Cardionerds: A Cardiology Podcast

This episode is part of our comprehensive Decipher the Guidelines Series covering the 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes. The following question refers to Section 8.2 of the 2025 ACS Guidelines. The question is asked by Johns Hopkins pre-medical undergraduate and CardioNerds Academy Intern Joshua Khorsandi, answered first by University of Wisconsin cardiology fellow and member of the CardioNerds Interventional Cardiology Council Dr. Shikha Jha, and then by expert faculty Dr. Venu Menon. Dr. Menon is the Section Head of Clinical Cardiology, Director of the Cardiac Intensive Care Unit, and Program Director of Cardiology Fellowship at the Cleveland Clinic. He is the Mehdi Razavi Endowed Chair and Professor of Medicine at the Cleveland Clinic Lerner College of Medicine. He was also a member of the 2025 ACS Guidelines writing committee. Question #11 A 58-year-old man with a past medical history of hypertension, hyperlipidemia, schizophrenia, atrial fibrillation (on apixaban), and prior tobacco use presents to the emergency department with chest tightness. ECG shows ST elevations in leads II, III, and aVF with reciprocal depressions in leads I and aVL. Emergency coronary angiography demonstrates 100% occlusion of the proximal RCA, and he undergoes PCI. Transthoracic echocardiogram afterward reveals normal LV function with inferior hypokinesis. On day 2, the patient experienced lightheadedness and has frequent melanic stools. His hemoglobin returns at 6 gm/dL (initial hemoglobin 11 g/dL). He undergoes EGD and colonoscopy with successful endoscopic treatment of a small gastric ulcer. True or False: it is reasonable to administer 3-4 units of packed red blood cells for a goal Hb ≥ 10 g/dL. True False Answer #11 Explanation The correct answer is True – it would be reasonable to administer 3-4 units of packed red blood cells for a goal Hb ≥ 10 g/dL. Anemia is common in patients with ACS and is associated with worse short- and long-term outcomes. Anemia is associated with adverse outcomes irrespective of whether the anemia is chronic and due to comorbid conditions, or acute and the result of bleeding related to antithrombotic therapy and/or invasive procedures. The adverse effects of anemia may be due to decreased myocardial oxygen delivery, increased myocardial oxygen demand due to increased cardiac output, or the avoidance of potentially beneficial antithrombotic drugs and/or procedures. Randomized trials in medically ill patients and those undergoing cardiac surgery have demonstrated similar or better outcomes with a restrictive transfusion strategy (targeting a blood hemoglobin level around 8 g/dL) than with a liberal transfusion strategy (targeting a blood hemoglobin level around 10 g/dL). However, randomized trial evidence for populations with ACS suggests possible clinical benefit for a more liberal transfusion strategy targeting a hemoglobin level above 10 g/dL compared with targeting a hemoglobin level above 7 g/dL to 8 g/dL The MINT (Myocardial Ischemia and Transfusion) trial randomly assigned 3,504 patients with acute STEMI or NSTEMI and anemia with a blood hemoglobin level of <10 g/dL (13% with recent bleeding) to a restrictive transfusion strategy (transfusing if the hemoglobin level was <7-8 g/dL) or a liberal transfusion strategy (transfusing if the hemoglobin level was <10 g/dL). Patients were ineligible for enrollment if they had uncontrolled bleeding, were receiving palliative treatment, or were scheduled to have cardiac surgery. Transfusion could be delayed for patients with volume overload or until the day of dialysis in patients with end-stage renal disease. The primary outcome of 30-day death or recurrent MI occurred in 16.9% of patients in the restrictive strategy and 14.5% of patients in the liberal strategy (relative risk, 1.15 [95% CI, 0.99-1.34]; P = 0.07). Death occurred in 9.9% of patients in the restrictive strategy and 8.3% of patients in the liberal strategy (relative risk, 1.19 [95% CI, 0.94-1.49]), and cardiac death occurred in 5.5% of patients in the restrictive strategy and 3.2% of patients in the liberal strategy (relative risk, 1.74 [95% CI, 1.26-2.40]). Although the MINT trial did not demonstrate a statistically significant reduction in its primary endpoint, the results suggest that a liberal blood transfusion strategy targeting a hemoglobin level around 10 g/dL may provide short-term clinical benefit over a restrictive transfusion strategy targeting a hemoglobin level above 7 g/dL or 8 g/dL in patients with AMI and anemia. The 2025 ACS guidelines give a Class 2b, LOE B-R recommendation for a liberal transfusion strategy targeting a hemoglobin of >10 g/dL in patients with ACS and acute or chronic anemia to reduce cardiovascular events. Main Takeaway In patients with ACS and acute or chronic anemia, blood transfusion to achieve a hemoglobin level of more than 10 g/dL may be reasonable to reduce cardiovascular events. Guideline Loc. Section 10.2

This episode is part of our comprehensive Decipher the Guidelines Series covering the 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes. The following question refers to Section 9.1 of the 2025 ACS Guidelines. The question is asked by Johns Hopkins pre-medical undergraduate and CardioNerds Academy Intern Joshua Khorsandi, answered first by Washington University cardiology fellow and member of the CardioNerds Interventional Cardiology Council Dr. Colin Martz, and then by expert faculty Dr. Venu Menon. Dr. Menon is the Section Head of Clinical Cardiology, Director of the Cardiac Intensive Care Unit, and Program Director of Cardiology Fellowship at the Cleveland Clinic. He is the Mehdi Razavi Endowed Chair and Professor of Medicine at the Cleveland Clinic Lerner College of Medicine. He was also a member of the 2025 ACS Guidelines writing committee. Question #8 A 65-year-old female with no significant prior cardiac history presents to the emergency department with 3 days of chest tightness associated with shortness of breath. ECG demonstrates anterior ST-segment elevation with reciprocal depressions. Coronary angiography reveals 100% occlusion of the mid left anterior descending artery. She undergoes PCI of the LAD. Two days later, she develops worsening shortness of breath. Her HR is 115 and BP 95/50. Lungs are clear on auscultation. Cardiac examination is significant for a harsh systolic murmur at the left sternal border with a palpable thrill. Transthoracic echocardiogram showed ventricular septal rupture with left-to-right shunt and Qp:Qs estimated at 2.5:1. What is the best next step? A Continue medical management B Proceed with repeat coronary angiogram and right heart catheterization with shunt run C Percutaneous ventricular septal defect closure D Intra-aortic balloon pump placement and cardiac surgical consultation Answer #8 Explanation The correct answer is D – placement of an intra-aortic balloon pump and CT surgical consultation. Timely reperfusion therapy has reduced the incidence of mechanical complications (ventricular septal rupture, mitral valve insufficiency due to papillary muscle infarction or rupture, or free wall rupture) after AMI. Although occasionally found incidentally, mechanical complications commonly present with recurrent or refractory chest pain or a new murmur accompanied by disproportionate heart failure, cardiogenic shock, or sudden cardiac death on clinical presentation within the first week after an AMI. Medical therapy alone is associated with high risk of early death; definitive surgical correction is frequently the treatment of choice. Mortality rates with surgery are highest in subjects with cardiogenic shock and in those requiring early emergency/urgent intervention after AMI. Observed mortality rates following delayed surgery (>7 days) are lower but patient selection and survivor bias contribute to this observation. The 2025 ACS guidelines give a Class 2a, LOE B-NR recommendation for the use of short-term MCS devices in patients with mechanical complications of ACS for hemodynamic stabilization and bridge to surgery. The availability of temporary MCS devices has led to increasing trends for delayed surgery due to concerns for the initial degree of extensive tissue destruction. Delayed surgical intervention may enable hemodynamic stabilization, lead to recovery of end-organ injury, and promote infarct tissue healing and maturation that could facilitate definitive repair. Percutaneous approaches toward repair have been used in patients with prohibitive surgical risk or contraindications to surgery as a primary or temporizing option in the setting of acute mitral regurgitation and ventricular septal rupture and remain an evolving area of investigation. This patient is not at prohibitive risk for surgery. Select patients with mechanical complications of ACS may be considered for cardiac transplantation or durable LVAD as a primary or bailout treatment strategy to improve survival. No RCTs evaluate the role of transfer of patients with mechanical complications after MI to dedicated centers with cardiac surgical expertise. Although overall surgical mortality is approximately 40%, it remains the treatment strategy of choice. Hemodynamic deterioration is unpredictable and can be precipitous in previously stable subjects. Consequently, transfer to a Level 1 cardiac intensive care unit (CICU) with access to various temporary MCS devices and multidisciplinary experienced teams of surgical, interventional, HF, and palliative care specialists is recommended. The guidelines give a Class 1, LOE C recommendation for management of patients with mechanical complications of ACS at centers with cardiac surgical expertise. Main Takeaway Patients with mechanical complications of ACS should be managed in a center with cardiac surgical expertise. In such patients, short-term MCS devices are reasonable for hemodynamical stabilization as a bridge to surgery. Guideline Loc. Section 9.1, Figure 9

CardioNerds (Drs. Billy Joe Mullinax, Dinu Balanescu, and Saahil Jumkhawala) discuss the 2026 American Heart Association (AHA)/American College of Cardiology (ACC) multisocietal guidelines for the evaluation and management of acute pulmonary embolism (PE) with Dr. Mark Creager, Director Emeritus of the Heart and Vascular Center at Dartmouth Health, past president of the AHA, and Chair of the Writing Committee for the 2026 AHA/ACC PE Guidelines. Audio editing by CardioNerds intern, Dr. Patrick Pekyi-Boateng. Pulmonary embolism is one of the most rapidly evolving conditions in cardiovascular medicine. The 2026 AHA/ACC multisocietal guideline, endorsed by ten professional societies, is the first de novo comprehensive guideline dedicated exclusively to acute PE in adults. It introduces a new five-category A-E risk classification system, a Class I recommendation for the Pulmonary Embolism Response Team (PERT), updated guidance on anticoagulation and advanced reperfusion therapies, and a structured framework for post-PE follow-up and chronic thromboembolic pulmonary hypertension (CTEPH) screening. This episode walks through all of it, using a high-risk clinical case as the backbone. Dr. Dinu Balanescu and Dr. Billy-Joe Mullinax are Co-chairs for the CardioNerds PE Series, developed in collaboration with the PERT Consortium.   Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Pulmonary Embolism PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls: The 2026 guideline replaces “massive/submassive/low-risk” language with a new five-category A-E classification. Category A is subclinical/incidental PE; B is symptomatic with a low clinical severity score; C1-C3 stratifies intermediate-risk patients by right ventricular (RV) function and biomarkers; D1-D2 captures incipient cardiopulmonary failure (transient hypotension vs. normotensive shock with end-organ dysfunction); and E1-E2 is frank cardiopulmonary failure up to cardiac arrest. Each category carries a respiratory modifier (R) for hypoxemia, tachypnea, or need for supplemental oxygen. PERT receives a Class I recommendation. Registry data show PERT reduces time to therapeutic anticoagulation, decreases unnecessary inferior vena cava (IVC) filter use, and shortens hospital and intensive care unit (ICU) length of stay. PERT is most impactful when advanced therapy decisions are on the table. Low molecular weight heparin (LMWH) is now preferred over unfractionated heparin (UFH) for initial parenteral anticoagulation in most patients (Category C and above), given superior venous thromboembolism (VTE) recurrence reduction, predictable pharmacokinetics, no routine monitoring, and lower heparin-induced thrombocytopenia (HIT) risk. UFH is still preferred when imminent reperfusion is planned, in severe renal failure, or when rapid reversal may be needed. Categories A and B go straight to a direct oral anticoagulant (DOAC). Advanced reperfusion therapies – systemic thrombolysis, catheter-directed thrombolysis (CDT), mechanical thrombectomy (MT), and surgical embolectomy – carry Class 2B recommendations for Category D PE because available trials used surrogate endpoints only. HI-PEITHO, which showed a composite 7-day benefit for CDT plus anticoagulation vs. anticoagulation alone, was published in March 2026 after guideline lock and could not influence the current document. More trials are coming (PEERLESS 2, PE-TRACT, PERSEVERE, TORPEDO). Post-PE follow-up is now structured: outreach within 1 week of discharge, office visit with a PE-experienced clinician by 3 months, and active chronic thromboembolic pulmonary disease (CTEPD) and CTEPH screening at every visit for at least 1 year. Persistent symptoms or functional limitation beyond 3 months should trigger evaluation with a ventilation-perfusion (V/Q) scan, echocardiogram, and right heart catheterization (RHC). Notes: Notes drafted by Dr. Saahil Jumkhawala. Why did the writing committee believe a new classification system was necessary in 2026? The 2011 AHA scientific statement used “low-risk,” “submassive,” and “massive” categories – broad, imprecise, and insufficient for guiding modern management decisions. The 2019 European Society of Cardiology (ESC) guideline improved on this with low, intermediate-low, intermediate-high, and high-risk categories, but still did not capture many clinical, imaging, and laboratory variables with reliable prognostic data. The writing committee wanted a classification system that: Was more nuanced and captured the full clinical spectrum of PE severity Incorporated the clinical, laboratory, and imaging variables with the strongest outcome data Mapped directly to management decisions and could serve as a shared communication tool The result is a five-category A-E system with subcategories and a respiratory modifier, easier to memorize and use in practice. How do we apply the new five-category system at the bedside? What data points drive category assignment, and what is the significance of the respiratory modifier? Category A – Subclinical/Incidental PE Asymptomatic; PE found incidentally (e.g., on staging computed tomography (CT) for cancer) Often subsegmental; typically appropriate for outpatient management Category B – Symptomatic, Low Severity Chest pain or dyspnea, but simplified Pulmonary Embolism Severity Index (sPESI) = 0 B1: subsegmental PE; B2: non-subsegmental PE Outpatient management appropriate unless confounding comorbidity present Category C – Symptomatic, Elevated Severity Score (analogous to ESC intermediate risk) C1: normal RV size/function, normal biomarkers C2: abnormal RV function OR elevated biomarker (one of the two) C3: both abnormal RV function AND at least one elevated biomarker Respiratory modifier (R): oxygen saturation (SpO2) <90%, respiratory rate (RR) >30, or need for supplemental O2 Category D – Incipient Cardiopulmonary Failure D1: transient hypotension (systolic blood pressure (SBP) <90 mmHg, but responsive/self-resolving) D2: normotensive shock – SBP >90 mmHg but with end-organ dysfunction (elevated lactate, rising creatinine) Respiratory modifier (R): >6 L nasal cannula O2 or non-rebreather mask required Category E – Frank Cardiopulmonary Failure E1: recurrent or persistent hypotension with cardiogenic shock E2: refractory cardiogenic shock or cardiac arrest Respiratory modifier (R): hypoxemic or ventilatory respiratory failure Mr. Osis (our case patient): tachycardic, transient SBP 84 mmHg, lactate 3.4, requiring 3L O2 – classified as D1R. What is the evidence behind the Class I PERT recommendation, and when should PERT be involved in the context of the new triage system? PERT provides: Improved risk stratification through multidisciplinary input Expert guidance on selection and timing of advanced therapies Implementation of evidence-based protocols Education of the broader care team PERT composition varies by institution but may include: pulmonary/critical care, general cardiology, interventional cardiology, cardiac surgery, vascular surgery, hematology/oncology, emergency medicine, and pharmacy. Published data supporting Class I recommendation: Reduced time to therapeutic anticoagulation Decreased unnecessary IVC filter placement Shorter hospital and ICU length of stay Possible mortality reduction (data conflicting across registries) PERT is most impactful in Category C3 and above, particularly when advanced therapy decisions are being contemplated – though the guideline does not restrict PERT activation to any specific category threshold. What does the 2026 guideline say about initial anticoagulation choice (UFH vs. LMWH)? LMWH is the preferred initial parenteral anticoagulant for most patients with acute PE (Category C and above). Meta-analytic evidence: LMWH reduces recurrent VTE more effectively than UFH without increasing bleeding Predictable pharmacokinetics – no routine activated partial thromboplastin time (aPTT) monitoring required Lower incidence of HIT UFH is preferred when: Imminent advanced reperfusion is anticipated (systemic lysis, MT, surgical embolectomy, or extracorporeal membrane oxygenation (ECMO) cannulation) Severe renal dysfunction (unpredictable LMWH pharmacokinetics) Rapid reversibility needed Categories A and B: proceed directly to a DOAC (no parenteral bridge needed). DOACs are preferred over vitamin K antagonists (VKA) for long-term therapy in most patients, including most with cancer-associated PE. Exception: LMWH preferred for luminal gastrointestinal (GI) or genitourinary (GU) malignancies due to bleeding risk DOACs are contraindicated in pregnancy; LMWH is generally used throughout gestation and for at least 6 weeks postpartum How does the guideline navigate Category D1-D2 patients? What is the evidence base for the Class 2B recommendation for advanced therapies, and how do we choose between CDT and MT? All advanced reperfusion therapies carry a Class 2B recommendation for Category D PE: Class 2B = “may be considered” – the intervention can be used, but evidence is less certain Applies to: systemic thrombolysis, CDT, MT, and surgical embolectomy Why Class 2B? Available trials at the time of guideline finalization (early fall 2025) relied on surrogate endpoints: ULTIMA: CDT vs. anticoagulation alone – surrogate RV/LV ratio endpoint OPTALYSE: CDT dose-finding – surrogate endpoints STORM-PE: surrogate endpoints PEERLESS (New England Journal of Medicine, 2024): MT vs. CDT – included mortality, intracranial hemorrhage (ICH), major bleed, ICU admission, but was not vs. anticoagulation alone HI-PEITHO (published March 2026 at the ACC annual meeting – after guideline lock): 7-day composite of PE-related death, clinical decompensation/collapse, or PE recurrence Primary outcome favored CDT plus anticoagulation vs. anticoagulation alone Composite driven primarily by clinical decompensation/collapse Could not be incorporated into current recommendations Upcoming trials expected to provide hard-outcome data: PEERLESS 2, PE-TRACT, PERSEVERE, TORPEDO. For Mr. Osis (post-op day 2, fresh anastomosis): systemic lysis and CDT carry high bleeding risk. MT is the most attractive option if hemodynamic deterioration progresses; anticoagulation alone with close monitoring is reasonable if he remains stable. In a Category E patient with major bleeding contraindications, how does the guideline structure the decision between systemic lysis, catheter-based therapies, surgical embolectomy, and venoarterial (VA)-ECMO? Category E1 (persistent hypotension with cardiogenic shock) – four options: Systemic thrombolysis: Class I in the absence of contraindications (alteplase 100 mg over 2 hours) CDT: Class 2B; a bleeding-conscious alternative to systemic lysis MT: Class 2A for selected E1 patients Surgical pulmonary embolectomy: Class 2A for selected E1; Class 2B in Category D when lysis fails or is contraindicated; preferred when cardiac surgery resources are available, and there is obstructing right heart thrombus or patent foramen ovale (PFO) clot VA-ECMO: explicitly endorsed in the 2026 guideline as a bridge to recovery, lysis-after-stabilization, MT, or surgical embolectomy in refractory cardiopulmonary collapse. Best outcomes when initiated early (pre-arrest is better than peri-arrest). Reduced-dose thrombolysis (25-50 mg alteplase): considered in patients with moderate bleeding risk; possible improvement in RV function with less bleeding, though mortality benefit unproven. Temporary mechanical circulatory support (MCS) – including Impella RP, ProtekDuo, and surgical right ventricular assist device (RVAD) – may bridge selected patients with refractory RV failure; data are observational and best deployed at centers with dedicated PE or shock teams. For Mr. Osis (post-op day 2 with fresh anastomosis): systemic lysis and CDT are essentially contraindicated. The PERT decision favored MT on VA-ECMO, which is consistent with the 2026 guideline framework for Category E patients with major bleeding contraindications. What is the structure of post-PE follow-up, and how do we approach anticoagulation duration in a patient with cancer-associated PE? Within 1 week of discharge: outreach or clinic visit (at minimum a phone call) to confirm anticoagulation adherence, assess for bleeding, and review symptoms. By 3 months: in-person office visit with a PE-experienced clinician to assess symptom trajectory and determine anticoagulation duration. Provoked PE with a resolved transient risk factor: 3-6 months is generally sufficient Unprovoked PE or persistent risk factors: extended anticoagulation generally warranted Cancer-associated PE: continue anticoagulation while cancer is active or under treatment (Class I) At every visit for at least 1 year: actively screen for CTEPD/CTEPH – ask about exertional dyspnea, fatigue, and functional decline. PERT or post-PE clinic models are associated with better adherence to follow-up and earlier CTEPH detection in registries. When does residual dyspnea after PE trigger a structured CTEPH workup, and what is the recommended diagnostic pathway? Approximately 50% of patients have residual symptoms at 3 months post-PE. After 3 months of therapeutic anticoagulation, persistent dyspnea or functional limitation triggers evaluation for CTEPD (chronic thromboembolic pulmonary disease) – this is a Class I recommendation. Diagnostic pathway: Echocardiogram: persistent RV dysfunction is a Class 2A indication for further evaluation V/Q scan: first-line imaging for CTEPH evaluation CT pulmonary angiography (CTPA): confirmatory imaging RHC: required to confirm CTEPH (mean pulmonary arterial pressure (PAP) >20 mmHg with pulmonary vascular resistance (PVR) >2 Wood units (WU) on anticoagulation) Cardiopulmonary exercise test (CPET): Class 2A option for patients with functional limitation but no overt pulmonary hypertension (PH) (CTEPD without H) Confirmed CTEPH: refer to an expert center for pulmonary endarterectomy (PEA) candidacy assessment, balloon pulmonary angioplasty (BPA), or PH-targeted medical therapy (riociguat, treprostinil). For Mr. Osis at 3 months (tricuspid annular plane systolic excursion (TAPSE) 16 mm, estimated pulmonary artery systolic pressure (PASP) 48 mmHg, exertional dyspnea): V/Q scan and RHC are indicated, with referral to a CTEPH center given high pre-test probability. Special populations: PE in pregnancy, cancer-associated PE, clot-in-transit, and IVC filters. Pregnancy: DOACs and warfarin are contraindicated (fetal harm, miscarriage risk) LMWH is preferred throughout pregnancy and for at least 6 weeks postpartum Anti-Xa monitoring is recommended in patients at weight extremes or with renal disease After delivery, LMWH or warfarin can be continued; insufficient data on DOACs in breastfeeding Cancer-associated PE: DOACs (apixaban, edoxaban, rivaroxaban) are first-line for most patients LMWH preferred for luminal GI or GU malignancies due to mucosal bleeding risk Long-term management: reduced-dose apixaban (2.5 mg twice daily) or rivaroxaban after the initial treatment period may be considered Continue anticoagulation while cancer is active Clot-in-transit (right heart thrombus): High-risk finding warranting active intervention Guideline endorses mechanical or surgical thrombectomy for removal IVC filters: Indicated only when anticoagulation is contraindicated in the setting of acute PE Use retrievable filters with a planned removal strategy Routine IVC filter use is not recommended – PERT implementation has already driven down unnecessary filter use significantly References: Creager MA, et al. 2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults. J Am Coll Cardiol. 2026. Available at: https://www.jacc.org/ Konstantinides SV, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405. Available at: https://pubmed.ncbi.nlm.nih.gov/31504429/ Jaff MR, et al. Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension: A Scientific Statement From the American Heart Association. Circulation. 2011;123(16):1788-1830. doi:10.1161/CIR.0b013e318214914f. Available at: https://pubmed.ncbi.nlm.nih.gov/21422387/ Piazza G, et al; HI-PEITHO Investigators. Catheter-Directed Thrombolysis in Intermediate-High-Risk Pulmonary Embolism. N Engl J Med. 2026. Available at: https://www.nejm.org/doi/10.1056/NEJMoa2503980 Bhatt DL, et al; PEERLESS Investigators. Mechanical Thrombectomy for Intermediate-Risk Pulmonary Embolism. N Engl J Med. 2024;391:2099-2110. doi:10.1056/NEJMoa2407772. Available at: https://pubmed.ncbi.nlm.nih.gov/39555838/ Creager MA, Geary J, Barnes J. Evidence and Future Directions in Acute Pulmonary Embolism Management. J Am Coll Cardiol. 2026. Available at: https://www.jacc.org/

This episode is part of our comprehensive Decipher the Guidelines Series covering the 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes. The following question refers to Section 4.3 of the 2025 ACS Guidelines. The question is asked by Thomas Jefferson medical student and CardioNerds Academy Intern Dr. Grace Qiu, answered first by Cleveland Clinic interventional and structural cardiology fellow and member of the CardioNerds Interventional Cardiology Council Dr. Eunice Dugan, and then by expert faculty Dr. Binita Shah. Dr. Binita Shah is an associate professor of medicine, interventional cardiologist, Director for research in Interventional Cardiology, and Director of the Department of Medicine Clinical Investigator Track at NYU. She is also an associate director of interventional cardiology and director of the transcatheter valve program at the VA New York Harbor Healthcare System. She was a member of the 2025 ACS Guidelines writing committee. Question #5 A 64-year-old woman with NSTE-ACS is taken to the cardiac catheterization laboratory. She is P2Y12 inhibitor-naive as she was unable to tolerate oral intake due to severe nausea and vomiting. Coronary angiography reveals a high-grade, thrombotic lesion in the mid-Right Coronary Artery. The interventionalist decides to initiate an intravenous P2Y12 inhibitor before proceeding with PCI. Which of the following is the most appropriate management strategy? A Administer Cangrelor as a 30 mcg/kg IV bolus followed by a 4 mcg/kg/min infusion for at least 2 hours or the duration of PCI, whichever is longer. B Administer Eptifibatide (GP IIb/IIIa inhibitor) as a routine double-bolus followed by an infusion to replace the need for P2Y12 inhibition. C Delay the procedure for 2 hours to allow for the administration and absorption of 600 mg of oral Clopidogrel. D Administer Cangrelor as a 180 mcg/kg bolus followed by a 2 mcg/kg/min infusion for exactly 1 hour. Answer #5 Explanation The correct answer is A. Cangrelor is the only intravenous P2Y12 inhibitor currently available. It is a direct-acting, intravenous antagonist of the P2Y12 receptor characterized by rapid and potent platelet inhibitory effects, with restoration of platelet function occurring within 1 hour of drug discontinuation. It also has a very short half-life (3–6 minutes). Among patients with ACS undergoing PCI who have not received a P2Y12 inhibitor, intravenous cangrelor may be reasonable to reduce periprocedural ischemic events (Class 2B; LOE B-R). Dosing Strategy: Bolus: 30mcg/kg IV bolus administered rapidly (under 1 minute) before PCI begins. Infusion: 4 mcg/kg/min IV infusion. Duration: The infusion must run for at least 2 hours or for the duration of the PCI, whichever is longer. Transition to Oral Therapy: Ticagrelor: 180mg can be given at any time (during or after the infusion). Prasugrel/Clopidogrel: loading dose must be given immediately after the infusion is stopped. Giving these earlier can lead to a drug-drug interaction where the Cangrelor prevents the active metabolite from binding to the receptor. In the CHAMPION PHOENIX trial, cangrelor was studied versus clopidogrel in patients undergoing PCI for acute or stable coronary syndromes. Cangrelor was administered as an intravenous bolus prior to PCI followed by an infusion for at least 2 hours or for the duration of the procedure, whichever was longer. In the control arm, clopidogrel was administered as a 600- or 300-mg loading dose immediately before or after PCI. At 48 hours, the primary endpoint of all- cause death, MI, ischemia-driven revascularization, or stent thrombosis was significantly reduced with cangrelor, with similar effects observed among those presenting with NSTE-ACS or STEMI. Glycoprotein IIb/IIIa receptor inhibitors are parenterally administered drugs that block platelet aggregation by preventing platelet cross-linking via fibrinogen or von Willebrand factor binding to the glycoprotein IIb/IIIa receptor. Routine administration of GP IIb/IIIa inhibitors before PCI is not recommended and is associated with increased bleeding without improving ischemic outcomes. (Class 3 – No Benefit). In current practice, the role of glycoprotein IIb/IIIa receptor inhibitors is largely limited to adjunctive use at the time of PCI in patients with large thrombus burden or as “rescue” or “bailout” therapy in patients with PCI complications such as no-reflow or persistent or recurring thrombus at the lesion. B is incorrect. Routine “upstream” or periprocedural use of GP IIb/IIIa inhibitors (GPI) is Class 3 (No Benefit) for most patients. Large trials (like EARLY-ACS) showed that routine GPI use significantly increases major bleeding without a proportional decrease in ischemic events compared to modern P2Y12 inhibitors. C is incorrect. In patients with NSTE-ACS or STEMI who are already in the lab, delaying the procedure to wait for oral drug absorption is not recommended. D is incorrect. The correct bolus is 30mcg/kg. Cangrelor must be infused for at least 2 hours or the duration of the PCI, whichever is longer. Stopping at 1 hour would leave a “gap” in platelet inhibition before an oral agent can take effect. Because Cangrelor’s half-life is only 3–6 minutes, a premature stop increases the risk of acute stent thrombosis. Main Takeaway Cangrelor may be reasonable among patients with ACS undergoing PCI who have not received a P2Y12 inhibitor to reduce periprocedural ischemic events (Class 2b, LOE B-R). Guideline Loc. Section 4.3.3-4.3.4

This episode is part of our comprehensive Decipher the Guidelines Series covering the 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes. The following question refers to Section 3.2 of the 2025 ACS Guidelines. The question is asked by Thomas Jefferson medical student and CardioNerds Academy Intern Dr. Grace Qiu, answered first by Cleveland Clinic interventional and structural cardiology fellow and member of the CardioNerds Interventional Cardiology Council Dr. Eunice Dugan, and then by expert faculty Dr. Binita Shah. Dr. Binita Shah is an associate professor of medicine, interventional cardiologist, Director for research in Interventional Cardiology, and Director of the Department of Medicine Clinical Investigator Track at NYU. She is also an associate director of interventional cardiology and director of the transcatheter valve program at the VA New York Harbor Healthcare System. She was a member of the 2025 ACS Guidelines writing committee. Question #3 A 55-year-old woman is brought to the Emergency Department after an out-of-hospital cardiac arrest. She had a witnessed collapse with an initial shockable rhythm. Return of Spontaneous Circulation (ROSC) was achieved after 15 minutes of Advanced Cardiac Life Support (ACLS). Her post-resuscitation ECG shows diffuse ST-segment depression but no ST-segment elevation. She remains comatose. Which of the following is the most appropriate next step in her management regarding coronary angiography? A Immediate emergency coronary angiography (within 2 hours) should be performed. B Routine emergency coronary angiography is not recommended in the absence of ST-segment elevation or hemodynamic instability. C Coronary angiography should be delayed for at least 72 hours to allow for neurological recovery. D Fibrinolytic therapy should be administered immediately if the patient cannot reach a cath lab within 90 minutes. Answer #3 Explanation The correct answer is B. In resuscitated patients who are comatose after cardiac arrest, electrically and hemodynamically stable, and without evidence of STEMI, immediate angiography is not recommended due to lack of benefit (Class 3: No Benefit; LOE A) Patients who have been resuscitated after cardiac arrest and are noncomatose or who are comatose with favorable prognostic features and with evidence of STEMI, should undergo PPCI to improve survival. (Class 1; LOE B-NR). For patients such as this one, a delayed or selective approach should be taken once the patient is stabilized. Early angiography should not be denied solely based on a comatose state, but it should be deferred if there are clear non-cardiac causes for the arrest or if the patient’s overall prognosis is futile. A is incorrect because recent evidence shows no benefit to “emergency” PPCI for stable patients without ST-elevation. C is incorrect because while we wait for stability, we don’t necessarily have a fixed 72-hour “mandatory” delay for the heart if ischemia is suspected. D is incorrect, as fibrinolysis is generally not indicated for post-arrest patients without clear STEMI and carries risks in a post-CPR setting due to potential trauma. The MIRACLE2 Score is a tool for neuroprognostication. It helps clinicians estimate the likelihood of a poor neurological outcome at 6 months. A high score suggests that the benefit of an invasive procedure may be outweighed by the severity of the brain injury. Components of MIRACLE2: M – Missed (unwitnessed) arrest I – Initial non-shockable rhythm R – Reactive pupils at ROSC A – Age (points increase significantly at >60 and >80) C – Rhythm change (e.g., VF to PEA) L – Low pH (pH < 7.20) E – Epinephrine (any dose given) Clinical Threshold: A score of >5 indicates a high risk of poor neurological recovery, which may lead a Heart Team to favor stabilization over immediate emergency angiography in patients without ST-elevation. Early recognition of STEMI in resuscitated patients and direct transfer to a PCI-capable center is associated with improved survival. Survival-to-hospital discharge in the patient who is comatose with out-of-hospital cardiac arrest is <10% regardless of etiology. Those with a witnessed arrest and a shockable rhythm have improved survival. Outcomes for patients with STEMI who are awake after resuscitated cardiac arrest are comparable to patients with STEMI who were not in cardiac arrest. For this reason, patients with cardiac arrest who have achieved return of spontaneous circulation (ROSC) and are awake with STEMI on ECG are candidates for PPCI. However, care should be individualized in the comatose patient with rapid assessment of the patient’s clinical features and cardiac arrest characteristics before proceeding with invasive angiography. In contrast, patients who are stable without ST-segment elevation after out-of-hospital cardiac arrest do not require immediate coronary angiography. Coronary angiography in this setting can be deferred pending further risk stratification. Main Takeaway Patients with cardiac arrest and STEMI who have been resuscitated should preferentially be transferred by EMS to a PPCI-capable center. Certain prognostic scores can help risk stratify patients prior to catheterization. Guideline Loc. Section 3.2. Management of Patients Presenting With Cardiac Arrest