ischemic – The Early Career Voice

Deep Dive in HARP Trial

November 15, 2020November 15, 2020 Purvi Parwani, MBBS, MPH

“Coronary Optical Coherence Tomography (OCT) and Cardiac Magnetic Resonance (CMR) Imaging to Determine Underlying Causes of MINOCA in Women” was presented on day 2 of AHA by Dr. Harmony R. Reynolds, MD during the late-breaking trial session. The trial is also simultaneously published in Circulation(1).

MINOCA (Myocardial Infarction with Nonobstructive Coronary Arteries) is quite a contemporary diagnosis. The term was initially coined by Dr. Beltram in an editorial, in response to a Swedish paper that described the cardiac magnetic resonance imaging findings in patients that had presented with myocardial infarction however did not have any significant coronary artery disease on cardiac catheterization(2). MINOCA affects 6-15% of the patients presenting with MI and disproportionately affects women(1). In 2017, The European Society of Cardiology developed the first international position article on MINOCA and proposed the following MINOCA criteria: (a) AMI criteria as defined by the “Third Universal Definition of Myocardial Infarction”; (b) nonobstructive coronary arteries as per angiographic guidelines, with no lesions ≥50% in a major epicardial vessel; and (c) no other clinically overt specific cause that can serve an alternative cause for the acute presentation (3). Fundamental to the definition of MINOCA is the diagnosis of AMI with an elevated cardiac biomarker, typically a cardiac troponin >99th percentile with a rise or fall in the level on serial assessment. Although elevated troponin levels are indicative of myocyte injury with the release of this intracellular protein into the systemic circulation, the process is not disease-specific and can result from either ischemic or nonischemic mechanisms. MINOCA thus, becomes a working diagnosis. The role of CMR is crucial to establish the etiology in these patients. In 2019, an AHA statement paper on MINOCA, presented a stepwise diagnostic approach to evaluate the etiology(4). This paper proposed the use of coronary imaging after the CMR diagnosis of MI was established to further evaluate coronary etiology in absence of significant atherosclerotic disease. Earlier this year, ESC NSTEMI guidelines suggested class IB indication to perform CMR in patients with MINOCA, recommended use of traffic light diagnostic algorithm, and mentioned the use of OCT for the detection of unrecognized causes at coronary angiography, especially in suspected cases of thrombus, plaque rupture or erosion or SCAD(5).

The goal of the Women’s Heart Attack Research Program (HARP) was to implement an imaging protocol to evaluate the underlying causes of MINOCA, in order to guide clinical practice.

They enrolled 301 women presenting with a diagnosis of MI before the coronary angiography was done, in a prospective manner. 170 patients were diagnosed with MINOCA, out of which 145 had OCT imaging while 116 underwent CMR. The study established the cause of MINOCA in 84.5% of the women who underwent multi-modality imaging (98/116), compared with either OCT or CMR alone. OCT was able to identify culprit lesion in 46% of the patient while 74% of the patients had abnormal CMR. 53% of the patients had late gadolinium enhancement or edema in the coronary territory and ischemic pattern while almost 21% of patients were found to have myocarditis, stress-induced cardiomyopathy, or other nonischemic cardiomyopathies. Almost 15.5% of patients had no identifiable mechanism by OCT or CMR. Half of the patients with ischemic patterns on CMR didn’t have any culprit lesion on OCT. Alternative mechanisms of MI like coronary spasm or thromboembolism leading to MI are suggested in those patients. The study however didn’t perform any provocative testing to induce spasm. Similarly, 40% of the patients with normal CMR had culprit lesion on the OCT. This is lower compared to the latest CMR MINOCA studies where a diagnosis was established up to 87% of the cases(6). Whether these findings are due to shorter duration of ischemic injury or due to longer time between diagnosis of MI and CMR or maybe due to overestimation of the prevalence of abnormalities on OCT given the blinded core laboratory review, remains the point of discussion.

The authors conclude that the Multi-modality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA in this observational study. The study was not designed to test the outcomes and further research is needed to establish if the OCT improves outcomes in patients with a working diagnosis of MINOCA. I am not certain if the trial will impact any OCT recommendation class in future guidelines given the absence of the outcome data and observational nature of the trial. The trial also suggested simultaneous use of OCT and CMR in cases of MINOCA however perhaps establishing the diagnosis MI with CMR, excluding myocarditis and nonischemic cardiomyopathy, in cases with a working diagnosis of MINOCA remains the key. As suggested by the diagnostic algorithm in the guidelines, once the MI diagnosis is established, OCT may be used to evaluate coronary mechanisms, however till the outcome data with OCT is available, this will probably depend on the preference of the clinical cardiologist and local availability. Given more than half of the patients with ischemic pattern on CMR had no culprit lesion on OCT in this trial, we may need more data before recommending regular simultaneous use of OCT and CMR.

References:

Coronary Optical Coherence Tomography and Cardiac Magnetic Resonance Imaging to Determine Underlying Causes of MINOCA in Women | Circulation [Internet]. [cited 2020 Nov 15]. Available from: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.052008
Beltrame JF. Assessing patients with myocardial infarction and nonobstructed coronary arteries (MINOCA). Journal of Internal Medicine. 2013;273(2):182–5.
Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, Caforio ALP, et al. ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J. 2017 Jan 14;38(3):143–53.
Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association | Circulation [Internet]. [cited 2020 Nov 15]. Available from: https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000000670
2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation | European Heart Journal | Oxford Academic [Internet]. [cited 2020 Nov 15]. Available from: https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa575/5898842
Troponin-positive chest pain with unobstructed coronary arteries: incremental diagnostic value of cardiovascular magnetic resonance imaging | European Heart Journal – Cardiovascular Imaging | Oxford Academic [Internet]. [cited 2020 Nov 15]. Available from: https://academic.oup.com/ehjcimaging/article/17/10/1146/2197117

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Joint Hypertension 2018 Scientific Sessions – You Should Have Been There

September 21, 2018March 28, 2019 Anberitha Matthews, PhD

hypertension 2018

Just as promised, the Joint Hypertension 2018 Scientific Sessions (Hypertension18) was indeed among the most impactful meetings one could have attended. Council on Hypertension Scientific Sessions Planning Committee Vice Chair Dr. Karen Griffin, FAHA was accurate in her statement that it would be “the premier scientific meeting.” There were experts from all parts of the world covering more cardiovascular topics that I think my fingers could not keep up with in note taking, and each session was more informative than the next with up-to-date information on hypertension.

During the President’s Welcome Address, Dr. Ivor Benjamin, FAHA foreshadowed what was to be expected during the meeting. He gave general overviews of the hypertension guidelines, what the changes mean to clinicians and researchers, as well as the role AHA will play in helping drive those changes forward. His welcome was a great introduction to the ‘Recent Advances in Hypertension’ Session chaired by Drs. Joey Granger from the University of Mississippi Medical Center and John Bisognano from University of Rochester Medical Center. This session covered the new guidelines, implementation, and basic research advances of clinical hypertension moving forward by Drs Basile, Egan, Oparil, and Ellison. The whirlwind of information was just the icebreaker! During the refreshment break and exhibits, I met a number of “Rockstars” including clinicians and researchers from University of Alabama Birmingham, Drs. David and Jennifer Pollock and AHA Early Career blogger Tanja Dudenbostel. Additionally, this was the only time I spent visiting with vendors. Among them, Hulu explained the importance of calibrating automatic blood pressure machines. Historically blood pressure was taken with a manual sphygmomanometer and a technician listening for ausculatory sounds via a stethoscope, but now it is all automated. Generally one machine is used for all patients. This technology forces us to question the accuracy of the readings of the machines. Are they calibrated? Should the BP be taken radially or at the wrist? Should the machine be changed throughout the day? There was Aegis representatives sharing information about products to assist medical professionals determine patient compliance to therapy and toxicology testing equipment. During these conversations, it was surprising to discover some of the rationales behind why people would opt to not take medicine as prescribed.

With my research being focused on oxidative stress-induced vascular injury and since I have become increasingly more interested in health and wellness, I took particular interest in the session focused on “Lifestyle Modifications and Impact on BP” chaired by the Associate Editor of Hypertension, David Harrison, MD, FACC, FAHA, “Recent Advances Obesity and Cardiovascular Disease” chaired by the consulting Editor of Hypertension Suzann Oparil, MD, FAHA, and “Obesity, Diabetes, and Metabolic Syndrome” chaired by Drs. Kamal Rahmouni and Carmen De Miguel. During these sessions, it was not surprising that regular exercise reduced vascular stiffness, but what was noteworthy was that weight training contributes to atherosclerosis. Additionally, the sympathetic nervous system seems to be important in glomerular filtration. Dr. Elizabeth Lambert delivered an intriguing talk about how diet and exercise can significantly decrease metabolic syndrome in middle aged obese individuals, which is consistent with a recent study (Hypertension18 Meeting Report P388) that suggests lifestyle changes can reduce hypertension in both men and women. Further, the study suggests that following the DASH diet, exercising, and weight management over a course of 16 weeks were contributing factors in reducing BP in test subjects. We all know anti-hypertensives work in reducing BP. Lifestyle changes should be the first line of defense in evading hypertension and getting it under control at the onset, according to the American Heart Association/American College of Cardiology Hypertension Guidelines. We have all heard that we have to get out there and get moving. Choosing the right exercise is just as important as exercising, according to Dr. Tanaka.

I recently wrote a blog discussing metabolic syndrome and therein indicated there is not a direct correlation between obesity and diet. During this conference, Dr. John Hall lectured on the recent advances in CVD and obesity. He suggested that epigenetic transmission of obesity in humans (and others) is associated with increased adiposity and insulin resistance, depletion of nuclear protein, influence chromatin conformation, and altered germ cell methylation and gamete micro RNA.

The new concurrent session Clinical Practice Clinical Science and Primary Care tracks did not go unnoticed. Although I did not get to attend many of these sessions, I did pass them to see that they were well attended. I did attend some of the lunch meetings and they were very insightful. Please refer to my Twitter to see my detailed notes. As mentioned in my pre-conference blog, with all the sessions that were available one should not have had an issue meeting the goals outlined in the program by coordinators (infra vide). Several sessions that met the interest of all researchers/clinicians, early career, and everyone in between. Not a person that attended Hypertension18 could say they could not find a learning opportunity at the Joint Hypertension 2018 Scientific Sessions! Even if one was merely a passerby, there was a session relevant to them. For example, I was on my way to get coffee when I encountered Drs. Yagna Jarajapu from North Dakota State University and Daniel Batlle from University of Chicago discussing research concerning STZ diabetic Foxn1 mice that were ischemic for several days. Subsequently, Eric Metterhausen shared his mission of services (MOS, for you military people) with me as we conversed about field medicine with the United States Public Health Services (USPHS). I did know our US Armed Forces had research officers and divisions of research, but the amount of detail that Major Metterhausen described was a beast that I had not known. Conversations such as these lead to increased mentoring relationship, as well as potential collaborations in research and grant proposals. We all go to conferences to learn, to purchase new research equipment, and to present our data, but we also should not forget to network and build relationships.

Conference Learning Objectives:

Discuss changes to the AHA/ACC guidelines for the management of hypertension and their clinical implications.

Describe opportunities to improve blood pressure measurement in the clinical setting to provide more accurate results.

Identify immune and inflammatory mechanisms that contribute to the development of hypertension and hypertension-related end-organ damage and discuss the research and clinical implications.

Educate participants about medical approaches for the management of comorbid obesity in patients with hypertension.

Describe new and emerging strategies for treating resistant hypertension.

Describe participants on the impact of value-based reimbursement on hypertension management and identify opportunities to improve its management.

See you all in Chicago at Scientific Sessions 2018!!!

Leave a comment and follow me on Twitter @AnberithaT and @AHAMeetings if you have questions or are interested in something else specifically.

Anberitha Matthews, PhD is a Postdoctoral Fellow at the University of Tennessee Health Science Center in Memphis TN. She is living a dream by researching vascular injury as it pertains to oxidative stress, volunteers with the Mississippi State University Alumni Association, serves as Chapter President and does consulting work with regard to scientific editing.

Science of Strokes

June 8, 2018March 28, 2019 Anberitha Matthews, PhD

types of strokes It has been well accepted that atherosclerosis is the result of chronic inflammation. I have spent several years exploring the role endocannabinoids, lipid-based neurotransmitters that bind to receptors that are expressed throughout the peripheral and central nervous system, play in decreasing oxyradical derived inflammation. Under normal conditions, lipids are metabolized and excreted from the body. It is my belief we have an endogenous mechanism that maintains balance within the vascular system that protects our arteries from becoming damaged; however, in the event of an injury the immune system is activated leading to cardiovascular dysfunction.

Flow resistance, sheer stress, ischemic reperfusion, and oxidized low-density lipoproteins (oxLDL) can contribute to microvascular dysfunction particularly at non-linear area of a vessel. The pathology of atherosclerosis/stroke starts with the monocytes being recruited to an injured site causing the production of NADPH oxidase-derived reactive oxygen species (ROS). The monocytes undergo a phenotypic change into macrophages and uncontrollably engulf the oxLDL and subsequently lead to the development of lipid laden foam cells. Apoptosis of the foam cells occurs due to their inability to metabolize the modified reactive lipid peroxidation products. The extracellular matrix becomes remodeled resulting in the formation of a fibrous cap. It is this cap that causes the occlusion of a vessel causing a heart attack or stroke.

circulating moncyte, macrophage and foam cell All strokes are not alike, they include ischemic, hemorrhagic, and transient ischemic attacks (TIA). Although older persons are thought to be the primary risk group for strokes, children and fetus can potentially be included in the risk population. The most common type is ischemic stroke caused by clots occluding the blood flow to the brain. The clots can be from congenital heart defects, sickle cell disease, and trauma that injures a large artery; however, they can also be a consequence of high cholesterol, oxLDL, and blood clots as well as exogenous and endogenous toxins. The foam cells in the artery can be either a stable plaque (solid fibrous extracellular tissue with small amounts of lipid) or vulnerable plaque (consist of macrophages and lipids in the artery wall that erosion prone). These “culprit” plaques are the cause of disruption in blood flow that leads to vascular events such as heart attacks and strokes. Hemorrhagic strokes are due to a rupture in the blood vessel that bleeds to the deep tissue of the brain; often caused by hypertension, but also aging vessels, arteriovenous malformations (cluster of deformed blood vessels), and aneurysms (a balloon of blood in the artery). Intracerebral hemorrhages are the most common type due to the prevalence of high blood pressure but can also be caused by exogenous toxins such as smoking, oral contraceptives with high estrogen, alcohol, and illegal drugs. TIAs often called mini-strokes, produce symptoms similar to those of stroke but without the lasting effects. They are thought to be warning signs to an ischemic stroke; the clots that cause them may be resolved without treatment, but without treatment they can lead to further strokes or death.

A recent report by Wang and colleagues demonstrated a linear correlation between oxLDL and the National Institutes of Health Stroke Scale (NIHSS). The results of their study indicated after adjusting for age, gender, ethnicity, and marriage, NIHSS score increased 1 μg/dL of oxLDL. Preparedness is the best defense to preventing a stroke. The Hip-Hop Stroke randomized trial suggest that preparedness can potentially delay a major thrombolysis event. Visits to a medical professional to recognize the symptoms will play a major role in prevention. Since atherosclerosis and stroke are complex process that involve oxyradical stress, immune dysfunction, and vulnerable vessels and the NIHSS score is widely used in the clinical setting to evaluate LDLs in plasma, one can only delineate that being prepared by getting tested is the best way to validly and reliably be prepared to combat a stroke. If you find someone displaying stroke symptoms act FAST to give the best prognosis. Share with me your experience or experiences you have heard of to combat the detrimental effects of stroke.