Cover Story | Acute Coronary Syndromes: New Perspectives, New Data

Acute Coronary Syndromes: New Perspectives, New Data

In the rapidly evolving health care landscape, acute coronary syndromes (ACS) continue to be a leading cause of morbidity and mortality worldwide. Each year, an estimated 1.2 million individuals in the U.S. are hospitalized with ACS.1 STEMI accounts for about 30% of these hospitalizations, while NSTEMI, or NSTE-ACS, accounts for the remaining 70%.

Despite significant advances in diagnostic techniques and therapeutic strategies, the timely identification and risk stratification of individuals with ACS in the early stage continues to be crucial yet complex, particularly for subgroups with underrecognized risk. Fortunately, new perspectives and data are now available to assist.

ACS as a Spectrum

The 2023 ESC Guidelines for the Management of Acute Coronary Syndromes consolidate recommendations for the entire ACS spectrum into one document, with clinical presentations progressing from oligo/asymptomatic to cardiac arrest and final diagnoses proceeding from unstable angina to NSTEMI to STEMI.2

According to guideline co-author and task force member, Nanette Kass Wenger, MD, MACC, at Emory University School of Medicine in Atlanta, a key highlight of the new ESC guideline is the integration of various separate guidelines into a single continuum.

This innovative approach addresses the entire ACS patient journey from initial chest pain presentation – emphasizing the differences between women and men – through to emergency department (ED) treatment, catheterization lab procedures, hospital stay, secondary prevention and long-term management.

 Considering acute chest pain from a more holistic perspective is particularly of benefit to patients with very high risk NSTEMI, or what we refer to as STEMI equivalents. 

Deepak L. Bhatt, MD, MPH, MBA, FACC

"Importantly, this approach addresses concisely what the clinician needs to think about with an ACS patient," says Wenger. Is the EKG abnormal? Is there a troponin rise? "And then decisions can be made about revascularization, antithrombotic therapy, proceeding to secondary prevention and long-term care."

Deepak L. Bhatt, MD, MPH, MBA, FACC, director of the Mount Sinai Fuster Heart Hospital in New York, also agrees with the ESC approach of viewing ACS as a continuum.

"There are more similarities than differences, especially in terms of initial medical care of patients in the ED, antithrombotic therapy and long-term management," he says. "Considering acute chest pain from a more holistic perspective is particularly of benefit to patients with very high risk NSTEMI, or what we refer to as STEMI equivalents."

In particular, vessels supplying the lateral wall of the left ventricle, such as the left circumflex or a large diagonal branch arising from the left anterior descending artery, may result in less characteristic changes, such as ST-segment depression, notes Bhatt.

"These are patients where it may not be a STEMI on the EKG, but the angiogram reveals, for instance, a blocked left circumflex artery," he says. "This is a patient who should be treated more similarly to a STEMI patient rather than one with a lower-risk NSTEMI."

According to the ACC/AHA guidelines and the ESC guideline, a tailored risk-based approach to angiography is recommended. For patients at very high-risk or high-risk, such as those experiencing ongoing chest pain, dynamic or persistent EKG changes, hemodynamic instability and life-threatening arrhythmias, an early invasive approach is appropriate.

Patients without high-risk features but who are at intermediate risk can benefit from angiography during the same hospitalization, preferably within 24 to 72 hours after admission. Those assessed as low risk following a thorough noninvasive evaluation may not require urgent angiography and can be considered for a more conservative approach or a delayed invasive strategy, depending on further evaluation and clinical judgment.

 Some of these ideas about educating and informing patients may seem obvious, but we often fail to implement them. Given the relatively short hospitalizations for ACS ... there must be a conscious effort to provide all the information that should be given to them. 

Nanette Kass Wenger, MD, MACC

The ESC guideline also offers an easy-to-remember "A.C.S." acronym for initial triage and assessment: 'A' stands for an abnormal ECG, which should be performed within 10 minutes of first medical contact; 'C' for clinical context, considering symptom presentation and any patient history available; and 'S' for clinical stability, which is crucial for immediate care decisions, says Wenger.

Of note, the ESC ACS guideline provides an extended section on patient perspectives. "We had a patient in the writing group, and there is some wonderful information on shared decision-making, even in the acute care setting. It includes what patients should expect in terms of being informed about their options and engaging in shared decision-making, says Wenger.

This guidance includes ensuring that patient values are used to inform all clinical decisions; assessing symptoms using methods that help patients describe their experiences; considering a patient's physical, emotional, psychosocial and environmental needs at every stage of their care; and educating and informing patients using the 'teach back' method.

"Some of these ideas about educating and informing patients may seem obvious, but we often fail to implement them," says Wenger. "Given the relatively short hospitalizations for ACS, typically four or five days if they undergo a catheterization lab procedure without complications, there must be a conscious effort to provide all the information that should be given to them."

 In MINOCA, the epicardial arteries may look normal on angiography – but without intravascular imaging the plaque characteristics can be missed that explain the patient's event. 

Megha Prasad, MD

The 2021 ACC/AHA Guideline for the Evaluation and Diagnosis of Chest Pain, took a similar patient-centric approach highlighting chest pain as it is the predominant symptom that initiates the ACS diagnostic and therapeutic pathway.3

The guideline addresses diagnostic and treatment pathways for both STEMI and NSTEMI but does not offer recommendations on revascularization, leaving that to the ACC/AHA Coronary Artery Revascularization guideline published in late 2021.

New ACC/AHA ACS guidelines are expected in the next year. There's a good chance they may adopt a similar approach, says Bhatt. The most recent ACC/AHA STEMI guideline is from 2012; the NSTEMI guideline was released in 2014. On both sides of the pond there is recognition that rapid brief updates must be provided for emerging data.

A Whole Heart Approach

For interventional cardiologist Megha Prasad, MD, at Columbia University in New York, the routine use of intravascular coronary imaging is one of the most impactful shifts in the field of ACS. IVUS and optical coherence tomography (OCT) are used for stent optimization and procedure planning, as well as allow for more detailed and finessed assessment of plaque morphology and disease process.

The focus used to be almost exclusively on the epicardial vessels as seen on angiography in patients with a STEMI or NSTEMI. Now she employs IVUS or OCT or both for all her patients, which allows appreciation of plaque erosion, thrombus, calcified bifurcation disease, calcium nodules and microvascular disease, thus guiding a better treatment plan.

Is MI Overdiagnosed?

Heightened vigilance has led to overdiagnosis of MI likely being the main form of MI misdiagnosis, according to McCarthy, Wasfy and Januzzi, in a recent Viewpoint published in JAMA that looks at the issue of overdiagnosis of MI in contrast with previous concerns of underdiagnosis.5 This has significant consequences, they say, including unnecessary medical treatments, costly testing, prolonged hospital stays, and potential adverse impacts on patients' mental health, finances and employment.

Evidence of overdiagnosis is seen particularly in the U.S., as evidenced by the positive predictive value of a troponin test for MI being significantly lower (approximately 16%) compared to the U.K. (approximately 60%). To address this, the authors, call for more precise diagnostic criteria with better adherence to the Universal Definition of MI guidelines; less liberal use of troponin testing; and prudent use of cardiac imaging to mitigate these issues.

They also note the need for studies to better understand the frequency and implications of overdiagnosis. Integrating machine learning models that incorporate fixed and dynamic variables to more accurately predict MI diagnosis and application of age-specific 99th percentile for troponin testing are suggested as strategies to enhance diagnostic accuracy and reduce overdiagnosis.

She says, "I always gain valuable information from these modalities that helps guide my pharmacotherapy and treatment plan."

However, intravascular imaging is underutilized in this setting across the country, notes Prasad. Greater use would improve identification of underrecognized entities like myocardial infarction with nonobstructive coronary arteries (MINOCA), plaque erosion and plaque rupture, while also optimizing stent durability by ensuring appropriate expansion.

MINOCA refers to the setting where a patient presents with symptoms suggestive of ACS and demonstrate troponin elevation and nonobstructive arteries on angiography. It is found in up to 14% of patients with ACS, with women being five times more likely than men to have MINOCA.

"In MINOCA, the epicardial arteries may look normal on angiography – but without intravascular imaging the plaque characteristics can be missed that explain the patient's event," says Prasad. Many patients present with signs and symptoms of an MI, but intravascular imaging is needed to know the cause of the event.

Beyond the use of intravascular imaging for patients with ambiguous culprit lesions, the guidelines support the use of cardiac magnetic resonance (CMR) imaging to identify wall motion abnormalities and myocardial edema and distinguish infarct-related scar from non-coronary artery disease (CAD) causes such as myocarditis and nonischemic cardiomyopathy. CMR is also useful for differentiating MINOCA from other causes of MI.

Stop Minding the Gap For Women – Close It!

Even though the conversation has been ongoing for many years, there are still ample data indicating that women with ACS are treated differently than men. According to Wenger, who has been a staunch advocate for women's cardiovascular health throughout her long career, detection of ACS, particularly in younger women, remains poor. "Young women are not expected to have heart attacks, even though they do, and their prognosis is worse, in part because they are often misclassified as having nonischemic chest pain."

Chest pain is the main and most frequent symptom for both women and men ultimately diagnosed with ACS. Women often experience chest pain symptoms similar with men but also have a higher prevalence of other symptoms such as nausea, shortness of breath and palpitations, as well as jaw, neck and back pain.

"I teach that men are noun-verb people, and women are adjective-adverb people," says Wenger. "When a woman presents, she will describe everything she feels, and somehow the chest pain or chest pressure may get overlooked, with her predominant symptom being acute fatigue, acute shortness of breath, or neck, back or shoulder pain."

 I teach my colleagues in the ED that any acute symptom in a woman between the mandible and the umbilicus should be considered a possible ACS. In this setting, obtain an EKG and a troponin immediately. 

Nanette Kass Wenger, MD, MACC

She adds: "I teach my colleagues in the ED that any acute symptom in a woman between the mandible and the umbilicus should be considered a possible ACS. In this setting, obtain an EKG and a troponin immediately."

Notably, chest pain terminology has changed since the 2021 ACC/AHA Chest Pain Guideline, with the term "atypical" replaced with "noncardiac." According to the guideline, "chest pain should not be described as atypical because it is not helpful in determining the cause and can be misinterpreted as benign in nature.

Instead, chest pain should be described as cardiac, possibly cardiac, or noncardiac because these terms are more specific to the potential underlying diagnosis." Additionally, cardiac pain is differentiated as coronary or noncoronary.

A key message in the current ESC ACS guideline is that although there are some sex differences in the epidemiology of ACS, both women and men derive equal benefit from invasive and noninvasive management strategies and, as a general rule, should be managed similarly.

Click here to read Cardiology's Spotlight Series on Microvascular Disease, including a look at invasive and noninvasive assessment of small vessel disease; limitations of PCI in patients with small vessel disease; patients with obstructive CAD; treatment options for coronary microvascular dysfunction; and invasive assessment of angina and nonobstructive coronary arteries.

The ACC/AHA revascularization guideline notes that, after controlling for baseline differences in presentation and treatment, women have similar outcomes after revascularization compared with men.6 To reduce disparities in care, the guideline recommends treatment decisions be based on indication, regardless of sex, race or ethnicity.

Patient education, addressing delays in the ED and increasing awareness about heart disease among all clinicians are three approaches that Wenger believes can help to close the gap in care between women and men. She emphasizes the importance of patient information and education in helping patients advocate for themselves. "Many young women do not believe they are having a heart attack and are afraid of being embarrassed when they go to the ED. So, either they don't go or they aren't as emphatic as they should be about their symptoms."

Wenger also calls out the "whole system" that delays care for a young woman presenting to the ED, whereas for a man presenting with chest pain there is automatically an immediate EKG and a troponin level obtained. Often, a woman will need to report her story three or four times before someone will listen. "It's the unconscious bias of the person receiving the chief complaint," that causes the delay says Wenger.

Despite some progress, too many clinicians are still less aware of and less attentive to women's heart disease, how it might manifest and how to listen to the complaints of women who present with chest pain, etc. Unfortunately, women themselves are less aware that they are at risk for heart disease, with a measurable drop in risk awareness in the last decade.4 This lack of awareness, says Wenger, means too many women do not heed prevention guidelines. "Women deserve better."

ACS Science From ACC.24

Here's a quick round of summaries and takeaways from the biggest ACS trials presented at ACC.24, with some commentary from our experts.

FULL REVASC: The registry-based FULL REVASC trial compared fractional flow reserve (FFR)-guided complete revascularization of nonculprit lesions or culprit-lesion revascularization in 1,542 patients (23% women) with STEMI or very-high-risk NSTEMI who also had multivessel CAD.

Over a median follow-up of 4.8 years, no difference was seen in the primary outcome (death, MI or unplanned revascularization) in those who underwent complete revascularization (19.0%) compared to the culprit-lesion-only group (20.4%; hazard ratio [HR], 0.93; p=0.53). There were similarly no significant between-group differences in the composite secondary outcome of all-cause death or MI, or for unplanned revascularization. Subgroup analyses indicated consistent effects across various patient groups.

Stent thrombosis, restenosis and target vessel revascularization were more common in the FFR-guided arm, with no apparent differences noted in stroke, bleeding, heart failure or acute kidney injury. The trial was limited by an early termination which may have affected the power and possibly the outcomes, noted the investigators.

"This appeared to be a well-done trial, so the results were a little bit surprising to me in that there wasn't a clear benefit identified, while a number of other trials that have looked at this idea of complete revascularization have shown benefit," says Bhatt.

"I don't discount these data, but I guess for now I continue to believe in the benefits of complete revascularization," he adds.

DanGer Shock: The wait for the DanGer Shock trial results has been long, especially for those involved in treating the 8% to 10% of STEMI patients who enter cardiogenic shock, from which they face a subsequent risk of death of 40% to 50%.

In this multicenter, open-label trial, 360 patients with STEMI complicated by cardiogenic shock were randomized to either standard care plus the Impella CP microaxial flow pump or standard care alone. The median patient age was 67 years and 79% were men. Median left ventricular ejection fraction (LVEF) at the time of randomization was 25%.

Death from any cause at 180 days, the study's primary endpoint, occurred in 45.8% of the microaxial-flow-pump group compared to 58.5% in the standard-care group, yielding an absolute 13% reduction in death and an HR of 0.74 in favor of the Impella CP device (95% CI, 0.55-0.99; p=0.04). There was an associated increase in adverse events (severe bleeding, limb ischemia, hemolysis, device failure and worsening of aortic regurgitation) with pump use (24% vs. 6.2%; HR, 4.74; 95% CI, 2.36-9.55).

"This long-awaited trial is important as these patients are sick with limited options and are difficult to study. As a field we needed a positive randomized controlled trial to help guide treatment of these patients," says Prasad, noting the very low numbers of women enrolled in the trial. "In addition to the immediate benefit, there appeared to be a sustained benefit, which may be due to reduced myocardial injury. I wonder if preservation of the microcirculation also contributes to this sustained improvement."

ULTIMATE DAPT: In this randomized, placebo-controlled, trial, 3,400 patients with ACS who had completed one month of dual antiplatelet therapy (DAPT) without experiencing major ischemic or bleeding events, were randomly assigned to receive ticagrelor (90 mg twice daily) plus aspirin (100 mg daily) or ticagrelor plus placebo.

Between one and 12 months after PCI, ticagrelor alone reduced the incidence of clinically relevant bleeding events compared to ticagrelor plus aspirin (2.1% vs. 4.6%, respectively; HR, 0.45; p<0.0001) without increasing major adverse cardiovascular or cerebrovascular events (3.6% and 3.7%, respectively; HR, 0.98; p<0.0001 for noninferiority, p=0.89 for superiority).

"I think this trial moves the needle on a topic on which we've collected a lot of data, that is, whether a strategy of shortening the duration of DAPT and deescalating to an ADP-receptor antagonist is an approach that preserves the efficacy of the antithrombotic strategy, but is safer," says Bhatt. "This trial shows it is, even in ACS patients, which is important," says Bhatt.

In terms of his personal practice, Bhatt says he still tends to keep patients at low risk of bleeding on 12 months of DAPT after ACS and then tries to deescalate to an ADP-receptor antagonist, if appropriate. "But in patients who are at higher bleeding risk, I've been comfortable deescalating at three months or if they're really high bleeding risk even a month, again to an ADP-receptor antagonist instead of aspirin," he adds.

REDUCE-AMI: Beta-blockers have played a role in the treatment of MI since the early 1970s when pivotal research by Eugene Braunwald, MD, MACC, Peter Maroko, MD, and colleagues demonstrated in dogs that these drugs, which decrease myocardial oxygen requirements, could limit myocardial injury following coronary artery ligation.

Trials conducted mostly in the 1980s showed that long-term beta-blocker therapy after MI reduced mortality by approximately 20%. But these trials were largely conducted in the era before modern reperfusion and PCI techniques and the current era of advanced secondary preventive medications.

The prospective, registry-based REDUCE-MI trial investigated the effect of long-term beta-blocker treatment in 5,020 patients with acute MI who had a preserved LVEF (≥50%) following early coronary angiography. Most participants were not elderly and were lower risk, often with single-vessel disease and limited diabetic comorbidity. Patients were randomly assigned to either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment.

The primary composite outcome of all-cause death or new MI, measured over a median follow-up of 3.5 years, showed no clear benefit for beta-blocker therapy (7.9% vs. 8.3% for no beta-blocker treatment; HR, 0.96; p=0.64). The results were consistent across all predefined subgroups and extended to no between-group differences in the incidence of any of the secondary endpoints, including all-cause death, cardiovascular death, MI, hospitalization due to atrial fibrillation, or hospital admission due to heart failure.

For Wenger, this is not the end of the line for beta-blockers post MI, even in patients with intact left ventricles. "Beta-blockers are antiarrhythmic, they're antihypertensive, and they improve myocardial contractility. My tendency is to say that before this changes behavior, we need this replicated in a larger population. The trial raises a question, but it doesn't give an answer."

Visit to read more on these studies and all the coverage, trial summaries, video wrap-ups and more from ACC.24.

This article was authored by Debra L. Beck, MSc.


  1. Martin SS, Aday AW, Almarzooq ZI, et al. 2024 heart disease and stroke statistics: A report of US and global data from the American Heart Association. Circulation 2024;149:e347-e913.
  2. Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC guidelines for the management of acute coronary syndromes. Eur Heart J 2023;44:3720-3826. [Erratum published in Eur Heart J 2024;45:1145.]
  3. Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR guideline for the evaluation and diagnosis of chest pain. J Am Coll Cardiol 2021;78:e187-e285.
  4. Wenger NK. The Feminine face of heart disease 2024. Circulation 2024;149:489-91.
  5. McCarthy CP, Wasfy JH, Januzzi JL Jr. Is mycoardial infarction overdiagnosed? JAMA 2024;April 24:[Epub ahead of print].
  6. Lawton JS, Tamis-Holland JE, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization. J Am Coll Cardiol 2022;79:e21-e129.

Clinical Topics: Acute Coronary Syndromes, Cardiovascular Care Team, Prevention, Stable Ischemic Heart Disease, Vascular Medicine, Chronic Angina

Keywords: Cardiology Magazine, ACC Publications, Acute Coronary Syndrome, Delivery of Health Care, Secondary Prevention, Non-ST Elevated Myocardial Infarction, ST Elevation Myocardial Infarction

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