Cardionerds: A Cardiology Podcast

CardioNerds (Drs. Rawan Amir, Tripti Gupta, and Alysha Joseph) discuss the fundamentals of adult congenital heart disease (ACHD) surgery with Dr. Elizabeth Stephens.  Audio editing by CardioNerds academy intern, Grace Qiu. 

Using a case of a young adult undergoing a Ross procedure, the episode walks through what happens in the operating room—from induction and intraoperative transesophageal echocardiography (TEE) to cardiopulmonary bypass (CPB), myocardial protection, and surgical repair. The discussion highlights key concepts including cardioplegia, cross-clamp and bypass times, hypothermic circulatory arrest, and the complexity of redo sternotomy. This episode provides learners with a practical framework to interpret operative reports, anticipate postoperative physiology, and better collaborate with surgical teams.

This episode was produced by the CardioNerds ACHD Council and planned by Dr. Rawan Amir. 

CardioNerds Adult Congenital Heart Disease Page
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Pearls

“LV distension kills patients.”
Preventing left ventricular distension with appropriate venting and awareness of aortic insufficiency is critical to intraoperative safety. 

TEE can change the surgical plan in real time.
Findings such as underestimated aortic regurgitation, mitral pathology, or a PFO may directly alter cannulation and cardioplegia strategy. 

Cross-clamp time = myocardial ischemic time; bypass time = systemic stress.
Both are key predictors of postoperative complications including renal injury, bleeding, and ventricular dysfunction. 

Redo sternotomy risk is driven by anatomy, not just number.
Aorta adherent to the sternum, conduit position, and chamber pressurization define risk more than the number of prior surgeries. 

Think longitudinally—ACHD surgery is lifetime planning.
Surgical materials and strategies must account for future interventions, especially in younger patients.

Notes:

Notes drafted by Dr. Alysha Joseph, aided by generative artificial intelligence.

What are the key steps in congenital cardiac surgery from incision to closure?

Preoperative planning is multidisciplinary, involving surgeon, anesthesia, cardiology, and ICU teams; high-risk inductions (e.g., critical AS, Williams syndrome) are identified early

TEE is performed immediately after induction to reassess anatomy and may reveal new findings (e.g., underestimated AI, mitral disease, PFO)

Median sternotomy is performed, followed by creation of a pericardial well to optimize exposure

Heparin is administered prior to cannulation; arterial and venous cannulas are placed for initiation of CPB

Cross-clamp is applied and cardioplegia delivered to arrest the heart, allowing a still and protected operative field

Surgical repair (e.g., Ross procedure) is performed, followed by de-airing, cross-clamp removal, and reperfusion

Patient is weaned from bypass with TEE reassessment, hemostasis achieved, and chest closed

What is cardioplegia and how is it delivered?

Cardioplegia is a potassium-rich solution that arrests myocardial activity and reduces metabolic demand

Most commonly used solution in the U.S. is Del Nido cardioplegia, originally developed for pediatric myocardium

Delivery strategies include:

Antegrade (via aortic root) – standard approach 

Ostial (direct coronary delivery) – used when aortic root cannot be relied upon 

Retrograde (via coronary sinus) – useful in severe AI or coronary disease

NOTE: Severe aortic regurgitation can impair antegrade delivery and requires alternative strategies and LV venting 

What do cross-clamp time and bypass time represent clinically?

Cross-clamp time = duration of myocardial ischemia while the heart is arrested

Bypass time = total duration on CPB, reflecting systemic exposure to non-physiologic circulation

Prolonged cross-clamp time (>2–3 hours) increases risk of myocardial dysfunction, especially with poor baseline function

Longer bypass time is associated with increased risk of renal injury, coagulopathy, and bleeding

These metrics often reflect both case complexity and intraoperative challenges

What is hypothermic circulatory arrest (HCA) and when is it used?

HCA involves complete cessation of blood flow to allow a bloodless surgical field

Typically used in complex aortic arch repairs

Patients are cooled to ~18°C to reduce metabolic demand and protect organs

Duration is ideally limited to <30 minutes to minimize neurologic injury

Adjuncts include:

Antegrade cerebral perfusion (ACP) – provides targeted brain perfusion 

Retrograde cerebral perfusion (RCP) – less effective for oxygen delivery 

What makes redo congenital cardiac surgery high risk?

Re-entry risk depends on anatomical relationships:

Aorta adherent to sternum (especially midline) poses high risk of catastrophic bleeding 

RVOT conduits or pressurized chambers near sternum increase injury risk

Loss of peripheral vascular access from prior procedures limits bailout options

Accumulated comorbidities (renal, hepatic dysfunction) increase perioperative risk

Diastolic dysfunction and ventricular impairment complicate weaning from bypass

Complexity of planned repair and institutional/surgeon experience significantly influence outcomes 

What does “venting the ventricle” mean and why is it important?

Venting refers to decompression of the left ventricle using a cannula (often via right superior pulmonary vein)

Prevents LV distension, which can impair myocardial protection and lead to hemodynamic collapse

Particularly important in the presence of aortic insufficiency or inadequate forward flow

Failure to adequately vent can result in arrhythmias, poor recovery, and adverse outcomes

What materials are used in congenital surgery and how do they impact long-term care?

Common patch materials include bovine pericardium (durable, non-stretch), Dacron, Gore-Tex, and autologous pericardium

Conduits (e.g., homografts, Contegra, Hancock) are used to connect cardiac structures and often contain valves

Most materials do not grow with the patient and are prone to calcification over time

Surgical decisions must consider future transcatheter or surgical interventions

Limited availability of certain graft sizes (e.g., pulmonary homografts) impacts real-world decision-making

References:

1. Salis, S. et al. Cardiopulmonary bypass duration is an independent predictor of morbidity and mortality after cardiac surgery. J Cardiothorac Vasc Anesth. 2008;22(6):814-822. doi:10.1053/j.jvca.2008.08.004

2. Al-Sarraf, N. et al.  Cross-clamp time is an independent predictor of mortality and morbidity in low- and high-risk cardiac patients. International journal of surgery (London, England). 2011; 9(1):104–109. https://doi.org/10.1016/j.ijsu.2010.10.007

3. Weiland, A. P. et al. Physiologic principles and clinical sequelae of cardiopulmonary bypass. Heart & lung : the journal of critical care. 1986;15(1):34–39.

4. Park, C. B. et al. Identifying patients at particular risk of injury during repeat sternotomy: analysis of 2555 cardiac reoperations. The Journal of thoracic and cardiovascular surgery. 2010;140(5):1028–1035. https://doi.org/10.1016/j.jtcvs.2010.07.086

5. Morales, D. L. et al. Repeat sternotomy in congenital heart surgery: no longer a risk factor. The Annals of thoracic surgery. 2008; 86(3):897–902. https://doi.org/10.1016/j.athoracsur.2008.04.044

6. Francica, A. et al. Cardioplegia between Evolution and Revolution: From Depolarized to Polarized Cardiac Arrest in Adult Cardiac Surgery. Journal of clinical medicine. 2021;10(19):4485. https://doi.org/10.3390/jcm10194485

7. Ghia, S. et al. Hypothermic Circulatory Arrest in Adult Aortic Arch Surgery: A Review of Hypothermic Circulatory Arrest and its Anesthetic Implications. Journal of cardiothoracic and vascular anesthesia. 2023; 37(12): 2634–2645. https://doi.org/10.1053/j.jvca.2023.08.139

8. Peivandi, A. D. et al. Grafts and Patches: Optimized but Not Optimal Materials for Congenital Heart Surgery. Pediatric cardiology. 2023;44(5):996–1002. https://doi.org/10.1007/s00246-023-03153-6

The following question refers to Section 7.1 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 Michigan fellow and CardioNerds FIT Ambassador Dr. Kayla Secrest, and then by expert faculty Dr. Sunil Rao.

Dr. Rao is an interventional cardiologist, Professor of Medicine at NYU Grossman School of Medicine, Deputy Director of the Leon H. Charney Division of Cardiology, and the Director of Interventional Cardiology for the NYU Langone Health System. He is the Editor-in-Chief for Circulation Cardiovascular Interventions and was the Chair of the Writing Committee for the 2025 ACS Guidelines.

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.





Question #1

A 68-year-old man with a history of hypertension, hyperlipidemia, stage III chronic kidney disease, and prior tobacco use presents to a local emergency department with reports of chest pain while raking leaves at home. Upon arrival, he is hemodynamically stable with a heart rate of 86 beats per minute and a blood pressure of 133/85 mmHg. His EKG reveals ST elevations in the septal and anterior leads (V1-V4). He is given 324mg of aspirin and is promptly evaluated by the interventional cardiology team, who elects to take him emergently to the catheterization lab. Upon arrival to the catheterization lab, the nurse asks the interventional fellow which access sites they should prep for this case? How should the interventional fellow respond?

A

Right radial artery only

B

Radial + bilateral femoral

C

Bilateral femoral only





Answer #1

Explanation 

The correct answer is B. Radial and bilateral femoral

Radial artery access is the preferred vascular access site for coronary angiography and PCI in patients with ACS. Transradial access has been shown to reduce mortality, bleeding, and vascular complications compared with transfemoral access (Class I, LOE A). Radial access also allows earlier ambulation and is associated with greater patient comfort.

Although the right radial artery is the most widely studied upper-extremity access site, alternative sites such as the ulnar and distal radial arteries have demonstrated similar outcomes.

However, the radial artery may be required as a bypass conduit for CABG. In institutions where the radial artery is routinely used for surgical grafting, this potential future use should be considered when selecting vascular access.

In addition, transfemoral access—preferably performed with ultrasound guidance—should be considered in patients in whom temporary mechanical circulatory support (MCS) is anticipated or in those for whom radial access is not feasible due to anatomical or technical constraints. Prepping bilateral groins in addition to the radial artery provides a backup strategy for urgent MCS placement or for transition to femoral access should radial access fail.

For these reasons, prepping both the radial artery and bilateral groins is the most appropriate response.

Radial-only preparation is incorrect because, although radial access is preferred, patients with STEMI may still require emergent MCS or alternative access if the radial artery is unsuitable. Preparing only the wrist without backup femoral access may delay care should hemodynamic instability occur.

Femoral-only preparation is incorrect because transradial access provides superior outcomes in ACS, including significant reductions in all-cause mortality, major bleeding, and vascular complications. RCTs and meta-analyses, including MATRIX (which showed lower MACE and net adverse clinical events with radial access) and SAFARI-STEMI (which showed no difference in mortality but was underpowered)—support radial as first-line access when feasible.

Main Takeaway

For patients with ACS undergoing PCI, radial access is strongly preferred to reduce mortality, bleeding, and vascular complications.

Guideline Loc.

Section 7.1

CardioNerds (Dr. Billy-Joe Mullinax, Dr. Dinu Balanescu, and Dr. Jane Ehret) discuss risk stratification in acute pulmonary embolism with Dr. Stavros Konstantinides, Chair of the 2019 ESC Pulmonary Embolism Guidelines. Using a real-world case, this episode explores how modern PE care has moved beyond “massive” and “submassive” labels toward a dynamic, physiology-based approach. The discussion highlights the limitations of static risk scores, the importance of right ventricular dysfunction and biomarkers, and why normotension does not imply stability. Special emphasis is placed on intermediate-high risk PE, early identification of impending hemodynamic collapse, and the role of lactate, serial reassessment, and PERT teams in guiding escalation of care. Audio editing by CardioNerds intern, Joshua Khorsandi.
The 2026 American multi-society PE guidelines were published after this episode was recorded.

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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Pearls

Stable blood pressure does not mean low risk in PE
Hypotension is a late finding. Patients may have severe RV failure, hypoxia, and tissue hypoperfusion while remaining normotensive — a key concept behind “normotensive shock.”

Risk stratification in PE must be dynamic, not static
Legacy scores like PESI and Bova provide a snapshot and predict 30-day mortality, but they do not capture short-term trajectory or impending hemodynamic collapse.

Intermediate-high risk PE is a dangerous and heterogeneous group
Patients with RV dysfunction, positive biomarkers, tachycardia, hypoxemia, and elevated lactate may have in-hospital mortality approaching 15%, rivaling STEMI.

Lactate is a critical but underutilized marker in PE
Elevated lactate reflects tissue hypoxia and early circulatory failure and may identify patients at risk for collapse before blood pressure declines.

PERT enables physiology-driven, patient-centered PE care
PERT teams operationalize continuous reassessment, integrate imaging, labs, and clinical trajectory, and allow timely escalation — shifting PE management from rigid categories to real-time decision-making.

Notes

Drafted by Dr. Jane Ehret.

1. What is the contemporary framework for risk stratification in acute pulmonary embolism?

Modern PE risk stratification prioritizes hemodynamics and right ventricular (RV) function rather than clot burden.

The 2019 ESC Guidelines classify PE into high risk, intermediate risk (low vs high), and low risk, based on: Hemodynamic status, RV dysfunction on imaging, and Cardiac biomarkers.

This framework emphasizes early mortality risk but requires clinical context to guide escalation decisions.

2. Why is normotension insufficient to define “stability” in PE?

Blood pressure is a late marker of circulatory failure in PE.

Patients can maintain normal BP through Tachycardia, Increased sympathetic tone, and RV compensation.

Many patients with preserved BP may already have shock physiology, including hypoxemia, elevated lactate, and RV failure — sometimes referred to as “normotensive shock.”

3. How should intermediate-risk PE be conceptualized clinically?

Intermediate-risk PE is heterogeneous, ranging from patients who do well on anticoagulation to those who deteriorate rapidly.

Intermediate-high risk PE is defined by RV dysfunction on imaging and positive cardiac biomarkers.

Clinical features such as tachycardia, increasing oxygen requirement, and elevated lactate identify patients at highest risk within this group.

4. What are the strengths and limitations of commonly used PE risk scores?

Legacy scores are useful for initial risk categorization but are static and limited in predicting short-term deterioration.

Most scores were developed to predict mortality or complications at fixed time points rather than dynamic clinical trajectory.

5. What are the commonly used risk scores and clinical tools in PE, and what is each designed to predict?

ESC Risk Stratification Algorithm: Identifies high-risk PE by hemodynamics. Uses PESI or sPESI in normotensive patients to distinguish low-risk from non–low-risk PE. Uses RV dysfunction and biomarkers to differentiate intermediate-low from intermediate-high risk. Forms the basis of many institutional PE pathways.

PESI and sPESI: Validated to predict 30-day mortality. Widely used to identify low-risk patients appropriate for outpatient management. Heavily influenced by age and comorbidities.

Bova Score: Predicts 30-day PE-related complications in normotensive patients.

Composite PE Shock Score (CPES): Predicts normotensive shock in hemodynamically stable PE patients.

Pulmonary Embolism Progression (PEP) Score: Predicts progression from intermediate-risk to high-risk PE within 72 hours of diagnosis.

PE Short-term Clinical Outcomes Risk Estimation (PE-SCORE): Predicts clinical deterioration or death within 5 days of PE diagnosis.

Hestia Criteria: Identifies low-risk PE patients safe for outpatient treatment.

Wells’ Criteria and Revised Geneva Score: Determine pretest probability for diagnostic triage.

PERC Score: Rules out PE in very low-risk patients.

6. What is the role of biomarkers in PE risk stratification?

Troponin and natriuretic peptides reflect RV myocardial injury and strain.

Current guidelines treat biomarkers as binary (positive vs negative), despite risk being continuous.

Biomarkers are most helpful for: Initial risk classification.

They are less useful for: Short-interval monitoring and Detecting rapid clinical deterioration.

7. Why is lactate an important physiologic marker in PE?

Lactate reflects global tissue hypoxia and impaired perfusion.

Elevated lactate may identify patients with: Early circulatory failure and Increased risk of imminent hemodynamic collapse.

Lactate is not currently included in ESC risk algorithms but may add important prognostic information in intermediate-risk patients.

8. How does trajectory influence decision-making in PE management?

Risk stratification should be viewed as a dynamic process, not a one-time label.

Worsening clinical trajectory may include: Rising heart rate, Increasing oxygen needs, Rising lactate, and Progressive RV dysfunction.

Serial reassessment is essential for timely escalation of care.

9. What role do Pulmonary Embolism Response Teams (PERT) play in risk stratification?

PERT facilitates: Multidisciplinary decision-making and Integration of imaging, biomarkers, and clinical physiology.

PERT is most valuable for: Intermediate-risk and high-risk PE and Patients with complex comorbidities or uncertain trajectory.

PERT enables a shift from category-based to physiology-driven PE care.

References

1. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). Eur Respir J. 2019;54(3):1901647. Published 2019 Oct 9. doi:10.1183/13993003.01647-2019

2. Leidi A, Bex S, Righini M, Berner A, Grosgurin O, Marti C. Risk Stratification in Patients with Acute Pulmonary Embolism: Current Evidence and Perspectives. J Clin Med. 2022;11(9):2533. Published 2022 Apr 30. doi:10.3390/jcm11092533

3. Choi WH, Kwon SU, Jwa YJ, et al. The pulmonary embolism severity index in predicting the prognosis of patients with pulmonary embolism. Korean J Intern Med. 2009;24(2):123-127. doi:10.3904/kjim.2009.24.2.123

4. Jiménez D, Aujesky D, Moores L, et al. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med. 2010;170(15):1383-1389. doi:10.1001/archinternmed.2010.199

5. Chen X, Shao X, Zhang Y, et al. Assessment of the Bova score for risk stratification of acute normotensive pulmonary embolism: A systematic review and meta-analysis. Thromb Res. 2020;193:99-106. doi:10.1016/j.thromres.2020.05.047

6. Zhang RS, Yuriditsky E, Zhang P, et al. Composite Pulmonary Embolism Shock Score and Risk of Adverse Outcomes in Patients With Pulmonary Embolism. Circ Cardiovasc Interv. 2024;17(8):e014088. doi:10.1161/CIRCINTERVENTIONS.124.014088

7. Zhang RS, Alam U, Sharp ASP, et al. Validating the Composite Pulmonary Embolism Shock Score for Predicting Normotensive Shock in Intermediate-Risk Pulmonary Embolism. Circ Cardiovasc Interv. 2024;17(2):e013399. doi:10.1161/CIRCINTERVENTIONS.123.013399

8. Ehret J, Wakefield D, Badlam J, Antkowiak M, Erdreich B. Development of the Pulmonary Embolism Progression (PEP) score for predicting short-term clinical deterioration in intermediate-risk pulmonary embolism: a single-center retrospective study. J Thromb Thrombolysis. 2025;58(2):243-253. doi:10.1007/s11239-024-03051-5

9. Weekes AJ, Raper JD, Lupez K, et al. Development and validation of a prognostic tool: Pulmonary embolism short-term clinical outcomes risk estimation (PE-SCORE). PLoS One. 2021;16(11):e0260036. Published 2021 Nov 18. doi:10.1371/journal.pone.0260036

10. Zondag W, Hiddinga BI, Crobach MJ, et al. Hestia criteria can discriminate high- from low-risk patients with pulmonary embolism. Eur Respir J. 2013;41(3):588-592. doi:10.1183/09031936.00030412

11. Wells PS, Anderson DR, Rodger M, et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. Ann Intern Med. 2001;135(2):98-107. doi:10.7326/0003-4819-135-2-200107170-00010

12. Wolf SJ, McCubbin TR, Feldhaus KM, Faragher JP, Adcock DM. Prospective validation of Wells Criteria in the evaluation of patients with suspected pulmonary embolism. Ann Emerg Med. 2004;44(5):503-510. doi:10.1016/j.annemergmed.2004.04.002

13. Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med. 2006;144(3):165-171. doi:10.7326/0003-4819-144-3-200602070-00004

14. Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost. 2004;2(8):1247-1255. doi:10.1111/j.1538-7836.2004.00790.x

15. Kline JA, Courtney DM, Kabrhel C, et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost. 2008;6(5):772-780. doi:10.1111/j.1538-7836.2008.02944.x

CardioNerds Dr. Joseph Kassab, Dr. Mariana Garcia-Arango, and Dr. Christopher Mason explore the technological revolution of Coronary CT Angiography (CCTA) with expert faculty Dr. Michael Gallagher. The discussion details how CCTA has evolved into a frontline diagnostic and preventive tool, moving beyond simple anatomy to incorporate physiology via CT-FFR and biology through AI-driven plaque quantification. The episode reviews landmark evidence like the SCOT-HEART and PROMISE trials, the nuances of CAD-RADS 2.0 reporting, and the emerging role of AI in monitoring treatment response and personalizing cardiovascular care. Critically, they also discuss some of the assumptions and limitations of these techniques.

Stay tuned for a matching review article to be submitted to US Cardiology Review, the official Journal of CardioNerds.

This episode was supported by an independent medical education grant from HeartFlow. All CardioNerds education is planned, produced, and reviewed solely by CardioNerds. 

Enjoy this Circulation Paths to Discovery article to learn more about the CardioNerds mission and journey.

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

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Pearls

Shift in Paradigm: CCTA is no longer just an anatomic test; with some key limitations, it can provide anatomy, physiology (CT-FFR), and plaque biology (AI-CPA) in a single non-invasive scan.

The “Power of Zero” vs. Plaque: While a normal CCTA has a >95% negative predictive value, future MIs often arise from non-obstructive plaque that traditional stress tests might miss.

CAD-RADS 2.0 Utility: The addition of plaque burden modifiers (P1–P4) is a “game changer,” allowing clinicians to identify high-risk patients who need aggressive lipid-lowering despite having only mild stenosis.

CT-FFR as a Virtual Stress Test: CT-FFR uses computational fluid dynamics to simulate blood flow, potentially reducing unnecessary invasive catheterizations by approximately 61% without sacrificing safety.

Seeing the Invisible: AI-based quantitative plaque analysis (QCPA) can identify “subvisual” plaque and low-attenuation (lipid-rich) components that are the primary drivers of acute coronary syndromes.

Show Notes

How has the role of CCTA changed compared to traditional functional testing?

Historically, stress testing answered “is there ischemia today?”, which often reflects late-stage disease.

CCTA identifies disease across the entire spectrum, asking “is there atherosclerosis and how much plaque is present?”.

Landmark evidence: SCOT-HEART showed a 41% relative risk reduction in MI at 5 years attributed to intensified preventive therapies, and PROMISE showed CCTA was better at selecting patients who truly needed invasive angiography.

Diagnostic CCTA imaging depends on the protocol, contrast timing, heart rate, heart rhythm, breathholding, scanner quality, and several patient factors (obesity, prior stents, heavy calcification, complex bypass anatomy, and motion artifact all may limit imaging). “CCTA is exceptional for the right patient, with the right scanner, and the right team.”

What are the key modifiers introduced in CAD-RADS 2.0, and why do they matter?

CAD-RADS 2.0 moved beyond stenosis severity to include plaque burden (P0 to P4), high-risk plaque (HRP) features, and the presence of ischemia based on CT-FFR.

It serves as a clinical decision support tool: a patient with mild (25-49%) stenosis but “extensive” (P4) plaque burden is considered high risk and warrants aggressive risk factor modification.

How is CT-FFR calculated, and when is it most useful in clinical practice?

CT-FFR uses resting CCTA data and computational fluid dynamics to create a 3D model of coronary flow during simulated maximal hyperemia.

It is often used for intermediate lesions (40–90% stenosis) to predict if they are  ischemia-producing, guiding the decision whether to proceed with invasive angiography. 

The assumptions necessary for this computational modeling may not apply well to patients with microvascular dysfunction, significant myocardial scar or prior infarction, or ventricular hypertrophy. Still, data indicate that CT-FFR performs similarly to PET in predicting hemodynamically significant lesions. 

CT-FFR performs well at the extremes (either clearly normal or clearly abnormal). Accuracy dips, however, in the intermediate range (~0.75-0.80), where decision-making is most critical. In this grey zone, additional factors can help guide the approach, including the amount of myocardium supplied, translesional gradient, and plaque features.  

CT-FFR has not been validated in distal segments, stented segments, heavily calcified coronary arteries, or in patients with severe aortic stenosis. Caution with CT-FFR should be utilized in very calcified coronary segments. 

What is AI-based quantitative plaque analysis (QCPA), and what metrics are ready for clinical use?

This is potentially a paradigm shift, moving away from stenosis-centric thinking to a more disease burden and plaque biology focus.

QCPA uses deep learning algorithms to automatically segment the vessel wall and quantify plaque volume in mm³.

Ready for “prime time” metrics include: Total Plaque Volume (TPV), non-calcified plaque volume, and Low-Attenuation Plaque (LAP) burden.

Can serial CCTA be used to monitor the effectiveness of medical therapies like statins?

While not yet a routine guideline-driven practice, trials like PARADIGM and EVAPORATE show that therapies can stabilize plaque; notably, CCTA is better for monitoring than CAC scores, which can be misleading as statins often increase plaque calcification as part of the stabilization process.

There are no randomized trials that serial CCTAs improve outcomes. Cost and radiation exposure will be notable limitations. Serial scan timing, scan acquisition and interpretation standardization would be key.

Dr. Gallagher notes that we are moving toward a world in which plaque burden may become a “treatment biomarker,” similar to tumor burden in oncology. 

References

1. Coronary Computed Tomography Angiography From Clinical Uses to Emerging Technologies: JACC State-of-the-Art Review. Abdelrahman KM, Chen MY, Dey AK, et al. Journal of the American College of Cardiology. 2020;76(10):1226-1243. doi:10.1016/j.jacc.2020.06.076.

2. Non-Invasive Imaging in Coronary Syndromes: Recommendations of the European Association of Cardiovascular Imaging and the American Society of Echocardiography, in Collaboration With the American Society of Nuclear Cardiology, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. Edvardsen T, Asch FM, Davidson B, et al. Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2022;35(4):329-354. doi:10.1016/j.echo.2021.12.012.

3. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Gulati M, Levy PD, Mukherjee D, et al. Journal of the American College of Cardiology. 2021;78(22):e187-e285. doi:10.1016/j.jacc.2021.07.053.

4. Contemporary, Non-Invasive Imaging Diagnosis of Chronic Coronary Artery Disease. van der Bijl P, Gulati M, Saraste A, et al. Lancet (London, England). 2025;406(10519):2577-2587. doi:10.1016/S0140-6736(25)01586-7.

5. State of the Art: Evaluation and Medical Management of Nonobstructive Coronary Artery Disease in Patients With Chest Pain: A Scientific Statement From the American Heart Association. Slipczuk L, Blankstein R, Bucciarelli-Ducci C, et al. Circulation. 2025;152(23):e443-e466. doi:10.1161/CIR.0000000000001394.

6. Diagnostic Performance of Fractional Flow Reserve Derived From Coronary CT Angiography: The ACCURATE-CT Study. Li C, Hu Y, Jiang J, et al. JACC. Cardiovascular Interventions. 2024;17(17):1980-1992. doi:10.1016/j.jcin.2024.06.027.

7. Clinical Outcomes Based on Coronary Computed Tomography-Derived Fractional Flow Reserve and Plaque Characterization. Sato Y, Motoyama S, Miyajima K, et al. JACC. Cardiovascular Imaging. 2024;17(3):284-297. doi:10.1016/j.jcmg.2023.07.013.

8. Clinical Use of Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve: Expert Consensus by an International Working Group. Tang CX, Leipsic JA, Nørgaard BL, et al. European Radiology. 2026;:10.1007/s00330-025-12313-6. doi:10.1007/s00330-025-12313-6.

9. Diagnostic accuracy of computed tomography–derived fractional flow reserve: a systematic review. Cook CM, Petraco R, Shun-Shin MJ, et al. JAMA Cardiol. 2017;2(7):803-810. Doi:10.1001/jamacardio.2017.1314

10. Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). Nørgaard BL, Leipsic J, Gaur S, et al. J Am Coll Cardiol. 2014;63(12):1145-1155. Doi:10.1016/j.jacc.2013.11.043

11. Comparison of coronary computed tomography angiography, fractional flow reserve, and perfusion imaging for ischemia diagnosis. Driessen RS, Danad I, Stuijfzand WJ, et al. J Am Coll Cardiol. 2019;73(2):161-173. Doi:10.1016/j.jacc.2018.10.056.

12. 1-year outcomes of FFRCT-guided care in patients with suspected coronary disease: the PLATFORM study. Douglas PS, De Bruyne B, Pontone G, et al. J Am Coll Cardiol. 2016;68(5):435-445. Doi:10.1016/j.jacc.2016.05.057.

13. Comparison of an initial risk-based testing strategy vs usual testing in stable symptomatic patients with suspected coronary artery disease: the PRECISE randomized clinical trial. Douglas PS, Nanna MG, Kelsey MD, et al; PRECISE Investigators. JAMA Cardiol. 2023;8(10):904-914. Doi:10.1001/jamacardio.2023.2595.

14. Diagnostic and clinical value of FFRCT in stable chest pain patients with extensive coronary calcification: the FACC study. Mickley H, Veien KT, Gerke O, et al. JACC Cardiovasc Imaging. 2022;15(6):1046-1058. doi:10.1016/j.jcmg.2021.12.010.

15. Low-Attenuation Noncalcified Plaque on Coronary Computed Tomography Angiography Predicts Myocardial Infarction: Results From the Multicenter SCOT-HEART Trial (Scottish Computed Tomography of the HEART). Williams MC, Kwiecinski J, Doris M, et al. Circulation. 2020;141(18):1452-1462. doi:10.1161/CIRCULATIONAHA.119.044720.

16. AI-Guided Quantitative Plaque Staging Predicts Long-Term Cardiovascular Outcomes in Patients at Risk for Atherosclerotic CVD. Nurmohamed NS, Bom MJ, Jukema RA, et al. JACC. Cardiovascular Imaging. 2024;17(3):269-280. doi:10.1016/j.jcmg.2023.05.020.

17. Interaction of AI-Enabled Quantitative Coronary Plaque Volumes on Coronary CT Angiography, FFRCT, and Clinical Outcomes: A Retrospective Analysis of the ADVANCE Registry. Dundas J, Leipsic J, Fairbairn T, et al. Circulation. Cardiovascular Imaging. 2024;17(3):e016143. doi:10.1161/CIRCIMAGING.123.016143.

18. Prognostic Value of AI-Based Quantitative Coronary CTA vs Human Reader-Based Visual Assessment: Results From the CONFIRM2 Registry. van Rosendael A, Nakanishi R, Bax JJ, et al. JACC. Cardiovascular Imaging. 2026;19(3):345-359. doi:10.1016/j.jcmg.2025.09.021.
13. Pericoronary Adipose Tissue as a Marker of Cardiovascular Risk: JACC Review Topic of the Week. Tan N, Dey D, Marwick TH, Nerlekar N. Journal of the American College of Cardiology. 2023;81(9):913-923. doi:10.1016/j.jacc.2022.12.021.

19. Effect of Icosapent Ethyl on Progression of Coronary Atherosclerosis in Patients With Elevated Triglycerides on Statin Therapy: Final Results of the EVAPORATE Trial. Budoff MJ, Bhatt DL, Kinninger A, et al. European Heart Journal. 2020;41(40):3925-3932. doi:10.1093/eurheartj/ehaa652.

20. Coronary CT Angiography Evaluation With Artificial Intelligence for Individualized Medical Treatment of Atherosclerosis: A Consensus Statement From the QCI Study Group. Schulze K, Stantien AM, Williams MC, et al. Nature Reviews. Cardiology. 2026;23(2):100-115. doi:10.1038/s41569-025-01191-6.

Join CardioNerds EP Council Chair Dr. Naima Maqsood and Episode Lead Dr. Sukriti Banthiya as they discuss the results of the International Collaborative LBBAP Study (I-CLAS) with expert faculty Dr. Theofanie Mela and Dr. Pugazhendhi Vijayraman. Audio editing by CardioNerds academy intern, Grace Qiu.

The International Collaborative LBBAP Study (I-CLAS) evaluated clinical outcomes between biventricular pacing (BVP) and left bundle branch area pacing (LBBAP) in patients with left ventricular ejection fraction (LVEF) ≤50% undergoing cardiac resynchronization therapy. Between January 2018 and June 2023, 2,579 patients were enrolled across 18 centers. The primary composite outcome was defined as all-cause mortality or heart failure hospitalization. LBBAP demonstrated a shorter paced QRS duration and was associated with a lower risk of primary composite outcome and heart failure hospitalization. No significant difference was observed in all-cause mortality. Additionally, procedural complications were lower with LBBAP.

This episode was planned in collaboration with  Heart Rhythm TV with mentorship from Dr. Daniel Alyesh and Dr. Mehak Dhande. 

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

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