No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Incidental Myocardial Infarction in Ehlers-Danlos Syndrome Type IV?
Abstract
Ehlers-Danlos Syndrome Type IV is an illness that often leads to premature death due to arterial rupture or dissection and is characterized by very fragile connective tissue. This report documents the death of a 30-year-old man with Ehlers-Danlos Syndrome Type IV from myocardial rupture and cardiac tamponade following a myocardial infarction. We believe that Ehlers-Danlos Syndrome Type IV contributed to the coronary atherosclerosis and myocardial rupture in this young man and that this disease led indirectly to his death by myocardial infarction, an unusual cause of death in this syndrome.
... A right paraclavicular hematoma amounting to 3 L of clotted blood extended to the neck, face, and chest, and a ruptured, dissecting aneurysm of the transverse aortic arch was also noted. Gilchrist and Duflou reported the case of a 30-year-old man who died because of cardiac tamponade from myocardial rupture complicating transmural myocardial infarction (17). The decedent had been previously diagnosed with EDS type IV, which, they hypothesized, may have played a role in his coronary atherosclerosis and subsequent myocardial rupture. ...
Ehlers–Danlos syndrome (EDS) type IV is a connective tissue disorder characterized by the inability to produce sufficient amounts of collagen or a defect in the structure of collagen. The most serious complications include a rupture of a viscus or vascular rupture with or without mural dissection. Death may result from internal hemorrhage. This report describes three cases of sudden and unexpected death caused by EDS type IV. Two cases involved hemothorax as a result of dissection of the subclavian artery and aorta, respectively. The third case represented spontaneous pulmonary rupture and hemorrhage. A detailed family history should be sought, and additional specimens collected to confirm the diagnosis, including skin fibroblasts for collagen testing and blood for DNA testing. The forensic pathologist should consider the possibility of EDS type IV upon discovery of spontaneous visceral or arterial rupture and should alert the family members of this hereditary and potentially fatal condition.
Potentially fatal diseases include vascular diseases, diseases of the cardiac valves, and metabolic disorders, many of which can only be identified or ruled out histopathologically. Arteriosclerosis is the most common vascular disease, and ruptured aortic aneurysms (rarely, coronary artery aneurysms) are often acutely fatal; on the other hand, inflammation or other vascular disorders (idiopathic cystic medial necrosis, syphilitic aortitis, primary coronary arteritis, coronary arteritis, Takayasu’s arteritis) are rarer. While primary vascular diseases are seen, drug-induced vasculitis is extremely rare. Congenital vascular anomalies such as arteriovenous malformations (Osler–Weber–Rendu syndrome) may remain undetected until death. Only occasionally can preexisting collagenosis be discussed as the cause of death (Marfan syndrome, Ehlers–Danlos syndrome), with the same applying to hemochromatosis. In the case of endocarditis, histopathology can contribute to determining the etiology of the disease and identifying bacterial ulcerative endocarditis, possibly with septic microembolisms.
Sudden death prompting a judicial postmortem can be attributed to natural causes arising from a spectrum of vascular, cardiac
valve, and metabolic diseases. The diseases most frequently reported in the forensic literature can only be diagnosed in part
using macroscopic methods; however, cardiac valve disease in particular often demonstrates macroscopic findings. Suspected
diagnoses require microscopic confirmation.
OBJECTIVE:: To provide the collected evidence from all literature reports. BACKGROUND:: Vascular Ehlers-Danlos syndrome (EDS) is a rare connective tissue disorder with serious hemorrhagic consequences. Most experience on treatment is based on case reports and small case series. METHOD:: A systematic literature review was performed. PubMed and reference lists were scrutinized. RESULTS:: A total of 231 patients were identified with no gender preponderance. Aneurysms were present in 40%, often multiple. In 33%, there was an arterial rupture without an underlying aneurysm. Carotidocavernous fistula was seen in 18%. After open surgery the mortality was 30%; after endovascular procedures, it was 24%; in a group of miscellaneous cases, it was 60%; and the overall mortality was 39%. The median age of patients at death was 31 years. The median follow-up time was 12 months (5 days-7 years), but in 20% cases, it was not reported. In only 29 of the 119 recent patients (24%) the mutation was verified with molecular genetic testing. CONCLUSIONS:: Vascular EDS is a serious disorder with high mortality, which does not seem to have been influenced by new treatment methods. Invasive methods should be used only when necessary, primarily to save the patients' life. Whenever possible, the genetic molecular defect should be identified. The results of this review may be affected by publications bias. Ideally, a prospective registry should be created.
Atherosclerotic coronary artery occlusive disease is very rare in cases of Ehlers-Danlos type IV syndrome. We report what we believe is a unique case of successful coronary artery bypass grafting for atherosclerotic coronary artery disease in a patient with this syndrome and examine the possible implications for the natural progression of the disease through a review of the literature. Nevertheless, we reiterate previous investigators' advice that any invasive procedure on these patients should be approached with extreme caution and that surgery should be performed as a last resort, considering the significantly elevated risks.
We describe a case of Ehlers-Danlos syndrome (EDS) type IV in a male in early half in his twenties, who experienced recurrent and eventually fatal pulmonary hemorrhage. EDS type IV is a rare disorder of type III collagen synthesis that is characterized by unusual facies, thin translucent skin with a venous vascular pattern, easy bruising, and hypermobility of the small joints. Autopsy findings showed hypermobility of the joints and distensibility of the skin. Microscopically, the abdominal skin showed substantially decreased dermal thickness. Moreover, the reticular dermis showed fine collagen bundles and large interstitial spaces compared with the skin from a normal control that showed large collagen bundles. Individual elastic fibers were also thicker than those observed in the skin of a normal control. The thoracic aorta showed thin adventitia and a relative increase in elastic fibers. The parenchyma of both the lungs showed markedly diffuse hemorrhage with hemosiderin-laden alveolar macrophages or old thrombi and organized thrombi in the small bronchi. Furthermore, both sections of the lung showed multiple fibrous nodules containing benign metaplastic bone. Vascular wall disruption and tearing of the vessel walls in the lung parenchyma were also observed. We concluded that EDS type IV led to the patient's death because of pulmonary hemorrhage. Because this syndrome resulted in the patient's death from arterial and bowel rupture, it is important to consider EDS as a potential cause of sudden death.
Patients with Ehlers-Danlos syndrome type IV have thin-walled, friable arteries and veins. Invasive procedures carry a significantly increased risk for perforation of blood vessels. The aim of this case report is to demonstrate the feasibility and potential benefits of using a stereotactic magnetic navigation system (MNS) for mapping and ablation under these very special circumstances. A 45-year-old woman is presented with daily episodes of typical atrio-ventricular nodal re-entry tachycardias (AVNRT) and known Ehlers-Danlos syndrome type IV. Transcatheter ablation procedure of the AVNRT was undertaken using the MNS, with a non-traumatic single floppy catheter and the capability of advanced navigation.
Categorization of the Ehlers-Danlos syndromes began in the late 1960s and was formalized in the Berlin nosology. Over time, it became apparent that the diagnostic criteria established and published in 1988 did not discriminate adequately between the different types of Ehlers-Danlos syndromes or between Ehlers-Danlos syndromes and other phenotypically related conditions. In addition, elucidation of the molecular basis of several Ehlers-Danlos syndromes has added a new dimension to the characterization of this group of disorders. We propose a revision of the classification of the Ehlers-Danlos syndromes based primarily on the cause of each type. Major and minor diagnostic criteria have been defined for each type and complemented whenever possible with laboratory findings. This simplified classification will facilitate an accurate diagnosis of the Ehlers-Danlos syndromes and contribute to the delineation of phenotypically related disorders.
Ehlers-Danlos syndrome type IV, the vascular type, results from mutations in the gene for type III procollagen (COL3A1). Affected patients are at risk for arterial, bowel, and uterine rupture, but the timing of these events, their frequency, and the course of the disease are not well documented.
We reviewed the clinical and family histories of and medical and surgical complications in 220 index patients with biochemically confirmed Ehlers-Danlos syndrome type IV and 199 of their affected relatives. We identified the underlying COL3A1 mutation in 135 index patients.
Complications were rare in childhood; 25 percent of the index patients had a first complication by the age of 20 years, and more than 80 percent had had at least one complication by the age of 40. The calculated median survival of the entire cohort was 48 years. Most deaths resulted from arterial rupture. Bowel rupture, which often involved the sigmoid colon, accounted for about a quarter of complications but rarely led to death. Complications of pregnancy led to death in 12 of the 81 women who became pregnant. The types of complications were not associated with specific mutations in COL3A1.
Although most affected patients survive the first and second major complications, Ehlers-Danlos syndrome type IV results in premature death. The diagnosis should be considered in young people who come to medical attention because of uterine rupture during pregnancy or arterial or visceral rupture.
Categorization of the Ehlers-Danlos syndromes began in the late 1960s and was formalized in the Berlin nosology. Over time, it became apparent that the diagnostic criteria established and published in 1988 did not discriminate adequately between the different types of Ehlers-Danlos syndromes or between Ehlers-Danlos syndromes and other phenotypically related conditions. In addition, elucidation of the molecular basis of several Ehlers-Danlos syndromes has added a new dimension to the characterization of this group of disorders. We propose a revision of the classification of the Ehlers-Danlos syndromes based primarily on the cause of each type. Major and minor diagnostic criteria have been defined for each type and complemented whenever possible with laboratory findings. This simplified classification will facilitate an accurate diagnosis of the Ehlers-Danlos syndromes and contribute to the delineation of phenotypically related disorders. Am. J. Med. Genet. 77:31–37, 1998. © 1998 Wiley-Liss, Inc.
5th Ed Bibliogr. na konci kapitol
There is reason to believe that calcium influx into heart muscle during acute myocardial infarction (AMI) can aggravate myocyte injury. Furthermore, the degree of such influx might correlate with the occurrence of microscopic myocyte calcification observed at autopsy. We have searched for evidence of myocyte calcification in hearts of patients found to have AMI at autopsy at the Veterans Administration Medical Center in Salt Lake City (SLCVA), a region with a low myocardial infection death rate, and at the George Washington University Medical Center in Washington, DC (GWUMC), a region with a high myocardial infection death rate. Of 23 consecutive cases examined under "blind" conditions at the GWUMC in which AMI was found, there were 15 instances of cardiac myocyte calcification observed in von Kossa-stained sections. Not a single example of myocyte calcification was found in 23 comparable cases at the SLCVA. The basis of this difference in myocyte calcification is unknown, but may be related to the fact that the Salt Lake City drinking water contains a higher level of magnesium, which is known to protect against soft tissue calcification, than does that of Washington, DC. This may be the basis for the apparent protection that dietary magnesium exerts against myocardial infarction death.
Ehlers-Danlos syndrome (EDS) is a rare, genetically transmitted connective tissue disorder which occurs with an incidence of 1 in 5000. Nine subtypes of EDS have been identified, with type IV being associated with sudden death due to rupture of the bowel, uterus, or major blood vessels. We describe a case of a patient with type IV EDS who presented at 30 weeks' gestation with preterm labor which was treated with subcutaneous terbutaline followed by oral maintenance therapy. Approximately 72 hours later she suffered a myocardial infarction, which led to coronary artery dissection and death. This is the first case of type IV EDS in pregnancy that resulted in maternal death due to coronary artery dissection. We suggest that betamimetic tocolytics should be avoided in patients with EDS and preterm labor.
Type III collagen is a fibrillar forming collagen comprising three alpha1(III) chains and is expressed in early embryos and throughout embryogenesis. In the adult, type III collagen is a major component of the extracellular matrix in a variety of internal organs and skin. Mutations in the COL3A1 gene have been implicated as a cause of type IV Ehlers-Danlos syndrome, a disease leading to aortic rupture in early adult life. To directly study the role of Col3a1 in development and disease, we have inactivated the Col3a1 gene in embryonic stem cells by homologous recombination. The mutated allele was transmitted through the mouse germ line and homozygous mutant animals were derived from heterozygous intercrosses. About 10% of the homozygous mutant animals survived to adulthood but have a much shorter life span compared with wild-type mice. The major cause of death of mutant mice was rupture of the major blood vessels, similar to patients with type IV Ehlers-Danlos syndrome. Ultrastructural analysis of tissues from mutant mice revealed that type III collagen is essential for normal collagen I fibrillogenesis in the cardiovascular system and other organs.
The extracellular collagen matrix of the myocardium plays an important role in maintaining muscle fiber and cardiac alignment and ventricular shape and size. It also influences tissue and ventricle stiffness. This network consists of an organized hierarchy of collagen that is intimately associated with individual and groups of myocyte and muscle fibers, as well as the coronary vasculature. In renovascular and genetic hypertension, the hypertrophic response of the myocardium includes an increase in collagen concentration, thickening of existing fibrillar collagen, and addition of newly synthesized collagen to all of the matrix components. The consequences of this remodeling are a stiffer myocardium and left ventricular diastolic dysfunction. With removal of less than half of the normal amount of collagen the opposite occurs. That is, the ventricle dilates and there is an increase in ventricular compliance. Thus an abnormal accumulation of collagen is a major distinguishing factor between physiologic and pathologic hypertrophy while an abrupt decrease in collagen concentration results in a ventricular remodeling similar to that of a heart in failure.
Myocardial infarction in persons under the age of 45 years accounts for 6% to 10% of all myocardial infarctions in the United States. In this age group, it is predominantly a disease of men. Important risk factors include a family history of myocardial infarction before age 55 years, hyperlipidemia, smoking, and obesity. Unlike older patients, approximately half of young patients have single-vessel coronary disease, and in up to 20%, the cause is not related to atherosclerosis. Coronary angiography may be warranted in young patients with myocardial infarction to define the anatomy of the disease and to permit optimal management.
Lapatto-Reiniluoto O, Vaalamo M, Takkunen O, Mänttäri M (Helsinki University Central Hospital, Helsinki, Finland). Left ventricular calcification following resuscitation (Case Report). J Intern Med 2000; 248: 85–87.
In this paper we report a case of 34-year-old man with a severe septic shock. Because of profound hypotension he was given massive amounts of catecholamines for 10 days. After a short recovery the function of his heart started to deteriorate again and clear calcification around the left ventricle was disclosed by computer tomography. Catecholamines are known to induce myocardial injury resulting in a special form of cardiomyopathy with eventual calcification, but there are no previous reports of myocardial calcification to this extent.
Histology: a text and atlas
- Mh Ross
- Lj Romrell
- Gi Kaye
Ross MH, Romrell LJ, Kaye GI. Histology: a text and atlas. 3rd ed.
Philadelphia: Lippincott, Williams and Wilkins, 1995.
Harrison's principles of internal medicine
- D J Prockop
- H Kuivaniemi
- G Tromp
- L Ala-Kokko
- E Braunwald
- A Fauci
- D Kasper
- S Hauser
- D Longo
- J Jameson
Prockop DJ, Kuivaniemi H, Tromp G, Ala-Kokko L. Inherited disorders of connective tissue. In: Braunwald E, Fauci A, Kasper D, Hauser
S, Longo D, & Jameson J, editors. Harrison's principles of internal
medicine. 15th ed. New York: McGraw-Hill, 2001, 2290-300.