Pathophysiologic and clinical basis for classification of patients after acute myocardial infarct

Non-invasive stratification of patients after AIM represents the basic procedure in identification of patients at high risk of the origin of complications after AIM. It enables to tip a group of patients at the highest risk of the development of reinfarction, sudden cardiac death (SCD) or general cardiac mortality, i.e. the patients who can benefit the most from the early therapy. The presented review describes pathophysiological and clinical aspects of stratification of patients after acute myocardial infarction.     

Non-pharmacologic prevention of sudden cardiac death

Non-pharmacologic therapy has revolutionized the management of arrhythmias and prevention of sudden cardiac death (SCD). Of particular importance is the introduction of radiofrequent catheter ablation (RFCA) and implantable cardioverter-defibrillator (ICD). RFCA is effective and useful in the treatment and prevention of SCD, especially in supraventricular tachyarrhythmias related to dual or accessory atrioventricular pathways. There are some limitations in using this method in the prevention of SCD in ventricular tachyarrhythmias. RFCA is very successful, particularly in the treatment of bundle branch reentrant ventricular tachycardia and ventricular tachycardia in patients without structural heart disease. RFCA can be used as a palliative treatment of incessant or frequent VT before and after ICD implantation. Antibradycardia pacing decreases SCD not only by the removal of serious bradyarrhythmias but also by prevention of the occurrence of malignant ventricular tachyarrhythmias induced by bradyarrhythmia. Antitachycardia pacing is used in the prevention of SCD only as a part of ICD device. Implantation of an antitachycardia pacemaker as an isolated permanent treatment of tachycardias is currently almost not used. This method was replaced by RFCA in supraventricular tachyarrhythmias and by ICD in ventricular tachyarrhythmias. ICD is a very perspective non-pharmacologic approach to SCD prevention, particularly as transvenous leads were introduced and device construction was simplified. ICD is indicated especially in patients with spontaneous sustained hemodynamically significant ventricular tachycardia/ventricular fibrillation and when antiarrhythmic drug treatment, RFCA or antitachycardia surgery are ineffective, intolerated, contraindicated or cannot be performed. ICD as the treatment of first choice instead of antiarrhythmic drugs as well as prophylactic ICD implantation in asymptomatic patients at high risk is a subject of discussion. ICD decreases the incidence of SCD significantly. However, the decrease in overall mortality was not verified. Antitachycardia surgery is less frequently used after RFCA, and ICD have been introduced. At present, this therapy is reserved only for the cases of failure of RFCA or the impossibility to use RFCA and ICD. Surgical therapy can be combined also with concommitant surgical correction of associated structural heart disease. Sympathectomy is used in prevention of malignant ventricular tachyarrhythmias and SCD in patients with congenital long Q-T syndrome. Selective left cardiac sympathetic denervation significantly reduces the risk of SCD in these patients but does not remove it completely. Heart transplantation is the last alternative of non-pharmacologic prevention of SCD. It is indicated in cases when all pharmacologic and non-pharmacologic approaches have been exhausted. Heart transplantation is the only effective modality for the improvement of long-term prognosis in patients with malignant ventricular tachyarrhythmias and advanced chronic heart failure.     

Anti-arrhythmia agents in the prevention of sudden cardiac death after myocardial infarct

Heart rhythm disturbances represent one of the most important causes of cardiovascular mortality and, in particular, sudden cardiac arrhythmic death. The persistent actuality of arrhythmias is currently characterized by: 1) better knowledge of pathogenetic mechanisms of arrhythmias and their modulating factors, 2) improved diagnostic possibilities of arrhythmias, 3) availability of a large number of effective antiarrhythmics, as well as of nonpharmacologic therapeutic approaches too. Despite the narrowing spectrum of indications to pharmacologic treatment, both chronic and prophylactic antiarrhythmic therapies have nor become less complicated, but on the contrary they are even more problematic. The most actual and at the same time most controversial question of everyday clinical practice is the long-term antiarrhythmic prevention of sudden cardiac death. The author's aim is to review: 1) survey of studies which have influenced in a more decisive manner the management of patients after myocardial infarction and preventive antiarrhythmic therapy, 2) current antiarrhythmic prevention of sudden cardiac death, 3) the importance of programmed ventricular stimulation regarding the antiarrhythmic therapy and risk stratification in patients after myocardial infarction.     

Sudden cardiac death in patients with arterial hypertension and left ventricular hypertrophy on antihypertensive therapy

The hypertrophy of the left ventricle in patients with arterial hypertension is an independent risk factor which increases c 9 times the probability of sudden cardiac death. Despite the fact that the incidence of sudden cardiac death in patients with arterial hypertension is low, regarding the high occurrence of hypertension it represents a significant medical problem. The therapy of arterial hypertension is able to decrease the general and cardiovascular mortalities with significant interspecies characteristics of individual antihypertensive drugs, as well as to promote the regression of hypertrophy of the left ventricle. The therapy per se can however increase the risk of cardiovascular complications: until now the complication of the therapy by diuretics rich in potassium and beta-blockers are best distinguished. Calcium antagonists are effective antihypertensive drugs but they do not decrease the total mortality. ACE inhibitors have a marked antihypertensive effect and few adverse effects, but until now there is not a sufficient number of large prospective studies which would definitely confirm the preliminary promising findings. Despite the presented problems the cured patients with arterial hypertension have a substantially better prognosis than patients that are not being cured.     

Renaissance of beta blocker therapy in myocardial infarct

Beta-adrenergic blocking drugs have been evaluated for the treatment of arrhythmias and for the prevention of sudden cardia death, particularly in post-myocardial infarction patients. Betablockers have been demonstrated to reduce mortality, reinfarction, ventricular fibrillation and cardiac rupture in acute infarction. Therefore, in patients with suspected myocardial infarction and without contraindications, treatment with betablockers should be initiated early and continued for at least 2 years. Side-effects are mild and occur in approximately 10% of patients. Patients who have contraindications for betablockers use early in myocardial infarction should be reevaluated before discharge from the hospital and considered for such therapy. Because betablockers prevent some of the adverse arrhythmogenic mechanisms seen in chronic heart failure, it may be reasonable to expect that these drugs could have a role in preventing sudden cardiac death in these patients. Analysis of some of the betablocker post-infarction trials indicate that betablockers reduced the risk of sudden death in patients with heart failure at baseline. Some studies demonstrated also the symptomatic improvement following therapy with betablockers in patients with heart failure. But the currently available data are too limited to provide conclusive information.     

Sudden cardiac death: definition, mechanisms and risk factors

Sudden cardiac death is defined as natural death due to cardiac causes, heralded by abrupt loss of consciousness within one hour after the onset of symptoms. The mechanisms are the following: 1. ventricular fibrillation, 2. ventricular tachycardia and flutter with subsequent ventricular fibrillation, 3. torsade de pointe, 4. bradyarrhythmias and asystolic arrest. White the main risk factor is the presence of coronary artery disease, any organic or functional disease of the heart can predispose for sudden cardiac death. To evaluate the risk of sudden cardiac death noninvasive (Holter, echocardiography, exercise test and signal averaged (ECG) and often invasive (electrophysiological study) tests are necessary. The therapy is based on drugs (mainly beta blockers and amiodarone), coronary revascularization, catheter ablation techniques and the implantation of a cardioverter defibrillator; the latter appears to be the most promising approach.     

Sudden cardiac death--preventable--reversible

SCD is defined as unexpected death due to cardiac causes that occurs within 1 hour of acute symptoms. SCD can be reversed with the use of an ICD. These devices now can be implanted by catheter techniques, obviating thoracotomy. SCD is preventable. The incidence of SCD can be significantly reduced by addressing the fundamental pathophysiology of SCD, which primarily is CAD. Our combined and aggressive implementation of preventive regimens to reduce the risk of cardiac events will save lives. These measures include diet, weight reduction, smoking cessation, regular exercise, and therapeutic drugs. Amiodarone, although effective in preventing lethal ventricular arrhythmias, has not matched the long-term results of the ICD in the successful management of SCD.     

Antiarrhythmic therapies for the prevention of sudden cardiac death

Despite remarkable advances in cardiovascular therapeutics, sudden cardiac death remains a significant problem. In this review, data from clinical trials and other studies on antiarrhythmic therapies have been evaluated in order to determine effective strategies for the prevention of sudden cardiac death in high risk patients. Overall, routine prophylactic use of class I antiarrhythmic agents in high risk patients, mostly survivors of acute myocardial infarction, is associated with increased risk of death [61 trials, 23,486 patients: odds ratio (OR) 1.13; 95% confidence interval (CI) 1.01 to 1.27, p < 0.05]. Conversely, beta-blockers are associated with highly significant reductions in risk of death in postinfarction patients (56 trials, 53,521 patients: OR 0.81; 95% CI 0.75 to 0.87, p < 0.00001). Overall data from the amiodarone trials on high risk patients, including postinfarction patients, patients with congestive heart failure or survivors of cardiac arrest, suggest that this agent is effective in reducing the risk of death (14 trials, 5713 patients: OR 0.83; 95% CI 0.72 to 0.95, p = 0.01) although further studies are needed to better define which types of patients will potentially benefit most from this agent. No benefits were seen with calcium channel blockers (26 trials, 21,644 patients: OR 1.03; 95% CI 0.94 to 1.13, p = NS). The implantable cardioverter-defibrillator is a promising option for high risk patients, but definition of its role awaits the completion of ongoing clinical trials. Since causes of sudden death are heterogeneous, the clinician should pursue a multifactorial approach to its prevention. Primary and secondary prevention of cardiac ischaemia, through the treatment of cardiovascular risk factors and maximising the use of aspirin, beta-blockers, lipid-lowering drugs, and angiotensin converting enzyme inhibitors after acute myocardial infarction, should lead to a future decrease in the incidence of sudden cardiac death.     

Care: a value expressed in philosophies of nursing services

Mitral Valve Prolapse (MVP) is the most frequently diagnosed cardiac valvular abnormality. It is a primary disorder with familial occurrence. MVP is a disease of the young with a significantly higher incidence in women compared to men. The most characteristic clinical finding is a midsystolic click and late systolic murmur detected on cardiac auscultation. Two-dimensional echocardiography is the diagnostic tool of choice. 2D echo also helps in stratification of MVP patients at risk of developing serious complications. Although MVP runs a benign course in the majority of patients, significant complications may occur. These include progressive mitral regurgitation with heart failure, infective endocarditis, systemic emboli, cardiac arrhythmias, and rarely sudden death. The focus of therapy is reassurance and symptom relief when possible. It is important to recognize those patients that are at risk of developing significant complications, follow them closely, and intervene appropriately when complications occur.     

QT interval dispersion in healthy subjects and survivors of sudden cardiac death: circadian variation in a twenty-four-hour assessment

Twenty-four-hour acquisition of QT dispersion (QTd) from the Holter and the circadian variation of QTd were evaluated in 20 survivors of sudden cardiac death (SCD), in 20 healthy subjects, and in 14 control patients without a history of cardiac arrest who were age, sex, diagnosis and therapy matched to 14 SCD patients. Computer-assisted QT measurements were performed on 24-hour Holter recordings; each recording was divided into 288 5-minute segments and templates representing the average QRST were generated. QTd was calculated as the difference between QT intervals in leads V1 and V5 for each template on Holter. The 24-hour mean QTd was significantly greater in SCD patients (40 +/- 28 ms) than in healthy subjects (20 +/- 10 ms) and control patients (15 +/- 5 ms) (p <0.05). There was a circadian variation in QTd with greater values at night (0 to 6 A.M.) than at daytime (10 A.M. to 4 P.M.) in healthy subjects (25 +/- 13 vs 15 +/- 8 ms, p <0.001) and control patients (18 +/- 10 vs 12 +/- 4 ms p <0.05), whereas in SCD patients there was no significant difference between night and day values (45 +/- 31 vs 37 +/- 28 ms, p = NS). It is concluded that QTd measured by Holter was greater in SCD patients than in healthy subjects and matched control patients during the entire day. QTd has a clear circadian variation in normal subjects, whereas this variation is blunted in SCD patients. QTd measured on Holter differentiates survivors of cardiac arrest and may be a useful tool for risk stratification.     

Ventricular arrhythmias and sudden cardiac death in acute myocardial infarct in the era of thrombolytics

Sudden cardiac death (SCD) in the setting of acute myocardial infarction (AMI) remains an actual problem. There is a very close relationship between ventricular arrhythmias and SCD in AMI. Malignant ventricular arrhythmias, such as ventricular fibrillation and ventricular tachycardia are the major causes of SCD in coincidence with AMI. Frequent and complex ventricular arrhythmias are also important predictors of the risk of SCD in coincidence with and after AMI. In this article the authors emphasize the importance of the complexity of pathophysiological mechanisms responsible for the genesis of ventricular arrhythmias in coincidence with AMI. The necessity of taking into account the current knowledge about pathophysiology in prevention and therapy of separate forms of ventricular arrhythmias is also emphasized. The incidence and time course of ventricular arrhythmias and SCD in coincidence with AIM in prethrombolytic and thrombolytic periods is described. The importance of separate forms of ventricular arrhythmias in coincidence with AMI with regard to short and long-term prognoses is described. There are discussed also the possible mechanisms of thrombolytic and adjuvant therapies that affect the incidence and frequency of ventricular arrhythmias. The authors recommend the optimal therapy for each form of ventricular arrhythmia and the following management of patients with AMI. In the prevention and therapy of ventricular arrhythmias in the setting of AMI the authors emphasize the importance of early recanalization and prevention of re-occlusion of the infarction-related coronary artery. Great importance is attributed also to other adjuvant measures directed to the restriction of the size of infarction, myocardium protection, prevention and attenuation of remodelling of the left ventricle and thereby to the prevention of heart failure and attenuation of adverse effects of the sympathetic nervous system. An early administration of beta-blockers which favourable effect in and after AMI was documented with conclusive evidence is considered as one of the most important measures in prevention and therapy of malignant ventricular arrhythmias and SCD. The occurrence of malignant ventricular arrhythmias in the setting of heart failure and/or 24-48 hours after AMI should be an indication for aggressive management directed to arrhythmia (programmed ventricular stimulation, electrophysiologically guided pharmacologic or nonpharmacologic therapy) as well as to underlying coronary heart disease (coronary angiography and revascularization).     

Characterisation, utilisation and clinical relevance of isolated perfused heart models of ischaemia-induced ventricular fibrillation

The isolated perfused heart has been used increasingly during the last decade as a model for identifying actions of drugs on ventricular fibrillation (VF) induced by myocardial ischaemia. In addition, it has been used to explore the mechanisms responsible for the initiation and maintenance of VF, the concept of endogenous myocardial protection and the phenomenon of preconditioning. This article is a review of the available data (effects of drugs, sources of variation, comparison with other models and man, etc.) and an attempt to evaluate the possible clinical relevance. For several reasons, it is not possible to make a precise judgement on the absolute value of the model in terms of its ability to accurately predict the effectiveness of drugs in the prevention of sudden cardiac death, the main reason being the lack of a positive control, i.e. a drug with proven effectiveness against sudden cardiac death caused by VF in man. Nevertheless, the means by which one may reliably and reproducibly generate ischaemia-induced VF in different isolated heart preparations, and the factors (such as species, heart rate, perfusion constituents and involved zone size) that determine the incidence of VF are now well documented. Careful selection of species and experimental conditions permits the isolated heart of smaller inexpensive animals to function as a first line model for detecting anti-VF activity of probable relevance to phase 1 arrhythmogenesis (i.e., arrhythmogenesis during the first 30 min of ischaemia). In view of the absence of a clinical template from which to evaluate how well it predicts drug effectiveness in man, this model's clinical relevance, like that of all other preparations and models, can yet be neither accepted nor dismissed. Recent publication patterns suggest an increasing use of the model. Therefore, recommendations are made to facilitate its effective use.     

Sudden death in hypertrophic myocardiopathy]

Hypertrophic cardiomyopathy is the most common cause of sudden death in young individuals who are otherwise healthy. Risk of sudden death is highest in patients who are between 14 and 35 years old. Several mechanisms are involved in sudden death: ventricular arrhythmias, supraventricular arrhythmias leading to cardiac collapse, bradycardias and severe ischemia. Many studies have analyzed how to identify high risk patients. The factors that best identify high risk patients are: previous history of sudden death or syncope, induction in adults of sustained ventricular arrhythmias, the presence of non-sustained ventricular tachycardia in symptomatic patients, the presence of ischemia associated with hypotension in children, the presence of mutations in the beta-myosin heavy chain together with a family history of sudden death and a poor left ventricular ejection fraction. Risk stratification should be done on an individualized basis. In those patients in whom a high risk for sudden arrhythmic death is suspected, the only current effective treatment is the implantable defibrillator.     

The implantable cardioverter/defibrillator

Despite all advances in the diagnosis and therapy of cardiovascular diseases, the mortality from malignant ventricular tachyarrhythmias is still a major health problem. In addition to established therapeutic strategies in the prevention of sudden cardiac death such as antiarrhythmic drug treatment, catheter ablation or antiarrhythmic drug treatment, cardioverter/defibrillator was introduced to clinical practice in 1980. The number of 50,000 overall implants reflects the current clinical status of the therapy with implantable cardioverter/defibrillators. Significant technical improvements in the defibrillator therapy may contribute to an increase in therapy acceptance. These advances include the introduction of nonthoracotomy lead systems, enhanced defibrillation efficacy, full programmable devices providing tiered electrical therapy, improved diagnostic Holter functions and enhanced arrhythmia detection algorithms. The major present goals of defibrillator therapy are detection and termination of malignant ventricular tachyarrhythmias, prevention of sudden cardiac death, reduction in patient's mortality and improvement in quality of life. The efficacy and safety of defibrillator therapy to prevent sudden arrhythmic death has been proven in several large clinical investigations In patients with this device the annual sudden cardiac death mortality is < 2% even in high-risk patient populations. Compared to sudden cardiac death rate there is a much higher rate of overall cardiac mortality because a defibrillator is not able to prevent nonarrhythmic cardiovascular deaths. There is a clinical impression that cardiovascular mortality is lower in patients treated with an implantable cardioverter/defibrillator compared to patients treated with other therapies. However, there are no results from controlled studies providing scientific evidence that defribillator therapy can decrease overall cardiovascular mortality.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antiarrhythmic versus antifibrillatory actions: inference from experimental studies

Pathophysiology of the coronary circulation is a major contributor to altering the myocardial substrate, rendering the heart susceptible to the onset of arrhythmias associated with sudden cardiac death. Antiarrhythmic drug therapy for the prevention of sudden cardiac death has been provided primarily on the basis of trial and error and in some instances based on ill-suited preclinical evaluations. The findings of the Cardiac Arrhythmia Suppression Trial (CAST) requires a reexamination of the manner in which antiarrhythmic drugs are developed before entering into clinical testing. The major deficiency in this area of experimental investigation has been the lack of animal models that would permit preclinical studies to identify potentially useful or deleterious therapeutic agents. Further, CAST has emphasized the need to distinguish between pharmacologic interventions that suppresses nonlethal disturbances of cardiac rhythm as opposed to those agents capable of preventing lethal ventricular tachycardia or ventricular fibrillation. Preclinical models for the testing of antifibrillatory agents must consider the fact that the superimposition of transient ischemic events on an underlying pathophysiologic substrate makes the heart susceptible to lethal arrhythmias. Proarrhythmic events, not observed in the normal heart, may become manifest only when the myocardial substrate has been altered. We describe a model of sudden cardiac death that may more closely simulate the clinical state in humans who are at risk. The experimental results show a good correlation with clinical data regarding agents known to reduce the incidence of lethal arrhythmias as well as those showing proarrhythmic actions.     

Corticosteroid therapy in cardiac sarcoidosis

Corticosteroid treatment of cardiac sarcoidosis is not conclusive, although sarcoid granulomas in the heart may be more responsive to steroid therapy than in other organs. Healing of sarcoidosis lesions in the heart results in fibrosis and sinning of the myocardium, which may lead to aneurysm formation causing congestive heart failure or sudden death. Congestive heart failure is the leading cause of death in patients with cardiac sarcoidosis in Japan. It is reasonable to initiate steroid therapy as soon as the diagnosis of cardiac sarcoidosis is established in order to prevent fibrosis. Early initiation of steroid therapy with conventional treatment for specific cardiac manifestations (antiarrhythmic therapy, pacemaker implantation and heart failure medication) should bring improvement in the left ventricular systolic and diastolic function with prevention from malignant arrhythmias. Systemic disorder represents a contraindication to organ transplantation, but heart transplantation is now a feasible treatment for patients with end-stage cardiac sarcoidosis with congestive heart failure.     

Inositolphosphoglycans possibly mediate the effects of glucagon-like peptide-1(7-36)amide on rat liver and adipose tissue

Cardiac disorders are increasingly recognised as an important source of cerebral embolism. Atrial fibrillation is the most common cardiac dysrrhythmia that can predispose to stroke. Recent advances have significantly increased the identification of clinical, hematological and echocardiographic risk factors that predict the occurrence of atrial fibrillation related stroke. Also, clinical risk stratification has been used to determine medical therapy (aspirin or warfarin) for prevention of atrial fibrillation related brain embolization. Among the various structural heart diseases causing stroke, the role of patent foramen ovale remains controversial. Strides have been made in the use of ultrasonographic techniques such as transesophageal echocardiography and contrast transcranial doppler to detect patent foramen ovale. Coronary artery bypass grafting is often performed in patients with concomitant aortic atheroma and carotid stenosis that may predispose to stroke in the perioperative period. It is now possible to identify perioperatively significant aortic atherosclerosis (using transesophageal echocardiography and aortic ultrasound) and significant carotid disease (using carotid ultrasound) and make appropriate modifications in surgical technique to reduce the incidence of coronary artery bypass grafting related stroke. Because of shared risk factors it is not surprising that coronary artery disease is frequently found in stroke patients. Recent studies suggest that more than one-third of stroke patients have asymptomatic coronary artery disease. Conversely, the brain damaged by infarction may itself be responsible for the production of cardiac structural and electrical abnormalities. Both these factors may contribute to the finding that cardiac events are the leading cause of death in stroke patients on long term follow-up. Recognition of these correlations has enhanced our ability to treat and prevent stroke related mortality.     

Implantable cardioverter-defibrillator therapy for prevention of sudden cardiac death

Patients with known symptomatic VT or VF are at high risk for sudden cardiac death. Various therapeutic choices can be used to reduce the incidence of arrhythmic sudden cardiac death. These include beta-blockers, class I and III antiarrhythmic agents, VT focal ablations, and ICD therapy. The overall incidence of sudden cardiac death in ICD recipients is less than 2% per year, a rate of survival not achieved with any of the available antiarrhythmic agents. VT surgical therapy can produce comparable survival results, but the minimal operative mortality is higher than that with ICD therapy. In patients with noninducible VT/VF or inducible polymorphic VT, and in those refractory to or intolerant of antiarrhythmic agents and poor left ventricular function, ICD therapy may be the only realistic option.     

Optimizing resuscitation outcomes with pharmacologic therapy

Pharmacologic therapy plays a key role in the emergency resuscitation of patients with cardiac arrest. The Advanced Cardiac Life Support guidelines sanctioned by the American Heart Association provide flexible treatment protocols (algorithms) that serve as a valuable tool for clinicians. Vasoactive (vasopressive) therapy with epinephrine is of primary importance in all patients with nonperfusing rhythms (for example, ventricular fibrillation [VF], pulseless ventricular tachycardia [VT], electromechanical dissociation [EMD], and asystole) because it raises myocardial and cerebral perfusion pressures, thereby increasing the likelihood of successful resuscitation. Antiarrhythmic drugs play a secondary role to electrocardioversion in the treatment of VF and pulseless VT. Despite continued investigation and recent advances in our understanding of the role of drugs and other therapeutic interventions, the short-term and long-term prognoses of patients with cardiac arrest, especially out-of-hospital arrest, remain dismal. Clearly, much study into the prevention and treatment of sudden cardiac death is desperately needed.     

Treatment of paroxysmal ventricular tachycardia]

The authors present a retrospective evaluation of the risk stratification and therapy of 53 patients with ventricular tachycardia. They present the diagnostical algorithm used for the detection of risk of sudden death. The most frequently used drug in the set of patients was amiodarone in monotherapy or in combination with other drugs. Sotalol was used for both, its antiarrhythmic nature, and for its ability to reduce the defibrillation threshold in patients with an implanted automatic implantable cardiovertor-defibrillator (AICD). Antiarrhythmic drugs of class I in monotherapy were used in patients with non-coronary causes of ventricular tachycardia and with normal left ventricular function. The authors, on the basis of sudden death of three patients with low ejection fraction of the left ventricle which were recorded even despite Holter apparatus and electophysiologically confirmed supression of ventricular tachycardia, recommend to consider in this group of patients the primary AICD implantation. (Tab. 4, Fig. 2, Ref. 13.)