Heart Failure

Find the Cause

100

What are the two major etiologic categories of cardiomyopathy?

Ischemic vs Nonischemic

Ischemic cardiomyopathy results from coronary artery disease.

Nonischemic cardiomyopathy includes multiple other causes.

200

Name at least four causes of nonischemic causes of reduced LV systolic function.

• Pressure 

  • Longstanding hypertension
  • Aortic stenosis

• Volume 

  • Chronic mitral or aortic regurgitation

• Arrhythmia-induced

  • Persistent tachyarrhythmias, including AF/flutter
  • High PVC burden

• Toxic / medication-related

  • Alcohol
  • Cocaine or methamphetamine
  • Cardiotoxic cancer therapies, such as anthracyclines or trastuzumab

• Inflammatory

  • Myocarditis
  • Cardiac sarcoidosis

• Genetic / familial

  • Inherited dilated cardiomyopathy
  • Neuromuscular disorders

• Infiltrative / storage

  • Cardiac amyloidosis
  • Iron overload / hemochromatosis

• Endocrine / metabolic / nutritional

  • Hyperthyroidism or hypothyroidism
  • Thiamine deficiency >> NAME IT!

• Pregnancy-associated

  • Peripartum cardiomyopathy

• Stress-induced

  • Takotsubo cardiomyopathy

300

What are the major etiologic categories of myocarditis?

• Infectious: Viral infections; Lyme disease (Borrelia); Chagas disease (T. cruzi).
• Immune-mediated / inflammatory: SLE, EGPA, cardiac sarcoidosis, or giant-cell myocarditis.
• Drug-related / hypersensitivity: Immune checkpoint inhibitors, clozapine, or hypersensitivity reactions to certain antibiotics, DRESS

400

A patient has HF, unexplained increased LV wall thickness, and bilateral carpal tunnel syndrome. What diagnosis should you suspect, and how would you begin the workup?

Cardiac amyloidosis, with ATTR particularly suggested by this pattern.

Begin with a monoclonal protein screen:

• Serum free light chains
• Serum immunofixation
• Urine immunofixation

If the screen is negative, technetium-99m PYP scintigraphy with SPECT can evaluate for ATTR.

500

A 48-year-old patient with unexplained cardiomyopathy develops high-grade AV block and ventricular arrhythmias. What underlying disease should you consider, and which imaging studies could help evaluate it?

Cardiac sarcoidosis.

Imaging:
- Cardiac MRI (gadolinium enhancement)

- FDG-PET >> also looks for extracardiac sites for possible biopsy?

Classify

100

What are the two main EF-based HF phenotypes and their cutoffs?

HFrEF (≤40%), HFmrEF (41–49%), and HFpEF (≥50%), with HFimpEF describing improvement over time.

The "Second Universal Definition of Heart Failure" (2026), jointly issued by AHA, ACC, ESC, and WHF, simplifies the categories to reduced, preserved, and improved EF, removing HFmrEF as a separate group and moving away from rigid EF cutoffs. This updates the international consensus definition but does not replace the current US management guideline.

200

Which classification system is used to describe symptom-related functional limitation in patients with HF?

New York Heart Association (NYHA) functional classification.

• Class I: No symptoms or limitation during usual daily activities.
• Class II: Symptoms with typical daily exertion, such as brisk walking or climbing stairs; comfortable at rest.
• Class III: Symptoms with light activity, such as getting dressed or walking a short distance; comfortable at rest.
• Class IV: Symptoms at rest; any physical activity increases discomfort.

300

A patient previously had symptomatic HFrEF but is now asymptomatic during daily activities on treatment. What ACC/AHA stage and NYHA class apply?

ACC/AHA Stage C; NYHA Class I.

ACC/AHA stages:

• A - At risk: HF risk factors, without symptoms, structural heart disease, or evidence of cardiac injury.
• B - Pre-HF: No HF symptoms, but structural heart disease, elevated filling pressures, or qualifying biomarker abnormalities.
• C - Symptomatic HF: Current or previous HF symptoms.
• D - Advanced HF: Severe symptoms limiting daily life and recurrent hospitalizations despite attempts to optimize treatment.

400

Which measurements assess left-sided filling pressures during right- and left-heart catheterization? What are their normal resting ranges?

• RHC: PCWP - estimates mean left atrial pressure; normally approximately 6-12 mmHg.

• LHC: LVEDP - directly measures LV end-diastolic pressure; normally approximately 5-12 mmHg.

PCWP ≥15 mmHg or LVEDP ≥16 mmHg are commonly used thresholds supporting elevated filling pressures

500

Which classification system is used to stage the severity of cardiogenic shock?

 The SCAI shock classification:

• A - At risk: Risk factors for shock, but stable hemodynamics and adequate perfusion.
• B - Beginning: Hypotension and/or tachycardia, but no hypoperfusion.
• C - Classic: Hypoperfusion requiring an inotrope, vasopressor, and/or mechanical circulatory support.
• D - Deteriorating: Hypoperfusion persists or worsens despite initial support, requiring higher doses, additional drugs, or escalation of mechanical support.
• E - Extremis: Profound circulatory collapse, often requiring multiple simultaneous rescue interventions, potentially including CPR.

Investigate it

100

What is the difference between hypokinesis, akinesis, and dyskinesis on echocardiography?

Description of wall motion:

• Hypokinesis: Reduced systolic contraction and wall thickening.
• Akinesis: Absent or essentially absent systolic contraction and wall thickening.
• Dyskinesis: Paradoxical outward movement during systole, rather than inward contraction.

200

What is the classic echocardiographic wall-motion pattern in Takotsubo syndrome?

Apical ballooning: 

Hypokinesis or akinesis of the apical and mid-LV segments with relative basal hyperkinesis. 

The abnormality typically extends beyond a single coronary artery territory.

300

When would you choose an exercise treadmill ECG, pharmacologic stress imaging, or invasive coronary angiography to evaluate suspected CAD?  

• Exercise treadmill ECG: A stable patient who can exercise has an interpretable resting ECG.

• Pharmacologic stress imaging: When the patient cannot exercise. With LBBB or ventricular pacing, prefer vasodilator nuclear perfusion imaging

• Invasive coronary angiography: Consider when there is:

  • ACS with ongoing ischemia or instability, such as persistent chest pain, cardiogenic shock, or ventricular arrhythmias.
  • Persistent angina despite medical therapy, when revascularization is a reasonable option.
  • New LV dysfunction with strong suspicion of an ischemic cause

400

What echocardiographic measurements define severe high-gradient aortic stenosis?

• Max velocity: Vmax ≥4.0 m/s
• Mean gradient ≥40 mmHg
• Valve area: AVA typically ≤1.0 cm²

500

Which echocardiographic findings should raise suspicion for cardiac amyloidosis?

• Unexplained increased LV wall thickness
• Diastolic dysfunction, sometimes with restrictive filling
• Reduced longitudinal strain with relative apical sparing
• Biatrial enlargement
• Thickening of the RV free wall, valves, or interatrial septum
• Small pericardial effusion

Treat it

100

What are the four pillars of guideline-directed medical therapy for HFrEF?

• ARNI: sacubitril/valsartan - preferred; an ACE inhibitor or ARB is an alternative when ARNI cannot be used.
• Evidence-based beta-blocker: carvedilol, metoprolol succinate, or bisoprolol.
• Mineralocorticoid receptor antagonist: spironolactone or eplerenone.
• SGLT2 inhibitor: dapagliflozin or empagliflozin

200

A patient’s LVEF improves from 25% to 55% on GDMT, and they are now asymptomatic. Can their HF medications be discontinued?

No, continue GDMT at tolerated doses. 

This is HF with improved EF (HFimpEF) >> normalization of EF does not establish that the underlying cardiomyopathy is cured. Guidelines recommend continuing treatment to prevent recurrent HF and LV dysfunction, even when symptoms resolve.

300

A patient with symptomatic HFrEF is taking lisinopril. You plan to switch to Entresto. 

What safety step is required before starting it, and why?

Stop lisinopril and wait at least 36 hours after the last dose before starting sacubitril/valsartan. 

Overlapping ACE inhibition and neprilysin inhibition increases the risk of angioedema, because both reduce bradykinin breakdown. They must never be administered together.

400

A patient has an LVEF of 30% and persistent NYHA class II symptoms despite four months of optimized GDMT. An ECG shows sinus rhythm with chronic LBBB. What should be considered next?

Consider ICD and CRT evaluation:

• ICD: Protects against sudden cardiac death from dangerous ventricular arrhythmias when EF remains ≤35% despite GDMT, assuming expected meaningful survival >1 year.
• CRT: Helps the ventricles contract more synchronously. In this patient with LBBB, check QRS duration; benefit is strongest with QRS ≥150 ms.
• CRT-D: Combines resynchronization with a defibrillator.

500

What disease-modifying treatments are available for ATTR cardiomyopathy, and how do their mechanisms differ?

• Tafamidis and acoramidis: TTR stabilizers >> stabilize the transthyretin protein to reduce its breakdown into components that can form amyloid. 
• Vutrisiran: A TTR silencer >> uses small interfering RNA (siRNA) to reduce transthyretin production in the liver. 

Vutrisiran (Amvuttra) requires vitamin A supplementation because it lowers serum vitamin A levels (Vitamin A deficiency symptoms: night blindness,...)

Of note: Amyloid-depleting therapies are currently being investigated in phase 3 clinical trials.