hardin Memorial Hospital," Druen said.

Jamie Armstrong, EMS Supervisor, also encouraged more people in Hardin County to get CPR training.

"It's easy to learn. There are classes available through the American Red Cross, Hardin County Government, HMH and the Lincoln Trail District Health Department," said Armstrong. "This is a very caring community. What better way to take care of one another than to learn CPR and download this app?"

Bob Hammonds, 911 Director, who was also on hand for the event, reiterated that the community is pivotal to the success of the PulsePoint partnership.

"PulsePoint notifications are generated by the 911 dispatch," Hammonds said. "It is important that all citizens know to call 911 in the event of a cardiac episode - no matter how seemingly small it is. Hesitating to call 911 could prevent life-saving CPR to be administered by a trained bystander."

The PulsePoint app also alerts bystanders to any nearby public access automated external defibrillators (AED) which is yet another tool proven critical to surviving a cardiac emergency.

PulsePoint leaders gave the Hardin County partners high praise.

"We are inspired by the strong collaboration between Hardin County EMS, Hardin County 911 and Hardin Memorial Health to bring the PulsePoint app to their community," said Richard Price, President of the PulsePoint Foundation. "PulsePoint will amplify the excellent work already accomplished around CPR training and public AED placement in the community. The leadership to drive early adoption of PulsePoint in Kentucky is exemplary."

To get the PulsePoint app, go to http://www.pulsepoint.org/download or simply search for PulsePoint in the Apple App Store or on Google Play.

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Kidney injury common following vascular surgery, associated with increased risk for cardiovascular-related death

Both acute kidney injury and chronic kidney disease were common in patients undergoing major vascular surgical procedures and were associated with an increase in long-term cardiovascular-specific death compared with patients with no kidney disease, according to a study published online by JAMA Surgery.

Azra Bihorac, M.D., M.S., of the University of Florida, Gainesville, and colleagues examined the association between acute kidney injury (AKI), chronic kidney disease (CKD) and long-term cardiovascular-specific mortality among patients who underwent inpatient vascular surgery between January 2000 and November 2010 at a tertiary care teaching hospital. Final follow-up was completed July 2014 to assess survival through January 2014.

Among the 3,646 patients undergoing vascular surgery, perioperative (around the time of surgery) AKI occurred in 1,801 (49 percent) and CKD was present in 496 (14 percent). The top 2 causes among the 1,577 deaths in this group were cardiovascular disease (54 percent) and cancer (11 percent). Adjusted cardiovascular mortality estimates at 10 years were 17 percent for patients with no kidney disease; 31 percent for patients with AKI without CKD; 30 percent for patients with CKD without AKI; and 41 percent for patients with AKI and CKD.

"These findings reinforce the importance of preoperative CKD risk stratification through the application of consensus staging criteria for CKD using estimated glomerular filtration rate [a measure of kidney function] and albuminuria [the presence of excessive protein in the urine] for all patients undergoing major vascular surgery. Preoperative and postoperative risk stratification for AKI using clinical scores and urinary biomarkers similarly can help to direct the implementation of simple and inexpensive preventive strategies in the perioperative period that could prevent or mitigate further decline in kidney function," the authors write.

"The appropriate transition of patients undergoing surgery to follow-up in the outpatient setting with an emphasis on the prevention of kidney disease progression and mitigation of cardiovascular risk can be an important factor in improving the care of the patient undergoing vascular surgery who has AKI and/or CKD. Our findings present compelling evidence that such efforts are warranted and justifiable."

Commentary: Transient Acute Kidney Injury in the Postoperative Period

"The results of the study by Huber and colleagues should prompt a call to action in terms of earlier diagnosis, treatment, and prevention of postoperative AKI," write Christian de Virgilio, M.D., and Dennis Yong Kim, M.D., of the Harbor-UCLA Medical Center, Torrance, Calif.

"Novel biomarkers may furnish physicians with a narrow window to reverse or altogether avoid the development of AKI. Goal-directed intraoperative measures to maximize renal perfusion and the early use of renal replacement therapy may also have a role in prevention and treatment, respectively. Perhaps even more exciting is the application of preoperative therapeutic interventions such as remote ischemic preconditioning, which in a recent trial was associated with a significantly reduced rate of AKI following cardiac surgery. Regardless of the strategies used, it is readily apparent that it is time to start paying closer attention to postoperative AKI."

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The AHA's 7 steps shown to reduce heart disease

People who score well on the American Heart Association's Life's Simple 7 checklist for a healthy heart are less likely to develop heart failure, a condition that reduces blood and oxygen flow to the body, according to research in the journal Circulation: Heart Failure.
[exercise and heart]
Exercise is one of the seven measures recommended to beat heart disease.

Cardiovascular disease (CVD) is the leading cause of death in the US. According to a recent American Heart Association (AHA) statistical update, there were 801,000 American deaths in 2013 due to cardiovascular diseases, including over 370,000 to heart disease. Around 750,000 Americans had a heart attack in that year.

According to the update, at 40 years of age, men and women have a 1 in 5 chance of developing heart failure during their lifetime.

The Life's Simple 7 checklist was designed by the AHA with the goal of improving public health through lifestyle education. Previous research has shown that improvements in the seven measures reduce the risk of heart attack and stroke.

The measures can be adopted by anyone, say the AHA; they are not expensive, and even modest implementation will improve an individual's health.

Life's Simple 7 measures

The recommended actions are:

Manage blood pressure (BP): keep BP within healthy ranges to reduce strain on the heart, arteries and kidneys Control cholesterol: high cholesterol contributes to plaque, clogging arteries and leading to heart disease and stroke Reduce blood sugar: most of our food turns into glucose, or blood sugar, to be used for energy. Excess blood sugar eventually damages the heart, kidneys, eyes and nerves Get active: daily physical activity increases the length and quality of life Eat better: a heart-healthy diet improves the chances of feeling good and staying healthy Lose weight: lower weight means less burden on the heart, lungs, blood vessels and skeleton Stop smoking: cigarette smokers have a higher risk of developing cardiovascular disease.

Researchers, led by Dr. Matthew Nayor, a cardiology fellow at Boston's Brigham and Women's Hospital in Massachusetts, analyzed data from the Framingham Offspring Study to evaluate the association between the Simple 7 and heart failure.

Lifestyle changes significantly decrease risk

The team followed 3,201 participants, with an average age of 59 years, for up to 12.3 years. During this period, 188 participants developed heart failure.

For each one-point higher cardiovascular health score, there was a 23% lower risk of developing heart failure. Those scoring in the middle third cut their risk of heart failure by nearly 50%, compared with those in the bottom third. Those in the top third reduced their risk even further.

Vanessa Xanthakis, PhD, senior author and assistant professor of medicine and biostatistics at Boston University, says:

"Even though there is awareness about the importance of a healthy lifestyle, many people do not act on those messages. This study points to the importance of knowing your numbers and speaking to your doctor about improving your score on each health metric and trying to get as close to ideal status as possible."

Researchers also found an association between poor heart health measures and unhealthy changes in the heart's structure and function, known as cardiac remodeling, which can occur during normal growth or as a result of illness such as myocardial infarction, cardiomyopathy, hypertension or valvular heart disease.

These changes, measured at the beginning of the study, appeared to put people at greater risk for heart failure later in life.

However, after adjusting for cardiac remodeling, low scores in the seven heart health factors remained predictors of heart failure.

Two limitations of the study were that participants were mostly white and of European ancestry, and their Life's Simple 7 score was assessed only once, at the beginning of the study.

Dr. Nayor says the findings give a strong message that these are useful measures for a healthy lifestyle that can help reduce the chance of heart attack and stroke, and also of developing heart failure in the future.

Medical News Today recently reported on the latest statistics from the AHA showing that CVD and stroke are still the two top killers worldwide.

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Actelion receives US FDA approval of Uptravi (selexipag) for the treatment of pulmonary arterial hypertension

Actelion has announced that the United States Food and Drug Administration (FDA) has approved the use of the orally active, selective IP prostacyclin receptor agonist Uptravi (selexipag),originally discovered and synthesized by Nippon Shinyaku, for the treatment of pulmonary arterial hypertension (PAH).

Uptravi is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.

Effectiveness was established in a long-term study in PAH patients with WHO Functional Class II-III symptoms. Patients had idiopathic and heritable PAH (58%), PAH associated with connective tissue disease (29%), PAH associated with congenital heart disease with repaired shunts (10%).

Vallerie McLaughlin MD, Director of the Pulmonary Hypertension Program in the Division of Cardiovascular Medicine at the University of Michigan, United States, commented: "The prostacyclin pathway has long been recognized as a key target in PAH treatment. However, until now, it has been underutilized. This is in part due to the significant burden existing prostanoid treatments have placed on the patients and on those supporting them. The approval of Uptravi with its convincing long-term outcome results means that many more patients can benefit from this pathway and be treated much earlier in the course of their disease."

Jean-Paul Clozel, MD and Chief Executive Officer of Actelion, commented: "Today's FDA approval of Uptravi is another major landmark for Actelion. Together with our partners at Nippon Shinyaku we are proud to be able to offer an outstanding oral therapy targeting the prostacyclin pathway. The label for Uptravi recognizes the improvement in long-term outcomes, including reducing the risk of hospitalization for PAH regardless of whether patients received background therapy including an ERA, a PDE-5 inhibitor, or - for the first time ever in PAH - on top of a combination of both, an ERA and a PDE-5 inhibitor."

Jean-Paul Clozel concluded: "Uptravi will significantly expand the options to delay disease progression after initiation of therapy with a baseline treatment like Opsumit and well ahead of Veletri for the late disease stage. Actelion now has an unparalleled portfolio of treatments across the continuum of care in PAH that offer a combination of long term-efficacy, safety and convenience."

The safety of Uptravi has been evaluated in a long-term, placebo-controlled study enrolling 1,156 patients with symptomatic PAH (GRIPHON study). The exposure to Uptravi in this trial was up to 4.2 years with median duration of exposure of 1.4 years.

Adverse reactions occurring more frequently on Uptravi compared to placebo - greater than or equal to 3% - over the course of the study, were headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, flushing, arthralgia, anemia, decreased appetite and rash. These adverse reactions are more frequent during the dose titration phase. Hyperthyroidism was observed in 1% (n=8) of patients on Uptravi and in none of the patients on placebo.

Actelion expects Uptravi to become available to patients in the United States in early January 2016. Outside of the United States, Actelion continues to work with health authorities to obtain regulatory approval for Uptravi.

About the GRIPHON Study Data

The Uptravi approval was based in part on data from the long-term, global, Phase III GRIPHON study in 1,156 patients treated for up to 4.2 years. The GRIPHON study, in which more than 80% of patients were already receiving PAH-specific therapies, showed that the risk of the primary composite endpoint was reduced by 40% (p

The benefit of selexipag was consistent across pre-specified patient subgroups such as disease etiology, functional class and baseline PAH therapy, including patients already receiving combination therapy with an ERA and a PDE-5 inhibitor.

Titrating selexipag to an individualized maintenance dose based on tolerability was effective in achieving long-term outcome benefits across the tested dose range. The dosing in GRIPHON was initiated at 200 micrograms (mcg) twice daily (b.i.d) and increased weekly in steps of 200 mcg up to a maximum of 1600 mcg b.i.d. After titrating to the highest tolerated dose, the benefit was consistent across the pre-specified low- (200, 400 mcg b.i.d), medium- (600, 800, 1'000 mcg b.i.d) and high-maintenance (1'200, 1'400, 1'600 mcg b.i.d) dose groups.

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Women with type 2 diabetes at greater cardiovascular risk than men

While it is well established that individuals with diabetes are at higher risk for cardiovascular disease, a new scientific statement from the American Heart Association claims this risk may be significantly greater for women with the condition.
[A woman clutching her chest]
Women with type 2 diabetes are twice as likely to develop coronary heart disease than men, according to the new statement.

Published in the journal Circulation, the statement also says women with type 2 diabetes may need to take more action than men to lower their risk for heart attack and stroke.

Type 2 diabetes accounts for around 90-95% of all diabetes cases in the US, affecting men and women at similar rates; around 12.6 million women and 13 million men aged 20 and older have the condition.

According to the American Heart Association (AHA), adults with diabetes are around two to four times more likely to have heart disease or stroke than those without diabetes, primarily because diabetes patients are at greater risk for high blood pressure, high cholesterol and obesity - key risk factors for cardiovascular problems.

Increasingly, however, studies have suggested that cardiovascular risks among adults with diabetes may vary by sex, and such findings are reflected in the new AHA scientific statement.

Judith G. Regensteiner, PhD, chair of the AHA's statement writing group and professor of medicine and director of the Center for Women's Health Research at the University of Colorado School of Medicine, and coauthors claim that women with type 2 diabetes are more than twice as likely to develop coronary heart disease - the most common form of heart disease - than men.

Fast facts about diabetes

Around 29.1 million people in the US have diabetes - 1 in 11 Americans Around 86 million adults in the US have pre-diabetes As well as heart disease, diabetes can cause blindness, kidney failure and lower-extremity amputations, among other serious health complications.

Black and Hispanic women with type 2 diabetes are also disproportionately affected by coronary heart disease compared with men, the authors note.

Women with type 2 diabetes are more likely to have heart attacks earlier in life than men and are more likely to die after a first heart attack, according to the statement.

Compared with men with type 2 diabetes, women with the condition may need to engage in more frequent and intense exercise in order to lower their risk for cardiovascular disease.

Regensteiner and colleagues also point to differences between men and women with type 2 diabetes in the use of strategies to protect cardiovascular health. For example, women were less likely than men to use cholesterol-lowering drugs - such as statins - blood pressure-lowering medications and aspirin.

Women with type 2 diabetes were also less likely to have their blood pressure under control than men and were less likely to undergo procedures to open blocked arteries, such as angioplasty.

Additionally, the statement authors found women with type 2 diabetes develop the condition based on sex-specific variances, including the presence of polycystic ovary syndrome (PCOS) and gestational diabetes.

Commenting on what the statement shows, Regensteiner says:

"Cardiovascular disease may be more deadly for women with type 2 diabetes than it is for men.

While we don't fully understand how the inherent hormonal differences between men and women affect risk, we do know that some risk factors for heart disease and stroke affect women differently than men and there are disparities in how these risk factors are treated."

The authors say further research is required in order to gain a better understanding of why women with type 2 diabetes are at greater cardiovascular risk than men, as well as the reasons why women of certain ethnicities appear to be at greater risk.

"To improve health equity in women and men with diabetes, we need to understand and improve both the biological reasons for the disparities and also control cardiovascular risk factors equally in both women and men," explains Regensteiner. "This statement is a call for action to do the compelling research that is so important for all people with diabetes."

Last month, Medical News Today reported on a study that linked exposure to air pollution among women with type 2 diabetes to increased risk of cardiovascular disease and stroke.

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Chronic kidney disease patients benefit from pacing left and right ventricles

Treatment may prevent hospitalization due to heart failure, though randomized studies needed.

Patients with moderate-to-severe chronic kidney disease who received cardiac resynchronization therapy with defibrillator had a lower risk of hospitalization for heart failure or death from this condition compared to patients who received only an implantable cardioverter defibrillator, according to a study published in the Journal of the American College of Cardiology.

An implantable cardioverter defibrillator is a device implanted in the chest that detects life-threatening abnormal heartbeats and treats them with an electric shock. Cardiac resynchronization therapy with defibrillator works in a similar way, with the difference being that, in addition to delivering a shock, it can pace both ventricles at the same time.

Using data from the National Cardiovascular Data Registry ICD Registry linked with claims from the Centers for Medicare and Medicaid, researchers examined records of 10,628 patients with kidney disease who were eligible for either of these devices between January 2006 and December 2009. Of that group, 87 percent received cardiac resynchronization therapy with defibrillator.

After adjusting for many factors, including age, sex, level of chronic kidney disease, and presence of atrial fibrillation or flutter, researchers found a 15 to 20 percent reduction in the risk of hospitalization for heart failure or death from heart failure in patients who received cardiac resynchronization therapy compared with those who received an implantable cardioverter defibrillator.

Daniel J. Friedman, M.D., the study's lead author and a fellow in cardiology at Duke University Hospital, in Durham, North Carolina, said that the results from the study corroborate the observed association between cardiac resynchronization with defibrillator and improved outcomes for patients with advanced kidney disease. But the study also showed that cardiac resynchronization therapy was no more effective than implantable cardioverter defibrillators in reducing progression to advanced kidney disease.

"Taken in sum, the results from this study support the use of cardiac resynchronization therapy independent of kidney function. The treatment is associated with a reduction in risk of heart failure hospitalization and mortality. These results, however, should be confirmed by prospective randomized studies," Friedman said.

In an accompanying editorial, John G.F. Cleland, M.D., Ph.D., professor of medicine at the National Heart and Lung Institute in London, said that with only a modest reduction in hospitalization risk for heart failure and death, it is unclear whether this population actually benefits from the treatment, especially without data from a device-free control group.

"Within three years, 61 percent of those with end-stage kidney disease who received an implantable cardiac defibrillator and 54 percent who received cardiac resynchronization therapy with defibrillator had died," Cleland said. In these instances, it may be better not to "implant, at some risk and discomfort, an expensive piece of technology, which may be attended by substantial morbidity" and instead "have a frank discussion with the patient about the limits of modern medicine," he said.

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Too few adults in US taking cholesterol-lowering drugs

Nearly half of those eligible for medications to lower cholesterol are not taking them, according to findings published in the Morbidity and Mortality Weekly Report.
[high cholesterol]
Many of those eligible for cholesterol-lowering interventions are not taking them up.

From 2007-14 there was a decline in the rate of high blood levels of  cholesterol among Americans, and there has been a recent increase in the use of cholesterol-lowering medications.

However, a high blood level of LDL cholesterol, also known as "bad" cholesterol, remains a major risk factor for heart disease and stroke.

In the US, there are 78.1 million adults with high LDL cholesterol and a risk of heart disease.

These people are advised to take preventive action combining cholesterol-lowering medications with lifestyle changes, such as regular exercise, a heart-healthy diet and weight loss.

Yet, fewer than half of those eligible for the medications are taking them, and fewer than half make the recommended lifestyle changes.

Black people and Mexican Americans are particularly affected.

Who should take the medication?

The American College of Cardiology (ACC) and the American Heart Association (AHA) recommend cholesterol-lowering medications for:

Heart disease, a prior heart attack or some types of stroke, or angina LDL cholesterol levels of 190 mg/dL or more Diabetes plus LDL cholesterol levels of 70-189 mg/dL in those aged 40-75 years LDL cholesterol levels of 70-189 mg/dL and an estimated 10-year risk of heart disease of 7.5% or more in those aged 40-75 years.

Researchers from the Centers for Disease Control and Prevention (CDC) examined data from the 2005-12 National Health and Nutrition Examination Surveys.

How many people follow the advice?

Overall, 36.7% of adults in the US aged 21 years and older were eligible for cholesterol-lowering medication or were already taking it.

Of these, 55.5% were currently taking cholesterol-lowering medication, and 46.6% reported making lifestyle changes; 37.1% reported making lifestyle modifications and taking medication; 35.5% were doing neither.

Gender, race and ethnicity made a difference:

Of 40.8% of all men eligible for or already on medication, 52.9% were taking it Of 32.9% of all women eligible for or already on medication, 58.6% were taking it Of 24.2% of all Mexican-Americans eligible for or already on medication, 47.1% were taking it Of 39.5% of all black adults eligible for or already on medication, 46% were taking it Of 38.4% of all white adults eligible for or already on medication, 58% were taking it.

Black people who did not have a routine place for health care had the lowest rate of taking recommended cholesterol-lowering medication, at 5.7%.

People who had adopted a heart-healthy lifestyle were most likely to be taking cholesterol-lowering medication, at 80%.

Dr. Carla Mercado, a scientist in the CDC's Division for Heart Disease and Stroke Prevention, says:

"Nearly 800,000 people die in the US each year from cardiovascular diseases, that is 1 in every 3 deaths, and high cholesterol continues to be a major risk factor. This study reveals opportunities to reduce existing disparities through targeted patient education and cholesterol-management programs."

The US Department of Health and Human Services' "Million Hearts" initiative aims to prevent 1 million heart attacks and strokes by 2017 through various targets, including getting 65% of Americans to manage their high LDL cholesterol. 

While the study included all forms of cholesterol-lowering medication, a statin was used in nearly 90% of cases.

Medical News Today recently reported on research showing that many people give up using statins as a result of negative news stories about the drugs.

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Can cancer itself damage the heart?

Both treated and untreated cancer patients had impaired heart function.

Research presented today at EuroEcho-Imaging 2015 raises the possibility that cancer itself may damage heart muscle irrespective of exposure to cancer drug therapies. Researchers from the UK's first dedicated cardio-oncology clinic found that both treated and untreated cancer patients had impaired heart function.

The annual meeting of the European Association of Cardiovascular Imaging (EACVI), a registered branch of the European Society of Cardiology (ESC), is held 2 to 5 December 2015 in Seville, Spain.

"It is well known that chemotherapy is potentially toxic to the heart, making cancer patients more prone to cardiovascular complications such as heart failure, hypertension or myocardial ischaemia," said Dr Rajdeep S. Khattar, last author of the abstract and consultant cardiologist at the Royal Brompton Hospital in London, UK. "Our study raises the possibility that tumour growth itself may also damage the heart which could have important implications for monitoring."

The definition of cardiotoxicity is based on a reduced ejection fraction (less than 55%) and symptoms of heart failure. Ejection fraction is a coarse measure of left ventricular function and is assessed by echocardiography. It refers to the percentage of blood pumped into the circulation when the heart contracts. For example, if there is 100 ml of blood in the left ventricle and 65 ml is pumped out, the ejection fraction is 65%.

The current study applied a more subtle measure of left ventricular function using echocardiography called strain. It indicates how well the myocardial fibres contract. Previous studies have shown that cancer patients who have had chemotherapy can have a normal ejection fraction but reduced strain and that this may predict subsequent cardiotoxicity.

Dr Khattar said: "Our study carried this finding a step further to see if untreated cancer patients with a normal ejection fraction also had reduced strain measurements."

The study compared myocardial strain in three groups with a normal ejection fraction (55% or more): 43 patients with cancer who were currently being treated or had received treatment in the past, 36 patients with as yet untreated cancer, and 20 healthy individuals matched to the cancer groups for age and gender.

The researchers found that both groups of cancer patients had similarly reduced strain measurements, indicating impaired heart function, compared to the healthy individuals.

"All of the cancer patients had a preserved ejection fraction so by this coarse measure their hearts were functioning normally," said Dr Khattar. "But the strain measurements showed that they did have myocardial dysfunction."

He continued: "What was really new was the finding of reduced strain, and therefore myocardial dysfunction, in the group of patients with cancer who had not yet received treatment. This raises the possibility that the tumour itself may have a direct and deleterious effect on the function of the heart."

Patients with reduced strain before they start their cancer drug therapies may be predisposed to developing heart failure during the course of their treatment. "These patients might need closer monitoring," said Dr Khattar. "This would be a real change because at the moment, cancer patients don't, as a matter of routine, have a cardiovascular risk assessment by a cardiologist."

This is only the second study in humans which suggests that cancer might have a direct effect on the heart. A study published in September found elevated cardiovascular biomarkers in patients with as yet untreated cancer.2,3 "It could be that the tumour produces these inflammatory markers which then leads to the reduction in myocardial function that we found," said Dr Khattar.

Dr Khattar will continue to follow the patients in the current study to find out if their rates of heart failure and death are predicted by the strain measurements. He said: "If it transpires that the patients with reduced strain prior to cancer treatment are more prone to heart failure and death then it would be important to implement closer monitoring of patients with cancer than is conducted currently."

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Can meditating reduce blood pressure?

Transcendental Meditation involves sitting comfortably and closing the eyes for 20 minutes, twice a day, to achieve a quality of rest in the mind and body. A new study suggests the technique stimulates genes that produce telomerase - an enzyme linked with reduced blood pressure and mortality.
Person meditating
The new study demonstrates how Transcendental Meditation has increased telomerase gene expression in people with high blood pressure.

The new study is published in the journal PLOS One.

Previous studies have reported benefits linked to meditation; Medical News Today recently covered a study that suggested mindfulness meditation reduces pain.

And another study published earlier this year suggested meditation can reduce brain aging.

The researchers from this latest study - led by Dr. Robert Schneider, director of the Institute for Natural Medicine and Prevention at the Maharishi University of Management in Fairfield, IA - say other research into Transcendental Meditation (TM) has been linked the practice to lower rates of high blood pressure, heart attack, stroke and death.

According to the team, stress, lifestyle and telomere dysfunction contribute to hypertension and cardiovascular disease. Telomeres are stretches of DNA at the ends of chromosomes that protect our genetic data.

They have often been compared to the plastic tips on shoelaces, protecting chromosome ends from fraying, which would destroy our genetic information. Shortening of telomeres has been linked with aging, cancer and a higher risk of death.

Telomerase, meanwhile, is an enzyme made of protein and RNA units that elongates chromosomes by adding sequences to the ends.

TM shown to increase telomerase gene expression

Dr. Schneider and colleagues note that hypertension is a major risk factor for cardiovascular disease (CVD). Regarding prevalence of hypertension in the US, however, there are racial and ethnic disparities.

Namely, hypertension prevalence is 48% higher in black Americans than in white Americans, which may contribute to the 50% higher mortality rate from CVD in black Americans, compared with white Americans.

To further investigate techniques that could help with this issue, the researchers conducted a pilot trial involving 48 black men and women with high blood pressure, who were recruited and studied at Howard University Medical Center in Washington, DC.

Of the participants, half were assigned to a group that learned the TM technique and received a basic health education course, and the other half were assigned to a group that focused on achieving lifestyle modifications, including weight reduction, reducing salt intake, taking up regular physical activity and moderating alcohol intake.

Results show that after 16 weeks, both groups exhibited significant increases in telomerase gene expression and reductions in blood pressure. Furthermore, there were no major differences between the changes in the two groups.

"The finding that telomerase gene expression is increased, and that this is associated with a reduction in blood pressure in a high-risk population, suggests that this may be a mechanism by which stress reduction improves cardiovascular health," says Dr. Schneider.

He adds:


"These findings are very encouraging for prevention. They show that both the Transcendental Meditation technique and active lifestyle modification can contribute to heart health."

Study limitations

Although the findings are significant, the authors point to some study limitations.

Firstly, they did not have an inactive control group. As such, they suggest future research "might use a three-arm design, including an inactive or placebo control group."

Additionally, the sample size of the study group was quite small, at 48 participants. The team says a larger sample size "would generate the statistical power needed to either confirm or disprove these findings."

Still, coauthor Dr. Otelio Randall, from Howard University notes that their result "is valuable new information, relevant both to cardiovascular disease and to the molecular mechanisms involved in Transcendental Meditation."

In 2014, MNT published an article by Dr. Schneider that investigated meditation's benefits for mind and body.

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Are blood clots in patients with heart-assist pumps decreasing or on the rise in 2015?

A Difficult Question to Answer, According to Studies Published in The Journal of Heart and Lung Transplantation

More left ventricular assist devices (LVADs), a mechanical heart that helps pump blood, are now implanted annually than hearts transplanted in patients with advanced stages of heart failure. Evidence-based data indicate that LVADs have saved many lives, whether as a bridge to heart transplantation or as a permanent therapy for heart failure. However, starting in 2011 device failures due to clots forming inside these pumps (pump thrombosis) appeared to rise dramatically. There is some indication that these failures may now be declining, but data analysis and interpretation are complex. In the current issue of The Journal of Heart and Lung Transplantation several studies suggest that management of patients with LVADs may have to change.

There has been vigorous debate within the medical community because multiple explanations for increased LVAD thrombosis rates have been posited. Using data from the Interagency Registry of Mechanically Assisted Circulation Support (INTERMACS), which tracks the use of LVADs worldwide, researchers from multiple centers analyzed information about contemporary trends in pump thrombosis following the spike in such events noted in 2011.

"In Late November of 2013, The Journal of Heart and Lung Transplantation first developed a compendium of articles on the emerging issue of pump thrombosis, which has led to a vigorous debate and attention to changed practices. We now present updated analyses to assess the impact of this renewed attentiveness to the issue," explained Mandeep R. Mehra, MD, Editor-in-Chief.

Two independent analyses, from the same databases appear in in this issue, the first from James K. Kirklin, MD, and co-investigators at the University of Alabama at Birmingham, and the second from Nicholas G. Smedira, MD, and colleagues at the Cleveland Clinic. Using the same INTERMACS data but analyzing with different statistical models, Kirklin confirmed an increasing risk of thrombosis from 2011 through 2013 followed by an observed decrease in risk in the first half of 2014, while Smedira's analysis concluded that there was no fallloff in 2014.

Neal Jeffries, PhD, and co-investigators at the National Heart, Lung, and Blood Institute, Bethesda, Maryland, ask, "What is the truth behind the recent trends - are thrombosis rates increasing, decreasing, or remaining relatively unchanged?" Their analysis of the INTERMACS data for the HeartMate II concluded that thrombosis risk has increased through 2011-2013 but whether this risk has been reduced in 2014 is inconclusive.

John M. Stulak, MD, and associates at the Mechanical Circulatory Support Research Network (Mayo Clinic College of Medicine, Vanderbilt Heart and Vascular Institute, and the University of Michigan) report on a study of treatment options for patients with a pump thrombosis while using the HeartWare device. Their conclusion was that the incidence of pump thrombosis with this device, approved for bridge to transplantation, is also significantly elevated and that medical therapy using anti-clotting and clot-dissolving drugs is unsuccessful in half of the cases, while pump replacement was uniformly successful. They also caution that, "the ideal approach remains elusive and will always depend heavily on a combination of patient-related and device-related factors and the weighing of risks of benefits of each approach."

An editorial by Garrick C. Stewart, MD, MPH, Michael M. Givertz, MD, and Mandeep R. Mehra, MD, from Brigham and Women's Hospital and Harvard Medical School, Boston, MA, discusses the current state of LVAD thromboses and patient care. Dr. Mehra noted that "These reports present sobering data on the consequences of pump thrombosis and suggest several important clinical directions. This series of studies is an important referendum on the INTERMACS registry, now entering its second decade, and confirm the vital role for collecting real-world data in cardiac device therapy." Importantly, they provide practical tips on communicating this information to patients who are being considered for heart pump implantation, to weigh the pros and cons of different devices and expected outcomes.

"Is there a glimmer of hope in reducing risk of pump thrombosis with newer devices?" asked Stewart, Givertz, and Mehra. "Promising preliminary data have emerged about the next-generation magnetically levitated centrifugal flow HeartMate 3. Engineering progress along with a better understanding of hemocompatibility will undoubtedly help to reduce the problem of pump thrombosis and will allow the expansion of mechanical circulatory support into broader groups of patients. Until then we must redouble our efforts to ensure that today's patients live longer and better with approved pump technology even as we look with hope to the future."

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A Japanese multicenter clinical study on the prevention of stroke recurrence by statin

The results of "The Japan Statin Treatment Against Recurrent Stroke (J-STARS)" study led to the hypothesis that statins reduce the occurrence of strokes due to larger artery atherosclerosis.

J-STARS examined whether pravastatin, a traditional statin widely used in the clinic, reduces the recurrence of strokes and respective subtypes in non-cardioembolic stroke patients. The study also examined whether the use of pravastatin favorably impacts the occurrence of other vascular events, and stroke-related functional outcomes were explored.

Statins are widely used to reduce cholesterol levels in blood. High cholesterol levels are associated with cardiovascular diseases such as strokes, so statins are thought to be beneficial for stroke prevention. However, these findings are obtained from patients without prior stroke, and the preventive effect is less robust in patients with prior stroke.

J-STARS is a multicenter, randomized, open-label, blinded-endpoint, parallel-group study of patients who experienced a non-cardioembolic ischemic stroke. In total, 1578 patients were recruited and randomly assigned to either the pravastatin group or the control group.

During a follow-up of about 5 years, the incidence of recurrent strokes was about 2.6%/year in both groups. The onset of atherothrombotic infarction, a stroke subtype, was clearly less frequent in the pravastatin group, whereas no significant difference was found for other stroke subtypes. No significant difference was found between the two groups in terms of the occurrence of adverse effects, which included cancer and laboratory examinations.

Professor Masayasu Matsumoto, a J-STARS principal investigator at Hiroshima University said "the pravastatin dose used in this study is lower than that used in studies from Western countries, but it is the approved standard dose in Japan." He explained "Stroke is a heterogeneous disease with different etiologies with or without underlying arterial pathologies. Thus, the benefits of statin may be different depending on the subtypes of the stroke."

The majority of previous studies defined stroke as a whole with no distinction between subtypes. Moreover, current international guidelines uniformly recommend the use of statin for secondary stroke prevention.

According to Professor Matsumoto, "Further studies are required to determine whether such guidelines are applicable for Asians. Although the current study has certain limitations, J-STARS can contribute to the establishment of guidelines for using statins to prevent strokes caused by larger artery atherosclerosis."

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Genetic condition could be putting more than 250,000 people at risk of early heart attack

BHF calls for national rollout of genetic testing for Familial Hypercholesterolaemia.

As many as 250,000 people in the UK may be living with the deadly inherited gene which causes Familial Hypercholesterolemia (FH), according to a revised estimate.1

The charity is calling on health services across the country to urgently rollout a nationwide cascade testing programme.

FH is a genetic condition caused by a genetic fault that leaves people with dangerously high cholesterol from birth which significantly increases their risk of a heart attack. On average, FH can shorten life expectancy by 20 to 30 years if left untreated. Only around 20,000 people are thought to be receiving full treatment in lipid clinics.

Despite recommendations by National Institute for Clinical Excellence (NICE) that NHS Trusts and health boards roll-out cascade testing for FH for families across the UK, setting up of FH services has been slow in England and Scotland.

To start tackling the problem, the BHF have funded 25 FH nursing posts across 13 different locations to make sure millions of people have access to testing. As those posts have been set up over the past two years, 974 people have been tested and 374 people (38% of those tested) have been shown to have FH, ensuring they get the treatment they need.

The charity believes that the slow response by health services is putting thousands of people across the UK at an unnecessary risk of heart attacks early in life.

If all of the estimated 250,000 people with the FH gene in the UK were identified and treated, as many as 25,000 deaths of people in the UK could be avoided2.

The BHF has funded Professor Steve Humphries and his research team at UCL over the past 30 years to find the genes responsible for the condition and develop genetic testing methods for FH. They used these techniques to establish a national DNA diagnostic service, which has already found many people with FH by tracing the relatives of known FH patients.

Thanks to Professor Humphries' research, genetic testing for FH is starting to be rolled out across the NHS. Thisensures close family members of people diagnosed will be tested to ensure they get treatment as soon as possible if they have FH too.

The key to preventing early heart attacks caused by FH is early diagnosis. The younger someone is identified, the earlier they can begin to be treated before the high cholesterol causes permanent harm to their arteries. When their diagnosis has been confirmed they can receive support for a healthy lifestyle and reduce their risk of dangerously high cholesterol. Statins may be prescribed adults or children over the age of 10.

Professor Peter Weissberg Medical Director at the British Heart Foundation, said: "Thirty years of BHF-funded research into this deadly genetic condition means we've now got the ability to identify people at high risk of a heart attack because of FH and give them treatment that could save their life. FH is often called a hidden killer, but the truth is it doesn't have to be hidden and it doesn't have to be fatal; treatment to prevent heart attacks is straightforward once the condition has been identified. The job we face now is to raise awareness of FH and change the hearts and minds of commissioners and others who purchase healthcare services to ensure that this is the last generation where families are left at high risk of early heart attacks."

If people are diagnosed early enough and given early statin treatment, lifestyle advice and careful monitoring, the life expectancy of someone with FH rises to match that of someone in the general population.

With a simple DNA blood test, it's relatively straightforward to find out whether someone carries the faulty FH gene. If this is found, they are then referred for family cascade testing, where all immediate first degree relatives are also invited for testing and treatment. Typically if one person is found to have FH, half of their brothers and sisters and half of their children will also have the faulty gene and be at a higher risk of early onset of heart disease, including a heart attack.

Professor Huon Gray, National Clinical Director for Heart Disease at NHS England said: "Research has given us a much better understanding of this illness and NICE has published guidance on how we should approach the better detection and management of affected families. A model for cascade testing is available, and treatments are widely available. The collaborative work by organisations that form the FH Steering Group is helping increase the identification of affected individuals but more work needs to be done. We all have a role to play in ensuring that future generations aren't put at an increased risk early heart attacks."

David Collings, a civil servant living in Mold in Flintshire has first-hand experience of living with FH. He said: "On Boxing Day 2010, I could feel my chest getting tighter and tighter as I was walking my dogs through the forest and I was feeling exhausted and breathless. After a few days of struggling, I went to my doctor who said he thought I had had a heart attack. I was absolutely shocked, particularly as I had never smoked and had been walking and cycling for years. After I was diagnosed, I was referred to the FH support group in Wrexham where I was living at the time. Not only did I have the gene, but six people in my immediate family were quickly identified, including my daughter Bethan who was 12 at the time.

"FH can be a ticking bomb and I feel so much better knowing that my daughter has been identified and can be monitored and treated. If my local clinic hadn't found the gene, the first sign of my daughter being affected could have been a heart attack in twenty years' time. Finding out that she carries the gene as well might well have saved her life."

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New heart failure therapy projected to increase life expectancy

Heart failure, the leading cause of hospitalization for Americans over the age of 65, accounts for more than one million hospitalizations in the US each year. Nearly six million Americans have heart failure, about half of whom have the reduced ejection fraction form, a reduced capability to pump blood from the heart. Heart failure patients with a reduced capability to pump blood from the heart have a marked increased risk for further cardiac events and death.

New research from Brigham and Women's Hospital finds that heart failure patients with reduced ejection fraction who are treated with sacubitril-valsartan have a projected increased life expectancy of one and a half to two years, as compared to those treated with enalapril, the current standard of care in heart failure. These findings are published in the December 3 issue of the New England Journal of Medicine.

"These results help both patients and their physicians understand the impact of switching from the standard of care to sacubitril-valsartan, in terms of a benefit that they can easily understand," said Scott D. Solomon, MD, senior author and director of Non-Invasive Cardiology at Brigham and Women's Hospital (BWH) and Professor of Medicine at Harvard Medical School. "Patients want to know how much longer they are going to live, rather than how much their risk will be reduced."

In this new analysis, researchers examined data from 8,399 patients in the PARADIGM-HF study, the largest clinical trial ever conducted in heart failure, and used actuarial methods that are typically used by the insurance industry, to measure the estimated lifetime benefits of treatment with sacubitril-valsartan as determined by age-specific cardiovascular events. Researchers derived expected survival times using data from the beginning of the study and the age at the time of a cardiovascular event. An average duration of event-free survival was estimated using long-term follow up data from the clinical trial.

Assuming that the protective effects of sacubitril-valsartan remain consistent with long-term use, researchers estimated that the benefits were similar across a wide range of ages. Specifically, patients 45-75 years old using sacubitril-valsartan had a projected extended benefit of one to two years of increased life expectancy, free from heart failure hospitalization, when compared to patients of the same age who were treated with enalapril.

The PARADIGM-HF trial was supported by Novartis. Novartis manufactures sacubitril-valsartan under the brand name, Entresto ™.

About PARADIGM-HF

The PARADIGM-HF trial previously showed that sacubitril-valsartan was superior to enalapril in reducing the rates of hospitalization for heart failure, death from cardiovascular causes, and death from any cause among heart failure patients with a reduced capability to pump blood from the heart (ejection fraction). Sacubitril-valsartan was shown in PARADIGM-HF to reduce cardiovascular death or heart failure hospitalization by 20 percent, and also improved overall survival by 16 percent, versus enalapril. The study was stopped early by the Data Monitoring Committee overseeing the study because of overwhelming benefit in patients treated with sacubitril-valsartan. The primary results of the PARADIGM-HF trial were published in The New England Journal of Medicine in 2014.

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Biophysicists develop a model for arterial thrombus formation

A group of biophysicists, including representatives from MIPT, has developed a mathematical model of arterial thrombus formation, which is the main cause of heart attacks and strokes. The scientists described the process of platelet aggregation as being similar to the popular video game Tetris and derived equations that allowed them to reproduce the wave process of platelet aggregate formation in a blood vessel.

Researchers from the Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology (FRCC PHOI), the Center for Theoretical Problems of Physico-Chemical Pharmacology, MIPT, Moscow State University, the Institute for Problems of Mechanical Engineering (St Petersburg), and the Free University of Berlin described the new model in the journal PLOS ONE. When discussing the development of the model and the members of the research team, Mikhail Panteleev, one of the authors of the publication, said: "Fazly Ataullakhanov and I formulated the problem and derived the equation, and Evgenia Babushkina (now a graduate student in Berlin), under the guidance of her mentor Nikolay Bessonov, developed solution methods for the two-dimensional case taking into account the changing hydrodynamics of the flow in which the thrombus is formed. She also performed all the simulations and analyses. Fazly and I are professors of the Department of Translational and Regenerative Medicine of MIPT's Faculty of Biological and Medical Physics, which is based at FRCC PHOI".

Develpoment of a continuous adsorption equation under assumption that thrombus formation occurs in the same way as the tiles become stacked up in the classic video game Tetris is a key aspect of the new model. In Tetris, the tiles either drop down onto a flat surface, or become attached to parts sticking out from the rest of the block. The only difference between thrombus formation and the game is that when a layer is complete, it does not disappear, therefore as time passes a thrombus is capable of obstructing the space it is in. In addition, the falling shapes are always the same: the model describes the aggregation of platelets, specialized blood cells.

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