Author Interviews, Heart Disease, JACC / 10.04.2019

MedicalResearch.com Interview with: Susana Ravassa PhD Program of Cardiovascular Diseases, CIMA University of Navarra, and IdiSNA Navarra Institute for Health Research Pamplona, Spain  MedicalResearch.com: What is the background for this study? Response: Atrial fibrillation (AF) is an evolving epidemic responsible for substantial morbidity, mortality and health-care expenditure. In particular, when AF and heart failure (HF) occur in combination, clinical evolution is particularly poor. Left atrial (LA) myocardial interstitial fibrosis (MIF) is the main structural lesion in AF and considered as the main factor responsible for the perpetuation of this pathology. In addition, it is known that MIF is associated with a lower effectiveness of the treatment of AF by pulmonary vein isolation with catheter ablation. Therefore, the identification of biomarkers related to MIF, as an affordable and minimally invasive approach, is of great interest to detect patients at risk of AF, as well as to monitor their response to the LA ablation therapy. We had previously demonstrated that the deleterious impact of MIF in the heart is due to alterations in both the quality (i.e., extent of cross-linking among collagen fibrils and type of collagen fibers that determine their rigidity and resistance to degradation [collagen cross-linking or CCL]) and the quantity (i.e., extent of collagen fibers that occupy the myocardial tissue [collagen deposition or CD]) of fibrotic tissue. We have shown that certain circulating biomarkers related to collagen type I metabolism are associated with CCL and CD. On the one hand, the serum carboxy-terminal propeptide of procollagen type I (PICP), released during the conversion of procollagen type I into fibril-forming mature collagen type I, is directly correlated with myocardial CD. On the other hand, the ratio of serum carboxy-terminal telopeptide of collagen type I to serum matrix metalloproteinase-1 (serum CITP:MMP-1 ratio) is inversely correlated with myocardial CCL, as the higher is the cross-linking among collagen type I fibrils the lower will be the cleavage of CITP by MMP-1 during the process of degradation of the fiber. Interestingly, we have previously reported that the combination of these biomarkers identifies patients with heart failure presenting with a complex pattern of MIF characterized by both increased CCL and CD (CCL+CD+) showing a higher risk of adverse clinical evolution as compared with heart failure  patients without this combination of biomarkers. As both increased CCL and CD have been found in the left atrial myocardium in patients with AF, we designed this investigation to explore whether the CCL+CD+ combination of biomarkers is associated with AF.
Author Interviews, Clots - Coagulation, Duke, Heart Disease, NEJM / 21.03.2019

MedicalResearch.com Interview with: [caption id="attachment_20394" align="alignleft" width="200"]Renato D. Lopes MD, MHS, PhD Duke University Medical Center Duke Clinical Research Institute Durham, NC 27705 Dr. Renato Lopes[/caption] Renato D. Lopes MD, MHS, PhD Professor of Medicine Division of Cardiology Duke University Medical Center Duke Clinical Research Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: In patients with acute coronary syndromes (ACS), approximately 20% to 30% of those with nonvalvular atrial fibrillation (NVAF) have concomitant coronary artery disease (CAD), and 5 to 10% of patients who undergo PCI have NVAF. These patients often receive both antiplatelet therapy and oral anticoagulants; and how best to combine these agents to minimize bleeding risk without compromising protection against thrombosis is an important unanswered question. Analysis of results for bleeding indicated no significant interaction between the two randomization factors permitting independent analysis of results for the two key comparisons. The first showed that apixaban was both non-inferior and significantly superior to VKA for the primary outcome with a 31% reduction in the relative risk for bleeding. Aspirin significantly increased the relative risk for bleeding versus placebo by 89%. Results for the composite of death and hospitalization showed that apixaban resulted in a relative risk reduction of 17%, primarily driven by a reduction in all cause hospitalization. There was no significant difference between results for aspirin versus placebo for this outcome. Analysis of the composite of death and ischemic events indicated no significant differences in results for apixaban versus VKA or aspirin versus placebo.
Author Interviews, Heart Disease, JAMA / 19.03.2019

MedicalResearch.com Interview with: [caption id="attachment_47952" align="alignleft" width="167"]Dr. Carina Blomström-Lundqvist, MDProfessor of CardiologyDepartment of CardioloyInstitution of Medical ScienceUppsala, Sweden Dr. Blomström-Lundqvist[/caption] Dr. Carina Blomström-Lundqvist, MD Professor of Cardiology Department of Cardioloy Institution of Medical Science Uppsala, Sweden MedicalResearch.com: What is the background for this study?   Response: While all previous trials comparing atrial fibrillation (AF) ablation and antiarrhythmic drugs to our best knowledge have evaluated the efficacy of these treatments in terms of atrial fibrillation (AF) recurrences (with an AF episode of 30 seconds duration as standard primary endpoint) we wanted to use quality of Life (QoL) - general health - as primary endpoint, since the indication for treatment is improving QoL. This was important since, despite the fact that the indication for treatment is to improve (QoL) and reduce symptom, all prior trials have used 30 seconds AF episodes as standard primary endpoint, which if occurred it would be defined as a failed treatment. We also wanted to assess effects on various clinical outcome events. We know from registries such as ORBIT AF registry that around 60 % of AF patients have symptoms resulting in repeated hospitalisation visits in at least 30-40% of patients annually, and that only around 5 % of the AF population are being referred for AF ablation. Previous trials have used intermittent 24 hours Holter recordings whioch does not give the true AF burden (% of time in AF). We therefore also wanted to assess and compare treatments effects on true AF burden by implanting an implantable cardiac monitor (ICM) which continuosly records the heart rhythm. We would then be able to prove that improvement in QoL was directly related to a reduction in AF burden and that treatment differences in QoL was related to a difference in reduction in AF burden. We also wanted to study an AF population in their early AF disease state so that we could offer atrial fibrillation ablation to a broader AF population before their atria have become remodelled and too damaged for a pulmonary vein isolation to be effective. 
Author Interviews, Heart Disease, JAMA / 10.08.2018

MedicalResearch.com Interview with: [caption id="attachment_43824" align="alignleft" width="143"]Seth Landefeld, M.D.  Dr. Landefeld is chairman of the department of medicine and the Spencer chair in medical science leadership at the University of Alabama at Birmingham (UAB) School of Medicine. Dr. Landefeld also serves on the board of directors of the American Board of Internal Medicine, the UAB Health System, and the University of Alabama Health Services Foundation Dr. Landefeld[/caption] Seth Landefeld, M.D.  Dr. Landefeld is chairman of the department of medicine and the Spencer chair in medical science leadership at the University of Alabama at Birmingham (UAB) School of Medicine. Dr. Landefeld also serves on the board of directors of the American Board of Internal Medicine, the UAB Health System, and the University of Alabama Health Services Foundation. MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by atrial fibrillation and whom it primarily affects? Response: Atrial fibrillation—or AF—is an irregular heartbeat. AF affects nearly 3 million Americans and is a leading cause of stroke. Older age and obesity increase the risk of AF, and the condition also occurs more in men than in women. With an aging society and the growing prevalence of obesity in the U.S., this was an important topic for the U.S. Preventive Services Task Force to review. The Task Force looked at the latest research to see if screening for atrial fibrillation using electrocardiography—or ECG, which is a test that records the activity of someone’s heart—to supplement traditional care is an effective way to diagnose AF and prevent stroke. We found that more research is needed to determine if screening with ECG can help to identify AF and prevent stroke in adults who are 65 and older and do not have signs or symptoms of the disease. 
Author Interviews, Biomarkers, Heart Disease, JACC / 09.08.2018

MedicalResearch.com Interview with: [caption id="attachment_43632" align="alignleft" width="200"]John D Horowitz, MBBS, PhD. Director of Cardiology/Clinical Pharmacology Queen Elizabeth Hospital University of Adelaide Australia Dr. Horowitz[/caption] John D Horowitz, MBBS, PhD. Director of Cardiology/Clinical Pharmacology Queen Elizabeth Hospital University of Adelaide Australia  MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Atrial fibrillation (AF) describes intermittent or permanent episodes of irregular pulse, due to rapid electrical activity within the atria (filling chambers) of the heart. During AF, the atria quiver, rather than contract, and the response of the ventricles is often rapid, resulting in palpitations and an increased risk of development of heart failure. AF may occur at any age, but is most common in ageing patients (typically over 75 years). The primary importance of AF is that it markedly increases the risk of thrombus formation in the atrium, with the resultant problem that these thrombi may dislodge (embolise), and commonly block arteries in the brain, causing strokes. Hence patients with AF are usually treated with anticoagulants. Although AF often occurs in patients with prior damage to their hearts and atrial distension, there has been evidence for about the past 8 years that AF also is caused, at least in part, by inflammatory changes: two components have been identified as possible causes for this inflammation: lack of nitric oxide (NO) effect[ NO is  an anti-inflammatory chemical formed by all tissues in the body],  and excess activity of the pro-inflammatory enzyme myeloperoxidase (MPO).  High concentrations of ADMA, which inhibits NO formation, may result from effects of MPO on tissues. SDMA, which is closely related to ADMA, also exerts pro-inflammatory effects and tends to suppress NO formation. The currently reported study began with the design of the ARISTOTLE trial, an investigation of the (then) novel anticoagulant apixaban as an alternative to warfarin therapy, as a means of preventing strokes in patients with AF. It was elected to perform a substudy to investigate the potential role of ADMA and SDMA as modulators of risk in patients with atrial fibrillation. This substudy, performed in just over 5000 patients from the ARISTOTLE trial, essentially asked two questions: (1) There are several indices of stroke risk in patients with atrial fibrillation, such as the CHADS2 score. These all rely on patient characteristics (eg age, presence of diabetes) rather than chemical changes. We postulated that there would be a direct relationship between clinically based risk scores and ADMA/SDMA concentrations. (2) More ambitiously, we postulated that ADMA and SDMA concentrations would represent INDEPENDENT risk markers for major adverse effects in atrial fibrillation patients on anticoagulant treatment, namely stroke, major bleeding and risk of mortality.  ADMA/SDMA concentrations were determined in Adelaide, Australia, while statistical analyses were performed in Uppsala, Sweden.
Author Interviews, Heart Disease, Surgical Research, Vitamin C / 06.02.2017

MedicalResearch.com Interview with: [caption id="attachment_25990" align="alignleft" width="180"]Dr-Harri-Hemilae.jpg Dr. Harri Hemilae[/caption] Harri Hemilä, MD, PhD Department of Public Health University of Helsinki MedicalResearch.com: What is the background for this study? Response: I have a long term interest in vitamin C. Previously I have shown that it alleviates exercise-induced bronchoconstriction (EIB) (http://dx.doi.org/10.1186/1710-1492-10-58 ) and shortens the duration of colds ( http://dx.doi.org/10.1371/journal.pmed.0020168 ). Now I had been following the literature and I noted that a number of randomized trials were being published about vitamin C for preventing post-operative atrial fibrillation (POAF). Therefore I reasoned that it is worthwhile to analyze that set of trials
Author Interviews, Heart Disease / 03.09.2014

Jean-Philippe Couderc, PhD, MBA Associate Professor of Medicine Research Associate professor of Electrical and Computer Engineering University of Rochester, NY Heart Research Follow-Up Program - Cardiology Department Rochester, New-York 14642MedicalResearch.com: Interview with: Jean-Philippe Couderc, PhD, MBA Associate Professor of Medicine Research Associate professor of Electrical and Computer Engineering University of Rochester, NY Heart Research Follow-Up Program - Cardiology Department Rochester, New-York 14642 Medical Research: What are the main findings of the study? Dr. Couderc: We have developed a unique technology which enables any individual to evaluate if he/she suffers from atrial fibrillation (AF) by using a simple video camera (webcam). There are approximately 3.2 million people with AF in the US, and estimated 30 million people in the world. It has been shown that around 30% of people suffering from AF are not aware of their disease, this form is called 'silent' atrial fibrillation.  AF is a progressive disease leading to stroke and heart failure.  It results in significant morbidity and mortality. The total cost of AF in the US is estimated to $7billion and 75% of this cost is associated with patient hospitalization.
AHA Journals, Author Interviews, Cost of Health Care, Heart Disease, JACC / 22.05.2014

MedicalResearch.com Interview with: Nileshkumar J. Patel MD Staten Island University Hospital Staten Island, NY, 10304 and Abhishek J. Deshmukh MD University of Arkansas Little Rock, AR MedicalResearch: What are the main findings of the study? Answer: We analyzed data from almost 4 million hospitalizations for atrial fibrillation (AF) from more than 1,200 hospitals across 45 states in last decade, and found that -   Hospitalization rates for atrial fibrillation have increased exponentially among US adults during the past 10 years, particularly in those 65 years or older. -   The most frequent coexisting conditions were hypertension (59.99%), diabetes (21.47%) and chronic pulmonary disease (20.01%). -   In terms of geographic distribution of admissions, the hospitals in the South constitute (38.5%) the highest percentage of atrial fibrillation hospitalizations, followed by Midwest (24.9%), Northeast (22.2%) and West (14.4%). -   Overall in-hospital mortality was 1%. The mortality rate was highest in >80 years age group (1.93%) and patients with concomitant heart failure (8.2%). -   The percentage of patients discharged to nursing facility increased from 8.1% in 2000 to 11.5% in 2010 and need for home health care increased from 6.7% to 13.1%. Approximately one fourth of the patients (25.83%) were discharged to long-term care institution if atrial fibrillation hospitalization was complicated by acute ischemic stroke. -   Mean cost of AF hospitalization increased significantly from $6,410 in 2001 to $8,439 in 2010 (24.04% increase, p <0.001) even after adjusting for inflation. This represents an absolute increment in annual national cost from approximate 2.15 billion dollars in 2001 to 3.46 billion dollars in 2010. The mean cost of care was highest if AF hospitalization was associated with heart failure ($33,161) and valvular disorders ($28,030).