Medical payments affect heart attack outcomes

Researchers from Beth Israel Deaconess Medical Center (BIDMC) analyzed if medical payments for acute myocardial infarction affects treatment outcomes for patients. Findings of this research are published in journal Circulation.

To cut down healthcare expenditure there has been a growing trend towards providing incentives to reduce cost at the same time maintaining acceptable outcomes. Hospital Value-Based Purchasing Program administered by the Centers for Medicare and Medicaid Services (CMS) is one such effort to reduce the cost of care. This program makes payments based on quality outcome measures for conditions such as acute myocardial infarction. Hospitals that perform poorly in these measures receive a reduced payment.

Researchers used national Medicare claims data and examined more than 640,000 hospitalizations involving patients 65 years or older hospitalized for heart attack and found that higher 30-day spending to care for Medicare beneficiaries with acute myocardial infarction was associated with a modest reduction inpatient mortality.

“Recent policy efforts have focused on improving the value of care, both in terms of total spending and patient outcomes,” said corresponding senior author Robert W. Yeh, MD, MSc, Director of the Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center. “We need to understand whether programs like the Hospital Value-Based Purchasing Program are able to globally reduce spending and improve outcomes for acute conditions like acute myocardial infarction, or whether the strong incentive to reduce hospital spending has unintended adverse consequences.”

“These findings have important implications for patient care,” said first author Rishi K. Wadhera, MD, MPhil, an investigator at the Smith Center at Beth Israel Deaconess Medical Center and a cardiology fellow at Brigham and Women’s Hospital.Wadhera. “While this study found that increased spending was associated with better outcomes, not all spending is of equal value and further research is needed to find out why higher-spending hospitals have better outcomes.”

Citation: Wadhera, Rishi K., Karen E. Joynt Maddox, Yun Wang, Changyu Shen, Deepak L. Bhatt, and Robert W. Yeh. “Association Between 30-Day Episode Payments and Acute Myocardial Infarction Outcomes Among Medicare Beneficiaries.” Circulation: Cardiovascular Quality and Outcomes 11, no. 3 (2018). doi:10.1161/circoutcomes.117.004397.

Research funding: National Institute of Health

Adapted from press release by Beth Israel Deaconess Medical Center.

Understanding interaction between heart muscle cells and nanoscaffoding

Researchers from Moscow Institute of Physics and Technology (MIPT) have researched nanofibrous scaffold structure and its interaction with rat heart muscle cells.  This study revealed that cardiac muscle cells envelop nanofibers as they grow, but fibroblasts tend to spread out on fibers forming several focal adhesion sites.

Nanofibers enveloped by Heart muscle cells. The 3-D model was reconstructed using scanning probe nanotomography.
Credit: Moscow Institute of Physics and Technology.

The study was conducted at MIPT’s Laboratory of Biophysics of Excitable Systems in collaboration with the researchers from the Shumakov Federal Research Center of Transplantology and Artificial Organs and the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences. The article is published in the journal Acta Biomaterialia.

“Using three independent methods, we discovered that during their development on a nanofibrous scaffold, cardiomyocytes wrap the fibers on all sides creating a ‘sheath’ structure in the majority of cases,” explains Professor Konstantin Agladze, head of the Laboratory of Biophysics of Excitable Systems. “Fibroblasts, by contrast, have a more rigid structure and a much smaller area of interaction with the substrate, touching it only on one side.”

The scaffolds used for cardiac tissue engineering are based on a matrix of polymer nanofibers. Nanofibers may vary regarding elasticity and electrical conductivity, or they may have additional “smart” functions allowing them to release biologically active molecules at a certain stage. Nanofibers are designed to mimic the extracellular matrix, which surrounds the cells, providing structural support. Also, nanofibers can be used as a medium for delivering substances into the surrounding cells to induce biochemical changes in them.

The team conducted a three-stage study. First, the researchers examined the structure of cardiomyocytes (heart muscle cells) and fibroblasts (connective tissue cells) grown on a substrate of nanofibers using confocal laser scanning microscopy. Cell samples were then sectioned into ultrathin slices in a plane perpendicular to the direction of the fibers and “photographed” using transmission electron microscopy (TEM). The researchers discovered that heart muscle cells envelop nanofibers on all sides so that the fiber ends up being in the middle of the cell. Nevertheless, it remains separated from the cytoplasm by the cell membrane.

Connective tissue cells, on the other hand, do not “swallow” the fiber; they only touch it on one side. Moreover, transmission electron microscopy images demonstrate that the nucleus of the fibroblast is relatively rigid compared to other cell components. This makes fibroblasts less flexible, reducing their ability to stretch along the fiber. Transmission electron microscopy made it possible to study the cross sections. Then, using scanning probe nanotomography, a comprehensive 3-D model was created.

Researchers observed some crucial aspects of the cell-fiber interaction. First of all, since stronger mechanical adhesion, i.e., the cell-scaffold attachment means cells are more stable growing on the substrate, heart muscle cells will be firmly attached to the scaffold, while fibroblasts will be less stable.

Secondly, additional “smart” scaffold functions, such as the release of growth factors will also differ depending on the cell type. In the case of heart muscle cells, which tend to envelop the nanofiber, the released substances will diffuse directly from the fiber through the cell membrane and into the cytoplasm. In the case of fibroblasts, on the other hand, a certain amount of these substances will leak out.

Thirdly, heart muscle cells isolate the polymer fibers from the surrounding solution. Since heart muscle cells are responsible for the transfer of electromagnetic waves within the heart immersing the fibers of the scaffold entirely in heart muscle cells will enable researchers to test the electrical conductivity of the cells.

Researchers feel that this study will enable the creation of nanofibers that would provide cells with the properties needed to form regenerative tissues.

Citation: Balashov, Victor, Anton Efimov, Olga Agapova, Alexander Pogorelov, Igor Agapov, and Konstantin Agladze. “High resolution 3D microscopy study of cardiomyocytes on polymer scaffold nanofibers reveals formation of unusual sheathed structure.” Acta Biomaterialia 68 (2018): 214-22. doi:10.1016/j.actbio.2017.12.031.

Research funding: Ministry of Education and Science of the Russian Federation

Adapted from press release by Moscow Institute of Physics and Technology  (MIPT)

Association between inflammatory bowel disease and heart disease found

Researchers analyzed medical-record data from more than 17.5 million patients found that people with inflammatory bowel disease (IBD) are at increased risk for a heart attack, regardless of whether or not they have risk factors for heart disease. This research is presented at the American College of Cardiology’s 67th Annual Scientific Session.

“Younger patients had about nine times the risk of a heart attack compared to their peers in the same age group [who didn’t have IBD], and this risk continued to decline with age,” said Muhammad S. Panhwar, MD, a resident in internal medicine at Case Western Reserve University/University Hospitals Cleveland Medical Center in Cleveland and lead author of the study. “Our findings suggest that IBD should be considered an independent risk factor for heart disease.”

Inflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis. Per Centers for Disease Control and Prevention (CDC) data, as of 2015, an estimated three million Americans have IBD, and about 70,000 new cases are diagnosed every year.

Researchers utilized IBM Explorys, a database of de-identified data from electronic records for patients of 26 nationwide health care systems in the U.S. They then identified 211,870 patients aged 18 to 65 diagnosed with of inflammatory bowel disease (IBD) between 2014 and 2017. Researchers then looked at the rate of heart attacks in the normal population and those with inflammatory bowel disease. Compared with patients who did not have Inflammatory bowel disease, heart attacks occurred roughly twice as often in those with Inflammatory bowel disease.

Researchers also found that people with Inflammatory bowel disease (IBD) were also more likely to have diabetes, hypertension, high cholesterol, and smoking than people without inflammatory bowel disease.  After adjusting for age, race, sex and traditional heart disease risk factors, Panhwar and his colleagues found that the patients with inflammatory bowel disease had about a 23 percent higher risk of having a heart attack. Women under the age of 40 with IBD were at higher risk for a heart attack than men with IBD in the same age group. In patients over the age of 40, heart attack risk was similar for men and women with inflammatory bowel disease.

“Our study adds considerably to a growing set of literature highlighting the importance of chronic inflammation in IBD as having a role in the development of heart disease,” Panhwar said.

Adapted from press release by the American College of Cardiology.

Animal study finds MeXis gene protective against coronary artery disease

UCLA scientists have identified a gene called MeXis that may play a protective role in preventing heart disease. Their findings suggests that this gene acts within macrophages inside clogged arteries to help remove excess cholesterol from blood vessels by controlling cholesterol pump protein expression. Research is published in the journal Nature Medicine.

MeXis is an example of a “selfish” gene, one that is presumed to have no function because it does not make a protein product. However, recent studies have suggested that these so-called “unhelpful” genes can actually perform important biological functions without making proteins and instead producing a special class of molecules called long non-coding RNAs, or lncRNAs.

“What this study tells us is that lncRNAs are important for the inner workings of cells involved in the development of heart disease,” said Dr. Peter Tontonoz, senior author of the study. “Considering many genes like MeXis have completely unknown functions, our study suggests that further exploring how other long non-coding RNAs act will lead to exciting insights into both normal physiology and disease.”

In the study, researchers found that mice lacking MeXis had almost twice as many blockages in their blood vessels compared to mice with normal MeXis levels. In addition, boosting MeXis levels made cells more effective at removing excess cholesterol. In the next phase of the study, researchers will further explore how MeXis affects the function of cells in the artery wall and will test various approaches to altering MeXis activity. The researchers are interested in finding out if MeXis could be targeted for therapy of cardiovascular disease.

Citation: Sallam, Tamer, Marius Jones, Brandon J. Thomas, Xiaohui Wu, Thomas Gilliland, Kevin Qian, Ascia Eskin, David Casero, Zhengyi Zhang, Jaspreet Sandhu, David Salisbury, Prashant Rajbhandari, Mete Civelek, Cynthia Hong, Ayaka Ito, Xin Liu, Bence Daniel, Aldons J. Lusis, Julian Whitelegge, Laszlo Nagy, Antonio Castrillo, Stephen Smale, and Peter Tontonoz. “Transcriptional regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA.” Nature Medicine, 2018. doi:10.1038/nm.4479.

Funding: NIH/National Heart, Lung and Blood Institute, Burroughs Wellcome Fund Career Awards for Medical Scientists, UCLA Cardiovascular Discovery Fund, Lauren B. Leichtman and Arthur E. Levine Investigator Award.

Adapted from press release by the University of California Los Angles Health Sciences.

I-Wire, a new Heart-on-a-Chip device to study biomechanical properties of heart

Scientists at Vanderbilt University have created a 3D organ-on-a-chip that can mimic the biomechanical properties of the heart. The device and the results of initial experiments are reported in the journal Acta Biomaterialia (for links see below).

View of the cardiac fiber in the I-Wire device at two levels of magnification.
Credit: VIIBRE Vanderbilt University

The unique aspect of the new device, which represents about two-millionths of a human heart, is that it controls the mechanical force applied to cardiac cells.  This allows the researchers to reproduce the mechanical conditions of the living heart in addition to its electrical and biochemical environment.

“We created the I-Wire Heart-on-a-Chip so that we can understand why cardiac cells behave the way they do by asking the cells questions, instead of just watching them,” said Gordon A. Cain University Professor John Wikswo, who heads up the project. “We believe it could prove invaluable in studying cardiac diseases, drug screening and drug development, and, in the future, in personalized medicine by identifying the cells taken from patients that can be used to patch damaged hearts effectively.”

The I-Wire device consists of a thin thread of human cardiac cells 0.014 inches thick (about the size of 20-pound monofilament fishing line) stretched between two perpendicular wire anchors. The amount of tension on the fiber can be varied by moving the anchors in and out, and the tension is measured with a flexible probe that pushes against the side of the fiber. The fiber is supported by wires and a frame in an optically clear well that is filled with a liquid medium like that which surrounds cardiac cells in the body. The apparatus is mounted on the stage of a powerful optical microscope that records the fiber’s physical changes. The microscope also acts as a spectroscope that can provide information about the chemical changes taking place in the fiber. A floating microelectrode also measures the cells’ electrical activity.

According to the researchers, the I-Wire system can be used to characterize how cardiac cells respond to electrical stimulation and mechanical loads and can be implemented at low cost, small size and low fluid volumes, which make it suitable for screening drugs and toxins. Because of its potential applications, Vanderbilt University has patented the device. Unlike other heart-on-a-chip designs, I-Wire allows the researchers to grow cardiac cells under controlled, time-varying tension similar to what they experience in living hearts.

To demonstrate the I-Wire’s value in determining the effects that different drugs have on the heart, the scientists tested its response with two drugs known to affect heart function in humans: isoproterenol and blebbistatin. Isoproterenol is a medication used to treat bradycardia (slow heart rate) and heart block (obstruction of the heart’s natural pacemaker). Blebbistatin inhibits contractions in all types of muscle tissue, including the heart.

According to Veniamin Sidorov, the research assistant professor at the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) who led its development, the device faithfully reproduces the response of cardiac cells in a living heart.

1. Sidorov, Veniamin Y., Philip C. Samson, Tatiana N. Sidorova, Jeffrey M. Davidson, Chee C. Lim, and John P. Wikswo. “I-Wire Heart-on-a-Chip I: Three-dimensional cardiac tissue constructs for physiology and pharmacology.” Acta Biomaterialia 48 (2017): 68-78. doi:10.1016/j.actbio.2016.11.009.
2. Schroer, Alison K., Matthew S. Shotwell, Veniamin Y. Sidorov, John P. Wikswo, and W. David Merryman. “I-Wire Heart-on-a-Chip II: Biomechanical analysis of contractile, three-dimensional cardiomyocyte tissue constructs.” Acta Biomaterialia 48 (2017): 79-87. doi:10.1016/j.actbio.2016.11.010.

Research funding: National Institutes of Health, National Science Foundation, Defense Threat Reduction Agency, American Heart Association, Department of Veterans Affairs.
Adapted from press release by Vanderbilt University. 

Price tag for cardiovascular disease to reach 1 trillion dollars by 2035

A new study projects that by 2035, cardiovascular disease, the most costly and prevalent killer, if left unchecked, will place a crushing economic and health burden on the nation’s financial and health care systems. According to the study, in the next two decades, the number of Americans with cardiovascular disease will rise to 131.2 million – 45 percent of the total U.S. population – with costs expected to reach $1.1 trillion.

The new projections are an update of those made by the association in 2011 that estimated around 100 million Americans would suffer from cardiovascular disease by 2030. In addition to the staggering human toll it takes on Americans’ lives and health, cardiovascular disease wreaks havoc on our economy.

Currently, cardiovascular disease is the costliest disease in our nation, with a price tag of $555 billion in 2016. Today’s study suggests that the economic burden of cardiovascular disease will only get worse. Specifically, the total cardiovascular disease costs across all conditions are projected to more than triple among those age 80 and more than double among those ages 65-79.

Direct medical costs related to cardiovascular disease will continue to rise, with costs expected to triple over the next 20 years for Hispanics, more than double among Blacks and be higher for women than men. Expenses associated with cardiovascular disease are expected to surpass medical cost estimates for other chronic diseases, such as diabetes and Alzheimer’s.

Indirect costs due to cardiovascular disease, or the costs related to lost productivity in the workplace and at home, are projected to be the highest for individuals age 45-64. On average, an employee with cardiovascular disease costs his or her employer nearly 60 hours and over $1,100 more in lost productivity per year than an employee without cardiovascular disease.

While white Americans face the highest indirect costs, the report stresses that Hispanics are expected to experience the largest relative increase in costs due to cardiovascular disease over the next 20 years.

To address the escalating burden highlighted in this report, the association recommends the following specific changes in federal policies: Increased funding for heart and stroke research by the National Institutes of Health Enhanced focus on prevention to improve and preserve population health from birth to old age Preservation and expansion of access to high-quality affordable health care Even though heart disease and stroke account for 23 percent and 4 percent of all deaths respectively, the NIH invests a meager 4 percent of its budget on heart disease research, a mere 1 percent on stroke research and only 2 percent on other cardiovascular disease research.

Prevention programs under the Affordable Care Act have enabled insured patients to obtain blood pressure and cholesterol screenings, smoking cessation services, behavioral counseling for obesity, as well as improved access to primary care and medications needed to help manage their diseases and reduce their risks. Retaining this emphasis on prevention and investments in it will be key to reducing health care costs moving forward. Finally, protections for patients with pre-existing conditions are vitally important for Americans who have or will develop cardiovascular disease.

“While we have made tremendous progress in fighting cardiovascular disease, recently reported death rates and these projections reinforce that now is not the time to relax,” said American Heart Association President Steven Houser, Ph.D., FAHA. “We must continue to be vigilant, because if these projections become reality, a serious health and economic crisis is on the horizon. The association welcomes the opportunity to work with Congress and the new administration to find ways to wipe out the burden of cardiovascular disease and build an improved culture of health in our country.”

Citation: Cardiovascular disease: a costly burden for America – projections through 2035. American Heart association CVD burden report. Accessed on 2017-2-14
Adapted from press release by RTI international.