The aim of the current paper is to publish the topic in a surgical journal to make aware also the cardiovascular surgeons on this important topic.
Autopsy is still unreplaceable to establish the cause of sudden death (SD)
Medical history:
A full autopsy should be performed to rule out extra-cardiac causes of SD
The search for the cardiac cause should be accomplished by exploring: great arteries, coronary arteries, myocardium, valves, conduction system
The standard gross examination of the heart should be carried out:
In case of rare cardiomyopathies (mitochondrial, storage, infiltrative, etc.), a small sample (2 × 2 mm) of myocardium should be fixed in 2.5% glutaraldehyde for ultrastructural examination.
If ECG tracing suggests disturbances of the origin and transmission of the electrical impulse, investigation of the conduction system should be carried out by serial sections technique, removing and including in paraffin two blocks of sinoatrial and av septal junctions
In case of Wolff-Parkinson-White syndrome, the serial sections investigation should be extended to the lateral left and right rings, in search of accessory pathways.
Molecular autopsy aims to study DNA/RNA in the setting of viral myocarditis or genetically determined heart disease
In both circumstances, EDTA blood and ventricular myocardium will be taken, frozen and stored at −80°C or alternatively stored in RNA later at 4˚C, with nucleic acid extraction accomplished through termocycler.
Gene sequencing in fresh tissue can be carried out with success up to 100% of cases
From formalin fixed and paraffin embedded tissue, nucleic acid extraction and gene sequencing is successful up to 85% of cases, if amplicon length is less than 300 bp
The toxicological investigation aims to understand if any xenobiotic was involved as a cause, contributing-cause or death mechanism
In case of suspicion, especially on unwitnessed SD or victims found dead at bed, peripheral blood from femoral veins (10 mL), heart blood (10 mL), urine (30 - 50 ml) or bile (20 - 30 ml) (if urine are not available), should be collected in tubes with sodium fluoride as a preservative and stored at −20˚C until toxicologic analysis are performed. Vitreous humor (from both eyes) can also be collected and stored at −20˚C.
One or more locks of hair (100 - 200 mg) should be cut and taken from the back head or from the pubis.
The toxicological analysis should be quantitative and performed in certified referral laboratories
A definitive cause of SD can be identified already at gross and histological investigations in the majority of cases.
However, different degrees of certainty exist in establishing the cause-effect relationship between the observed cardiovascular substrate and SD.
The causes of SD should be considered as certain, highly probable or uncertain (
Certain |
Highly probable |
Uncertain |
Massive pulmonary embolism |
Stable atherosclerotic plaque with luminal stenosis > 75%, with or without acute or healed myocardial infarction |
Minor anomalies of the coronary arteries from the aorta (RCA from the left sinus, LCA from the right without inter-arterial course, high take-off from the tubular portion, LCx originating from the right sinus or RCA, with retroaortic course, coronary ostia plication, fibromuscular dysplasia, intramural small vessel disease) |
Hemopericardium due to aortic or cardiac rupture |
Anomalous origin of the LCA from the right sinus with intramural and inter-arterial course |
Intra-myocardial course of a coronary artery (myocardial bridge) |
Mitral valve papillary muscle or chordae tendineae rupture with acute mitral valve incompetence and pulmonary edema |
Cardiomyopathies (hypertrophic, arrhythmogenic right ventricular, dilated, others) |
Focal myocarditis, hypertensive heart disease, idiopathic left ventricular hypertrophy |
Acute coronary occlusion due to thrombosis, dissection or embolism |
Myxoid degeneration of the mitral valve with prolapse, ventricular fibrosis and intact chordae |
Myxoid degeneration of the mitral valve with prolapse, without atrial dilatation or left ventricular/papillary muscles fibrosis and intact chordae |
Anomalous origin of the coronary artery from the pulmonary trunk |
Aortic stenosis with left ventricular hypertrophy |
Dystrophic calcification of the membranous septum (±mitral annulus/aortic valve) |
Neoplasm/thrombus obstructing the valve orifice |
ECG documented ventricular pre-excitation (Wolff-Parkinson-White syndrome, Lown Ganong Levine syndrome) |
Atrial septum lipomatosis |
Thrombotic block of valve prosthesis |
ECG documented sino-atrial or AV block |
AV node cystic tumor without ECG evidence of AV block, conducting system pathology without ECG documentation |
Laceration/dehiscence/poppet escape of the valve prosthesis with acute valve incompetence |
Operated congenital heart diseases |
|
Massive acute myocarditis |
Not-operated congenital heart diseases, with Eisenmenger syndrome |
atherosclerosis stenosis exceeds 75% degree, the cause may be considered highly probable.
Coronary artery congenital anomalies like left circumflex arterial branch from the right coronary artery-right aortic sinus with retroaortic course or myocardial bridge should be regarded as uncertain, since they may be variants of the normal. In these circumstances, arrhythmic diseases like ion channel mutations should be always excluded through molecular investigation and illicit substance should be ruled out by toxicological examination.
In the case of unlikely or uncertain causes, the case should be evaluated on individual level since the clinical history and the circumstances of death may help to achieve the final diagnosis.
Finally, there are “gray zones” in which the border between physiologic and pathologic changes is poorly defined, like fatty tissue of the right ventricular free wall vs arrhythmogenic cardiomyopathy, athlete’s heart versus hypertrophic cardiomyopathy, focal inflammatory infiltrates versus overt myocarditis.
Finally, extensive photographic documentation should be carried out with precise indication where blocks were taken from. Moreover, send the entire heart to specialized centers or preserve the heart, for leaving the possibility of a second opinion.
Ethical Approval and Consent to participate: In Italy autopsy procedure is considered a regular laboratory investigation to establish the cause of death, which does not require family consent and is left to discretion of the doctor. Moreover, in case of suspicion of unnatural death, the autopsy is ordered by judicial authority.
Human Ethics: the need of family screening, to identify genetic diseases, is clearly highlighted.
Consent for publication: Publication is a self-decision of the authors, to make public the results of research plans.
Availability of supporting data: The contents of the paper derived from a longstanding experience of our group on pathology of sudden death, dating back 1980.
Competing interests: The authors declare no conflict of interest.
Funding: Our research project has been supported by the Registry of Cardio-Cerebro-Vascular Pathology, Veneto Region, Venice.
Authors’ contributions:
1) conceived and designed the experiments (G. Thiene, D. Favretto);
2) performed the experiments (G. Thiene, D. Favretto);
3) analyzed and interpreted the data (G. Thiene, D. Favretto);
4) contributed reagents, materials, analysis tools or data (Department of Cardiac, Thoracic, Vascular Sciences and Public Health—University of Padua);
5) wrote the paper (G. Thiene, D. Favretto).
Our research project has been planned by ARCA Foundation, Padua, Italy.
All authors of the manuscript have read and agreed to its content and are accountable for all aspects of the accuracy and integrity of the manuscript.
The submitted article is original work that is not being considered or reviewed by any other publication and has not been published elsewhere in the same or a similar form.