Unexplained Sudden Cardiac Death Research Articles

Pokkuri Death Syndrome; sudden cardiac death cases without coronary atherosclerosis in South Asian young males

Sudden death is one of the major concerns in forensic medicine. Especially when the deceased is a young subject without significant history, the case will be of major interest to the authorities. Sudden unexplained cardiac death has been known as "Pokkuri Death Syndrome" (PDS) in Japan, "Lai Tai" in Thailand, "Bangungut" in the Philippines, "Dream Disease" in Hawaii, and "Sudden Unexpected Nocturnal Death Syndrome" among South Asian immigrants in the USA. However, the clinical and pathological features of these sudden death cases, especially the characteristics of no coronary atherosclerosis, are surprisingly similar and mainly occur among Southeast Asian young males during sleep in the midnight. In this manuscript, we have reviewed the pathological characteristics and the possible mechanism of death in PDS cases, which were associated with significantly elevated remnant lipoproteins in plasma as revealed from our studies during the past 15 years in Japan. Although elevated plasma remnant lipoproteins have been known to be strongly atherogenic, coronary atherosclerosis was not observed in PDS cases. PDS cases were shown to be an interesting cardiovascular disease death discovered in forensic medicine research, which may suggest the difference between the occurrence of cardiovascular events and the severity of coronary atherosclerosis as separate factors. These observations in PDS cases suggest the possibility that the intervention could be more targeted to suppress the cardiovascular events rather than to slow down the progression of atherosclerosis, which is now most extensively targeted for the therapy of cardiovascular disease in Western countries.

Drug-Induced Arrhythmia

Prolongation of the QTc interval has been associated with proarrhythmia resulting from a potentially fatal form of polymorphic ventricular tachycardia called torsades de pointes (TdP). Genetic forms of the long-QT syndrome (LQTS) associated with high arrhythmic risk have been causally related to mutations in ion channels responsible for the cardiac action potential; genetic factors associated with milder degrees of QTc prolongation and arrhythmic risk have also been described. Acquired forms of QTc prolongation and proarrhythmia, particularly related to drug therapy, are frequently related to drug effects on the same ion channels involved in genetic forms of LQTS. As is true for genetic forms of LQTS, there is a wide spectrum of potential drug effects on the QTc interval ranging from trivial to potentially lethal. Drug-induced QTc prolongation is a complicated phenomenon related not just to the properties or dose of a particular drug but also to drug-drug interactions and a variety of patient factors, including age, gender, the presence and severity of underlying heart disease, and genetic predisposition. Additionally, drug effects on other ion channels, including blockade of sodium channels (causing prolongation of the QRS interval rather than the QTc interval), are an important cause of drug-induced proarrhythmia. The purpose of this review is to summarize the available data related to acquired forms of LQTS, with particular focus on drug-related LQTS and proarrhythmia. A brief summary is presented here of genetic LQTS because the relevant genes and proteins form the basis for an understanding of the causes of acquired LQTS, and in any given patient, the QTc is determined by genetic, substrate, and environmental factors. Emphasis is placed on practical strategies for clinicians, with the goal of minimizing the risk of dangerous proarrhythmia related to the use of both cardiac and noncardiac drugs with the potential for QTc prolongation. Genetic …

Unexplained sudden cardiac death—back to clinical evaluation

The diagnosis of unexplained cardiac arrest could soon become obsolete, as so-called molecular autopsy can now be used to identify its underlying causes. The current view of this subject is discussed, and some personal opinions are presented on the assessment of survivors of sudden cardiac arrest and relatives of individuals who do not survive.

State of Postmortem Genetic Testing Known as the Cardiac Channel Molecular Autopsy in the Forensic Evaluation of Unexplained Sudden Cardiac Death in the Young

Thousands of infants, children, adolescents, and young adults die sudden and unexpectedly each year in the United States. A significant proportion are autopsy negative and are classified as autopsy negative sudden unexplained death (SUD) after the first year of life and as sudden infant death syndrome (SIDS) if prior to their first birthday. Postmortem genetic testing known as the cardiac channel molecular autopsy is capable of identifying the subset of channelopathic SUD/SIDS. Review of the literature and analysis of the state of such postmortem genetic testing in the evaluation of SUD/SIDS. Although still confined to anecdotal reports, relatively small case series of coroner/medical examiner-referred cases of SUD/SIDS, and one population-based cohort of SIDS, it is estimated that approximately 25-35% of autopsy-negative SUD and approximately 10% of SIDS may stem from mutations in either long QT syndrome (LQTS)- or catecholaminergic polymorphic ventricular tachycardia (CPVT)-susceptibility genes. Whether the cardiac channel molecular autopsy should become the standard of care in the postmortem evaluation of autopsy negative SUD or SIDS will require further scrutiny. Cost effectiveness analyses of a more intense postmortem focus on the decedent compared to the current battery of tests recommended for the deceased SUD victim's first degree relatives should be performed. If deemed justified to upgrade such postmortem genetic testing from "investigational" to clinically indicated, uniform "standard operating procedures" to ensure that tissue is acquired and archived in a manner that is "DNA friendly" and insurance coverage that extends beyond one's final breath will be needed.

AJR Teaching File: Asymptomatic Man with Giant Negative T Waves on ECG

Received July 31, 2008; accepted without revision August 12, 2008. 1Department of Radiology, Division of Cardiothoracic Radiology, East Ann Arbor Health and Geriatrics Center, University of Michigan, 4260 Plymouth Rd., Rm. 1847 SPC 2713, Ann Arbor, MI 48109-2713. Address correspondence to A. Attili (aattili@umich.edu). 2Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical Center, Ann Arbor, MI. AJR 2009;192:S57–S61 0361–803X/09/1923–S57 © American Roentgen Ray Society Case History A 40-year-old asymptomatic man presents for a routine health maintenance examination. The physical examination is normal; in particular, he is normotensive. ECG reveals diffuse deep T wave inversion. His family history is significant for unexplained sudden cardiac death in his father. MRI was performed to further evaluate an abnormality revealed on echocardiography.

Induced Brugada-Type Electrocardiogram, a Sign for Imminent Malignant Arrhythmias

Case presentation: A previously healthy 20-year-old man arrives at the emergency department for a consultation for mild fever. During his initial interview, he complains of palpitations to the triage nurse and therefore he undergoes an ECG, which is placed in the chart. A few minutes later, while awaiting his turn to be seen, he goes into cardiac arrest. The patient does not respond to resuscitation and dies in the emergency department. The autopsy reveals no cardiac structural abnormalities or evidence of myocarditis. The cause of death is determined as sudden unexplained cardiac death. The ECG from the emergency department revealed ST-segment elevation in the right precordial leads consistent with a Brugada ECG pattern. The Brugada syndrome is a heterogeneous genetic disease that predisposes to life-threatening ventricular tachyarrhythmias and sudden cardiac death (SCD). The syndrome is usually identified by a characteristic Brugada-type ECG that consists of ST elevation of a coved type in the precordial leads V1 to V3, although affected individuals may have a normal ECG.1,2 Because patients with Brugada syndrome usually become symptomatic at a relatively young age, early diagnosis is crucial to prevent SCD in those with a higher risk of developing an arrhythmic event.3 Approximately one fourth of the cases of Brugada syndrome are caused by loss of function mutations in the cardiac sodium channel SCN5A. Several nongenetic factors have been mentioned in the literature as possible inductors of the ECG pattern resembling Brugada syndrome.2 As such, a Brugada-type ECG may appear in some patients during febrile states …

Abstract 2565: Predictors For Very Late Stent Thrombosis After Drug-eluting Stent Implantation In Diabetic Patients.

Background: Despite encouraging results with drug-eluting stents (DES) reported in diabetes mellitus (DM) patients (pts) with coronary artery disease, the long-term safety is unknown, because of late-onset stent thrombosis (LST). We investigated the incidence, risk factors and association of antiplatelet treatment (APLT) interruption for the development of LST in DM pts treated with DES during long-term clinical follow-up (FU). Methods: A total of 610 consecutive DM pts (male 80%, mean age 65 ± 9 years) had been treated with DES (sirolimus 80%, paclitaxel 10%, zotarolimus 2% combination 8%); 133 (22%) were on insulin treatment. Dual APLT treatment for 12 months received 93%, more than 12 months 72% and statin treatment 93% of pts. Clinical FU at least 12 months post-PCI (median 29 months, interquartile range 21 to 40) was obtained in 597/610 (98%) of pts. LST was defined as angiographic documentation of stent occlusion associated with an acute ischemic event, unexplained sudden cardiac death (D) or myocardial infarction (MI) not clearly attributable to another coronary lesion. Results: The incidence of LST was 2.18% (13 of 597 pts) and 6 additional pts (1%) developed stent thrombosis before 12 months (EST). All pts with LST (median time 19 months, interquartile range 14 to 24) had unexplained sudden cardiac D and 2/6 pts with EST non-fatal MI. Eleven out of 13 pts (85%) were on dual antiplatelet treatment at the time of LST. There was no difference in the incidence of LST between pts on oral antidiabetic medications and insulin treatment (2,1% vs. 2.3%, p:ns). In a multivariate model including clinical and angiographic factors, the only predictor for LST was ejection fraction <40% (OR 0.10, 95% CI 0.03– 0.43, p<0.05). Conclusion: LST in DM pts occurred in 2.18% after DES implantation; most of these pts were on dual APLT treatment. The only predictor of LST was depressed left ventricular function.

Contribution of Inherited Heart Disease to Sudden Cardiac Death in Childhood

In children aged 1 to 18 years, the causes of sudden cardiac death may remain unresolved when autopsy results are negative. Because inherited cardiac diseases are likely, cardiologic and genetic investigations of relatives may still yield the diagnosis in these cases. Moreover, these investigations provide timely identification of relatives who are also at risk of sudden cardiac death. We aimed to establish the cause of sudden cardiac death in the children of whom the family was referred to our cardiogenetics department and the diagnostic yield of these investigations. We genetically counseled 25 consecutive, unrelated families after sudden cardiac death of a child (aged 1 to 18 years) who was disease-free during lifetime and in whose family there was no known inherited heart disease. We performed cardiac investigation (electrocardiography, exercise testing, and echocardiography) of first-degree and second-degree relatives and performed diagnosis-directed DNA analysis. Autopsy was performed in 20 case subjects. A diagnosis was identified in 14 of 25 families. In addition, we studied 10 children after aborted sudden cardiac death; in 6 of them, a diagnosis was made. Overall, in 17 of the 19 families in whom an inherited disease was diagnosed, a disease-causing mutation in either a first-degree relative or the index patient confirmed the diagnosis. Sudden cardiac death in children seems to be caused often by inherited cardiac diseases. Cardiac and genetic examination of relatives combined, if possible, with postmortem analysis after sudden cardiac death of a child has a high diagnostic yield (14 of 25), comparable to analysis in surviving victims of sudden cardiac death (6 of 10). Because sudden cardiac death can be prevented by timely treatment, these results warrant active family screening after unexplained sudden cardiac death of a child.

The Long QT Syndrome

The long QT syndrome (LQTS) is a genetically transmitted cardiac arrhythmia due to ion channel protein abnormalities, which affects the transport of potassium and sodium ions across the cell membrane. Patients with LQTS may present with syncope, seizures or aborted cardiac arrest. LQTS is also an important cause of unexplained sudden cardiac death in the young. The diagnosis of LQTS is generally made on an ECG showing the prolonged QT interval. The establishment of LQTS registry and the discovery of genetic mutations causing LQTS have contributed greatly to the understanding of this condition and have also provided an impetus in understanding of other inherited cardiac arrhythmias. Genotype-phenotype correlation studies have allowed risk stratification of LQTS patients. Life style modification to avoid triggers for malignant cardiac arrhythmias, and the use of beta-blockers, pacemakers and implantable defibrillators, help to treat symptoms and reduce mortality in these patients.

The role of molecular autopsy in unexplained sudden cardiac death

Sudden cardiac death (SCD) is one of the most common causes of death, with many attributable to cardiac/coronary abnormalities evident at autopsy. A significant number of SCDs, however, particularly in young people, remain unexplained following a medico-legal investigation, including autopsy, and are referred to as autopsy-negative sudden unexplained death (SUD). Due to molecular advances, however, a cardiac channel molecular autopsy may potentially provide a pathogenic basis for SUD and establish cause and manner of death. Over the past decade, five population-based investigations of sudden death in young people elucidated the frequency of and causes responsible for these tragic events. The most inclusive epidemiologic study concluded that nearly 30% of SCDs in young people are autopsy-negative (i.e. SUD) and most likely secondary to cardiac channelopathies. Case reports on the post-mortem molecular diagnosis of cardiac channelopathies through the use of a molecular autopsy have been presented. Recently, a molecular autopsy series of SUD identified pathogenic mutations in long QT syndrome and catecholaminergic polymorphic ventricular tachycardia-associated genes in over one-third of cases. Similar post-mortem cardiac channel genetic testing in a large population-based cohort of sudden infant death syndrome has elucidated mutations in 5-10% of cases. With autopsy-negative SUD accounting for a significant number of sudden deaths in young people, a new role for the medical examiner is emerging. An accurate diagnosis, derived from a molecular autopsy, will guide the appropriate initiation of pre-emptive strategies in hopes of preventing future tragedies among those left behind.

Depolarization/repolarization, electrocardiographic abnormalities, and arrhythmias in cardiac channelopathies

Investigation of the etiology and pathogeneses of the genetic cardiac channelopathies has provided important insight into the mechanisms of ventricular arrhythmias. Some of these diseases are rare, such as the short QT-interval syndrome, but others such as the Brugada syndrome are the most common cause of unexplained sudden cardiac death in young men in Southeast Asia and Japan. Knowledge of the specific ion-channel defect causing the disease or syndrome is leading to pharmacological approaches that attempt to correct the ion transfer defects in channelopathies. The most clinically important challenge is to recognize which patients with the Brugada electrocardiogram who do not have a positive family history of this condition and do not have a history of syncope or aborted sudden death are at risk for arrhythmic death.

Neoadjuvant and Adjuvant Chemotherapy with Doxorubicin and Docetaxel in Locally Advanced Breast Cancer

Fifty patients with histologically confirmed stage III breast cancer were enrolled in this study of doxorubicin 50 mg/m 2 and docetaxel 75 mg/m 2 intravenously infused over 1 hour every 21 days with granulocyte colonystimulating factor for 4 cycles. This was followed by surgery (mastectomy or lumpectomy) and 4 more cycles of doxorubicin/docetaxel postoperatively, then radiation and tamoxifen as indicated. Forty-six of the 50 patients (92%) completed neoadjuvant chemotherapy, and 38 patients (76%) completed adjuvant chemotherapy. Clinical response (defined as > 50% decrease in size of tumor) was achieved after 2 cycles in 37 patients (74%) and after 4 cycles in 42 of the 46 patients (91%) who finished neoadjuvant chemotherapy. Pathologic complete response (pCR; no pathologic invasive cancer) at the primary site was obtained in 7 of 46 patients (15%); 11 had no residual gross disease but did have microscopic persistence or microscopic complete response (mCR), for a combined pCR and mCR of 18 of 46 patients (39%). No treatment-related deaths occurred, but 3 patients died during treatment: 1 from progressive disease, 1 from a gastrointestinal bleeding, and 1 from unexplained sudden cardiac death. Dose-limiting toxicities were hematologic (grade 3 neutropenia in 5 patients and grade 4 in 23 patients). Congestive heart failure developed in 4 of 50 patients (8%), with a mean decrease in left ventricular ejection fraction (LVEF) of 20% in affected patients and 1 asymptomatic decrease in LVEF of 25%. At last follow-up, 10 patients had died of progressive disease, and 1 each from sudden cardiac death and lower gastrointestinal bleeding. In locally advanced breast cancer, neoadjuvant doxorubicin/docetaxel is a very active regimen that achieved pCR of 15% and a combined pCR and mCR of 39%, for an overall clinical response rate of 91%. Adjuvant chemotherapy was complicated by dropouts and congestive heart failure. This regimen should be used with close monitoring of cardiac function.

Postmortem molecular screening in unexplained sudden death

ObjectivesWe examined the prevalence of defects in arrhythmia-related candidate genes among patients with unexplained sudden cardiac death (SCD). BackgroundPatients with unexplained sudden death may constitute up to 5% of overall SCD cases. For such patients, systematic postmortem genetic analysis of archived tissue, using a candidate gene approach, may identify etiologies of SCD. MethodsWe performed analysis of KCNQ1 (KVLQT1), KCNH2 (HERG), SCN5A, KCNE1,and KCNE2defects in a subgroup of 12 adult subjects with unexplained sudden death, derived from a 13-year, 270-patient autopsy series of SCD. Archived, paraffin-embedded myocardial tissue blocks obtained at the original postmortem examination were the source of deoxyribonucleic acid for genetic analysis. ResultsTwo patients were found to have the same HERGdefect, a missense mutation in exon 7 (nucleotide change G1681A, coding effect A561T).The mutation was heterozygous in Patient 1, but Patient 2 appeared to be homozygous for the defect. Patch-clamp recordings showed that the A561T mutant channel expressed in human embryonic kidney cells failed to generate HERGcurrent. Western blot analysis implicated a trafficking defect in the protein, resulting in loss of post-translational processing from the immature to the mature form of HERG. No mutations were detected among the remaining four candidate genes. ConclusionsIn this autopsy series, only 2 of 12 patients with unexplained sudden death were observed to have a defect in HERGamong five candidate genes tested. It is likely that elucidation of SCD mechanisms in such patients will await the discovery of multiple, novel arrhythmia-causing gene defects.

Sex selection in unexplained sudden cardiac death

Sex selection in unexplained sudden cardiac death

Clinical characteristics of unexplained sudden cardiac death in Korea.

In Western countries, sudden cardiac death (SCD) is closely related to coronary artery disease, but in Korea the clinical characteristics of SCD are not well determined. Over a 4-year period (June 1995 to May 1999), 186 cases of SCD, ranging in age from 16 to 75 years, were admitted to the Chonnam National University Hospital. In 82 (44.1%) of these, neither symptoms nor evidence of structural heart disease was found and so their clinical characteristics were investigated. There were 66 (80.5%) men and 16 (19.5%) women (male/female ratio = 4.1:1). The mean age was 50 +/- 14 years: 19 (23.2%) were in their 40s, 21 (25.6%) in their 50s, and 17 (20.7%) in their 60s. The time of circulatory collapse witnessed in 68 cases of SCD showed 2 peaks: between midnight and 03.00h (n=16, 23.5%) and between 09.00h and midday (n=15, 22.1%). Unexplained SCD occurred at home in 48 (64.9%) cases and on the street in 12 (16.2%); it occurred during normal daily routine activity in 23 (39.6%) and during sleep in 15 (25.9%). Thirty-three patients (40.2%) experienced various prodromal symptoms, including chest discomfort (n=13, 15.9%) and dyspnea (n=8, 9.8%). The electrocardiogram taken on arrival recorded asystole in 65 (79.3%) and ventricular fibrillation in 17 (20.7%). Idiopathic ventricular fibrillation was diagnosed in 14 (10 men, 4 women; 45 +/- 11 years) of 21 patients who recovered spontaneous circulation. Five (6.1%) patients were discharged alive, and an implantable cardioverter-defibrillator was implanted in 2. Unexplained SCD is common in Korea and develops predominantly in middle-aged males around midnight or in the late morning usually with no prodromal symptoms (59.8%). Idiopathic ventricular fibrillation is thought to be one of the important causes.

Heterogeneous cardiac sympathetic denervation and decreased myocardial nerve growth factor in streptozotocin-induced diabetic rats: implications for cardiac sympathetic dysinnervation complicating diabetes.

Heterogeneous myocardial sympathetic denervation complicating diabetes has been invoked as a factor contributing to sudden unexplained cardiac death. In subjects with diabetic autonomic neuropathy (DAN), distal left ventricular (LV) denervation contrasts with preservation of islands of proximal innervation, which exhibit impaired vascular responsiveness. The aims of this study were to determine whether this heterogeneous pattern of myocardial sympathetic denervation occurs in a rat model of diabetes and to explore a potential association with regional fluctuations in myocardial nerve growth factor (NGF) protein. Myocardial sympathetic denervation was characterized scintigraphically using the sympathetic neurotransmitter analog C-11 hydroxyephedrine ([11C]HED) and compared with regional changes in myocardial NGF protein abundance and norepinephrine content after 6 and 9 months in nondiabetic (ND) and streptozotocin-induced diabetic (STZ-D) rats. In ND rats, no difference in [11C]HED retention or norepinephrine content was detected in the proximal versus distal myocardium. After 6 months, compared with ND rats, myocardial [11C]HED retention had declined in the proximal segments of STZ-D rats by only 9% (NS) compared with a 33% decrease in the distal myocardium (P < 0.05). Myocardial norepinephrine content was similar in both ND and STZ-D rats. At 6 months, LV myocardial NGF protein content in STZ-D rats decreased by 52% in the proximal myocardial segments (P < 0.01 vs. ND rats) and by 82% distally (P < 0.01 vs. ND rats, P < 0.05 vs. proximal segments). By 9 months, [11C]HED retention had declined in both the proximal and distal myocardial segments of the STZ-D rats by 42% (P < 0.01 vs. ND rats), and LV norepinephrine content and NGF protein were decreased in parallel. Therefore, 6 months of STZ-induced diabetes results in heterogeneous cardiac sympathetic denervation in the rat, with maximal denervation occurring distally, and is associated with a proximal-to-distal gradient of LV NGF protein depletion. It is tempting to speculate that regional fluctuations of NGF protein in the diabetic myocardium contribute to heterogeneous cardiac sympathetic denervation complicating diabetes.

Atrioventricular node fetal dispersion and His bundle fragmentation of the cardiac conduction system in sudden cardiac death.

This study sought to examine the frequency of persistent fetal dispersion of the atrioventricular (AV) node and fragmentation of the atrioventricular bundle (His) bundle in the cardiac conduction system of sudden cardiac death cases and control subjects to establish their importance as the cause of death. These are two of the most frequent lesions reported in published reports in the cardiac conduction system in unexplained sudden deaths. We have studied the conduction system of 347 hearts: 249 hearts from sudden cardiac death cases and 98 control hearts. The sudden cardiac death cases were divided, according to the pathology found, in three groups: group I: ischemic heart disease, 137 cases; group II: nonischemic heart disease, 48 cases, and group III: unexplained sudden cardiac deaths, 64 cases. The control group (group IV) consisted of patients with unnatural deaths and extracardiac natural deaths. Persistent fetal dispersion of the AV node was observed in 70 cases (20.17%) of all groups with a frequency (40.81%) statistically higher in the control group. Fragmentation of the His bundle was observed in 95 cases (31.77%), and the frequency was statistically higher in the control group, too (47.67%). Persistent fetal dispersion of the AV node and fragmentation of the His bundle can be a normal variation present during many years in life and must not be considered the anatomic substrate for arrhythmias and sudden death without electrocardiographic abnormalities.

Scintigraphic Assessment of Regionalized Defects in Myocardial Sympathetic Innervation and Blood Flow Regulation in Diabetic Patients With Autonomic Neuropathy

Objectives. This study sought to evaluate whether regional sympathetic myocardial denervation in diabetes is associated with abnormal myocardial blood flow under rest and adenosine-stimulated conditions.Background. Diabetic autonomic neuropathy (DAN) has been invoked as a cause of unexplained sudden cardiac death, potentially by altering electrical stability or impairing myocardial blood flow, or both. The effects of denervation on cardiac blood flow in diabetes are unknown.Methods. We studied 14 diabetic subjects (7 without DAN, 7 with advanced DAN) and 13 nondiabetic control subjects without known coronary artery disease. Positron emission tomography using carbon-11 hydroxyephedrine was used to characterize left ventricular cardiac sympathetic innervation and nitrogen-13 ammonia to measure myocardial blood flow at rest and after intravenous administration of adenosine (140 μg/kg body weight per min).Results. Persistent sympathetic left ventricular proximal wall innervation was observed, even in advanced neuropathy. Rest myocardial blood flow was higher in the neuropathic subjects (109 ± 29 ml/100 g per min) than in either the nondiabetic (69 ± 8 ml/100 g per min, p < 0.01) or the nonneuropathic diabetic subjects (79 ± 23 ml/100 g per min, p < 0.05). During adenosine infusion, global left ventricular myocardial blood flow was significantly less in the neuropathic subjects (204 ± 73 ml/100 g per min) than in the nonneuropathic diabetic group (324 ± 135 ml/100 g per min, p < 0.05). Coronary flow reserve was also decreased in the neuropathic subjects, who achieved only 46% (p < 0.01) and 44% (p < 0.01) of the values measured in nondiabetic and nonneuropathic diabetic subjects, respectively. Assessment of the myocardial innervation/blood flow relation during adenosine infusion showed that myocardial blood flow in neuropathic subjects was virtually identical to that in nonneuropathic diabetic subjects in the distal denervated myocardium but was 43% (p < 0.05) lower than that in the nonneuropathic diabetic subjects in the proximal innervated segments.Conclusions. DAN is associated with altered myocardial blood flow, with regions of persistent sympathetic innervation exhibiting the greatest deficits of vasodilator reserve. Future studies are required to evaluate the etiology of these abnormalities and to evaluate the contribution of the persistent islands of innervation to sudden cardiac death complicating diabetes.

Nonatherosclerotic narrowing of the atrioventricular node artery and sudden death

Objectives. This study was undertaken to determine whether thickening of the atrioventricular (AV) node artery is a cause of sudden cardiac death.Background. Thickening of the AV node artery has been implicated as a cause of sudden death primarily on the basis of case reports. Few pathologic studies have compared subjects who died of sudden cardiac death with normal control subjects who died traumatically.Methods. The AV node artery in 27 patients with unexplained sudden cardiac death (mean age 24.8 ± 7.4 years) was compared with that in 17 control subjects who died traumatically (mean age 25.6 ± 7.0 years). No anatomic cause of death was found at autopsy in the subjects with sudden death, all of whom died of presumed cardiac arrhythmias. The conduction system of all hearts was studied by semiserial sections and Movat pentachrome stains. At the point of greatest narrowing of the AV node artery, the outer circumference and lumen outline were traced by computerized morphometry, the ratio of enter vessel area to lemea area was calculated and the histopathologic changes were noted.Results. The rank-sum of ratios was significantly greater in the sudden death group than in the control group (p = 0.031, Wilcoxon rank-sum/Mann-Whitney statistic). A dysplastic AV node artery with significant acid mucopolysaccharide deposition was seen almost exclusively in the sudden death group (12 of 27 vs. 1 of 17, p = 0.006). In 10 subjects with sudden death a dysplastic AV node artery was narrowed >2 SD over the control value; half of this subgroup died during exercise and one third had a family history of sudden unexplained cardiac death.Conclusions. Dysplasia of the AV node artery may contribute to death in a substantial portion of patients with unexplained sudden death, and such death is often associated with exercise and a family history of unexplained sudden death.

Clinical Correlations

SummaryThere are two aspects which are clinically relevant in the relationships among thrombosis and arteriosclerosis. First, the relationship of thrombosis to atherogenesis. Thrombosis is closely related to endothelial injury and there is recent evidence that repeated or continuous endothelial damage leads to the development of all the lesions seen in human atherosclerosis. This occurs in the absence of dietary lipid supplement. The relative importance of the parts played by injury and thrombosis in this process need further delineation. Secondly, established arteriosclerotic disease is associated with thrombosis. This thrombosis is usually mural, seldom occlusive. Embolism by platelet aggregates which has been well described in the retinal and cerebral circulations may affect other vascular territories such as the heart and the kidney. Such a mechanism may explain some cases of otherwise unexplained sudden cardiac death and some cases of hypertension. We need better clinical tools to detect the occurrence of thrombo-embolism and to monitor it’s progress. Measures to modify thrombosis and embolism may be as useful or more useful than those we currently employ in the clinical management of atherosclerotic disease.