*Use of Cardiac Troponin for the Diagnosis of Cardiac Pathology in Postmortem Samples Taken… DOI: http://dx.doi.org/10.5772/intechopen.111799*

Using monoclonal antibodies specific to the cardiac isoforms, immunoassay technologies can quantify the amount of cTnT or cTnI in a biological matrix [6]. Initially, early immunoassays utilised high clinical cut-off values (high specificity and low sensitivity) allowed the separation of patients with overt acute myocardial infarction (AMI) from apparently healthy persons who were deemed negative for cTn based on the equivalent cTnT or cTnI concentration to the then-used gold standard tests (CK or CK-MB). Subsequently, the large body of evidence demonstrating elevation of CK and CK-MB in the absence of an elevated cTn questioned the cardio-specificity of the enzyme markers, along with approximately 30% of patients ruled out with AMI

#### **Figure 2.**

*Categories of cardiac troponin release in acute and chronic diseases. All conditions have documented evidence of elevated cTn. AF, atrial fibrillation; CAD, coronary artery disease; CHF, chronic heart failure; CKD, chronic kidney disease; ESRD end-stage renal disease; LV left ventricle; MVO2, myocardial oxygen consumption; PAH, pulmonary artery hypertension; RAAS, renin-angiotensin-aldosterone system; RV, right ventricle (source: [2], with authors permission).*

demonstrating positive cTn which is associated with poor prognosis, resulted in the adoption of cTn as the gold standard test for diagnosis of AMI [6].

Integral to the adoption of cTn was the appropriate definition of cut-off to confer an abnormal concentration. This was subsequently defined as the 99th percentile value of an apparently healthy population. When adopted into routine clinical practice, this lowered the sensitivity of the assays allowing early diagnosis in the evolving infarction but at the cost of specificity. Initially, this caused clinical confusion with a larger number of patients presenting with low concentrations of cTn just above the AMI cut-off value, but further research of such patients found the presence of comorbid conditions (**Figure 2**) often with underlying cardiovascular pathophysiology [2].

## **3. Biochemical testing in assisting cause of death at postmortem**

Biochemical testing in postmortem investigations (termed thanatochemistry, necrochemistry or the chemistry of death) was initially established in the early 1950s, and a great number of biochemical analytes have proved an adjunctive tool to assist the cause of death at postmortem [7]. Adoption of biochemical testing especially in the medico-legal forensic autopsy has often been limited. The determination of death may have significant impact on those directly or indirectly involved in the death of an individual and can carry a custodial sentence. Thus, the scientific evidence presented in court is intensely scrutinised both by the prosecution and defence counsels. Whilst no biochemical test is infallible, many are associated with the likelihood of a disease process rather than a definitive diagnosis of the disease. Often the barrier to use is the interpretation of results of biochemical assays from cadaveric sampling, hindered by the lack of reference normality in death; thus, results are compared to reference intervals generated in the living [7, 8] with few studies demonstrating corresponding histopathological findings to the biochemical results. Interpretation is further complicated by factors such as postmortem interference in the assay technology, appropriate sampling matrices, postmortem autolysis, microbial metabolism, fluid redistribution, and postmortem interval (PMI). Molecular biophysical properties such as molecular weight, structure, intracellular location, electrical charge, ionic strength, protein affinity, and cell membrane permeability may differ between life and death and can influence interpretation in both situations [7].

There are a number of fluid components which are suitable for cadaveric biochemical testing, namely vitreous humour from the posterior segment of the eye, cerebral spinal fluid (CSF), synovial fluid, pericardial fluid (PCF), venous femoral blood, venous jugular blood, peripheral blood sampling, urine, gastric contents and right ventricle heart whole blood [7–9]. Analytes and potential uses in postmortem samples are listed in **Table 1**.

## **4. Conventional cardiac biomarkers at postmortem**

The importance of cardiac biomarkers assisting in postmortem diagnosis was highlighted in cases where a suspected myocardial lesion cannot be diagnosed by routine histological analysis. They were utilised initially for the determination of sudden cardiac death. Initially, CK and lactate dehydrogenase isoenzyme analysis of pericardial fluid was utilised [10, 11], followed by K:Na ratio [12]; CK isoenzymes,

*Use of Cardiac Troponin for the Diagnosis of Cardiac Pathology in Postmortem Samples Taken… DOI: http://dx.doi.org/10.5772/intechopen.111799*


*AKI, acute kidney injury; CKD, chronic kidney disease; CK-MB, creatine kinase-MB isoform, CK-BB; creatine kinase-BB isoform; CSF, cerebrospinal fluid.*

**Table 1.**

*Biochemical analytes, sample matrices, and potential forensic utility.*

aspartate aminotransferase and hydroxybutyrate dehydrogenase [13] and myosin and cathepsin D, a lysosomal aspartyl protease that degrades proteins [14, 15].
