What powers the pumping heart?

 

Led by University of Toronto Physiology Professor Anthony Gramolini and his collaborator, Professor Thomas Kislinger in the Department of Medical Biophysics, the team used high-throughput methods to identify more than 500 membrane proteins on the surfaces of cardiac contractile cells, which are likely to have a critical role in normal heart function. Credit: Image courtesy of University of Toronto Researchers at the Ted Rogers Centre for Heart Research have uncovered a treasure trove of proteins, which hold answers about how our heart pumps -- a phenomenon known as contractility. Led by University of Toronto Physiology Professor Anthony Gramolini and his collaborator, Professor Thomas Kislinger in the Department of Medical Biophysics, the team used high-throughput methods to identify more than 500 membrane proteins on the surfaces of cardiac contractile cells, which are likely to have a critical role in normal heart function. The proteins may also play a part in heart failure and abnormal heartbeat patterns known as arrhythmias. "In addition to providing a new understanding of what makes our hearts pump, these findings could also help researchers uncover new information about how heart disease affects the signal pathways in our hearts. That might pave the way to find ways to prevent or reverse those changes," says Gramolini. During the study, the researchers found about 500 novel molecules that have been conserved throughout evolution. These molecules haven't been studied in the heart and little is known about what they do in other tissues. The group's research focused on a protein called transmembrane protein 65 (Tmem65). By studying human stem cells and zebrafish using cell imaging and biochemical techniques, the researchers discovered that Tmem65 is involved in communication and electrical processes known as electrical coupling and calcium signaling. The team showed that Tmem65 regulates the connection point between adjacent cardiac contractile cells where it contributes to making the heart contract normally. Removing the protein had fatal consequences. The team also identified Tmem65 as the first critical tool for stem-cell researchers to monitor the maturation of cells in the heart's two main chambers, known as ventricles. "These proteins are theoretically targetable for intervention as well as basic study. In this study, our focus was on Tmem65, but there are 555 proteins that we identified and showed that they are present throughout many species and are conserved throughout evolution-- at least in the mouse and the human -- in the heart's membrane-enriched contractile cells. Tmem65 was only the number-one candidate in our study, but theoretically, we have 554 other proteins to work through," says Gramolini. The study, published in Nature Communications, also provides the first resource of healthy human and mouse heart-cell proteins that will help scientists develop a better understanding the mechanisms involved in cardiac disease. Gramolini says the findings are essential for understanding cardiac biology and hopes they open the door for further study into health and disease in his lab and others. "We need to figure out what all of these molecules are doing. My team and I hope our research sets the stage for other people to begin to pick up some of this work," says Gramolini. "These are molecules that haven't been studied, but must play some role in heart function. If a protein is conserved in evolution, generally it must have a critical function. We are very excited to look at the role of a number of these new proteins." Story Source: The above post is reprinted from materials provided by University of Toronto. The original item was written by Erin Howe. Note: Materials may be edited for content and length. Journal Reference: Parveen Sharma, Cynthia Abbasi, Savo Lazic, Allen C. T. Teng, Dingyan Wang, Nicole Dubois, Vladimir Ignatchenko, Victoria Wong, Jun Liu, Toshiyuki Araki, Malte Tiburcy, Cameron Ackerley, Wolfram H. Zimmermann, Robert Hamilton, Yu Sun, Peter P. Liu, Gordon Keller, Igor Stagljar, Ian C. Scott, Thomas Kislinger, Anthony O. Gramolini.Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function. Nature Communications, 2015; 6: 8391 DOI: 10.1038/ncomms9391 http://www.sciencedaily.com/releases/2015/09/150925131425.htm

Echocardiography and CT combined to produce heart model

 

Pictured above is another 3D heart model. Credit: Courtesy of Materialise Congenital heart experts from Spectrum Health Helen DeVos Children's Hospital have successfully integrated two common imaging techniques to produce a three-dimensional anatomic model of a patient's heart. The 3D model printing of patients' hearts has become more common in recent years as part of an emerging, experimental field devoted to enhanced visualization of individual cardiac structures and characteristics. But this is the first time the integration of computed tomography (CT) and three-dimensional transesophageal echocardiography (3DTEE) has successfully been used for printing a hybrid 3D model of a patient's heart. A proof-of-concept study authored by the Spectrum Health experts also opens the way for these techniques to be used in combination with a third tool -- magnetic resonance imaging (MRI). "Hybrid 3D printing integrates the best aspects of two or more imaging modalities, which can potentially enhance diagnosis, as well as interventional and surgical planning," said Jordan Gosnell, Helen DeVos Children's Hospital cardiac sonographer, and lead author of the study. "Previous methods of 3D printing utilize only one imaging modality, which may not be as accurate as merging two or more datasets." The team used specialized software to register images from the two imaging modalities to selectively integrate datasets to produce an accurate anatomic model of the heart. The result creates more detailed and anatomically accurate 3D renderings and printed models, which may enable physicians to better diagnose and treat heart disease. Computed tomography (CT) and magnetic resonance imaging (MRI) are established imaging tools for producing 3D printable models. Three-dimensional transesophageal echocardiography (3DTEE) recently was reported by Joseph Vettukattil, M.D., and his Helen DeVos Children's Hospital colleagues to be a feasible imaging technique to generate 3D printing in congenital heart disease. Vettukattil is co-director of the Helen DeVos Children's Hospital Congenital Heart Center, division chief, pediatric cardiology, and senior author of the study. According to Vettukattil and his colleagues, each imaging tool has different strengths, which can improve and enhance 3D printing: CT enhances visualization of the outside anatomy of the heart. MRI is superior to other imaging techniques for measuring the interior of the heart, including the right and left ventricles or main chambers of the heart, as well as the heart's muscular tissue. 3DTEE provides the best visualization of valve anatomy. "This is a huge leap for individualized medicine in cardiology and congenital heart disease," said Vettukattil. "The technology could be beneficial to cardiologists and surgeons. The model will promote better diagnostic capability and improved interventional and surgical planning, which will help determine whether a condition can be treated via transcatheter route or if it requires surgery." Vettukattil is known internationally for his work and research with three- and four-dimensional echocardiography. Most notably, Vettukattil developed the advanced technique of multiplanar reformatting in echocardiography, a method used to slice heart structures in infinite planes through the three dimensions in a virtual environment similar to a cardiac pathologist dissecting the heart to reveal underlying pathology. Commonly used with other diagnostic technologies, such as CTs, Vettukattil pioneered its use in echocardiography to evaluate complex heart defects. Vettukattil is presenting the findings of the proof-of-concept study June 24-27 at the CSI 2015 -- Catheter Interventions in Congenital, Structural and Valvular Heart Diseases Congress in Frankfurt, Germany to demonstrate the feasibility of printing 3D cardiovascular models derived from multiple imaging modalities. The Helen DeVos Children's Hospital team worked with the Mimics® Innovation Suite software from Materialise, a provider of 3D printing software and services based in Belgium, which printed the model using its HeartPrint® Flex technology. Gosnell worked on integration of the imaging modalities, collaborating with Materialise's U.S. Headquarters in Plymouth, Mich., to produce the final 3D rendering. Vettukattil devised the concept of integrating two or more imaging modalities for 3D printing. Further research is required to evaluate the efficacy of hybrid 3D models in decision-making for transcatheter or surgical interventions.

Nanotubes help healing hearts keep the beat

 

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Carbon nanotubes serve as bridges that allow electrical signals to pass unhindered through new pediatric heart-defect patches invented at Rice University and Texas Children's Hospital.

A team led by bioengineer Jeffrey Jacot and chemical engineer and chemist Matteo Pasquali created the patches infused with conductive single-walled carbon nanotubes. The patches are made of a sponge-like bioscaffold that contains microscopic pores and mimics the body's extracellular matrix.

The nanotubes overcome a limitation of current patches in which pore walls hinder the transfer of electrical signals between cardiomyocytes, the heart muscle's beating cells, which take up residence in the patch and eventually replace it with new muscle.

The work appears this month in the American Chemical Society journal ACS Nano. The researchers said their invention could serve as a full-thickness patch to repair defects due to Tetralogy of Fallot, atrial and ventricular septal defects and other defects without the risk of inducing abnormal cardiac rhythms.

The original patches created by Jacot's lab consist primarily of hydrogel and chitosan, a widely used material made from the shells of shrimp and other crustaceans. The patch is attached to a polymer backbone that can hold a stitch and keep it in place to cover a hole in the heart. The pores allow natural cells to invade the patch, which degrades as the cells form networks of their own. The patch, including the backbone, degrades in weeks or months as it is replaced by natural tissue.

Researchers at Rice and elsewhere have found that once cells take their place in the patches, they have difficulty synchronizing with the rest of the beating heart because the scaffold mutes electrical signals that pass from cell to cell. That temporary loss of signal transduction results in arrhythmias.

Nanotubes can fix that, and Jacot, who has a joint appointment at Rice and Texas Children's, took advantage of the surrounding collaborative research environment.

"This stemmed from talking with Dr. Pasquali's lab as well as interventional cardiologists in the Texas Medical Center," Jacot said. "We've been looking for a way to get better cell-to-cell communications and were concentrating on the speed of electrical conduction through the patch. We thought nanotubes could be easily integrated."

Nanotubes enhance the electrical coupling between cells that invade the patch, helping them keep up with the heart's steady beat. "When cells first populate a patch, their connections are immature compared with native tissue," Jacot said. The insulating scaffold can delay the cell-to-cell signal further, but the nanotubes forge a path around the obstacles.

Jacot said the relatively low concentration of nanotubes -- 67 parts per million in the patches that tested best -- is key. Earlier attempts to use nanotubes in heart patches employed much higher quantities and different methods of dispersing them.

Jacot's lab found a component they were already using in their patches -- chitosan -- keeps the nanotubes spread out. "Chitosan is amphiphilic, meaning it has hydrophobic and hydrophilic portions, so it can associate with nanotubes (which are hydrophobic) and keep them from clumping. That's what allows us to use much lower concentrations than others have tried."

Because the toxicity of carbon nanotubes in biological applications remains an open question, Pasquali said, the fewer one uses, the better. "We want to stay at the percolation threshold, and get to it with the fewest nanotubes possible," he said. "We can do this if we control dispersion well and use high-quality nanotubes."

The patches start as a liquid. When nanotubes are added, the mixture is shaken through sonication to disperse the tubes, which would otherwise clump, due to van der Waals attraction. Clumping may have been an issue for experiments that used higher nanotube concentrations, Pasquali said.

The material is spun in a centrifuge to eliminate stray clumps and formed into thin, fingernail-sized discs with a biodegradable polycaprolactone backbone that allows the patch to be sutured into place. Freeze-drying sets the size of the discs' pores, which are large enough for natural heart cells to infiltrate and for nutrients and waste to pass through.

As a side benefit, nanotubes also make the patches stronger and lower their tendency to swell while providing a handle to precisely tune their rate of degradation, giving hearts enough time to replace them with natural tissue, Jacot said.

"If there's a hole in the heart, a patch has to take the full mechanical stress," he said. "It can't degrade too fast, but it also can't degrade too slow, because it would end up becoming scar tissue. We want to avoid that."

Pasquali noted that Rice's nanotechnology expertise and Texas Medical Center membership offers great synergy. "This is a good example of how it's much better for an application person like Dr. Jacot to work with experts who know how to handle nanotubes, rather than trying to go solo, as many do," he said. "We end up with a much better control of the material. The converse is also true, of course, and working with leaders in the biomedical field can really accelerate the path to adoption for these new materials."

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Story Source:

The above story is based on materials provided by Rice University. The original article was written by Mike Williams. Note: Materials may be edited for content and length.

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Journal Reference:

1. Seokwon Pok, Flavia Vitale, Shannon L. Eichmann, Omar M. Benavides, Matteo Pasquali, Jeffrey G Jacot. Biocompatible Carbon Nanotube – Chitosan Cardiac Scaffold Matching the Electrical Conductivity of the Heart. ACS Nano, 2014; 140918182222001 DOI: 10.1021/nn503693h

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What Your Heart Needs Now

 

 

Things to do in your 30s, 40s, and beyond

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The statistics are sobering: Heart disease is the number-one killer of women in the United States. And an estimated eight million women have it. Whats more, a new study shows that in recent years, the overall heart disease risk for Americans—especially women—hasnt continued the healthy downward trend it showed in previous decades. Ready for some good news? You can do more to prevent heart disease than almost any other serious condition. Start with these age-specific steps.

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Declare a trans fat–free zone
Commonly used to extend the shelf life of packaged foods like cookies and crackers, and also found in margarine, trans fats pack a double whammy: They raise bad cholesterol (LDL), while lowering good, protective HDL (your LDL should be below 100; your HDL, above 60). In a Harvard University study, women with the highest level of trans fats in their blood had triple the risk of heart disease. Take a cue from major U.S. cities like New York and Philadelphia (which have banned trans fats from restaurants), and pitch them out of your pantry.
On ingredient lists, they show up as “hydrogenated” and “partially hydrogenated” oils. But scrutinize any product touted as “trans fat–free” at the supermarket too: Some manufacturers have replaced hydrogenated oils with tropical oils that are high in saturated fat, which also raises LDL cholesterol. Eating out in a city where trans fats arent banned? Skip the fried stuff; many restaurants still use the oils for frying.

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Use your ob-gyn as a partner
During your prime reproductive years, you may visit your ob-gyn more than you go to your regular doctor. Make sure you talk to her about your heart as well as gynecological health, particularly because blood pressure (BP) can rise if youre taking birth control pills or when youre pregnant.
Women who develop preeclampsia (pregnancy-related hypertension) are prone to heart disease later in life. And, in general, “how your heart handles pregnancy offers a snapshot of how it will look in middle age,” says Sharonne Hayes, MD, director of the Womens Heart Clinic at the Mayo Clinic, in Rochester, Minn. To keep BP from creeping up (the safe zone is lower than 120 over 80), substitute herbs and spices for salt; try cumin for a healthy twist on popcorn, for instance. Too much salt causes blood vessels to retain water, which can lead to high BP.

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Simmer down
If you boil over when the shopper in front of you has 16 grocery items in the 15-or-fewer lane, beware: Losing your temper can damage your arteries, according to research by C. Noel Bairey Merz, MD, director of the Womens Heart Center and endowed chair in Womens Health at the Cedars-Sinai Heart Institute in Los Angeles. “Raging causes your blood pressure to surge and stay up there,” Dr. Merz says. Thats why its crucial to get a grip on anger at an early age, before it takes a toll. Instead of venting when a situation makes you furious, take a few deep breaths and describe to yourself whats making you angry. That should help you calm down.

Targeting heart failure may reduce readmissions, save lives, studies find

 

May 17, 2014

European Society of Cardiology (ESC)

Worsening symptoms and signs of heart failure (HF) in patients admitted to a hospital is a common sign of treatment failure and can lead to long-term consequences for the patient, including longer length of hospitalization and a higher risk for readmission and death, according to a recent study. Heart failure is the most common reason for admission to hospital in people over 65 years old and affects millions of people each year.

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Worsening symptoms and signs of heart failure (WHF) in patients admitted to a hospital is a common sign of treatment failure and can lead to long-term consequences for the patient, including longer length of hospitalization and a higher risk for readmission and death, according to a late-breaking study (RELAX-AHF, PROTECT) presented in Athens at the ESC's Heart Failure Congress 2014.

Heart failure is the most common reason for admission to hospital in people over 65 years old and affects millions of people each year. Research has shown that the outcomes of patients admitted with Acute Heart Failure (AHF) are dire with significant time spent in the hospital and high rates of readmissions or death within 6 months. Currently available therapies such as i.v. diuretics and vasodilators, may relieve some of the symptoms of AHF including dyspnoea, but most probably do not affect short term outcomes.

"Worsening heart failure is a clinical event occurring during an admission for acute heart failure defined as worsening of the symptoms and signs that brought the patient to the hospital requiring additional intravenous or mechanical therapy," said Beth Davison, lead author on the RELAX-AHF study and vice president of Momentum Research Inc. "It prolongs the hospital stay and is associated with increased risk for heart failure readmission within 2 months and death within 6 months. Preventing this early event would not only reduce the patient's suffering during the admission but possibly also reduce its longer-term consequences." In data pooled from the PROTECT Pilot, PROTECT, Pre-RELAX-AHF, and RELAX-AHF studies the association of WHF with length of stay, mortality and HF re-hospitalization were examined. In 3691 patients, death or WHF occurred in 12.4%. WHF was associated with a mean increase in the length of hospital stay of 5.2 days (95% confidence intervals [CI] 4.6-5.8 days); a hazard ratio (HR) for 60-day HF readmission or CV death of 1.64 (CI 1.34-2.01) and a HR for 180-day mortality of 1.93 (1.55-2.41) -- all P< 0.001. WHF was also associated with larger increases in markers of renal and hepatic dysfunction during the first days of admission.

The association of WHF with these outcomes remained robust after adjustment for changes in these markers at day 2 on top of adjustment for baseline characteristics. The association of WHF with mortality was significant regardless of what therapy was given for WHF, although patients who needed IV inotropes or mechanical support had higher mortality.

"Because WHF is associated with more adverse outcome physicians should monitor closely patients who develop WHF during admission," said Dr. Davison. "As suggested by the results of the RELAX-AHF study, future therapy may reduce the occurrence of WHF and some of its downstream effects."

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Story Source:

The above story is based on materials provided by European Society of Cardiology (ESC). Note: Materials may be edited for content and length.

Negative iron balance predicts acute heart failure survival

 

May 17, 2014

European Society of Cardiology (ESC)

Negative iron balance predicts survival in patients with acute heart failure, according to research. “Patients with acute heart failure have a major collapse in homeostasis. Iron is a key micronutrient that is required for the maintenance of homeostasis. Iron is needed for cellular metabolism and deficiency leads to severely impaired energy metabolism and mitochondrial dysfunction,” the first author said.

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Negative iron balance predicts survival in patients with acute heart failure, according to research presented for the first time today at the Heart Failure Congress 2014 in Athens, Greece. The Congress is the main annual meeting of the Heart Failure Association of the European Society of Cardiology.

Professor Ewa Jankowska, first author of the study, said: “Patients with acute heart failure have a major collapse in homeostasis. Iron is a key micronutrient that is required for the maintenance of homeostasis. Iron is needed for cellular metabolism and deficiency leads to severely impaired energy metabolism and mitochondrial dysfunction.”

She continued: “Previous studies have shown that patients at high cardiovascular risk – for example diabetics with coronary artery disease or patients with stable chronic heart failure – may develop iron deficiency which leads to recurrent hospitalisations and increased mortality.”

Professor Piotr Ponikowski, last author, said: “We have data showing that iron may be important for clinical outcomes in chronic heart failure and correction of iron deficiency in these patients is beneficial. This is the first study of iron status in acute heart failure.”

Iron deficiency has traditionally been measured using serum ferritin to track iron stores and transferrin saturation (TSAT) to assess iron utilisation in the cell. These measures cannot be reliably interpreted in acute clinical settings because they are influenced by inflammation and oxidative stress.

The researchers therefore proposed a new, more sensitive, measure for acute heart failure which can best characterise iron deficiency in these settings. This refers to both depleted iron stores, measured by circulating hepcidin, and unmet cellular iron needs, measured by soluble transferrin receptor. The receptor is expressed on all cells and enables iron to enter the cell. When there is not enough iron in the cell, the receptor is overexpressed and shed into the circulation. Concomitance of low hepcidin and high soluble transferrin receptor reflects the most severe form of iron deficiency (lack of iron in the body accompanied by iron need), which the investigators called negative iron balance (NIB).

This prospective, observational study included 165 patients hospitalized for acute heart failure. The researchers assessed the prevalence of NIB and its impact on 12 month mortality.

NIB was found in 37% of patients. Just 29% had only high soluble transferrin receptor, while 9% had only low hepcidin and 25% had none of these abnormalities. Twelve month mortality was 20% for the whole group. Patients with NIB had the highest 12 month mortality (41%) compared to those with only high soluble transferrin receptor (15%), only low hepcidin (7%) and none of these abnormalities (0%) (p<0.001). During the hospital stay 3 patients died and all had NIB.

Professor Jankowska said: “Our study shows that deranged iron status is common in acute heart failure. Mortality in the patients with NIB was high during the 12 month follow up, whereas all of the patients with no iron abnormalities survived to one year.”

NIB led to poorer survival in acute heart failure patients regardless of whether they were anaemic or not.

The researchers also measured the standard parameters of iron status, serum ferritin and TSAT, and found that they were less able to predict 12 month mortality than NIB. Levels of serum ferritin and TSAT were only weakly correlated with hepcidin and soluble transferrin receptor.

Professor Ponikowski said: “Levels of hepcidin and soluble transferrin receptor are more clinically relevant in patients with acute heart failure than traditional measures of iron status. We propose a new pathophysiological definition of iron deficiency which accurately reflects stored and utilised iron in patients with acute heart failure.”

Both concluded: “Iron supplementation may reverse NIB and improve survival in acute heart failure patients but this needs to be tested in a randomised clinical trial. We hope to initiate such trial soon.”

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Story Source:

The above story is based on materials provided by European Society of Cardiology (ESC). Note: Materials may be edited for content and length.

High dose of radiation on heart attack patients.

 

Heart Tests|Study: Heart Attack Patients Receive High Dose of Radiation - Heart Disease - Health.com

Young at Heart? Tool Calculates True Heart Age

 

Young at heart? A new tool developed by British scientists may be able to tell you. The calculator assesses the true age of your heart, and how long you are likely to live before suffering a heart attack or stroke, by evaluating a series of cardiovascular risk factors tied to genetics and lifestyle.

The tool, created by researchers from several British medical societies, is being recommended to determine the risk of developing heart disease later in life, according to a report on the calculator by the LiveScience Website

Current prevention strategies for heart disease are based on short-term estimates, which are heavily dependent on age and gender, researchers said. Therefore, younger people and women tend to be excluded even if they are leading a lifestyle that puts them at high risk later in life.

The new tool, detailed in the British Medical Journal Heart, has been designed to identify at-risk individuals and predict how many years they can expect to live before they have a heart attack or stroke. It is based on the growing body of evidence showing that there is a long buildup to heart disease, said the researchers from Joint British Societies. It takes into account people's current lifestyle, blood pressure, cholesterol level, and medical conditions that may affect their heart.

Special: Coronary Heart Disease: 5 Tips to Reduce Your Risk

For example, a 35-year-old woman with a family history of heart disease who smokes, has high blood pressure, and elevated total cholesterol would have a true heart age of 47 and could expect to survive to age 71 before having a heart attack or stroke, according to the calculator.
But if she quit smoking, cut her total cholesterol, and lowered her blood pressure, her heart age would fall to 30 and she could expect to live to age 85 before having a heart attack or stroke.

For most people, the researchers said, the calculator can show the potential gains from an early and sustained change to a healthier lifestyle — such as quitting smoking, eating a healthy diet, exercising, and reducing sedentary activity — rather than taking prescription  drugs.

Heart disease is the No. 1 killer in the United States, causing nearly 600,000 deaths every year, according to the Centers for Disease Control and Prevention.