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PubMed1985

Endomyocardial biopsy.

Endomyocardial biopsy is an accepted, useful invasive tool for the analysis of human endomyocardium at the cellular and subcellular levels. It is applicable in the evaluation of specific diseases including cardiac allograft rejection, myocarditis, anthracycline cardiotoxicity, and infiltrative cardiomyopathies. The procedure can be performed in a cardiac catheterization room on an outpatient basis. The technique is quite safe when performed by trained cardiologists. Left ventricular biopsies are also safe but require systemic heparinization to prevent thromboembolization. The clinical indications for performing an endomyocardial biopsy include routine followup and suspected rejection of cardiac allograft, suspected myocarditis, monitoring or diagnosis of suspected anthracycline cardiotoxicity, and suspected secondary cardiomyopathies. Left ventricular endomyocardial biopsy is indicated for diseases that predominantly involve the left side of the heart, including left heart irradiation, cardiac fibroelastosis in infants, endomyocardial fibrosis, and scleroderma heart disease, and when right ventricular biopsy is unsuccessful. Endomyocardial biopsy is increasingly being used for research in the areas of tissue biochemistry, primary and valvular cardiomyopathies, immunology, beta receptor enzymology, drug interactions, and myocardial fibrosis. Endomyocardial biopsy has not been shown to be clinically useful in the evaluation of primary, dilated, hypertrophic, or alcoholic cardiomyopathies. These disease processes all lack pathognomomic microscopic abnormalities, and subclassification has neither been successful nor therapeutically useful. In addition, this technique is limited in diagnosing any cardiac abnormality that is not diffuse, inasmuch as only a few samples of the endomyocardial layer are obtained for evaluation. Therefore, a negative biopsy result is not 100 percent specific in excluding certain diseases. A further limitation of this technique is the need for an experienced cardiac pathologist who is well versed in interpretation of biopsy specimens. Finally, there should be a sufficiently large case load to train and to maintain skilled practitioners so that the procedure can be performed with little risk. The role of endomyocardial biopsy will continue to expand as research continues to find more uses for the technique and as more clinicians become skilled in its use.

Antibiotics, Antineoplastic↗
PubMed1991

Rationale and design of a secondary prevention trial of lowering normal plasma cholesterol levels after acute myocardial infarction: the Cholesterol and Recurrent Events trial (CARE)

Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol decreases the incidence of coronary heart disease in patients with elevated plasma cholesterol. However, it is not known whether patients with established coronary artery disease and normal plasma cholesterol can be benefited. Several previous prevention trials reviewed in this report found that patients who had plasma cholesterol levels at baseline in the upper portion of the eligibility range (e.g., greater than 240 mg/dl) received greater benefit from hypolipidemic diet or drug therapy than patients who had lower plasma cholesterol levels at baseline. The recent availability of drugs that are more potent and less prone to cause adverse reactions than previous regimens permits this important question to be addressed. The Cholesterol and Recurrent Events trial is testing whether pravastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, will decrease the sum of fatal coronary heart disease and nonfatal myocardial infarction (MI) in patients who have recovered from a MI and who have normal total cholesterol levels. Fatal cardiovascular disease and total mortality are important secondary end points. The trial is enrolling 4,000 men and women from 80 centers throughout North America, age 21 to 75 years, who have survived MI for 3 to 20 months, who have plasma total cholesterol less than 240 mg/dl (6.2 mmol/liter) and low-density cholesterol of 115 to 174 mg/dl (3.0 to 4.5 mmol/liter), and who are representative of the general population of patients with MI. Patients are randomized to either active or inactive drug therapy. Active therapy consists of pravastatin, 40 mg/day, designed to achieve an average decrease in low-density lipoprotein cholesterol of approximately 30%, and an increase in high-density lipoprotein of 5%. The average duration of follow-up will be greater than or equal to 5 years. To protect against a lower than expected rate of recurrent events, the trial will be continued until a predetermined fixed number of coronary heart disease events occurs in the entire cohort so that the original sensitivity of the trial will be maintained.

Adult↗
PubMed2000

[Aspirin and prevention of cardiovascular risk].

PURPOSE: Aspirin, a potent platelet inhibitor, is widely used in patients with cardiovascular diseases. Platelet aggregation is the cornerstone of acute atherothrombotic complications. ACTUALITIES: Aspirin showed significant benefits when administered in patients with acute myocardial infarction or unstable angina, and also when used for secondary prevention in patients with known coronary artery disease. Aspirin has been evaluated in primary prevention, with interesting results in high-risk patients. Finally, aspirin can be used in some patients with supraventricular arrhythmias or with mechanical valves. PERSPECTIVES: Further investigation concerning the exact role of aspirin in primary prevention is currently being done. The association of aspirin with new antiplatelet agents in patients with acute coronary syndromes has shown interesting results.

Angina Pectoris↗
PubMed1998

Significance of development of late potentials after anterior wall acute myocardial infarction despite successful primary angioplasty of the left anterior descending coronary artery.

We classified 33 patients with a first anterior infarction and single-vessel disease who had undergone successful primary angioplasty and had a patent infarct-related artery into groups based on the development of late potentials. Left ventricular function improved between 1 and 3 months after angioplasty only in patients without late potentials; the development of late potentials after acute anterior infarction was associated with prolonged left ventricular dysfunction despite successful revascularization with primary angioplasty.

Aged↗
PubMed1995

Long-term effect of gemfibrozil on coronary heart disease risk profile of patients with primary combined hyperlipidaemia.

BACKGROUND: The purpose of the present study was to assess the effect of gemfibrozil on 12 independent coronary heart disease risk factors in patients with primary combined hyperlipidaemia. METHODS: One hundred and five patients (62 men and 43 women), aged 53.2 +/- 4.8 years, were studied. The 10-year probability of myocardial infarction for the patients was calculated using the TYPMI (Ten-Year Probability for Myocardial Infarction) computer program, which is constructed to co-evaluate 12 independent coronary artery disease risk factors. All patients followed a lipid-lowering diet and placebo for 3 months. At month 0, the patients received 1200 mg gemfibrozil daily, divided into two equal doses, for a period of 12 months. At months -3, 0, 1, 3, 6, and 12, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides [only if the low-density lipoprotein (LDL) cholesterol to high-density lipoprotein cholesterol ratio was above 5], systolic blood pressure, plasma glucose, left ventricular mass index, and plasma fibrinogen were measured. Smoking habits, sex, age, physical activity and family history of coronary heart disease were also evaluated. The mean 10-year probability of myocardial infarction of all 105 patients at month 0 was 27.8%. This was significantly higher than the anticipated probability (10.4%, P < 0.001), resulting from an age- and sex-matched group of general population. RESULTS: During the third month of treatment, the following changes were recorded: total cholesterol -17%, LDL cholesterol -18%, very-low-density lipoprotein (VLDL) cholesterol -45%, HDL cholesterol 20%, triglycerides -43%, apoprotein B -12%, apoprotein A-I 9% and plasma fibrinogen -21%. The estimated risk for myocardial infarction was reduced to 13.5% (delta m = -51%). All changes were significant and sustained until the twelfth treatment month. None of the patients were withdrawn from the study because of adverse effects of the treatment. CONCLUSION: Gemfibrozil reduces the estimated risk for myocardial infarction in patients with primary combined hyperlipidaemia at a level no different from the one of the general population. This beneficial effect of gemfibrozil, which was expressed by the third month and was evident for some time afterwards, was attributed to a significant reduction of triglyceride and fibrinogen levels, an increase of HDL cholesterol concentrations and a moderate decrease of total cholesterol and LDL cholesterol levels.

Coronary Disease↗
PubMedDate not supplied

Measurement and management of hyperlipidemia for the primary prevention of coronary heart disease.

BACKGROUND: As part of the National Cholesterol Education Program (NCEP) two expert panel reports (1988, 1993) recommend serum cholesterol measurements in all adults aged 20 years and older and cholesterol-lowering treatment for those with abnormal levels. METHODS: All major drug intervention trials for primary prevention of coronary heart disease were reviewed. Similarly, selected studies on risks of dyslipidemia and benefit of therapy for the elderly and for women without coronary heart disease were analyzed. These studies were evaluated to test the soundness of the NCEP panel's recommendations. RESULTS AND CONCLUSIONS: Five major randomized drug intervention trials for primary prevention of coronary heart disease showed that cholestyramine, gemfibrozil, clofibrate, and pravastatin can reduce the rate of nonfatal myocardial infarctions in middle-aged men. All-cause and ischemic heart disease mortality were increased by clofibrate and unaffected by the other three drugs. Extrapolation of these findings to women and older and younger men is unwarranted because there is no evidence that either diet or drugs provide primary protection from coronary heart disease in these groups. It is uncertain whether dyslipidemia is a risk factor for coronary heart disease in the elderly. The annual cost of drugs for full implementation of the panel's recommendations ranges from $6 billion to $11.5 billion and an additional $13 billion will be required for initial screening, classifying, and monitoring serum cholesterol levels. Potential adverse consequences of a national program include possible risks from low cholesterol levels, drug side-effects, and disease labeling.

Adult↗
PubMed1976

Unstable angina pectoris.

Unstable angina is a syndrome which comprises a spectrum of symptomatic manifestations of coronary artery disease which lies between stable angina pectoris and acute myocardial infarction. Patients fall into three groups: angina of recent onset (4 weeks), angina of changing pattern, and angina occurring at rest (longer than 15 minutes). The syndrome may presage acute myocardial infarction or sudden death, or may itself be the manifestation of a myocardial infarction. The pathophysiology may involve primary cardiac events or extracardiac precipitating factors, and does not appear to be the consequence of a particular anatomic pattern of coronary artery disease. Pain may occur as a result of regional reduction of coronary flow to pressure-dependent areas of myocardium during states of increased myocardial oxygen demand. Persisting ischemia leads to infarction via a series of events which may include myocardial edema formation, increased beta-sympathetic tone, and others which have been experimentally modified by interventions designed to limit infarct size. Although the incidence of acute myocardial infarction and death was high in early studies, in recent reports acute infarction occurs in under 15.5 per cent and death in under 2 per cent. Patients at high risk are those pain persists with bed rest, and those with preceding stable angina pectoris or myocardial infarction. Prognostic differences among Groups 1, 2, and 3 may exist but cannot be assessed from available studies. Studies of the management of unstable angina have generally been uncontrolled. Hospitalization, bed rest, and short- and long-acting nitrates are generally employed in Groups 2 and 3 patients and the marked reduction in myocardial infarction rates from early to recent studies tends to support these approaches. Anticoagulants are less used now than formerly. Propranolol can produce a significant reduction of myocardial oxygen consumption and may redirect coronary flow to ischemic areas. The drug has effectively controlled pain in several studies and is now widely used to manage unstable angina. Aortocoronary bypass surgery has been extensively employed but there is only one preliminary report of a controlled study available. The role of surgery is not yet defined. The optimal approach to therapy may eventually involve the use of medical therapy, including beta-blockade to stabilize patients, with delayed semielective coronary angiography and surgery in those who respond. Emergency angiography and surgery might then be reserved for the high-risk group of patients whose pain persists during optimal medical therapy.

Angina Pectoris↗
PubMed1981

[Left ventricular relaxation in myocardial diseases. Hemodynamic study].

Left ventricular relaxation as opposed to contraction, was studied by recordings of left ventricular pressure and its first derivation in primary hypertrophic cardiomyopathy without obstruction (25 cases, Group II) in primary dilated cardiomyopathy (33 cases, Group III) and in normal subjects (22 cases, Group I). Simultaneous recording of the pressure, the first derivation and intraventricular and intraaortic phonocardiogrammes showed the significance of certain features of the tracings and allowed a simplified protocol: ventricular relaxation was then defined from the pressure tracing (high fidelity recording) and its first derivation. The onset of isovolumic relaxation corresponded to the point of inflection on the descending part of the first derivation tracing, preceding its negative peak by an average of 0.02 s. The end of isovolumic relaxation corresponded to the crossing point of the atrial and ventricular pressure curves. In the absence of atrial pressure tracings the initial part of the rapid filling phase was included as far as the return of the first derivation tracing to its baseline (early diastole on the ventricular pressure tracing) as the duration of this period seemed remarkably constant (0.07 s). The parameters studied were: duration of isovolumic relaxation or the period defined above including the rapid filling phase; the average rate of fall of left ventricular pressure during this part of diastole; the value of the negative peak of the first derivation (dp/dt min); the rate of lengthening of the contractile elements at minimum dp/dt (dp/dt min/28P). Changes in relaxation were obvious in the pathological groups. The duration was increased and its average speed, dp/dt min, and dp/dt min/28 P were reduced. In the hypertrophic group, however, these changes seemed to be primary and contractility was usually unaffected. In dilated cardiomyopathy these changes could be considered secondary to decreased contractility. The hypothesis that changes in relaxation are specific for hypertrophic forms, and that changes in contractility are specific for dilated forms of primary cardiomyopathy may therefore be proposed.

Adolescent↗
PubMed1999

Clinical epidemiology of acute myocardial infarction.

In the United States by mid-century, cardiovascular disease accounted for more than half of all deaths. In the second half of this century, 85% of reduction in age-adjusted mortality rates from all causes can be ascribed to the decline in death from cardiovascular disease and stroke. Approximately half of such dramatic decline in mortality rates from ischemic heart disease (IHD) can be explained by primary and secondary prevention and half by therapeutic improvements. Epidemiology of therapeutic regimens in acute myocardial infarction (AMI) indicates substantial increases in the use of thrombolytic therapy, aspirin, beta-blockers and, in some countries, coronary angioplasty. The long-term results of several thrombolytic trials have shown the persistence of early benefit until 10 years after AMI. However, approximately half of the patients with AMI are admitted to the hospital too late to fully benefit from thrombolytic therapy, and one fourth of eligible patients do not receive any form of reperfusion. Primary angioplasty is advocated by some as the treatment of choice in AMI. The present results are not convincing enough to induce the enormously complex and costly reorganization of the health system, allowing the immediate access to coronary angiography for all or most patients with AMI. However, stenting the infarct coronary artery at the site of previous occlusion appears to improve the immediate and medium-term results of coronary revascularization procedures. Approximately half of the AMI survivors are rehospitalized within 1 year after the index event, and postinfarction mortality rate remains exceedingly high. After AMI, prognostic and therapeutic procedures have been introduced in the absence of evidence from controlled trials of their effectiveness profile. Outcome research is needed to standardize effective post-AMI policies. Moreover, new strategies are needed to reduce the incidence and mortality rates of acute ischemic events. A number of new candidate risk factors for IHD are emerging; they are associated with endothelial dysfunction, thrombogenic state, and inflammatory state. It is hoped that advances in molecular approach to cardiovascular disease, molecular genetics and transgenic techniques will allow better understanding and more effective therapeutic strategies to prevent and control IHD.

Angioplasty, Balloon, Coronary↗
PubMed2006

High risk of cardiovascular disease in patients with type 1 diabetes in the U.K.: a cohort study using the general practice research database.

OBJECTIVE: To estimate the absolute and relative risk of cardiovascular disease (CVD) in patients with type 1 diabetes in the U.K. RESEARCH DESIGN AND METHODS: Subjects with type 1 diabetes (n = 7,479) and five age- and sex-matched subjects without diabetes (n = 38,116) and free of CVD at baseline were selected from the General Practice Research Database (GPRD), a large primary care database representative of the U.K. population. Incident major CVD events, comprising myocardial infarction, acute coronary heart disease death, coronary revascularizations, or stroke, were captured for the period 1992-1999. RESULTS: The hazard ratio (HR) for major CVD was 3.6 (95% CI 2.9-4.5) in type 1 diabetic men compared with those without diabetes and 7.7 (5.5-10.7) in women. Increased HRs were found for acute coronary events (3.0 and 7.6 in type 1 diabetic men and women, respectively, versus nondiabetic subjects), coronary revascularizations (5.0 in men, 16.8 in women), and for stroke (3.7 in men, 4.8 in women). Type 1 diabetic men aged 45-55 years had an absolute CVD risk similar to that of men in the general population 10-15 years older, with an even greater difference in women. CONCLUSIONS: Despite advances in care, these data show that absolute and relative risks of CVD remain extremely high in patients with type 1 diabetes. Women with type 1 diabetes continue to experience greater relative risks of CVD than men compared with those without diabetes.

Adult↗
PubMed2000

Pharmacotherapy following myocardial infarction--a review of current treatment practices.

Modern treatment of acute myocardial infarction (AMI), including thrombolysis and early interventional strategies, has reduced mortality rates but increased the number of patients requiring medical treatment. Post infarction treatment with aspirin, statins, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors has improved morbidity and mortality and is cost-effective. The major successes of secondary prevention have been seen in the prevention of reinfarction, recurrent ischaemia and the development of heart failure. However, in spite of recent advances and increasing knowledge, the mortality rates remain high, partly due to the under use of the established and documented medical strategies. Implementation of the current treatment strategies into general practice remains a challenge. The field is undergoing rapid change due to the increasing use of early invasive strategies. The primary objective should remain the prevention of underlying aetiology: coronary artery disease (CAD). Secondary prevention following myocardial infarction (MI) will remain a major challenge in clinical practice within the foreseeable future.

Adrenergic beta-Antagonists↗
PubMed1995

[Serum C3 as a screening factor in the primary prevention of myocardial infarct].

This study addresses the possible use of serum C3 (third component of the complement system) to select the subjects to be submitted to diet or drug therapy in the primary prevention of myocardial infarction. C3 is synthesized by macrophages, which are the main cells involved in atheroma formation, and an association between serum C3 and the risk of myocardial infarction has recently been found in the male sex. We have studied 332 men aged 45-75 years, who had no cardiovascular disease at any time before blood sampling. In their sera C3 measurement was performed by nephelometry. The 4 year follow-up was known for all of these subjects: in particular, 11 had a myocardial infarction. The average LDL cholesterol (LDL-C) levels in the whole population were rather high (162.2 +/- 45.8 (1 SD) mg/dl). As standard treatment criteria (A), those suggested for primary prevention by the National Cholesterol Education Program panel of experts were adopted: diet if LDL-C > or = 160 mg/dl, or LDL-C > or = 130 mg/dl + 2 additional risk factors; drugs if, after diet, LDL-C > or = 190 mg/dl, or LDL-C > or = 160 mg/dl + 2 risk factors. This scheme was compared with two models of treatment which included the measurement of serum C3. According to the first of such models (B), diet should be prescribed when C3 levels are within the high third of distribution (> or = 135 mg/dl) with LDL-C > or = 100 mg/dl, and drugs should be given if, after diet, serum C3 is > or = 135 mg/dl with LDL-C > or = 130 mg/dl. The second model based on C3 (C) is of combined type since, in addition to model B criteria, it also suggests to prescribe a diet if LDL-C > or = 190 mg/dl, while drugs should be given if, after diet, LDL-C levels persist > or = 190 mg/dl. The effect of diet has been simulated by assuming a 10% decrease in LDL-C levels. According to all of these criteria, the subjects to treat with diet with the models A, B and C would have been, respectively, 71, 27 (p < 0.0001 vs mod A) and 45% (p < 0.0001 vs mod A) of the whole population, including among them, respectively, 82, 82 and 100% of the future myocardial infarctions. After diet, according to the three models A, B and C -29, 20 (p = 0.0117 vs mod A) and 30% of the whole population should have been treated with drugs, including, respectively, 54, 64 and 82% of the future myocardial infarctions. In conclusion, the use of criteria based on serum C3, with respect to more traditional guidelines, might allow a more precise identification of the subjects to submit to diet and drug treatment in the primary prevention of myocardial infarction.

Aged↗
PubMed2001

Advanced glycation endproducts: activators of cardiac remodeling in primary fibroblasts from adult rat hearts.

BACKGROUND: Cardiovascular diseases are the leading cause of death in the Western world, especially in the elderly. Myocardial fibrosis induced by activated cardiac fibroblasts is thought to play a key role in the pathogenesis of cardiovascular disease. Accumulation of advanced glycation endproducts (AGEs), products of nonenzymatic glycation of proteins, correlate with the stiffness of the heart and large vessels. To elucidate a potential role of AGEs as a trigger of fibrosis, the effects of AGEs on primary fibroblasts from hearts of adult rats were investigated. MATERIAL AND METHODS: The activation of intracellular signaling pathways was shown by Western blotting. In addition, the expression of genes of the extracellular matrix proteins, metalloproteases (MMPs), their inhibitors, and TGF-beta were analyzed by semiquantitative PCR. Activation of MMPs were controlled by Zymography. RESULTS: It was shown that treatment of cardiac fibroblasts with AGEs leads to an activation of different signaling molecules, such as the p38MAP-kinase, the extracellular regulated kinases (ERKs), the jun kinase (JNK), as well as transcription factors like ATF-2 and NF-kappaB. In addition, the expression and activation of MMP-2, MMP-9, and MMP-13 were induced, which may be responsible for tissue remodeling followed by fibrosis. CONCLUSION: Due to their effects on the expression and activation of metalloproteases, AGEs should be regarded as a potential therapeutic target for the prevention of pathologic remodeling.

Animals↗
PubMed2003

Usefulness of 1H MR spectroscopy in the evaluation of myocardial metabolism in patients with dilated idiopathic cardiomyopathy: pilot study.

RATIONALE AND OBJECTIVES: Primary dilated cardiomyopathy is a disease of unknown etiology, and it leads to severe heart failure. Abnormalities of the cardiac metabolism can play an important role in prognosis and influence the symptomatology in this group. The aim of this study was to assess cardiac metabolism using proton spectroscopy magnetic resonance (1H MRS) and to examine whether there is any correlation between cardiac metabolites and functional New York Heart Association (NYHA) class and left ventricular function parameters obtained in echocardiography. MATERIALS AND METHODS: Fifteen patients with documented idiopathic dilated cardiomyopathy and 12 healthy volunteers were examined. The study protocol included clinical examination, 12-lead electrocardiogram, two-dimensional echocardiogram, and 1H MRS with voxel localized at interventricular septum area. The contents of total creatine (CR) ie, creatine + phosphocreatine, lipids (LIP), lactates (LAC) and their ratios (CR1A, CR2A, CR1/H20, CR2/H20, CR2/CR1, LIPA, LIP/H20, LIP/CR1, LACA, LAC/H20, LAC/CR1) were examined. RESULTS: Patients with dilated cardiomyopathy had significantly lower levels of creatine CRIA (5.04 +/- 0.88 vs 5.94 +/- 1.15, P < .02) and ratios LIP/H20 (4.34 +/- 2.3 vs 15.46 +/- 20.39, P < .04) and LIP/CR1 (24.49 +/- 21.26 vs 34.08 +/- 13.36, P < .05) compared with healthy volunteers. Significant correlations between NYHA functional class and the ratios CR2/CR1, CR2/H20 (r = 0.59, P < .038, r = 0.59, P < .02, respectively) and between %LVEF and LIP/CR1 (r = 0.64, P < .036), as well as between the duration of the disease (TCH) and LIP/CR1 (r = 0.67, P < .046) were found. CONCLUSION: A pilot study with proton spectroscopy magnetic resonance showed impairment of the cardiac metabolism in patients with idiopathic dilated cardiomyopathy. A trend to lower values of creatine and lipids, and to lower ratios of some of these metabolites was observed in the dilated cardiomyopathy group compared with healthy subjects. The results require further study.

Adult↗
PubMed2004

The role of aspirin in cardiovascular diseases--forgotten benefits?

The increasing burden of cardiovascular diseases in developed, as well as developing countries, underscores the need for the more widespread and appropriate use of aspirin in secondary prevention of occlusive vascular events during acute evolving myocardial infarction (MI) and in primary prevention. Aspirin should be far more widely used in a wide range of patients who have suffered a prior occlusive vascular event and in all patients suffering acute MI or occlusive stroke. Finally, in primary prevention, aspirin should be considered for individuals whose 10-year risks of a coronary event are > or = 10%, as an adjunct not alternative to the management of other risk factors. The more widespread and appropriate use of aspirin will avoid many premature deaths in secondary prevention and MIs in primary prevention.

Aspirin↗