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PubMed2005

An isoform shift in the cardiac adenine nucleotide translocase expression alters the kinetic properties of the carrier in dilated cardiomyopathy.

BACKGROUND: Impaired mitochondrial ADP/ATP transport and altered adenine nucleotide translocase (ANT) isoform expression characterized by enhanced ANT1 and decreased ANT2 expression have been implicated in the pathophysiology of dilated cardiomyopathy (DCM). It is still unknown whether restricted ANT function results from exogenous factors, or mutations in the ANT genes, or whether the imbalance in the isoform composition causes the reduced ADP/ATP transport. We performed DNA mutation screening of ANT genes and analyzed the kinetic properties of ANT protein isolated from DCM hearts and controls in a reconstituted system excluding natural environmental influences. RESULTS: A G1409T polymorphism in ANT2 leads to an exchange from Arg111 to Leu111 in healthy blood donors (n = 60) with allele frequencies of 76% and 24%. This polymorphism was neither associated with DCM (74%, 26%; n = 93) nor with altered myocardial ANT isoform expression or restricted ANT function (89%, 11%; n = 8). However, there was a remarkable reduction in the maximum transport activity (v(max)) of reconstituted ANT from DCM hearts with altered ANT isoform expression (498 +/- 113 micromol min(-1) g(-1) incorporated protein vs. 1112 +/- 178 micromol min(-1) g(-1) incorporated protein, p < 0.01). Moreover, the substrate affinity of DCM myocardial ANT to ATP was slightly reduced with an increased K(m) value of 104.3 +/- 2.4 microM vs. 90.4 +/- 2.9 microM in controls (p < 0.03). CONCLUSION: The altered isoform expression in DCM hearts entails changes in the kinetic properties of total ANT protein restricting ANT function and contributing to disturbed energy metabolism in DCM.

Adenine Nucleotide Translocator 1↗
PubMed2003

Inhibition of cardiac myocyte apoptosis improves cardiac function and abolishes mortality in the peripartum cardiomyopathy of Galpha(q) transgenic mice.

BACKGROUND: Although the occurrence of cardiac myocyte apoptosis during heart failure has been documented, its importance in pathogenesis is unknown. Transgenic mice with cardiac-restricted overexpression of Galpha(q) exhibit a lethal, peripartum cardiomyopathy accompanied by apoptosis. To test whether apoptosis is causally linked to heart failure, we assessed whether inhibiting this cell death would improve left ventricular function and survival in the Galpha(q) peripartum cardiomyopathy model. METHODS AND RESULTS: The potent polycaspase inhibitor IDN-1965 or vehicle was administered subcutaneously to Galpha(q) mice by osmotic minipump beginning on day 12 of pregnancy and continuing through euthanasia at day 14 postpartum. As expected, IDN-1965 markedly suppressed cardiac caspase-3-like activity (86.5%; P<0.01), accompanied by reduction in the frequency of cardiac myocyte apoptosis from 1.9+/-0.3% to 0.2+/-0.1% (P<0.01). Animals receiving IDN-1965 exhibited significant improvements in left ventricular end-diastolic dimension (vehicle, 4.7+/-0.1 mm; IDN-1965, 4.2+/-0.1 mm; P<0.01), fractional shortening (vehicle, 30.7+/-1.2%; IDN-1965, 38.9+/-1.0%; P<0.01), positive (vehicle, 3972+/-412; IDN-1965, 5870+/-295; P<0.01) and negative (vehicle, 2365+/-213; IDN-1965, 3413+/-201; P<0.01) dP/dt, and complete suppression of mortality (vehicle, 6 of 20 died; IDN-1965, 0 of 14 died; P<0.05). CONCLUSIONS: Reduction in cardiac myocyte apoptosis by caspase inhibition improved left ventricular function and survival in pregnant Galpha(q) mice. These data indicate that cardiac myocyte apoptosis plays a causal role in the pathogenesis of cardiomyopathy in this model. Caspase inhibition may provide a novel therapeutic target for heart failure.

Animals↗
PubMed1978

Treatment of congestive cardiomyopathy.

Although the majority of patients with cardiomyopathy are in the category of primary or idiopathic cardiomyopathy, for which therapy is symptomatic and non-specific, there are a number of secondary forms of cardiomyopathy for which specific therapy is available, thus giving impetus to prompt and accurate diagnosis. Among inflammatory lesions, brucellosis, psittacosis and toxoplasmosis are examples. Treatable metabolic causes include thyrotoxicosis and thiamine deficiency, the latter as well as calorie-protein malnutrition are also preventable. There is presumptive evidence that the cardiomyopathy of haemochromatosis is benefited by repeated phlebotomies. Symptomatic relief of obstructive cardiomyopathy is achieved by beta-adrenergic blockade, although resection of obstructing myocardium still has a place. The therapeutic approach to the vast majority of cases of congestive cardiomyopathy is non-specific, comprising controlled activity, sodium restriction, digitalis and diuretics. Vasodilators and, occasionally, beta-adrenergic blockade may be beneficial. Pacemakers may be life-saving, whereas the place of anti-arrhythmics remains uncertain. Transplantation warrants further application. Valve replacement has little to offer. Primary prevention, comprising balanced nutrition, vaccines and genetic counselling, merits wider application. In individuals at risk or already afflicted, programmes of secondary prevention should include good nutrition, abstinence from alcohol and protection from drugs and toxins.

Cardiomyopathies↗
PubMed1991

[Charcot-Marie-Tooth disease associated with dilated cardiomyopathy: an autopsy case report].

This is a clinical report of a rare case of Charcot-Marie-Tooth disease associated with dilated cardiomyopathy. A seventy-seven-year-old Japanese male first visited our outpatient clinic with a ten-year history of muscular weakness in his bilateral lower extremities and gait disturbance characterized by classical features of peroneal muscular atrophy and inverted champagne bottle legs. Biopsy findings of the m. quadriceps femoris and the n. gastrocnemius revealed clustered atrophy of myofibrils and segmental demyelinization mingled with remyelinization. Because of his other problem of dilated cardiomyopathy, he had been treated with salt restriction, digitalis, diuretics and vasodilators, until his third hospitalization, when he developed terminal stage of severe congestive heart failure. Despite our intensive cardiac care, the patient died because of profound pump failure. Autopsy findings disclosed a remarkably dilated left ventricular chamber and an increased total heart weight of 600 grams. Grossly, the cross sectional view of the left ventricle revealed diffuse, but not homogenous fibrosis that was most prominent in the posterior wall. On light microscopic examination, the left ventricular myocardium revealed diffusely scattered muscular degeneration interlaced with fibrosis. Although large epicardial coronary arteries revealed only mild intimal atheromatous thickening, most of the small intramuscular coronary arteries were free from atherosclerosis. Neither diabetic nor amyloid lesions could be detected. It has been well known that cardiomyopathy is often associated with various forms of muscular dystrophy and Friedreich's ataxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrophy↗
PubMed1988

[Echocardiography methods in the diagnosis of cardiomyopathies in children].

We investigated 59 children with cardiomyopathy (CMP) by echocardiographic methods (ECHO). 29 children with dilated CMP showed typical enlargement of the left ventricle 159 +/- 31%, xxx; (% of normal value +/- SD) and of the left atrium (143 +/- 27%, xxx). Systolic and diastolic function of the left ventricle were decreased, systolic change in size of the left ventricle % delta D = 16 +/- 7%; xxx; systolic change in area of the left ventricle % delta A = 20 +/- 8%; xxx; maximum filling rate of the left ventricle in the phase of quick filling E max = 0.37 +/- 0.09 m. sec-1, xxx; the percentage of filling in the first third of diastole 0.33 DA = 37 +/- 9%, xx. Mitral insufficiency was found by us in 81% of children. In 25 children with hypertrophic CMP the size of left ventricle was decreased (81 +/- 13%, xxx). Asymmetric septal hypertrophy was found by us in 69% of children, symmetric hypertrophy in 27%, local hypertrophy of the apex in 4%. Systolic function of the left ventricle was increased (% delta D = 47 +/- 10%, xxx; % delta A = 70 +/- 10%, xxx). Diastolic dysfunction manifested itself by reduced E max (0.71 +/- 0.19 m.sec-1, xx) and 0.33 DA (45 +/- 12%, x). Mitral insufficiency was found in 54% of the children. In the case of the 5 children with restrictive CMP an extreme enlargement of left atrium (195 +/- 41%, xxx) was typical, as well as diastolic dysfunction of the left ventricle (0.33 DA = 67 +/- 6%, x).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1999

Familial dilated cardiomyopathy: evidence for genetic and phenotypic heterogeneity. Heart Muscle Disease Study Group.

OBJECTIVES: This study was performed to evaluate the characteristics, mode of inheritance and etiology of familial dilated cardiomyopathy (FDC). BACKGROUND: A genetic form of disease transmission has been identified in a relevant proportion of patients with dilated cardiomyopathy (DCM). Variable clinical characteristics and patterns of inheritance, and an increased frequency of cardiac antibodies have been reported. An analysis of FDC may improve the understanding of the disease and the management of patients. METHODS: Of 350 consecutive patients with idiopathic DCM, 281 relatives from 60 families were examined. Family studies included clinical examination, electrocardiography, echocardiography and blood sampling. Of the 60 DCM index patients examined, 39 were attributable to FDC and 21 were due to sporadic DCM. Clinical features, histology, mode of inheritance and autoimmune serology were examined, molecular genetic studies were undertaken and the difference between familial and sporadic forms was analyzed. RESULTS: Only a younger age (p = 0.0005) and a higher ejection fraction (p = 0.03) could clinically distinguish FDC patients from those with sporadic DCM. However, a number of distinct subtypes of FDC were identified: 1) autosomal dominant, the most frequent form (56%); 2) autosomal recessive (16%), characterized by worse prognosis; 3) X-linked FDC (10%), with different mutations of the dystrophin gene; 4) a novel form of autosomal dominant DCM with subclinical skeletal muscle disease (7.7%); 5) FDC with conduction defects (2.6%), and 6) rare unclassifiable forms (7.7%). The forms with skeletal muscle involvement were characterized by a restrictive filling pattern; the forms with isolated cardiomyopathy had an increased frequency of organ-specific cardiac autoantibodies. Histologic signs of myocarditis were frequent and nonspecific. CONCLUSIONS: Familial dilated cardiomyopathy is frequent, cannot be predicted on a clinical or morphologic basis and requires family screening for identification. The phenotypic heterogeneity, different patterns of transmission, different frequencies of cardiac autoantibodies and the initial molecular genetic data indicate that multiple genes and pathogenetic mechanisms can lead to FDC.

Adolescent↗
PubMed1990

[The causes and mechanisms of death in cardiomyopathies].

The author presents a retrospective and complex pathomorphological analysis in 152 autopsy cases. Death was caused by different forms of cardiomyopathies. Aim of the study to reveal the frequency of pathology, causes and mechanisms of death. The prevailing frequency of dilated cardiomyopathy was established--106 cases, 0.88%. Hypertrophic and restrictive forms--32 (0.27%) and 14 (0.12%) of cases. the dominating cause of death (42.7%) was chronic cardiac failure. Other death causes were as follows: thrombosis and embolism--17.8%; arrhythmic collapse--13.2%; ventricular fibrillation--9.9%; acute left-ventricular failure--8.6%; real cardiogenic shock--7.8% of all cases of cardiomyopathies.

Adult↗
PubMed2006

Factors associated with establishing a causal diagnosis for children with cardiomyopathy.

OBJECTIVE: The goal was to identify the clinical variables associated with establishing a cause of cardiomyopathy in children. METHODS: The Pediatric Cardiomyopathy Registry contains clinical and causal testing information for 916 children who were diagnosed as having cardiomyopathy in North America between 1990 and 1995. Children with a causal diagnosis were compared with those without with respect to several demographic, clinical, and causal testing variables. RESULTS: Cardiomyopathy was 1 of 4 types, hypertrophic (34.2%), dilated (53.8%), restrictive (3.2%), or other or mixed (8.9%). Only one third of cases had a known cause. Children with a known cause for hypertrophic cardiomyopathy were more likely to be female, to be relatively smaller, to present with congestive heart failure, and to have increased left ventricular posterior wall thickness without outflow tract obstruction. For dilated cardiomyopathy, a known cause was associated with older age, lower heart rate, smaller left ventricular dimensions, and greater shortening fraction. Family history of cardiomyopathy predicted a significantly higher rate of causal diagnoses for all cardiomyopathy types, whereas family histories of genetic syndromes and sudden death were also predictive of a cause for hypertrophic and dilated cardiomyopathies. For hypertrophic cardiomyopathy, only blood and urine testing was associated with a causal diagnosis, whereas both viral serologic testing or culture and endomyocardial biopsy were independent predictors of a causal diagnosis in dilated cardiomyopathy. CONCLUSIONS: Certain patient characteristics, family history, echocardiographic findings, laboratory testing, and biopsy were associated significantly with establishing a cause of pediatric cardiomyopathy. Early endomyocardial biopsy should be considered strongly for children with dilated cardiomyopathy, for definitive diagnosis of viral myocarditis. Although not widely used, skeletal muscle biopsy may yield a cause for some patients with hypertrophic cardiomyopathy and for patients suspected of having a mitochondrial disorder.

Biopsy↗
PubMed2025

Granulopoietic Dysregulation in a Patient-Tailored Mouse Model of Barth Syndrome.

Barth syndrome (BTHS) is an X-linked recessive disorder characterized by cardiomyopathy, skeletal muscle myopathy and fatigue, growth restriction, and neutropenia. Neutropenia increases the risk of life-threatening bacterial infections, a major cause of death in individuals with BTHS. Currently, there is no curative treatment for BTHS or associated neutropenia. The development of therapeutic strategies to correct BTHS-associated neutropenia has been hindered by a limited understanding of the underlying molecular mechanisms involved. BTHS is caused by a mutation in the Tafazzin gene encoding a transacylase required for the maturation of cardiolipin, an inner mitochondrial membrane phospholipid crucial for mitochondrial structure and function. We introduced a BTHS patient's point mutation (TAZD75H) into the mouse Tafazzin enzyme's critical acyltransferase site using CRISPR/Cas9-mediated genome editing, resulting in a patient-tailored point mutant knock-in BTHS model (TazD75H) that expresses a stable mutant TazD75H protein lacking transacylase activity. TazD75H&#xa0;mice were then used to investigate how loss of Tafazzin enzymatic activity impacts hematopoiesis. Male TazD75H mice exhibited impaired granulopoiesis and neutropenia secondary to impaired function of hematopoietic progenitors. Furthermore, they demonstrated age-dependent neutrophil maturation impairment reflecting the variable neutropenia observed in BTHS patients. Additionally, male TazD75H mice exhibit chronic lymphopenia that persists post TazD75H bone marrow transplantation. Mechanistically, the TAZD75H point mutation caused hematopoietic cell mitochondrial dysfunction in patient-derived immortalized TAZD75H lymphoblasts, increasing reactive oxygen species production and mitochondrial membrane depolarization. Likewise, Cyclosporine A treatment rescued these mitochondrial phenotypes in vitro, confirming TAZD75H mitochondrial dysfunction. Overall, our findings demonstrate that mitochondrial dysfunction secondary to TAFAZZIN loss of enzymatic function underlies BTHS-associated neutropenia and lymphopenia.

Animals↗
PubMed2004

First experiences with a novel magnetically suspended axial flow left ventricular assist device.

UNLABELLED: Axial flow pumps have gained increased acceptance since their first clinical use in 1998. The present report summarizes the clinical experience with patients treated for severe cardiogenic shock for the first time with a newly developed axial flow pump with magnetically levitated bearings. MATERIAL AND METHODS: The axial flow pump Incor was implanted in 24 patients between June 2002 and June 2003. All except one patient were men. In 16 patients dilative cardiomyopathy, in seven ischemic and in one restrictive cardiomypathy had been diagnosed. All patients presented with catecholamine-dependent end-stage heart failure, seven of them were on an artificial ventilator and three were dependent on intraaortic balloon pump support. All patients suffered from organ dysfunction resulting from low cardiac output. RESULTS: There were no perioperative deaths. The 30-day mortality rate was 8% (n = 2); 79% ( n = 19) of patients reached a condition to be discharged home. The cumulative time on the device is 6.9 years; the longest individual time up to July 1, 2003 is 12.6 months. There were no structural defects or failures of the system. In one case the controller had to be exchanged because of intermittent malfunction. Cardiac output ranged between 4 and 6 l in all instances and there were no cases of infection of the drive-line or the system. Hemolysis was present initially but was not detectable in the later course. There were three instances of transient ischemic attacks. Two patients developed late cardiac tamponade with re-opening of the chest after 9 and 14 days. In one patient persistent gastrointestinal bleeding required re-hospitalization and transfusion therapy. Two patients were weaned from the device after 6 and 7 months of support, respectively. CONCLUSION: The preliminary clinical experience with Incor is promising. The flow is sufficient for recovery from multiorgan failure and the pump allows long-term hemolysis-free support. The concept of magnetically levitated bearings has proven to be durable and reliable. In the case that the heart may recover through unloading, weaning from the pump is possible.

Adult↗
PubMed2000

Exercise in Heart Failure: A Synthesis of Current Research.

Exercise intolerance, as a hallmark symptom in patients with heart failure, has been the focus of numerous research initiatives in recent years. The purpose of this review is to synthesize the current literature in order to provide the clinician with an understanding of the state of knowledge regarding the role of exercise in treatment of heart failure. Many studies speak to the effect of exercise training in this population. While sample sizes have been small and restricted predominantly to male subjects with ischemic cardiomyopathies, strong support has been documented in favor of beneficial effects of exercise in heart failure. Future research should target more representative subject pools (i.e., females, non-ischemic cardiomyopathies, cultural minorities, frail elderly, and NYHA class IV), evaluation of impact on quality of life outcomes, exploration of different types and intensity of exercise, and formulation of specific activity prescription tools which can guide practitioners in making activity and/or exercise recommendations to those patients who have no access, or limited access, to cardiac rehabilitation programs.

Journal Article↗
PubMed2003

[Functional assessment of patients with hypertrophic cardiomyopathy by maximal oxygen consumption].

INTRODUCTION AND OBJECTIVES: Differences between anatomical severity and clinical manifestations are frequent in patients with hypertrophic cardiomyopathy. Our objective was to assess functional capacity in a consecutive group of patients with hypertrophic cardiomyopathy measuring exercise aerobic parameters, as well as clinical and echocardiographic variables. PATIENTS AND METHOD: We studied 98 consecutive patients with hypertrophic cardiomyopathy. All patients underwent both echocardiographic and cardiopulmonary exercise testing. The control group consisted of 22 untrained persons. We studied exercise capacity by analyzing maximal oxygen consumption and aerobic functional capacity, among other variables. RESULTS: Patients with hypertrophic cardiomyopathy attained significantly lower maximal oxygen consumption values than controls (24.1 5.9 vs 36.4 5.9 ml/kg/min; p = 0.0001). Maximal aerobic capacity was significantly different among patients with NYHA functional capacity class I, II or III (78.9 13.5%; 71.9 14.7%; 63.9 15.7%; p = 0.009). However, considerable overlap was found between groups in maximal aerobic capacity. Functional impairment was greater in patients with left ventricular thickness > 20 mm, ejection fraction < 50%, left atrial dimension > 45 mm and pseudonormal or restrictive transmitral flow pattern. CONCLUSIONS: Patients with hypertrophic cardiomyopathy show significant functional impairment, which is difficult to detect from their clinical manifestations. Optimal assessment requires cardiopulmonary exercise testing.

Adult↗
PubMed1996

Stroke normalized pressure: a useful parameter for the analysis of left ventricular outflow obstruction.

A new method of presenting the in vivo left ventricular pressure-flow data is developed in the present study. This separates left ventricle ejection into unrestricted, progressively restricted and severely restricted cases. This method uses ejection volume and time to define a normalizing 'stroke' pressure, which is successful in collapsing the large variability of in vivo data to a few curves with characteristic shapes, depending on the degree of obstruction. Hypertrophic cardiomyopathy is shown to fall into both unrestricted and progressively restricted categories. Normal hearts form the unrestricted case, while a severe aortic valvular stenosis is characteristic of the severely restricted case.

Aortic Valve Stenosis↗
PubMed2006

Measuring mechanical function in the failing heart.

A common pathology in heart failure is a detrimental change in the mechanics of both contraction and filling. In familial hypertrophic cardiomyopathy, a genetic disease characterized by left ventricular hypertrophy and myofiber disarray, left ventricular diastolic dysfunction is common and contributes to congestive heart failure. In dilated cardiomyopathy, a common correlate to reduced wall thickening and increased chamber volume is an asynchronous activation of the left ventricle due to left bundle branch block. Local measures of the timing and magnitude of myocardial shortening and relaxation can be obtained with magnetic resonance (MR) tissue tagging, MR cine phase contrast, or MR cine displacement encoding. In familial hypertrophic cardiomyopathy, these methods have been shown to quantify the restrictive filling of the ventricle. Characterizing the regions of the failing heart which are activated late has allowed investigators to measure the change in protein expression in those regions compared to normal myocardium. Also, these MR imaging methods have led to a better quantification of the asynchronous activation in dilated cardiomyopathy, which can be used to predict response to resynchronization therapy with pacing.

Adult↗
PubMed1998

Changes in protein kinase C in early cardiomyopathy and in gracilis muscle in the BB/Wor diabetic rat.

Hyperglycemia can upregulate protein kinase C (PKC), which may be an important mediator of the progression from normal heart and muscle function to diabetic myopathy in the myocardium and skeletal muscle in type 1 insulin-dependent diabetes mellitus (IDM). We evaluated this possibility during the early stage of IDM in BB/Wor diabetic (D) rats and age-matched BB/Wor diabetes-resistant (DR) rats. Interventricular septal thickness, E wave peak velocity of tricuspid inflow (both minimum and maximum), and left ventricular (LV) weight index were increased, and the rate of change in LV pressure (LV dP/dt) decreased in D rats subjected to M-mode and two-dimensional echocardiography and hemodynamic recording of heart rate, LV pressure (LVP), + LV dP/dt, -LV dP/dt, and LV end-diastolic pressure (LVEDP) in vivo and in vitro 41 days after the onset of hyperglycemia. Whole ventricle basal PKC activity was increased by 44.4 and 18.4% in the particulate and soluble fractions, respectively, from D rats compared with that from DR rats using r-32P phosphorylation of appropriate peptide substrates. When measured by Western blot gel densitometry, particulate PKC-alpha and PKC-delta content increased by 89 and 24%, respectively, but soluble PKC-beta and soluble and particulate PKC-epsilon were unchanged compared with that of DR rats. Similarly, gracilis muscle PKC activity and PKC-alpha and PKC-delta were elevated in the gracilis muscle, whereas that of the circulating neutrophil did not differ between the D and DR rats. Thus, in vivo, the early diabetic cardiomyopathy of the D rat is characterized by a restrictive LV with increased septal thickness and is associated with elevated PKC activity and increased amounts of myocardial particulate PKC-alpha and PKC-delta, which are also seen in the skeletal muscle. We conclude that increased PKC isozymes may play a pivotal role during IDM in the development of diabetic cardiomyopathy and skeletal muscle myopathy.

Animals↗
PubMed1990

Degenerative, non-atherosclerotic cardiovascular disease in the elderly: a clinico-pathological survey.

Cardiovascular disease, the major cause of death in the elderly, is mostly ascribable to complications of coronary atherosclerosis: angina pectoris, myocardial infarction, and sudden death. However, other degenerative diseases involving several cardiac structures exist, and should be distinguished from age-related cardiac changes. Extensive dystrophic calcification determines aortic stenosis, and may affect either a normally tricuspid or a congenitally bicuspid valve. Surgical valve replacement is now a low risk option, even in elderly persons, whereas the efficacy of balloon valvuloplasty is questionable. Aortic incompetence in adults and aged persons is mostly the consequence of aortic tunica media atrophy with anular ectasia, in the setting of nearly normal aortic leaflets. Mitral valve prolapse is the main cause of mitral incompetence; spontaneous cordal rupture is a late complication in the natural history of this disease, thus warranting prompt surgical valve repair or replacement. The entire spectrum of cardiomyopathies is observed in the elderly: dilated, hypertrophic, restrictive, arrhythmogenic. Cardiac amyloidosis is by far the most frequent secondary form and leads to congestive heart failure by impairing ventricular compliance. Idiopathic fibrosis of the specialized AV junction or dystrophic calcification of central fibrous body are the usual substrates of AV block, which requires pace-maker implantation. Nonrheumatic atrial fibrillation, due to fibro-fatty degeneration of the atrial musculature or dilated left atrium, carries a high risk of thromboembolic complications and cerebral accidents; oral anticoagulants have proven to be effective in preventing stroke. Aortic dissecting aneurysm is a spontaneous laceration, and usually a complication of longstanding systemic hypertension; exceptionally, spontaneous dissection may primarily occur in the coronary arteries. In conclusion, longevity at present is mostly threatened by cardiovascular disease, among which the role of degenerative, non-atherosclerotic disorders may be greater than thought.

Aged↗