Pathophysiology Of Sudden Cardiac Death Research Articles

Evaluation of the risk factors of hemodialysis procedure-associated cardiac arrhythmias in end stage renal disease Egyptian patients

Background: Hemodialysis patients carry a large burden of cardiovascular disease, accounting for up to 41% of deaths, of which half are ascribed to sudden cardiac death (SCD). The pathophysiology of SCD is thought to result from the combination of a vulnerable myocardium and an acute pro-arrhythmic trigger that leads to a terminal arrhythmia. Approximately two thirds of the cardiac deaths are consistently attributed to arrhythmias. Aim: The study aimed to improve the clinical status of hemodialysis (HD) patients through detection of HD procedure associated cardiac arrhythmias, prevention of its risk factors and related complications. Subjects and Methods: Observational study that included 60 maintenance HD patients to assess the prevalence of electrocardiographic changes before, during, and after HD in patients who are on maintenance HD in the out/inpatient departments of Suez Canal University. Results: The study showed a high prevalence of electrocardiographic changes among the studied sample, representing 78.3%. Receiving HD for more than 5 years, glomerulonephritis (GN) being the primary cause of end stage renal disease (ESRD), intradialytic hypotension (IDH), and high pre-dialysis Na, K, and Po4 were all factors that were statistically significant associated with electrocardiographic changes.

Ryanodine receptor 2 inhibition reduces dispersion of cardiac repolarization, improves contractile function, and prevents sudden arrhythmic death in failing hearts

Sudden cardiac death (SCD) from ventricular tachycardia/fibrillation (VT/VF) is a leading cause of death, but current therapies are limited. Despite extensive research on drugs targeting sarcolemmal ion channels, none have proven sufficiently effective for preventing SCD. Sarcoplasmic ryanodine receptor 2 (RyR2) Ca2+ release channels, the downstream effectors of sarcolemmal ion channels, are underexplored in this context. Recent evidence implicates reactive oxygen species (ROS)-mediated oxidation and hyperactivity of RyR2s in the pathophysiology of SCD. We tested the hypothesis that RyR2 inhibition of failing arrhythmogenic hearts reduces sarcoplasmic Ca2+ leak and repolarization lability, mitigates VT/VF/SCD and improves contractile function. We used a guinea pig model that replicates key clinical aspects of human nonischemic HF, such as a prolonged QT interval, a high prevalence of spontaneous arrhythmic SCD, and profound Ca2+ leak via a hyperactive RyR2. HF animals were randomized to receive dantrolene (DS) or placebo in early or chronic HF. We assessed the incidence of VT/VF and SCD (primary outcome), ECG heart rate and QT variability, echocardiographic left ventricular (LV) structure and function, immunohistochemical LV fibrosis, and sarcoplasmic RyR2 oxidation. DS treatment prevented VT/VF and SCD by decreasing dispersion of repolarization and ventricular arrhythmias. Compared to placebo, DS lowered resting heart rate, preserved chronotropic competency during transient β-adrenergic challenge, and improved heart rate variability and cardiac function. Inhibition of RyR2 hyperactivity with dantrolene mitigates the vicious cycle of sarcoplasmic Ca2+ leak-induced increases in diastolic Ca2+ and ROS-mediated RyR2 oxidation, thereby reducing repolarization lability and protecting against VT/VF/SCD. Moreover, the consequent increase in sarcoplasmic Ca2+ load improves contractile function. These potentially life-saving effects of RyR2 inhibition warrant further investigation, such as clinical studies of repurposing dantrolene as a potential new therapy for heart failure and/or SCD.

Abstract 11634: Fatty Acid Length Dictates Association of Sphingomyelins With Sudden Cardiac Death

Background: Sudden cardiac death (SCD) is a leading cause of mortality worldwide and is precipitated primarily by ventricular tachyarrhythmias related to coronary artery disease. Sphingolipids, composed of ceramides and sphingomyelins, may influence the pathophysiology and risk of SCD through multiple biological activities. Whether the length of the fatty acid conjugated to the sphingolipid species is associated with SCD risk is not known. Methods and Results: Among 4612 Cardiovascular Health Study participants, we identified 215 patients who experienced SCD over a median follow up of 10.2 years. We examined 8 sphingolipids: ceramide and sphingomyelin species containing palmitic acid and species containing, respectively, the very-long-chain saturated fatty acids (VLSFA) arachidic, behenic, and lignoceric acids. In adjusted Cox regression analyses, ceramides and sphingomyelins with palmitic acid were associated with increased SCD risk per standard deviation log difference (ceramide with palmitic acid: hazard ratio 1.34, 95% CI 1.12-1.59; sphingomyelin with palmitic acid: hazard ratio 1.37, 95% CI 1.12-1.67). In contrast, one sphingomyelin with a VLSFA trended towards an association with reduced SCD risk (sphingomyelin with arachidic acid: hazard ratio 0.83, 95% CI 0.71-0.98). Associations were weakened when adjusted for C-reactive protein (CRP), B-type natriuretic peptide, and troponin-T, but did not differ significantly by age, sex, race, body-mass index, or history of coronary heart disease. In comparison, ceramide with palmitic acid was associated with higher risk of nonfatal myocardial infarction, and ceramide with the VLSFA lignoceric acid trended towards lower risk. Conclusions: Our results suggest associations between sphingolipid species and SCD, differing by the length of the acylated saturated fatty acid. Palmitic acid-containing sphingolipids were strongly associated with increased SCD risk, whereas VLSFA-containing sphingomyelins trended toward reduced SCD risk. The study indicates that plasma sphingolipids may influence the risk of SCD, independent of traditional cardiovascular risk factors. Our findings may provide further insight into the pathogenesis of SCD and enhance risk stratification tools.

Avalanches in cardiology.

Sudden cardiac death (SCD) accounts for 15%–60% of mortality in patients with heart disease. Generally, this has been attributed to ventricular tachyarrhythmia. However, ventricular tachyarrhythmia has been documented or strongly suspected on clinical grounds in a relatively small proportion of SCD patients (8%–50%). Attempted prophylaxis of SCD by implantation of cardioverter-defibrillator is associated with variable success in different subsets of high-risk cardiac patients (30%–70%). A significant number of SCD, therefore, appear to be due to catastrophic circulatory failure. Multiple interdependent compensatory mechanisms help to maintain circulation in advanced cardiac disease. Rapid, unexpected, and massive breakdown of the compensated state can be precipitated by small and often imperceptible triggers. The initial critical but stable state followed by rapid circulatory failure and death has been considered to be analogous to snow avalanches. It is typically described in patients with left ventricular (LV) dysfunction (ischemic or nonischemic). It is now recognized that SCD can also happen in conditions where the right ventricle (RV) takes the brunt of the hemodynamic load. Advanced pulmonary arterial hypertension and operated patients of tetralogy of Fallot with pulmonary regurgitation are of particular interest to pediatric cardiologists. A large amount of data is available on LV changes and mechanics, while relatively little information is available on the mechanisms of RV adaptation to increased load and RV failure. Whether the triggers and the decompensatory processes are similar for the two ventricles is a moot point. This article highlights the currently available knowledge on the pathophysiology of SCD in RV overload states, with special reference to RV adaptive and decompensatory mechanisms, and therapeutic measures that can potentially interrupt the vicious downward course (cardiac avalanches).

Current Management of Anomalous Aortic Origin of a Coronary Artery: A Pan-Canadian Survey.

Background:Anomalous aortic origin of a coronary artery (AAOCA) is a significant cause of sudden cardiac death (SCD) in children and adolescents. The natural history of AAOCA and the pathophysiology of AAOCA-related SCD are poorly understood. Therefore, the evaluation and management of AAOCA remain controversial. This survey-based study aims to report the current AAOCA management tendencies in Canada.Methods:We built a 23-question survey on AAOCA. Questions pertained to patient presentation, investigations, morphology of the anomaly, management, and follow-up. We sent the survey to all the Canadian congenital cardiac surgeons, pediatric cardiologists, and adult congenital cardiologists. Data were anonymized and analysis was performed using descriptive statistics.Results:According to our survey participants (N = 47), patient age (94%) and amount of physical activity (60%) are the most influential factors when deciding whether to offer surgical correction. Aborted SCD, exercise-induced syncope, typical chest pain, and left jaw or arm pain are the most important clinical presentations indicating surgery. The most commonly used preoperative investigations are rest echocardiography (75%), electrocardiogram (68%), and exercise stress test (62%). Most respondents favor the unroofing procedure (78%) for surgical correction. For nonsurgical candidates, most physicians choose competitive exercise restriction (64%).Conclusion:We found a divergence between current practices and expert consensus guidelines regarding the treatment of asymptomatic left AAOCA with high-risk features. Our survey also revealed a lack of consensus among clinicians regarding the management of asymptomatic patients, very young patients, and those with right-sided AAOCA. Evidence-based criteria derived from sufficiently powered studies remain to be established to standardize AAOCA treatment.

Gaps in Evidence for Risk Stratification for Sudden Cardiac Death in Hypertrophic Cardiomyopathy.

Gaps in Evidence for Risk Stratification for Sudden Cardiac Death in Hypertrophic Cardiomyopathy.

Abnormalities in sodium current and calcium homoeostasis as drivers of arrhythmogenesis in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common inherited monogenic disease with a prevalence of 1/500 in the general population, representing an important cause of arrhythmic sudden cardiac death (SCD), heart failure, and atrial fibrillation in the young. HCM is a global condition, diagnosed in >50 countries and in all continents. HCM affects people of both sexes and various ethnic and racial origins, with similar clinical course and phenotypic expression. The most unpredictable and devastating consequence of HCM is represented by arrhythmic SCD, most commonly caused by sustained ventricular tachycardia or ventricular fibrillation. Indeed, HCM represents one of the main causes of arrhythmic SCD in the young, with a marked preference for children and adults <30 years. SCD is most prevalent in patients with paediatric onset of HCM but may occur at any age. However, risk is substantially lower after 60 years, suggesting that the potential for ventricular tachyarrhythmias is mitigated by ageing. SCD had been linked originally to sports and vigorous activity in HCM patients. However, it is increasingly clear that the majority of events occurs at rest or during routine daily occupations, suggesting that triggers are far from consistent. In general, the pathophysiology of SCD in HCM remains unresolved. While the pathologic and physiologic substrates abound and have been described in detail, specific factors precipitating ventricular tachyarrhythmias are still unknown. SCD is a rare phenomenon in HCM cohorts (<1%/year) and attempts to identify patients at risk, while generating clinically useful algorithms for primary prevention, remain very inaccurate on an individual basis. One of the reasons for our limited understanding of these phenomena is that limited translational research exists in the field, while most efforts have focused on clinical markers of risk derived from pathology, instrumental patient evaluation, and imaging. Specifically, few studies conducted in animal models and human samples have focused on targeting the cellular mechanisms of arrhythmogenesis in HCM, despite potential implications for therapeutic innovation and SCD prevention. These studies found that altered intracellular Ca2+ homoeostasis and increased late Na+ current, leading to an increased likelihood of early and delayed after-depolarizations, contribute to generate arrhythmic events in diseased cardiomyocytes. As an array of novel experimental opportunities have emerged to investigate these mechanisms, including novel 'disease-in-the-dish' cellular models with patient-specific induced pluripotent stem cell-derived cardiomyocytes, important gaps in knowledge remain. Accordingly, the aim of the present review is to provide a contemporary reappraisal of the cellular basis of SCD-predisposing arrhythmias in patients with HCM and discuss the implications for risk stratification and management.

Galactin-3 and soluble ST2 as complementary tools to cardiac MRI for sudden cardiac death risk stratification in heart failure: A review.

Heart failure (HF) is recognized as one of the leading causes of morbidity and mortality worldwide. Every year about 500,000 new cases of HF are diagnosed in the United States. The predominant etiology of death in HF patients include sudden cardiac death (SCD) and pump failure. Prediction of mode of death may help in devising management decisions. In patients with HF, the presence of myocardial fibrosis has been a known risk factor for SCD and thus it could be used as a criterion in risk stratification for SCD. However, the underlying pathophysiology of SCD is uncertain and controversial, which makes it necessary to develop newer tools to enhance SCD risk stratification. The newer tools should be innovative enough either to complement or to replace the currently available tools. In this scoping review, we highlighted the utilization of novel biomarkers galectin-3 (gal-3) and soluble ST2 (sST2) and discussed that how they might complement currently available tools such as, cardiac MRI (CMR) for SCD risk stratification in HF patients.

CURRENT UNDERSTANDING AND MANAGEMENT OF ANOMALOUS AORTIC ORIGIN OF CORONARY ARTERIES: A PANCANADIAN SURVEY

Anomalous aortic origin of coronary arteries (AAOCA) is a significant cause of sudden cardiac death (SCD) in children and adolescents. This is a rare congenital anomaly in which a coronary artery does not originate from its respective sinus of Valsalva, and follows an abnormal course. Because most AAOCA patients are likely asymptomatic, the prevalence of AAOCA remains unknown. When symptomatic, patients mostly present with angina, syncope or dyspnea on exertion. The natural history of AAOCA and the pathophysiology of AAOCA-related SCD are poorly understood, thus AAOCA evaluation and management remain controversial.

Usefulness of Single Nucleotide Polymorphisms as Predictors of Sudden Cardiac Death

The pathophysiology of sudden cardiac death (SCD) remains incompletely understood. Genetic mutations can create a favorable substrate for SCD. Our aim is to evaluate the evidence of single nucleotide polymorphisms (SNPs) as predictors of SCD. We searched the Medline database (2000 to 2017) and selected all case-control or cohort studies that reported associations between SNPs and SCD. Our search terms included "polymorphisms" and "sudden death." We collected the study design, population ethnic background, gene testing strategy, the association between the SNP and SCD, and the cardiovascular comorbidities of the population. Our search yielded 723 studies, of which we included 24 based upon our inclusion criteria. The studies had a total population of 78,165 participants, with a median age of 62.5 years (IQR 56 to 66) and 35% (IQR 13 to 32) were female. Almost all studies were conducted in white patients of European descent and the most commonly used genetic strategy was candidate gene panels. Fifteen of the studies had a case-control design that included SCD patients without known heart disease as the comparison group and the other 9 studies included patients with heart failure and coronary artery disease. The studies evaluated 53 SNPs and the most common genetic loci were SCN5A, RyR2, CASQ2, NOSA1P, and AGTR. SNPs with the 3 strongest statistically significant ORs >1 were: rs6684209 of CASQ2 (odds ratio [OR] 19), rs3814843 of CALM1 (OR 5.5), and rs35594137 of GJA5 (OR 3.6). In Conclusion, many SNPs are associated with SCD, with the strongest associations seen in SNPs of genes related to intracellular calcium handling. These findings were generated primarily using a candidate gene strategy in white patients with European descent.

Sudden Cardiac Death Among Hemodialysis Patients

Hemodialysis patients carry a large burden of cardiovascular disease; most onerous is the high risk for sudden cardiac death. Defining sudden cardiac death among hemodialysis patients and understanding its pathogenesis are challenging, but inferences from the existing literature reveal differences between sudden cardiac death among hemodialysis patients and the general population. Vascular calcifications and left ventricular hypertrophy may play a role in the pathophysiology of sudden cardiac death, whereas traditional cardiovascular risk factors seem to have a more muted effect. Arrhythmic triggers also differ in this group as compared to the general population, with some arising uniquely from the hemodialysis procedure. Combined, these factors may alter the types of terminal arrhythmias that lead to sudden cardiac death among hemodialysis patients, having important implications for prevention strategies. This review highlights current knowledge on the epidemiology, pathophysiology, and risk factors for sudden cardiac death among hemodialysis patients. We then examine strategies for prevention, including the use of specific cardiac medications and device-based therapies such as implantable defibrillators. We also discuss dialysis-specific prevention strategies, including minimizing exposure to low potassium and calcium dialysate concentrations, extending dialysis treatment times or adding sessions to avoid rapid ultrafiltration, and lowering dialysate temperature.

Invited Commentary

The optimal treatment for anomalous aortic origin of a coronary artery (AAOCA) is controversial. At the crux of the controversy lies an incomplete understanding of the pathophysiology of sudden cardiac death in these patients, the actual risk conferred by different anatomies, and the uncertain effects of surgical intervention on reducing that risk. Multiple different techniques have been used in an attempt to rectify the anatomy and reduce the risk in AAOCA. Law and colleagues [1Law T. Dunne B. Stamp N. Ho K.M. Andrews D. Surgical results and outcomes after reimplantation for the management of anomalous aortic origin of the right coronary artery.Ann Thorac Surg. 2016; 102: 192-199Google Scholar] present a series of 16 patients that underwent coronary translocation. Based on their midterm outcomes, they suggest that coronary translocation should be the treatment of choice for surgical management of AAOCA. Other series have advocated surgical unroofing as the best treatment for these patients [2Sharma V. Burkhart H.M. Dearani J.A. et al.Surgical unroofing of anomalous aortic origin of a coronary artery: a single-center experience.Ann Thorac Surg. 2014; 98: 941-946Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar], a technique that accounts for almost 90% of cases on AAOCA patients <30 years of age in the United States [3Poynter J.A. Bondarenko I. Austin E.H. et al.Repair of anomalous aortic origin of a coronary artery in 113 patients: a Congenital Heart Surgeons’ Society report.World J Pediatr Congenit Heart Surg. 2014; 5: 507-514Crossref PubMed Scopus (45) Google Scholar]. Coronary translocation is an attractive technique because it not only addresses the intramural segment (if the coronary is divided at its exit point rather than harvested as a button) but also places the ostium in its correct sinus, therefore addressing the interarterial segment that some consider important in the pathophysiology. On the other hand, it implies manipulating the coronary itself and creating a circumferential anastomosis, with its unknown long-term consequences. This is a major consideration since a large proportion of patients with AAOCA are children and adolescents with an expected life expectancy that should be measured in decades, rather than years. This series, just as all other AAOCA series, suffers from a relatively short follow-up (mean follow-up of 5 years). It may also be naïve to think that a one-size-fits-all strategy will ultimately be the optimal approach for AAOCA. It is possible (and likely) that different techniques may be best for different patients with different specific morphologies. Coronary translocation may be useful in patients with a short intramural segment in which surgical unroofing fails to move the ostium to the correct sinus or those with a thick intercoronary column that could still impinge on the coronary ostium after unroofing. On the other hand, surgical unroofing may well be the optimal technique on younger patients with a long intramural segment. Only one thing is clear: we need more data. Only by aggregating experience from different centers and compulsively following patients for a long time will we achieve our ultimate goal of understanding AAOCA and provide the right treatment for the right patient at the right time. Surgical Results and Outcomes After Reimplantation for the Management of Anomalous Aortic Origin of the Right Coronary ArteryThe Annals of Thoracic SurgeryVol. 102Issue 1PreviewAnomalous aortic origin of the right coronary artery (AAORCA) has been reported to cause myocardial ischemia, leading to angina, dyspnea, and decreased exercise tolerance. Reimplantation is a repair technique devised to exclude the abnormal intramural portion of the anomalous artery and avoid the known late attrition of saphenous vein grafts. Our study aims to evaluate the medium-term clinical outcomes with this technique. Full-Text PDF

Domperidone, Parkinson disease and sudden cardiac death: Mice and men show the way

Domperidone, Parkinson disease and sudden cardiac death: Mice and men show the way

A Clinical Perspective on Sudden Cardiac Death.

This article presents the epidemiology, aetiology and pathophysiology of sudden cardiac death. The modern management of survivors as well as of family members of victims is discussed, as are the relevant recommendations of guidelines prepared by learned societies.

Surgical Unroofing for Anomalous Aortic Origin of Coronary Arteries

Anomalous aortic origin of a coronary artery (AAOCA) from an opposite sinus of Valsalva is an uncommon congenital defect that is typically only discovered on cardiac catheterization or on autopsy following sudden cardiac death. Conjectured mechanisms for the ischemia are generally believed to relate to the unique and easily obstructed geometry of the coronary ostium and the stenotic intramural coronary segment. Given the potentially devastating consequences of not repairing an AAOCA—that is, sudden cardiac death—these patients should undergo repair of the anomaly when it is discovered. Multiple options for surgically correcting the AAOCA have been developed, and the most used approaches include coronary artery bypass grafting, coronary reimplantation, and unroofing of the intramural segment. Here we present the technique for surgical unroofing of the intramural segment of an anomalous coronary artery of aortic origin.

Comprehensive multilevel in vivo and in vitro analysis of heart rate fluctuations in mice by ECG telemetry and electrophysiology.

The normal heartbeat slightly fluctuates around a mean value; this phenomenon is called physiological heart rate variability (HRV). It is well known that altered HRV is a risk factor for sudden cardiac death. The availability of genetic mouse models makes it possible to experimentally dissect the mechanism of pathological changes in HRV and its relation to sudden cardiac death. Here we provide a protocol that allows for a comprehensive multilevel analysis of heart rate (HR) fluctuations. The protocol comprises a set of techniques that include in vivo telemetry and in vitro electrophysiology of intact sinoatrial network preparations or isolated single sinoatrial node (SAN) cells. In vitro preparations can be completed within a few hours, with data acquisition within 1 d. In vivo telemetric ECG requires 1 h for surgery and several weeks for data acquisition and analysis. This protocol is of interest to researchers investigating cardiovascular physiology and the pathophysiology of sudden cardiac death.

DOES PROGNOSIS CHANGE DEPENDING ON NUMBER AND COMPOSITION OF NON OBSTRUCTIVE PLAQUES? RESULTS FROM THE MULTINATIONAL CORONARY CT ANGIOGRAPHY EVALUATION FOR CLINICAL OUTCOME: AN INTERNATIONAL MULTICENTER REGISTRY (CONFIRM)

Obstructive coronary artery disease (CAD) has worse prognosis compare to non-obstructive CAD. However, non-obstructive plaques have been implicated in pathophysiology of sudden cardiac death and myocardial infarction (MI). It is not known whether there is an incremental risk of major adverse cardiac

Cardiomyocyte Injury Assessed by a Highly Sensitive Troponin Assay and Sudden Cardiac Death in the Community: The Cardiovascular Health Study

This study sought to determine the association between markers of cardiomyocyte injury in ambulatory subjects and sudden cardiac death (SCD). The pathophysiology of SCD is complex but is believed to be associated with an abnormal cardiac substrate in most cases. The association between biomarkers of cardiomyocyte injury in ambulatory subjects and SCD has not been investigated. Levels of cardiac troponin T, a biomarker of cardiomyocyte injury, were measured by a highly sensitive assay (hsTnT) in 4,431 ambulatory participants in the Cardiovascular Health Study, a longitudinal community-based prospective cohort study. Serial measures were obtained in 3,089 subjects. All deaths, including SCD, were adjudicated by a central events committee. Over a median follow-up of 13.1 years, 246 participants had SCD. Baseline levels of hsTnT were significantly associated with SCD (hazard ratio [HR] for +1 log(hsTnT): 2.04, 95% confidence interval [CI]: 1.78 to 2.34]. This association persisted in covariate-adjusted Cox analyses accounting for baseline risk factors (HR: 1.30, 95% CI: 1.05 to 1.62), as well as for incident heart failure and myocardial infarction (HR: 1.26, 95% CI: 1.01 to 1.57). The population was also categorized into 3 groups based on baseline hsTnT levels and SCD risk [fully adjusted HR: 1.89 vs. 1.55 vs. 1 (reference group) for hsTnT ≥12.10 vs. 5.01 to 12.09 vs. ≤ 5.00 pg/ml, respectively; p trend = 0.005]. On serial measurements, change in hsTnT levels was also associated with SCD risk (fully adjusted HR for +1 pg/ml per year increase from baseline: 1.03, 95% CI: 1.01 to 1.06). The findings suggest an association between cardiomyocyte injury in ambulatory subjects and SCD risk beyond that of traditional risk factors.

Correlations Between CCN1 Immunoexpression and Myocardial Histologic Lesions in Sudden Cardiac Death

CCN1 (CYR61) is a member of the CCN family of secreted matricellular proteins; it can regulate the expression of genes involved in angiogenesis and matrix remodeling. The latter mechanisms seem to be of vital importance in the pathophysiology of sudden cardiac death. We performed an immunohistochemical analysis on 62 cardiac tissue specimens derived from individuals of young and middle age who had died of sudden cardiac death. CCN1 immunopositivity was detected in 80.6% of all specimens. Semiquantitative statistical analysis of the staining results revealed that CCN1 immunoreactivity was significantly associated with ischemic morphology and hypertrophy of myocardial fibers, interstitial edema, and atheromatosis of coronary arteries in more than 10% of the myocardial fibers. Taking the previously mentioned correlations into account, ischemia seems to induce myocardial expression of CCN1; therefore, CCN1 immunostaining could be evaluated as a complementary tool in the assessment of ischemic areas when no tissue evidence of necrosis is available.

Pathophysiology of sudden cardiac death as demonstrated by molecular pathology of natriuretic peptides in the myocardium

Various heart diseases present with sudden death; however, it is difficult to interpret the severity of or difference in respective preexisting and terminal cardiac dysfunction based on conventional morphology. The present study investigated the cardiac pathophysiology employing quantitative mRNA measurement of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium as markers of cardiac strain, using autopsy materials consisting of acute ischemic heart disease (AIHD, n=40) with/without the pathology of apparent myocardial necrosis (n=19/21), recurrent myocardial infarction (RMI, n=19), chronic congestive heart disease (CHD, n=11) and right ventricular cardiomyopathy (RVC, n=5), as well as hemopericardium (HP, n=11) due to myocardial infarction (n=5) and aortic rupture (n=6), and acute pulmonary thromboembolism (PTE, n=5). Cardiac death groups showed higher ANP and/or BNP mRNA expressions in the left ventricle than acute fatal bleeding (sharp instrumental injury; n=15) and/or mechanical asphyxiation (strangulation; n=10). AIHD and RMI cases had similar ANP and BNP mRNA expressions in bilateral ventricular walls, but their bilateral atrial levels were lower in RMI. RVC showed higher mRNA expressions of posterior left ventricular BNP, and right ventricular and bilateral atrial ANP and BNP. HP cases had lower BNP mRNA expression in the right ventricular wall, but PTE showed lower ANP and BNP mRNA expressions in the left ventricular wall; however, these mRNA expressions at other sites were similar to those of AIHD. CHD presented findings similar to those of AIHD, but the pericardial BNP level was significantly increased. These observations indicate characteristic molecular biological responses of myocardial natriuretic peptides in individual heart diseases and suggest the possible application of molecular pathology to demonstrate cardiac dysfunction even after death.