Author Interviews, Biomarkers, Heart Disease, JAMA / 01.06.2016
Heart Attack Can Be Ruled-Out in One Hour with High-Sensitivity Troponin I Assay
MedicalResearch.com Interview with:
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Dr. Johannes Neumann[/caption]
Dr. med. Johannes Neumann
Resident physician
University Heart Center Hamburg
Department of General and Interventional Cardiology
Universitätsklinikum Hamburg-Eppendorf
Hamburg
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The early decision making in patients with suspected acute myocardial infarction is important. Current guidelines recommend measurement of cardiac troponin at admission and after 3 hours. In our study we evaluated the performance of a high-sensitivity troponin I assay with a rapid measurement after only 1 hour. We included 1040 patients with new onset chest pain and could show, that a low cutoff concentration of 6 ng/L after 1 hour allows safe rule-out of acute myocardial infarction. The results were comparable to the recommended 3-hour approach and were validated in 2 external cohorts. When using the 99th percentile to rule-out myocardial infarction, as recommended by current guidelines, the negative predictive value was much lower. Furthermore, a troponin I concentration above 6 ng/L in combination with an absolute change of 12 ng/L after 1 hour showed a high positive predictive value for the final diagnosis of myocardial infarction. This allows early decision making after only 1 hour.
Dr. Johannes Neumann[/caption]
Dr. med. Johannes Neumann
Resident physician
University Heart Center Hamburg
Department of General and Interventional Cardiology
Universitätsklinikum Hamburg-Eppendorf
Hamburg
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The early decision making in patients with suspected acute myocardial infarction is important. Current guidelines recommend measurement of cardiac troponin at admission and after 3 hours. In our study we evaluated the performance of a high-sensitivity troponin I assay with a rapid measurement after only 1 hour. We included 1040 patients with new onset chest pain and could show, that a low cutoff concentration of 6 ng/L after 1 hour allows safe rule-out of acute myocardial infarction. The results were comparable to the recommended 3-hour approach and were validated in 2 external cohorts. When using the 99th percentile to rule-out myocardial infarction, as recommended by current guidelines, the negative predictive value was much lower. Furthermore, a troponin I concentration above 6 ng/L in combination with an absolute change of 12 ng/L after 1 hour showed a high positive predictive value for the final diagnosis of myocardial infarction. This allows early decision making after only 1 hour.
Dr. Nicole Pratt[/caption]
Nicole Pratt PhD
Senior Research Fellow
Quality Use of Medicines and Pharmacy Research Centre
Sansom Institute, School of Pharmacy and Medical Sciences
University of South Australia
Adelaide South Australia
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Pratt: The cardiac safety of methylphenidate has been debated. This study aimed to measure the risk of cardiac events in a large population of children treated with these medicines. We found that there was a significantly raised risk of arrhythmia in time periods when children were treated with methylphenidate compared to time periods when they were not. While the relative risk of cardiac events was significant the absolute risk is likely to be low as cardiac events are rare in children.
Dr. Nina Berentzen[/caption]
Dr. Nina Berentzen PhD
National Institute for Public Health and the Environment
Bilthoven, the Netherlands
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Berentzen: Cardiovascular disease and type 2 diabetes often occur together and share risk factors including an unhealthy diet, a lack of physical activity, and being overweight or obese. This study is the first to investigate the occurrence of both diabetes and CVD across two generations of parents and grandparents, and relate it to measurable risk factors in children. We found that one third of the 12-year-olds studied had a strong family history of one or both of cardiovascular disease (myocardial infarction and stroke) and type 2 diabetes. Children had a ‘strong family history’ if they had one affected parent, or at least one grandparent with early disease onset, or 3–4 grandparents with late disease onset. These children had higher levels of total cholesterol, and a higher ratio of total/HDL cholesterol than children with no family history of disease.
Dr. Robert Levenson[/caption]
Robert W. Levenson, Ph.D.
Professor, Department of Psychology
Director, Institute of Personality
and Social Research (IPSR)
University of California
Berkeley, CA
MedicalResearch.com: What is the background for this study?
Dr. Levenson: This study comes from a 20-year longitudinal study of Bay Area married couples that we began in the late 1980s. The main purpose of the study was to understand the emotional qualities of successful marriages. Couples came to our laboratory every five years so that we could get a snapshot of the way they interacted with each. We also measured their psychological and physical health. This new paper connects the emotional behaviors we observed when couples discussed a problem in their marriage at the start of the study with the kinds of illnesses they developed over the ensuing decades.
Dr. Ingrid Elisabeth-Christophersen[/caption]
Ingrid Elisabeth Christophersen MD PhD
Postdoctoral research fellow
Cardiovascular Research Center (CVRC)
Massachusetts General Hospital
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Christophersen: Several recent studies have utilized the CHA2DS2-VASc risk score to predict risk of atrial fibrillation (AF). However, the CHA2DS2-VASc was developed for prediction of stroke risk in patients with AF and has not been validated for prediction of AF risk. We have evaluated how well the CHA2DS2-VASc performed at predicting risk of AF compared with the most validated clinical risk score for AF - the CHARGE-AF risk score - in the Framingham Heart Study. We showed that the CHARGE-AF risk score performed better at predicting risk of AF than the CHA2DS2-VASc.
Dr. James Kirkpatrick[/caption]
James N. Kirkpatrick, MD
Director of the Echocardiography Laboratory
Division of Cardiology
Ethics Consultation Service
University of Washington, Seattle
MedicalResearch.com: What is the background for this study?
Dr. Kirkpatrick: With significant advances in technology, implanted cardiac devices like pacemakers and defibrillators, replacement heart valves, and mechanical pumps which assist or replace the pumping function of the heart have become standard therapies for patients with severe cardiac disease. Many patients who would previously have died after living with severe symptoms live longer and with improved quality of life. This is particularly true for elderly patients who receive transcatheter aortic valve replacement (TAVR—valve replacement that doesn’t require open heart surgery) and ventricular assist device (VAD—a durable mechanical heart pump) implantation.
However, like everyone, these patients will die, and some of the patients will experience device complications which will shorten their lives. Elderly patients, in particular, are at risk for device complications, high symptom burden, and loss of the ability to make healthcare decisions, due to illnesses like strokes or dementia. Symptom management and advance care planning are the hallmarks of the medical specialty of Palliative Care and are particularly important in patients with TAVR and VADs, yet patients and clinicians don’t often think of Palliative Care when considering high tech, life-prolonging therapies. The Palliative Care Working Group of the American College of Cardiology’s Geriatrics Section therefore sought to gather data on the attitudes toward Palliative Care among cardiovascular clinicians and the current state of involvement of Palliative Care in the care of patients with TAVR and VAD.
Yunsheng Ma, MD, PhD MPH
University of Massachusetts Medical School
Worcester
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Ma: The cardiovascular benefit of lowering LDL cholesterol with statins exceeds all known risk, even in individuals with < 5% risk of CVD over 5 year. Nevertheless, statins are associated with increased incidence of new-onset diabetes, women were disproportionately at higher risk for diabetes while on statins. However, there are no studies comparing CVD and CVD mortality outcomes for women who develop diabetes while not taking statins, to compare their CVD and CVD mortality outcomes against those who develop diabetes while taking statins.
We hypothesized that new clinical diabetes related to statin use may be milder on CVD. However, our findings did not support this hypothesis, as we discovered that statin-related diabetes is no different from diabetes developed outside statin use in its significant impact on CVD and CVD mortality.
Dr. Yvan Devaux[/caption]
Yvan Devaux, PhD
Associate Head of Laboratory
Cardiovascular Research Unit
Department of Population Health
Dr. Ambay Pandey[/caption]
Ambarish Pandey, MD
Cardiology Fellow, PGY5
University of Texas Southwestern Medical Center
Dallas, Texas
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Pandey: Previous studies have reported an underutilization of guideline based heart failure therapies among patients with heart failure (HF) and end-stage renal diseases. However, it is not known if the proportional use of these evidence-based medical therapies and associated clinical outcomes among these patients has changed over time. In this study, we observed a significant increase in adherence to heart failure process of care measures over time among dialysis patients with no significant change in clinical outcomes over time.
Dr. Michael Miller[/caption]
Michael Miller, MD, FACC, FAHA
Professor of Cardiovascular Medicine, Epidemiology & Public Health
University of Maryland School of Medicine
Staff Physician, Baltimore VAMC
Director, Center for Preventive Cardiology
University of Maryland Medical Center
Baltimore, Maryland
MedicalResearch.com: What is the background for this study?
Dr. Miller: It has become an article of faith that HDL (the good cholesterol) is an independent risk factor for heart disease. However, previous studies did not examine the importance of HDL after accounting for both LDL (bad cholesterol) and triglycerides (blood fats). This is important because HDL is associated with LDL and triglycerides. We hypothesized that if HDL is truly an independent risk factor, then low HDL levels in isolation would continue to be linked to an increased risk of heart disease while high HDL levels would continue to protect the heart even if LDL and triglycerides levels were elevated.
Dr. Jaimin Trivedi[/caption]
Jaimin Trivedi, MD, MPH
Instructor
Department of Cardiovascular and Thoracic Surgery
University of Louisville
Louisville, KY 40202
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Trivedi: There is a donor heart shortage in United States and certain donor hearts are likely to be turned down because the donors required cardiopulmonary resuscitation (CPR) prior to procurement. The rationale behind conducting the study was to identify impact of donor CPR and its duration on recipient survival after transplantation.
Our findings show that presence of CPR and duration of CPR does not adversely impact the post heart transplant survival. The study also shows that ejection fraction and peak cardiac troponins between the CPR and non-CPR donors were comparable at time of transplant suggesting recovery of cardiac function.
Dr. Erica Spatz[/caption]
Erica Spatz, MD, MHS
Assistant Professor, Section of Cardiovascular Medicine
Center for Outcomes Research and Evaluation
Yale University School of Medicine/Yale-New Haven Hospital
New Haven, CT 06520
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Spatz: Rates of heart attack have declined during the last 15 years. But whether communities of different economic status or in different geographic regions experienced similar declines is unknown, especially as efforts to prevent cardiovascular disease and manage heart attacks may not have been equally successful in communities with different resource capacity.
Our study shows that trends in the incidence of and mortality from heart attack were similar in low, average and high income communities. However, low-income communities had higher hospitalization rates than average and high income communities throughout the 15 year study period. Interestingly mortality rates were similar.
Dr. Natalia Trayanova[/caption]
Natalia Trayanova PhD, FHRS, FAHA
Murray B. Sachs Endowed Chair
Professor of Biomedical Engineering
Joint Appointment, Medicine
Johns Hopkins University
Institute for Computational Medicine
Johns Hopkins University
Baltimore, MD
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Trayanova: The methodology for modeling cardiac electrical function has matured sufficiently that we can now create computational models of the electrical functioning of the entire heart. My research is focused on translating this methodology into the clinic. The goal is to create, if you will, "a virtual heart for every patient", that will enable the physician to play our scenarios that manifest the heart dysfunction in the given patient, and to enable physicians to make personalized decisions about patient treatment. The present paper is the first application of this overall vision.
The motivation for this particular paper was that determining which patients are at risk for sudden cardiac death represents a major unmet clinical need. Patients at risk receive life-saving implantable defibrillators (ICDs), but because of the low sensitivity and specificity of current approach (based on low ejection fraction), risk assessment is inaccurate. Thus, many patients receive ICDs without needing them, while others die of sudden cardiac death because they are not targeted for 
Dr. Timothy Henry[/caption]
Timothy D. Henry, MD, MSCAI
Director, Division of Cardiology
Cedars-Sinai Heart Institute
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Henry: Heart failure it the #1 cause of morbidity, mortality and cost in the United States today. Patients with Class 3 heart failure, despite optimal medical therapy and device therapy have limited options beyond heart transplantation and left ventricular cyst device.
Transplantation and LVAD are expensive and are challenged by both availability and complications. Therefore, treatment for patients with ongoing symptoms despite medical therapy is an admiral goal. Stem cell therapy appears to be an attractive choice for these patients, in particular patients with ischemic cardiomyopathy.
The ATHENA trial was designed to treat patients with ischemic cardiomyopathy and ongoing ischemia with autologous adipose-derived regenerative cells. Patients would undergo liposuction with onsite processing of their stem cells in 1 ½ - 2 hours, followed by intramyocardial injection of adipose-derived regenerative cells (ADCRs) vs. placebo.
Dr. Alexander Turchin[/caption]
Alexander Turchin, MD, MS
Associate Physician, Brigham and Women's Hospital
Associate Professor of Medicine, Harvard Medical School
Brigham and Women's Hospital
Department of Medicine
Endocrinology
Boston, MA 02115
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Turchin: It is known that fewer women than men at high risk for cardiovascular disease are treated with statins.
However, the reasons for this sex disparity are not fully understood.
Our study identified 4 factors that accounted for over 90% of the difference in statin therapy between women and men with coronary artery disease:
Dr. Kevin Curl[/caption]
Dr. Kevin Curl, MD
Sidney Kimmel Medical College
Jefferson University
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Curl: If left untreated, half of coronary bypass vein grafts will become occluded within 10 years of surgery. We reviewed the health records of over 350 patients who had a previous coronary artery bypass graft (CABG) a minimum of three years prior. Our goal was to identify the long-term trends with medication adherence in this high risk population, namely aspirin and statin medications. The American College of Cardiology and the American Heart Association recommend both statins and aspirin medications unless they are unsafe for the individual patient. The mean age of the study population was 69 years, most patients had previously undergone "triple bypass" with 3 grafts, and the mean time from surgery was 11 years. We found that only 52 percent of patients were taking both aspirin and a statin medication. In addition, patients not taking a statin had higher (22 percent) low-density lipid or “bad” cholesterol.
Dr. Reina Haque[/caption]
Reina Haque, PhD MPH
Research scientist
Kaiser Permanente Southern California Department of Research & Evaluation
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Haque: The study fills an important knowledge gap about the long-term association of aromatase inhibitors on cardiovascular disease risk in breast cancer survivors.
This was a retrospective cohort study that included a cohort of 13,273 postmenopausal breast cancer survivors who were diagnosed with breast cancer, either estrogen or progesterone receptor positive, from 1991 to 2010. The patients were followed through 2011, or a maximum of 21 years. The study participants were divided into four groups based on the drugs they received: 31.7 percent were treated only with tamoxifen; 28.6 percent only with aromatase inhibitors; 20.2 percent used both; and 19.4 percent did not use any of these drugs. These oral drugs are used to combat breast cancer recurrence, but may have long-term side effects on other organs.
The study determined that the risk of cardiac ischemia (which can lead to a heart attack) and stroke were not elevated in patients who only took aromatase inhibitors compared to those who only took tamoxifen. These results provide reassurance that aromatase inhibitors may not increase risk of the potentially fatal cardiovascular outcomes compared to tamoxifen.
Dr. Lihi Eder[/caption]
Lihi Eder, MD, PhD
Assistant Professor of Medicine
University of Toronto
Scientist, Women’s College Research Institute,Room 6326
Women’s College Hospital
Toronto, ON, Canada
MedicalResearch.com: What is the background for this study?
Dr. Eder: Psoriasis is a chronic immune-mediated skin disease affecting 2-3% of the general population. Psoriatic arthritis (PsA) affects 15-30% of patients with psoriasis. Until recently, only few studies assessed the risk of developing cardiovascular events in patients with PsA and while most studies found a higher cardiovascular risk in these patients, others reported cardiovascular rates that were similar to the general population.
Dr. Thijs Eijsvogels[/caption]
Thijs M.H. Eijsvogels, PhD
Department of Physiology
Radboud University Medical Center
Nijmegen, The Netherlands
MedicalResearch.com: What is the background for this study?
Dr. Eijsvogels: Regular exercise training is known to reduce the risk for future morbidity and mortality in the general and athletic population. For this purpose, national guidelines recommend to exercise 150 min/week at a moderate intensity or 75 min/week at a high intensity. Recent studies explored the dose-response relationship between weekly exercise volume and cardiovascular health and reported a potential U-shaped association, suggesting that high exercise volumes may attenuate the beneficial health effects.
The aim of the present study was to determine the relationship between lifelong exercise dose and the prevalence of cardiovascular morbidity in a physically active population. Therefore, we collected data in 21,266 participants of the Nijmegen Exercise Study.
Dr. Sherry Grace[/caption]
Sherry L. Grace, PhD
Professor, School of Kinesiology and Health Science
York University
Sr. Scientist, Cardiorespiratory Fitness Team
Toronto Rehabilitation Institute, University Health Network
Toronto Western Hospital
Toronto, ON
MedicalResearch.com: What is the background for this study?
Dr. Grace: Cardiac rehabilitation is an outpatient chronic disease management program. It is a standardized model of care, comprised of risk factor assessment and management, exercise training, patient education, as well and dietary and psychosocial counseling. Patients generally attend two times a week for several months.
Participation in cardiac rehab has been shown to reduce death and disability. This is a dose-response association, such that more cardiac rehab participation is associated with even less death, etc. Therefore, it is important that patients adhere to the program, or participate in all the prescribed sessions.
No one has ever reviewed patient adherence to cardiac rehab in a systematic way. It has always been assumed that patients only attend about half of prescribed sessions. Also, many studies have shown that women attend fewer sessions than men. However, this has been known for some time, so we would hope that in the current era, this sex difference would not exist. No study has ever aggregated and analyzed sex differences in program adherence, so we set out to do this.
Dr. Tanush Gupta[/caption]
Tanush Gupta, MD
Chief Resident & Instructor of Medicine
Department of Medicine
New York Medical College & Westchester Medical Center
Valhalla, NY
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Gupta: Cigarette smoking is the leading preventable cause of premature death in the United States (U.S.). Approximately one-third of all coronary artery disease related deaths in the U.S. annually can be attributed to cigarette smoking. However, studies from the pre-thrombolytic and thrombolytic eras have shown that mortality in smokers with ST-segment elevation myocardial infarction (STEMI) may be lower than in nonsmokers, a phenomenon called the “smoker’s paradox.”
The majority of STEMI patients in contemporary practice are treated with primary percutaneous coronary intervention (pPCI). Data on the association of smoking with outcomes in STEMI patients undergoing pPCI are limited and also conflicting as to whether the smoker’s paradox exists in this population. Hence, the purpose of our study was to examine the association of smoking status with in-hospital outcomes in a nationwide cohort of STEMI patients undergoing pPCI, included in the U.S. National Inpatient Sample, over a 10-year time period from 2003 to 2012. Our primary outcome of interest was in-hospital mortality and secondary outcomes were post-procedure hemorrhage, in-hospital cardiac arrest, and average length of stay.
Of 985,174 STEMI patients who underwent pPCI in the U.S. over this time period, 438,954 (44.6%) were smokers. Smokers were on an average 8 years younger than nonsmokers and had lower prevalence of most cardiovascular comorbidities. Smoking status was associated with lower risk-adjusted in-hospital mortality (2.0% vs. 5.9%, adjusted OR 0.60, p<0.001), lower incidence of post-procedure hemorrhage (4.2% vs. 6.1%, adjusted OR 0.81, p<0.001) and in-hospital cardiac arrest (1.3% vs. 2.1%, adjusted OR 0.78, p<0.001), and shorter average length of stay (3.5 days vs. 4.5 days, p<0.001). To assess whether younger age of smokers was influencing the association with in-hospital mortality, we also performed an age-stratified analyses in different age groups. The smoker’s paradox largely persisted in age-stratified analyses suggesting that younger age of smokers was not the sole explanation for this paradox.
We performed additional assessment for confounding to explore whether the paradoxically lower risk-adjusted in-hospital mortality in smokers with STEMI was driven by differences in baseline demographics and comorbidities between hospitalized smokers and nonsmokers in general. To test for such confounding, we examined the association of smoking with in-hospital mortality in 2 conditions in which this association has not been previously studied – hip fractures and severe sepsis – using similar statistical regression models. In both these study populations, smokers were on average younger than nonsmokers and had lower risk-adjusted in-hospital mortality, but, the paradoxical association in both these conditions was weaker in magnitude than in STEMI patients. Since there is no cogent biological hypothesis to explain the lower mortality in smokers with sepsis or hip fractures, it is likely that the smoker’s paradox in STEMI is also at least partly driven by residual confounding due to inadequate adjustment for the biological effects of age. However, as this paradox was stronger in STEMI patients than in patients with hip fractures or severe sepsis, we believe that additional true biological differences between smokers and nonsmokers with STEMI also contribute to the paradoxically lower in-hospital mortality.
