Cardiovascular pathology: guide to practice and training

Heart weights and measurements

Recording of accurate weights and measures of the heart and other organs is essential. Many studies have been performed with the goal of establishing normal values for cardiac weights with surprising variability in the reported reference range of normal values . This variability appears to be related to differences in composition and ethnicity of study populations, methodology, and use of forensic cases or hospitalized subjects. Table 1.4 presents mean values for cardiac weights, ventricular wall thicknesses, and valve circumferences for the normal adult heart from selected studies . A web app based on this data is available for evaluation of heart weight obtained at autopsy in relationship to the reference table ( http://calc.chuv.ch/heartweight#use ). Values for normal heart weights based on body weights in adults and subjects less than 20 years are presented in Table 2.2, Table 2.3 , Anatomic Considerations and Examination of Cardiovascular Specimens (Excluding Devices). Table 1.5 shows values from a more recent study for normal heart weights over a range of body weights in adults with a link to an internet application . Measurements of ventricular wall thickness and valve circumference in subjects less than 20 years old also are available . The strength of the statistical relationships of heart weight with age, gender, body weight, body length, body mass index (BMI), and body surface area (BSA) varies in different studies . The range of normal values found in studies based on forensic cases is lower than the studies performed in hospitalized subjects (compare values in Tables 1.4 and 1.5 ). Table 1.6 presents a method for separate determination of normal values for right and left ventricles (RVs and LVs) . This method is useful for selected applications, including research studies.

Based on considerable personal experience, R.E.B. Hudson has derived general formulas for normality of heart weights are as follows: adult male heart (fresh) weight: 0.45% of body weight; average 300 g, range 250–350 g, and adult female heart (fresh) weight 0.40% of body weight; average 250 g, range 200–300 g . Skurdal and Nordrum endorse the percentage method, but state that a fixed percentage cannot be used to calculate the upper limits of normal heart weight when the body weight approaches the outer range of body weights (i.e., marked obesity) . This approach can result in very heavy heart weights being designated as normal using a web app for calculation ( http://lundforensicmedicine.com ).

The authors endorse the general principle that a heart weight of more than 500 g is never normal . This is particularly relevant for establishment of cardiac hypertrophy in markedly obese individuals . This principle also correlates with the concept of a critical heart weight, determined to be 500 g (220 g LV), which when exceeded, leads to accelerated pathological remodeling of the ventricle .

In addition to cardiac weight, the shape of the ventricles and pattern of cardiac enlargement, that is, cardiomegaly, provide important information for categorizing the presence and type of heart disease ( Table 1.7 ). The patterns include: normal, ventricular dilatation without hypertrophy, concentric hypertrophy, eccentric hypertrophy, and asymmetric hypertrophy ( Fig. 1.1 ). Concentric hypertrophy is characterized by increased wall thickness and reduced ventricular cavity in response to a pressure load, that is, afterload. Eccentric hypertrophy is characterized by ventricular cavity dilatation and increased ventricular mass with no or mild increase in wall thickness in response to a volume load, that is, preload. Asymmetric septal hypertrophy is a pattern seen in hypertrophic cardiomyopathy. Detailed measurements have been made of cardiac size, chamber volumes, valve orifices, and shape of the ventricles at autopsy . Differences in the shape of the RVs and LVs when arrested in systole or diastole were shown . In making a determination of pathological hypertrophy, it is important to correlate the cardiac weight with wall thickness and chamber volume of the ventricles, noting systolic or diastolic configuration, as well as the presence or absence of histological features of cardiomyocyte hypertrophy, including enlarged polyploid hyperchromatic nuclei, and myocardial fibrosis.

There is a dichotomy between premortem radiological measurements of wall thickness by echocardiography, CT and magnetic resonance imaging (MRI), and corresponding autopsy measurements . The source of the discrepancy is that imaging measurements in life typically are made in diastole whereas postmortem measurements are made with the heart usually arrested in systole . Also, several studies have shown that postmortem measurements of wall thicknesses by CT and MRI differ from corresponding autopsy measurements . Paradoxically, there appears to be better agreement for wall thickness measurements between echocardiography and cineangiography in living patients and postmortem measurements of wall thicknesses. By echocardiography in living patients, a left ventricular wall measurement of 12 mm or less is normal, and 13–15 mm is a gray zone in which additional testing is needed to distinguish physiologic hypertrophy from early pathological hypertrophy, whereas a measurement of more than 15 mm is indicative of pathological hypertrophy . Postmortem measurement of left ventricular free wall thickness (excluding trabeculae and papillary muscles) of 12 mm or less also is normal.

Cardiac dimensions also are obtained during cardiac catheterization . By cineangiography, average LV wall thickness is 9 mm for women and 12 mm for men . These values are in reasonable agreement with the mean postmortem LV wall thickness of 12.3 mm (see Table 1.5 ). By cineangiography, average LV wall mass is 76 g/m ² for women and 99 g/m ² for men . Average BSA is 1.9 m ² for men and 1.6 m ² for women . Calculated average LV mass is 99×1.9=188 g for men and 76×1.6=121 g for women. These values are in reasonable agreement with anatomic determinations of normal LV weight of 190–225 g or less ( Table 1.6 ).

Sudden cardiac death

SCD warrants special consideration. SCD is strictly defined as the unexpected death without an obvious noncardiac cause that occurs within 1 h of witnessed onset of symptoms (established SCD) or within 24 h of unwitnessed onset of clinical manifestations (probable SCD) . SCD includes deaths due to nonarrhythmic, mechanical causes such as ruptured acute myocardial infarction (AMI), and deaths due to fatal ventricular arrhythmia, that is, sudden arrhythmic death syndrome (SADS), the latter also is included in sudden unexplained death syndrome (SUDS) . Unfortunately, there is variability in the meaning and use of these terms among pathologists and clinicians. Cardiologists may designate SADS when both autopsy and toxicology investigations are inconclusive, the heart is structurally normal at gross and histological examination and noncardiac etiologies are excluded (in infants it is called sudden infant death syndrome, SIDS) . SUDS also has been used for a death which is without an apparent cause and an autopsy has not been performed (in infants it is called sudden unexplained death in infancy, SUDI) .

If the decedent has a cardiac implantable electron device, interrogation of the device can provide documentation of a fatal arrhythmic event . Many cases of SCD have ischemic heart disease (IHD) as the pathological substrate . Left ventricular hypertrophy may be present with or without coronary artery disease. Other causes of SCD include coronary artery anomalies, hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, and acute aortic dissection . Acute aortic dissection is reported to have an outside-of-hospital death rate of 20% . Aortic rupture or dissection as immediate cause of sudden death is encountered in forensic and clinical autopsy practice .

Genetic factors contribute importantly to SCD, SADS, and SUDS . Subjects with primary arrhythmias, including prolonged QT syndromes and channelopathies, typically have hearts with no gross or histopathological findings . The only pathological finding in other subjects may be significant left ventricular hypertrophy, with underlying causes being systemic hypertension and primary cardiomyopathy. Regardless of cause, left ventricular hypertrophy is a well-documented, independent risk factor for SCD . Postmortem genetic testing can contribute significant information in determining the substrate for SCD, SADS, and SUDS .

Regarding accident victims, criteria have been developed for distinguishing cardiovascular disease as the primary event leading to accident versus accident being primary with cardiovascular disease being an accompanying finding ( Table 1.8 ) . Details of forensic investigation are discussed in various monographs .

A special approach has been developed for the investigation of perinatal deaths which constitute a continuum involving sudden intrauterine death syndrome (SIUDS), sudden perinatal unexpected death (SPUD), and SIDS. Careful autopsy examination is required to rule out various causes and to document subtle changes associated with unexplained perinatal and infant deaths . Protocols also have been established for evaluation of SCD in youths .