Cardionerds: A Cardiology Podcast

This inaugural episode of the CardioNerds Pulmonary Embolism (PE) Series explores the evolution of acute PE care. Dr. Ibrahim Zahid, Dr. Dinu Balanescu, and Dr. Billy Joe Mullinax join guest expert Dr. Kenneth Rosenfield to discuss the shifting landscape of PE management.

Pulmonary embolism (PE) remains a leading cause of cardiovascular mortality and a frequent diagnostic challenge, often masquerading as myocardial infarction or a benign illness. Over the past decade, PE care has evolved from anticoagulation-only strategies to nuanced, risk-stratified, multidisciplinary management. Modern approaches integrate hemodynamics, biomarkers, and advanced imaging to guide therapy, including catheter-directed interventions and large-bore thrombectomy. The Pulmonary Embolism Response Team (PERT) model addresses historical gaps by coordinating rapid, multispecialty decision-making and standardizing care pathways. The PERT Consortium further advances PE care through education, research, and the world’s largest PE registry, while fostering leadership and research opportunities for trainees. Despite advances, long-term outcomes and post-PE syndromes remain important areas for future investigation. Audio editing by CardioNerds Academy intern, student doctor, Pace Wetstein.

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

CardioNerds Pulmonary Embolism Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls

PE is a “master masquerader”—maintain suspicion for atypical presentations like myocardial infarction, heart failure, flu, or anxiety.

Multidisciplinary management mediated through pulmonary embolism response teams improves outcomes and standardizes care.

Risk stratification integrates hemodynamics, biomarkers, and imaging.

Advanced therapies have expanded beyond anticoagulation.

Long‑term follow‑up and post‑PE syndrome need more research.

Notes

Notes: Notes drafted by Dr. Ibrahim Zahid.

1. How has the clinical approach to PE changed over the past decade?

PE is the third leading cause of cardiovascular death and historically under‑recognized.

Symptoms mimic MI, HF, asthma, syncope, and more.PE is a silent killer, and it should be recognized more as a cause of spontaneous cardiac arrest.

Where life threatening disease like stroke which is owned by neurological specialists and MI is primarily managed by cardiac specialists, PE is an entity without a professional home. The PERT Consortium brings the specialties together for PE care.

2. Ten years ago, a 58-year-old patient with a large bilateral PE, RV dilation, and positive biomarkers might have been managed with anticoagulation and close observation alone. Today, with evolving—but still uneven—data on advanced therapies, PE care feels far more nuanced and highly dependent on where you practice. What are the major gaps in traditional PE management that clinicians should recognize, and what care pathways should they be aware of across different hospital systems?

Care has shifted from anticoagulation‑only to multidisciplinary approaches like catheter directed thrombectomy.

Risk‑based pathways and the use of CT angiogram has improved early recognition. Risk stratification tools must be used as tools for early recognition of intermediate risk PE.

Untreated PE leads to chronic complications like chronic thromboembolic disease and chronic thromboembolic pulmonary hypertension, which requires long term clinic follow up.

3. What is the role of risk stratification tools such as PeSI, sPeSI scores, cardiac biomarkers, and imaging findings in PE, and how do they guide treatment decisions in real world practice?

Integrate vitals (blood pressure and heart rate), biomarkers (troponin, pro-BNP), RV/LV ratio assessment, acid‑base status, and scores.

Tools include PESI, sPESI, BOVA, HESTIA, FAST, Geneva, NEWS, shock index.

Vitals, lactate, acid-base status, and tools like NEWS or shock index track clinical evolution.

PESI/sPESI estimate 30-day mortality and help identify low-risk patients who may be candidates for early discharge or outpatient therapy.

Clinical judgment matters—scores don’t fully capture clot burden, trajectory, or bleeding risk.

4. How was the pulmonary embolism response team created, and since its creation, what evidence or outcome data became available to support the PERT model?

Originated after a sentinel case at MGH: A young, pregnant woman in her 30s, who collapsed at home, underwent thrombectomy, and had to be on ECMO for a few days. The case brought cardiology, cardiac surgeons and critical care physicians together for planning and improvement in her health, which was rewarding.

Thereby, it was decided to bring specialties involved in PE care together to create a response team.

The name of the team, Pulmonary Embolism Response Team (PERT), was coined by Richard Channick in the first meeting.

Posters were set up all over the hospital to call a centralized line when an acute PE is recognized

A meeting was held to present the concept of putting together a consortium, with development of action items and a PERT database.

Enabled rapid multidisciplinary input using early teleconferencing tools.

5. Given concerns about having too many ‘cooks in the kitchen’ during the initial PE call—especially with rotating teams—how can institutions reconcile workflow complexity with standardized pathways in a way that meaningfully supports and justifies the added burden on frontline clinicians?

Every hospital’s PERT is different, catering to their needs and workflow

At least two disciplines are needed to make a PERTData is currently being collected to guide further on how the workflow can be standardized

Most importantly, the team brings in resources that were not available prior to PERT formation.

6. What are the main goals of the PERT consortium, and how does it support clinicians and institutions involved?

To improve care and improve outcomes for patients with PE

Expand education, refine algorithms, standardize care with Centers of Excellence.

Maintain the largest PE registry for research and outcomes improvement.

7. Beyond global networking, shared learning from successful systems, and the pathway toward Center of Excellence designation, what additional benefits can clinicians and health systems gain by participating in the PERT Consortium?

The ability to learn from other systems, the ability to share experiences.

Allow people to develop their professional careers like leadership experience, becoming a member of the trainee council

Initiate projects and receive funding for your ideas

8. For trainees interested in pulmonary embolism care, how can a trainee be a champion at their institution? Does PERT provide assistance and how can they really contribute meaningfully even before becoming a fellow/attending?

Medical students and residents interested in PE should reach out to the consortium and the consortium will hook you up with the correct mentors who can nurture you along.

Listen to the podcasts.

Participate with your local PERT team

PERT wants involvement of people who are social media savvy to help spread the word on PE.

Top three take-away points from this episode

Acute PE care has advanced and multiple treatment modalities for acute PE including catheter directed therapy, large bore thrombectomy, are becoming standard of care.

Multidisciplinary models like PERT improve coordination and outcomes.

Trainees play a vital role in advancing PE care through involvement, research, and education

References

Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, Huisman MV, Humbert M, Jennings CS, Jiménez D, Kucher N, Lang IM, Lankeit M, Lorusso R, Mazzolai L, Meneveau N, Ní Áinle F, Prandoni P, Pruszczyk P, Righini M, Torbicki A, Van Belle E, Zamorano JL; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020 Jan 21;41(4):543-603. doi: 10.1093/eurheartj/ehz405. PMID: 31504429. https://pubmed.ncbi.nlm.nih.gov/31504429/

Rosovsky R, Zhao K, Sista A, Rivera-Lebron B, Kabrhel C. Pulmonary embolism response teams: Purpose, evidence for efficacy, and future research directions. Res Pract Thromb Haemost. 2019 Jun 9;3(3):315-330. doi: 10.1002/rth2.12216. PMID: 31294318; PMCID: PMC6611377. https://pmc.ncbi.nlm.nih.gov/articles/PMC6611377/

Rosenfield K, Bowers TR, Barnett CF, Davis GA, Giri J, Horowitz JM, Huisman MV, Hunt BJ, Keeling B, Kline JA, Klok FA, Konstantinides SV, Lanno MT, Lookstein R, Moriarty JM, Ní Áinle F, Reed JL, Rosovsky RP, Royce SM, Secemsky EA, Sharp ASP, Sista AK, Smith RE, Wells P, Yang J, Whatley EM; Pulmonary Embolism Research Collaborative (PERC) Attendees. Standardized Data Elements for Patients With Acute Pulmonary Embolism: A Consensus Report From the Pulmonary Embolism Research Collaborative. Circulation. 2024 Oct;150(14):1140-1150. doi: 10.1161/CIRCULATIONAHA.124.067482. Epub 2024 Sep 12. PMID: 39263752; PMCID: PMC11698503. https://pubmed.ncbi.nlm.nih.gov/39263752/

Sharifi M, Awdisho A, Schroeder B, Jiménez J, Iyer P, Bay C. Retrospective comparison of ultrasound facilitated catheter-directed thrombolysis and systemically administered half-dose thrombolysis in treatment of pulmonary embolism. Vasc Med. 2019 Apr;24(2):103-109. doi: 10.1177/1358863X18824159. Epub 2019 Mar 5. PMID: 30834822. https://pubmed.ncbi.nlm.nih.gov/30834822/

Pandya V, Chandra AA, Scotti A, Assafin M, Schenone AL, Latib A, Slipczuk L, Khaliq A. Evolution of Pulmonary Embolism Response Teams in the United States: A Review of the Literature. J Clin Med. 2024 Jul 8;13(13):3984. doi: 10.3390/jcm13133984. PMID: 38999548; PMCID: PMC11242386. https://pubmed.ncbi.nlm.nih.gov/38999548/

Rivera-Lebron B., McDaniel M., Ahrar K., Alrifai A., Dudzinski D.M., Fanola C., Blais D., Janicke D., Melamed R., Mohrien K., et al. Diagnosis, Treatment and Follow Up of Acute Pulmonary Embolism: Consensus Practice from the PERT Consortium. Clin. Appl. Thromb. Hemost. 2019;25:1076029619853037. doi: 10.1177/1076029619853037.
https://pubmed.ncbi.nlm.nih.gov/31185730/

CardioNerds (Dr. Jenna Skowronski [Heart Failure Council Chair], Dr. Shazli Khan, and Dr. Josh Longinow) are joined by renowned leaders in the field of AHFTC (Advanced Heart Failure and Transplant Cardiology) and mechanical circulatory support, Dr. Jeff Teuteberg and Dr. Mani Daneshmand to continue the discussion of advanced heart failure therapies by taking a deep dive into the world of durable LVADs (Left Ventricular Assist Devices). In this episode, we will review the history of ventricular assist devices, the basics of LVAD function, selection criteria for LVAD therapy, and surgical nuances of LVAD implantation. Audio Editing by CardioNerds intern, Joshua Khorsandi.

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

CardioNerds Heart Success Series Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls

There have been significant advances in the field of MCS/LVAD therapy since the first implanted LVAD in the 1960s, to the first FDA approved device in the early 2000’s, to now the HM3 LVAD, with the most important change being a centrifugal flow/magnetically levitated design that led to minimized hemocompatibility-related adverse events (HRAE’s) (MOMENTUM 3 trial comparing HM2 and HM3). 

The REMATCH trial in 2001 was a pivotal trial for LVAD therapy, demonstrating that in a population of patients with advanced HF (70% IV inotrope dependent), LVAD therapy significantly improved survival at both 1 and 2 years as compared to medical therapy alone.   

MOMENTUM 3 trial was a landmark trial for the HM3 device, showing that in a population of end stage HF patients (86% inotrope dependent, 32% INTERMACS 1-2, and 60% DT strategy), 5-year survival with HM3 was 58% and HM3 had lower HRAE’s compared with HM2. 

There are both patient-specific factors and surgical considerations when it comes to candidacy for LVAD therapy. 

RV function prior to LVAD is a key determinant for success post-LVAD 

Many patients being considered for LVAD may not have robust RV function, however, predicting RV failure after LVAD is exceedingly difficult.  

In general, it doesn’t matter how bad the RV may look on imaging; we care more about the pre-LVAD hemodynamics (look at the PAPi and RA/wedge ratio).  

What happens in the OR may be the most important determinant of how the RV will do with the LVAD! 

Notes

Notes drafted by Dr. Josh Longinow. 

1. Historical background of heart pumps and LVADs 

LVAD Evolution  

FDA approval year 
2001 
2008 
2012 
2017 

Pump 
HeartMate XVE  
HeartMate II 
Heartware HVAD 
HeartMate III 

Flow/Design Features 
Pulsatile Technology  
Continuous flow Axial design 
Continuous flow  Centrifugal design 
Continuous flow   Full MagLev + Centrifugal design 

The 1960’s ushered in the first ‘LVADs’, when the first air-powered ‘LVAD’ was implanted. It kept the patient alive for four days before the patient expired.  

The first generation of LVADs were pulsatile pumps  

The first nationally recognized, FDA approved LVAD was the HeartMate XVE (late 1990s to early 2000s, REMATCH trial). The XVE pump used compressed air (pneumatically driven) to power the pump.  

Prior to the XVE, OHT was the standard of care for patients with advanced, end-stage heart failure.  

The second and third generations of LVADs were non-pulsatile, continuous flow devices and included the HVAD, HM2, and HM3 devices.  

MOMENTUM 3 was a landmark trial for the HM3 device, showing that in a population of sick patients with end stage HF (86% inotrope dependent, 32% INTERMACS 1-2, and 60% DT strategy), 5-year survival with HM3 was 58% and HM3 had lower HRAE’s compared with HM2.  

The only pump that is currently FDA approved for implant is the HM3, although other pumps are in clinical trials (BrioVAD system, INNOVATE Trial). 

2. What are LVADs, and how do they work?  

In simplest terms, the LVAD is a heart pump comprised of several key mechanistic components:  

Inflow cannula 

Mechanical pump  

Outflow cannula 

Driveline 

Controller/Power source 

The HM3 differs from its predecessors (HM2 and HVAD) in several key ways;  

HM3 is placed intrapericardial whereas the HM2 was placed pre-peritoneal.  

Perhaps most importantly, the HM3 is a fully magnetically levitated, centrifugal flow pump, whereas the HM2 is an axial flow device. 

Axial flow pumps are not magnetically levitated, leading to more friction produced between the ruby bearing’s contact with the pump rotors, and higher rates of hemocompatibility related adverse events (HRAEs, i.e. pump thrombosis) and the HM2 was ultimately discontinued in favor of the HM3 (MOMENTUM 3 trial). 

3. What do the terms ‘Destination Therapy’ (DT) or ‘Bridge to Transplant’ (BTT) mean when it comes to LVADs?  

When LVADs first came on the stage, EVERYONE was a BTT; these early pumps weren’t designed for long term use (I.e. REMATCH Trial, Heartmate XVE) 

Destination therapy means the LVAD was placed in leu of transplant because there are contraindications to transplant  

REMATCH trial brought about the concept of “Destination therapy”, comparing outcomes in patients (with contraindications for transplant) who received an LVAD vs optimal medical therapy 

Bridge to transplant means we are placing the LVAD in a patient who may not be a transplant candidate at this moment in time (is too sick, or conversely, not sick enough), but may be down the line  

Bridge to recovery is another term used when the LVAD is being placed for a patient we think may have a recoverable cardiomyopathy 

4. What are some factors we should consider when assessing a patient’s candidacy for LVAD, in general, and from a surgical perspective?  

Patient factors  

Older age might push us towards thinking LVAD rather than transplant 

In general, age > 70 is the cutoff for transplant, but this is not a hard cut off and varies institution to institution   

In general, think about things that help predict recovery after a major surgery; Frailty and Nutritional status are important, we try to optimize these prior to LVAD implant  

Right ventricular function remains the Achilles heel of LV support 

We know that needing temporary RV support post LVAD puts you on a different survival curve than patients who don’t need RVAD support 

Studies have not been able to successfully predict who will develop RV failure after LVAD implantation 

What happens in the time between when the patient goes to the OR and when they get back to the ICU is an important determinant who might develop RV failure post LVAD  

Surgical techniques such as implanting the HM3 in the intra-thoracic cavity, rather than intra-pericardial may help maintain LV/RV geometry to help optimize the RV post LVAD  

Surgical considerations for LVAD candidacy 

Small, hypertrophied LV: HM3 inflow cannula is small, but small hypertrophied ventricles tend towards chamber collapse during systole causing suction, needing to run slower with lower flow rates 

Chest size/diameter: pumps have gotten so small now, that for adults, these have become less of a consideration 

BMI: low BMI used to be more of a concern with the older pumps due to where they were placed, and the relative size of the pump itself, not so much now with the smaller HM 3 pumps 

Calcified LV apex: would increase risk of stroke, bleeding  

Driveline tunneling becomes a concern in the super obese population, higher risk for driveline infections (might tunnel these driveline’s shorter, and to a less fatty region of the abdomen, could even tunnel out the thoracic cavity in the super obese to limit skin motion)   

5. Is there a role for MCS (i.e. temporary LVAD such as Impella) in pre-habilitation of patients prior to LVAD surgery?  

The theory of being able to improve systemic perfusion, decongest the organs, and make the patient feel better prior to surgery makes sense, but becomes problematic due to the lack of a hard end point/time for prehabilitation which might risk delays in surgery  

More likely that it can lead to delay in the surgery, with less-than-optimal benefit; you don’t want to prolong the wait for surgery and increase the risk for complications prior to surgery   

An Impella 5.5 is currently FDA approved for 2 weeks of support, not 2 months so timing is important to keep in mind 

It’s unlikely that you will take a patient and convert them from a malnourished, cachectic person in 2 weeks’ time  

6. Is there a role for LVAD therapy in the younger patient population? Should we be thinking of LVAD up front for these patients, with the goal of transplanting down the line?  

Recovery may be more likely in certain populations, particularly younger females with smaller LV’s; in those populations, perhaps bridge to recovery should be the focus, optimizing them on GDMT etc.  

The replacement of transplant, with MCS (LVAD) in young patients has become a topic of discussion, because these pumps have become better and better, with the thinking that an LVAD could bridge a patient for 10 years or so, and they could get a transplant later  

It is still a big unknown, but several concerns exist 

Patients who get LVADs might end up with complications that become contraindication to transplant down the line (stroke, sensitization etc)  

Patients and providers are more hesitant because of the more recent iteration for the UNOS criteria for OHT listing which no longer gives patients with an uncomplicated LVAD higher priority, and therefore they could end up waiting a longer time for a heart after undergoing LVAD 

References

Rose EA, Gelijns AC, Moskowitz AJ, et al. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med. 2001;345(20):1435-1443. doi:10.1056/NEJMoa012175 

Mehra MR, Uriel N, Naka Y, et al. A Fully Magnetically Levitated Left Ventricular Assist Device – Final Report. N Engl J Med. 2019;380(17):1618-1627. doi:10.1056/NEJMoa1900486 

Mancini D, Colombo PC. Left Ventricular Assist Devices: A Rapidly Evolving Alternative to Transplant. J Am Coll Cardiol. 2015;65(23):2542-2555. doi:10.1016/j.jacc.2015.04.039 

Mehra MR, Goldstein DJ, Cleveland JC, et al. Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices in the MOMENTUM 3 Randomized Trial. JAMA. 2022;328(12):1233-1242. doi:10.1001/jama.2022.16197 

Rose EA, Moskowitz AJ, Packer M, et al. The REMATCH trial: rationale, design, and end points. Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure. Ann Thorac Surg. 1999;67(3):723-730. doi:10.1016/s0003-4975(99)00042-9 

Kittleson MM, Shah P, Lala A, et al. INTERMACS profiles and outcomes of ambulatory advanced heart failure patients: A report from the REVIVAL Registry. J Heart Lung Transplant. 2020;39(1):16-26. doi:10.1016/j.healun.2019.08.017 

Mehra MR, Netuka I, Uriel N, et al. Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure: The ARIES-HM3 Randomized Clinical Trial. JAMA. 2023;330(22):2171-2181. doi:10.1001/jama.2023.23204 

Mehra MR, Nayak A, Morris AA, et al. Prediction of Survival After Implantation of a Fully Magnetically Levitated Left Ventricular Assist Device. JACC Heart Fail. 2022;10(12):948-959. doi:10.1016/j.jchf.2022.08.002 

Bhardwaj A, Salas de Armas IA, Bergeron A, et al. Prehabilitation Maximizing Functional Mobility in Patients With Cardiogenic Shock Supported on Axillary Impella. ASAIO J. 2024;70(8):661-666. doi:10.1097/MAT.0000000000002170 

CardioNerds (Dr. Ramy Doss, Dr. Kelly Arps, and Dr. Naima Maqsood) dive into the nuances of atrial fibrillation (AF) ablation with Dr. Jon Piccini. They provide a high-yield overview of AF ablation, guiding listeners from patient selection through post-procedural management. We review appropriate candidacy for catheter ablation across AF phenotypes, key elements of pre-procedural evaluation including imaging and anticoagulation strategy, and the fundamental procedural steps with pulmonary vein isolation as the cornerstone. The discussion compares lesion set strategies in de novo ablation and reviews currently used energy sources—including radiofrequency, cryoablation, and pulsed-field ablation—highlighting differences in safety and efficacy. They also examine surgical and hybrid approaches for selected patients and outline essential components of post-ablation care, including rhythm monitoring, anticoagulation decisions, and management of complications. This episode integrates contemporary evidence with practical insights to support clinicians delivering comprehensive AF ablation care. Audio editing for this episode was performed by CardioNerds intern Dr. Bhavya Shah.

NOTE: This episode was recorded in March 2025. Since then, the OCEAN trial showed that among patients who had had successful catheter ablation for atrial fibrillation at least 1 year earlier and had risk factors for stroke, treatment with rivaroxaban did not result in a significantly lower incidence of a composite of stroke, systemic embolism, or new covert embolic stroke than treatment with aspirin. 

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

CardioNerds Atrial Fibrillation Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

PEARLS 

Pulmonary veins (PVs) are the dominant triggers in early AF due to their unique myocardial sleeve electrophysiology.  

Pulmonary vein isolation (PVI) remains the cornerstone of AF ablation by blocking PV triggers from reaching the left atrium. Posterior wall isolation is sometimes performed in persistent AFib, but large RCTs found no significant benefit over PVI alone. 

Paroxysmal AF has the highest ablation success rates.  Left atrial health remains the major determinant of outcome. 

Ablation modalities include pulsed field ablation, radiofrequency ablation, and cryo-balloon ablation. PFA offers advantage of relative myocardial selectivity with near zero risk of atrio-esophageal fistula. 

Long-term anticoagulation decisions after ablation currently depend on CHA₂DS₂-VASc score. Recent evidence suggests the safety of stopping anticoagulation in low-risk patients after ablation. 

Early atrial arrhythmia recurrence during a blanking period after ablation (≤3 months) often reflects inflammation — not procedural failure. Late recurrence suggests PV reconnection or residual substrate and often requires repeat ablation.  

Hybrid surgical and catheter Afib ablation represent an aggressive strategy for rhythm control in patients with persistent or long-standing persistent AF with extensive substrate and/or patients who have had multiple failed catheter ablations. 

Notes

1. What is the mechanism behind AF initiation?

Atrial fibrillation (AF) is a progressive condition.

Early AF is primarily trigger-driven, most commonly from the pulmonary veins.

Pulmonary vein myocardial sleeves have unique electrophysiologic properties that promote premature beats and afterdepolarizations.

As AF progresses, atrial remodeling (fibrosis and scar) leads to a more substrate-driven arrhythmia.

2. How does early catheter ablation for atrial fibrillation work?

Electrical Isolation of pulmonary veins, blocking PV triggers from reaching the left atrium.

By reducing burden of atrial fibrillation, this may slow adverse atrial remodeling.

3. Which patients are good candidates for Afib ablation?

Functional Status: ambulatory, active patients derive the greatest benefit. Advanced frailty or severe end-stage cardiovascular disease reduces expected benefit.

Comorbidity Burden: CHA₂DS₂-VASc score helps risk-stratify not only stroke risk but also rhythm-control outcomes.

Type and Duration of AF

Paroxysmal AF → highest likelihood of success (burden reduction often 95–99%).

Long-standing persistent AF → lower suppression rates (often 50–80%).

Left Atrial Health: a major determinant of outcomes.

LA diameter >5.5 cm associated with significantly worse outcomes.

LA volume index (normal ≤34 mL/m²) is preferred over diameter for assessment.

4. What are the predictors of complications from AFib ablation procedures?

Low and high body mass index (BMI)

Chronic corticosteroid use

Severe enlargement of other cardiac chambers

Female gender is associated with a numerically higher risk of complications.

5. Role of preprocedural imaging with cardiac CT or MRI

Cardiac CT

Faster and convenient

Help define LA geometry and Pulmonary vein anatomy

Anatomic Variants as Right middle pulmonary vein, accessory pulmonary veins common pulmonary vein ostium, Atrial diverticula or Accessory left atrial appendage

Consider Cardiac MRI when:

Strong family history of atrial fibrillation or cardiomyopathy

Suspicion of occult structural heart disease

6. Key Procedural Steps in AF Ablation

There is significant variation across centers in anesthesia, mapping, and ablation strategies.

The following outline reflects a common contemporary approach.

Anesthesia & Monitoring

Most commonly performed under general anesthesia.

Benefits include improved catheter stability, enhanced patient comfort, and controlled ventilation (e.g., low-volume, high-frequency).

Invasive arterial line (A-line) is preferred for rapid detection of hypotension.

Vascular Access

Ultrasound-guided femoral venous access with multiple sheaths.

Micropuncture technique is ideal to minimize complications.

Intracardiac Echocardiography (ICE)

ICE catheter insertion.

Reduces complications, guides transseptal puncture, assesses catheter contact, and monitors for pericardial effusion.

Anticoagulation

Systemic heparin initiated before or immediately after transseptal access.

Activated clotting time (ACT) maintained in therapeutic range (typically >300 seconds).

Transseptal Puncture

Access to the left atrium via transseptal sheath.

Often uses electrocautery-assisted wire, with ICE guidance to improve safety.

Left Atrial Mapping

Creation of electroanatomic map (common in many centers).

Ideally performed in sinus rhythm.

Assesses left atrial geometry, voltage (for scar/substrate), and activation timing.

Ablation Strategy

Core component is pulmonary vein isolation (PVI).

Technology options include pulse field ablation (PFA), radiofrequency ablation, and cryoballoon ablation.

Additional ablation (case-dependent):

Posterior wall isolation

Targeting non-pulmonary vein triggers

Linear lesions

Ablation of organized atrial tachycardias/flutters

Emerging approaches include AI-guided strategies.

Post-Ablation Assessment

Confirm pulmonary vein entrance and exit block.

Remap left atrium (in many practices) to evaluate lesion completeness.

Check for complications (e.g., ICE assessment for pericardial effusion).

7. What is Electroanatomic Mapping?

Combines 3D geometry (anatomic reconstruction of cardiac chamber) with electrophysiology (electrical signals from tissue).

How it works:

Mapping catheter is moved along the atrial wall

Records electrograms

System generates:

3D chamber model

Voltage map (tissue health/scar)

Activation map (depolarization timing)

Key information provided

Voltage map (substrate assessment):

High voltage = healthy tissue

Low voltage = scar/fibrosis

Identifies areas needing additional ablation (e.g., posterior wall scar)

Activation map:

Visualizes wavefront propagation

Essential for diagnosing and ablating macroreentrant atrial flutters and organized atrial tachycardias

8. What is the current role of Afib ablaton outside pulmonary vein isolation?

While Pulmonary Vein Isolation (PVI) remains the cornerstone of atrial fibrillation (AF) ablation, adjunctive strategies are increasingly used for persistent AF, with varying levels of supporting data.

Non-PVI Triggers:

Arrhythmogenic foci found outside the pulmonary veins in 10% to 20% of patients.

Common sites include SVC, LAA, CS, and Crista Terminalis.

Identifying and ablating these inducible triggers—often provoked by isoproterenol—can reduce recurrence in persistent AF.

Posterior Wall Isolation (PWI):

The posterior wall is a driver for persistent AF.

Randomized evidence for routine PWI is conflicting.

Large RCTs found no significant benefit over PVI alone for first-time ablations.

Remains a primary adjunctive target for redo procedures.

AI-Guided Ablation:

Uses AI to identify “spatio-temporal dispersion” areas.

Recent TAILORED-AF trial demonstrate increased freedom from AF at 12 months compared to conventional PVI.

9. Comparison of ablation techniques

Pulsed Field Ablation (PFA) – Non-Thermal

Mechanism: irreversible electroporation

Key advantages:

Shorter procedural time

Comparable efficacy to thermal ablation

Higher myocardial tissue selectivity

No known risk of esophageal fistula or pulmonary vein stenosis

Low risk of phrenic nerve (usually transient)

Disadvantages:

Less flexibility for complex substrate

Hemolysis with possible AKI

Early and delayed coronary spasms

Skeletal muscle stimulation during energy delivery

Loss of all electrograms even with reversible injury can be misleading

Limited long term data

Radiofrequency Ablation (RFA) – Thermal (Heat)

Mechanism: resistive heating

Key advantages:

Highly versatile

Can tailor lesions

Long term experience

Disadvantages:

More procedural time (less with ultrahigh power RFA)

Very small risk of esophageal fistula (1/2000 but 50% mortality!)

Pulmonary vein stenosis

Rare Phrenic nerve palsy

Stem pops

Cryoballoon Ablation (CBA) – Thermal (Cold)

Mechanism: Uses extreme cold

Key Advantages:

Short learning curve

Single shot balloon

Highly reproducible

Good catheter stability (adhesion during freeze)

Low risk of thrombus

Disadvantages:

Similar to RFA

More phrenic nerve palsy

Less esophageal fistula and pulmonary vein stenosis

10. Other Complications of AF Catheter Ablation common to all modalities

Pericardial effusion/tamponade: 0.4–2.2%

Stroke/TIA: ~0.2–1.8%

In-hospital mortality: Very low (0.05–0.46%)

Often overstated in studies based on National Inpatient Sample (NIS) due to selection bias

Vascular access complications: Hematoma

11. Expert approach to Antiarrhythmic Drug (AAD) Therapy After AF Ablation

Continue AAD for the 3-month blanking period after catheter ablation.

Supported by multiple trials to reduce early AF recurrences.

Decreases hospitalizations during the healing phase by suppressing inflammation-related arrhythmias.

AADs do not clearly improve long-term freedom from AF.

At the 3-month follow-up:

If the patient is asymptomatic with no documented recurrence → discontinue AAD.

If recurrent AF occurs or high substrate burden persists → consider continuing AAD.

12. Expert approach to Anticoagulation After AF Ablation

All patients require anticoagulation for at least 3 months post–ablation.

Current guidelines recommend long-term anticoagulation decisions guided solely by CHA₂DS₂-VASc score.

Decisions should not be based on ablation success or arrhythmia burden.

New data support discontinuation in low-risk patients after careful shared decision-making.

In high-risk patients:

Observational data indicate ~2.5-fold increased stroke risk when anticoagulation is stopped.

OCEAN trial:

Generally low risk patients (mean CHA2DS2-VASc score 2.2).

Rivaroxaban did not significantly reduce composite stroke outcomes compared with aspirin.

13. Approach to recurrent Atrial Arrhythmias After AF Ablation

Early (≤3 months – blanking period):

True blanking probably less (6 weeks to 2 months)

Likely less with PFA

Often due to inflammation or lesion maturation

Should not be considered procedural failure

Management:

Continue or restart AAD

Electrical cardioversion for persistent symptomatic episodes

Avoid early repeat ablation

Late (>3 months) recurrences:

More likely due to pulmonary vein reconnection or residual atrial substrate

Arrhythmias include:

Recurrent atrial fibrillation

Atypical (macroreentrant) atrial flutter

Typical atrial flutter (cavotricuspid isthmus–dependent)

Focal atrial tachycardia

Management is often challenging and may include AAD, cardioversion, or repeat ablation.

14. When to Consider Hybrid Surgical and Catheter Ablation for Atrial Fibrillation?

Aggressive rhythm control strategy when standard endocardial approaches are insufficient.

Typically for persistent or long-standing persistent AF (>12 months).

Often used in patients with extensive substrate or multiple failed catheter ablations.

Can be performed during concomitant cardiac surgery or as a stand-alone hybrid procedure.

Benefits of surgical approach:

Epicardial posterior wall/dome ablation

PVI

Ligation of the ligament of Marshall

Left atrial appendage closure (e.g., AtriClip)

Approach:

Subxiphoid/minimally invasive surgical access

Endocardial EP confirmation

Additional PVI ablation and gap closure

Evidence suggests increased freedom from atrial arrhythmias at the expense of higher major adverse event risk.

CardioNerds (Dr. Shazli Khan, Dr. Jenna Skowronski, and Dr. Shiva Patlolla) discuss the management of patients post‑heart transplantation with Dr. Shelley Hall from Baylor University Medical Center and Dr. MaryJane Farr from UTSW. In this comprehensive review, we cover the physiology of the transplanted heart, immunosuppression strategies, rejection surveillance, and long-term complications including cardiac allograft vasculopathy (CAV) and malignancy. Audio editing for this episode was performed by CardioNerds intern Dr. Bhavya Shah.

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

CardioNerds Heart Success Series Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls

The Denervated Heart: The donor heart is surgically severed from the autonomic nervous system, leading to a higher resting heart rate (90-110 bpm) due to loss of vagal tone. Because the heart relies on circulating catecholamines rather than neural input to increase heart rate, patients experience a delayed chronotropic response to exercise and stress. Importantly, because afferent pain fibers are severed, ischemia is often painless.

Rejection Surveillance: Rejection is classified into Acute Cellular Rejection (ACR), which is T-cell mediated, and Antibody-Mediated Rejection (AMR), which is B-cell mediated. While endomyocardial biopsy remains the gold standard for diagnosis, non-invasive surveillance using gene-expression profiling (e.g., AlloMap) and donor-derived cell-free DNA (dd-cfDNA) is increasingly utilized to reduce the burden of invasive procedures.

The Infection Timeline: The risk of infection follows a predictable timeline based on the intensity of immunosuppression. The first month is dominated by nosocomial infections. Months one through six are the peak for opportunistic infections (Cytomegalovirus, Pneumocystis, Toxoplasmosis) requiring prophylaxis. After six months, patients are primarily at risk for community-acquired pathogens, though late viral reactivation can occur.

Cardiac Allograft Vasculopathy (CAV): Unlike native coronary artery disease, CAV presents as diffuse, concentric intimal thickening that affects the entire length of the vessel, including the microvasculature. Due to denervation, patients rarely present with angina; instead, CAV manifests as unexplained heart failure, fatigue, or sudden cardiac death.

Malignancy Risk: Long-term immunosuppression significantly increases the risk of malignancy. Skin cancers (squamous and basal cell) are the most common, followed by Post-Transplant Lymphoproliferative Disorder (PTLD), which is often driven by Epstein-Barr Virus (EBV) reactivation.

Notes

Notes: Notes drafted by Dr. Patlolla

1. What are the unique physiological features of the transplanted heart?

The hallmark of the transplanted heart is denervation. Because the autonomic nerve fibers are severed during harvest, the heart loses parasympathetic or vagal tone, resulting in a resting tachycardia (typically 90-110 bpm). The heart also loses the ability to mount a reflex tachycardia; thus, the heart rate response to exercise or hypovolemia relies on circulating catecholamines, which results in a slower “warm-up” and “cool-down” period during exertion.

2. What are the pillars of maintenance immunosuppression regimen?

The triple drug maintenance regimen typically consists of:

Calcineurin Inhibitor (CNI): Tacrolimus is preferred over cyclosporine. Key side effects include nephrotoxicity, hypertension, tremor, hyperkalemia, and hypomagnesemia.

Antimetabolite: Mycophenolate mofetil (MMF) inhibits lymphocyte proliferation. Key side effects include leukopenia and GI distress.

Corticosteroids: Prednisone is used for maintenance but is often weaned to low doses or discontinued after the first year to mitigate metabolic side effects (diabetes, osteoporosis, weight gain).

3. How is rejection classified and diagnosed?

Rejection is the immune system’s response to the foreign graft and is categorized by the arm of the immune system involved:

Acute Cellular Rejection (ACR): Mediated by T-lymphocytes infiltrating the myocardium. It is graded from 1R (mild) to 3R (severe) based on the extent of infiltration and myocyte damage.

Antibody-Mediated Rejection (AMR): Mediated by B-cells producing donor-specific antibodies (DSAs) that attack the graft endothelium. It is diagnosed via histology (capillary swelling) and immunofluorescence (C4d staining).

Diagnosis has historically relied on endomyocardial biopsy. However, non-invasive tools are gaining traction. Gene Expression Profiling (GEP) assesses the expression of genes associated with immune activation to rule out rejection in low-risk patients. Donor-Derived Cell-Free DNA (dd-cfDNA) measures the fraction of donor DNA in the recipient’s blood. Elevated levels suggest graft injury which can occur in both ACR and AMR.

4. What is the timeline of infectious risk and how does it guide prophylaxis?

Infectious risk correlates with the net state of immunosuppression.

< 1 Month (Nosocomial): Risks include surgical site infections, catheter-associated infections, and aspiration pneumonia.

1 – 6 Months (Opportunistic): This is the period of peak immunosuppression. Patients are at risk for PJP, CMV, Toxoplasma, and fungal infections. Prophylaxis typically includes Trimethoprim-Sulfamethoxazole (for PJP/Toxo) and Valganciclovir (for CMV, dependent on donor/recipient serostatus).

> 6 Months (Community-Acquired): As immunosuppression is weaned, the risk profile shifts toward community-acquired respiratory viruses (Influenza, RSV) and pneumonias. However, patients with recurrent rejection requiring boosted immunosuppression remain at risk for opportunistic pathogens.

5. How does Cardiac Allograft Vasculopathy (CAV) differ from native CAD?

CAV is the leading cause of late graft failure. Unlike the focal, eccentric plaques seen in native atherosclerosis, CAV is an immunologically driven process causing diffuse, concentric intimal hyperplasia. It affects both epicardial vessels and the microvasculature. Because of this diffuse nature, percutaneous coronary intervention (PCI) is often technically difficult and provides only temporary palliation. The only definitive treatment for severe CAV is re-transplantation. Surveillance is critical and is typically performed via annual coronary angiography, often using intravascular ultrasound (IVUS) to detect early intimal thickening before it is visible on the angiogram.

References

Costanzo MR, Dipchand A, Starling R, et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010;29(8):914-956. doi:10.1016/j.healun.2010.05.034. https://www.jhltonline.org/article/S1053-2498(10)00358-X/fulltext

Kittleson MM, Kobashigawa JA. Cardiac Allograft Vasculopathy: Current Understanding and Treatment. JACC Heart Fail. 2017;5(12):857-868. doi:10.1016/j.jchf.2017.07.003. https://www.jacc.org/doi/10.1016/j.jchf.2017.07.003

Velleca A, Shullo MA, Dhital K, et al. The International Society for Heart and Lung Transplantation (ISHLT) guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2023;42(5):e1-e141. doi:10.1016/j.healun.2022.10.015. https://www.jhltonline.org/article/S1053-2498(22)02187-5/fulltext

CardioNerds (Dr. Colin Blumenthal, Dr. Kelly Arps, and Dr. Natalie Marrero) discuss anti-arrhythmic drugs in the management of atrial fibrillation and atrial flutter with electrophysiologist Dr. Andrew Epstein. We discuss two major classes of anti-arrhythmic drugs, class IC and class III, as well as digoxin. Dr. Epstein explains their mechanisms of action, indications and specific patient populations in which they would be particularly helpful, efficacy, adverse side effects, contraindications, and key drug-drug interactions. We also elaborate on defining clinical trials and their clinical implications. Given the large burden of atrial fibrillation and atrial flutter in our patient population and the high prevalence of anti-arrhythmic drug use, this episode is sure to be applicable to many practicing physicians and trainees. Audio editing by CardioNerds academy intern, Grace Qiu. 

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

CardioNerds Atrial Fibrillation Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll

CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!

Pearls

Anti-arrhythmic drugs should not be thought of as an alternative to ablation but, instead, should be considered an adjunct to catheter ablation.  

Class IC anti-arrhythmic drugs, flecainide and propafenone, are highly efficacious for acute cardioversion and a great option for patients with infrequent episodes of AF who do not have a history of ischemic heart disease.   

Class III anti-arrhythmic drugs like ibutilide, sotalol, and dofetilide, are highly effective for acute conversion; however, they require hospitalization for close monitoring during initiation and dose titration given the risk of prolonged QT.  

Amiodarone should not be used as a first line agent given its toxicities, prolonged half-life, large volume of distribution, and drug-drug interactions.  

Dr. Epstein notes that, “All drugs are poisons with a few beneficial side effects,” when highlighting the many adverse side effects of anti-arrhythmic drugs, particularly amiodarone, and the importance of balancing their benefit in rhythm control with their side effect profile.  

Notes

Notes: Notes drafted by Dr. Natalie Marrero. 

What are the Class IC anti-arrhythmic drugs and what indications exist for their use?  

Class IC anti-arrhythmic drugs are anti-arrhythmic drugs that work by blocking sodium channels and, thereby, prolonging depolarizing.  

Class IC anti-arrhythmic drugs include flecainide and propafenone.  

Class IC anti-arrhythmic drugs are good agents to use in patients that have infrequent episodes of AF and do not want daily dosing as these agents can be used by patients when they feel palpitations and desire acute conversion back to sinus rhythm (“pill in the pocket” approach).   

What are the adverse consequences and/or contraindications to using a class IC agent? 

Class IC anti-arrhythmic agents are contraindicated in patients with a history of ischemic heart disease based on increased mortality associated with their use in these patients in the CAST trial.  

Given the results of the CAST trial, providers should screen annually for ischemia via a functional stress test in patients on these drugs at risk for coronary disease.  

These drugs can increase 1:1 conduction of atrial flutter and, therefore, require concomitant use of a beta blocker.  

These agents are generally well-tolerated without any organ toxicities; however, they can precipitate heart failure in patients with cardiomyopathies, cause sinus node depression, and unmask genetic arrythmias such as a Brugada pattern.  

What are the class III agents and what are indications for their use?  

Class III agents are drugs that block the potassium channel, prolonging the QT, and include Ibutilide, Sotalol, and Dofetilide.   

Class III agents can be considered in patients with or without a history of ischemic heart disease that desire effective acute chemical cardioversion and are willing to go to the hospital for close monitoring during dose initiation and titration.  

Other specific circumstances in which one can use these agents, specifically Ibutilide, are in patients with recurrent atrial fibrillation and Wolf Parkinson White (due to slowed conduction via the accessory pathway). 

What are the adverse consequences and/or contraindications to using a class III agent? 

Ibutilide, Sotalol, and Dofetilide prolong the QT and increase the risk of torsade de pointes, which is why they require ECG monitoring in-patient during drug initiation and dose titration.   

These agents are generally well-tolerated.  

Sotalol should be avoided or used cautiously in patients with left ventricular dysfunction, while dofetilide can be used and has dose-response beneficial effects in patients with left ventricular dysfunction.  

Both sotalol and dofetilide are renally cleared with specific creatinine clearance cutoffs (CrCl < 20 for dofetilide and CrCl <40 for sotalol) and their dose should be adjusted based on the patient’s creatinine clearance (not eGFR). 

What is the mechanism of action and indications for using amiodarone?  

Amiodarone is a class III anti-arrhythmic agent, so it blocks the potassium channel prolonging the QT. Amiodarone is a “dirty drug” as it also has Class I (sodium channel blockade), Class II (antisympathetic action), and Class IV (calcium channel blockade) actions.   

Amiodarone should be used as a second line agent.  

Amiodarone can be considered in young, stable outpatients who are already in sinus rhythm especially greater than 60 beats per minute for outpatient loading.  

What are the drawbacks of amiodarone?  

Amiodarone, given its large volume of distribution and need to reach ~10 g for efficacy in conversion, takes a longer time to load and, therefore, a longer time to cardiovert.  

Amiodarone is associated with multiple organ toxicities including pulmonary fibrosis, thyroid toxicity (both hypothyroidism and hyperthyroidism), peripheral neuropathy, sinus bradycardia, QT prolongation, corneal deposits, retinitis and vision loss.  

Given the organ toxicities, patients on amiodarone should have their LFTs and TSH, a chest X-ray, and electrocardiogram checked at least every 6 months.  

Amiodarone sensitizes patients to warfarin and increases digoxin levels, so if patients are on amiodarone with warfarin or digoxin, lower levels of warfarin or digoxin should be used.  

What is dronedarone? How does it differ from amiodarone?  

Dronedarone is a class III antiarrhythmic, which means it works by blocking the potassium channel and prolonging the QT.  

Dronedarone differs from amiodarone in that it lacks iodine moiety and, therefore, does not have the associated thyroid toxicities. It also has a shorter half-life and smaller volume of distribution.  

What are the contraindications to using dronedarone?  

In the PALACE trial, dronedarone was associated with increased mortality in patients with heart failure, so it should be avoided in patients with clinical heart failure within the last six months.  

What is the mechanism of action and indication for using digoxin?  

Digoxin has several mechanisms of action including increasing vagal tone, inhibiting the sodium potassium ATPase, and acting as a positive inotrope. 

Digoxin is indicated as a second line drug when better rate control is needed.  

Digoxin improves rate control by increasing vagal tone and so may have an impact on resting rates. However, exertional rates may remain unctonrolled since these are mediated by sympathetic tone.  

Digoxin is a good option in patients that are not particularly active given that it decreases ventricular rate at rest, but not with exercise. 

Digoxin may be particularly beneficial in patients with heart failure given its positive ionotropic effects.  

What are the adverse side effects of digoxin and special monitoring required for patients on digoxin?  

Typically, digoxin levels are monitored, however they are usually not helpful as the levels are often drawn randomly. To be informative, the levels need to be a trough levels drawn right before the drug is given.  

The literature contains conflicting results on the mortality associated with digoxin levels.  

In general, the consensus in the field is that lower levels are better.  

Digoxin is renally cleared, so levels should be closely monitored in patients with renal failure.  

References

1. Mar PL, Horbal P, Chung MK, et al. Drug interactions affecting antiarrhythmic drug use. Circulation: Arrhythmia and Electrophysiology. 2022;15(5):e007955. https://doi.org/10.1161/CIRCEP.121.007955. doi: 10.1161/CIRCEP.121.007955. 

2. Gianfranchi L, Luzi M, Solano A, et al. Outpatient treatment of recent-onset atrial fibrillation with the “pill-in-the-pocket” approach. N Engl J Med. 2004;351(23):2384–2391. https://doi.org/10.1056/NEJMoa041233. doi: 10.1056/NEJMoa041233. 

3. Barker AH, Echt DS, Arensberg D, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. N Engl J Med. 1991;324(12):781–788. https://doi.org/10.1056/NEJM199103213241201. doi: 10.1056/NEJM199103213241201. 

4. Markman Timothy M., Jarrah Andrew A., Ye T, et al. Safety of pill-in-the-pocket class 1C antiarrhythmic drugs for atrial fibrillation. JACC: Clinical Electrophysiology. 2022;8(12):1515–1520. https://doi.org/10.1016/j.jacep.2022.07.010. doi: 10.1016/j.jacep.2022.07.010. 

5. Joglar JA, Chung MK, Armbruster AL, et al. 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation: A report of the american college of cardiology/american heart association joint committee on clinical practice guidelines. Circulation. 2024;149(1):e1–e156. https://doi.org/10.1161/CIR.0000000000001193. doi: 10.1161/CIR.0000000000001193. 

6. Ferrari F, Santander IRMF, Stein R. Digoxin in Atrial Fibrillation: An Old Topic Revisited. Curr Cardiol Rev. 2020;16(2):141-146. doi:10.2174/1573403X15666190618110941 

7. Van Gelder I,C., Rienstra M, Bunting KV, et al. 2024 ESC guidelines for the management of atrial fibrillation developed in collaboration with the european association for cardio-thoracic surgery (EACTS): Developed by the task force for the management of atrial fibrillation of the european society of cardiology (ESC), with the special contribution of the european heart rhythm association (EHRA) of the ESC. endorsed by the european stroke organisation (ESO). Eur Heart J. 2024;45(36):3314–3414. https://doi.org/10.1093/eurheartj/ehae176. doi: 10.1093/eurheartj/ehae176. 

8. Copaescu AM, Vogrin S, James F, et al. Efficacy of a Clinical Decision Rule to Enable Direct Oral Challenge in Patients With Low-Risk Penicillin Allergy: The PALACE Randomized Clinical Trial. JAMA Intern Med. 2023;183(9):944-952. doi:10.1001/jamainternmed.2023.2986 

9. Kirchhof P, Camm AJ, Goette A, et al. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. N Engl J Med. 2020;383(14):1305-1316. doi:10.1056/NEJMoa2019422 

10. Anderson JL, Platia EV, Hallstrom A, et al. Interaction of baseline characteristics with the hazard of encainide, flecainide, and moricizine therapy in patients with myocardial infarction. A possible explanation for increased mortality in the Cardiac Arrhythmia Suppression Trial (CAST). Circulation. 1994;90(6):2843-2852. doi:10.1161/01.cir.90.6.2843 

11.Akiyama T, Pawitan Y, Greenberg H, Kuo C, Reynolds-Haertle R, The CI. Increased risk of death and cardiac arrest from encainide and flecainide in patients after non-Q-wave acute myocardial infarction in the cardiac arrhythmia suppression trial. Am J Cardiol. 1991;68(17):1551–1555. https://doi.org/10.1016/0002-9149(91)90308-8. doi: 10.1016/0002-9149(91)90308-8. 

12. Parkash R, Wells GA, Rouleau J, et al. Randomized Ablation-Based Rhythm-Control Versus Rate-Control Trial in Patients With Heart Failure and Atrial Fibrillation: Results from the RAFT-AF trial. Circulation. 2022;145(23):1693-1704. doi:10.1161/CIRCULATIONAHA.121.057095