James Fang discusses LVADs for End-Stage Heart Failure with WebMD

More than 5 million Americans have heart failure, a progressive and often lethal condition that weakens the heart and saps its pumping power. The mainstays of treatment — including drug therapy, lifestyle modification, and surgery to implant pacemakers or defibrillators — can be quite effective at managing symptoms of mild to moderate heart failure.

But what about the estimated 150,000 Americans who suffer from chronic, severe heart failure?

Doctors traditionally have had little to offer these patients in the way of lifesaving treatment, short of a heart transplant. But with only about 2,100 donor hearts available each year, the demand for hearts inevitably outweighs the supply. And some patients are simply too old to qualify for a transplant. For them, what’s the alternative?

There’s now an option that could change the outlook for many with severe heart failure: implantable mechanical pumps called left ventricular-assist devices (LVADs or sometimes simply VADs.)

These devices were once just used as a “bridge” — a temporary stopgap to keep heart failure patients alive until they could get a heart transplant. But now, they have become so effective that doctors use them as a treatment in themselves. LVADs are now an alternative to heart transplants, permanently augmenting the action of a heart’s main pumping chamber.

In addition, the continuous-flow LVAD was associated with fewer infections and a significantly lower rate of failure.

“The continuous-flow LVAD has changed the landscape of advanced heart failure,” says James C. Fang, MD, chief medical officer of the Harrington-McLaughlin Heart and Vascular Institute at University Hospitals Case Medical Center in Cleveland and the author of an editorial on LVADs that accompanied the study in the New England Journal of Medicine.

“In addition to being more durable, the new device is a lot smaller – about the size of a D battery. It’s also quiet. You can barely hear it. With the old devices, you could hear them coming down the street.”

Find the full article on CWRUmedicine.org

Susan Redline discusses Sleep Apnea Increases Stroke Risk with WebMD

Moderate to Severe Sleep Apnea Triples Stroke Risk in Men, Study Finds

WebMD | April 8, 2010

Obstructive sleep apnea more than doubles the risk of stroke in men and also increases the danger in women, new research indicates.

The finding comes from a major study of 5,422 people aged 40 and older who had no history of stroke. Researchers say increased risk of stroke appeared in men with mild sleep apnea and rose with severity.

Men with moderate to severe sleep apnea were about three times more likely to have a stroke than men with mild or no sleep apnea, researchers say.

The increased risk of stroke in women with obstructive sleep apnea was significant only in cases of severe apnea, according to the study, published in the American Journal of Respiratory and Critical Care Medicine.

Obstructive Sleep Apnea and Stroke
Data were taken from the Sleep Heart Health Study, which is ongoing at a number of locations. The participants in the beginning performed a standard at-home sleep test to determine whether they had sleep apnea, and if so, its severity.

They were followed for about nine years, and during that time, 193 suffered strokes — 85 men out of 2,462 enrolled and 108 women out of 2,960.

“Although more women had strokes, relatively more men with sleep apnea than without sleep apnea had strokes, and less so in women,” study author Susan Redline, MD, MPH, of Case Western Reserve University in Cleveland, tells WebMD in an email. “I think that the relatively greater impact of sleep apnea on risk of stroke in men relates to the likely longer duration of sleep apnea in men than women.”

Researchers say more than 15 million strokes occur worldwide every year, and that about a third are fatal. Increased risk of stroke in people with sleep apnea exists even without other risk factors, such as weight, high blood pressure, race, diabetes, and smoking.

Men may be more at risk because they develop sleep apnea at younger ages, the researchers say, and thus go untreated for longer periods.

Learn more at CWRUmedicine.org

theHeart.org feature CWRUmedicine research on shared molecular pathway identified for cardiac and vascular disease

theHeart.org | US researchers have pinpointed a genetic factor that affects diseases of both the heart and blood vessels and identified a molecular pathway shared between the two. They propose that a subset of human heart and vascular disease may be due to deficiency of this genetic factor, known as Krüppel-like factor 15 (Klf15), and that amending the pathway in some way could help ameliorate both diseases.

Dr Saptarsi M Haldar (Case Western Reserve University, Cleveland, OH) and colleagues report their findings online April 7, 2010 in Science Translational Medicine.

“Often, people think of cardiac disease and vascular disease as separate entities, but they often run together—for example, in Marfan’s syndrome or in aging, when there are degenerative changes to both the heart and blood vessels,” senior author Dr Mukesh K Jain (Case Western Reserve University) explained to heartwire.

Some years ago, his research team identified the genetic factor Klf15 and showed that it was expressed in both the heart and aorta; they also demonstrated that in human tissue from patients with heart failure or aortic aneurysmal disease, the expression of Klf15 was markedly reduced. The new research is an attempt to identify a common molecular pathway for these effects that could represent a potential therapeutic target.

Both heart and blood vessels affected by Klf15 deficiency

“We hypothesized that maybe the absence of Klf15 or its relative deficiency might be unhealthy, so we generated mice to mimic this,” Jain explains. The mice, which were completely deficient in Klf15, were then stressed using angiotensin 2, and they developed heart failure and, “quite unusually,” aneurysms at the same time, he notes, “so we showed that both the heart and blood vessels of the mice were affected by deficiency of Klf15.

“We then wondered whether there was a common molecular mechanism that might explain this shared pathology,” he continued.

They went on to show that enhancement of the activity of p53—a protein most often associated with protection against cancer—appeared to be causing the adverse effects in the setting of Klf15 deficiency.

Furthermore, they showed that Klf15 functions as a “molecular brake” on p53 function by inhibiting p53 acetylation, which is a critical “on” switch for this protein.

These molecular effects were operative both in the Klf15-deficient mice and in human tissues from heart-failure patients, which were also found to be Klf15 deficient.

Boosting Klf15 production or blocking p53 acetylation may be of benefit

“This now lends us the opportunity to try to identify a chemical compound that might either boost the activity of Klf15 or somehow block the acetylation of p53, which might help ameliorate diseases affecting both the heart and blood vessels,” Jain noted. As well as aging and Marfan’s syndrome, this includes peripartum cardiomyopathy and in particular a subset of women who develop aortic dilatation as well as heart failure in the setting of pregnancy, he explained.

The discovery of new molecular pathways that are amenable to therapeutic manipulation is of immense clinical value,” he says, adding that research into compounds targeting Klf15 or p53 is already under way. Researchers have already demonstrated that a compound called curcumin, the active constituent of the spice turmeric that is often used in Asian cooking, is able to block the acetylation of p53, and they are actively trying to identify other compounds that could enhance the expression of Klf15.

Read the abstract on CWRUmedicine.org

Case Western Reserve University School of Medicine researchers have identified a major indicator of two deadly diseases of the heart and blood vessels: heart failure and aortic aneurysm

Case Western Reserve University School of Medicine researchers have identified a major indicator of two deadly diseases of the heart and blood vessels: heart failure and aortic aneurysm.

The absence of the Kruppel-like Factor 15 (KLF15), when combined with stress, leads to both heart failure and aortic aneurysms. The genetic factor, KLF15, protects the heart and aorta’s ability to maintain structural and functional integrity. Patients with these diseases were found to have reduced levels of the protective gene, and in an animal study, the researchers proved that deficiency of this single gene predisposes one to these cardiovascular diseases. Furthermore, they show that KLF15 exerts its protective effects in the heart and aorta through a common molecular mechanism. Lastly, the researchers show that drugs targeting this molecular pathway can be used to treat heart failure and aortic aneurysms. The unprecedented findings are published in the April 7th online edition of Science Translational Medicine, an American Association for the Advancement of Science publication.

All the blood circulating through the human body must be pumped out by the heart and flow though the aorta. These two vital organs must maintain structural integrity in the face of mechanical and biochemical stress, otherwise lethal consequences such as heart failure, aortic aneurysms, and aortic dissection can develop. While it has been known that diseases of the heart and aorta can co-exist, for example in Marfan’s syndrome, pregnancy, aging, and growth hormone excess, the cardiovascular diseases are typically treated independently. The identification of shared molecular mechanism offers new promise for current and future treatment options.

“This is very rare to find a singular genetic factor that governs the response of the entire cardiovascular system. Our research proves KLF15 governs the shared diseases of the heart and blood vessels,” says Mukesh K. Jain, M.D., F.A.H.A., senior author of the study and Director of the Case Cardiovascular Research Institute at Case Western Reserve University and the Chief Research Officer for the Harrington-McLaughlin Heart and Vascular Institute at University Hospitals Case Medical Center. In 2002, while at Brigham and Women’s Hospital/Harvard Medical School, Dr. Jain and his team of researchers discovered KLF15.

Read the full article at CWRUmedicine.org

CWRUmedicine and UH develops New Drugs to improve oxygen delivery to tissues

Case Western Reserve University and University Hospitals are pleased to announce the awarding of a $4.7 million contract from the Defense Advanced Research Projects Agency (DARPA) to Dr. Jonathan Stamler, Director of the Institute for Transformative Molecular Medicine (ITMM).

The grant will fund development of a new class of drugs that selectively vasodilate under hypoxia and thereby enhance performance at high altitude (e.g. soldiers on mountains in Afganistan).

It is also anticipated that the grant will generate new physiologic information on high-altitude adaptation and new therapeutic interventions to treat patients suffering from conditions where oxygen delivery is impaired, including heart failure, ischemic heart disease, stroke, sickle cell disease and diabetes.

Studies will involve a transdisciplinary approach, including the Department of Anesthesia (James Reynolds) the division of Pulmonary Medicine (Kingman Stroh), and the Harrington-McLaughlin Cardiovascular Institute (Sahil Parikh).

Learn more at CWRUmedicine.org

New Research from the Division of Infectious Disease on Beta-Lactamases

Penicillin sulfone inhibitors of class D beta-lactamases
Antimicrob Agents Chemother. 2010 Apr

Drawz SM, Bethel CR, Doppalapudi VR,Hujer AM, Skalweit MJ, Anderson VE, Chen SG, Buynak JD, Bonomo RA.
Departments of Pathology, Case Western Reserve School of Medicine, Cleveland

Armand Krikorian, MD publishes “Comparisons of Different Insulin Infusion Protocols”

“Comparisons of different insulin infusion protocols: a review of recent literature”

Curr Opin Clin Nutr Metab Care. 2010 March
Krikorian A, Ismail-Beigi F, Moghissi ES.

Division of Clinical & Molecular Endocrinology
Case Western Reserve University
University Hospitals, Cleveland

Read the abstract at CWRUmedicine.org

Journal of Lipid Research publish Dr Charles Hoppels recent work on the inner mitochondrial membrane

“Separation and characterization of cardiolipin molecular species by reverse-phase ion pair high-performance liquid chromatography-mass spectrometry”

J Lipid Res. 2010 Apr
Minkler PE, Hoppel CL.

Center for Mitochondrial Diseases, Division of Pharmacology, Department of Medicine, Case Medical Center, University Hospitals, Cleveland

Read the full abstract on CWRUmedicine.org

Message from Richard A. Walsh, MD

We have over 250 full time faculty, 120 medical housestaff, 80 fellows and 400 support staff working at the CWRU School of Medicine, University Hospitals Case Medical Center and the Cleveland VA Medical Center Wade Park Campus.

We are proud of our premier, extramurally funded research programs, our delivery of high-quality, cost-effective patient care at University Hospitals (ranked as a Top Ten Health Care System by Thompson Reuters) and our VA Hospital (ranked first in the entire VA system for Health Care Delivery Measures).

We are also deeply committed to medical student, graduate student and post graduate training.

Our faculty, trainees and staff are committed to the highest standard of excellence in all of our activities in a collegial, integrated and interactive work environment.

We invite you to navigate our website to learn more about who we are and what we do. Visit us at CWRUmedicine.org
If we can be of help, please contact us.

Richard A. Walsh, MD

Chair, Department of Medicine

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It doesn’t take much effort to see the impact social media is having on almost every avenue of our lives, both professionally and personally. Tools such as LinkedIn, Twitter and Facebook, just to name a few, are changing the way and frequency in which we communicate. It should be no surprise, then, that even Healthcare would find itself impacted by the influence and immediacy that social media provides.

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