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Which Medicine Can Cause Heart Attack and Is Not Discovered in Autopsy

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Non-diagnostic autopsy findings in sudden unexplained death victims

  • Alex Hørby Christensenone,2,
  • Jacob Tfelt-Hansenone,three,
  • Henning Bundgaardane &
  • Bo Gregers Winkel ORCID: orcid.org/0000-0002-3063-4712 1

BMC Cardiovascular Disorders volume 20, Article number:58 (2020) Cite this article

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Abstract

Background

Several inherited cardiac diseases may lead to sudden cardiac expiry (SCD) a devastating event in the families. It is crucial to establish a post mortem diagnosis to facilitate relevant work-up and treatment of family members. Sudden unexplained decease (SUD) victims constitute roughly i 3rd of all SCD cases in Denmark.

Methods

This was a single center, retrospective study investigating SUD cases. Victims who died unexplained due to suspected or confirmed cardiac affliction were consecutively referred to a tertiary line referral heart established in 2005. All autopsy reports were investigated. Victims were divided into ii groups: non-diagnostic cardiac findings and normal cardiac findings. None of the included victims had findings consequent with a diagnosis based on existing criteria.

Results

In total, 99 SUD cases were referred. The mean age of the victims was 37 years (range 0–62 years, 75% males). A total of 14 (14%) victims had a cardiovascular diagnosis pre-mortem. Thirty-seven cases had normal cardiac findings and non-diagnostic cardiac findings were found in 62 cases (63%). The v most mutual findings included ventricular hypertrophy and/or enlarged eye (north = 35, 35%), coronary atheromatosis (n = 31, 31%), myocardial fibrosis (northward = xix, 19%), dilated chambers (n = 7, 7%) and myocardial inflammation (n = 5, v%).

Conclusion

One 3rd of SUD victims had normal cardiac findings and non-diagnostic cardiac findings were seen in almost ii thirds of the SUD victims. These non-diagnostic findings may be precursors or early markers for underlying structural cardiac disorders or may exist innocent bystanders in some cases. Further studies and improved post-mortem test methods are needed for optimization of diagnostics in SUD.

Peer Review reports

Background

Sudden cardiac death (SCD) leads to tragedies in families with huge social and psychological consequences and is an important contributor to years of life lost among the young. Information technology is crucial to establish a postal service mortem diagnosis to facilitate relevant treatment of family members and avert further deaths as inherited cardiac diseases play an important role in SCD of the young.

SCD in the immature is attributed to a variety of causes of which more a third is due to ischemic eye disease [1]. Other reasons include cardiomyopathies (hypertrophic, dilated and arrhythmogenic cardiomyopathy), myocarditis, aortic disease, valvular heart disease, and built heart defects. In cases where autopsies take not reported structural cardiac abnormalities, expiry may exist due to an underlying chief arrhythmogenic disease such as long or brusk QT syndrome (LQTS/SQTS), Brugada Syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT) [2, 3]. Establishing a post mortem diagnosis remains challenging despite standardized autopsy guidelines [4] and review of known medical conditions. In a nationwide setting, up to 31% of SCD victims below age fifty years remain undiagnosed after autopsy [1]. However, even though the dissection does not provide a cause of death, unspecific cardiac findings with questionable causality to the occurred death are frequently reported. Very few systematic presentations of these autopsy findings have been reported before [five].

The purpose of this study was to systematically present non-diagnostic autopsy findings in sudden unexplained death (SUD) victims.

Methods

Study design and population

This written report was a single center, retrospective report investigating SUD cases. Cases with patients who died all of a sudden, unexpected and unexplained due to suspected or confirmed cardiac disease were consecutively referred to our third line referral centre, Rigshospitalet, Copenhagen University Hospital, Denmark for evaluation. The establishment covers the entire Zealand region of Kingdom of denmark (total population 2.66 factory). For the present analysis, we included all referred cases that had not received a conclusive mail mortem diagnosis later conscientious review of all available data, including autopsy reports and prior medical records. Victims for whom toxicology results indicated a likely intoxication every bit the cause of death were also excluded from the analysis. The autopsied victims were classified into two different groups: victims with non-diagnostic cardiac findings and victims with a normal autopsy (no findings).

All medical records and autopsies reports were caused digitally. All individuals in Denmark have a unique civil registration number that can be used to acquire archived data. The electronic records comprise information from multiple sources including data on medical history, received treatments and paraclinical findings, including autopsy reports. The records were meticulously investigated for all relevant data on the autopsied victims.

Autopsies

In Kingdom of denmark, forensic autopsies are requested when the cause of expiry cannot be established by a full exterior examination of the corpse or in relation to police investigations. Coroners from Departments of Forensic Medicine do a complete autopsy of all organs following a standardized protocol. Autopsies are always supervised by some other forensic pathologist. All findings are presented and findings of significance are given in a conclusion. Histopathology is conducted routinely and if deemed relevant toxicology screening is performed as well. Hospital autopsies are conducted in the local hospital'due south pathology department. These can exist requested by a physician with consent from relatives when no forensic autopsy has been ordered.

Definitions

SCD were defined in autopsied cases as the sudden, natural and unexpected death of unknown or cardiac cause. In unwitnessed cases the deceased person had to be seen alive and performance usually no more than 24 h earlier being found dead, and in witnessed cases an acute alter in cardiovascular status had to accept occurred with the time to death being less than one hour [6, 7]. Unexplained SCD cases were categorized as sudden unexplained decease (SUD). In addition, sudden arrhythmic death syndrome (SADS) was a subdivision of SUD requiring a negative toxicology alongside the negative autopsy.

Autopsies were considered normal or bare (no extra-cardiac or cardiac related findings) if all measures were within normal range as defined [8]. Not-diagnostic findings were those that did not fulfill criteria for neither a structural normal heart, nor a specific disease [1, 8].

Microscopic and macroscopic criteria for non-diagnostic cardiac abnormalities were equally follows: Hypertrophic and/or enlarged Centre: Unexplained localized or concentric hypertrophy (> fifteen mm) of the left ventricular wall and/or abnormal eye weight when corrected for body surface area (> 0.5% of full body weight or in a higher place 500 g), not fulfilling criteria for hypertrophic cardiomyopathy (no myocyte disarray). Coronary artery atheromatosis: The presence of coronary artery atherosclerosis being less than 75% of the circumference of the arterial vessel, with no signs of stenosis or acute myocardial infarction. Myocardial fibrosis: Whatever degree of myocardial fibrosis in the left and/or right ventricle without whatever concomitant signs of structural or ischemic heart disease. The location of fibrosis tin be focal (gathered in a region, eg. septum), Diffuse (evenly spread over the entire myocardium) and patchy (being gathered in patches over multiple myocardial regions). Dilated chambers: Dilatation of the left/right ventricle (measured transverse and longitudinal intraventricular size [four]) with or without wall thinning but with no bear witness of significant fibrosis. Congenital heart defects: Presence of congenital defects, including but not express to patent foramen ovale (in victims older than 5 years of historic period) and septal defects, but not considered a likely substrate for ventricular arrhythmias or heart failure-related death. Myocardial inflammation: Depression degree of leukocyte or neutrophilic infiltrations of the myocardium with or without fibrosis. Not considered pathognomic for myocarditis, due to not having whatever presence of necrosis within the examined surface area, thus not fulfilling revised Dallas criteria [nine]. Valvular heart illness: Presence of valvular heart affliction, simply not of a severity to exist the likely cause of decease.

Additionally, not-diagnostic findings unrelated to cardiac abnormalities were divers as follows: Atherosclerosis of the great vessels: Any degree of atherosclerosis described by the coroner in the arterial vessels of the body. Aspiration: The presence of ventricular substance within the airways. Cerebral hemorrhage: The presence of hemorrhage within the cranial cavity not considered equally cause of expiry. Pneumonia: The presence of lymphocyte infiltrations inside the lungs, not considered piffling but likewise not considered as the cause of death.

Statistical analysis

Data is presented equally number (percentage), mean ± standard deviations (SD). Statistical analysis was performed using two sampled means comparisons tests (t-test). Where appropriate linear regressions were performed with Pearson's correlation. P value of less than 5% were considered meaning. Confidence intervals were set at 95%. Data were candy using STATA 13.0 (StataCorp, United states of america).

Results

Study population

In total, 99 SUD cases were identified. The age of the victims was between 0 and 62 years (hateful 34.3 years, SD fourteen.4) and 74 were men (75%). Two victims were nether 1 twelvemonth of age (Table 1). Twenty-nine (29%) of all SUD victims could be classified as SADS every bit they had a negative toxicology screen performed. SADS victims were younger than SUD victims (hateful age 28 years compared to 37 years, p = 0.048).

Table 1 Characteristics of the Sudden Unexplained Death (SUD) population (n = 99)

Total size tabular array

Previous health status

Amid all victims 21 (21%) had a cardiac assessment performed prior to their expiry. All had electrocardiograms taken (due north = 21, 100%), eleven (52%) had echocardiography, five (23%) had cardiac CT or MRI, four (19%) had coronary angiographies, iv (19%) had Holter monitorings, and four (19%) had an practice test performed. 1 (5%) victim was previously cardioverted for atrial fibrillation.

Xiv (14%) had at to the lowest degree one established cardiovascular diagnosis during their lifetime: hypertension (northward = 5, 36%), atrial fibrillation/flutter (n = 4, 29%), dyslipidemia (n = iv, 29%), valvular heart illness (n = three, 21%), second degree AV block (n = 1, 7%), acute myocardial infarction (n = i, vii%), and stroke (n = 1, 7%). In addition, 8 victims (8%) had a psychiatric diagnosis (schizophrenia/bipolar disorder/depression, all treated with QT prolonging drugs).

We observed no divergence in having had a cardiac cess prior to death compared to being in the group with non-diagnostic autopsy findings or having a blank autopsy (p = 0.79). Nor did we observe whatever deviation in victims having had a cardiac related diagnosis prior to expiry and being in the group with non-diagnostic dissection findings or having a blank autopsy (p = 0.60).

Autopsy findings

Non-diagnostic cardiac findings were reported in 62 cases (63%) and normal cardiac findings were institute in the remaining 37 individuals (37%) (Fig. 1). SADS and SUD victims had the same amount of non-diagnostic findings (p = 0.64). Non-diagnostic autopsy findings are presented in Table 2. The iii main findings in the 62 cases with non-diagnostic findings included ventricular hypertrophy and/or enlarged heart (north = 35, 56%), coronary atheromatosis (n = 31, 50%) and myocardial fibrosis (n = 19, 31%). In 10 victims, fibrosis was described being diffuse/spread interstitial. V victims had focal spots of fibrosis (iii of these in the posterior left ventricular wall, one subendocardial fibrosis, one had septal fibrosis) and finally i victim had fibrosis of the conduction system. In three cases specific information regarding fibrosis was non available. The co-presence of fibrosis and hypertrophy/enlarged heart was seen in 12 (nineteen%) victims.

Fig. 1
figure 1

Victims of Unexplained Sudden Cardiac Death. Flowchart with included SUD victims. SUD = Sudden Unexplained Death

Full size image

Table ii Autopsy Findings from 99 Victims of Sudden Unexplained Death (SUD)

Full size table

Cardiac mass was significantly larger for men compared to women after correction for torso surface expanse (BSA); 217 k/mtwo vs 173 g/thousand2, p = 0.0026). We observed a human relationship between age and BSA corrected cardiac mass (r = 0.57, p < 0.001).

Dilated chambers were nowadays in seven (11%) cases with non-diagnostic findings. Iii of these victims had both dilated left and right ventricle with normal microscopic findings. Two victims had dilated left ventricles with microscopic evidence of fatty infiltrations in the right ventricle and one victim had biventricular dilatation and microscopic testify of fatty infiltrations in the right ventricle. Even so, none of these victims fulfilled the criteria for having arrhythmogenic right ventricular cardiomyopathy. The terminal victim had a dilated left ventricle and moderate ventricular hypertrophy.

Minor congenital defects were seen in 5 victims with not-diagnostic findings (viii%) and included 3 victims with patent foramen ovale (anile 18, 28, 42 years), one victim had an atrial septal defect (historic period 17 years), finally in one victim no specific information was available other than it was 'modest' (age 32 years). Myocardial inflammation was seen in v (8%) victims with non-diagnostic findings: one victim with minimal signs of inflammation, one victim with acute inflammatory signs (predominantly neutrophilic cells), ane victim with inflammation and eosinophilia possibly due to hypersensibility, 1 victim with chronic inflammatory cells in the myocardium, and finally no specific information was bachelor on the terminal victim. Valvular centre defects were seen in 3 (five%) victims with non-diagnostic findings and included i victim with dilated mitral and tricuspidal valves with universally dilated chambers. Two victims had moderate degrees of mitral valve calcifications, but no significant stenosis.

Discussion

Non-diagnostic findings were identified in 62 (63%) of SUD cases. The nearly common findings were hypertrophy/enlarged centre in 35 (35%), coronary avenue atherosclerosis in 31 (31%), and myocardial fibrosis in xix (19%). In full 21 (21%) had a cardiovascular evaluation prior to death, with fourteen (14%) having been diagnosed with a cardiovascular disorder, mainly hypertension (northward = five), atrial fibrillation/palpitate (n = 4), and dyslipidemia (northward = 4).

Our findings are in agreement with a recent study of 98 SUD cases [5], in which 60% of the cases were categorized with non-diagnostic findings, mainly related to presence of left ventricular hypertrophy, cardiomegaly, inflammation and fibrosis.

While non diagnostically conclusive information technology is well established that left ventricular hypertrophy increases risk of mortality independently of other factors [10]. In extension to this a conceivable increment in risk of ventricular arrhythmias has been reported in patients with left ventricular hypertrophy [11, 12]. Experiments in animal models have shown left ventricular hypertrophy increases refractoriness and prolongation of action potentials leading to increased vulnerability to arrhythmias [13]. In addition, increased cardiac mass leads to ascent force per unit area on vessels which ultimately reduces perfusion of the myocardium increasing susceptibility to ischemic damage and scarring [13].

As depicted in Tables ii, 19 (19%) of the victims had some caste of cardiac interstitial fibrosis. The degree of fibrosis was not sufficient to reach a diagnostic conclusion, all the same the literature suggests an association between non-specific interstitial fibrosis and ventricular arrhythmias due to reentrant mechanisms [ii]. These reentries can occur due to several reasons, whether it be resulting in ho-hum and fast pathways that tin facilitate a reentry excursion or reentries around a focal scar than can operate as an ectopic point sending out electric impulses to the rest of the middle [14, xv]. Fibrosis may represent cellular degeneration due to hypoxia or spontaneous cellular degeneration due to an underlying genetic cause such as hypertrophic cardiomyopathy (HCM). Several studies have shown the presence of fibrosis in the myocardium and the activation of profibrotic pathways can be an early on predictor for HCM despite the lack of ventricular hypertrophy [16, 17]. While the literature does exclude the possibility that the victims had early manifestations of HCM fiddling testify exists that link these unspecific cardiac alterations to SCD. While the unspecific findings may exist a precursor for affliction, it could also merely be age-related cardiac phenonenoms [18].

One of the hallmarks of hypertrophic cardiomyopathy is the presence of myocardial disarray in conjunction with hypertrophy and fibrosis of the heart [19]. We plant 12 (12%) victims with non-diagnostic fibrosis and/or hypertrophy/enlargement of the heart. None of these victims had histologically verified myocyte disarray, yet it is possible the disarray is focal and patchy non involving the entire myocardium [twenty]. One study based on late gadolinium enhancement cardiac MR imaging concludes that patients with identifiable HCM mutations more frequently had localized focal cardiac fibrosis instead of diffuse cardiac fibrosis [21]. Thus, the selected sites for microscopic investigation may have missed the disarray. On the contrary, a hypertrophic heart could besides bespeak towards hypertension as the primary cause, therefore having picayune to no relevance in the crusade of death. Although not formally quantified the typical description of the fibroses was lengthened, which may indicate that the victims had hypertension and other non-HCM causes [22,23,24]. Sudden death is unlikely to exist the first finding as the result of hypertension, nonetheless it has been seen that hypertension and left ventricular hypertrophy tin can outcome in premature ventricular activity that in rare cases tin can atomic number 82 to fatal arrhythmias [25]. However, nosotros cannot dominion out that the hypertrophic/enlarged heart could also be an innocent bystander non related to the victim'due south decease.

Dilated heart chambers were seen in vii (7%) of the victims. It is possible this finding may represent a variation of dilated cardiomyopathy (DCM). In a Danish nationwide study 3% of the autopsied-explained SCD victims had DCM [i]. The clinical manifestations of DCM are heterogeneous, only near cases nowadays with middle failure symptoms simply the presentation tin be SCD [26]. Mail mortem diagnosis of DCM is performed by observing the gross heart size/weight and dilated ventricles and may be supported by genetic testing. Roughly 30–l% of DCM cases are confirmed via genetics while other causes can be due to autoimmunity, narcotics and viral infections [26]. Viral infections accept been linked to heart failure and DCM [27,28,29,30]. While the machinery still remains uncertain some believe that a combination of stress-induced cellular apoptosis due to loftier viral RNA load and T-prison cell mediated cell decease are important factors in the development of DCM [27]. Depression degrees myocardial inflammation was seen in 5 victims, but the degree of lymphocyte infiltration was deemed unlikely to be the cause of expiry. However, only 1 victim had both dilated chambers and myocardial inflammation. Inflammatory findings are likewise typical findings postal service myocardial infarction and one study described co-occurrence of myocardial infarction and myocarditis [31]. Based on existing knowledge myocardial inflammation can issue in multiple outcomes, nevertheless information technology may also be a non-relevant coincidental finding within these victims.

Xxx-one (31%) of the victims with non-diagnostic findings had some degree of coronary artery atheromatosis. In these cases, it is exceedingly difficult to assess the importance of the atherosclerosis in the coronary arteries since often it could be a coincidental finding. One written report reported that atherosclerosis in the coronary vessels was nowadays in 73% of a group of deceased individuals that died from non-cardiac causes [32]. However, it is as well well known that thrombus autolysis tin can occur spontaneously, and it takes several hours for the myocardial ischemic changes to be microscopically visible. Therefore, we cannot exclude that some victims may have died due to myocardial infarction, only post mortem investigations were without diagnostic findings disclosing rapid thrombus autolysis. Coronary avenue atheromatosis and atherosclerosis of great arteries are oft seen together. Nosotros reported a total rate of 24% atherosclerosis in the major arteries in the victims with non-diagnostic findings. Information technology is well recognized that light degrees of atherosclerosis is seen in healthy individuals progressing every bit a person ages [33].

In total 37 (37%) of all victims had no cardiac findings on autopsy. In cases with lack of structural cardiac abnormalities deaths may be attributed to inherited arrhythmogenic disorders (i.eastward. BrS, LQTS, SQTS, CPVT) [34, 35]. These channelopathies are diagnosed past ECG, practice ECG, and ECG-induced drug-challenges making a post mortem diagnosis incommunicable. The autopsy usually presents without structural cardiac findings. Although purely speculative, subtle findings in otherwise dissection-negative cases of SCD might besides exist due to primary arrhythmogenic disorders. For instance, information technology is well known that variants in the gene SCN5A phenotypically can give rise to both structural cardiac disease (DCM), conduction abnormalities, and principal arrhythmogenic disorders (LQTS and BrS) [36]. In these cases the post mortem diagnosis relies on genetic testing with many genetic variants remaining unclassifiable and variable penetrance/expressivity hampering cosegregation analyses in families [37,38,39,40,41]. At our institution nosotros do not routinely perform genetic testing in unexplained SCD cases. While a molecular autopsy could exist used in autopsied cases which fulfills diagnostic criteria for sure cardiomyopathies (eastward.chiliad. HCM, DCM, and ARVC). Variants of unknown significance (VUS) also as the lack of genotype-phenotype correlation tin brand interpretation difficult, peculiarly in unexplained SCD cases. Current guidelines state that targeted post-mortem genetic analysis of potentially disease-causing genes should be considered in all sudden death victims in whom a specific inheritable channelopathy or cardiomyopathy is suspected (class IIa, level of show C) [42].

Limitation

The retrospective nature of the study unfortunately led to unavoidable missing data points. We did not compare the amount of cardiac non-diagnostic autopsy findings in our cohort with a control grouping, this was however done in a recent study were they found far more not-diagnostic findings in the SUD cohort compared to cardiac healthy controls [5]. In relations, it is also a limitation that we did non accept admission to family unit evaluation in this study. Moreover, we take not performed systematic molecular autopsies. Molecular dissection might take resulted in diagnosing some SCD cases. In addition, our middle is a referral center, thus victims are referred to this center for evaluation, this may ultimately result in choice bias. Furthermore, autopsy protocols evolved over time resulting in variations among autopsies.

Conclusion

In a referred cohort of SUD cases, unspecific cardiac findings were seen in 63% of the autopsied with the most common findings including hypertrophy/enlargement of heart, coronary avenue atheromatosis and diffuse fibrosis. These unspecific findings may be precursors or early signs of underlying structural cardiac disorders just could also exist spur findings in patients with inherited arrhythmogenic disorders. In total, 37% of all victims had no cardiac finding on autopsy. These cases could represent underlying inherited arrhythmogenic disorders, every bit has been shown in previous studies.

Availability of data and materials

The datasets used and/or analyzed during the electric current written report are available from the corresponding author on reasonable request.

Abbreviations

ARVC:

Arrhythmogenic right ventricular cardiomyopathy

BrS:

Brugada syndrome

BSA:

Body expanse

CPVT:

Catecholaminergic polymorphic ventricular tachycardia

DCM:

Dilated cardiomyopathy

HCM:

Hypertrophic cardiomyopathy

LQTS:

Long QT syndrome

SADS:

Sudden arrhythmic decease syndrome

SCD:

Sudden cardiac death

SD:

Standard deviations

SQTS:

Curt QT syndrome

SUD:

Sudden unexplained expiry

VUS:

Variants of unknown significance

References

  1. Risgaard B, Winkel BG, Jabbari R, Behr ER, Ingemann-Hansen O, Thomsen JL, et al. Brunt of sudden cardiac death in persons aged 1 to 49 years nationwide study in Denmark. Circ Arrhythmia Electrophysiol. 2014;vii:205–xi.

    Commodity  Google Scholar

  2. Chugh SS, Kelly KL, Titus JL. Sudden cardiac death with apparently Normal eye. Circulation. 2000;102:649–54. https://doi.org/10.1161/01.CIR.102.6.649.

    Article  PubMed  CAS  Google Scholar

  3. Zipes DP, Wellens HJJ. Sudden cardiac death. Circulation. 1998;98:2334–51.

    Article  CAS  Google Scholar

  4. Basso C, Aguilera B, Banner J, Cohle S, d'Amati 1000, de Gouveia RH, et al. Guidelines for dissection investigation of sudden cardiac death: 2022 update from the Association for European Cardiovascular Pathology. Virchows Arch. 2017;471:691–705.

    Commodity  Google Scholar

  5. Raju H, Parsons S, Thompson TN, Morgan N, Zentner D, Trainer AH, et al. Insights into sudden cardiac death: exploring the potential relevance of not-diagnostic autopsy findings. Eur Eye J. 2018;forty:831–viii.

    Article  Google Scholar

  6. Kong MH, Fonarow GC, Peterson ED, Curtis AB, Hernandez AF, Sanders GD, et al. Systematic review of the incidence of sudden cardiac death in the United States. J Am Coll Cardiol. 2011;57:794–801. https://doi.org/10.1016/j.jacc.2010.09.064.

    Article  PubMed  PubMed Central  Google Scholar

  7. Winkel BG, Holst AG, Theilade J, Kristensen IB, Thomsen JL, Ottesen GL, et al. Nationwide study of sudden cardiac expiry in persons aged 1-35 years. Eur Heart J. 2011;32:983–90.

    Article  Google Scholar

  8. Scholz DG, Gastroenterology D, Medicine I, Dalane Due west, Medicine I, Hagen PT. Age-Related Changes in Normal Human Hearts During the Start 10 Decades of Life . Part I ( Growth ): A Quantitative Anatomic Study of 200 Specimens From Subjects From Nascence to 19 Years Old. 1988:126–136.

  9. Aretz HT. Myocarditis: The Dallas Criteria. Hum Pathol. 1987;18:619–24. https://doi.org/10.1016/S0046-8177(87)80363-v.

    Article  CAS  Google Scholar

  10. Ghali JK, Liao Y, Simmons B, Castaner A, Cao 1000, Cooper RS. The prognostic role of left ventricular hypertrophy in patients with or without coronary artery disease. Ann Intern Med. 1992;117:831–6. https://doi.org/10.7326/0003-4819-117-ten-831.

    Commodity  PubMed  CAS  Google Scholar

  11. Levy D, Anderson KM, Brutal DD, Balkus SA, Kannel WB, Castelli WP. Take chances of ventricular arrhythmias in left ventricular hypertrophy: the Framingham middle study. Am J Cardiol. 1987;lx:560–5.

    Commodity  CAS  Google Scholar

  12. Cooper RS, Liao Y. Impact of left ventricular hypertrophy on ventricular arrhythmias in the absenteeism of coronary artery disease. J Am Coll Cardiol. 1991;17:1277–82.

    Commodity  Google Scholar

  13. Benjamin EJ, Levy D. Why is left ventricular hypertrophy so predictive of morbidity and mortality? Am J Med Sci. 1999;317:168–75.

    Article  CAS  Google Scholar

  14. Wit AL, Rosen MR. Pathophysiologic mechanisms of cardiac arrhythmias. Am Centre J 1983;106 4 Pt 2:798–811. http://www.ncbi.nlm.nih.gov/pubmed/6310978. Accessed 31 Jan 2019.

    Article  CAS  Google Scholar

  15. Martin CA, Matthews GDK, Huang CL-H. Sudden cardiac death and inherited channelopathy: the basic electrophysiology of the myocyte and myocardium in ion aqueduct disease. Middle. 2012;98(7):536–43. https://doi.org/10.1136/heartjnl-2011-300953.

    Commodity  PubMed  PubMed Central  Google Scholar

  16. Kim JB, Porreca GJ, Song L, Greenway SC, Gorham JM, Church GM, et al. Polony Multiplex Analysis of Factor Expression (PMAGE) in Mouse Hypertrophic Cardiomyopathy. Scientific discipline (80- ). 2007;316:1481–4. https://doi.org/10.1126/science.1137325.

    Article  CAS  Google Scholar

  17. Ho CY, López B, Coelho-Filho OR, Lakdawala NK, Cirino AL, Jarolim P, et al. Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy. N Engl J Med. 2010;363:552–63. https://doi.org/10.1056/NEJMoa1002659.

    Commodity  PubMed  PubMed Key  CAS  Google Scholar

  18. Biernacka A, Frangogiannis NG. Crumbling and cardiac fibrosis. Aging Dis 2011;2:158–173. http://world wide web.ncbi.nlm.nih.gov/pubmed/21837283. Accessed 1 February 2019.

  19. Prinz C, Farr K, Hering D, Horstkotte D, Faber L. The diagnosis and treatment of hypertrophic cardiomyopathy. Dtsch Arztebl Int. 2011;108:209–xv. https://doi.org/ten.3238/arztebl.2011.0209.

    Article  PubMed  PubMed Fundamental  Google Scholar

  20. Varnava AM. Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and minor vessel disease. Middle. 2000;84:476–82. https://doi.org/10.1136/heart.84.5.476.

    Article  PubMed  PubMed Cardinal  CAS  Google Scholar

  21. Ellims AH, Iles LM, Ling L-H, Chong B, Macciocca I, Slavin GS, et al. A comprehensive evaluation of myocardial fibrosis in hypertrophic cardiomyopathy with cardiac magnetic resonance imaging: linking genotype with fibrotic phenotype. Eur Hear J - Cardiovasc Imaging. 2014;fifteen:1108–xvi. https://doi.org/10.1093/ehjci/jeu077.

    Article  Google Scholar

  22. Marcos RA. Pathologic fibrosis and connective tissue matrix in left ventricular hypertrophy due to chronic arterial hypertension in humans. J Hypertens. 1998;16:1031–41. https://doi.org/ten.1097/00004872-199816070-00018.

    Article  Google Scholar

  23. Wu LM, Wu R, Ou Year, Chen BH, Yao QY, Lu Q, et al. Fibrosis quantification in hypertensive heart affliction with LVH and non-LVH: findings from T1 mapping and dissimilarity-free cardiac diffusion-weighted imaging. Sci Rep. 2017;7:559. https://doi.org/10.1038/s41598-017-00627-5.

    Article  PubMed  PubMed Cardinal  CAS  Google Scholar

  24. Janardhanan R, Adenaw Due north, Jiji R, Brooks J, Epstein FH, Kramer CM, et al. Quantifying myocardial fibrosis in hypertensive left ventricular hypertrophy using T1 mapping. J Cardiovasc Magn Reson. 2012;14(Suppl 1):P172. https://doi.org/x.1002/mrd.1041.

    Article  PubMed Key  Google Scholar

  25. Messerli F. Hypertension and sudden cardiac death. Am J Hypertens. 1999;12:181–8. https://doi.org/x.1016/S0895-7061(99)00106-5.

    Commodity  Google Scholar

  26. Basso C, Calabrese F, Corrado D, Thiene G. Postmortem diagnosis in sudden cardiac death victims: macroscopic, microscopic and molecular findings. Cardiovasc Res. 2001;50:290–300. https://doi.org/10.1016/S0008-6363(01)00261-9.

    Article  CAS  Google Scholar

  27. Buggey J, Elamm CA. Myocarditis and cardiomyopathy. Curr Opin Cardiol. 2018;33:341–half dozen. https://doi.org/x.1097/HCO.0000000000000514.

    Article  PubMed  Google Scholar

  28. Kereiakes DJ, Parmley WW. Myocarditis and cardiomyopathy. Am Heart J. 1984;108:1318–26. https://doi.org/10.1016/0002-8703(84)90760-ix.

    Article  PubMed  CAS  Google Scholar

  29. Andreoletti L, Hober D, Decoene C, Copin MC, Lobert PE, Dewilde A, et al. Detection of enteroviral RNA by polymerase chain reaction in endomyocardial tissue of patients with chronic cardiac diseases. J Med Virol. 1996;48:53–9. https://doi.org/ten.1002/(SICI)1096-9071(199601)48:i<53::Assistance-JMV9>3.0.CO;2-Grand.

    Commodity  PubMed  CAS  Google Scholar

  30. Regional K, Orleans N. Ovid: from myocarditis to Cardiomyopathy: mechanisms of inflammation and cell Decease: learning from the past for the time to come. Circulation 2015;99 1999:ane–17. http://ahajournals.org. Accessed 31 Jan 2019.

  31. Woudstra L, Biesbroek PS, Emmens RW, Heymans S, Juffermans LJ, van Rossum Air conditioning, et al. Lymphocytic myocarditis occurs with myocardial infarction and coincides with increased inflammation, hemorrhage and instability in coronary artery atherosclerotic plaques. Int J Cardiol. 2017;232:53–62. https://doi.org/10.1016/j.ijcard.2017.01.052.

    Article  PubMed  Google Scholar

  32. Vyas P, Gonsai R, Meenakshi C, Nanavati M. Coronary atherosclerosis in noncardiac deaths: an autopsy study. J Midlife Health. 2015;half dozen:five. https://doi.org/10.4103/0976-7800.153596.

    Commodity  PubMed  PubMed Key  CAS  Google Scholar

  33. Roberts JC, Wilkins RH, Moses C. Dissection Studies in Atherosclerosis I. Distribution and Severity of Atherosclerosis in Patients Dying without Morphoogic Evidence of Atherosclerotic Catasrophy. Circulation. 1959;20:511–nine.

    Commodity  Google Scholar

  34. Semsarian C, Ingles J. Molecular autopsy in victims of inherited arrhythmias. J Arrhythm. 2016;32:359–65. https://doi.org/10.1016/j.joa.2015.09.010.

    Article  PubMed  Google Scholar

  35. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, et al. HRS/EHRA/APHRS expert consensus argument on the diagnosis and Management of Patients with inherited chief arrhythmia syndromes. Hear Rhythm. 2013;x:1932–63. https://doi.org/10.1016/j.hrthm.2013.05.014.

    Article  Google Scholar

  36. Tfelt-hansen J, Winkel BG, Grunnet M, Jespersen T, et al. Molecular Perspectives Inherited Cardiac Diseases Caused by Mutations in the Nav1. 5 Sodium Channel. J Cardiovasc Electrophysiol. 2010:107–15.

  37. Garcia-Elias A, Benito B. Ion Channel disorders and sudden cardiac death. Int J Mol Sci. 2018;xix. https://doi.org/ten.3390/ijms19030692.

    Article  CAS  Google Scholar

  38. Fernández-Falgueras A, Sarquella-Brugada G, Brugada J, Brugada R, Campuzano O. Cardiac Channelopathies and Sudden Death: Contempo Clinical and Genetic Advances. Biological science (Basel). 2017;half-dozen. https://doi.org/10.3390/biology6010007.

    Article  CAS  Google Scholar

  39. Lahrouchi Due north, Raju H, Lodder EM, Papatheodorou East, Ware JS, Papadakis M, et al. Utility of post-mortem genetic testing in cases of sudden arrhythmic death syndrome. J Am Coll Cardiol. 2017;69:2134–45.

    Article  Google Scholar

  40. Christiansen SL, Hertz CL, Ferrero-Miliani L, Dahl M, Weeke PE, Lucamp L, et al. Genetic investigation of 100 middle genes in sudden unexplained decease victims in a forensic setting. Eur J Hum Genet. 2016;24:1797–802.

    Article  CAS  Google Scholar

  41. Winkel BG, Larsen MK, Berge KE, Leren TP, Nissen PH, Olesen MS, et al. The prevalence of mutations in KCNQ1, KCNH2, and SCN5A in an unselected national cohort of immature sudden unexplained death cases. J Cardiovasc Electrophysiol. 2012;23:1092–8.

    Commodity  Google Scholar

  42. Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Bloma Northward, Borggrefe 1000, Camm J, et al. ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death the job force for the Direction of Patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Order of Cardiology (ESC) endorsed by: Association for European Paediatric and Built Cardiology (AEPC). Eur Heart J. 2015;36:2793–2867l.

    Commodity  Google Scholar

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Acknowledgements

Not applicative.

Funding

The Danish Heart Foundation has given a grant to BGW.

Author data

Affiliations

  1. Section of Cardiology The Centre Center, Copenhagen University Infirmary Rigshospitalet, Blegdamsvej 9, 2142, 2100, Copenhagen, Denmark

    Puriya Daniel Yazdanfard, Alex Hørby Christensen, Jacob Tfelt-Hansen, Henning Bundgaard & Bo Gregers Winkel

  2. Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen Academy Infirmary, Copenhagen, Denmark

    Alex Hørby Christensen

  3. Section of Forensic Medicine, Faculty of Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Jacob Tfelt-Hansen

Contributions

BGW, HB, AHC and JTH contributed to the conception and design of the work. PDY has collected data and drafted the manuscript. All authors took part in analyzing information, read and approved the concluding manuscript. All authors take responsibility of the data.

Corresponding author

Correspondence to Bo Gregers Winkel.

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Ethics blessing and consent to participate

The study was canonical by the Danish Information Protection Bureau and Danish Patient Condom Authorization (3–3013-2380/one) in accordance with Helsinki Annunciation. Consent to participate: Not applicable as per approval (retrospective study).

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Non applicable.

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The authors declare no competing interests.

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Yazdanfard, P.D., Christensen, A.H., Tfelt-Hansen, J. et al. Not-diagnostic autopsy findings in sudden unexplained death victims. BMC Cardiovasc Disord 20, 58 (2020). https://doi.org/ten.1186/s12872-020-01361-z

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  • DOI : https://doi.org/10.1186/s12872-020-01361-z

Keywords

  • Autopsy
  • Autopsy findings
  • Cardiac illness
  • Non-diagnostic findings
  • Sudden Cardiac Death
  • Sudden Unexplained Death
  • Sudden Arrhythmic Death Syndrome
  • SCD
  • SUD
  • SADS

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