MedicalResearch.com Interview with:
Paolo Cavoretto MD PhD
San Raffaele Scientific Centre
Obstetrics and Gynaecology Department
Milan Italy
MedicalResearch.com: What is the background for this study?Response: Congenital heart defects (CHD) are the most common forms of congenital disorders and a relevant cause of perinatal morbidity and mortality involving about 0.8% of pregnancies. IVF pregnancies are very common nowadays with increasing rates in the developed countries worldwide. There is no consensus in current practice guidelines whether IVF/ICSI conception represents an indication for performing a fetal echocardiogram according to different eminent scientific societies due to differences in the estimations of the risk for CHD in the available literature.
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MedicalResearch.com Interview with:
Nenad Bursac PhD
Professor of Biomedical Engineering
Associate Professor of Medicine
Duke University
Durham, NCMedicalResearch.com: What is the background for this study? What are the main findings?Response: Every year about 1 million new people in US suffers from heart attack, resulting in death of hundreds of millions of cardiac muscle cells. This massive cell loss leads to gradual deterioration of heart function, which for many patients results in the occurrence of heart failure that ultimately will require heart transplant. Heart transplantation is complicated and expensive procedure and donor hearts are in short supply, rendering this disease to be not only highly prevalent but ultimately lethal.
For almost 30 years, researchers have been exploring transplantation of stem cells into injured hearts as a means to replace dead cardiac muscle with new muscle cells that would yield improved heart function. However, injections of stem cells in the heart have so far met with limited clinical success and surgical implantation of pre-made heart muscle tissue in a form of a "cardiac patch" has been explored as an alternative strategy with a proven benefit of enhancing transplanted cell survival. Others and we have engineered cardiac tissue patches in a dish starting from human pluripotent stem cells, which have advantage of being able to become bona fide contracting cardiac muscle cells. So far, however, no one has been able to engineer a highly functional cardiac muscle patch of a size that is large enough to be used in human therapies for heart disease.
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MedicalResearch.com Interview with:
Dr. Jay Edelberg MD, PhD
VP Head of CV Development and
Head Global CV Medical Affairs
SanofiMedicalResearch.com: What is the background for this study? What are the main findings?Response: Patients with heterozygous familial hypercholesterolemia (HeFH) are often not able to achieve their target low-density lipoprotein cholesterol (LDL-C) levels, and some may require lipoprotein apheresis (LA) to lower their “bad cholesterol.” Apheresis is a procedure similar to kidney dialysis, where bad cholesterol is mechanically removed from the blood. It is an invasive, expensive, and time-consuming treatment for patients, as well as physicians.
The Phase III ESCAPE clinical study looked at the potential effect of LA on total Praluent, free and total PCSK9 concentrations, as well as the combined pharmacodynamics effect of total Praluent on LDL-C-lowering.
Praluent levels remained unaffected by apheresis, and Praluent consistently suppressed free PCSK9 levels in patients with HeFH, regardless of LA treatment. This analysis further confirms clinical ESCAPE data that Praluent can be used in conjunction with LA and may reduce or potentially eliminate the need for LA in some patients.
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MedicalResearch.com Interview with:
Anirban Datta, PhD
Director Discovery Biology
Verseon Corporation
MedicalResearch.com: What is the background for this study?
Response: Today’s anticoagulant market is dominated by the NOACs. These oral anticoagulants require less constant monitoring and have reduced drug and food interactions compared to their predecessors, warfarin and heparin. However, there is still a significant bleeding risk associated with the NOACs. This is particularly problematic when they are co-dosed with antiplatelet drugs. While life-long therapy combining an oral anticoagulant with one or two antiplatelet drugs is desired for the many patients suffering from both non-valvular atrial fibrillation and coronary artery disease, current treatment guidelines limit such therapy to a maximum of six months to a year due to safety concerns.
At Verseon, we are developing a novel class of precision anticoagulants that combine efficacy comparable to the NOACs with a significantly reduced bleeding risk in preclinical testing. We believe that this profile can have a positive impact on the lives of the many patients in need of long-term anticoagulation-antiplatelet combination therapy.
We are currently advancing two development candidates toward clinical trials in 2018. VE-1902, our first development candidate, is scheduled to enter phase I in the first half of the year. (more…)
MedicalResearch.com Interview with:
Prof Kazem Rahimi FRCP
The George Institute for Global Health
Oxford Martin School
University of Oxford, Oxford
MedicalResearch.com: What is the background for this study? Response: We decided to investigate this topic because disease incidence data is very important for public health bodies; for example, for the allocation of healthcare resources or for the design and assessment of disease prevention measures.
When we reviewed the literature, we found that estimates of heart failure incidence, temporal trends, and association by patient features were scarce. Studies often referred to restricted populations (such as relatively small cohorts that may or may not be representative of the general population), or limited data sources (for example, only including patients hospitalized for their heart failure and not considering those diagnosed by clinicians outside of hospitals). Few studies reported comparable, age-standardized rates, with the result that the rates reported varied considerably across the literature.
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MedicalResearch.com Interview with:
Dr. Shaista Malik MD PhD MPH
Director of Samueli Center For Integrative Medicine
Assistant Professor, School of Medicine
University of California, Irvine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Having diabetes has been considered to be a risk equivalent to already had a myocardial infarction for predicting future cardiovascular events. We were interested in testing whether further risk stratification in those with diabetes and metabolic syndrome, using coronary artery calcium (CAC), would result in improved prediction of cardiovascular events.
We found that CAC score was associated with incident coronary heart disease and cardiovascular disease more than a decade after the scoring was performed. We also found that even after we controlled for the duration of diabetes (of 10 years or more), insulin use, or hemoglobin A1c level, coronary artery calcium remained a predictor of cardiovascular events.
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Interview with:
Dr Xiaoxi Yao PhD
Assistant Professor
Researcher
Mayo Clinic
What is the background for this study? What are the main findings?
Response: Lifelong oral anticoagulation, either with warfarin or a non-vitamin K antagonist oral anticoagulant (NOAC), is indicated for stroke prevention in most patients with atrial fibrillation (AF). Emerging evidence suggests that NOACs may be associated with better renal outcomes than warfarin.
The study found renal function decline is common among patients with atrial fibrillation treated with oral anticoagulants. NOACs, particularly dabigatran and rivaroxaban, may be associated with lower risks of adverse renal outcomes than warfarin.
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MedicalResearch.com Interview with:
Marta Guasch-Ferre, PhD
Research Fellow
Department of Nutrition. Harvard TH Chan School of Public Health
655 Huntington Ave, Building 2
Boston, Ma, 02115MedicalResearch.com: What is the background for this study? What are the main findings?Response: Although previous evidence has shown that frequent nut consumption is associated with reduced cardiovascular risk factors including dyslipidaemia, type 2 diabetes and metabolic syndrome; as well as with lower risk of coronary heart disease (CHD); most of the previous prospective studies have focused on total nut consumption in relation to the risk of CVD. However, the associations between peanut butter and specific types of nuts, such as peanuts and walnuts, with major cardiovascular events, and specifically the relation with stroke were unclear. Of note, because the nutritional composition of peanuts and walnuts differs from other nuts, it was of particular interest to evaluate the health effects of specific types of nuts. Therefore, our main aim was to look at several types of nuts including total nut consumption, peanuts, walnuts, and tree nuts.
Briefly, in three large prospective cohorts with up to 32 years of follow-up, people who regularly eat nuts, including peanuts, walnuts and tree nuts, have a lower risk of developing cardiovascular disease or coronary heart disease compared to people who never or almost never eat nuts. We found a consistent inverse association between total nut consumption and total cardiovascular disease (14% lower risk for those consuming nuts five or more times per week) and coronary heart disease (20% lower risk).
Also, after looking at individual nut consumption, eating walnuts one or more times per week was associated with a 19 percent lower risk of cardiovascular disease and 21 percent lower risk of coronary heart disease. Participants who ate peanuts or tree nuts two or more times per week had a 15 percent and 23 percent, respectively, lower risk of coronary heart disease compared to those who never consumed nuts.
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MedicalResearch.com Interview with:
Dr. Carlos Aurelio SchiavonResearch Institute, Heart Hospital
São Paulo, BrazilMedicalResearch.com: What is the background for this study? What are the main findings?
Response: Obesity and hypertension are highly prevalent diseases and when they are associated, cardiovascular risk is almost double over patients with obesity alone. 60-70% of hypertension in adults may be attributable to adiposity.
To address both problems, we designed the GATEWAY TRIAL to evaluate the efficacy of Gastric Bypass in the reduction of antihypertensive medications in obese patients using at least 2 medications at maximum doses.
After 1 year, results were very consistent. 83.7 % of the patients submitted to Gastric Bypass reduced at least 30% of the total number of medications maintaining a controlled blood pressure (<140/90 mm Hg) and 51% remitted from hypertension, defined by controlled blood pressure without medications. When we evaluated the reduction of the medication maintaining the Systolic blood pressure below 120 mmHg (SPRINT TARGET), 22.4% of the patients showed remission of hypertension.
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MedicalResearch.com Interview with:
David L. Brown, MD, FACC
Professor of Medicine
Cardiovascular Division
Washington University School of Medicine
St. Louis, MO 63110
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Approximately 10 million patients present to emergency rooms in the US annually for evaluation of acute chest pain.
The goal of that evaluation is to rule out the diagnosis of an acute heart attack. Imaging with coronary CT angiography and stress testing are not part of the diagnostic algorithm for acute heart attack. Nevertheless many chest pain patients undergo some form of noninvasive cardiac testing in the ER. We found that CCTA or stress testing adding nothing to the care of chest pain patients beyond what is achieved by a history, physical examination, ECG and troponin test.
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MedicalResearch.com Interview with:
Hao Yu Chen, MScDepartment of Medicine
McGill University
Montreal, Quebec, Canada
Senior author: George Thanassoulis, MD, MScMedicalResearch.com: What is the background for this study?
Response: Aortic stenosis, a narrowing of the main valve of the heart, is the most common type of valve disease in the US. Present in more than 2.5 million individuals in North America, aortic stenosis can lead to heart failure and death. However, there is little known about the causes of aortic stenosis and how it should be treated.
Previously, we have demonstrated that variants of the gene LPA are associated with the development of aortic stenosis. A better understanding of how this region contributes to aortic stenosis could identify higher-risk individuals and inform the development of new medical therapies for aortic stenosis.(more…)
MedicalResearch.com Interview with:
Jesper Svane
Medical student
The Heart Center, University Hospital Rigshospitalet
CopenhagenMedicalResearch.com: What is the background for this study?
Response: At the beginning of this research project, we were aware that persons with diabetes have an increased risk of death, which is partly explained by an increased risk of sudden cardiac death. However, previous studies on causes of death and mortality among young persons with diabetes, particularly type 2 diabetes, are sparse. Furthermore the incidence of sudden cardiac death among young persons with diabetes in a nationwide setting is unknown.
The main purpose of the study was to illuminate the risk of death and especially the risk of cardiac death among children/young adults with diabetes.
On a personal note, a friend of mine, who was healthy and fit, died suddenly a few years ago at the age of 19. This tragic death raised a lot of feelings as well as questions in me. When I got the chance to work with Dr. Lynge and Dr. Tfelt, I saw this as an opportunity to expand my knowledge of sudden cardiac death among the young. Furthermore, the opportunity of contributing to research in order to prevent these devastating events in the future was personally appealing to me.
I initiated the project together with Thomas Hadberg Lynge, MD, last year, with Jacob Tfelt-Hansen, MD, DMSc as supervisor. Both are experienced researchers within the field of sudden cardiac death. Dr. Tfelt-Hansen leads a very productive research group at Rigshospitalet, Copenhagen, whose main focus is arrhythmias and sudden cardiac death.
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MedicalResearch.com Interview with:
Laura StevensUniversity of Colorado
Aurora, COMedicalResearch.com: What is the background for this study? What are the main findings?
Response: We started with asking ourselves how we could better predict cardiovascular and stroke outcomes. In an ideal world, we would be able to predict cardiovascular disease (CVD) and stroke with 100% accuracy long before the occurrence of the event. The challenge here is there are so many potential risk factors, and testing each one using traditional methods would be extremely time consuming, and possibly infeasible.
Therefore, we used artificial intelligence to find potential risk factors that could be important for risk of CVD and stroke. The results of this analysis pointed to consumption of coffee cups per day and the number of times red meat was consumed per week as being potentially important predictors of CVD.
We then looked into these findings further using traditional statistical analyses to determine that increased coffee consumption and red meat consumption appeared to be associated with decreased risk of CVD. The study initially used data from the Framingham Heart Study (FHS) original cohort.
The findings from this data were then tested using data from 2 independent studies, the Cardiovascular Heart Study (CHS) and the Atherosclerosis Risk in Communities Study (ARIC), which both supported the association of increased coffee consumption with decreased CVD risk.
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MedicalResearch.com Interview with:
Dr. Mattias Brunström
Department of Public Health and Clinical Medicine
Umeå University,Sweden
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Current guidelines recommend a systolic blood pressure treatment target below 140 mm Hg for most people. Since the publication of SPRINT however, many have suggested guidelines should be changed, recommending further blood pressure lowering.
We performed a systematic review and meta-analysis of randomized clinical trials comparing different blood pressure targets or antihypertensive treatment verus placebo. We separated primary preventive trials from secondary preventive trials, and stratified primary preventive trials by mean baseline systolic blood pressure. The analyses included 74 trials, with in total > 300 000 participants. Interestingly, we found that treatment effect was dependent on baseline systolic blood pressure in people without previous CVD.
While primary preventive treatment reduced the risk of death and cardiovascular disease if systolic blood pressure was 140 mm Hg or higher, treatment effect was neutral if systolic blood pressure was below 140 mm Hg.
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MedicalResearch.com Interview with:
Dr Andrew R. Chapman
BHF Clinical Research Fellow
University of Edinburgh
Chancellors Building
EdinburghMedicalResearch.com: What is the background for this study? What are the main findings?Response: High-sensitivity cardiac troponin tests allow accurate measurement of cardiac troponin in the bloodstream. Currently, guidelines recommend we evaluate patients with suspected myocardial infarction using these tests, by looking for levels which are above the upper reference limit (99th centile). These troponin measurements are taken on arrival, and often repeated after admission to hospital up to six hours later. When levels are below this limit, the diagnosis of myocardial infarction is ruled out. However, using such a high limit in patients on arrival to hospital may not be safe, as lower risk stratification thresholds has been shown to reduce missed events, and in these patients admission to hospital for repeat testing may not be necessary. However, there is no consensus as to the optimal threshold for use in practice.
In a worldwide study of 23,000 patients from 9 countries, we have shown when high-sensitivity cardiac troponin I concentrations are below a risk stratification threshold of 5 ng/L at presentation, patients are at extremely low risk of myocardial infarction or cardiac death at 30 days, with fewer than 1 in 200 patients missed. Importantly, this threshold identifies almost 50% of all patients as low risk after a single blood test. As admission or observation of these patients is estimated to cost as much as $11 billion per year in the United States, this strategy has major potential to improve the efficiency of our practice.
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MedicalResearch.com Interview with:
Avinainder Singh, M.B.B.S.
Research Fellow
Cardiovascular Medicine
Brigham & Women's Hospital
Harvard Medical School
Boston, MAMedicalResearch.com: What is the background for this study? What are the main findings?Response: Overall, the incidence of myocardial infarction (MI) in the US has declined. However, it has remained stable in adults <50 years of age.
We evaluated the statin eligibility of a cohort of adults who had an MI at a young age using current guidelines - the 2013 ACC/AHA guidelines for cholesterol treatment and the 2016 USPSTF guidelines on use of statins for primary prevention.
In, our study we found that only 49% of these young adults would have been eligible for statin therapy prior to their MI according the 2013 ACC/AHA guidelines, and only 29% would have been eligible according to the USPSTF guidelines, despite a high prevalence of cardiovascular risk factors. These numbers were even more striking for women where only 18% were eligible for statin therapy according to the USPSTF guidelines.
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MedicalResearch.com Interview with:
Abdul Wase MD FACC FACP FHRS
Clinical Professor of Medicine &
Director, Cardiology Fellowship Program,
Wright State University Boonshoft School of Medicine,
Director, Electrophysiology Laboratories
Good Samaritan Hospital,
Dayton, OH
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Implantable cardiac defibrillators (ICD) patients are subject to electromagnetic interferences (EMI) from outside electrical sources.
TESLA electric vehicle has a large battery underneath the surface of vehicles, which may potentially interfere with the functioning of these devices. In the owner’s manual, TESLA warns that using mobile connector may impair the functioning of implantable pacemaker or a defibrillator.
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MedicalResearch.com Interview with:
Dr. Kyla M Lara
Icahn School of Medicine at Mount SinaiMedicalResearch.com: What is the background for this study? What are the main findings?Response: This was the first study to evaluate whether dietary patterns of black and white adults living in the United States were associated with developing heart failure. We’re hearing a lot in the news about specific diets like low-fat, high protein, low carb, and other diets that decrease cardiovascular risk. We would love it, as physicians, if we could prescribe a specific diet to limit cardiovascular risk in our patients. I’m really excited about our study because instead of examining patterns of what we already know are healthy, we looked at foods people were regularly consuming in the United States and developed dietary patterns from this. This study is similar to other work we have done with stroke and heart attack.
We used data from the NIH funded REGARDS study, also known as the Reasons for Geographic and Racial Differences in Stroke. More than 30,000 white and African-American adults were recruited from 2003-2007. From this group, we studied over 18,000 adults who successfully completed a dietary assessment called the Food Frequency Questionnaire. This was a really great group to study because people who live in this particular geographic area of the Southeastern United States, also known as the stroke belt, suffer from a higher risk of death from stroke. It’s extremely important for us to better understand the major risk factors that contribute to this and also cardiovascular disease.
We used statistical techniques to derive 5 dietary patterns based on the types of foods participants tended to eat.
• Convenience - Mexican and Chinese food, mixed dishes (both meat and bean)
• Sweets - added fats, bread, chocolate, desserts, sweet breakfast foods
• Southern - added fats, fried food, organ and processed meat, fatty milk
• Alcohol/Salads - beer, wine, liquor, green leafy vegetables, salad dressings, nuts and seeds, coffee
• Plant Based- fruit, vegetables, fruit juice, cereal, fish, poultry
Each participant received a score for each pattern that reflected how closely their diet resembled that dietary pattern. This approach reflects the real world and how people eat.
Over the 3135 days (8.6 years) of median follow up, 594 participants were hospitalized for incident HF. Greatest adherence to the plant-based dietary pattern during the study period was associated with a 28% risk reduction of developing heart failure.
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MedicalResearch.com Interview with:
Kevin S. Shah, M.D.
Cardiology Fellow, University of California, Los Angeles
Ronald Reagan UCLA Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Heart failure (HF) is a chronic condition and progressive disease which is associated with a high-risk of hospitalization and death. One of the principle ways in which heart function is estimated is the use of ultrasound to calculate the ejection fraction of the heart, an estimate of the heart’s pump function. The ejection fraction can help predict how long patients will live and affects decision-making with regards to what medications may help their condition.
A total of 39,982 patients from 254 hospitals who were admitted for Heart failure between 2005 and 2009 were included. They were followed over time to see if they were admitted to the hospital again or if they died during this period. We compared three subgroups within this large group of patients based on their estimated ejection fraction. Across subgroups, the 5-year risk of hospitalization and death was high when compared with the U.S. population. Furthermore, the survival for patients with a diagnosis of heart failure who have been hospitalized once for this condition have a similarly poor 5-year risk of death and re-hospitalization, regardless of their estimated ejection fraction.
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MedicalResearch.com Interview with:
Ankur Gupta, MD, PhD
Division of Cardiovascular Medicine
Brigham and Women’s Hospital Heart & Vascular Center and
Harvard Medical School,
Boston, MassachusettsMedicalResearch.com: What is the background for this study? What are the main findings?
Response: The Hospital Readmissions Reduction Program (HRRP), established under the Affordable Care Act, aimed to reduce readmissions from various medical conditions including heart failure - the leading cause of readmissions among Medicare beneficiaries. The program financially penalizes hospitals with high readmission rates. However, there have been concerns of unintended consequences especially on mortality due to this program.
Using American Heart Association's Get With The Guidelines-Heart Failure (GWTG-HF) data linked to Medicare data, we found that the policy of reducing readmissions after heart failure hospitalizations was associated with reduction in 30-day and 1-year readmissions yet an increase in 30-day and 1-year mortality.
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MedicalResearch.com Interview with:
Mimi Biswas M.D., MHSc
University of California Riverside School of Medicine and
Riverside Community HospitalMedicalResearch.com: What is the background for this study? What are the main findings?
Response: This started as My son's science project. He wanted to make a video game to teach CPR based on a science fair website. It grew to teaching the whole 6th grade using the AHA CPR training kit alone vs adding the video game or music, staying alive, to help with compression rate. We found that a 12 year can easily learn the basic concepts of calling for help and starting hands only CPR and they can physically perform effective CPR at this age.
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MedicalResearch.com Interview with:
Stephen P. Juraschek, MD, PhD
Instructor of Medicine
Beth Israel Deaconess Medical Center/Harvard Medical SchoolMedicalResearch.com: What is the background for this study? What are the main findings?
Response: The DASH-Sodium trial demonstrated that both the DASH diet and sodium restriction, individually and combined, lowered blood pressure in adults with pre-hypertension or stage 1 hypertension. Whether these effects varied by level of blood pressure prior to starting these interventions was unknown. In a secondary analysis of the original DASH diet it had been observed that the effects from DASH were greater among adults with higher blood pressure (systolic greater than or equal to 140 mm Hg) at baseline with the appearance of even greater effects among people with baseline systolic blood pressures above 150 mm Hg. However, this has never been shown. Furthermore, it was unknown whether sodium reduction followed a similar linear trend of greater effects among adults with more severely uncontrolled systolic blood pressure.
In our study, we found that effects were indeed greater in adults with a baseline systolic blood pressure of 150 mm Hg or greater. Furthermore, the combined systolic blood pressure-lowering effect from both interventions was as high was 20 mm Hg. This is a magnitude comparable if not greater than medications for lowering blood pressure.
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MedicalResearch.com Interview with:
Dr. Keun-Hwa Jung MD PhD
Program in Neuroscience, Neuroscience Research Institute of SNUMRC
College of Medicine
Seoul National University
First author: Dr. Woo-Jin Lee MD
Department of Neurology
Seoul National University Hospital
Seoul, South KoreaMedicalResearch.com: What is the background for this study? What are the main findings?Response: Cerebral white matter hyperintensity is a prevalent consequence of brain aging process and associated with various complications. One of the main mechanisms underlying the progression of white matter hyperintensity is chronic dysfunction of the glymphatic system which maintains metabolic homeostasis in brain. Glymphatic system is the route where the cerebrospinal fluid enters into the brain parenchyma and is cleared out with soluble wastes to the perivascular space of the cerebral small veins, peri-meningeal lymphatic vessels, deep cervical lymph nodes, and finally to the right atrium.
Although the integrity of the glymphatic system is dependent on the adequate drainage of cerebral veins and lymphatics to the downstream chamber, the right atrium, the impact of hemodynamic changes in right-sided cardiac chambers on the development of white matter hyperintensity have not been elucidated.
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MedicalResearch.com Interview with:
Nayan Agarwal MD
Intervention Cardiology Fellow
University of Florida,
Gainesville, FL
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Optimal antiplatelet strategy post CABG remains controversial with guidelines still evolving. Though aspirin monotherapy is the therapy of choice, but some studies have suggested a benefit of dual antiplatelet (DAPT). Question also remains if choice of antiplatelet therapy strategy is influenced by clinical presentation (acute coronary syndrome [ACS] versus non ACS) or CABG technique ( off pump versus on pump).
The current meta-analysis of 8 randomized control trials and 9 observational studies with a total of 11,135 patients demonstrated that at a mean follow up of 23 months, major adverse cardiac events (MACE) (10.3% versus 12.1%, RR 0.84, confidence interval (CI) 0.71-0.99); all-cause mortality (5.7% versus 7.0%, RR 0.67, CI 0.48-0.94) and graft occlusion (11.3% versus 14.2%, RR- 0.79, CI- 0.63- 0.98) were less with DAPT compared with aspirin monotherapy. There was no difference in myocardial infarction, stroke, or major bleeding between the 2 groups. Subgroup analysis demonstrated that benefit of DAPT was independent of clinical presentation (ACS versus non ACS) or CABG technique (off pump versus on pump).
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MedicalResearch.com Interview with:
Bruno Péault PhDProfessor and Chair, Vascular Regeneration
Center For Cardiovascular Science
MRC Centre for Regenerative Medicine
Scientific Director, BHF Laboratories
The University of Edinburgh and
Professor, David Geffen School of Medicine at UCLA
Orthopaedic Hospital Research Center
University of California at Los Angeles
Los Angeles, CA 90095-7358
MedicalResearch.com: What is the background for this study?
Response: Kidney, lung, liver, muscle, heart are among the many organs which can be severely affected by fibrosis, a natural scarring process whereby healthy tissues are replaced by a fibrous non-functional substitute. For instance, the billions of cardiac muscle cells that die after a heart infarct, consequently to blood supply interruption, are replaced by a fibrotic scar that cannot contract, reducing the capacity of the heart to pump blood, and leading often to heart failure. There is currently no efficient treatment of fibrotic scars, the basic cellular component of which is the myofibroblast, a cell of unremarkable appearance and unclear origin. The transforming growth factor β (TGFβ) molecule triggers fibrosis development after being activated, via the extra-cellular matrix, by αv integrins, which are adhesion molecules present at the surface of the target cells.
To gain further insight into the cells that drive fibrosis in the heart and skeletal muscle, and explore ways to control this deleterious process, mice were used in which cells expressing the β receptor for PDGF (platelet derived growth factor) have been genetically tagged with a green fluorescent protein, a system previously used by Prof. Neil Henderson to trace fibrosis in the diseased liver (cells naturally expressing PDGFRβ are, in their vast majority, perivascular cells surrounding small blood vessels, as well as some interstitial fibroblasts). Skeletal muscle was injured by a small incision or with a targeted injection of cardiotoxin, a snake venom compound that locally kills myofibers, while the heart was damaged by prolonged infusion of angiotensin II. In both settings, progression of fibrosis was followed over time and contribution of green fluorescent cells – i.e. those expressing PDGFRβ – was assessed.
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MedicalResearch.com Interview with:
Prof David Montaigne MD
Faculté de Médecine de Lille H Warembourg
Lille, France
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: It is well known for many decades that cardiovascular diseases exhibit a diurnal variation with for instance higher incidence of myocardial infarction in the early morning as opposed to the evening. Although studies on circadian gene knock-out and mutant mice argue for a biorhythm in myocardial ischemia-reperfusion tolerance, whether a biorhythm in the myocardial tolerance to ischemia, exists in humans was unclear because of conflicting reports in the context of myocardial infarction.
We demonstrated for the first time in humans that the myocardial tolerance to ischemia-reperfusion is different along the day, in line with rodent experiments performed in the early 2010s.
We demonstrated that this biorhythm is clinically meaningful and that it can be targeted as a cardioprotective strategy.
In this topic, Rever-alpha is of specific interest. It belongs at the same time to circadian genes and nuclear receptor families: being a nuclear receptor, it is a feasible pharmacological target, conversely to other circadian genes.
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MedicalResearch.com Interview with:
Dr. Evan L. Brittain, MD
Assistant Professor of Medicine
Vanderbilt University School of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The purpose of this study was to determine whether pulmonary pressure values below the diagnostic threshold for pulmonary hypertension (25mmHg) are associated with an increased risk of mortality. We studied over 4,000 consecutive individuals referred for right heart catheterization, the “gold-standard” procedure for measuring pulmonary pressure. We found that borderline levels of mean pulmonary pressure (19-24mmHg) were common, representing 18% of all patients referred for this procedure. Borderline mean pulmonary pressure values were also associated with 31% increase in mortality after accounting for many other clinical factors. Finally, we found that most of the patients with borderline pulmonary hypertension who underwent repeat catheterization often progressed to overt pulmonary hypertension.
This study suggests that patients with borderline pulmonary hypertension should be considered an at-risk group.
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MedicalResearch.com Interview with:
Elad Asher, M.D, M.H.A
Interventional Cardiologist,
Director Intensive Cardiac Care Unit
Deputy Director Heart Institute
Assuta Ashdod Medical Center
MedicalResearch.com: What is the background for this study?
Response: Dual antiplatelet therapy represents the standard care for treating ST elevation myocardial infarction (STEMI) patients. Given the higher risk of peri-procedural thrombotic events in patients undergoing primary percutaneous coronary intervention (PPCI), there is a need to achieve inhibition of platelet aggregation (IPA) more promptly. Although chewing ticagrelor has been shown to be more efficient for IPA in stable coronary disease and in patients with acute coronary syndrome (ACS)/non-ST elevation myocardial infarction (NSETMI), there are no studies that have specifically assessed the efficacy and safety of chewing ticagrelor in STEMI patients. Therefore, the aim of our study was to investigate whether chewing ticagrelor (180mg) loading dose is associated with more favorable platelet inhibitory effects compared with the conventional way of swallowing whole tablets loading dose in STEMI patients undergoing PPCI.
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MedicalResearch.com Interview with:
Dr. Leif Friberg MD, PhD
Associate professor in cardiology
Karolinska Institute
Friberg Resarch
Stockholm, SwedenMedicalResearch.com: What is the background for this study? What are the main findings?Response: I have been doing research on atrial fibrillation and stroke risk for many years and knew that the very common heart arrhythmia is associated with a 40% increased risk of dementia. Considering that that 12-15% of 75 years olds have this arrhythmia, and even more at higher ages, the problem is significant to say the least.
The mechanism behind stroke in atrial fibrillation is that blood clots are formed in the heart. When these are dislodged they travel with the blood stream and may get stuck in the narrow vessels of the brain where they stop blood flow causing brain infarction or stroke. Oral anticoagulant drugs like warfarin or the newer so called NOAC (new oral anticoagulant) drugs are highly efficient in preventing formation of these large blood clots and offer at least 70% risk reduction. Now, blood clots come in different sizes. There are also microscopic clots that do not cause symptoms of stroke but all the same eat away at the brain at a slow but steady pace. Imaging studies shows this after only a few months or even weeks of atrial fibrillation. Our hypothesis was therefore: If anticoagulants are so effective in protecting against large clots, will they not help against the small ones too?
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MedicalResearch.com Interview with: Christine Baumgartner MD
Inselspital
Universitätsspital Bern
Bern, Switzerland
Research Fellow, Division of Hospital Medicine
UCSF
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Overt and subclinical hyperthyroidism increase the risk of atrial fibrillation, but it is unclear whether subclinical hypothyroidism, which is known to increase cardiovascular events, or thyroid function in the normal range are also associated with incident atrial fibrillation. Given the high prevalence of atrial fibrillation and its associated morbidity and mortality, identifying potentially modifiable risk factors is important. Therefore, we aimed to assess the risk of atrial fibrillation in individuals with subclinical hypothyroidism or variations of thyroid function within the normal range.
Our main findings are that higher free thyroxine levels are associated with an increased risk of atrial fibrillation in euthyroid individuals, but thyroid-stimulating hormone levels within the euthyroid or subclinical hypothyroid range was not related to atrial fibrillation risk.
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