Authors: Sam Engrav MD, Denise Dailey MD, & Darren Salmi MD
Background
Congestive Heart Failure (CHF) is defined as “a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood” by the American College of Cardiology and the American Heart Association.
The most common etiologies of CHF are ischemic heart disease, chronic obstructive pulmonary disease (COPD), hypertensive heart disease, and rheumatic heart disease. The numerous etiologies of CHF can be categorized as intrinsic heart disease, congenital, myocarditis related, and infiltrative diseases like cancer, autoimmune or infectious causes. Ischemic heart disease as the single most common cause of CHF worldwide has an estimated prevalence of 26 million, and concurrently is associated with a high mortality and morbidity rate. The pathophysiology of CHF typically involves the loss of blood supply to heart muscle, which can be secondary to nonfunctional valves, hormone levels, arrhythmias, coronary artery disease, inflammatory reactions, or hypertensive related changes in afterload and ventricular mass. These ultimately lead to decreased energy supply and subsequent reduced ejection fraction.
Age is a major risk factor for CHF. The Framingham Heart Study showed CHF prevalence to be 8 per 1000 males aged 50 to 59 years, with an increase to 66 per 1000 males aged 80 to 89. The incidence of HF in men doubles with each 10-year age increase after the age of 65, whereas in women, for the same age cohort, the incidence triples.
Quick Tips at Time of Autopsy
Clinical History
The clinical history is useful in determining the etiology of a decedent’s heart failure, and potential acute exacerbations of an individual’s disease resulting in their death.
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- Past Medical History
- Symptoms
- Left-sided heart failure (due to fluid accumulation in the lungs): Dyspnea, orthopnea, paroxysmal nocturnal dyspnea (PND), cough, hemoptysis, exertional fatigue
- Failure of the left heart to effectively pump blood through systemic circulation
- Right sided heart failure (due to extravascular fluid accumulation throughout the body):
- Failure of the right heart to effectively pump blood through pulmonary circulation
- Nausea/anorexia (due to venous stasis of abdominal organs)
- Weight gain/ascites/edema
- Pronounced in lower extremities
- Hepatomegaly (due to venous engorgement of the liver, may result in symptoms of liver failure and cardiac cirrhosis)
- Distended neck veins/jugular venous distention (due to venous pooling in the neck)
- Biventricular failure will show aspects of left and right heart failure
- Left-sided heart failure (due to fluid accumulation in the lungs): Dyspnea, orthopnea, paroxysmal nocturnal dyspnea (PND), cough, hemoptysis, exertional fatigue
- Symptoms
- Past Medical History
- The most common cause of right heart failure is left heart failure
- Grading schema (click here)
- Underlying etiology of heart failure (if known):
- Ischemia/atherosclerosis/hypertensive disease
- Pulmonary (COPD)
- Post-infectious (i.e. myocarditis, rheumatic heart disease)
- Malignancy (directly related to cancer or as a result of treatment – i.e. doxorubicin cardiomyopathy)
- Autoimmune
- Infiltrative disease (ex. amyloid)
- Congenital cardiac diseases (even if surgically corrected)
- Other comorbidities: smoking, diabetes, obesity, hyperlipidemia, increased age
- Previous acute exacerbations (and suspected cause, if known)
- Underlying infection
- Medication nonadherence and/or medication complications
- Changes in diet
- Previous ischemic events (i.e. stroke)
- Even if an individual’s heart failure is not due to ischemic disease, ischemic events can indicate comorbid disease and/or indicate levels of disease severity
- Medications
- Heart failure treatment:
- Guideline-directed medical therapy (mortality-benefit)
- ACE/ARB/ARNi (lisinopril/losartan/sacubitril-valsartan)
- MRA (spironolactone)
- Beta-blockers (carvedilol, metoprolol)
- SGLT2 inhibitor (empagliflozin)
- Symptom management
- Ivabradine
- Digoxin
- Guideline-directed medical therapy (mortality-benefit)
- Medications known to cause/exacerbate heart failure
- Exacerbate:
- NSAIDS (and other COX inhibitors) – renal dysfunction
- Anesthesia medications
- Thiazolidinediones (diabetes medications) – increase fluid retention
- Cardiotoxic medications
- Amphotericin B
- Anthracyclines (doxorubicin)
- Clozapine
- High-dose cyclophosphamide
- 5-Fluorouracil (5-FU)
- Monoclonal antibody treatments (ex. bevacizumab, trastuzumab)
- Previous chest radiation (breast/lung/esophageal cancer, Hodgkin lymphoma)
- Exacerbate:
- Heart failure treatment:
- Labs
- Decreased renal function (elevated creatinine, decreased GFR)
- Electrolyte abnormalities (associated with poor renal function): hyponatremia, hyperkalemia
- Decreased liver function: hypoalbuminemia, elevated bilirubin, thrombocytopenia (the latter is caused by platelet sequestration in the spleen in conjunction with decreased thrombopoietin levels with concurrent liver failure)
- Elevated BNP/proBNP/NT proBNP
- No specific number/cut-off for “advanced” disease
- Can be artificially lower in obese patients
- Can be artificially higher in those with advanced kidney and liver disease and volume overload
- Elevated troponins may indicate an acute ischemic event that exacerbated an individual’s underlying heart failure. (See the Myocardial Infarction article for more information).
- Imaging
- Cardiac imaging/scans can be very helpful to review abnormalities in structure and function. (e.g. echocardiography – useful in distinguishing systolic and diastolic heart failure, ECG, cardiac MRI, cardiac angiography, chest radiograph, carotid artery ultrasonography, and cardiac catheterization to measure intracardiac pressures)
- Patients may have associated prior procedures (e.g. congenital cardiac corrections, cardiac valve replacements, coronary artery bypass graft (CABG), coronary artery stents, carotid artery stents, thrombectomy (stroke), pacemaker or implantable cardioverter-defibrillator (ICD) placement, and – while not routine – some patients undergo endomyocardial biopsies for suspected infectious/infiltrative diseases that may indicate the underlying etiology of their heart failure.)
External examination
- Look for evidence of edema/ascites, and/or hepatomegaly
- Left-sided heart failure predominantly results in pulmonary edema and pleural effusion, potentially resulting in cyanosis
- Right-sided heart failure predominantly impacts the remainder of the body resulting in:
- Lower extremity edema/venous stasis
- Ascites
- Hepatomegaly
- Clubbing (in cases of significant portal hypertension)
- Chronic CHF patients may present cachectic due to poor volume retention which may be supported with a history of poor urine output and poor perfusion.
Internal examination
- If the case qualifies as sudden death then consensus guidelines for autopsy investigation of sudden cardiac death should be followed.
Cardiac Findings
- Increased heart weight (cardiomegaly) is a good indicator of underlying cardiac pathology
- Increased epicardial fat, though a nonspecific finding, is also seen more frequently in chronic heart failure
- Endocardium
- Trabecular hypertrophy can be seen in response to increased work loads in either the right or left chambers
- Chronic stretching can produce thickening of the endocardium which leads to a whiter appearance of the endocardium
- Valves
- Structural abnormalities (ex. bicuspid aortic valve)
- Valve stenosis
- Hooding of atrioventricular valves (to suggest a history of regurgitation)
- Vegetations (infection) and/or thrombi
- Valve circumferences should be measured – upper limits as follows:
| Men | Women | |
| Tricuspid | 9.9 cm | 9.1 cm |
| Pulmonic | 8.5 cm | 7.9 cm |
| Mitral | 11.8 cm | 11.1 cm |
| Aortic | 7.5 cm | 7.4 cm |
- Myocardium: the myocardium is often hypertrophied – can be concentric, eccentric, or both
- Measurements of the right ventricular wall, interventricular septum, and left ventricle should be taken. Normal values:
- RV wall (without trabeculae): 3-5 mm
- Interventricular septum: 8-11 mm
- LV wall: 10-12 mm
- Concentric hypertrophy (usually in the ventricles): increased wall thickness, normal/reduced chamber size
- Due to pressure overload (aortic stenosis, hypertension, etc.)
- An asymmetric hypertrophy of the interventricular septum is potentially indicative of hypertrophic cardiomyopathy
- Eccentric hypertrophy (predominantly left ventricle): increased chamber size, normal/reduced wall thickness
- Due to volume overload (valve regurgitation, dilated cardiomyopathies, pregnancy)
- A significantly dilated left ventricle can indicate an underlying dilated cardiomyopathy
- Biatrial dilation can indicate an underlying restrictive cardiomyopathy
- Can observe myocardial scarring/fibrosis from previous ischemia or restrictive/infiltrative diseases. (See the Myocardial Infarction article for more information).
- Measurements of the right ventricular wall, interventricular septum, and left ventricle should be taken. Normal values:
Image: Diagram illustrating different patterns of cardiac hypertrophy in cross section (Image credit: Basso et. al).
Image: Cross sections of heart with concentric (a) and eccentric (b) hypertrophy (Image credit: Basso et. al).
A “globoid heart” describes the rounded, rather than apical, shape of a heart with biventricular or four chamber dilation. It is non-specific and can be the end stage shape of multiple common chronic heart failure conditions such as dilated cardiomyopathy, ischemic cardiomyopathy, storage disorders, and others. (Image credit: Meagan Chambers/Stanford Hospital).
- Fibrous exudate +/- rough/granular patches on the epicardium or pericardium is suggestive of pericardial disease
- Coronary arteries may have atherosclerosis and/or stents. (See Atherosclerosis for sampling recommendations for coronary arteries).
Systemic findings:
- Left heart failure
- Pulmonary edema – excess fluid and increased lung weights. (Water‑logged lungs that exude frothy, blood‑tinged fluid and show variegated red‑brown/tan mottling on cut surface.)
- Pleural effusion
- Right heart failure
- Congestive hepatopathy/portal hypertension (see cirrhosis) – can result in a “nutmeg” appearance of the liver grossly
- Esophageal varices
- Congested hepatomegaly
- Congested splenomegaly
- Portal vein thrombosis
- Jaundice – observed well in the meninges
- Edematous tissue (positional – often most pronounced in the lower limbs)
- Peritoneal ascites/effusions
- Renal subcapsular hemorrhagic spots or embolic scars and a congested medulla / pale cortex pattern (gross corticomedullary contrast) in congestive nephropathy.
- Congestive hepatopathy/portal hypertension (see cirrhosis) – can result in a “nutmeg” appearance of the liver grossly
- Diffuse cerebral edema with flattened gyri and narrowed sulci in advanced or low‑output HF.
- Watershed cortical infarcts and multifocal lacunar infarcts secondary to hypotension or emboli.
Image: Cross section of a liver with “nutmeg” appearance due to sinusoidal congestion. (Image credit: Meagan Chambers/Stanford Hospital).
Ancillary Testing
- Genetic testing if a congenital disease is suspected
- Toxicology if suspicious of a drug related cause of heart failure.
- Microbiology stains may be used if an infectious cause is suspected.
Quick Tips at Time of Histology Evaluation
- The cardiac histology of heart failure is generally nonspecific. One may see various patterns of myocardial fibrosis, cardiac myocyte disarray (including irregular hypertrophy and/or atrophy), and nonspecific inflammation
- However, there are various histologic findings that may indicate the underlying etiology of heart failure in an individual, and/or what led to an acute episode/decompensation of chronic heart failure
Cardiovascular tissue evaluation
- Coronary arteries
- Histologic evaluation can be used to confirm the degree of stenosis, plaque stability and evaluate for other pathology (i.e. dissection)
- Great vessels
- In the case of suspected connective tissue disease leading to heart failure, the aorta can be sampled to look for dissection
- Periodic acid schiff (PAS), colloidal iron, or elastin stains (Verhoeff-Van Gieson/VVG, trichrome, and Movat’s pentachrome) can highlight tunica media degeneration in the aorta consistent with connective tissue disease
- In the case of suspected connective tissue disease leading to heart failure, the aorta can be sampled to look for dissection
- Endocardium
- In cases of eccentric hypertrophy where the chamber is chronically stretched, the endocardium may show fibroelastotic thickening
- For suspected infective endocarditis, the combination of a Gram stain, Methenamine silver stain (GMS) and PAS can identify fungal organisms and help highlight unique bacteria
- In culture negative endocarditis – suspect Bartonella henselae and/or Coxiella species
- Giemsa and GMS can be used to identify Coxiella
- Warthin-Starry or Steiner stains can be used to identify Bartonella species
- In culture negative endocarditis – suspect Bartonella henselae and/or Coxiella species
- For noninfective endocarditis, need to rule out potential infectious etiologies
- Noninfective endocarditis will appear as an eosinophilic mass of platelets intermixed with fibrin
- Healed lesions have dense fibrous tissue
- Noninfective endocarditis will appear as an eosinophilic mass of platelets intermixed with fibrin
- Degenerative valve disease predominantly affects the mitral valve, but can impact the aortic valve as well
- Can see nodular calcifications on the valve area
- Mucoid myxomatous material can be seen in the lamina spongiosa (making it appear thicker) – a sign of degeneration
- This is well visualized with mucicarmine and PAS stains
Image: Endocardial fibroelastosis from a chronically dilated heart. (Image credit: Darren Salmi/Stanford Hospital).
Image: Low power H&E stain of mitral valve with fibromyxoid degeneration (Image credit: PathologyOutlines).
Myocardium
- Further histologic evaluation of the myocardium will be informed by the gross findings and clinical history
- Ischemic changes follow a distinct evolution over time from an initial inflammatory response to a final fibrotic scar which may undergo fatty metaplasia over time
- Hypertrophic cardiomyopathy: myocyte hypertrophy and disarray (can be branched and multinucleated) in the appropriate locations (i.e. not the apex or where free walls join the septum)
Image: H&E stain of myocardium with fibrosis and hypertrophied, disorganized myocytes (Image credit: PathologyOutlines).
- Dilated cardiomyopathy: can see an increase in myocyte nuclear size (sometimes even multinucleation) and myocyte length, focal myocyte death, interstitial fibrosis
- Many of the etiologies of dilated cardiomyopathy result in similar histologic presentations
- In the case of an infectious etiology (myocarditis transforming into dilated cardiomyopathy, culture testing, PCR, or IHC can potentially be used to identify a causative agent)
- Most cases are viral (lymphocyte predominant)
- Sarcoidosis can result in non necrotizing granulomas and multinucleated giant cells and surrounding fibrosis
Image: High power H&E stain of cardiac sarcoidosis with non-necrotizing granulomas (arrows) and mononuclear cell involvement of the myocardium (asterisk) (Image credit: Kurmann, Mankad, Mankad, Bois).
- Restrictive cardiomyopathy: can lead to myocardial fibrosis, with compensatory (remaining) myocyte hypertrophy, may see disarray in congenital forms (usually sarcomeric mutations)
- Infiltrative disease (amyloid, iron,metabolic products, etc.)
- Amyloid is most commonly seen in the myocardium, but can impact all aspects of the heart
- AL amyloid is usually diffuse, while ATTR amyloid is nodular
- Both result in surrounding fibrosis and myocyte atrophy
- Congo Red staining – “Apple Green” in birefringence
- Sarcoidosis can also present as a restrictive cardiomyopathy
- Treatment/medication related – should be clinically correlated as will appear as fibrosis and nonspecific myocyte atrophy
- Infiltrative disease (amyloid, iron,metabolic products, etc.)
Image: (Left) H&E stain of cardiac amyloidosis (Right) Polarized Congo Red stain of the myocardium consistent with amyloidosis (Image credit: PathologyOutlines).
Epi/pericardium
- Mixed inflammation in the pericardium (usually lymphocytes and plasma cells) can indicate pericarditis
- Thickened, fibrotic pericardium may represent constrictive pericarditis which can lead to symptoms of HF
There are additional extra-cardiac histologic findings that support a diagnosis of heart failure (and its potential underlying etiologies)
- Lung (predominantly chronic left heart failure)
- Potential to see pulmonary edema and congestion with blood in the alveolar spaces (largely due to left heart failure)
- This can lead to the presence of hemosiderin-laden macrophages (“Heart failure cells”)
- Potential to see pulmonary edema and congestion with blood in the alveolar spaces (largely due to left heart failure)
Image: High power image of the lung showing pulmonary congestion (with scant blood in the alveolar spaces) and brown hemosiderin-laden macrophages (“heart failure cells”) (Image credit: Meagan Chambers/Stanford Hospital).
Left sided heart failure may result in increased pressures in pulmonary veins leading to hyalinization. (Image credit: Meagan Chambers/Stanford Hospital).
- Alveolar septae may increase/”thicken” due to deposition of fibrous tissue
- The increase in pulmonary vasculature pressures can result in the hyalinized thickening of small pulmonary veins
- Over time veins can undergo “arterialization” with medial hypertrophy and acquisition of an external elastic lamina (normally they only have an internal elastic lamina)
- May also see thickening of the tunica media and tunica intima (often eccentric) in small arteries
- Liver (predominantly chronic right heart failure)
- Similar to pulmonary findings, will see congestion in the hepatic sinusoids with potential dilation
- Chronic congestion can lead to “cardiac cirrhosis”/”cardiac sclerosis” – wherein fibrotic tissue bridges the central zone regions
- Typically has less nodular regeneration than typical cirrhosis
- Chronic congestion can lead to “cardiac cirrhosis”/”cardiac sclerosis” – wherein fibrotic tissue bridges the central zone regions
- Portal fibrosis (both centrilobular and perisinusoidal)
- Fibrosis extending from centrilobular areas into portal triads is an indicator of increasing right atrial pressures (more severe heart failure)
- May also see centrilobular hepatocyte atrophy or loss
- May see regenerative hyperplasia
- Severe congestion may result in cirrhosis/cirrhosis-like histology
- Similar to pulmonary findings, will see congestion in the hepatic sinusoids with potential dilation
Image: A trichrome stain of a liver with “cardiac cirrhosis” with fibrotic tissue bridging degenerated central veins (dots) with more preserved portal areas (stars). There is also significant congestion. (Image credit: Meagan Chambers/Stanford Hospital).
- Splenic congestion/splenomegaly
- Kidney
- In cases of acute heart failure (or an acute decompensation), may see findings consistent with acute tubular injury:
- Loss of brush border epithelium
- Increased eosinophilic staining
- Nuclear changes – condensed chromatin, loss of nuclear contour
- Tubular lumens with necrotic cells and debris
- Extensive necrosis should raise a question of toxin-mediated damage (versus purely ischemic etiology)
- More likely to see left-sided heart failure findings:
- Glomerular sclerosis – partial or whole (glomerular tuft may collapse)
- Hyaline arteriosclerosis, predominantly in the afferent arteriole – highly eosinophilic
- In severe cases, can lead to hyperplastic arteriolitis (concentric/”onion-skin” thickening of arteriolar walls that can lead to complete lumen obstruction)
- Best observed with PAS/trichrome/Jones silver stains
- Thickening of the tunica media of arteries and/or subintimal fibrosis
- Fibrosis well observed on trichrome stain
- Tubulointerstitial fibrosis, potentially atrophy in cases with significant underlying hypertensive disease
- While less common, congestive nephropathy has been observed in individuals with severe right-sided heart failure
- Congestion and edema, frequently around the glomerular tuft
- Potential widening of Bowman’s space
- Glomerular atrophy
- Tubules containing epithelial cell debris/shedding
- Congestion and edema, frequently around the glomerular tuft
- In cases of acute heart failure (or an acute decompensation), may see findings consistent with acute tubular injury:
Quick Tips at Time of Reporting
Examples of cause of death statements:
- Congestive heart failure secondary to hypertensive cardiovascular disease.
- Respiratory failure due to acute exacerbation of congestive heart failure.
Chronic heart failure (HF) is a progressive, life-threatening syndrome in which patients ultimately die either from sudden cardiac death (SCD) or progressive pump failure (worsening HF). In those with reduced ejection fraction (HFrEF), SCD historically accounts for about 30–50% of deaths, whereas the remainder often succumb to gradual decompensation of pump function or other causes. Patients with preserved ejection fraction (HFpEF) also face high mortality, though a larger proportion of their deaths are non-cardiac; still, roughly 25–30% of HFpEF patient deaths are sudden and ~20–30% are due to end-stage HF. Remember that HF is a clinical syndrome, not a pathological diagnosis, so always correlate with the clinical history.
Recommended References
- Han HC et al: Mitral valve prolapse and sudden cardiac death: a systematic review. J Am Heart Assoc. 7(23):e010584, 2018
- Kumar V et al: Robbins Basic Pathology, 10th ed. Elsevier, 2018
- Fyfe B et al: Diagnostic Pathology: Hospital Autopsy. Elsevier, 2016
- Kuriachan VP et al: Sudden cardiac death. Curr Probl Cardiol. 40(4):133-200, 2015
- Dolinak D et al: Forensic Pathology: Principles and Practice. Elsevier, 2005
- Finkbeiner W et al: Autopsy Pathology: A Manual and Atlas. Churchill Livingstone, 2004
- DiMaio D et al: Forensic Pathology, 2nd ed. CRC Press, 2001
Additional References
- Malik A, Brito D, Vaqar S, et al. Congestive Heart Failure. [Updated 2023 Nov 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430873/
- Unverferth DV, Fetters JK, Unverferth BJ, Leier CV, Magorien RD, Arn AR, Baker PB. Human myocardial histologic characteristics in congestive heart failure. Circulation. 1983 Dec;68(6):1194-200. doi: 10.1161/01.cir.68.6.1194. PMID: 6640872.
- Page RL. et al. Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association. 2016. 134(6). Drugs That May Cause or Exacerbate Heart Failure
- Packer M. What causes sudden death in patients with chronic heart failure and a reduced ejection fraction? Eur Heart J. 2020 May 7;41(18):1757-1763. doi: 10.1093/eurheartj/ehz553. PMID: 31390006; PMCID: PMC7205466.
- Yuyun MF, Kinlay S, Singh JP, Joseph J. Are arrhythmias the drivers of sudden cardiac death in heart failure with preserved ejection fraction? A review. ESC Heart Fail. 2023 Jun;10(3):1555-1569. doi: 10.1002/ehf2.14248. Epub 2022 Dec 9. PMID: 36495033; PMCID: PMC10192266.
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- Amita R. Noninfective Endocarditis. PathologyOutlines. 2014. Last Updated: 2020 Noninfective Endocarditis
- Ammash NM. Restrictive cardiomyopathies. UptoDate. Updated 2024. Restrictive cardiomyopathies
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- Bashir A., Memon AH. Malignant hypertension and accelerated nephrosclerosis. PathologyOutlines. Last Updated: 2025. Malignant hypertension and accelerated nephrosclerosis
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