2026 AHA科学声明：绝经前期女性急性冠状动脉综合征

Symptoms and Clinical Presentation

Further complicating matters, women with ACS may report a range of symptoms such as pain/discomfort (back, shoulder, chest, neck, and jaw), epigastric and gastrointestinal symptoms (indigestion, nausea, stomach pain, vomiting, pressure, burning, discomfort), nonspecific symptoms (sweating, anxiety, fatigue and dizziness), and nuanced/subtle symptoms (feeling “something is off”).$^{26}$⁻$^{28}$ Although less common, cardiac arrest and sudden cardiac death are other potential mechanisms of presentation with ACS, and it is noteworthy that compared with age-matched men, premenopausal women may have a higher likelihood of survival.$^{29}$,$^{30}$ Despite the variability of presentation and symptoms, the most common symptom in young women with ACS is chest pain, described as pain, pressure, tightness, or discomfort.$^{26}$,$^{28}$,$^{31}$ Serial online American Heart Association surveys of US women (≥25 years of age) conducted in 2009 and 2019 have demonstrated poor awareness of MI symptoms among young women.$^{32}$ Furthermore, overemphasis on relatively modest differences between women and men in symptoms during MI presentation has proved to be confusing for some health care professionals and patients.$^{27}$,$^{31}$ This issue is compounded by a lower likelihood of ST-segment-elevation MI (STEMI) and higher likelihood of unstable angina among young women with ACS compared with other patient groups.$^{27}$,$^{33}$,$^{34}$

Delays in Care

Premenopausal women with ACS experience gaps in care resulting from delays in seeking acute/emergency care and in ED diagnosis and treatment.$^{28}$ Women may defer seeking care for various reasons, including incorrectly attributing symptoms to noncardiac causes, recently decreasing awareness of heart attack symptoms in young US women,$^{32}$ attempting self-treatment, lacking awareness of their personal risk for cardiovascular disease, and prioritizing family, work, and social responsibilities.$^{28,35}$ A lack of social support for young mothers also affects delays. If emergency medical services are accessed, there can be additional delays and disparities in prehospital care of women with chest pain or MI

compared with men, for example, in the use of lights and sirens during transport or the appropriate prehospital administration of medications such as aspirin.$^{36}$ Compared with men, young women presenting to the ED with chest pain are less likely to be traged as immediate/emergency and wait longer before being seen by an ED professional, especially women of color.$^{35}$ Factors that contribute to delays in ED diagnosis and treatment include the misattribution of symptoms to noncardiac causes by health care professionals, variability of symptom phenotypes, implicit gender bias, and underuse of diagnostic tests in women, including even simple tests such as an ECG or tronponin level.$^{28,35,37}$ As a result, young women are particularly vulnerable to missed acute MI and inappropriate discharge from the ED.$^{38}$ Systematic interventions and public policy changes are needed to remedy these concerns.

Diagnostic Testing

Focused history taking and physical examination and obtaining an ECG within 10 minutes in the ED are critical to facilitate accurate patient triage and to reduce missed/delayed diagnosis.$^{39}$ For diagnosing STEMI, the ST-segment elevation threshold in leads $V_2$ and $V_3$ differs between sexes, and in women, the threshold is 1.5 mm regardless of age. In other contiguous leads, the threshold is 1 mm for both men and women,$^{40}$ Troponin levels should be obtained, preferably with a high-sensitivity troponin assy and with sex-specific diagnostic thresholds if a high-sensitivity troponin assay is available.$^{39,41}$ Unfortunately, troponin testing occurs 22% less often in women <50 years of age even when chest pain has cardiac features.$^{42}$ Testing for pregnancy is important for individuals of childbearing age to help guide decisions on medication and imaging tests.

INVASIVE ANGIOGRAPHY, CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY, OR NEITHER?

The selection of premenopausal women with ACS for invasive versus noninvasive diagnostic testing should be based primarily on risk. Women with STEMI are at high risk and should have invasive angiography emergently unless the clinical syndrome is clearly due to pericarditis. Similarly, women with non-ST-segment-elevation ACS should also be referred for invasive angiography unless they are at low risk for ischemic events. This is concordant with current guidelines that recommend an invasive strategy in non-ST-segment-elevation ACS for those at intermediate to high risk for ischemic events and a selectively invasive strategy for patients at a low risk of ischemic events.$^{39}$ This guide-line recommendation is supported by earlier data from a

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meta-analysis of 8 trials of women and men with non-ST-segment-elevation ACS (70% men) that demonstrated a 33% lower odds of death or MI with invasive versus conservative management in biomarker-positive women but no benefit in biomarker-negative women.$^{43}$ Troponin elevation indicates that symptoms are likely cardiac in origin even if the degree of elevation is relatively small. High-sensitivity assays are particularly important for women, who are at similar risk after MI that is diagnosed from a high-sensitivity or older troponin assay.$^{44}$ For this reason, unless a specific nonischemic diagnosis such as myocarditis or pulmonary embolism is made on dedicated testing, women with elevated troponin levels should be understood to have MI. We also advise strong consideration of invasive angiography in patients with recent triptan use based on its association with SCAD.$^{45}$ Figure 2 provides a coronary imaging algorithm.

Invasive angiography offers several advantages over coronary computed tomography angiography (CCTA):

$\bullet$ Higher accuracy for SCAD identification, particularly in nonproximal segments$^{46-48}$; $\bullet$ Option for revascularization in the same setting; * Easier control of radiation and contrast exposure; * Option for functional testing for coronary artery spasm and coronary microvascular dysfunction (CMD) when available and if appropriate; and * Avoidance of multiple tests with radiation exposure.

Notably, invasive angiography is preferable in pregnant patients with MI because observational data indicate lower risk in pregnant women managed invasively than in those managed conservatively.$^{49}$ Furthermore, this approach provides greater certainty about clinical diagnosis to guide medical and obstetric care.

There is a broad differential diagnosis in low-risk pre-menopausal women with an unstable angina syndrome. In addition to atherosclerosis, coronary artery spasm, and CMD, the differential diagnosis may include non-cardiac causes of chest pain. For this reason, although patients with low-risk unstable angina may still be suitable for invasive testing, clinicians may wish to consider CCTA. CCTA is favored over stress imaging for premenopausal women for several reasons, including that CCTA is more accurate than stress testing in identifying atherosclerotic CAD and can identify anomalous coronary arteries. The finding of nonobstructive atherosclerotic CAD on CCTA has treatment implications (eg, statins). In most centers, CCTA has radiation exposures equivalent to or lower than stress nuclear imaging. Stress echocardiography, although radiation free, is less sensitive than nuclear imaging.$^{50}$ Stress cardiac magnetic resonance imaging (cMRI) has limited availability but is otherwise a good option for the assessment of obstructive epicardial coronary disease; it is also an emerging modality for the diagnosis of CMD, although quantitative perfusion assessment is necessary to yield high accuracy of that diagnosis.$^{51,52}$ On the other hand, positron emission tomography is the established gold standard for the noninvasive diagnosis of CMD.$^{53}$ In patients with unstable angina and low-risk features, if invasive angiography and noninvasive angiography are not feasible, then stress testing (exercise ECG or functional imaging) may be a pragmatic alternative option to guide onward management.

Because about half of recurrent MIs after MINOCA are due to obstructive atherosclerotic CAD, invasive angiography for women with prior MINOCA is preferred.$^{54}$ Furthermore, intracoronary imaging and coronary

![graph TD\n A1[ST segment elevation: ≥1.5 mm in leads V2 and V3, or≥1 mm in other contiguous leads*] -->|NO| A2[Troponin rise and fall?]\n A2 -->|YES| A3[Is myocarditis the leading clinical diagnosis?]\n A2 -->|NO| A4[Invasive angiography preferred*]\n A3 -->|NO| A4\n A3 -->|YES*| A5[CCTA preferred]\n](1/parseimages/figure2fdb8708309b410e82d79281b8581011_0_8.png) *If the pattern of ST-segment elevation strongly suggests pericarditis and there are no regional wall motion abnormalities on echocardiography, then coronary computed tomography angiography (CCTA) is preferred, although in selected cases foregoing any angiography may be reasonable. †For example, fever with positive viral polymerase chain reaction. #Includes pregnant women, suspected spontaneous coronary artery dissection (SCAD), prior myocardial infarction with no obstructive coronary arteries. Further to this algorithm, based on an association with SCAD,$^{45}$ we advise strong consideration of invasive angiography if there has been recent triptan use.

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functional testing are of particular importance in case of recurrent MINOCA to evaluate for coronary artery spasm and potentially CMD. Consideration of referral to a specialized or tertiary referral center may be appropriate if evaluation for coronary artery spasm and CMD is not available at the presenting institution.

In considering which test(s) to perform in premeno-pausal women with recurrent symptoms after ACS with CCTA showing normal coronary arteries or nonobstruc-tive atherosclerotic CAD, it is important to appreciate that noninvasive testing does not rule out angina with nonob-structive coronary arteries, with the exception of positron emission tomography or cMRI evaluating for CMD (how-ever, neither positron emission tomography or cMRI can properly evaluate for coronary spasm). In these patients, invasive angiography with coronary function testing may be helpful to exclude coronary artery spasm and poten-tially CMD.

CONSIDERATIONS FOR INVASIVE ANGIOGRAPHY AND REVASCULARIZATION

Arterial Access

Current guidelines recommend radial artery access for patients with ACS undergoing percutaneous coronary intervention (PCI) on the basis of numerous clinical trials and meta-analyses demonstrating improved outcomes with this approach.$^{39,55}$ Women with ACS are at greater risk for bleeding and vascular complications than men$^{56,57}$ even with radial artery access.$^{56-58}$ In a large observational study examining >5000 patients with STEMI undergoing PCI for which the default access was right radial, a larger proportion of women than men had tortuous anatomy, radial loops, and radial artery spasm or required access site crossover.$^{58}$ Despite greater challenges with radial artery catheterization in women, randomized trials of radial artery access have shown that women and men derive a similar relative benefit from radial artery access (compared with femoral artery access).$^{55-57}$ For this reason, we emphasize the importance of radial artery access in younger women with ACS as the default strategy. Because of the potentiabstacles that can be encountered in younger women, it is important that physicians develop techniques and skills to overcome these barriers. When coronary angiography and PCI are performed, adequate procedural sedation and the use of intra-arterial vasodilating agents and hydrophilic/slender sheaths are critical to success. When there is difficulty advancing equipment, angiography should be performed, and when indicated, the use of smaller (0.014-in) wires with balloon-assisted tracking, hydrophilic catheters, or long (75 cm) sheaths is helpful to overcome tortuosity in the radial or subclavian arteries. If spasm of the radial, brachial, or other access arteries is encountered, this should alert the operator to

the possibility of coronary spasm being potentially more likely as a cause of ACS, particularly if angiography does not reveal an obstructive coronary lesion.

Intravascular Imaging

Intravascular imaging with optical coherence tomography (OCT) or intravascular ultrasound provides superior identification of the culprit vessel and assessment of plaque morphology in ACS due to atherosclerotic CAD compared with angiography alone.$^{59}$ Current guidelines recommend intracoronary imaging to guide PCI in patients with ACS or complex CAD,$^{39}$ but there are no specific recommendations for its use to assess plaque morphology in ACS. In premenopausal women, intracoronary imaging is particularly valuable in MINOCA or with uncertain lesion morphology when nonatherosclerotic causes are suspected. Plaque rupture and plaque erosion are best seen with OCT imaging, and when feasible, OCT is preferred over intravascular ultrasound. In women with MINOCA, multimodality imaging with OCT and cMRI determined MINOCA pathogenesis in 85% of cases, with a definite or possible culprit lesion identified in 46% of 145 patients in a multicenter study.$^{11}$ The most common abnormalities found on OCT were plaque rupture, intraplaque hemorrhage, or layered plaque, which are findings indicative of plaque disruption. In some cases when SCAD is suspected but angiographic images are inconclusive, intracoronary imaging can aid in confirming the diagnosis. In these cases, the decision to use intracoronary imaging and the choice of modalities should take into account operator and center experience, the risk related to the inadvertent wiring of the false lumen, and the potential for the propagation of the dissection or hydraulic expansion of the intramural hematoma.

Left Ventricular Angiography

Left ventricular angiography is infrequently used in ACS because of the widespread use of echocardiograms or bedside point-of-care ultrasounds. However, when urgent angiography occurs before noninvasive studies can be performed, measurement of left ventricular end-diastolic pressure and left ventricular angiography will enable more timely assessment of ventricular function. This is especially important in patients with MINOCA because identification of focal wall motion abnormalities can prompt a more thorough review of the coronary angiogram to assess for missed “flush occlusions” or to identify other MINOCA mimics such as takotsubo syndrome.

Invasive Physiology or Provocative Testing

Coronary artery spasm (epicardial or microvascular) is a common mechanism of MINOCA, with some degree of coronary spasm present in up to 70% of cases.$^{9}$ CMD

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frequently coexists with coronary spasm,$^{18}$ although the prevalence of CMD in the setting of MINOCA has been difficult to establish because myocardial injury itself causes dysfunction of the coronary microvasculature.$^{60}$ A diagnosis of coronary spasm involves provocative testing in the catheterization laboratory with intracoronary administration of acetylcholine or ergonovine and testing for CMD by measuring coronary flow reserve with thermodilution or Doppler before and after administration of a vasodilator. Although studies have suggested that provocative/invasive testing can be performed at the time of ACS with relative safety,$^{61}$ in reality, these studies are often performed later. Understandably, there is a reluctance in attempting to provoke spasm in the setting of an ACS for fear that this might trigger or worsen the causative problem. Logistic considerations, including the availability of provocative/invasive testing or the practicality of performing these tests if catheterization is done after hours, may also preclude such testing. When feasible, we suggest proceeding with provocative spasm studies at the time of the angiography for ACS when there is a high index of suspicion such as in patients with recurrent MINOCA who are hemodynamically stable. Otherwise, provocative testing should be considered to be undertaken as a separate, elective procedure.

Consideration for Revascularization in SCAD

Current guidelines and scientific statements recommend an initial conservative approach for the management of SCAD unless there are high-risk features such as ongoing ischemia typically with dynamic electrocardiographic changes or persistent troponin elevation, left main dissection, or electrical or hemodynamic instability.$^{5,25,6,63}$ These recommendations are based on the premise that SCAD usually heals spontaneously$^{64}$ and that revascularization is associated with high failure rates and increased complication risks.$^{5,25,6,63}$ If revascularization is warranted, PCI is preferred, and coronary artery bypass grafting (CABG) is generally reserved for PCI failure, extensive SCAD (≥100-mm length), multivessel SCAD involving ≥2 proximal vessels, or left main involvement.$^{65}$ In CanSCAD (Canadian SCAD Cohort Study), only 0.7% of the 750 patients with SCAD required CABG.$^{66}$ Figure 3 outlines a recommended approach when revascularization for SCAD is considered.$^{67}$

The aims of PCI for SCAD are to scaffold the dissection and to improve distal coronary flow until the dissection has healed. PCI can be technically challenging with success rates ranging from 47% to 91%$^{63}$ and a high risk of complications, including iatrogenic catheter-induced coronary artery dissection and propagation of dissection or intramural hematoma with wiring, angioplasty, or stenting. If stenting is required, the dissected segments are often extensive, requiring long stents that can increase the risk for restenosis and stent thrombosis. In the CanSCAD study, TIMI flow improved in 57.6%,

remained unchanged in 38.8%, and worsened in 3.9% with PCI, with propagation of dissection in one-third of cases and a PCI failure rate of 30.1%.$^{66,68}$

When PCI is performed, advancing the coronary guide-wire into the true lumen may be challenging, especially with a dissected intima (type 1 SCAD). If the true lumen cannot be wired, the procedure should probably be abandoned unless the operator is skilled with reentry techniques. After successful wiring, the potential PCI strategy depends on the lesion characteristics (Figure 3).$^{69}$ In less extensive dissections, direct stenting may be contem-plated, but the stent length should cover ≥5 mm proximal and distal to the dissection edges to minimize propagation of intramural hematoma. In most other cases, angioplasty (with standard or cutting balloons) is necessary with low-pressure inflations, followed by stenting as indicated. Several case series showed good success with the use of cutting balloons with SCAD.$^{70}$,$^{71}$ We suggest using short cutting balloons (6–10 mm) inflated to low pressures (4 atm) to fenestrate the false lumen and to debulk the intramural hematoma. To minimize perforation risk, the recommended balloon diameter would be ≈0.5 mm smaller than the vessel diameter.$^{71}$ If a longer segment of artery needs treating, shorter proximal and distal stents may first be placed at just beyond the dissection edges to limit propagation of the intramural hematoma before the middle segment is stented $^{69}$. Stent underexpansion can be problematic; subsequent resorption of the intramural hematoma can lead to late stent malapposition.$^{72}$ Intracoronary imaging may aid stent sizing and length; however, in 1 series, intracoronary imaging was associated with an 6,6% complication rate$^{73}$ and therefore should be performed sparingly and carefully during PCI for SCAD. Given all of these challenges with PCI for SCAD, we again emphasize that conservative management is strongly preferred in stable patients with SCAD without high-risk features.$^{5}$,$^{25}$,$^{62}$,$^{63}$

CABG has inherent limitations; anastomoses to frail and dissected coronary segments are challenging and may not reliably hold sutures, and competitive flow after healing of the SCAD artery can decrease graft patency.$^{63}$,$^{74}$ Grafts should be placed distal to the dissection when feasible, although distal targets may be limited by vessel caliber, spasm, or dissection extent. True lumen entry must be confirmed visually; the arteriotomy should be placed at the most technically favorable site, with meticulous reapproximation of vessel layers into the anastomosis. Ligation of the native vessel is generally undesirable because healing often restores native flow and ligation risks full dependency on the graft. Saphe-nous vein grafts provide immediate high flow and are reasonable in unstable patients, whereas internal thoracic artery grafts are preferred because of their superior long-term patency. Despite technical challenges, successful revascularization of primary vessels is typically achieved.$^{74}$,$^{75}$

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![graph TD\n A1[SCAD diagnosis] --> A2[High-risk features?]\n A2 -->|No| A3[Stop]\n A2 -->|Yes| A4[Consider revascularization]\n A4 --> A5[Left main coronary artery involvement]\n A4 --> A6[No left main coronary artery involvement]\n A5 --> A7[CABG]\n A5 --> A8[PCI only if: • Emergency CABG not available • Cardiogenic shock, VT/VF • Technically feasible • (especially if not involving bifurcation)]\n A6 -->|PCI if feasible Very careful wiring(esp type 1)| A9[Wired distal true lumen?]\n A9 -->|Yes| A10[Angiographic SCAD]\n A9 -->|Uncertain| A11[OCT/IVUS]\n A9 -->|No| A12[Stop]\n A10 --> A13[Type 1]\n A10 --> A14[Type 3]\n A10 --> A15[Type 2A]\n A10 --> A16[Type 2B]\n A11 -->|Or check with OTW balloon| A10\n A13 --> A17[Can cover with single stent(≥5 mm edges)?]\n A14 --> A17\n A15 --> A17\n A16 --> A18[1. Cutting balloon±prox stent* 2. POBA±stent* 3. Stent proximal(if ostial LAD/LCx)]\n A17 -->|No| A19[POBA±stent* Any sequence of stents]\n A17 -->|Yes| A20[Direct stent +/- predilation(CB/POBA)]\n A17 -->|Yes| A20\n A17 -->|No| A21[1. Cutting balloon±prox stent* 2. POBA±stent* 3. Stent edges first, then middle 3. Stent proximal(if ostial LAD/LCx)]\n A21 -->|*Can avoid stenting especially if normal flow+no residual dissection| A22[Stop]\n](1/parseimages/figureaed03fb4f0564e66ac3efc4e25b13be1_0_3.png) Figure 3. Algorithm for management and revascularization in SCAD.

The figure provides a sequential approach for managing spontaneous coronary artery dissection (SCAD) and when to perform percutaneous coronary intervention (PCI), intravascular imaging, or both. CABG indicates coronary artery bypass grafting; CB, cutting balloon; IVUS, intravascular ultrasound; LAD, left anterior descending coronary artery; LCx, left circumflex coronary artery; OCT, optical coherence tomography; OTW, over the wire; POBA, plain old balloon angioplasty; VF, ventricular fibrillation; and VT, ventricular tachycardia. Adapted with permission from Saw$^{67}$; permission conveyed through Copyright Clearance Center.

Considerations for CABG in Atherosclerotic Disease

Younger women undergoing CABG for atherosclerotic CAD represent a unique population. Although surgical

revascularization is effective, compared with older patients and men, younger women face higher risks of MI and repeat revascularization after CABG. These inferior outcomes in younger women after CABG may in part reflect technical challenges related to smaller,

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more spastic coronary arteries and grafts and a lack of rigorously implemented guideline-directed medical therapy.$^{76,77}$

Angiography and Revascularization Considerations for the Pregnant Patient

MI during pregnancy requires a multidisciplinary team involving cardiology, maternal-fetal medicine, and obstetrics to address key issues such as minimizing fetal radiation exposure during diagnostic testing and medical therapy risks and benefits to mother and fetus. Shared decision-making with patients is of paramount importance.

Observational data indicate that women with MI in pregnancy or soon after delivery who are treated invasively have better outcomes than those not undergoing angiography, yet only about half of such patients receive invasive management.$^{49}$ Nevertheless, there are inevitably great concerns about the radiation risks to the fetus and young pregnant women referred for coronary angiography. For this reason, a multidisciplinary team that includes an interventional cardiologist is critical.$^{78}$ The informed consent process should review the risks and benefits of invasive coronary angiography and the dangers of radiation exposure.$^{79}$ Potential risks to the fetus include intrauterine growth retardation, spontaneous abortion, congenital malformations, and increased risk of childhood cancer.$^{79,80}$ Radiation vulnerability of the fetus is highest during the first trimester of pregnancy.$^{80}$ The principles put forth by the Nuclear Regulatory Commission emphasizing that radiation dose exposure should be kept as low as reasonably achievable become particularly important in pregnant women. It is recommended that radiation exposure to the fetus should not exceed 5 mSv during the entire pregnancy or 0.5 mSv per month of pregnancy, which is equivalent to ≈50 adult chest x-rays for the entire pregnancy or 5 adult chest x-rays per month.$^{79}$ Reducing x-ray time and use of selective shielding should be adhered to.$^{81}$ Several techniques to reduce radiation dose exposure are outlined in Table 2.$^{81-84}$

Many of the medications used during cardiac catheterization and PCI are safe in pregnancy,$^{78}$ and a full review of the safety of cardiac medications in pregnancy and lactation has been published.$^{85}$ Although heparin is safe and the preferred anticoagulant, therapeutic activated clotting time monitoring for intravenous heparin is important given the hypercoagulable state of pregnancy, and supratherapeutic levels of anticoagulation should be avoided. Low-dose aspirin is generally safe in pregnancy and is recommended beginning in the second trimester for patients at high risk of pre-eclampsia.$^{78,86,87}$ Clopidogrel has not been shown to have adverse effects in animal models and is the preferred P2Y12 inhibitor for pregnant women.$^{22,78}$ There are limited data on the safety of the more potent P2Y12 inhibitors, including ticagrelor, prosagrel, and

|Techniques to reduce radiation exposure|References| |---|---| |Avoid including the fetus/uterus in the x-ray beam, including by the use of abdominal shielding|Dauer et $al^{82}$| |Minimize fluoroscopy time|Biso and $Vidovich^{83}$| |Keep the fluoroscopy frame rate as low as possible (7.5 frames/s)|$Marx^{84}$| |Use fluoro save instead of cine save for spot digital image acquisition|$Marx^{84}$| |Minimize the use of boost mode or override mode|Biso and $Vidovich^{83}$| |Use low-dose-per-frame and low-pulse-rate fluoroscopy|Biso and $Vidovich^{83}$| |Use collimation to reduce the area exposed to the radiation beam and to decrease scatter radiation|Toma et $al^{81}$ Biso and $Vidovich^{83}$ and $Marx^{84}$| |Table positioning: Keep the fluoroscopy table far away from the x-ray source to minimize the entrance dose to the skin and to keep the image intensifier close to the patient|Dauer et $al^{82}$|

In addition, although not related to radiation exposure, as much as is reasonably possible, heavily gravid women should be kept in a partial left lateral position during angiography.

cangrelor, in pregnancy. Similarly, glycoprotein IIb/IIIa inhibitors should be avoided or used with caution.$^{22}$ In addition, iodinated contrast media can cross the placenta and potentially cause thyroid function suppres- sion in fetus.$^{78}$ A key additional consideration is that the previous comments on the safety of medications in pregnancy generally refer to the potential for causing abnormal fetal development or teratogenicity. Bleeding risks to the mother and fetus must also be considered, particularly at the time of delivery and including the risk of postpartum hemorrhage. Moreover, a healthy mother is integral to a healthy fetus and newborn, and the risks to the mother of both starting and withholding medica- tions must be carefully balanced against other compet- ing factors.

Angiography and Revascularization

Considerations for Breastfeeding Women With ACS

There are unique considerations for breastfeeding women presenting with ACS, and the involvement of an appropriate multidisciplinary team, likely including a lactation consultant and pharmacist, is again critical. It is important to note that iodinated contrast agents used in angiography are minimally excreted in breast milk and are poorly absorbed by the infant's gut, making them relatively safe and allowing breastfeeding to continue.$^{88}$ Early resumption of breastfeeding after the procedure is generally recommended, assuming that the patient is hemodynamically stable and there are no medical contraindications. Heparin and low-molecular-weight heparin either are not excreted in breast milk or are secreted

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in small amounts, and no special precautions are required.$^{99}$ Further information about other medications during breastfeeding is provided in the subsequent section about medical therapies. Shared decision-making for breastfeeding mothers with ACS is critical, particularly for decisions that balance infant exposure and maternal risk.

MEDICAL THERAPIES AND MANAGING RISK FACTORS

Cardiovascular Risk Factors

Young women presenting with acute MI due to atherosclerotic CAD have a high prevalence of cardiometabolic comorbidities. Compared with their male counterparts, they are more likely to have ≥3 cardiovascular risk factors, including diabetes, hypertension, hypercholesterolemia, smoking, and obesity, as well as a history of cancer, autoimmune disorders, and psychiatric disorders.$^{1,90}$ Cigarette smoking is a particularly strong risk factor, increasing the risk of MI 7-fold, and is a leading cause of MI in women <55 years of age, to an even greater degree than in older women with MI. Smoking cessation should be emphasized at every clinical encounter because the cardiovascular risk declines significantly within 1 to 2 years of quitting and approximates that of nonsmokers within 10 to 15 years.$^{91}$ Hypertension, diabetes, obesity, and smoking confer a higher relative risk of cardiovascular disease in women compared with men.$^{92}$ Risk factor prevalence is particularly high among Black women, who also have a higher risk of recurrent MI than White women.$^{93}$ The prevalence of traditional risk factors is on the rise among young women with MI, with variation by racial and ethnic group.$^{94}$ Adverse pregnancy outcomes, particularly preeclampsia, are also independently associated with increased cardiovascular risk: Women with preeclampsia are at 2-fold higher risk of MI within the decade after delivery,$^{95}$ with even higher risk in women with preterm preeclampsia (<34 weeks).$^{96}$ The fetus and newborns of mothers with adverse pregnancy outcomes may also be at increased risk of adverse outcomes, including placental abruption, preterm birth, and growth restriction, and early involvement of a neonatal pediatrician may be advisable.

cardiovascular risk declines significantly within 1 to 2 years of quitting and approximates that of nonsmokers within 10 to 15 years.$^{91}$ Hypertension, diabetes, obesity, and smoking confer a higher relative risk of cardiovascular disease in women compared with men.$^{92}$ Risk factor prevalence is particularly high among Black women, who also have a higher risk of recurrent MI than White women.$^{93}$ The prevalence of traditional risk factors is on the rise among young women with MI, with variation by racial and ethnic group.$^{94}$ Adverse pregnancy outcomes, particularly preeclampsia, are also independently associated with increased cardiovascular risk: Women with preeclampsia are at 2-fold higher risk of MI within the decade after delivery,$^{95}$ with even higher risk in women with preterm preeclampsia (<34 weeks).$^{96}$ The fetus and newborns of mothers with adverse pregnancy outcomes may also be at increased risk of adverse outcomes, including placental abruption, preterm birth, and growth restriction, and early involvement of a neonatal pediatrician may be advisable.

in human presenting with acute MI due to atherosclerotic CAD have a high prevalence of cardiometabolic comorbidities. Compared with their male counterparts, they are more likely to have ≥3 cardiovascular risk factors, including diabetes, hypertension, hypercholeterolemia, smoking, and obesity, as well as a history of cancer, autoimmune disorders, and psychiatric disorders.$^{1,92}$ Cigarette smoking is a particularly strong risk factor, increasing the risk of MI 7-fold, and is a leading cause of MI in women <55 years of age, to an even greater degree than in older women with MI. Smoking cessation should be emphasized at every clinical encounter because the cardiovascular risk declines significantly within 1 to 2 years of quitting and approximates that of nonsmokers within 10 to 15 years.$^{91}$ Hypertension, diabetes, obesity, and smoking confer a higher relative risk of cardiovascular disease is compared with men.$^{92}$ Risk factor prevalence is particularly high among Black women, who also have a higher risk of recurrent MI than White women.$^{93}$ The prevalence of traditional risk factors is on the rise among young women with MI, with variation by racial and ethnic group.$^{94}$ Adverse pregnancy outcomes, particularly preeclampsia, are also independently associated with increased cardiovascular risk: Women with preeclampsia are at 2-fold higher risk of MI within the decade after delivery,$^{95}$ with even higher risk in women with preterm preeclampsia (<34 weeks).$^{96}$ The fetus and newborns of mothers with adverse pregnancy outcomes may also be at increased risk of adverse outcomes, including placental abruption, preterm birth, and growth restriction, and early involvement of a neonatal pediatrician may be advisable.

Risk assessment in young women should extend beyond traditional factors to consider pregnancy history, familial hypercholesterolemia, lipoprotein(a), and C-reactive protein. Genetic testing to assess risk may also be considered.$^{97-99}$ Diagnosing familial hypercholesterolemia or elevated lipoprotein(a) has implications not only for the management of the patient but also for family members. Elevated C-reactive protein is an independent predictor of cardiovascular risk in women$^{100}$ with an evolving landscape of potential therapeutic targets.

Medical Management of Risk Factors and Other Additional Therapies After ACS

Given the long-term risk of recurrent events, young women should be aggressively treated for secondary prevention. However, the reality is that young women are less likely than young men to receive guideline-directed medical therapy after MI, including lipid-lowering treatment, β-blockers, and nonaspirin antiplatelet agents, the last perhaps related to lower rates of coronary revascularization among women. According to recent trials, β-blockers should likely be reserved for women with MI who have reduced left ventricular ejection fraction.$^{101,102}$ This treatment gap persists across MI subtypes (non-ST-segment-elevation ACS and STEMI) and has shown no significant improvement over several decades (1995–2014).$^{1}$

Current American Heart Association/American College of Cardiology guidelines for ACS recommend aggressive treatment with maximally tolerated high-intensity statin therapy and the addition of nonstatin lipid-lowering therapies if patients cannot achieve a low-density lipoprotein (LDL) target of <70 mg/dL on maximally tolerated statins.$^{39}$ In patients with LDL levels between 55 and 69 mg/dL despite maximally tolerated statins, further intensification of therapies is reasonable.$^{39}$ Similarly, current European Society of Cardiology guidelines recommend an LDL target of <55 mg/dL.$^{97,103}$ In young patients with MI attributable to atherosclerotic CAD, a lower LDL target should be considered given their longer exposure to risk and potential for sustained benefit from aggressive lipid lowering across the life span. Management of hypertension by addressing lifestyle factors and pharmacotherapy is essential, and young women may benefit from lower cutoff targets for blood pressure management if tolerated.$^{87,104}$

Treatment after ACS should be tailored to the underlying cause. Women with SCAD may not benefit from conventional secondary prevention therapy with statins.$^{5}$ The optimal antiplatelet regimen after SCAD is an area of active investigation. However, the use of aspirin in combination with the more potent P2Y12 inhibitors (ticagrelor, prasugrel) should likely be avoided.$^{105}$ On the other hand, β-blockers have been associated with reduced risk of recurrent SCAD in observational studies and, pending dedicated clinical trials in patients with SCAD,$^{106}$ should be considered in every patient.$^{107}$ MINOCA is due to various underlying causes, most commonly atherothrombosis or coronary spasm, and requires additional diagnostic testing to guide treatment.$^{9}$ We treat women with MINOCA in whom additional testing has not been performed with antiplatelet therapy, statins, angiotensin-converting enzyme inhibitors, and calcium channel blockers if blood pressure allows.

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Considerations for Medical Therapies and Risk Factor Management During Pregnancy and Lactation

ACS during pregnancy is a high-risk scenario that requires intensive management with a dedicated multidisciplinary team and shared decision-making to address issues that may include delivery planning, particular management of antiplatelet therapy during delivery, and medical therapy risks versus benefits for mother and baby (see prior section on angiography and revascularization during pregnancy and lactation). In terms of specific medication use, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are contradicated in pregnancy because of the risk of fetal toxicity and congenital malformations,$^{87}$ especially in the last part of pregnancy, but certain angiotensin-converting enzyme inhibitors, specifically captopil, benzaseil, and enalapril, can be initiated during breastfeeding.$^{85}$ With respect to statins, the US Food and Drug Administration removed the pregnancy-related black box warning in 2021, and their use may be considered during pregnancy in high-risk patients such as those with ACS due to atherosclerosis.$^{108}$ However, the same US Food and Drug Administration recommendations state that statins are contraindicated during lactation, and they should be suspended until breastfeeding ends, or if on-going statin treatment is required, then women should not breastfeed and instead use infant formula or other alternatives. An important additional consideration is that stopping and (re)starting statins may add risk resulting from high maternal cholesterol exposure, even if this increased exposure is only for several months of pregnancy or breastfeeding.$^{108}$ Lipoprotein apheresis is another option for LDL lowering in pregnancy for those with homozygous familial hypercholesterolemia.$^{109}$ A recent statement addressed assisted reproductive therapy in high-risk women.$^{110}$

Other Special Issues

Contraception counseling is critical because of the teratogenicity of several cardiac medications (particularly angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), importance of avoiding unpanned pregnancy, and avoidance of estrogen-based contraceptives when there is concern about thrombosis risk.$^{111}$ Health care professionals should counsel patients that the annual risk of unintended pregnancy without contraception exceeds 85%.$^{112}$ Future pregnancies require a cardio-obstetrics team discussion about timing, management of cardiovascular medications, and risks of pregnancy for those with persistent left ventricular dysfunction.

Given that contraceptives containing estrogen are associated with increased rates of thrombosis, an

intrauterine device or other progestin-only option may be considered. Comanagement with the primary care professionals and gynecologist is advised. Long-acting reversible contraception is an attractive contraceptive modality for premenopausal women after MI, as is vasectomy if the partner is agreeable. Copper intrauterine devices, unlike hormonal intrauterine devices, have been linked to bleeding concerns,$^{113}$ which may be particularly relevant for premenopausal women on dual antiplatelet therapy.

Women with ACS, particularly those with SCAD, often report a higher baseline prevalence of migraine headaches, which can limit nitrate use because of headache exacerbation. In such cases, counseling on the gradual tolerance to nitrates or the use of transdermal nitroglycer patches may be helpful when nitrates are needed for recurrent chest pain.$^{114}$ Alternatively, propranolol can be considered for β-blocker therapy after SCAD because of its efficacy as a preventive therapy for migraines.

OTHER ASPECTS OF HOSPITAL MANAGEMENT

Hospitalization for ACS offers a critical opportunity to optimize long-term cardiovascular care. This period should be leveraged for appropriate diagnostic evaluation, initiation of guideline-directed medical therapy, individualized education, early introduction of mental health support, and establishment of a comprehensive follow-up plan. The inpatient hospitalization phase should be seen not only as a time for acute management but also as a crucial time for secondary prevention counseling and to initiate preventive strategies, to engage in multidisciplinary care, to discuss implications of any current or potential future pregnancies, and to empower young women with knowledge and tools to manage their cardiovascular health. Furthermore, depending on the underlying cause and clinical context, consideration of referral for genetic evaluation for conditions such as familial hypercholes-terolemia or monogenic arteriopathies associated with SCAD (vascular Ehlers-Danlos syndrome)$^{115}$ may be appropriate.

For women presenting with MINOCA, further evaluation of the underlying cause (Table 1) is necessary to guide treatment.$^{116}$ Early use of cMRI$^{117}$ is a Class I guideline recommendation because it can enhance diagnostic certainty before discharge and has important implications for both immediate and long-term management.$^{118}$ Although gadolinium contrast is generally contraindicated in pregnancy, the use of cMRI is otherwise especially important for women of childbearing age for whom diagnostic clarity informs preconception counseling, risk-benefit discussions, and planning for future pregnancies.

For women diagnosed with SCAD, additional vascular screening is recommended because of the

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association with fibromuscular dysplasia and other arteriopathies.$^{5,25,63}$ Head-to-pelvis imaging with either computed tomographic or magnetic resonance angiography (less preferred because of lower resolution) should be performed to assess for extracoronary vascular abnormalities, ideally during the initial hospitalization to ensure completion and to guide follow-up care. For pregnant patients, screening for fibromuscular dysplasia is often deferred until after delivery because, as mentioned, gadolinium contrast is generally contraindicated in pregnancy for magnetic resonance angiography, and computed tomographic angiography is associated with radiation risk to the fetus.

For women diagnosed with takotsubo syndrome, cMRI is useful because it may identify an alternative diagnosis such as MI or a predisposing condition such as hypertrophic cardiomyopathy.$^{119,120}$

CARDIAC REHABILITATION

Cardiac rehabilitation (CR) improves mortality after MI in both women and men; however, the risk reduction is more pronounced in women, as reviewed in a recent American Heart Association statement.$^{121,122}$ Premeno-pausal women may be particularly likely to benefit from CR given that young women are less active after MI than young men.$^{123}$ CR has been shown to be beneficial for both sexes after MI from atherosclerotic CAD, but CR has also shown benefit in a number of cardiac disorders that disproportionately affect women, including CMD$^{124-126}$ and after SCAD.$^{127}$ Despite evidence demonstrating the benefit of CR in improving cardiovascular risk factors, decreasing hospital readmission, improving quality of life, and improving mortality, women are less likely than men to be referred for$^{128}$ and to complete CR.$^{129}$

Compared with women >55 years of age, before initiating CR, young women (≤55 years of age) have worse health perceptions; report worse quality of life; perceive less social support and more stress related to family, work, finances, and health; and report greater symptoms

of anxiety and depression.$^{130}$ Furthermore, compared with women who complete CR, those who do not complete 36 sessions are more likely to be younger (≤55 years of age) with a higher prevalence of uncontrolled cardiovascular risk factors and poorer baseline psycho-social characteristics.$^{130}$ These adverse physiological and psychosocial findings in younger women place them at higher risk for further cardiovascular events and highlight the need to address barriers that are both sex and age specific.

A number of barriers account for the lower rates of referral, use, and completion of CR by women, and several key recommendations have been proposed to address these barriers: increasing the awareness of the benefits of CR among patients; using automatic referral systems; expanding access by enhancing accessibility through flexible CR schedules to accommodate working or caregiving hours; implementing gender-sensitive and culturally sensitive programming; providing tailored support to meet the emotional and social needs of women and consideration of the unique diagnoses such as SCAD and MINOCA; and supporting research that explores nontraditional CR models such as virtual delivery models.$^{122}$

MANAGEMENT OF POST-ACS DEPRESSION AND ANXIETY

Depression is a risk factor for adverse outcomes in patients with ACS.$^{131}$ Evidence has continued to mount that there is a significant, likely bidirectional, relationship between anxiety, depression, and cardiovascular disease that is driven by multiple biological (eg, genetic, hypothalamic-pituitary-adrenal axis, limbic system, inflammatory, hormonal), psychological, and sociodemographic factors.$^{132-134}$ Indeed, socioeconomic and sociodemographic factors are likely to be particularly important in premenopausal women with ACS.$^{135}$ Anxiety and depression are common in women after ACS,$^{136,137}$ and patients with depression after ACS are

![graph TD\n A1[Screening] --> A2[Diagnosis]\n A2 --> A3[Treatment]\n A3 --> A4[Re-Assessment]\n](1/parseimages/figuree07a9ad0419540ab81ea89c242fe368b_0_12.png) ACS indicates acute coronary syndrome; BDI-II, Beck Depression Inventory-II; CBT, Cognitive Behavioral Therapy; GDS, Geriatric Depression Scale; HADS, Hospital Anxiety and Depression Scale; PHO-9, Patient Health Questionnaire-9; and SSRI, selective serotonin reuptake inhibitor.

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|Inclusion of premenopausal women in clinical trials| |---| |Identify and implement strategies to increase participation of women in clinical trials, including premenopausal women, across the spectrum of CVD, including $ACS^{150}$| |Primary prevention| |Understand and implement ways to address risk factors and to prevent ACS in premenopausal women, including those who may go on to pregnancy Understand and intervene to reduce the impact of female-specific risk factors (eg, preeclampsia, premature menopause) Institute policy measures to address social determinants of health that increase the risk of and from ACS in premenopausal women| |Diagnostic strategies| |Provide randomized evidence comparing CCTA with invasive angiography in medically stable premenopausal women with suspected ACS Establish sex-specific reference values for intracoronary imaging to improve diagnostic accuracy in women Compare and identify the optimal diagnostic algorithm for premenopausal women with MINOCA Identify how best to monitor young women with post-ACS chest pain| |Therapeutic strategies and secondary prevention| |Compare early and late outcomes for revascularization (by PCI or CABG) and a conservative strategy (medical therapy only) in complex SCAD Investigate the optimal duration of antiplatelet therapy after ACS in women vs men, noting that this will require separate studies for atherosclerotic obstructive ACS, SCAD, MINOCA, and coronary spasm Evaluate the efficacy and safety of secondary preventive therapies after SCAD and MINOCA Investigate the effect of anti-inflammatory therapies on plaque progression and cardiovascular risk in premenopausal women| |Pregnancy and ACS| |Provide evidence for the short- and longer-term management of MI during pregnancy Establish protocols to minimize maternal and fetal radiation exposure during cardiac catheterization in pregnancy| |Mental health and recovery| |Determine the best methods to increase referral to and completion of CR in young women with ACS, including tailoring to the needs and preferences of young women Assess sex-specific responses to pharmacological and behavioral interventions for post-ACS depression and anxiety Investigate whether the effectiveness of mental health interventions varies by ACS subtype| |ACS indicates acute coronary syndrome; CABG, coronary artery bypass grafting; CCTA, coronary computed tomographic angiography; CR, cardiac rehabilitation; CVD, cardiovascular disease; MI, myocardial infarction; MINOCA, myocardial infarction with no obstructive coronary arteries; PCI, percutaneous coronary intervention; and SCAD, spontaneous coronary artery dissection.| |at higher risk of rehospitalization.$^{138}$ According to meta-analytic data, ≈38% of women experience depression after ACS compared with 30% of men, both higher than the population prevalence.$^{136}$ Screening for anxiety and depression is important after ACS$^{132,139}$ and is often integrated into CR programs,$^{132}$ but there is variation in the timing and method of screening, and the ideal|

ACS indicates acute coronary syndrome; CABG, coronary artery bypass grafting; CCTA, coronary computed tomographic angiography; CR, cardiac rehabilitation; CVD, cardiovascular disease; MI, myocardial infarction; MINOCA, myocardial infarction with no obstructive coronary arteries; PCI, percutaneous coronary intervention; and SCAD, spontaneous coronary artery dissection.

at higher risk of rehospitalization.$^{138}$ According to meta-analytic data, ≈38% of women experience depression after ACS compared with 30% of men, both higher than the population prevalence.$^{136}$ Screening for anxiety and depression is important after ACS$^{132}$,$^{139}$ and is often integrated into CR programs,$^{132}$ but there is variation in the timing and method of screening, and the ideal

timing is uncertain.$^{140}$ A 2017 systematic review found that the Beck Depression Inventory-II has the strongest evidence for use in patients after ACS.$^{141}$ However, other scores also appear to perform adequately, including the Patient Health Questionnaire-2 and -9, the Hospital Anxiety and Depression Scale, and the Geriatric Depression Scale.$^{141}$

Systematic reviews support the effectiveness of pharmacological (eg, antidepressants) and psychological (eg, cognitive behavioral therapy) therapies at reducing depressive symptoms and anxiety in patients with cardiovascular disease,$^{142,143}$ including ACS.$^{141}$ A combination of the two may be superior.$^{141}$ A recent retrospective cohort study supported the efficacy of psychotherapy and antidepressants in reducing hospitalizations and ED visits for patients with ischemic heart disease.$^{144}$ However, it remains unclear whether treating depression after ACS reduces major adverse cardiovascular events and improves cardiovascular health, and more robust trials are needed.$^{145}$ Generally, selective serotonin reuptake inhibitors are used as first-line therapy for anxiety and depression, and tricyclic antidepressants should be avoided given their various adverse cardiovascular effects.$^{146}$ The EsDEPACS randomized controlled trial (Escitalopram for Depression in Acute Coronary Syndrome) found that 24 weeks of treatment with escitalopram, a selective serotonin reuptake inhibitor, reduced the risk of major adverse cardiovascular events compared with placebo after ACS (hazard ratio, 0.69; P=0.03) based on a median 8.1 years of follow-up.$^{147}$ Exercise, including CR,$^{139}$ is also associated with a reduction in depressive symptoms and anxiety, especially when coupled with cognitive therapy.$^{148}$ A team-based approach to the management of anxiety and depression is important.$^{132}$ Open dialog between clinicians and patients about anxiety and depression symptoms is critical, and individual psychological stressors$^{133}$ and social determinants of health$^{149}$ require attention to address underlying contributors to these problems. A proposed management pathway for the screening, diagnosis, treatment, and further management of depression and anxiety in premenopausal women with ACS is provided in Figure 4.

FUTURE DIRECTIONS

Although the potential research that needs to be conducted in this area is vast, we suggest several key unresolved questions and areas for near-term focused research efforts in Table 3.$^{150}$

CONCLUSIONS

The management of ACS in premenopausal women presentes numerous unique challenges. The facts that many of the relevant causes of ACS in premenopausal women are

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seen less commonly than atherosclerotic CAD in general and that there is a corresponding lack of robust clinical data unfortunately mean that clinicians are less certain about the optimal diagnostic and management pathways. Indeed, specific pathways for premenopausal women with ACS have not yet been developed, an issue that this scientific statement has sought to address.

We trust that this scientific statement serves as a useful guide for clinicians managing premenopausal women with ACS but also as an urgent call to action to drive further research and to address the poorer outcomes that are often seen in these young patients.

ARTICLE INFORMATION

The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on December 8, 2025, and the

American Heart Association Executive Committee on January 26, 2026. A copy of the document is available at https://professional.heart.org/state-ments by using either "Search for Guidelines & Statements" or the "Browse by Topic" area. To purchase additional reprints, call 215-356-2721 or email Meredith.Edelman@wolterskuwer.com

The American Heart Association requests that this document be cited as follows: Kovacic JC, Reynolds HR, Alasnag M, Blakeman JR, Ijioma NN, Kim ESH, Sandner S, Sanghavi M, Saw J, Tamis-Holland JE; on behalf of the American Heart Association Cardiovascular Interventions Committee of the Council on Clinical Cardiology and the Women's Health Science Committee of the Council on Clinical Cardiology and Stroke Council; Council on Cardiovascular Surgery and Anes-thesia; Council on Lifelong Congenital Heart Disease and Heart Health in the Young; and Council on Quality of Care and Outcomes Research. Acute coro-nary syndromes in premenopausal women: a scientific statement from the American Heart Association. Circulation. 2026;153:e***-e***. doi: 10.1161/CIR.0000000000001416

The expert peer review of AHA-commissioned documents (eg, scientific statements, clinical practice guidelines, systematic reviews) is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit https://professional.heart.org/statements. Select the "Guidelines & Statements" drop-down menu, then click "Publication Development".

Permissions: Multiple copies, modification, alteration, enhancement, and distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at https://www.heartorg/pemissions. A link to the "Copyright Permissions Request Form" appears in the second paragraph (https://www.heartorg/en/about-us/statements-and-policies/copyright-request-form).

Disclosures

Writing Group Disclosures

|Writing group member|Employment|Research grant|Other research support|Speakers bureau/honoraria|Expert witness|Ownership interest|Consultant/ advisory board|Other| |---|---|---|---|---|---|---|---|---| |Jason C. Kovacic|Victor Chang Cardiac Research Institute (Australia)|None|None|None|None|None|None|None| |Harmony R. Reynolds|New York University Grossman School of Medicine|None|None|None|None|None|Heartflow*|None| |Mirvat Alasnag|King Fahd Armed Forces (Saudi Arabia)|None|None|None|None|None|None|None| |John R. Blakeman|Illinois State University Mennonite College of Nursing|None|None|None|None|None|None|None| |Nkechinyere N. Ijioma|Davis Heart and Lung Research Institute, The Ohio State University|None|None|None|None|None|None|None| |Esther S.H. Kim|Atrium Health|None|None|None|None|None|None|None| |Sigrid Sandner|Medical University of Vienna (Austria)|None|None|None|None|None|None|None| |Monika Sanghavi|University of Pennsylvania School of Medicine|None|None|None|None|None|None|None| |Jacqueline Saw|Vancouver General Hospital (Canada)|None|None|Boston Scientific*; Abbott*|None|None|Abbott*; Boston Scientific*|None| |Jacqueline E. Tamis-Holland|Cleveland Clinic|None|None|None|None|None|None|None|

This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be "significant" if (a) the person receives $5000 or more during any 12-month period, or 5% or more of the person's gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $5000 or more of the fair market value of the entity. A relationship is considered to be "modest" if it is less than "significant" under the preceding definition. *Modest.

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Reviewer Disclosures

|Reviewer|Employment|Research grant|Other research support|Speakers' bureau/ honoraria|Expert witness|Ownership interest|Consultant/advisory board|Other| |---|---|---|---|---|---|---|---|---| |Colin Berry|University of Glasgow (United Kingdom)|British Heart Foundation (academic work relevant to subject area)†|Abbott Vascular, AskBio, AstraZeneca, Boehringer Ingelheim, CorFlow, Edwards Lifesciences, Merck, Servier, Novartis, Xylocor, Zoll Medical (Colin Berry is employed by the University of Glasgow, which holds consultancy and research agreements.)†|None|None|None|Abbott Vascular, AskBio, AstraZeneca, Boehringer Ingelheim, CorFlow, Edwards Lifesciences, Merck, Servier, Novartis, Xylocor, Zoll Medical*|None| |Rina Mauricio|University of Texas Southwestern|None|None|None|None|None|None|None| |C. Noel Bairey Merz|Cedars-Sinai Smidt Heart Institute|None|None|None|None|None|None|None| |Elizabeth D. Paratz|St Vincent's Institute of Medical Research (Australia)|None|None|None|None|None|None|None| |Nanette Kass Wenger|Emory University School of Medicine|None|None|None|None|None|None|None|

This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be "significant" if (a) the person receives $5000 or more during any 12-month period, or 5% or more of the person's gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $5000 or more of the fair market value of the entity. A relationship is considered to be "modest" if it is less than "significant" under the preceding definition. Association. *Modest.

*Modest.

†Significant.

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