Sudden deaths due to acute aortic wall failure: A 10-year forensic autopsy series

Abstract

Background

Acute aortic wall failure (AAWF), including rupture and/or dissection phenotypes, represents a rare but often fatal acute aortic event that may develop without overt aneurysmal dilatation. The underlying pathological substrate remains incompletely characterized, although standardized histopathological criteria proposed by the Society for Cardiovascular Pathology (SCVP) have recently improved the consistency of aortic wall assessment in forensic investigations.

Methods

In this retrospective autopsy-based study, 5,277 adult autopsies performed between 2013 and 2023 were reviewed. Non-traumatic fatal AAWF, confirmed by macroscopic and histopathological examination, was included. A total of 93 cases were identified, of which 78 were evaluable histologically according to the SCVP criteria. Cases were classified as rupture without dissection, dissection with rupture, and dissection without rupture. The latter was included as a comparative subgroup to contextualize medial degeneration patterns within the spectrum. Demographic characteristics, comorbidities, event location, cardiac findings, and toxicological results were recorded.

Results

AAWF accounted for 6.7% of cardiovascular deaths. Median age was 58 years (interquartile range 49-67), and 68.8% were male. Eighty cases demonstrated rupture (rupture without dissection or dissection with rupture). Younger decedents (19-45 years) had lower rates of documented hypertension and atherosclerosis, while a comparable proportion met ≥3 SCVP medial degeneration criteria. The ascending aorta was most frequently involved (62.4%). Among histologically examined cases, mucoid extracellular matrix accumulation (65.4%), elastic fiber fragmentation (60.3%), and smooth muscle cell depletion (55.1%) was the most prevalent SCVP features; 43.6% met ≥3 SCVP criteria. Documented hypertension was associated with more advanced medial degeneration on univariable analysis (p=0.002) and was interpreted as pathological coexistence rather than an independent causal determinant. Increased heart weight consistent with cardiac hypertrophy was observed in 80.5% of cases.

Conclusion

Fatal AAWF is characterized by structural medial degeneration identifiable using SCVP criteria and frequently coexists with hypertensive cardiac remodeling in forensic autopsy findings. Standardized SCVP-based assessment may improve diagnostic consistency in forensic practice. Molecular autopsy, particularly in younger decedents, may further clarify etiopathogenesis and support targeted evaluation.

Acute aortic wall failure (AAWF), encompassing rupture and/or dissection phenotypes, represents a rare yet devastating vascular condition and one of the most lethal causes of non-traumatic sudden death.^{[1, 2]} While aortic dissection typically begins with an intimal tear and propagates along the medial plane, spontaneous aortic rupture may occur abruptly without prior clinical symptoms, resulting in full-thickness disruption of the aortic wall and massive hemorrhage.^[3] Owing to the rapid progression of these events and their frequent diagnosis at autopsy, fatal aortic wall failure remains underrepresented in the literature, and the underlying pathophysiological mechanisms are incompletely understood.^[3]

Histopathologically, fatal aortic wall failure is closely associated with structural weakening of the aortic media, often related to chronic hypertension and age-related degeneration of connective tissue.^[4] The 2016 Consensus Guidelines issued by the Society for Cardiovascular Pathology (SCVP) and the Association for European Cardiovascular Pathology (AECVP) proposed a standardized nomenclature and scoring system for medial degeneration, incorporating eight histological criteria, including mucoid extracellular matrix accumulation (MEMA), elastic fiber fragmentation, and smooth muscle cell (SMC) loss.^[5] These degenerative alterations increase the fragility of the aortic wall and predispose it to catastrophic mechanical failure, particularly in the ascending aorta, where hemodynamic stress is greatest.^[5]

Although fatal aortic wall failure predominantly affects older adults, cases occurring in younger individuals raise the possibility of underlying inherited connective tissue disorders, which may remain undiagnosed in the absence of postmortem genetic analysis.^{[6, 7, 8, 9]}

The primary aim of this study was to characterize the structural and histopathological features underlying fatal AAWF using standardized SCVP criteria in a large forensic autopsy cohort. Rupture and dissection phenotypes were evaluated within the spectrum of AAWF using a structured pathological framework. Accordingly, we performed a retrospective autopsy-based analysis of 93 fatal AAWF cases, focusing on anatomical rupture distribution, associated comorbidities, and histopathological findings, and mapped these observations to the SCVP 2016 classification framework to highlight the diagnostic value of standardized histopathological assessment in forensic practice.

Methods

Study design: This retrospective, autopsy-based observational study used forensic pathology data, covering the period from January 2013 to December 2023.

The inclusion criteria were as follows: (1) Age ≥18 years at the time of death; (2) death attributed to fatal spontaneous acute aortic wall failure, defined as non-traumatic aortic rupture and/or acute aortic dissection, confirmed by a complete autopsy, including gross and histological examination; and (3) availability of at least two representative, full-thickness transverse histological sections from the affected aortic segment (event site and adjacent macroscopically intact areas), suitable for semi-quantitative evaluation according to the 2016 SCVP/AECVP criteria.

The exclusion criteria were as follows: (1) Aortic wall failure secondary to trauma (blunt, penetrating, or iatrogenic), surgical intervention, or medical instrumentation; (2) incomplete autopsy records or missing key anatomical structures; and (3) absence of histological tissue samples from the aortic wall or presence of severe autolysis, diffuse hemorrhagic infiltration, or processing artifacts that rendered histological interpretation unreliable.

Case classification: Cases were stratified into three categories based on the presence or absence of dissection and rupture: (1) Spontaneous rupture without dissection, (2) dissection with secondary rupture, and (3) dissection without rupture. This classification reflects phenotypic variation within the spectrum of fatal AAWF and was adopted to enhance pathological clarity and consistency in autopsy-based documentation. Rupture without dissection and dissection with rupture constituted the rupture phenotype, whereas dissection without rupture was included as a comparative phenotype to contextualize medial degeneration patterns across the spectrum of aortic wall failure. Accordingly, cases of dissection without rupture were excluded from rupture-specific etiological interpretations but contributed to the descriptive pathological framework of the cohort.

Data collection and autopsy protocol: Demographic data, including age and sex, and medical history, including hypertension, diabetes mellitus, atherosclerosis, and alcohol or tobacco use, were extracted from institutional digital archives and pathology reports. A standardized data collection form was used to ensure consistency of data collection. The autopsy variables included the anatomical location of the rupture (ascending, descending, or thoracoabdominal aorta), heart weight, presence of left ventricular hypertrophy (LVH) (defined as left ventricular wall thickness >15 mm), and coronary artery disease (CAD). Additionally, toxicological screening results for substances such as alcohol, cannabis, cocaine, and prescription drugs were recorded.

Gross examination of the thoracic aorta was performed during autopsy using a standardized protocol. The ascending and descending aortic diameters were measured using a caliper at the widest transverse cross-section. The aortic valve annulus circumference was recorded in a subset of patients with preserved valvular function. The hemopericardial volume was quantified using a graduated container. In cases exhibiting features of dissection, the DeBakey classification was retrospectively applied based on the dissection origin and extent. The presence of a linear transmural rupture, intimal tear, or intramural hematoma was also recorded.

Histopathological processing and SCVP scoring: Representative full-thickness transverse sections were obtained from the affected aortic segment in each case, including the rupture site and adjacent macroscopically intact region. Samples were fixed in 10% buffered formalin, embedded in paraffin, sectioned at 4-5 μm, and stained with

• Hematoxylin and eosin for general morphology,

• Elastic Van Gieson for elastic fiber integrity,

• Masson’s trichrome for collagen and fibrosis assessment.

Evaluation followed the 2016 Consensus Guidelines of the SCVP and the AECVP. Eight features of medial degeneration were assessed.

1. MEMA

2. Elastic fiber fragmentation

3. Elastic fiber thinning

4. SMC loss

5. Laminar medial collapse

6. Medial fibrosis

7. Cystic spaces (in cases where architectural preservation allowed detection)

8. Inflammatory cell infiltration.

Each feature was scored semi-quantitatively as follows:

- Absent (0), Mild (1), Moderate (2), or Severe (3).

In cases of MEMA, the distinction between intralamellar and translamellar accumulation was recorded.

Histological analysis was performed in 78 of the 93 cases. The remaining 15 cases were excluded based on histopathological review indicating poor tissue integrity: Eight cases demonstrated advanced autolysis with nuclear loss and cytoplasmic dissolution, four cases were fragmented due to extensive hemorrhagic infiltration, and three cases exhibited fixation or processing artifacts that impaired structural assessment. No case was excluded solely because of hemorrhagic infiltration or minor technical artifacts; exclusions were made only when tissue integrity was insufficient to allow reliable histopathological evaluation. Sampling was performed in accordance with the SCVP/AECVP guidelines for forensic cardiovascular autopsy, including transverse sections from the ascending aorta, aortic arch, and descending thoracic aorta.

Histological evaluation was performed independently by two senior pathologists with expertise in cardiovascular and forensic pathology. Reviewers were blinded to premortem clinical history, toxicological results, and documented demographic risk factors during microscopic assessment. Complete blinding to gross pathological context was not feasible, as histological sampling and slide labeling are intrinsically linked to macroscopic autopsy findings and anatomical localization in routine forensic practice. Interobserver discrepancies were infrequent and primarily related to the grading of severity rather than the presence or absence of specific histopathological features. All discrepancies were resolved through joint slide review and consensus discussion. Given the descriptive and semi-quantitative nature of the assessment and the low frequency of discordance, formal interobserver agreement statistics (e.g., kappa coefficients) were not calculated.

Ethical approval: The study protocol was approved by the Committee of Education and Scientific Research, Council of Forensic Medicine (approval number: 21589509/2024/1414, date: 03.12.2024). All data were anonymized to ensure that no identifiable personal information was collected. This study adhered to the principles of the Declaration of Helsinki.

Statistical Analysis

Statistical analyses were performed using IBM SPSS Statistics version 28.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics for continuous variables are presented as median [interquartile range (IQR)], and categorical variables are summarized as frequencies and percentages. Spearman’s rank correlation coefficient was used to assess the relationship between age and anatomical rupture location. Associations between categorical variables, including hypertension and the severity of medial degeneration, were evaluated using the chi-square test. All statistical tests were two-sided, and a p-value of <0.05 was considered statistically significant. Given the retrospective forensic autopsy design and the incomplete documentation of premortem clinical variables inherent to postmortem datasets, statistical analyses were deliberately limited to descriptive statistics and univariable association testing. The study was not designed to identify independent predictors or to perform causal or multivariable modeling; therefore, all statistical findings are interpreted within a descriptive and pathological framework.

Results

Between 2013 and 2023, 5,277 autopsies were conducted, of which 1,381 (26.2%) were attributed to cardiovascular disease. Among them, 93 cases (6.7%) were classified as fatal AAWF. Based on anatomical and histological evaluations, the cohort included 52 cases of rupture without dissection (55.9%), 28 cases of dissection with rupture (30.1%), and 13 cases of dissection without rupture (14.0%). The median age at death was 58 years (IQR: 49-67; range: 19-91 years), with 77.4% (n=72) of decedents older than 46 years. A marked male predominance was observed (male/female ratio: 64/29). Documented comorbidities included hypertension in 43.0% (n=40), atherosclerosis in 23.7% (n=22), and diabetes mellitus in 19.3% (n=18) of cases. A history of tobacco or alcohol use was infrequently reported (4.3%, n=4).

Age-stratified analysis revealed that younger decedents aged 19-45 years (n=21) exhibited a lower prevalence of hypertension (23.8%) and atherosclerosis (9.5%) compared with the overall cohort. Notably, despite the lower burden of traditional cardiovascular risk factors, 42.9% of younger cases met ≥3 SCVP medial degeneration criteria. The distribution of rupture-only, dissection with rupture, and dissection without rupture cases did not differ significantly between age groups (c² test, p=0.93) (Table 1).

Table 1. Comparison of overall cohort and younger decedents (19-45 years).

Parameter	Overall cohort (n=93)	Young subgroup (19-45 years) (n=21)
Age, years (median, IQR)	58 (49-67)	33 (26-41)
Male sex, n (%)	64 (68.8%)	15 (71.4%)
Hypertension, n (%)	40 (43.0%)	5 (23.8%)
Atherosclerosis, n (%)	22 (23.7%)	2 (9.5%)
Diabetes mellitus, n (%)	18 (19.3%)	3 (14.3%)
≥3 SCVP medial degeneration criteria*, n (%)	34 (43.6%)	9 (42.9%)
Rupture only, n (%)	52 (55.9%)	11 (52.4%)
Dissection with rupture, n (%)	28 (30.1%)	7 (33.3%)
Dissection without rupture, n (%)	13 (14.0%)	3 (14.3%)
Cocaine/cannabis detected, n (%)	2 (2.2%)	2 (9.5%)

*: SCVP criteria assessed in histologically evaluable cases (n=78); phenotype distribution between age groups: c² p=0.93; IQR: Interquartile range; SCVP: Society for Cardiovascular Pathology.

Spearman correlation analysis revealed no significant association between age and anatomical event location (r=0.12, p=0.28).

The anatomical distribution of events revealed that the ascending aorta was the most frequently affected segment (=58, 62.4%), followed by the descending aorta (n=5, 5.4%) and thoracoabdominal aorta (n=25, 26.9%). In five cases (5.4%), the precise location of the rupture could not be determined because of extensive hemorrhagic disruption (Table 2).

Table 2. Anatomical distribution of AAWF events.

Rupture location	n	%
Ascending aorta	58	62.4%
Descending aorta	5	5.4%
Thoracoabdominal aorta	25	26.9%
Unspecified due to tissue destruction	5	5.4%
Total	93	100%

AAWF: Acute aortic wall failure.

Macroscopic examination frequently revealed hemopericardium with dense clotted blood, suggesting cardiac tamponade. In a subset of cases, linear or irregular full-thickness wall ruptures traversing the tunica media and adventitia were identified. In others, intramedial separation or laminar dissection without an overt intimal tear was observed. Prominent atherosclerotic changes were observed in several specimens, often coexisting with structural medial disorganization. Representative examples of the observed macroscopic and histopathological alterations are shown in Figures 1, 2, 3.

Figure 1.

Histological section of the ascending aorta demonstrating medial separation accompanied by marked elastic fiber fragmentation and MEMA. These findings fulfill key SCVP criteria for advanced medial degeneration and illustrate the structural vulnerability underlying fatal AAWF.

MEMA: Mucoid extracellular matrix accumulation; SCVP: Society for Cardiovascular Pathology; AAWF: Acute aortic wall failure.

Figure 2.

Macroscopic image of the ascending aorta showing intramedial separation of the aortic wall layers with irregular intimal surface and underlying medial disorganization. These gross pathological features correspond to chronic degenerative changes of the aortic wall and provide macroscopic correlates to the histopathological findings defined by SCVP criteria.

SCVP: Society for Cardiovascular Pathology.

Figure 3.

Gross autopsy photograph of the ascending aorta demonstrating acute separation of medial layers consistent with aortic dissection. This image illustrates the spectrum of AAWF and supports the comparative pathological framework used to contextualize rupture and dissection phenotypes.

AAWF: Acute aortic wall failure.

Quantitative gross measurements were available for a subset of cases. Owing to the non-normal distribution of most continuous variables in this forensic autopsy cohort, quantitative data are presented as medians with IQRs rather than mean values. The median ascending aortic diameter was 4.2 cm (IQR: 3.8-4.6; range: 3.2-5.8 cm). Although advanced aneurysmal dilatation was not universally observed, mild or borderline ascending aortic ectasia (diameter >4.0 cm) was present in nearly half of the measured cases.

Based on established upper physiological reference values, an ascending aortic diameter >4.0 cm and a descending aortic diameter 3.5 cm were considered abnormal. Accordingly, 48.3% of the ascending aortic measurements and 26.7% of the descending aortic measurements exceeded these thresholds (Table 3). In all cases with available data, the median hemopericardium volume exceeded 300 mL, consistent with fatal cardiac tamponade. Intimal tears and intramural hematomas were identified in a substantial proportion of dissection-related cases. Measurement of the aortic valve circumference was not routinely performed but was documented in a limited subset of well-preserved specimens.

Table 3. Gross morphological findings of the aorta.

Parameter	Mean ± SD (range)	Data available (n)	% with abnormal finding
Ascending aortic diameter (cm)	4.2±0.6 (3.2-5.8)	58	28/58 (48.3%) >4.0 cm
Descending aortic diameter (cm)	3.1±0.5 (2.4-4.6)	30	8/30 (26.7%) >3.5 cm
Aortic valve annulus circumference (cm)	7.8±0.9 (6.5-9.2)	21	-
Hemopericardium volume (mL)	580±140 (300-900)	62	62/62 (100%) >300 mL
Linear full-thickness wall disruption	-	51	39/51 (76.4%)
Intimal tear	-	35	24/35 (68.6%)
Intramural hematoma	-	28	15/28 (53.6%)

SD: Standard deviation.

Semiquantitative grading of the eight SCVP-defined features of medial degeneration was performed in all histologically evaluable cases (n=78). MEMA was the most prevalent feature, observed at varying degrees in 51 cases (65.4%), with 14 (17.9%) exhibiting severe accumulation. Among these, 38 cases demonstrated intralamellar MEMA, characterized by mucoid accumulation confined between elastic lamellae, while 13 showed the translamellar form, where the extracellular matrix disrupted the integrity of multiple adjacent lamellar units. The latter is considered a marker of more advanced medial degeneration, indicating increased biomechanical vulnerability of the aortic wall. Elastic fiber fragmentation and thinning were identified in 47 (60.3%) and 44 (56.4%) patients, respectively, with moderate-to-severe changes in 21 patients. SMC loss was noted in 43 (55.1%) patients, with severe depletion in 9 patients. Laminar medial collapse was less frequently observed (35 cases, 44.9%) and predominantly mild in severity. Medial fibrosis, cystic spaces, and inflammatory infiltration were present in 20-25% of cases, typically in milder forms. These findings demonstrate the spectrum and intensity of medial degeneration across fatal aortic wall failure phenotypes (Table 4).

Table 4. Semiquantitative histopathological grading of medial degeneration features.

Histopathological feature (SCVP criteria)	Absent	Mild	Moderate	Severe	MEMA type
MEMA	27	18	19	14	Intralamellar: 38
					Translamellar: 13
Elastic fiber fragmentation	31	23	16	8	-
Elastic fiber thinning	34	24	15	5	-
SMC loss	35	20	14	9	-
Laminar medial collapse	50	15	8	5	-
Medial fibrosis	58	12	6	2	-
Cystic spaces	62	9	5	2	-
Inflammatory infiltration	63	8	5	2	-

SCVP: Society for Cardiovascular Pathology; SMC: Smooth muscle cell; MEMA: Mucoid extracellular matrix accumulation.

Among individuals with documented hypertension, advanced medial degeneration was observed more frequently than in non-hypertensive cases. Specifically, 71.4% (n=20) of hypertensive decedents demonstrated moderate-to-severe alterations in at least two major SCVP-defined criteria, most commonly mucoid extracellular matrix accumulation, elastic fiber fragmentation, and SMC depletion (p=0.002, chi-square).

Cardiac examination further revealed that 80.5% of the decedents had increased heart weight, consistent with pathological cardiac hypertrophy commonly associated with chronic hemodynamic load. These findings indicate a frequent pathological coexistence identified at autopsy. However, in the absence of multivariable analysis and given the limitations of retrospective forensic data, these associations should not be interpreted as evidence of an independent or causal relationship.

Toxicological screening revealed the absence of substances in 39.8% (n=37) of cases. Prescription medications, including antihypertensives and anticoagulants, were detected in 43.0% (n=40) of the cases. Resuscitation-related agents, such as epinephrine and vasopressors, were identified in 11.8% (n=11) of cases; these were interpreted as postmortem pharmacological artifacts rather than indicators of pre-existing drug use. Detection was more common in individuals who died in the hospital or during attempted resuscitation and were thus excluded from the toxicological interpretation of etiological relevance. Ethanol was detected in 3.2% (n=3) of cases, and cannabis or cocaine was found in 2.2% (n=2), predominantly among younger individuals aged 19-35 years. These substances are not considered causative but are interpreted as potential acute triggers in predisposed individuals rather than as primary etiological factors. Ketamine was identified in a single case (1.1%) without a clear clinical correlation.

The findings highlight that medial degeneration, particularly in the ascending aorta, frequently coexists with hypertensive cardiac remodeling in cases of fatal AAWF. The histological criteria based on the SCVP offer reproducible and clinically significant insights into the structural vulnerabilities underlying fatal vascular events.

Discussion

Fatal AAWF represents a rare yet life-threatening clinical and forensic condition, frequently leading to sudden death prior to the possibility of medical intervention. This autopsy-based study, encompassing 93 fatal AAWF cases over a ten-year period, offers substantial insights into the demographic, morphological, histopathological, and cardiotoxicological characteristics of this condition, with a particular focus on structural aortic degeneration and associated cardiovascular comorbidities. From a forensic perspective, the primary macroscopic finding, hemopericardium with dense clotted blood, was indicative of cardiac tamponade secondary to rupture. This supports the assertion that many AAWF cases are immediately lethal, particularly when the ascending aorta is involved. Clinical series of ruptured aortic aneurysms have consistently demonstrated that mortality is highest in the early period following rupture, with most deaths occurring before or shortly after hospital admission, even in settings where advanced surgical interventions are available.^[10] The low percentage of individuals who reached a healthcare facility prior to death (18.3%) highlights the acute nature of events and underscores the need for improved pre-hospital recognition. Although emergency surgical repair is potentially life-saving, it remains inaccessible to many individuals, particularly in rural and underserved regions.

Unlike prior studies that often use the terms rupture and dissection interchangeably, we attempted to separate these entities based on their gross and microscopic features. This approach improves diagnostic specificity and reflects the true diversity of aortic catastrophes encountered in forensic practices. The SCVP criteria for medial degeneration provide an objective framework for evaluating the aortic wall fragility.

Consistent with prior large-scale investigations, including the International Registry of Acute Aortic Dissection, our findings demonstrate a significant male predominance (68.8%) and a median age of 58 years, with more than three-quarters of cases occurring in individuals older than 46 years.^[11] This demographic pattern corroborates the established understanding that AAWF disproportionately affects older men with chronic vascular comorbidities. This male-specific vulnerability may be attributed to the higher incidence of systemic hypertension, smoking, and connective tissue disorders in this demographic group.^[12]

The ascending aorta was the most frequently affected site (62.4%), likely due to its exposure to the peak systolic pressure, dynamic wall stress, and complex hemodynamic shear forces. Histologically, this segment contains a dense network of elastic lamellae and a relatively thick medial layer that accommodates these forces. However, this unique biomechanical environment may paradoxically predispose the vessel wall to fatigue and degeneration over time, particularly in patients with systemic hypertension. Quantitative measurements further supported structural vulnerability in this region. Although advanced aneurysmal dilatation was not universally present, the median ascending aortic diameter was 4.2 cm (IQR: 3.8-4.6), and nearly half of the measured cases exceeded 4.0 cm, consistent with mild or borderline ascending aortic ectasia rather than normal dimensions. These findings suggest that spontaneous aortic wall failure may occur in the context of early structural enlargement, prior to the development of overt aneurysmal dilatation.^{[13, 14]}

A significant strength of this study is its histopathological assessment, which utilized updated SCVP criteria. Among the cases evaluated, the most common features observed were MEMA (65.4%), elastic fiber fragmentation (60.3%), and SMC depletion (55.1%). Notably, nearly half (43.6%) of the cases satisfied three or more SCVP criteria, suggesting advanced and multifactorial medial degeneration. These findings are consistent with those of Guía-Pérez et al.,^[15] who documented that medial degeneration is present in 60-70% of fatal thoracic aortic rupture cases. Unlike our study, which utilized SCVP-defined criteria across a decade-long dataset, their analysis did not stratify cases by age or associated comorbidities, limiting its applicability to broader forensic contexts.^[15] The SCVP criteria provide a reproducible, evidence-based method for identifying high-risk aortas during autopsy, thereby enhancing diagnostic accuracy in cases of unexplained sudden death.^[5] Representative macroscopic and histopathological examples of these degenerative changes are illustrated in Figures 1, 2, 3, demonstrating the coexistence of elastic fiber disruption, medial disorganization, and full-thickness wall failure across fatal phenotypes.

In forensic autopsy-based studies, documentation of chronic medical conditions such as hypertension may be incomplete; therefore, causal interpretations must be made with caution. In the present study, hypertension was significantly associated with the severity of medial degeneration. Among hypertensive individuals who underwent histological evaluation, 71.4% exhibited at least two major SCVP features (p=0.002). Chronic hypertension is known to increase aortic wall stress and may contribute to progressive structural weakening through mechanisms including enhanced collagen turnover, elastolysis, and SMC apoptosis.^[16] These processes promote medial degeneration characterized by mucoid extracellular matrix accumulation, thereby increasing susceptibility to rupture even in the absence of overt aneurysmal dilatation.^{[5, 14]} Accordingly, hypertension in this study is interpreted as a frequent accompanying pathological condition rather than an independent determinant of fatal AAWF.

The relatively low prevalence of atherosclerosis (23.7%) and diabetes mellitus (19.3%) suggests that AAWF is more closely associated with structural medial weakness than with luminal narrowing or plaque burden. In a clinicopathological comparison of aortic dissection and penetrating atherosclerotic ulcer, entrance tears in dissection were shown to arise predominantly in non-atherosclerotic intima and media, whereas ulcer-related lesions were closely linked to advanced and complicated atherosclerotic plaques.^[17]

These observations support the concept that structural medial degeneration, rather than advanced atherosclerosis, represents the dominant pathological substrate in many fatal ascending aortic wall failure events. This interpretation is further reinforced by recent molecular studies highlighting the roles of SMC loss, extracellular matrix remodeling, and dysregulated transforming growth factor (TGF)-b signaling in promoting medial fragility and susceptibility to rupture.^[18]

A subset of cases, particularly among younger individuals aged 19-45 years, demonstrated medial degeneration despite a lower prevalence of hypertension and atherosclerosis. As shown in Table 1, a substantial proportion of younger decedents met ≥3 SCVP medial degeneration criteria, suggesting that structural aortic vulnerability may develop independently of traditional cardiovascular risk factors in this age group.

In the absence of molecular autopsy or genetic testing, these findings should be interpreted as hypothesis-generating rather than confirmatory. Nevertheless, they raise the possibility of underlying inherited connective tissue disorders contributing to aortic wall fragility. Postmortem genetic analysis may provide valuable diagnostic insights in such cases, as conditions including Marfan syndrome, Loeys-Dietz syndrome, and vascular Ehlers-Danlos syndrome have been linked to pathogenic alterations in fibrillin architecture and TGF-b signaling pathways.^{[19, 20]}

In our cohort, cardiac examination revealed markedly increased heart weights, with 80.5% of the decedents demonstrating values above expected physiological reference ranges. Given the non-normal distribution of heart weight measurements, values are presented descriptively; the median heart weight was 512 g (IQR: 435-590 g). These measurements substantially exceed commonly accepted physiological reference ranges (typically <350 g in men and <300 g in women), consistent with pathological cardiac hypertrophy.

Increased heart weight may reflect chronic hemodynamic overload, even in the absence of documented hypertension in forensic autopsy records. This observation is in line with data from the Framingham Heart Study, which demonstrated an association between LVH and increased cardiovascular mortality.^[21] In the present study, elevated heart weight is interpreted as a frequent pathological accompaniment in fatal AAWF rather than as a diagnostic or independent predictive marker.

CAD was identified in 63.4% of cases. Although CAD is not a direct etiological factor for AAWF, it represents a shared vascular pathology associated with hypertension, endothelial dysfunction, and systemic inflammation. The coexistence of CAD and LVH likely compounds myocardial stress, impairs perfusion, and potentially contributes to collapse during acute aortic events.^[22]

Although substances such as ethanol, cannabis, ketamine, and vasopressors have been detected in a minority of cases, the current literature does not support a direct causal role for these agents in AAWF. Vasopressor detection is often linked to attempted resuscitation and interpreted as a postmortem pharmacological artifact. Therefore, toxicological findings were evaluated contextually and were not considered etiologically contributory.

Although substances such as cocaine and cannabis were detected in only a small proportion of cases, all positive findings occurred among younger decedents. These substances were not interpreted as primary etiological factors for fatal AAWF. However, stimulant agents such as cocaine are well known to provoke acute hypertension, tachycardia, and intense vasoconstriction via sympathetic nervous system activation, leading to abrupt increases in aortic wall stress. In individuals with pre-existing structural vulnerability of the aortic media, such acute hemodynamic surges may plausibly act as precipitating triggers for rupture or dissection, as previously reported in cocaine-associated acute aortic syndromes.^{[23, 24]} Accordingly, these findings are best interpreted as supportive of a potential trigger effect rather than as evidence of direct causation.

Cases of dissection without rupture were included as part of the overall pathological spectrum but did not influence interpretations specific to the rupture phenotype. This subclassification approach facilitates clearer forensic interpretation and reflects the pathological continuum of AAWF events encountered in autopsy practice.

Several limitations should be acknowledged. First, this was a retrospective, autopsy-based study, and premortem clinical information—particularly documentation of chronic conditions such as hypertension—was incomplete; therefore, observed associations should be interpreted as descriptive rather than causal. Second, histological assessment was performed using SCVP criteria by two experienced pathologists; however, formal interobserver agreement statistics were not calculated and complete blinding to macroscopic findings was not feasible in routine autopsy practice. Third, aortic diameter measurements were not indexed to sex or body surface area, and absolute cutoff values should therefore be interpreted cautiously in the postmortem setting. Despite these limitations, the study provides a structured and standardized pathological characterization of fatal AAWF and supports the utility of SCVP-based histopathological assessment in forensic autopsy practice.

Fatal AAWF is a rare but lethal vascular condition, most commonly occurring in the setting of advanced structural medial degeneration and often without preceding clinical warning. This autopsy-based study demonstrates that fatal AAWF is consistently associated with structural medial degeneration identifiable by standardized SCVP histopathological criteria, frequently coexisting with hypertensive cardiac remodeling. Rather than proposing novel etiological factors, this work provides a structured pathological framework for interpreting fatal aortic wall failure in forensic practice.

Our findings underscore the importance of effective hypertension control, increased prehospital awareness of acute aortic events, and the potential value of molecular autopsy—particularly in younger, non-hypertensive decedents in whom inherited structural vulnerability of the aortic wall cannot be excluded.

Considering dissection without rupture as part of the pathological spectrum provides a more comprehensive forensic framework for interpreting fatal AAWF and may inform future research.

Ethics

Ethics Committee Approval: The study protocol was approved by the Committee of Education and Scientific Research, Council of Forensic Medicine (approval number: 21589509/2024/1414, date: 03.12.2024).

Informed Consent: All data were anonymized to ensure that no identifiable personal information was collected.