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Large hearts

Many pathogeneses
Associated with cardiac arrhythmias – some fatal

Strain effect

LV +/- RV hypertrophy

Cor pulmonale due to RVH

RV hypertrophy is simpler to deal with
Limited, understood, causes of pulmonary artery hypertension (PAHT)

LV hypertrophy is more problematic
Several unclear syndromes

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Large hearts

1a. Cardiac arrhythmia
1b. LV hypertrophy OR
1b. RV hypertrophy

But should not be used without some depiction as to aetiology
Even if uncertain

Normal heart/body weight ratio = 0.3 – 0.5%
Works within wide weight & BMI range
Any ratio > 0.5% makes you think

Athlete heart = LVH
Starvation = apparent LVH

More reliable than usual:-

Male LVH >500gm

Female LVH >400gm

LV thickness > 1.5cm

RV thickness >0.5cm

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PAHT with RVH

RV LV

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These metrics are important in coronial autopsy work

Sudden unexpected death in the community
No witness account of final hours/minutes/seconds of person’s life
GP records vague/absent on blood pressure etc

Not usual coronary ischaemic heart disease

Other organ pathologies noted
Lungs and kidneys
Toxicology screen
Mast cell tryptase analysis

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Case

M60, BMI = 47
Known abuse of alcohol & cannabis
Known COPD (emphysema) and chronic cough
No recorded BP in GP notes

Sudden unexpected unwitnessed death at home

All organs congested++
Fluid in mouth
Brain normal
Heart: 750gm = 0.58% TBWt
LV 2cm, RV 0.4cm
Coronary arteries clear
Severe emphysema, possible fluid aspiration.
Kidney – normal, no hypertensive arteriopathy
Liver – mild steatosis & fibrosis
Tox screen: no ethanol or acetone; pregabalin 23mg/L; cannabis++

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LVH but not RVH on histology

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Lung��Emphysema��One bronchus contains clear fluid

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Cause of death? has to be cardio-respiratory arrest

LVH?

Idiopathic
Obesity CM?

Emphysema?

But RV not much hypertrophied
Not cor pulmonale/PAHT

Morbid obesity per se?
Drug toxicity?

Proffered MCCD:
“1a. Acute cardiorespiratory arrest from choking
1b. LVH, emphysema, morbid obesity
2. pregabalin & cannabis toxicity –see Commentary”

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What is obesity cardiomyopathy (OCM)?

AHA definition:
“myocardial disorder, alterations in ventricular morphology & function;
LVH

eccentric or concentric

RV dysfunction
In setting of MO”

Functional in vivo abnormalities
Inflammatory systemic processes

Fatty heart
Fatty infiltration
Lipotoxic CM
Cardiac steatosis
Adiposity of the heart

There is no agreed morphological case definition of OCM – be careful

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Hypertension

Look at hospital and GP records – if available

Look for renal failure metrics

On treatment?

+/- diabetes?

Importance of kidney histopathology

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LV hypertrophy - hypertension

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Heart histology – default 5-block sampling

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LVH��thickened myofibres��brick-shaped nuclei��interstitial fibrosis

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Kidney arterial system�

Cortex

Medulla

glom

Lobar artery:

One per renal papilla

Interlobar arteries

Arcuate arteries

Interlobular arteries

Glomerular

arterioles

ATHEROSCLEROSIS &

HYPERTENSIVE ARTERIOSCLEROSIS

DIABETIC & HYPERTENSIVE ARTERIOLAR HYALINOSIS

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Arteriosclerosis��medium and small size arteries

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Hyaline arteriolosclerosis of the glomerular arterioles

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Hyalinosis & glomerular �loss (balls of fibrous tissue)

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DD – diabetic kidney disease – arterioles and glomeruli

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Amyloidosis

Immunoglobulin

Secondary inflammation AA

Transthryetin (TTR)

Age-related

A good reason for doing heart histology

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Case – male 86 years

Reported heart attack 5 years ago.
At home, he complained of chest pains, went pale, and collapsed.
CPR was unavailing.

Heart = 630 gm = 1.05% TBWt
Coronary arteries: atheroma, and one artery lumen 1mm
No coronary thrombosis

Amyloid in heart only
Referred heart block to Royal Free Hospital Amyloid Unit
= transthyretin amyloid

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LVH�RVH�Asymmetry�No scar�No acute lesion

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Congo red stain – ‘apple-green dichroism’

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Cocaine and related sympathomimetic drugs

LVH

Contraction bands

Acute myocardial ischaemia

Irregular (non-coronary distribution) fibrosis

Coronary arteriosclerosis

Sudden cardiac arrhythmic death

Body fluid analysis for cocaine may be negative at time of death

History important

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Acute cocaine toxicity – blotchy myocardium

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Cautionary note

CPR with cardiac compression plus adrenalin into the heart

Produces contraction bands and necroses

True cocaine toxicity

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Case – male 34 years, living at home

No known cardiac history
No family history
Once seen drunk at GP surgery
Found dead at home in bed one morning

BMI = 27
Heart = 775gm
H/B wt ratio = 0.78%

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1^st impression�� = Inherited HCM?��Keep spleen sample in freezer��Do toxicology screen��

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LVH and RVH – no myofibre disarray [note RV………..]

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Toxicology data

Ethanol: 83 md/dL in blood, 120mg/dL in urine.

Cocaine: blood, not detected

Cocaethylene – not detected

Benzoylecgonine, cocaine metabolite detected in urine and blood; <1ng/ml in blood.

No other drugs detected.

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Update on cocaine case

Chronic ‘snuff’ taker

Material retrieved and being sent to the tox lab for analysis

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Inherited cardiac disease identification

Cardiomyopathies
Sudden cardiac death syndromes

Channelopathies – SADS/MNH

Genetic aortic dissection

Increasing knowledge about the genetic links
NHS program directive

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Cardiomyopathy

Pathologists’ definition: heart disease NOT due to:

Coronary artery disease
Hypertension
Valvular disease
Known infective myocarditis

ie secondary CMs excluded

Clinicians use the term much more loosely

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Current classification

HCM – hypertrophic
DCM – dilated
ARVC – arrhythmogenic RV
RCM - restrictive
Unclassified CM

LVH – no cause
LV fibrosis – no cause

Familial/genetic

Non-familial/non-genetic

Idiopathic

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HCM and sudden death – male 29 years

Subaortic

impact

lesion

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Myofibre disarray = classical hypertrophic cardiomyopathy (HCM) with proven genetic abnormality [10% rule]

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DCM- pathologically ill-defined

Systolic dysfunction = heart failure

LV dilatation and thinning
RV – later
Increased heart weight
Myofibre degeneration
Replacement fibrosis

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Heart failure – no hypertension or valve disease

Attenuated myofibers

Interstitial fibrosis

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DCM heart failure lung – pulmonary vein thickening + haemosiderosis (heart failure cells)

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Myocardial fat only is not ARVC

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HCM and ARVC

If suspected
Full histopathology
Ask a colleague

Mary Sheppard: “ARVC is over diagnosed’

Spleen sample for DNA

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Unclassified Idiopathic CM?

Unexplained LVH +/- interstitial fibrosis

New genetic cardiomyopathies waiting to be discovered?

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51yr female; 11 children; mild hypertension; sudden collapse whilst shopping

900gm = 1.2% total body weight

Survived one day in A&E

Heart scan = “HCM”

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But histology = LV hypertrophy NOS, not HCM disarray

Kidney normal

Spleen sample retained

Family recommended to attend cardiac genetic clinic for assessment

No DNA result yet

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LVH – no obvious cause – fine diffuse interstitial fibrosis��?a cardiomyopathy��you will encounter a lot of this scenario;�set your own rules on how to interpret the heart morphology

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NHS and Coronial Sudden Unexpected Death (NHS-C-SUD) Programme Summary Briefing Paper

A pilot program to test the feasibility of maximising the identification of families with inherited cardiac conditions

7 coronial jurisdiction areas in England

1 in London – London Inner South

Cases derived from pathologists identifying or suspected likely cases from autopsies

Who identifies/confirms the pathomorphology?

Coordinator:
Liaise with coroners
Relatives’ consent
Liaise with cardiac clinics
Collect spleen DNA for sequencing

Network of genetic lab hubs

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Unascertained cause of death*:

Morphologically normal heart. Sudden arrhythmic/adult death syndrome (SADS)
Equivocal/uncertain/borderline findings

A dilated, thin walled, hypertrophied, scarred or fatty heart with normal or unobstructed coronary arteries:

Hypertrophic cardiomyopathy (HCM)
Dilated cardiomyopathy (DCM)
Arrhythmogenic cardiomyopathy (ACM)/arrhythmogenic right ventricular cardiomyopathy
Unexplained cardiac hypertrophy
Unexplained cardiac scarring/ fibrosis

Severe mitral valve prolapse with myxomatous degenerative valvular disease (<40 years**)

Thoracic aortic aneurysm +/- dissection/rupture (<40 years**)

Others – i.e. idiopathic calcification of infancy, possible metabolic/storage cardiomyopathy

* Toxicology will be required and will only likely be available at a later stage.

** If there is additional family history of sudden death or similar heart disease then older cases may be included.

NB cases where a non-cardiac cause of death was indicated (e.g. trauma) but a genetic heart disease has been identified incidentally will be included.

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