Cardionerds: A Cardiology Podcast

CardioNerds (Drs. Apoorva Gangavelli, Cory Sejo, and Joseph Kassab) discuss the hemodynamics of valvular heart disease with Dr. Michael Brener. Using pressure-volume loops and clinical cases, they explain ventricular loading, myocardial energetics, and ventricular-arterial coupling, then apply these concepts to aortic stenosis, mitral regurgitation, and tricuspid regurgitation. Audio editing by CardioNerds Academy intern, Joshua Khorsandi.

This episode was produced as part of the CardioNerds Academy curriculum by House Einthoven under the guidance of House Chief, Dr. Apoorva Gangavelli, and Academy Program Director, Dr. Gurleen Kaur. A matching review article will be published in US Cardiology Review, the official journal of CardioNerds.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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CardioNerds guest hosts Dr. Apoorva Gangavelli and Dr. Georgia Vasilakis, alongside Dr. Flavia Tejada, Dr. Ahmad Ahmad, and Dr. Blanca Simon Frances from MedStar Washington Hospital Center/Georgetown University for a case discussion on rapidly progressive heart failure and the urgency of recognizing infiltrative cardiomyopathy. They discuss a 65-year-old man with newly diagnosed HFrEF and CKD who presented with acute decompensated heart failure, low-voltage ECG, concentric LV thickening, renal dysfunction, and abnormal lambda free light chains. His course was complicated by PEA arrest when laid supine, cardiogenic shock physiology, bilateral pleural effusions, and biopsy-confirmed AL cardiac amyloidosis. The episode focuses on clinical red flags, diagnostic algorithms, hemodynamic fragility, and why suspected AL amyloidosis is a hematologic and cardiac emergency. Expert commentary is provided by Dr. Ajay Kadakkal. Audio editing for this episode was performed by CardioNerds Intern, Dr. Julia Marques Fernandes.

“To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” – Sir William Osler. CardioNerds thank the patients and their loved ones whose stories teach us the Art of Medicine and support our Mission to Democratize Cardiovascular Medicine.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

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Notes were drafted by Dr. Flavia Tejada Frisancho, Dr. Ahmad Ahmad and Dr. Blanca Simon Frances.

This case highlights how patients with cardiac amyloidosis can be extremely hemodynamically fragile.

In this episode, the CardioNerds (Dr. Dinu Balanescu, Dr. Billy Joe Mullinax, and Dr. Akiva Rosenzveig) take a deep dive into the world of the surgical management of pulmonary embolism (PE) with faculty expert, Dr. Joshua Goldberg. We start from the pathophysiology of PE and its impact on right ventricular, and thereby left ventricular, hemodynamics. We then discuss the management of high-risk PE and where catheter-based therapies, surgical management and mechanical circulatory support via ECMO find their roles. Dr. Goldberg also provides a historical overview of the evolution of the surgical management of PE. We conclude by briefly discussing the management of chronic thromboembolic pulmonary hypertension (CTEPH) as a long-term complication of PE. Audio editing for this episode was performed by CardioNerds Intern, Dr. Julia Marques Fernandes. 

NOTE: this episode was recorded before the publication of the 2026 AHA/ACC Acute PE Guidelines.

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.

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Notes: Notes drafted by Dr. Akiva Rosenzveig.

Sudden increase in RV afterload which leads to RV volume and pressure overload which leads to neurohormonal activation, increased oxygen demand and RV ischemia, reduced RV contractility leading to reduced left ventricular (LV) preload and reduced cardiac output

We need to focus on not only treating the clot but supporting the RV concurrently. This is analogous to supporting the LV with mechanical circulatory support while also opening the culprit coronary lesion in acute myocardial infarction related cardiogenic shock (AMI-CS). The reason why High-risk/Massive PE has historically had poor outcomes may be because treatment modalities focused on treating the clot and not supporting the RV as well.

With the increased role of catheter-based therapies, the role of surgery is narrowing to a more nuanced patient population. Surgery should be considered when we don’t have other treatment options. It remains especially useful in more subacute clots where it is more difficult to extract with catheter-based interventions. In those cases, surgical pulmonary embolectomy can be useful as you have direct visualization of the pulmonary arteries and its branches.

In the early 1900’s, the Trendelenburg procedure was performed but had a very high mortality rate. This was because they waited for the patients to decompensate and then once the patient was peri-arrest, they would take them urgently to the operating room, snare the aorta and pulmonary artery and open the artery and remove the clot. By manipulating the PA in this way they detrimentally increased the RV afterload on an already failing RV. In the 1930’s, John Gibbon started working on developing cardiopulmonary bypass. Now, surgeons can put the patient on cardiopulmonary bypass and create incisions on both the left and right pulmonary arteries to extract the clot.

Contrary to what we are used to hearing, the lack of a saddle PE shouldn’t be comforting. The more distal clot is more concerning as that’s where there is more significant flow resistance. The saddle embolus takes up a small proportion of the PA cross-sectional area and, therefore, the flow obstruction does not come from there.

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.

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

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 9.2 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.

A 74-year-old man with past medical history significant for hyperlipidemia, obstructive sleep apnea, hypertension, tobacco use, type 2 diabetes mellitus, and chronic obstructive pulmonary disease presents to the emergency department with two days of chest tightness and worsening shortness of breath at rest. He is found to have ST elevations in the anterolateral leads. Emergent coronary angiography demonstrates 90% stenosis of proximal to mid LAD and he is treated with two drug-eluting stents. Transthoracic echocardiograms during hospitalization showed an LVEF of 25% with anterior and apical wall motion abnormalities. He is discharged on dual antiplatelet therapy along with metoprolol, valsartan, spironolactone, SGLT2 inhibitor, and rosuvastatin. At follow-up 3 months later, he reports home BP readings in 90s/50s mm Hg with intermittent shortness of breath and lightheadedness. Blood pressure in the office is 92/54 mmHg. ECG shows normal sinus rhythm with anterior Q waves, a narrow QRS, and no acute ST-segment or T-wave changes.  Repeat transthoracic echocardiogram shows an LVEF of 30%. What is the most appropriate next step?

A

Switch valsartan to sacubitril-valsartan

B

Consider implantable cardioverter defibrillator (ICD) placement

C

Consider cardiac resynchronization therapy 

D

Consider additional cardiac rehabilitation sessions

Explanation 

The correct answer is B – consider implantable cardioverter defibrillator (ICD) placement.

Generally, arrhythmic complications increase both morbidity and mortality rates in patients after ACS. Patients who present with AMI with reduced LVEF (≤40%) have increased risk of new-onset atrial fibrillation, bradyarrhythmias, and ventricular arrhythmias. Ventricular arrhythmias are common after ACS and more common in patients with reduced LVEF. The MADIT II trial (Multicenter Automatic Defibrillator Implantation Trial) demonstrated a 31% reduction in all-cause mortality (HR, 0.69 [95% CI, 0.51-0.93]) for prophylactic implantation of a cardiac defibrillator in patients with an LVEF ≤30% who were at least 30 days after MI or 3 months after revascularization for MI and had an anticipated life expectancy longer than 1 year. A mortality benefit for prophylactic ICD implantation has also been shown in patients with an LVEF ≤35% and New York Heart Association class II or III HF symptoms, as well as in patients with inducible ventricular tachycardia or ventricular fibrillation and an LVEF ≤40%.

This patient has an LVEF of <30% with at least NYHA class II symptoms, now 90 days post-revascularization for MI, which means he is a candidate for ICD placement for primary prevention of sudden cardiac death.

Answer choice A is incorrect because hypotension in this patient is a limitation to adding any more guideline-directed medical treatment, such as sacubitril/valsartan. This patient does not meet criteria for CRT implantation given his narrow QRS complex, so answer choice C is incorrect. Additional cardiac rehabilitation sessions (answer choice D) would not treat patients’ ongoing cardiomyopathy and SCD risk.

The 2025 ACS guidelines give a Class 1, LOE A recommendation for ICD implantation in patients post-MI with LVEF ≤40% at least 40 days post-MI and at least 90 days post-revascularization to reduce mortality.

In addition, in patients post-ACS, ICD implantation is reasonable in patients with clinically relevant ventricular arrhythmias >48 hours and within 40 days post-MI to improve survival (LOE 2a, LOE C-EO).

Some may wonder about the use of a temporary wearable cardioverter-defibrillator after the initial presentation. In the VEST trial, this strategy did not significantly reduce the primary endpoint, a composite of sudden death or death from ventricular tachyarrhythmias at 90 days) in patients with AMI and LVEF ≤ 35%. Notably, there was a lower incidence of death from any cause in the wearable vest group compared to the no-device group and overall, greater benefit was seen in those who were compliant with the device. As such, use of a wearable cardioverter-defibrillator could be considered in high-risk patients with reduced LVEF as a bridge to consideration for the need for an ICD. Per the guidelines, in patients early after MI, usefulness of a temporary wearable cardioverter-defibrillator is uncertain in patients with an LVEF ≤35% to improve survival (COR 2b, LOE B-R).

Main Takeaway

In patients post MI, implantable cardioverter defibrillator (ICD) implantation is recommended in selected patients with an LVEF of less than or equal to 40% at least 40 days post MI and at least 90 days post revascularization to reduced death.

Guideline Loc.

Section 9.2

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.

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

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

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.

A 72-year-old gentleman with past medical history significant for hypertension, hyperlipidemia, type 2 diabetes, and tobacco use is brought to the ED with chief complaint of chest tightness. He is found to have ST elevations in leads V1 to V4 and is taken for emergency coronary angiography, which demonstrates 99% proximal LAD occlusion. During the procedure, he becomes hypotensive (BP 74/55 mm Hg) and tachycardic (HR 122 bpm). Norepinephrine is initiated. Right heart catheterization demonstrates elevated left and right-sided filling pressures with low cardiac index. Besides immediate revascularization, which of the following would be the best next step? 

A

Cannulate for VA-ECMO

B

Placement of microaxial intravascular flow pump

C

Administration of intravenous fluid

D

Placement of an intraaortic balloon pump

Explanation 

The correct answer is B – Placement of microaxial intravascular flow pump.

Cardiogenic shock is estimated to occur in approximately 10% of patients with STEMI and is associated with an early mortality rate of 40% to 50%. Several types of devices for temporary mechanical circulatory support (MCS) are available and have been studied in patients with cardiogenic shock, with variable efficacy and increased risk of vascular complications. IABP counterpulsation improves coronary perfusion and reduces cardiac afterload. It is relatively easy to use and has a smaller insertion profile (8 French), which is associated with lower rates of vascular access site complications when compared with other MCS devices. Left ventricular percutaneous microaxial flow pumps unload the LV by draining blood from the LV and pumping it to the ascending aorta. They are dependent on adequate right ventricular function to fill the LV and require adequate oxygenation of blood. VA-ECMO provides both blood flow and gas exchange, providing full cardiopulmonary bypass, but increases afterload. 

Randomized trials of MCS devices remain challenging to conduct due to relative lack of equipoise on the part of treating physicians, leading to selective patient enrollment and limiting the generalizability of study results. The DanGer-Shock randomized 360 patients presenting with STEMI and cardiogenic shock of <24 hours duration to either microaxial flow pump or standard of care. The trial demonstrated a 26% reduction of all-cause mortality at 180 days (HR, 0.74 [95% CI, 0.55-0.99]; P = 0.04; absolute risk reduction, 12.7%; number needed to treat = 8) compared with standard of care. However, this came at the cost of increased risk of complications like bleeding, limb ischemia and renal replacement therapy in the microaxial flow pump group.

In light of this and other trial data, the guidelines give a Class 2a, LOE B recommendation for the use of a microaxial intravascular flow pump in patients with STEMI complicated by severe or refractory cardiogenic shock to reduce mortality. These patients should be noncomatose and have adequate peripheral vasculature to accommodate large-bore access.

Answer choice A is not correct as the use of VA-ECMO cannulation in this setting has been given a class 3 recommendation for lack of benefit. VA-ECMO has not been shown to reduce death compared with medical therapy alone in patients with cardiogenic shock in the setting of MI but increases major bleeding and vascular complications. In the absence of severe concomitant respiratory failure requiring oxygenation support, this strategy is not indicated in the patient described here. Further fluid resuscitation (answer choice C) is not likely to be helpful as right heart catheterization demonstrated elevated filling pressures. Placement of an intraaortic balloon pump (IABP) is not the next best step.  The IABP-SHOCK II trial, which randomized patients with acute MI and severe cardiogenic shock to IABP or medical therapy showed no differences at 30 days or at long-term follow-up in the primary outcome of all-cause death. The use of IABP has a class 3 recommendation for lack of benefit in patients with cardiogenic shock secondary to acute myocardial infarction.

Main Takeaway

In selected patients with STEMI and severe or refractory cardiogenic shock, insertion of microaxial intravascular flow pump is reasonable to reduce death in a noncomatose patient with adequate vascular access. 

Guideline Loc.

Section 8.2

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.

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Notes drafted by Dr. Saahil Jumkhawala.

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 4.4 of the 2025 ACS Guidelines.

The question is asked by Thomas Jefferson medical student and CardioNerds Academy Intern Dr. Grace Qiu, answered first by University of Miami cardiology fellow and member of the CardioNerds Interventional Cardiology Council Dr. Saahil Jumkhawala, 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.

A 64-year-old male with a history of hypertension and dyslipidemia presents to the emergency department with crescendo angina. His ECG shows ST-segment depression in leads V4–V6, and high-sensitivity troponin levels are significantly elevated. A diagnosis of NSTE-ACS is made, and the patient is scheduled for an early invasive strategy with percutaneous coronary intervention (PCI). Which of the following parenteral anticoagulants is NOT recommended for use as a standalone agent during the PCI procedure itself?

A

Fondaparinux

B

Bivalirudin

C

Unfractionated Heparin

D

Enoxaparin

Explanation

The correct answer is A. 

The choice of parenteral anticoagulation for a patient with Non-ST-Elevation Acute Coronary Syndrome (NSTE-ACS) undergoing Percutaneous Coronary Intervention (PCI) is governed by both efficacy in preventing ischemic events and the safety profile regarding bleeding.

The following are the recommended Agents for PCI:

Unfractionated Heparin (UFH): In patients with NSTE-ACS, intravenous unfractionated heparin (UFH) is useful to reduce ischemic events (Class 1, LOE C-EO).

Bivalirudin: This direct thrombin inhibitor is recommended as an alternative to UFH. In patients with NSTE-ACS undergoing PCI, bivalirudin may be reasonable as an alternative to UFH to reduce bleeding and mortality (Class 2b, LOE B-R)

Enoxaparin: In patients with ACS, intravenous enoxaparin may be considered as an alternative to UFH at the time of PCI to reduce ischemic events (Class 2B, LOE B)

In patients with ACS, fondaparinux should not be used to support PCI because of the risk of catheter thrombosis (Class 3: Harm; LOE B-R). The primary reason is due to the risk of catheter thrombosis. Large-scale trials (notably the OASIS-5 trial) demonstrated that using fondaparinux alone during PCI led to a significantly higher rate of thrombus formation on the diagnostic and therapeutic catheters. In the OASIS-5 trial, an increase was observed in the rate of catheter-related thrombus with fondaparinux compared with enoxaparin (0.9% versus 0.4%). Similar results were observed in the OASIS-6 trial, in which a higher rate of guiding-catheter thrombosis and more coronary complications with fondaparinux were observed when used during PCI.

Main Takeaway

– Parenteral anticoagulation for a patient with Non-ST-Elevation Acute Coronary Syndrome (NSTE-ACS) undergoing Percutaneous Coronary Intervention (PCI) is governed by both efficacy in preventing ischemic events and the safety profile regarding bleeding.

Expert Suggestions

Guideline Loc.

Section 4.4 

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 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.

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.

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