Cardionerds: A Cardiology Podcast

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.

CardioNerds Case Reports 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 combination of low voltage on ECG and increased wall thickness on echocardiogram should always raise suspicion for an infiltrative cardiomyopathy, not hypertensive heart disease.

A negative SPEP does not exclude a plasma cell dyscrasia; serum free light chains and urine immunofixation are required, and PYP should only be used to support a noninvasive ATTR diagnosis after a monoclonal process has been excluded.

Nearly one in four ATTR patients have a coexisting MGUS, making serum markers alone insufficient to distinguish AL from ATTR; when cardiac involvement is suspected, endomyocardial biopsy remains the gold standard for confirming amyloid deposition.

Preload dependence and low stroke volume in cardiac amyloidosis create extreme sensitivity to volume shifts and positional changes, requiring a much narrower margin of safety than typical heart failure.

In advanced cardiac AL amyloidosis, delays in initiating anti-plasma cell therapy can rapidly narrow the therapeutic window, making urgent multidisciplinary coordination essential.

Notes

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

1. What clinical features should raise suspicion for cardiac amyloidosis in a patient presenting with heart failure?

Cardiac amyloidosis should be considered when the clinical picture does not behave like typical hypertensive, ischemic, or dilated cardiomyopathy. In this case, the key clue was pattern recognition: new heart failure, rapid progression, low-voltage ECG, severe concentric LV thickening, small LV cavity, biventricular dysfunction, renal dysfunction, pleural effusions, and abnormal light chains. 

Shared cardiac red flags include increased LV wall thickness out of proportion to hypertension or valvular heart disease, diastolic dysfunction, biatrial enlargement, restrictive filling physiology, biventricular involvement, atrial fibrillation or conduction disease, elevated natriuretic peptides and troponin out of proportion to symptoms, and intolerance of standard heart failure therapies. 

Extracardiac manifestations can provide important clues and include proteinuria, peripheral or autonomic neuropathy, bilateral carpal tunnel syndrome, lumbar spinal stenosis, and spontaneous biceps tendon rupture. 

AL-predominant clues include rapid clinical progression over weeks to months, fatigue, weight loss, nephrotic-range proteinuria or renal dysfunction, pleural effusions, hypotension or shock physiology, low-voltage ECG, and evidence of a monoclonal protein or abnormal serum free light chains. 

Pathognomonic extracardiac findings for AL amyloidosis include macroglossia, periorbital purpura, and acquired factor X deficiency. 

ATTR-predominant clues often evolve over years and include bilateral carpal tunnel syndrome, lumbar spinal stenosis, spontaneous biceps tendon rupture, aortic stenosis, and HFpEF with increased wall thickness. Low-voltage ECG can occur but is less common in ATTR than AL. 

The key bedside teaching point is to lean into the inconsistency. Hypertension can cause LVH, but hypertension does not fully explain low voltage, rapid biventricular failure, renal dysfunction with monoclonal light chains, pleural effusions, and severe hemodynamic fragility. 

2. Once cardiac amyloidosis is suspected, how should we approach the diagnosis?

The diagnostic approach begins with suspicion and then immediately separates two pathways:

rule out AL amyloidosis 

evaluate for ATTR amyloidosis

3. Why is it so important to rule out AL amyloidosis early?

AL amyloidosis is both a hematologic and cardiac emergency. 

The underlying plasma cell clone produces misfolded immunoglobulin light chains that:

deposit as amyloid fibrils 

exert direct cardiotoxic effects on cardiomyocytes 

Light chains impair lysosomal function, disrupt autophagy, increase oxidative stress, and contribute to progressive cellular injury and death. 

Cardiac involvement is the primary determinant of prognosis in AL amyloidosis. 

Risk stratification commonly incorporates:

troponin 

NT-proBNP 

serum free light chain burden 

Mayo staging systems use these biomarkers to estimate prognosis and identify patients at especially high early mortality risk. 

Patients with advanced cardiac involvement can deteriorate over days to weeks, particularly when there is hypotension, markedly elevated NT-proBNP, elevated troponin, renal dysfunction, low output physiology. 

Early hematology involvement is essential because treatment targets the plasma cell clone. 

Daratumumab combined with bortezomib, cyclophosphamide, and dexamethasone (D-VCd) is now considered standard first-line therapy for newly diagnosed AL amyloidosis. 

The addition of daratumumab has been associated with deeper, faster responses, improved organ outcomes and improved survival. 

Treatment logistics matter. In advanced cardiac AL amyloidosis, delaying therapy until outpatient follow-up may be dangerous if the patient is unstable or has high-risk features. 

The practical takeaway:

once AL is suspected, do not wait for every outpatient test to return before escalating care.

send the full monoclonal protein workup.

involve hematology and amyloid specialists early.

expedite tissue diagnosis and treatment planning.

4. How does cardiac amyloidosis affect hemodynamics and response to therapy?

Amyloid infiltration produces restrictive cardiomyopathy characterized by: impaired ventricular compliance, elevated right- and left-sided filling pressures, low stroke volume, preload dependence, afterload intolerance, and limited ability to augment cardiac output.

Because stroke volume is fixed, heart rate becomes an important contributor to cardiac output. Beta blockers, non-dihydropyridine calcium channel blockers, and aggressive vasodilators may be poorly tolerated, particularly in AL cardiac amyloidosis with hypotension or advanced restrictive physiology.

Patients may appear profoundly volume overloaded while remaining severely forward-flow limited. This explains why diuresis can be difficult until perfusion improves, and why inotropes may produce a dramatic improvement in urine output in selected patients with low-output physiology.

Right heart catheterization can help characterize the physiology. In this case, invasive hemodynamics showed elevated filling pressures and pulmonary hypertension due to left-sided disease: RA 12 mmHg, PA 58/26 mmHg, mean PA 39 mmHg, PCW 20 mmHg, and cardiac index approximately 2.2-2.3 L/min/m2.

Positioning and respiratory mechanics matter. In this case, lying supine during renal ultrasound likely worsened respiratory mechanics in the setting of large pleural effusions and restrictive physiology, contributing to hypoxia and PEA arrest. 

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

5. What management principles are important once AL cardiac amyloidosis is suspected or confirmed?

Management requires multidisciplinary coordination among Advanced Heart Failure, Hematology/Oncology, Nephrology, Critical Care, Pathology, and, when needed, amyloid specialty clinics.

Supportive heart failure therapy centers on careful volume management. Loop diuretics are often needed, sometimes with sequential nephron blockade, but the margin between congestion and underfilling is narrow due to preload dependence. 

Guideline-directed medical therapy for conventional HFrEF may be limited by hypotension, renal dysfunction, low stroke volume, and autonomic dysfunction. The goal is not to force standard HFrEF therapy when the physiology does not support it.

Pleural effusions may be large and recurrent. Drainage can improve respiratory mechanics, but it does not treat the underlying restrictive cardiomyopathy or plasma cell disorder.

For AL amyloidosis, definitive therapy targets the plasma cell clone. Cardiac stabilization and chemotherapy planning must proceed in parallel, because ongoing light-chain production can drive rapid organ injury even after temporary hemodynamic improvement.

The major clinical pearl from this case is that AL cardiac amyloidosis should be approached with the urgency of both advanced heart failure and an aggressive hematologic malignancy. Early recognition and expedited evaluation can be life-saving.

Media



[data-source-id="source-fd45c57b-1d05-41df-b86d-7d7d6ab1001e"] .ose-embedpress-responsive{
width: 600px!important;
height: 600px!important;
max-height: 600px!important;
}
[data-source-id="source-fd45c57b-1d05-41df-b86d-7d7d6ab1001e"] iframe{
width: 600px!important;
height: 600px!important;
max-height: 600px!important;
}
[data-source-id="source-fd45c57b-1d05-41df-b86d-7d7d6ab1001e"] .embedpress-yt-subscribe iframe{
height: 100%!important;
}
[data-source-id="source-fd45c57b-1d05-41df-b86d-7d7d6ab1001e"] .ose-youtube > iframe{
height: 600px!important;
width: 600px!important;
max-width: 100%!important;
}
[data-source-id="source-fd45c57b-1d05-41df-b86d-7d7d6ab1001e"] .ose-youtube{
height: 600px!important;
width: 600px!important;
}
[data-source-id="source-fd45c57b-1d05-41df-b86d-7d7d6ab1001e"] .ose-giphy img{
height: 600px!important;
width: 600px!important;
}
[data-source-id="source-fd45c57b-1d05-41df-b86d-7d7d6ab1001e"] .ose-google-docs img{
height: 600px!important;
width: 600px!important;
}
[data-source-id="source-fd45c57b-1d05-41df-b86d-7d7d6ab1001e"] .ose-embedpress-responsive.ose-google-photos{
height: 100% !important;
max-height: 100% !important;
}

[data-source-id="source-fd45c57b-1d05-41df-b86d-7d7d6ab1001e"] .embera-embed-responsive-provider-gettyimages,
[data-source-id="source-fd45c57b-1d05-41df-b86d-7d7d6ab1001e"] .embera-embed-responsive-provider-gettyimages iframe,
[data-source-id="source-fd45c57b-1d05-41df-b86d-7d7d6ab1001e"] .getty{
width: 600px!important;
height: 600px!important;
max-height: 600px!important;
max-width: 100%!important;
}


References

Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure. J Am Coll Cardiol. 2022;79(17):e263-e421.

Kittleson MM, Maurer MS, Ambardekar AV, et al. Cardiac amyloidosis: evolving diagnosis and management: a scientific statement from the American Heart Association. Circulation. 2020;142(1):e7-e22.

Writing Committee, Kittleson MM, Ruberg FL, et al. 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis. J Am Coll Cardiol. 2023;81(11):1076-1126.

Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2021;42(16):1554-1568.

Falk RH, Quarta CC, Dorbala S. How to image cardiac amyloidosis. Circ Cardiovasc Imaging. 2014;7(3):552-562.

Felker GM, Boehmer JP, Hruban RH, et al. Echocardiographic findings in fulminant and acute myocarditis. J Am Coll Cardiol. 2000;36(1):227-232.

Ioannou A, Massa P, Patel RK, et al. Conventional heart failure therapy in cardiac ATTR amyloidosis. Eur Heart J. 2023;44(31):2893-2907.

Palladini G, Merlini G. How I treat AL amyloidosis. Blood. 2022;139(19):2918-2930.

Dorbala S, Ando Y, Bokhari S, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis. J Card Fail. 2019;25(11):e1-e39.

Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133(24):2404-2412.

Dispenzieri A, Gertz MA, Kyle RA, et al. Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol. 2004;22(18):3751-3757. [Mayo 2004 staging]

Kumar S, Dispenzieri A, Lacy MQ, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 2012;30(9):1055-1062. [Mayo 2012 staging]

Kastritis E, Leleu X, Arnulf B, et al. Daratumumab-based treatment for immunoglobulin light-chain amyloidosis (ANDROMEDA): a randomised, phase 3 trial. Lancet. 2021;397(10292):2337-2347.

Martens P, Bhattacharya S, Longinow J, et al. Hemodynamic profiling and prognosis in cardiac amyloidosis. Circ Heart Fail. 2023;16(3):e010078.

Porcari A, Fontana M, Gillmore JD. Transthyretin cardiac amyloidosis. Cardiovasc Res. 2023;118(18):3517-3535.

Ruberg FL, Maurer MS. Cardiac amyloidosis due to transthyretin protein: a review. JAMA. 2024;331(9):778-791.

Ikura H, Endo J, Kitakata H, Moriyama H, Sano M, Fukuda K. Untangling amyloidosis: recent advances in cardiac amyloidosis. Korean Circ J. 2022;52(10):725-742.

Larsen SB, Ladefoged B, Pedersen ALD, et al. Changes of clinical characteristics, distribution of red flags and prognosis in contemporary patients with wild-type transthyretin amyloidosis cardiomyopathy. Ann Med. 2024;56(1):2398735.

Transthyretin Cardiac Amyloidosis Evaluation and Management: 2025 ACC Concise Clinical Guidance. J Am Coll Cardiol. 2025. doi:10.1016/j.jacc.2025.09.004.

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.

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:

Beware of the RV death spiral. Hypotension occurs late in the acute PE pathophysiology as the LV function is preserved. A patient becomes hypotensive once all compensatory mechanisms have failed.

Don’t just treat the clot. Support the RV as well and think more seriously about ECMO.

One needs to be very careful intubating these patients, as sedating them will counteract many of the hemodynamic compensatory mechanisms and will lead to cardiac arrest. 

With the increasing role of catheter-based therapies, surgery’s role in acute PE is becoming more nuanced. Surgery is most useful in those patients with predominantly subacute clot, which is difficult to extract via catheter-based therapies.

Notes:

Notes: Notes drafted by Dr. Akiva Rosenzveig.

What is the hemodynamic consequences of high-risk PE and what is the Right ventricular (RV) “death spiral?”

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

What is the role of ECMO in acute PE?

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.

When is surgical embolectomy considered in the treatment of acute PE?

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.

What is the historical evolution of surgical management of PE?

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.

Can we be reassured if the patient does not have a saddle embolus?

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.

References:

Goldberg JB, Spevack DM, Ahsan S, et al. Survival and Right Ventricular Function After Surgical Management of Acute Pulmonary Embolism. J Am Coll Cardiol. 2020;76(8):903-911. doi:10.1016/j.jacc.2020.06.065

Goldberg JB, Giri J, Kobayashi T, et al. Surgical Management and Mechanical Circulatory Support in High-Risk Pulmonary Embolisms: Historical Context, Current Status, and Future Directions: A Scientific Statement From the American Heart Association. Circulation. 2023;147(9):e628-e647. doi:10.1161/CIR.0000000000001117

Delcroix M, Pepke-Zaba J, D’Armini AM, et al. Worldwide CTEPH Registry: Long-Term Outcomes With Pulmonary Endarterectomy, Balloon Pulmonary Angioplasty, and Medical Therapy. Circulation. 2024;150(17):1354-1365. doi:10.1161/CIRCULATIONAHA.124.068610

This episode is part of our comprehensive Decipher the Guidelines Series covering the 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes.

The following question refers to Section 8.2 of the 2025 ACS Guidelines.

The question is asked by Johns Hopkins pre-medical undergraduate and CardioNerds Academy Intern Joshua Khorsandi, answered first by University of Wisconsin cardiology fellow and member of the CardioNerds Interventional Cardiology Council Dr. Shikha Jha, and then by expert faculty Dr. Venu Menon.

Dr. Menon is the Section Head of Clinical Cardiology, Director of the Cardiac Intensive Care Unit, and Program Director of Cardiology Fellowship at the Cleveland Clinic. He is the Mehdi Razavi Endowed Chair and Professor of Medicine at the Cleveland Clinic Lerner College of Medicine. He was also a member of the 2025 ACS Guidelines writing committee.





Question #11

A 58-year-old man with a past medical history of hypertension, hyperlipidemia, schizophrenia, atrial fibrillation (on apixaban), and prior tobacco use presents to the emergency department with chest tightness. ECG shows ST elevations in leads II, III, and aVF with reciprocal depressions in leads I and aVL. Emergency coronary angiography demonstrates 100% occlusion of the proximal RCA, and he undergoes PCI. Transthoracic echocardiogram afterward reveals normal LV function with inferior hypokinesis. On day 2, the patient experienced lightheadedness and has frequent melanic stools. His hemoglobin returns at 6 gm/dL (initial hemoglobin 11 g/dL). He undergoes EGD and colonoscopy with successful endoscopic treatment of a small gastric ulcer. 

True or False: it is reasonable to administer 3-4 units of packed red blood cells for a goal Hb ≥ 10 g/dL.

True

False





Answer #11

Explanation 

The correct answer is True – it would be reasonable to administer 3-4 units of packed red blood cells for a goal Hb ≥ 10 g/dL.

Anemia is common in patients with ACS and is associated with worse short- and long-term outcomes. Anemia is associated with adverse outcomes irrespective of whether the anemia is chronic and due to comorbid conditions, or acute and the result of bleeding related to antithrombotic therapy and/or invasive procedures. The adverse effects of anemia may be due to decreased myocardial oxygen delivery, increased myocardial oxygen demand due to increased cardiac output, or the avoidance of potentially beneficial antithrombotic drugs and/or procedures. Randomized trials in medically ill patients and those undergoing cardiac surgery have demonstrated similar or better outcomes with a restrictive transfusion strategy (targeting a blood hemoglobin level around 8 g/dL) than with a liberal transfusion strategy (targeting a blood hemoglobin level around 10 g/dL). However, randomized trial evidence for populations with ACS suggests possible clinical benefit for a more liberal transfusion strategy targeting a hemoglobin level above 10 g/dL compared with targeting a hemoglobin level above 7 g/dL to 8 g/dL 

The MINT (Myocardial Ischemia and Transfusion) trial randomly assigned 3,504 patients with acute STEMI or NSTEMI and anemia with a blood hemoglobin level of <10 g/dL (13% with recent bleeding) to a restrictive transfusion strategy (transfusing if the hemoglobin level was <7-8 g/dL) or a liberal transfusion strategy (transfusing if the hemoglobin level was <10 g/dL). Patients were ineligible for enrollment if they had uncontrolled bleeding, were receiving palliative treatment, or were scheduled to have cardiac surgery. Transfusion could be delayed for patients with volume overload or until the day of dialysis in patients with end-stage renal disease. The primary outcome of 30-day death or recurrent MI occurred in 16.9% of patients in the restrictive strategy and 14.5% of patients in the liberal strategy (relative risk, 1.15 [95% CI, 0.99-1.34]; P = 0.07). Death occurred in 9.9% of patients in the restrictive strategy and 8.3% of patients in the liberal strategy (relative risk, 1.19 [95% CI, 0.94-1.49]), and cardiac death occurred in 5.5% of patients in the restrictive strategy and 3.2% of patients in the liberal strategy (relative risk, 1.74 [95% CI, 1.26-2.40]). Although the MINT trial did not demonstrate a statistically significant reduction in its primary endpoint, the results suggest that a liberal blood transfusion strategy targeting a hemoglobin level around 10 g/dL may provide short-term clinical benefit over a restrictive transfusion strategy targeting a hemoglobin level above 7 g/dL or 8 g/dL in patients with AMI and anemia. 

The 2025 ACS guidelines give a Class 2b, LOE B-R recommendation for a liberal transfusion strategy targeting a hemoglobin of >10 g/dL in patients with ACS and acute or chronic anemia to reduce cardiovascular events.

Main Takeaway

In patients with ACS and acute or chronic anemia, blood transfusion to achieve a hemoglobin level of more than 10 g/dL may be reasonable to reduce cardiovascular events.

Guideline Loc.

Section 10.2

This episode is part of our comprehensive Decipher the Guidelines Series covering the 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes.

The following question refers to Section 9.2 of the 2025 ACS Guidelines.

The question is asked by Johns Hopkins pre-medical undergraduate and CardioNerds Academy Intern Joshua Khorsandi, answered first by University of Wisconsin cardiology fellow and member of the CardioNerds Interventional Cardiology Council Dr. Shikha Jha, and then by expert faculty Dr. Venu Menon.

Dr. Menon is the Section Head of Clinical Cardiology, Director of the Cardiac Intensive Care Unit, and Program Director of Cardiology Fellowship at the Cleveland Clinic. He is the Mehdi Razavi Endowed Chair and Professor of Medicine at the Cleveland Clinic Lerner College of Medicine. He was also a member of the 2025 ACS Guidelines writing committee.





Question #9

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





Answer #9

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.





Question #8

A 65-year-old female with no significant prior cardiac history presents to the emergency department with 3 days of chest tightness associated with shortness of breath. ECG demonstrates anterior ST-segment elevation with reciprocal depressions. Coronary angiography reveals 100% occlusion of the mid left anterior descending artery. She undergoes PCI of the LAD. Two days later, she develops worsening shortness of breath. Her HR is 115 and BP 95/50. Lungs are clear on auscultation. Cardiac examination is significant for a harsh systolic murmur at the left sternal border with a palpable thrill. Transthoracic echocardiogram showed ventricular septal rupture with left-to-right shunt and Qp:Qs estimated at 2.5:1. What is the best next step?

A

Continue medical management

B

Proceed with repeat coronary angiogram and right heart catheterization with shunt run

C

Percutaneous ventricular septal defect closure

D

Intra-aortic balloon pump placement and cardiac surgical consultation





Answer #8

Explanation 

The correct answer is D – placement of an intra-aortic balloon pump and CT surgical consultation.

Timely reperfusion therapy has reduced the incidence of mechanical complications (ventricular septal rupture, mitral valve insufficiency due to papillary muscle infarction or rupture, or free wall rupture) after AMI. Although occasionally found incidentally, mechanical complications commonly present with recurrent or refractory chest pain or a new murmur accompanied by disproportionate heart failure, cardiogenic shock, or sudden cardiac death on clinical presentation within the first week after an AMI. Medical therapy alone is associated with high risk of early death; definitive surgical correction is frequently the treatment of choice. Mortality rates with surgery are highest in subjects with cardiogenic shock and in those requiring early emergency/urgent intervention after AMI. Observed mortality rates following delayed surgery (>7 days) are lower but patient selection and survivor bias contribute to this observation.

The 2025 ACS guidelines give a Class 2a, LOE B-NR recommendation for the use of short-term MCS devices in patients with mechanical complications of ACS for hemodynamic stabilization and bridge to surgery. The availability of temporary MCS devices has led to increasing trends for delayed surgery due to concerns for the initial degree of extensive tissue destruction. Delayed surgical intervention may enable hemodynamic stabilization, lead to recovery of end-organ injury, and promote infarct tissue healing and maturation that could facilitate definitive repair. Percutaneous approaches toward repair have been used in patients with prohibitive surgical risk or contraindications to surgery as a primary or temporizing option in the setting of acute mitral regurgitation and ventricular septal rupture and

remain an evolving area of investigation. This patient is not at prohibitive risk for surgery. Select patients with mechanical complications of ACS may be considered for cardiac transplantation or durable LVAD as a primary or bailout treatment strategy to improve survival. 

No RCTs evaluate the role of transfer of patients with mechanical complications after MI to dedicated centers with cardiac surgical expertise. Although overall surgical mortality is approximately 40%, it remains the treatment strategy of choice. Hemodynamic deterioration is unpredictable and can be precipitous in previously stable subjects. Consequently, transfer to a Level 1 cardiac intensive care unit (CICU) with access to various temporary MCS devices and multidisciplinary experienced teams of surgical, interventional, HF, and palliative care specialists is recommended. The guidelines give a Class 1, LOE C recommendation for management of patients with mechanical complications of ACS at centers with cardiac surgical expertise.

Main Takeaway

Patients with mechanical complications of ACS should be managed in a center with cardiac surgical expertise. In such patients, short-term MCS devices are reasonable for hemodynamical stabilization as a bridge to surgery.

Guideline Loc.

Section 9.1, Figure 9