AHA20 – Page 4 – The Early Career Voice

Late-Breaking Science Presented at AHA20

November 16, 2020November 16, 2020 Purvi Parwani, MBBS, MPH

For this blog dedicated to #AHA20, I decided to put together a list of majority of American Heart Association (AHA) late-breaking study presentations at the 2020 Virtual AHA meeting from Day 1 to Day 3. So far, the late-breaking studies at AHA have covered a wide range of topics from heart failure, cardiovascular prevention focusing on a statin, newer LDL lowering therapies, Omge-3 fatty acid supplements, to polypills and imaging in women with MINOCA. Day 4 and Day 5 will cover multiple trials on atrial fibrillation, dual SGLT inhibitor, COVID, and Telemedicine.

Day 1

Name

Trials

Study Population

Results

Conclusion

GALACTIC HF

cardiac myosin activator Omecamtiv Mecarbil In Chronic Heart Failure with Reduced Ejection Fraction: The Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility In Heart Failure

Inclusion Criteria

Patients 18-85 years of age with CHF and NYHA class II, III, or IV symptoms

LVEF ≤35% and pro-BNP ≥400 pg/ml

N= 8256

Follow up= 21.8 months

Mean Age= 65 years

Primary Outcome=

cardiovascular death or CHF event

Mean LVEF: 27%

ACEi/ARNI 87%

Beta-blocker: 94%

Aldactone 78%

SGLT2iinhibitor: 2.5%

Primary Outcome

37.0% of the omecamtiv mecarbil group compared with 39.1% of the placebo group (p = 0.03).

Among patients with HFrEF on GDMT, the selective cardiac myosin activator omecamtiv mecarbil was superior to placebo. It was associated with a reduction in the primary composite outcome; however, no benefit in outcomes of CV Death, all cause death, or change in KCCQ total symptoms score.

AFFIRM-AHF

Ferric Carboxymaltose In Iron Deficient Patients Admitted for Acute Heart Failure

Inclusion Criteria

Hospitalization for CHF, and iron deficiency anemia- Serum ferritin <100 ng/ml or serum ferritin 100-299 ng/ml and transferrin saturation <20%, LVEF <50%

N= 1132

Follow up= 52 weeks

Mean Age= 71 yrs

Primary Outcome=

total heart failure hospitalizations and cardiovascular death

Primary Outcome

52.5% of the ferric carboxymaltose group compared with 67.6% of the placebo group (p = 0.059).

Among patients with CHF with iron deficiency, intravenous ferric carboxymaltose was associated with a numerical reduction in total heart failure hospitalizations and cardiovascular death.

VITAL

Omega-3 Fatty Acid and Vitamin D Supplementation In The Primary Prevention Of CV or cancer events

Inclusion Criteria

Men >50 years or women >55 years without any known known cardiovascular disease or cancer

N= 25,871

Follow up= 5.3 yrs

Mean Age= 67.1 yrs

Primary Outcome= CV death, nonfatal myocardial infarction (MI), or stroke

Primary Outcome

The primary CV outcome of CV death, nonfatal myocardial infarction (MI), or stroke, for vitamin D3 vs. placebo, was 3.1% vs. 3.2%, hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.85-1.1, p = 0.69.

The results of this trial indicate that supplementation with either n–3 fatty acid at a dose of 1 g/day or vitamin D3 at a dose of 2000 IU/day was not effective in prevention of CV or cancer events

TIPS-3

A Polypill For Primary Prevention Of Cardiovascular Disease In Intermediate Risk People: Results Of The International Polycap Study

Inclusion Criteria

Target CV disease (CVD) risk: >1.0%/year

Men ≥50 years and women ≥55 years with an INTERHEART Risk Score (IHRS) of ≥10, or men and women ≥65 years with an IHRS of ≥5

N= 5713

Follow up= 4.6 yrs

Mean Age= 63.9 yrs

Primary Outcome= CV death, myocardial infarction (MI), stroke, heart failure (HF), cardiac arrest, revascularization

Primary Outcome

Polypill vs placebo

4.4% vs. 5.5% (hazard ratio [HR] 0.79

Once-daily polypill (fixed-dose combination of simvastatin, atenolol, ramipril, HCTZ) was superior to placebo in reducing systolic BP, LDL-C, and nonfatal CV events at approximately 5 years among intermediate CV risk patients, mostly in Southeast Asia

Day 2-3

Name

Trials

Topic of Interest

Hypothesis

Results

ALPHEUS

Ticagrelor Versus Clopidogrel In Elective Percutaneous Coronary Intervention

Inclusion Criteria

Patients undergoing nonemergent PCI

At least one high-risk criteria: age >75 years, renal insufficiency, diabetes, body mass index >30 kg/m2, ACS in last year, LVEF <40% and/or prior episode of heart failure, multivessel disease, need for multiple stents, left main, bifurcation or complex PCI

N= 1910

Follow up= 30 days

Mean Age= 66 yrs

Primary Outcome=

Primary Outcome

MI ype 4a, 4b (stent thrombosis) or major myocardial injury at 48 hours

Among patients undergoing elective and planned PCI, ticagrelor loading was not superior to clopidogrel loading. Ticagrelor failed to reduce the incidence of periprocedural myocardial infarction. Major bleeding was also similar between the groups, although an increase in nuisance or minor bleeding with ticagrelor.

HARP-MINOCA

Coronary OCT and Cardiac MRI to Determine Underlying Causes of Minoca in Women

Inclusion Criteria

prospective, multicenter, international, observational study, women with a clinical diagnosis of MI were enrolled

N= 170

145 with OCT;

116 with CMR

46% pts with culprit lesion on OCT.

Abnormal CMR in 74% pts, ischemic pattern in 53%, nonischemic pattern in 20.7%,

Multi-modality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA, three-quarters of which were ischemic and one-quarter of which were non-ischemic, alternate diagnoses to MI

RIVER

Rivaroxaban Versus Warfarin In Patients With Bioprosthetic Mitral Valves And Atrial Fibrillation Or Flutter: Primary Results From The RIVER Randomized Trial

Inclusion Criteria

≥18 years with bioprosthetic MV + AF/AFl without any contraindication to the AC

N= 1005

Follow up= 1 yr

Mean Age= 59.3 yrs

Primary Outcome= death, major adverse cardiac events, major bleeding

Mean CHAD2vASC score= 2.6, HAS-Bled Score =1.6, 18% <3 months from MV surgery, 31% >5 yrs

Primary Outcome

The mean time to the primary outcome for rivaroxaban vs. warfarin was 347.5 vs. 340.1 days (p < 0.0001 for noninferiority, p = 0.1 for superiority).

rivaroxaban is noninferior to warfarin for prevention of thromboembolic events among patients with AF/AFL and a bioprosthetic mitral valve. All strokes were lower with rivaroxaban.

STRENGTH

Cardiovascular Outcomes with Omega-3 Carboxylic Acids (Epanova) In Patients With High Vascular Risk And Atherogenic Dyslipidemia

Inclusion Criteria

Statin-treated patients ≥18 yrs with or at high risk for cardiovascular disease and TG 180-500 mg/dl, HDL <42 mg/dl (men) or 47 mg/dl (women)

N= 13,078

Follow up= 42M

Mean Age= 63Yrs

Omega-3 CA Dose: 4 g/day

Primary Outcome=

cardiovascular death, MI, CVA, coronary revascularization, or hospitalization for unstable angina

Primary Outcome met in

12.0% of the omega-3 CA group compared with 12.2% of the placebo group (p = 0.84).

Among statin-treated patients with dyslipidemia and high cardiovascular risk, omega-3 CA was not superior compared to placebo.

OMEMI

Effects Of N-3 Fatty Acid Supplements on Clinical Outcome After Myocardial Infarction In The Elderly: Results Of The Omemi Trial

Inclusion Criteria

Patients 70-82 years of age

With Myocardial infarction 2-8 weeks prior to randomization

N=1,027

Follow up= 24M

Mean Age= 74Yrs

PUFA dose: 930g EPA+ 660g DHA

Primary Outcome=

all-cause death, nonfatal MI, revascularization, CVA, or hospitalization for heart failure

Primary Outcome

21.0% of the PUFA group compared with 19.8% of the placebo group (p = 0.62).

Among elderly patients with recent myocardial infarction, PUFA was not beneficial.

SAMSON

A Three-arm N-of-1 Trial with Statin, Placebo And Tablet Free Periods, To Verify Side Effects And Identify Their Cause

Inclusion Criteria

Patients with any adverse event within 2 weeks of starting a previous statin

N= 60

Follow up= 12 months

Primary Outcome:

placebo symptoms divided by statin symptoms= termed nocebo ratio

Nocebo ratio was 0.90- meaning 90% of symptoms elicited by placebo tablets

Patients with previous adverse event to statin, 90% of the symptoms could be attributed to the nocebo effect

EVINACUMAB

The Efficacy and Safety Of angiopoietin-like 3 (ANGPTL3) inhibitor

-Evinacumab In Patients With Refractory Hypercholesterolemia

Inclusion Criteria

Diagnosis of primary hypercholesterolemia (either heterozygous familial hypercholesterolemia [HeFH] or non-HeFH) with clinical atherosclerotic cardiovascular disease (ASCVD) with statin (± ezetimibe) at the maximum tolerated dose, PCSK9 inhibitor for at least 8 weeks with LDL-C ≥70 mg/dl or 100 mg/dl with or without clinical ASCVD, respectively

N= 160 (SC), 106 (IV)

Follow up= 16 weeks

Mean Age= 54 years

Primary Outcome=

Primary Outcome

percent change in LDL-C from baseline

Phase II trial

small and underpowered for clinical outcomes

Evinacumab is superior to placebo in reducing LDL-C among patients with refractory hypercholesterolemia despite being on statins, ezetimibe, and PCSK9 inhibitors (baseline LDL-C: ~150 mg/dl)

SHORT-DAPT

One Month Dual Antiplatelet Therapy Followed By Aspirin Monotherapy After Drug Eluting Stent Implantation

Inclusion Criteria

Patients ≥19 years of age

undergoing PCI for stable or unstable ischemic heart disease

AMI excluded

N= 3020

Follow up= 12 months

Mean Age= 67 yrs

Primary Outcome=

cardiac death, nonfatal myocardial infarction, target-vessel revascularization, stroke, or major bleeding at 12 months

Primary Outcome

5.9% of the 1-month DAPT group compared with 6.5% of the 6- to 12-month DAPT group (p for noninferiority < 0.001; p for superiority = 0.48).

Among patients undergoing PCI for stable or unstable coronary artery disease, 1 month of DAPT was noninferior to 6-12 months of DAPT

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

FA… wha? Oh… FAHA! Becoming a Fellow of the American Heart Association (FAHA)

November 16, 2020November 16, 2020 Jennifer Kong, PhD

Curious about what a Fellow of the American Heart Association (FAHA) was, I attended the “Journey to becoming FAHA” panel discussion this afternoon to learn more from Dr. Annet Kirabo (Vanderbilt University), Dr. Nasrien Ibrahim (Massachusetts General Hospital), Dr. Swapnil Hiremath (Ottawa Hospital Research Institute), and Dr. Antonio Cabrera (University of Utah). Collectively, this panel covered many topics for the FAHA curious. Below are some of the major questions answered.

What is a FAHA and how do I become one?
Broadly speaking, a Fellow of the American Heart Association (FAHA) is a physician, scientist, nurse, or other healthcare professionals that has made sustained contributions to the field of cardiovascular disease and/or stroke. General FAHA requirements include a history of AHA membership (i.e.being an AHA partner for at least two years), holding a Premium Professional or Premium Professional Plus membership, possessing an affiliation with one of the 16 AHA Scientific Councils, and a letter of recommendation from an existing FAHA member. However, each Scientific Council has an additional set of FAHA criteria that must be met for a successful application, so do your research and make sure you qualify. Each year, there are two FAHA application due dates, meaning there are many opportunities to apply. To learn more, check out the American Heart Association (AHA) website: https://professional.heart.org/en/partners/fellow-of-aha.

What are the benefits of becoming a FAHA?
As stated on the AHA website, the many benefits of becoming a FAHA include free online access to AHA journals, priority registration for AHA Scientific Sessions, and reduced registration fees to AHA meetings. However, all of the panelists highlighted the additional networking benefits of being a FAHA that have helped them in their early careers. Dr. Cabrera specifically noted that the AHA is an excellent source of role models and mentors for both scientists and clinicians. In addition, Dr. Ibrahim noted that being a FAHA has been helpful for her research, with networking ultimately resulting in more publication and speaking opportunities.

How can I showcase my commitment to the AHA? What kinds of AHA service opportunities are there?
To successfully become a FAHA means showing sustained commitment and service to the AHA. Thankfully, the AHA makes this easy. As Dr. Kirabo noted, on the AHA website you can fill out the Science Volunteer Form to receive emails with volunteer opportunities. In addition, Dr. Ibrahim promoted the AHA Early Career and FIT Blogging Program, which initially allowed her to amplify her voice in the cardiovascular health and clinical cardiology fields.

If I am not a researcher, does a lack of published paper prevent you from becoming a FAHA?

Depending on the Scientific Council you are applying to, a lack of publications can play a role. However, Dr. Cabrera noted that there is a great deal of variation in assessing productivity and scholarship and that the AHA tries to create opportunities for teachers and clinicians (not only research scientists) by assessing achievement using criteria beyond publications.

If I applied but was not approved to be a FAHA the first time, what should I do? How can I improve my chances?
Check the criteria for becoming a FAHA. Check with a FAHA on your Scientific Council and determine where the gap is and how it can be filled. Most importantly, don’t give up — try again!

Do you have any last pieces of advice for FAHA applicants?

Use your two years of required AHA membership to build up your AHA service — most importantly, commit this service to something you are genuinely interested in. Get a solid personalized letter of recommendation from an existing FAHA member for your application. Lastly, don’t hesitate, just do it.

Find out more about FAHA: https://professional.heart.org/en/partners/fellow-of-aha

An ALL-Woman Trial on MINOCA Takes a Seat in the Main Area as Late Breaking Science Addressing Challenges in Coronary Care

November 16, 2020November 17, 2020 Sheila Sahni, MD, FSCAI

As an interventional cardiologist who’s passionate about reducing the disparities in diagnosis and management in women with cardiovascular disease, I was captivated by the late-breaking science that took the main arena for Current Challenges in Coronary and Valve Disease at Scientific Sessions 2020. The Coronary OCT and Cardiac MRI (CMR) to Determine Underlying Cause of MINOCA (Myocardial Infarction with Nonobstructive Coronary Arteries) in Women Trial from the HARP (Women’s Heart Attack Research Program) investigators led by Dr. Reynolds and colleagues is truly groundbreaking for women patients with MINOCA (1). HARP-MINOCA was a multimodality imaging trial that included all women. Yes—that’s correct. An ALL Woman Trial. Why would a study enroll all women? Because MINOCA is a condition that disproportionately affects women (3). In women presenting with MI, the presence of MINOCA is 10.5% compared to 3.4% in men (4). MINOCA is a disease process that has largely been met with controversy such that clinicians have challenged the presence of a “true” myocardial infarction in the absence of coronary artery disease. Furthermore, the lack of an obstructive lesion on a coronary angiogram has misled women to believe that they’re “fine” just because their coronary arteries don’t require stenting. This is completely false. Patients with MINOCA have clinical outcomes similar to patients with obstructive CAD at the time of myocardial infarction (MI) (3). Our patients have suffered in this variability of treatment and assessment which ultimately impacts their care. The findings of this study area additive to the American Heart Association’s scientific statement on the contemporary diagnosis and management of MINOCA which sought to standardize the definition of MINOCA and create a clinically useful diagnostic framework and treatment algorithm (2). Thus, the HARP-MINOCA multimodality imaging findings deepen the roots of MINOCA as a true disease process that requires a proper diagnosis with multimodality imaging to optimize management for improved patient outcomes.

This prospective multicenter study enrolled women a total of 301 women with a clinical diagnosis of MI across 16 different sites of which 170 had MINOCA. Once invasive coronary angiography was performed and revealed <50% stenosis in all major arteries, multi-vessel optical coherence tomography (OCT) was performed, followed by CMR (cine imaging, late gadolinium enhancement, and T2-weighted imaging and/or T1 mapping). [Figure 1]

Figure 1

Dual imaging allowed for a thorough investigation of the following: 1) Vascular causes of MINOCA by OCT, 2) Myocardial abnormalities on CMR and 3) integration of the various underlying etiologies on OCT and CMR. The findings from OCT investigation revealed that a culprit lesion in 46% of cases included plaque rupture, thrombus without plaque rupture, intra-plaque cavity, layered plaque, dissection, or spasm. The CMR findings revealed infarction with late gadolinium enhancement 33% of cases, regional pattern of ischemic injury in 21% and 21% had non-ischemic pattern giving them an alternate diagnosis. The study did have a few limitations included a low rate of STEMI enrollment, regional myocarditis cannot be excluded from the CMR definition of ischemic injury (defined as a single coronary territory with myocardial edema) that was used, the contribution of coronary vasospasm to the presentation was not evaluated, and not all women underwent 3-vessel OCT and CMR leaving some diagnoses that may have been missed.

The integration of the dual-imaging findings revealed a specific cause for MINOCA in 85% of cases. When an OCT culprit lesion, there was CMR evidence of infarction or regional ischemic injury in 75% of cases. Multi-modality imaging was better than either imaging modality alone leading to an identified cause of MINOCA in 85% of cases. One of the cases shared during the trial presentation was eye-opening. Despite no evidence of an obstructive lesion in the LAD vessel on a coronary angiogram, OCT performed in the LAD revealed plaque rupture and subsequent CMR demonstrated a small, transmural infarction in the terminal segment of the LAD. [Figure 2]. The importance of establishing the diagnosis with additional multimodality imaging is the key findings here. MINOCA patients have pathophysiology hidden deep beyond the limitations of coronary angiography and without additional imaging, they could be subject to a missed diagnosis and ultimately poor long-term care and management.

Figure 2

The 2020 European Society of Cardiology for non-ST elevation MI gave the use of CMR a Class IB recommendation for MINOCA evaluation. Unfortunately, there are no such recommendations for the use of intracoronary imaging. As a community-based interventionalist who performs emergent percutaneous coronary interventions at ST-Elevation MI (STEMI) receiving centers without cardiothoracic surgical support, we have restrictions as operators when performing interventions such an intravascular imaging when no intervention is planned. The implications of this OCT relevant data would be practice-changing for interventional cardiologists practicing in my clinical setting. The feasibility of OCT may bring its own challenges with operator-experience, staff support, and contrast use. However, education regarding the important data noted from OCT in MINOCA patients is a very important first step to implement change in one’s cath lab.

This study presented here at sessions continues to advance the growing field of MINOCA science. Late-breaking science advancing the understanding of this heterogeneous population of MINOCA patients is incredibly exciting and I’m looking forward to the continuum of knowledge to transform the algorithm for diagnostic assessment and framework for MINOCA treatment.

References:

Reynolds et al. Coronary Optical Coherence Tomography and Cardiac Magnetic Resonance Imaging to Determine Underlying Causes of MINOCA in Women. Circulation 2020; Epub. 10.1161/CIRCULATIONAHA.120.052008
Tamis-Holland JE et al. 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. 2019;139(18):e891–908.
Safdar B et al. Presentation, clinical profile, and prognosis of young patients with myocardial infarction with nonobstructive coronary arteries (MINOCA): results from the VIRGO study. J Am Heart Assoc. 2018;7(13)
Smilowitz NR et al. Mortality of myocardial infarction by sex, age, and obstructive coronary artery disease status in the ACTION registry-GWTG (acute coronary treatment and intervention outcomes network registry-get with the guidelines). Circ Cardiovasc Qual Outcomes. 2017;10(12):e003443.

Late-Breaking Highlights: Fish Oils and Frustrations in Lipid Management

November 16, 2020November 16, 2020 Andi Shahu, MD, MHS

It was another exciting day of virtual sessions at #AHA20, led by intriguing findings from a few late-breaking trials!

First, the STRENGTH and OMEMI trials added nuance to ongoing discussions about the cardiovascular benefits of fish oils and cardiovascular risk reduction. The REDUCE-IT trial, published in the New England Journal of Medicine (NEJM) in 2019, showed that the highly purified fish oil icosapent ethyl improved cardiovascular outcomes in high-risk participants who had elevated triglycerides despite statin therapy. The STRENGTH and OMEMI trial, however, may temper enthusiasm about the use of fish oils in high-risk patients.

The STRENGTH trial randomized 13,000 participants in 22 countries to an omega-3 carboxylic acid or corn oil placebo, with a primary endpoint of cardiovascular death, myocardial infraction, stroke, coronary revascularization or hospitalization for unstable angina. The trial was stopped early due to “futility,” though it still achieved 1580 of the target 1600 endpoints needed for results to be sufficiently powered. Compared with those receiving corn oil placebo, participants in the omega-3 fatty acid group experienced a 19% reduction in triglycerides, 20% reduction in C-reactive protein and 269% increase in plasma eicosapentanoic acid (EPA; icosapent ethyl is a highly purified and stable version of this fatty acid). Despite these biochemical differences, there was no difference in the primary outcome between the two groups, 54 months after randomization. The major adverse outcome, atrial fibrillation, was significantly more likely in the treatment arm.

Why do STRENGTH findings differ from those of REDUCE-IT? STRENGTH and REDUCE-IT participants had similar triglyceride levels, but patients in the STRENGTH intervention arm had lower EPA levels than those in the REDUCE-IT treatment arm. Moreover, REDUCE-IT contained more participants with established CAD. Additionally, STRENGTH used a corn oil placebo, while REDUCE-IT used a mineral oil placebo. Corn oil has been shown to have a neutral effect on triglycerides and potentially some cardioprotective effects, while mineral oil may result in unfavorable increases in triglycerides and LDL. Some may argue that the use of mineral oil in REDUCE-IT might have exaggerated the efficacy of icosapent ethyl.

The OMEMI trial, meanwhile, randomized 1,000 elderly, 70-82 year old patients (who had had a myocardial infarction [MI] in the 2-8 weeks prior to enrollment) to 1.8 grams of omega-3 fatty acids or a matching corn oil placebo for 2 years. It excluded participants who could not tolerate fatty acids or who had diseases that would impact their ability to survive the 2 year study period. OMEMI found no difference in the composite primary outcome (non-fatal MI, unscheduled revascularization, stroke, hospitalization for heart failure or all-cause death). There were no significant differences in key clinical subgroup analyses, and there was a greater (though not statistically significant) risk of atrial fibrillation in the treatment arm. There was no difference in major bleeding.

Taken together, findings from STRENGTH and OMEMI complicate the picture of fish oil utilization and raise further questions about whether the cardiovascular effects of fish oils in some populations are beneficial or neutral. More work needs to be done to better elucidate the effects of fish oils on cardiovascular risk reduction in high-risk patients.

Nevertheless, while STRENGTH and OMEMI made waves owing to their potential practice-changing implications, I left the day feeling particularly inspired by the SAMSON trial. This ingeniously designed trial enrolled 60 participants who had stopped taking statins due to symptoms arising within two weeks. Any symptom was eligible if it was severe enough to lead to statin discontinuation in that time span. The most common symptoms were muscle aches, fatigue, and cramps. Participants were given four bottles containing atorvastatin 10 mg tablets, four bottles containing placebo pills and four empty bottles. Each month, they were randomly assigned to take the contents of one of the bottles, in a crossover fashion, with no washout between months. They were asked to rate the severity symptoms they experienced using a mobile phone app. They were also asked 6 months after the conclusion of the trial if they had resumed taking statins. Investigators combined symptom ratings, reporting average symptoms levels during “statin”, “placebo” and “no treatment” months.

SAMSON found that the severity of symptoms reported was substantially higher during statin months than during no treatment months; however, this was also true for placebo. Reported symptom levels during statin and placebo months were no different from each other. The nocebo proportion was 0.9; that is, 90% of symptoms reported during statin months were elicited by taking placebo tablets as well. Even more importantly, half of the participants resumed statins again after the trial!

SAMSON serves as a lesson to aspiring cardiovascular researchers that even a small study can have a major impact. It displays respect and empathy for the patient experience by acknowledging rather than denying that patients do experience side effects from statins. However, it also strongly suggests that these symptoms may be attributable to the act of taking a pill rather than the medication content of the pill itself. Lastly, SAMSON proves that patients who realize that statin side effects may not actually be specific to statins themselves may be willing to resume taking statins. These findings further support the foundational concept that we as physicians must respect our patients by engaging them in shared decision-making and give patients an opportunity to understand the science, rather than simply telling them what to do.

Key Studies for the Peripheral Vascular Disease Specialist

November 15, 2020November 15, 2020 Sanjum Sethi, MD, MPH

On Saturday, November 14, 2020 there was an interesting session evaluating new data that impacts the care of patients with lower extremity peripheral arterial disease. For those of us involved in the daily care of these patients, we welcome new insights to help improve outcomes in this high risk patient population.

First, Dr. Mary McDermott from Northwestern University presented the LITE randomized clinical trial which compared a low versus high intensity home based walking program for lower extremity PAD patients. While the benefits of supervised walking programs is well known from the literature (1), in practice we often have difficulty in convincing our patients to proceed even when experiencing lower extremity pain. Only recently has CMS approved reimbursement for supervised exercise programs (1). ‘

In this multicenter trial, 305 participants were randomized to low intensity exercise, high intensity exercise, and attention control groups. All groups received weekly telephone education. Both exercise groups consisted of exercise 5 days/week for upto 50 minutes/session with the low intensity intervention consisting of a comfortable walking pace without ischemic symptoms. In contrast, the high intensity group exercised to maximal ischemic leg pain. The primary outcome measure was 6 minute walk time at 12 months. The high intensity exercise group had a statistically significant increase in the 6 minute walk time (53.9 meters) versus the low intensity (11.7 meters) and the control group (4.0 meters). Similarly, there was improvement in the patient reported measures of walk distance based on the WIQ distance score in both the high intensity and low intensity groups.

These data suggest that we can prescribe high intensity exercise programs for our PAD patients and expect both objective and subjective improvement. An especially important finding when many options for supervised walking programs are restricted during the current pandemic.

Next in the session were a pair of important substudies from the VOYAGER PAD trial (2). First, Dr. Marc Bonaca from the University of Colorado presented an analysis evaluating the highest risk patients, those with critical limb ischemia (CLI). This subgroup of PAD tends to have the worse outcomes both from a standpoint of cardiovascular and lower extremity disease.

VOYAGER PAD randomized 6,564 patients with symptomatic lower extremity peripheral arterial disease who were undergoing peripheral revascularization. The patients were randomized 1:1 in a double-blind fashion to rivaroxaban 2.5 mg twice a day versus placebo. All patients received low dose aspirin with clopidogrel at the operator’s discretion. The main trial had a statistically significant benefit in the rivaroxaban group with a 15% relative risk reduction and 2.6% absolute risk reduction relative to control (19.9% versus 17.3%) (2). The number needed to treat (NNT) was 39 with a number needed to harm (NNH) due to TIMI major bleeding of 125.

The critical limb ischemia patients comprised nearly a quarter of the overall population (n=1533). Compared to the claudication patients, the CLI patients were at higher risk with more complex anatomy and a much higher baseline event rate (27% versus 17% at 3 years). Since the CLI patients were at higher risk, the benefit was greater with ARR of 4.5% in the CLI group. This was consistent across all subgroups and was primarily driven by less acute limb ischemia and lower extremity amputations. The NNT was 23.

Next, Dr. Manesh Patel presented an analysis from VOYAGER PAD evaluating rivaroxaban therapy plus aspirin versus aspirin alone after endovascular revascularization (3). Currently, we often use dual antiplatelet therapy in this population lasting anywhere from 1 month to 12 months post endovascular revascularization depending on the device used and patient risk profile.

With the results of COMPASS PAD (4) and VOYAGER PAD, it was unclear how to integrate this dose into the clinical care of patients receiving endovascular revascularization. Therefore, this analysis has been highly anticipated to understand the best post-treatment antiplatelet/antithrombotic regimen. About two-thirds of the patient population had endovascular revascularization versus one third in the surgical group. Clopidogrel was used in 69% of the patients. The endovascular patients had findings consistent with the overall trial with an absolute risk reduction of 1.7%. However, major adverse limb events were reduced by (ARR) 2.4% with an NNT of 42. There was an increase in TIMI major bleeding (NNT = 100), but not fatal bleeding. Clopidogrel didn’t change the MALE outcomes.

Taken together, this data certainly informs our clinical practice for a wide variety of lower extremity PAD patients. Dr. McDermott’s study reinforces the need for exercise therapy to improve walking distance and suggest that this can be done even in a home-based environment. The VOYAGER PAD substudies suggest that low dose rivaroxaban is especially beneficial in the highest risk patients, those with CLI and has a role to reduce long term adverse limb events in all patients undergoing endovascular revascularization. We should be strongly considering this therapy for those PAD patients that are at higher ischemic risk (diabetes, smoking, CLI) and do not have an excess in bleeding risk.

This is just a snapshot of some of the peripheral arterial disease-focused studies discussed at AHA Scientific Sessions 2020. I encourage everyone to utilize the on-demand content including many of the abstract sections for even more PAD focused content.

References:

Treat-Jacobson D, McDermott MM, Beckman JA, Burt MA, Creager MA, Ehrman JK, Gardner AW, Mays RJ, Regensteiner JG, Salisbury DL, Schorr EN, Walsh ME; American Heart Association Council on Peripheral Vascular Disease; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; and Council on Lifestyle and Cardiometabolic Health. Implementation of Supervised Exercise Therapy for Patients With Symptomatic Peripheral Artery Disease: A Science Advisory From the American Heart Association. Circulation. 2019 Sep 24;140(13):e700-e710. PMID: 31446770.
Bonaca MP, Bauersachs RM, Anand SS, Debus ES, Nehler MR, Patel MR, Fanelli F, Capell WH, Diao L, Jaeger N, Hess CN, Pap AF, Kittelson JM, Gudz I, Mátyás L, Krievins DK, Diaz R, Brodmann M, Muehlhofer E, Haskell LP, Berkowitz SD, Hiatt WR. Rivaroxaban in Peripheral Artery Disease after Revascularization. N Engl J Med. 2020 May 21;382(21):1994-2004. PMID: 32222135.
Hiatt WR, Bonaca MP, Patel MR, Nehler MR, Debus ES, Anand SS, Capell WH, Brackin T, Jaeger N, Hess C, Pap AF, Berkowitz SD, Muehlhofer E, Haskell L, Brasil D, Madaric J, Sillesen H, Szalay D, Bauersachs R. Rivaroxaban and Aspirin in Peripheral Artery Disease Lower Extremity Revascularization: Impact of Concomitant Clopidogrel on Efficacy and Safety. Circulation. 2020 Nov 3. PMID: 33138628.
Kaplovitch E, Eikelboom JW, Dyal L, Aboyans V, Abola MT, Verhamme P, Avezum A, Fox KAA, Berkowitz SD, Bangdiwala SI, Yusuf S, Anand SS. Rivaroxaban and Aspirin in Patients With Symptomatic Lower Extremity Peripheral Artery Disease: A Subanalysis of the COMPASS Randomized Clinical Trial. JAMA Cardiol. 2020 Sep 30:e204390. PMID: 32997098.

Big Data: The Double-Edged Sword

November 15, 2020November 17, 2020 Chayakrit Krittanawong, MD

In today’s climate, industries often talk about the new buzz word of this era, Big data. In this case, Big data refers to data on the macro scale (mostly unorganized and unstructured). The utilization of Big data has tremendous potential for various industries, healthcare included. Facebook, Amazon, Netflix, for example, incorporate big data for their digital structures, creating algorithms to match customers with their interests. Some experts in discussing big data have described it as the three or four Vs; Volume rereferring to a large amount of data; Velocity referring to the timely generation of data; Variety rereferring to the multiple forms of data (e.g., genetics, emails, numbers, surveys); Veracity referring to the quality of the data. I recently discussed the potential of big data in medicine in my expert review article (https://www.tandfonline.com/doi/abs/10.1080/23808993.2018.1528871).

For example, Big data can be utilized to improve decision-making when combined with other emerging technology such as artificial intelligence or quantum internet. It is possible that Big data can combine clinical characteristics (e.g., high HbA1C, high cholesterol, hypertension), multi-omics (e.g., genes, protein, metabolites), lifestyle (e.g., smoking cigarettes, exercise, physical activities, sleep hygiene), and environmental factors (e.g., air pollution, PM2.5, traffic noises) with artificial intelligence in future clinical trials. (Figure) As Dr. Jacqueline Tamis-Holland discussed in the AHA meeting today, current clinical trials do not confirm the genotype-guided antiplatelet therapy. However, this remains just a pipe dream at the present moment. So far, all Big data techniques are primarily descriptive and retrospective. In the future, with advanced computational power (aka quantum computing), leveraging Big data in medicine is promising.

Source: Krittanawong et al. JACC 2017

Big data also has its limitations, and there are several lessons we must learn before implementing it effectively. First, big data is never well-curated and comes with a large degree of heterogeneity. Thus, selecting the correct technology with human power to curate Big data is crucial. Second, analytic companies can misinterpret big data by using incorrect research questions to test their hypothesis or using the wrong tool to analyze the associated data, resulting in delivering false messages. Surgisphere is a prime example of what can go wrong through the analysis of big data. Surgisphere claimed to collect data from over 1000 hospitals worldwide. Although this is possible and emerging technology can accomplish this task with minimal human resources, it is unlikely that this data can also be well-curated. In addition, healthcare data is challenging to work with, as the integration of electronic medical records (EHRs) and data privacy are primary barriers. Another example is the Cambridge Analytica case, where data obtained from Facebook was used without consent.

When appropriately utilized, Big data can be a game-changer for various industries, including the healthcare industry. This requires well-curated data, pertinent research questions, transparency, appropriate analytic tools, and advanced computational powers. In the wrong hands, Big data can be a potent threat that can disrupt industries as a whole.

AHA20 Scientific Sessions From the Perspective of a New Attendee

November 15, 2020November 15, 2020 Sasha Prisco, MD, PhD

I was overwhelmed when I attended Scientific Sessions for the first time last year. There were thousands of participants and dozens of sessions occurring simultaneously in a very large convention center. It was challenging to try to attend all of the sessions that I was interested in. I was frequently disoriented in the large convention center. Coordinating central meeting spots with colleagues was difficult. Although AHA20 is virtual this year, seeing the vast number of sessions available covering many important topics can still be overwhelming, especially to a first-time attendee. As I mentioned in my last blog, trying to prioritize live events over OnDemand events may help keep you engaged during the conference.

For this blog, I wanted to feature the perspective of Javier E. Sierra-Pagan, a first-time attendee of Scientific Sessions. Javier is an F30-funded medical scientist (MD/PhD) trainee (who is in his 5th year in the program, 3rd year as a PhD student) at the University of Minnesota Medical School. He is currently studying mechanisms of cardiovascular development and regeneration. He is interested in Cardiology. I am fortunate to work at the same research institute as Javier and have his lab bench next to mine!

Question: What are you looking forward to at AHA Scientific Sessions this year? Any specific events that you are interested in?

Javier: I’m really looking forward to listening to good talks regarding cardiovascular development and disease. Given the current pandemic, I am particularly interested in any talks regarding SARS-CoV-2 and its implications on cardiovascular disease. As a young trainee, I’m interested in attending some of the networking events to get to know more individuals in my field of research.

Question: How has your experience with AHA Scientific Sessions been so far?

Javier: It has been great so far. I felt a little overwhelmed at the beginning with how big this conference is, but after setting my agenda and identifying good talks to attend to, I felt more comfortable and very excited about Scientific Sessions.

Question: How are you preparing for AHA Scientific Sessions?

Javier: I’m approaching Scientific Sessions with an open mind. It is my first time attending it and I’m just trying to learn as much as I can from both basic science, as well as clinical medicine. The benefit of having such a big conference is that I can learn a little bit from so many different areas in the field of cardiology.

Question: How has COVID-19 affected your research?

Javier: The pandemic has put a lot of stress on everybody for sure. At the beginning of the pandemic, I was fortunate to be primarily focused on writing and submitting a manuscript, which allowed me to work from home. Now we are in a different situation entering November. I am working more hours in the laboratory and trying to stay safe while also maintaining my productivity. I haven’t had any significant setbacks with regards to my thesis, but I did want to attend some conferences in the Spring that were ultimately canceled because of COVID-19.

Question: Anything else you want to add?

Javier: I look forward to attending more AHA meetings in the future (hopefully in person) and interacting with colleagues from the field. I definitely miss the scientific conversations that happen in the hallways or in the elevators when you are trying to get to a lecture room.

Thank you, Javier, for discussing your experience with other trainees!

Remember that you can watch all of the OnDemand AHA20 content until January 4, 2021, which can help relieve the stress of cramming in as many sessions as possible into 5 days. If you are an early career investigator or trainee and would like to be featured in one of my upcoming monthly blogs, please let me know (you can message me on Twitter or email me at [email protected])!

Highlights from Day 3 of #AHA20

November 15, 2020November 17, 2020 Baljash Cheema, MD, MSCI

What an end to the weekend! As Day 3 of AHA 2020 continues, there is already much to digest and discuss. From Late-Breaking Trials to specific programming for Fellows in Training and Early Career individuals, there was something for us all. My time was spent tuning in to informative discussions from leaders in the advanced heart failure world, and below I reflect on some of what stood out to me today.

Implementation science matters as Dr. Saurer shares with us on Twitter. As our armamentarium of GDMT grows, it will be key to figure out how best to get these medications prescribed to our patients in order to maximize therapy while minimizing side effects and managing cost. But how do we do that? What order should be prescribed our drugs in? What about devices? Is the same approach applies to all? There is an area primed for more research. What an exciting time to be in the heart failure space.
Take note of the trajectory. It is important to be aware of and routinely reassess the trajectory of our patients with heart failure, both in the inpatient and outpatient setting, as discussed by Dr. Hollenberg. In our sickest patients, those with Stage D heart failure, we have the option of considering VAD or transplant as well as palliative care approaches including home inotropes, but patients are often flagged too late and no longer eligible for certain therapies. Use the “I NEED HELP” mnemonic to try and identify these patients early, as Dr. Breathett shares with us.
Know when to escalate care. While it is not always crystal clear who needs a higher level of support, Dr. Cogswell gives us a clinical pearl: if your patient is hypotensive with heart failure, start to think about what is next, whether that is temporary support or a durable device or ultimately both. She gives an example of pausing an IABP and seeing if her patient becomes hypotensive in order to consider an Impella or LVAD, as opposed to adding more drips which may not ultimately be enough.
#ReviveTheSwan! As eloquently and definitively stated by Dr. Hall, all patients with cardiogenic shock need a Swan-Ganz catheter. Our physical exam “just is not that good”. Care is improved by using invasive hemodynamics
A civilized debate is possible! Despite the politics in our country as of late, today’s sessions clearly showed the civil, intellectual, informative debates are still possible in our society, and they are for the betterment of all involved! Kudos to all who gave us their time and wisdom today.

While the day is early and there is much yet to be seen, the teaching on Day 3 of AHA20 has already been fantastic.

Highlights of “Not to Miss Sessions” at the #AHA20 Virtual Meeting!!

November 15, 2020November 15, 2020 Lina Ya'qoub, MD

AHA20 virtual meeting has been packed by so many amazing sessions, covering all aspects of cardiovascular disease from basic science to clinical outcomes. I wanted to share some of the sessions “not to miss sessions” at AHA20 virtual meeting!!

Opening Session

Dr. Braunwald and Dr. Wenger, two of the legends in cardiology, took us back to history, structural racism, and correlated what we are living now during the pandemic and the social justice crisis to how it was when living in war!!!! Dr Harrington and Dr Yancy led a great discussion. Definitely, a very interesting talk that everyone should listen to!!

Structural Racism Session

This is a novel yet a wonderful session at AHA20!!! It is part of AHA leadership commitment to equity, diversity, social justice in healthcare across the nation and the globe. There were several amazing discussions with experts and leaders in the field, sharing data on how structural racism can in fact affect the health of both healthcare employees and patients, calling for action to increase diversity and inclusion in leadership positions for minorities and women. If you missed this session, you should check out the on-demand portal and listen to it. Kudos to everyone involved in this and who made this happen!!

Presidential Session

This was an inspiring session by Dr. Elkind, MD, AHA President about his journey in neurology and science. This was followed by an amazing talk by Nancy Brown, AHA CEO, emphasizing the AHA vision on social equity, diversity, and inclusion in research, science, and access to health care. Then, we watched many inspiring women receiving distinguished AHA awards for their excellence in leadership and academic achievement. They all share the AHA’s vision and commitment to lead science in order to have comprehensive policies and unite team efforts for better healthcare for all as well as bridge the AHA’s visions into actual practice not only across the nation and also across the globe.

Late-Breaking Science and Meet the Trialist Sessions

There are late-breaking science sessions on multiple days on various sub-specialties of cardiovascular diseases, including preventive cardiology, resuscitation, heart failure, interventional cardiology, structural heart disease, electrophysiology, among other specialties. Later each day, there are sessions where you can meet the trialist, ask questions through Q&A side chat and you’ll hear their input on the trials they presented earlier in the day.

Move More and Dance Break Session

This is a fun session to motivate us to move more!! It was the first session of each day on AHA20 but you can watch it on-demand anytime whenever you want!!

#AHA20 is packed with so many great sessions for all sub-specialties in cardiology!! I look forward to AHA21, and hopefully, it will be an in-person meeting next year!!

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