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1.1 Introduction

Pathological study of the heart can be performed either after the death of a subject (during an autopsy) or during the lifetime of a patient (biopsy and cardiac transplantation). The purpose of each of these studies is summarised in Table 1.1.

Table 1.1 Purpose of the histopathological study of the heart
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Presently, the largest number of histopathological studies on the whole heart is carried out in forensic investigation due to the following reasons:

  1. 1.

    Cardiac pathology is responsible for 80 % of the sudden deaths that require a forensic autopsy to discard a violent cause of death.

  2. 2.

    Cardiac pathology can be a coadjuvant factor for deaths that occur during extracardiac surgical interventions or during hospital stays; situations where medical malpractice claims are frequent.

  3. 3.

    Cardiovascular surgical procedures such as correction of congenital defects, catheterizations, ablations, pacemaker implantations, prostheses, coronary by-pass grafts, etc., can result in fatal outcomes that also require legal investigation.

  4. 4.

    Cardiac pathology can be responsible for traffic-related accidents, or work or home-related accidents, which cause death due to traumatic lesions.

In the context of sudden death, it is also essential to study the heart in order to identify potential hereditary diseases, and through this offer counselling and protect other family members. Logically, before performing an autopsy on the heart it is necessary to have as much information as possible regarding: family and personal history, previous cardiovascular events, surgical interventions and circumstances of the death (whether witnessed, related to physical activity, duration and type of resuscitation manoeuvres attempted).

1.2 Study of the Heart

The study of the heart begins with the removal of the sternum and the inspection for possible intrapericardial effusion (quantity and characteristics: haematic, serous, purulent); or mediastinal haemorrhage due to rupture of the extrapericardial aorta. If gas embolism is suspected, the pericardial sac must be opened under water to check for leakage of gas bubbles through an incision on the pericardial surface. Once the pericardial sac is opened, and to discard thromboembolism, the trunk of the pulmonary artery can be sectioned 2 cm above the pulmonary valve, although many authors recommend for this purpose the opening of the pulmonary arteries from the posterior side. In cases of aortic dissection, the aorta should be examined along its entire length to look for a tear in the intima, and also in the external wall in cases of cardiac tamponade or mediastinal or retroperitoneal haemorrhage.

The heart must be removed as a whole by cutting the inferior vena cava close to and above the diaphragm; the pulmonary veins after checking their correct drainage in the left atrium; and the aorta and pulmonary trunk 2 cm above the semilunar valves.

Once the heart has been removed it should be washed to eliminate blood clots, and weighed. The heart weight must be compared with the expected weight for the gender and body weight. It is estimated that there is an increase of 5 % in the weight of a fixed heart in formalin. It can also be useful to measure the ventricular axes in the posterior surface of the heart, taking as a reference the crux cordis (indicative of the presence of dilation and/or ventricular hypertrophy). A transversal axis of 10–11 cm, and a longitudinal axis of 9–10 cm, is considered normal. Next, a macroscopic study is initiated, which is summarised in Table 1.2. The Annex at the end of this chapter provides the normal reference values for cardiac dimensions and weight. It is recommended that photographs of any lesions are taken, or even the absence of alterations, in specific legal cases.

Table 1.2 Gross examination of the heart
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The study of the heart begins with an external examination to assess its shape, appearance of the pericardium, absolute mass of epicardial adipose tissue, etc. (Fig. 1.1).

Fig. 1.1
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(a) Normal heart with epicardial adipose tissue distributed along the AV groove and in the course of the anterior descending coronary artery. (b) Whitish patches (Soldier’s patches) in visceral pericardium classically attributed to mechanical trauma or healed pericarditis

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There are several methods to open and dissect the heart depending on the pathology to be studied but, taking into account that in the majority of forensic cases there is no medical antecedents or clinical records of the deceased, the method of choice to study the heart must be the one that allows the diagnosis of the most frequent diseases. The classical method of dissection following the direction of the blood flow can be used in cases of congenital heart disease in children, but not for the study of adult heart pathology (myocardial infarction, cardiomyopathies, infiltrating diseases, etc.) in which several parameters such as the presence of myocardial lesions, wall thickness and ventricular size need to be evaluated. For this reason the most convenient method of dissection of the adult heart involves sectioning the ventricular cone into slices of 1–2 cm in thickness, parallel to the posterior atrioventricular groove, starting from the apex to the base of the papillary muscles. Using this method, about four or five biventricular slices are obtained and the cardiac base is left intact (Fig. 1.2). This sectioning is best performed on a fixed heart and with long-bladed knives.

Fig. 1.2
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(a–c). Protocol to study the heart by transversal sectioning from the apex to the papillary muscles, obtaining a closed base with intact valves and four to five biventricular slices

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1.2.1 Study of the Myocardium

The location and distribution of myocardial lesions, together with the diameter of the ventricles, should be evaluated in the sliced biventricular sections. The anterior wall of the LV spans from the anterolateral papillary muscle to the septum; the lateral wall is situated between the two papillary muscles; and the posterior/inferior LV wall is adjacent to the posterior papillary muscle (Fig. 1.3). Pathologists maintain the posterior wall terminology, whereas clinicians, in keeping with the heart anatomical position, prefer to name it inferior wall.

Fig. 1.3
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Nomenclature of the ventricle walls

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The mid-ventricular slice should be used to measure the wall thickness and the diameter of the LV, excluding the trabeculae and papillary muscles (Fig. 1.4). A possible dilation of the RV should be evaluated in the cardiac apex. The thickness of the anatomical sections is not equivalent to those obtained by echocardiography since this is performed with the heart in telediastole. Values considered normal are 10–15 mm for the thickness of the LV and the septum, and 3–4 mm for the RV, during necropsy. Larger values are indicative of cardiac hypertrophy; however, diagnosis of hypertrophy should be based chiefly on the weight of the heart relative to that expected for the body weight.

Fig. 1.4
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Measurement of the ventricular thickness and the diameter of the LV, excluding the papillary muscles and trabeculae. The thickness of the RV is measured at its posterior wall since the anterior wall presents more epicardial adipose tissue and adipose infiltration, especially in elderly people

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1.2.2 Study of the Cardiac Base and Valves

The cardiac base is opened following the direction of blood flow, starting in the right atrium that is opened from the inferior vena cava to the apex of the right atrial appendage, to preserve the sinoatrial node of the conduction system (Fig. 1.5) (see Chap. 10). Then examine the tricuspid valve through which, in normal conditions, three average-sized fingers can be placed.

Fig. 1.5
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(a) The discontinous arrow points to the direction of the cut to open the right atrium. The asterisk indicates the position of the sinoatrial node. (b) Opening with scissors

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Then, open the lateral border of the RV (Fig. 1.6a) and inspect the opened tricuspid valve, the right atrium and the basal portion of the RV. The perimeter of the valve is measured at the level of the annulus (Fig. 1.6b).

Fig. 1.6
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(a) Opening of the lateral border of the RV. (b) Measurement of the tricuspid valve perimeter with the aid of a length of string

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The most important structures of the right side of the heart are compiled in Fig. 1.7. The AV node is positioned in front of the mouth of the coronary sinus (see Chap. 10). The tricuspid valve has one large anterior papillary muscle, a septal muscle (Lancisi’s muscle) which can be double or multiple, and a posterior papillary muscle formed by several smaller ones. The septomarginal trabecula (also known as moderator band) extends from the inferior part of the septum (continuation of the septal band of the supraventricular crest) to the base of the anterior papillary muscle at the tricuspid valve. This is the inferior limit of the inflow tract of the RV and through its interior runs the continuation of the right bundle of the conduction system.

Fig. 1.7
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View of the right chambers after opening through the lateral border. The most relevant structures are indicated

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In one third of adults, the foramen ovale does not close correctly (Patent foramen ovale) and functions as a competent flap valve, ensuring that the orifice remains closed since greater pressure exists in the left atrium (Fig. 1.15).

After, following in the direction of the blood flow, open the outflow tract of the RV and the pulmonary artery (Fig. 1.8). The annulus of the pulmonary artery is located 1.5 cm above the annulus of the aortic valve and has three leaflets: the right leaflet is located near to the aortic valve right leaflet, and the left leaflet is found near the aortic valve left leaflet (Fig. 1.9). The valve perimeter is measured at the sinotubular junction.

Fig. 1.8
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(a) Sectioning through the RV outflow tract. (b) View of the opened pulmonary valve and the origin of the pulmonary arteries. In the bottom, the moderator band can be observed (arrow). In some cases the pulmonary valve can have four leaflets (see Chap. 7)

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Fig. 1.9
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Transversal section at the level of the semilunar valves. At the top of the image, the pulmonary artery and, at the bottom, the aortic valve where the ostium of the right coronary artery and the origin of the left coronary artery trunk can be visualised

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The opening of the LA is more arbitrary, generally between the left and right pulmonary veins, but attention must be paid to the atrial appendage in case possible thrombus is present (Fig. 1.10). View the mitral valve from the left atrium searching for prolapse, fusion of commissures, etc. (Fig. 1.11). It is estimated that two fingers can pass through the mitral annulus. Exceptionally, anomalous muscular bands can be found in the atria, similar to the false tendons of the LV (Fig. 1.12), which are associated in some cases with patent foramen ovale and to Chiari’s network, and can cause mitral valve insufficiency.

Fig. 1.10
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Opening of the left atrium and appendage

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Fig. 1.11
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(a) A normal mitral valve as seen from the left atrium. (b) A rheumatic mitral valve: the atrium is dilated, with valvular fibrosis in the leaflets and commissure fusion

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Fig. 1.12
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(a) An anomalous band between the anterior and posterior wall of the left atrium. (b) False tendons between the papillary muscles and the septum, and in the RV

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Next, open the LV laterally with a longitudinal cut between the papillary muscles (Fig. 1.13) to view the left atrium, the opened mitral valve (its perimeter is measured at the annulus level) and the left ventricle, paying special attention to the internal structure of the chambers and the mitral valve. The mitral valve consists of two leaflets: the anterior one is semicircular and forms part of the left ventricular outflow tract; the posterior leaflet has a scalloped appearance. The anterior papillary muscle is single whereas the posterior papillary muscle is usually double (Fig. 1.14). The area facing the LV is very trabeculated (1/4 of the total thickness).

Fig. 1.13
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Opening of the lateral border of the LV

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Fig. 1.14
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View of the opened mitral valve

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Fig. 1.15
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Patent foramen ovale as seen from the left side

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Visual inspection of the aortic valve should be performed from above before its opening to determine the number of cusps, the presence of calcifications, commissural fusion, etc. (Fig. 1.16). Next, the outflow tract of the LV is opened by an oblique cut in the anterior wall proximal to the septum (Fig. 1.17) to inspect the ascending aorta (check for atheromas, aneurysms, intimal tears in aortic dissections, intramural haematomas, origin of coronary bypass, etc.) and the aortic root (consisting of the fibrous annulus, the sinuses of Valsalva and the sinotubular junction).

Fig. 1.16
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(a) Inspection of the aortic valve before its opening. (b) Aortic valve with calcification in the three leaflets, in an 82-year-old woman with senile aortic stenosis

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Fig. 1.17
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Opening of the LV outflow tract. Long forceps serve as a guide

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The aortic and mitral annuli are fused through the intervalvular fibrosa (fibrous continuity between the anterior leaflet of the mitral valve and the left and posterior sigmoids) (Fig. 1.18). The anterior Valsalva sinuses give rise to the coronary arteries (Fig. 1.9). Fenestrations are frequently found between the valve closure line and its free border (lunula) (Fig. 1.21a), and also fibrocartilaginous nodules (Arancio-Morgagni’s nodules) and papillary excrescences (Lambl’s excrescences) in the valve closure line (Fig. 1.19).

Fig. 1.18
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Normal opened aortic valve where the Valsalva sinuses can be seen, with the origin of the coronary arteries (right (RC) and left (LC)). Discontinuos line = dashed line

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Fig. 1.19
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Fibrous nodules and Lambl’s excrescences in the valve closure line (arrow)

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1.2.3 Study of the Coronary Arteries

The left and right coronary arteries arise from the corresponding aortic Valsalva sinuses, and their branches irrigate the entire heart. The most frequent coronary artery tree is depicted in Fig. 1.20. According to this tree, the posterior descending coronary artery originates from the right coronary artery (right dominance), although there are three possible types of dominance whose characteristics and frequency are described in Table 1.3.

Fig. 1.20
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Scheme of the coronary artery tree. RCA right coronary artery, PDCA posterior descending coronary artery, LC left coronary artery trunk, LAD left anterior descending coronary artery, Dg diagonal, LCx left circumflex, Mg marginal

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Table 1.3 Types of coronary dominance (Baroldi 1967)
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In one third of the population, the left main coronary artery is divided in three branches: the left anterior descending coronary artery (LAD), the circumflex coronary artery (Cx) and in between the intermediate branch (not shown in the figure). In these cases, the intermediate coronary artery replaces the first diagonal.

1.2.3.1 Study of the Origin of the Coronary Arteries

The study of the coronary arteries begins by examining their origin in the corresponding Valsalva sinuses. The diameter of the right coronary artery at its ostium is commonly slightly smaller than that of the left coronary artery ostium. There is usually one ostium in the sinus, in a central position, although in some cases variations occur that are considered normal: two or more ostia in the right sinus or two ostia in the left sinus (Fig. 1.21). When both coronary arteries arise from the same sinus, sudden death can occur (see Chap. 6). In up to 30 % of human hearts, the left anterior descending coronary artery penetrates the myocardial septum to 2–3 mm depth and for a length of 10 mm in the basal third portion (Fig. 1.22). When the depth is more than 4 mm, the permeability of the artery during contraction of the ventricle can be compromised, provoking myocardial ischaemia (see Chap. 6).

Fig. 1.21
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Normal variations in the origin of the coronary arteries. (a) A unique ostium in each coronary sinus. The posterior leaflet is fenestrated. (b) Two orifices in the right sinus; the smallest one is the origin of the conus artery. This occurs in more than half of the hearts examined. (c) Independent origins of the left anterior descending and circumflex arteries in the left sinus (very infrequent). (d) In the right sinus three ostia can be recognized, corresponding to the right coronary artery, the conus artery and the right superior septal artery

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Fig. 1.22
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Intramural course of the left anterior descending coronary artery

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1.2.3.2 Study of the Distribution and Permeability of the Coronary Arteries

In cases of ischaemic heart disease, the ideal method is to perform radiography on the whole heart before sectioning, in order to identify calcified portions in the coronary arteries, possible stents, valve calcification, etc. It is also useful to carry out a post-mortem angiography by inserting contrast material through the origin of the coronary arteries, followed by radiography (Fig. 1.23) (the downside of this method is that the coronary ostia cannot be properly examined).

Fig. 1.23
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(a) Post-mortem coronary angiography, where an absence of filling in the proximal segment of the left anterior descending coronary artery (arrow) can be appreciated. (b) In the histology, an occlusive platelet thrombus adherent to a fibrous atheroma plaque (arrow) was found. Results are from a 33-year-old man that had been examined in a casualty department with precordial pain one hour before his death. The ECG was negative

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The study of coronary permeability, with or without previous radiological study, should be performed with transversal 3–4 mm sections through the entire length of the coronary arteries (Fig. 1.24a). This study offers better results if the heart has been previously fixed in formaldehyde. To examine the proximal segment of the circumflex coronary artery, it is useful to lift, or even better, to resect, the left atrial appendage. If there is calcification in the coronary arteries, they have to be dissected (the entire artery or the affected segments only), and decalcified in 7 % nitric acid (or an alternative decalcifying solution) before performing the transversal sections, as mentioned before (Fig. 1.24b). Classically, the degree of coronary stenosis can fall within four grades: light (25–50 % stenosis); moderate (50–75 %); severe (>75 %); and occlusive (100 %) (Fig. 1.24c).

Fig. 1.24
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(a) Transversal sections along the right coronary artery. (b) Dissected coronary segment ready for decalcification and serial sectioning. (c) Serial study of the coronary segment after decalcification, where an obstruction of >75 % of the lumen can be appreciated

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Afterwards, the portions with the greatest degrees of stenosis are subjected to microscopic analysis, noting its location (proximal, medial or distal). The right, left main, left anterior descending and circumflex arteries must always be examined and, optionally, the marginal, diagonal, posterior descending and intermediate coronary arteries also.

1.2.4 Study of Stent-carrying Coronary Arteries

In hearts with coronary artery stents, as mentioned previously, it is convenient to take an X-ray of the heart before its manipulation. An additional option is to dissect the coronary artery and then perform the radiological study (Figs. 1.25 and 1.26). The X-ray result allows the determination of the type of stent used, whether it has been implanted in the appropriate vessel, and if the stent has expanded adequately.

Fig. 1.25
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(a) Dissection of the left coronary arterial tree. LC left coronary artery trunk, LAD left anterior descending coronary artery, Dg diagonal, Int intermediate coronary artery, LCx left circumflex coronary artery. (b) Radiography of the segment, where the calcified atheroma plaques and the stents implanted in the anterior descending and intermediate coronary arteries (arrows) can be appreciated

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Ideally, a histological study of intravascular stents requires methacrylate-embedding of stents in situ followed by sectioning at 4–5 μm. This is the method of choice if stents have been implanted for less than 1 month and are scarcely covered by thrombuses and newly-formed intimal tissue (Fig. 1.26). For longer-term stents, the coronary artery can be sectioned with scissors every 3–4 mm to carefully extract the metallic wire for routine processing (Fig. 1.27).

Fig. 1.26
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A 68-year-old male was admitted to hospital with precordial pain. After catheterization, stents were implanted in the right and left anterior descending coronary arteries. The patient died at home on the day of his release. (a) Radiography of the coronary arteries after dissection, where a stent of 15 mm in the proximal segment of the right coronary artery (RCA) and another of 25 mm in the left anterior descending coronary artery (LAD) can be identified. (b) After removing the stent wires, an occlusive thrombus can be observed in the right coronary artery. (c) Image of the left anterior descending coronary artery after removal of the stent. In both cases, the metallic imprint of the stent can be recognised (arrows). The posterior/inferior wall of the LV showed an acute infarct of >2 weeks and the posterior wall of the RV revealed an infarct of 1–3 days evolution (Masson’s trichrome)

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Fig. 1.27
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A 44-year-old male who died in a motorbike accident. During the examination of the coronary arteries, a stent of 15 mm could be identified in the left anterior descending coronary artery. (a) Image of the coronary artery after removal of the stent. (b) Detail of the previous figure. In the arterial wall, restenosis of the coronary segment due to concentric intimal fibrosis can be observed. The orifices left behind after stent removal can be seen near the medial layer (arrows) (Masson’s trichrome)

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1.2.5 Study of Coronary By-pass Grafts

The classical aortocoronary bypass involves the connection of the aorta or some of its branches, to portions of the coronary arteries distal to the obstructive lesions through a vascular graft. The vascular graft can be a vein, an artery, or prosthetic. The anastomosis of the venous graft to the ascending aorta and coronary artery is of the terminolateral type (Fig. 1.28). The most commonly-used vein is the internal saphenous vein, while the external saphenous and cephalic veins are less used. The arterial grafts can be pediculated or free. In pediculated arterial grafts, one of the ends is kept in its anatomical location while the other end is directed to the coronary artery that requires re-vascularization. The arterial graft most widely used is the pediculated internal mammary artery, which remains connected to its natural site of origin, the subclavian artery. The internal mammary graft is the best choice to re-vascularize the left anterior descending artery (Fig. 1.29). In the majority of cases, pathological examination of coronary bypass is difficult due to post-surgical pericardial adherences. The inspection for possible tightness and twisted areas is necessary. Macroscopic study, as in the native coronary arteries, is done by transversal sectioning of the vessel every 3–4 mm and, for the microscopic study, the section containing the area of anastomosis with the native artery must always be examined (Fig. 1.30). Generally, with very recent grafts (the first 3 days) it is necessary to look for thrombus, compression in the insertion site and severe atherosclerosis in the native coronary artery distal to the insertion; in older grafts, stenosis due to fibrointimal proliferation and atherosclerosis should be explored.

Fig. 1.28
figure 28

(a) Two venous grafts at the left oblique posterior and left marginal coronary arteries (arrows). (b) Image of the ascending aorta from the same case showing the origin of a triple by-pass (arrows) (the third graft is anastomosed in the posterior descending coronary artery and is not visible in the photographs). (c) Microscopic image of a venous graft at the left marginal artery. Hyperplasia of the intima can be observed (Weigert)

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Fig. 1.29
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Pediculated arterial graft from the internal mammary artery (arrow)

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Fig. 1.30
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(a) Double by-pass to the left anterior descending and intermediate coronary arteries (arrows). The image shows transversal cuts in the area of anastomoses to the left anterior descending coronary artery and in the native coronary artery distal to it. (b) Microscopic image of the area of the venous graft insertion to the native anterior descending coronary artery (LAD) showing significant atheromatosis (Masson’s trichrome)

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1.2.6 Study of Prosthetic Valves

The purpose of the pathological study of heart valve prostheses is to identify the type of prosthesis (biological or mechanical); determine the size and position in relation to the annulus and cardiac chamber; evaluate the valve movement; search for thrombi, abscesses, vegetations or paravalvular leaks; and assess degenerative alterations (see Chap. 7).

Initially, the prosthesis needs to be examined in situ, to identify paravalvular leaks, tissue overgrowth (pannus) surrounding the prosthesis, and to evaluate its correct orientation (Figs. 1.31 and 1.32). Next, the prosthesis is removed and the native annulus is examined to discard paravalvular abscesses. Later, the prosthesis is carefully examined on both sides (Fig. 1.33) and, if possible, radiography is performed (Fig. 1.34). Histological study can be done from the annulus, possible thrombus, vegetations or from the leaflets when the prosthesis is biological. Table 1.4 summarises the alterations to search for in the macroscopic, microscopic and radiological studies. For more specialised studies, techniques such as scanning electron microscopy, transmission electron microscopy, calcium/phosphorus determination, lipid biochemistry, etc. are used.

Table 1.4 Lesions to evaluate in a prosthetic valve study
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Fig. 1.31
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View of a mitral prosthesis after sectioning the base near the atrioventricular junction. Circumferential tissue growth over the prosthesis can be appreciated

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Fig. 1.32
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Biological aortic prosthesis and orifices of the origin of two aortocoronary bypass grafts (arrows)

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Fig. 1.33
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(a) Mechanical prosthetic bi-leaflet mitral valve (St. Jude Medical) viewed from the atrial side. (b) Biological aortic prosthesis viewed from the aortic side

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Fig. 1.34
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(a) Biological valve with tearing of cusps. (b) The type of scaffolding observed in the radiological study allows the identification of the prosthesis as Ionescu-Shiley type

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1.2.7 Selection of Samples for Microscopic Study

The selection of samples for microscopic study is summarised in Table 1.5. There are some areas of the heart that must always be studied, whereas other areas are examined only under certain circumstances. The study of the conduction system can be performed by a simplified method described in Chap. 10. The stain routinely used is haematoxylin-eosin and, depending on the pathological findings, other stains such as Masson’s trichrome or Weigert’s stain for connective tissue, Congo red stain for amyloid, PAS-Alcian blue staining for mucopolysaccharides, etc. are used. In cases of myocarditis, immunohistochemistry for CD3, CD20, CD68, etc. is recommended.

Table 1.5 Sampling of the heart for microscopic study
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1.3 Age-Related Changes

Analogous to other organs, the heart suffers age-related modifications that must be differentiated from possible concomitant cardiac pathologies. The most important modifications are summarised in Table 1.6.

Table 1.6 Age-related cardiac changes (Figs. 1.35, 1.36, 1.37, 1.38, 1.39 and 1.40)
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Fig. 1.35
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(a) Marked increase in the mass of epicardial adipose tissue in a 79-year-old male. (b) Rigid coronary arteries with a tortuous course in a woman of advanced age

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Fig. 1.36
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(a) Sigmoid-shaped septum with endocardial fibrosis. (b) Adipose infiltration in the RV

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Fig. 1.37
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Dilated left atrium with rough endocardium and yellowish plaques in the anterior mitral valve leaflet, in a 77-year-old male

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Fig. 1.38
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Granular appearance of the endocardium of the left atrial wall characteristic of amyloid, in a 66-year-old male

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Fig. 1.39
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A 90-year-old female. Dilation of the left atrium, atheromas in the anterior leaflet, thickening of the closure line and calcification in the mitral valve annulus (arrow)

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Fig. 1.40
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(a) Basophilic degeneration of myocytes (Haematoxylin-eosin). (b) Positive PAS stain

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1.4 Molecular Studies

As previously mentioned in the introduction, cardiac pathology accounts for 80 % of sudden deaths, and thus the anatomopathological study of the heart following defined protocols described in this chapter is essential. However, there are numerous cases, especially among the young, in which sudden death, although cardiac in nature, arises from illnesses where the heart structure is normal but the ionic channels responsible for its electrical activity do not function correctly. These are the so-called channelopathies, that include primarily the long QT syndrome, Brugada’s syndrome, short QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). These are hereditary syndromes and, during the last decades, mutations in genes encoding different components of these ionic channels, particularly the sodium and potassium channels, have been discovered. The diagnosis of these channelopathies during an autopsy can be achieved through the genetic study from blood or tissue samples from the deceased, the so-called molecular autopsy (term given by Ackerman in 2001).

Furthermore, etiological diagnosis in cases of myocarditis also requires molecular studies by PCR to identify virus or bacterial genetic material. Recently, viruses have been detected in hearts without histological lesions.

It is also very important to carry out a genetic analysis in cases of structural cardiomyopathies or aortic disease to detect mutations present in other family members.

During the last years, special attention has been paid to the study of sudden death, especially among young people, which has led to the publication of several guidelines (Basso et al. 2008; TRAGADY 2008; Oliva et al. 2011), that expressly indicate which samples need to be taken for molecular studies (Table 1.7). It is important to remember the need to carry out toxicological determinations in cases of sudden death, especially among adolescents and young adults, to discard the involvement of alcohol or drug abuse.

Table 1.7 Samples to be collected at the autopsy for molecular studies
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Finally, as mentioned in the introduction of this chapter, we cannot forget the fact that in order to determine the cause of death, a histopathological study of the heart and other organs is not sufficient. It is essential to be aware of the clinical antecedents, the circumstances surrounding the death, and the symptoms previous to the death, in order to perform an effective and complete clinico-pathological correlation that allows us to determine the cause and mechanisms of death.