Recent findings suggest that patients with heart failure (HF), treated with combination angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor-blocker (ARB) therapy suffer significantly more adverse effects compared with those treated with ACE inhibitor and background therapy only.
Researchers identified and analyzed results from retrospective, randomized controlled trials that compared ACE inhibitor plus ARB combinations therapy with treat left ventricular dysfunction with a control therapy, such as ACE inhibitors alone. They selected only studies with a minimum of 3-months follow-up and at least 500 study participants. This resulted in the analysis of 17,337 patients with a mean follow-up of 25 months.
The authors noted that the combination therapy was associated with a higher incidence of discontinuing medication, due to adverse effects (relative risk: 1.38) than with standard therapy in patients with heart failure. There was also an increase in risk for hyperkalemia, symptomatic hypertension and the decline of renal function in combination therapy patients compared with those being administered standard therapy.
Interestingly, despite the increase in adverse effects observed in combination therapy patients, lower rates of hospitalization were found in patients treated with both ARBs and ACE-inhibitors compared with those being treated with standard therapy.
Lead author, Christopher Phillips (Cleveland Clinic Lerner College of Medicine, OH, USA) explains, “our overall findings place the known benefit of combination therapy in reducing morbidity within the context of expected risks of adverse effects and may provide a more rational approach to clinical decision making.”
The group, however, insist that the results from these analysis ‘are consistent with current HF guidelines that have expressed reservations about a routine strategy for dual angiotensin inhibition using ARBs plus ACE inhibitors.’
Source: Phillips CO, Kashani A, Ko DK, Francis G, Krumholz HM. Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials. Arch. Intern. Med. 167(18), 1930–1936 (2007).
Slowing down the development of atherosclerosis
Scientists from the Instituto de Biologia Molecular e Celular (Portugal) have discovered that a protein known as transthyretin (TTR), present in the blood, may accelerate the development of atherosclerosis. This finding could lead to new therapeutics to counteract this development thereby slowing down the progression of this potentially fatal heart disease.
Atherosclerosis is a chronic inflammatory response in the walls of arteries, largely as a result of the deposition of lipoproteins leading to hardening or furring of the arteries. Progressively the arteries become narrowed and hardened over time, reducing blood flow to the heart.
The investigators found that TTR cleaves the compound apolipoprotein A (ApoA) I, which is found in the blood and can produce structures called fibrils that are the strand-shaped and accumulate in blood vessels. These fibrils have been found in people who possess a mutation in the ApoA-I producing gene. However, whether cleavage of ApoA I leads to fibril formation has yet to be determined.
The investigators discovered that when ApoA I is cleaved by TTR it tends to form fibrils faster than the uncleaved ApoA I. This new finding could lead the way toward new approaches for the treatment of patients with atherosclerosis by preventing TTR from cleaving ApoA I and thereby slowing the formation of fibrils in blood vessels.
Source: www.asbmb.org; Liz MA, Gomes CM, Saraiva MJ, Sousa MM. ApoA-I cleaved by transthyretin has reduced ability to promote cholesterol efflux and increased amyloidogenicity. J. Lipid Res. 48(11), 2385–2395 (2007).
Cardiac testing may be transformed with the aid of whole blood sensor research
Scientists from the University of Ulster (UK) and the Indian Institute of Technology (India) have combined forces to develop a low-volume whole blood sensor that may be set to transform current point-of-care cardiac testing.
For patients experiencing life-threatening cardiac events, fast and accurate diagnosis is vital. “If you have a suspected heart attack medical staff will monitor your ECG, respiration rate, SP02 and eye dilation. But it is also vitally important that your blood is analysed as quickly as possible. Analysing cardiac enzymes in the blood will enable medical staff to determine the correct treatment. It will guide them on whether to administer clot-busting drugs, insert a stent or attempt defibrillation, for example”, said Professor Jim McLaughlin, Director of the University of Ulster’s Nanotechnology and Advanced Materials Research Institute (UK), head of the project team.
Carbon nanotube technology is utilized in the sensor system in order to remove blood cells, thereby preventing them from sticking to the sensor and distorting the result.
The system will be used to monitor cardiac enzymes, such as troponin I, which acts as a biomarker for cardiac attack. Ultimately, it is hoped that the sensor will be important for bed-side monitoring, triage and emergency scenarios.
The initiative is part of the UK–India Education and Research Initiative (UKERI), a program funded by the governments of the UK and India for collaborative projects between educational institutes in the two countries.
Source: www.ulst.ac.uk
Study reveals key to blood vessel growth and potential drug target
Working on zebrafish, researchers from the University of California, San Francisco (UCSF; CA, USA) have pinpointed a molecular pathway critical to the growth of blood vessels. The finding offers important implications not only for the vascular system, and therefore cardiovascular medicine, but also for the inhibition of blood vessels that fuel cancers and diabetic eye complications.
“We expect this finding will offer important insights into blood vessel formation in humans,” says lead author Massimo Santoro, UCSF visiting postdoctoral fellow in the laboratory of senior author Didier Stainier, UCSF professor of biochemistry and biophysics. “The zebrafish has proven to be an important model for discovering molecules relevant to human disease.”
Angiogenesis is the process by which new blood vessels are formed; it is active both during embryonic development and throughout life. While vital to life, it is notably active in a number of disease states, such as cancer. Cancer tumors release chemical signals that stimulate healthy blood vessels to produce new vessels in order to supply the tumor. A number of molecules have recently been discovered that promote angiogenesis and now a drug that inhibits these molecules is available and further drugs are being investigated.
Stainier and Santoro’s current study found that two well-known signaling molecules, birc2 and TNF, are crucial to the survival of endothelial cells – the cells that line blood vessel walls and maintain their integrity during vascular development – in zebrafish embryos.
“The pathway these molecules make up during vascular development has not been looked at before,” says Stainier. “It offers a new target for therapeutic strategies.”
“Studies on vascular development are important so that we can better understand the molecular basis of how endothelial cell-related pathologies such as cancer, diabetic eye complications…, atherosclerosis and system lupus develop”, Santoro said, “It can also help us design new therapeutic strategies for these diseases.”
The team hopes that future researchers will investigate other avenues and alternative pathways. “Because vascular health impacts many different diseases, understanding how to genetically control endothelial cell survival and apoptosis is critical to future work in these areas”, Stainier said.
The study was published online on October 14th in Nature Genetics.
Source: www.ucsf.edu
Cholesterol-lowering snacks launched
An attempt to create several healthy snacks has been initiated by an exclusive licensing agreement between Corazonas Foods, Inc. (CA, USA) and Brandeis University (MA, USA). It is hoped that by using Brandeis’s innovative technology, snacks can be created that contain large quantities of plant sterols without compromising on flavor.
In 2006 the first snack to be produced by the partnership, Corazonas Heart-Healthy Tortilla Chips, was introduced. They remain the only clinically proven snack chips to reduce low-density lipoprotein (LDL) cholesterol by up to 15%. The success of these chips clearly demonstrates that there is a huge market for healthy-snack alternatives that retain high-quality taste.
The technology used by Brandeis allows the implementation of natural plant sterols into foods. Usually the levels are too low to combat LDL cholesterol effectively but the unique technology used by Brandeis allows natural plant sterols to be biologically available at concentrations of 2–25%. At these levels they are able to effectively block cholesterol absorption and help to reduce LDL levels.
Plant sterols have been shown, in various studies, to reduce blood cholesterol and lower the risk of coronary disease when added to other foods and so the partnership aims to expand to other products via this exclusive agreement. They hope to branch out to other foods, such as biscuits, crackers and potato chips.
Ramona Cappello, chief executive of Corazonas Foods, is delighted with the partnership. He believes that Brandeis University has been an ideal partner for them and that the existing and future snacks will help improve people’s health.
Brandeis is equally thrilled that: “Corazonas is successfully turning our basic discovery into products that have both a positive health benefit and are gaining broad acceptance by consumers”, explains Irene Abrams, executive director of the Office of Technology Licensing at Brandeis University. She remains confident that Corazonas will be as successful with the new line of products as it was with original snack.
Source: www.brandeis.edu
GORE HELEX® Septal Occluder approved for treatment of atrial septal defect
The approval of the GORE HELEX® Septal Occluder with a modified catheter delivery system, indicated for the transcatheter closure of atrial septal defect (ASD), by the US FDA has recently been announced by Gore & Associates.
Thousands of patients are affected every year with ASD, which is a congenital defect. ASD is an abnormal hole in the wall between the upper chambers of the heart, which allows blood to flow improperly from the left side of the heart to the right, forcing the right side of the heart and lungs to overexert to compensate for the problem. If it is not treated, ASD can cause the heart to enlarge or weaken, which can result in the patient being at risk for serious conditions, such as atrial fibrillation, pulmonary hypertension, heart failure or stroke. Most patients treated are children.
“In treating such a delicate area of the heart, particularly in small children, interventional cardiologists need to be confident that treatment will be effective for the long term,” said Alexander Javois of The Heart Institute for Children, Advocate Hope Children’s Hospital, Oak Lawn (IL, USA). “Percutaneous ASD closure is successful in the very young patient using the GORE HELEX Septal Occluder. Its design and conformity allows tissue to incorporate the device easily so that it becomes part of the heart’s anatomy, sealing the ASD successfully and improving, even normalizing, the patient’s heart function without open heart surgery.”
The GORE HELEX Septal Occluder is an implanted prosthesis, which is permanent and the first device of its kind to use expanded polytetrafluoroethylene (ePTFE), a biocompatible material that enables tissue ingrowth to seal the defect. It is composed of ePTFE patch material that is supported by a single nitinol wire frame. This frame bridges and eventually occludes the septal defect to stop the shunting of blood between the atria. Following implantation of the GORE HELEX Septal Occluder, cells begin to infiltrate and grow over the ePTFE membrane during the subsequent weeks to months. This results in the closure of the defect.
“Open heart surgery is no longer the only available option to correct an ASD in young children and in patients with complicating health factors. Interventional cardiologists can close the defect permanently through a minimally invasive procedure with a shorter recovery time,” said Peter Zeller, Gore Product Specialist. “The GORE HELEX Septal Occluder has been used in thousands of successful implants worldwide, and we are excited that the device is now available to physicians so that they can treat many more patients in the US.”
The GORE HELEX Septal Occluder’s efficacy has been tested over several years, resulting in strong clinical data from several thousand successful implants. It has been available in Europe, Latin America and Australia and also under an investigational device exemption in the USA. This recently approved catheter-based delivery system enables easier device deployment through standard femoral venous access, which brings the GORE HELEX Septal Occluder to the forefront of nonsurgical ASD repair.
Source: Gore Medical Products www.goremedical.com
Catheter delivery of adult stem cells for heart regeneration
Cardiologists from the University Hospital of Navarre (Spain), in collaboration with the Gregorio Marañón Hospital in Madrid (Spain), have carried out Phase II clinical trials on 50 patients in order to test the efficacy of adult stem cell transplants to regenerate the hearts of patients following a myocardial infarction.
Although previous studies have transplanted stem cells for the same purpose, in this study the transplantation of the cells took place via the use of a catheter, as opposed to via open surgery – therefore obviating any operative complications.
Myoblast cells are extracted from the leg of the patient. From the tissue obtained the researchers isolate the adult muscle stem cells, which are cultured for 1 month in order to achieve a sufficient quantity for transplantation. The cells are then injected in and around the damaged heart tissue of the patient using a special injection catheter.
The investigators were very strict to ensure that the patients involved in the trial were not undergoing any other treatment that may interfere with the clinical outcome. In this way, Dr Gavira pointed out “the results obtained are much purer, given that no other treatment interferes with them”. Having obtained the adult stem cells, a sample thereof is analysed in the Microbiology Laboratory in order to discard the existence of infections and to certify its perfect state.
Source: www.basqueresearch.com