How long should angiotensin-converting enzyme inhibitors be given to patients following myocardial infarction: implications of the HOPE trial

Long-term treatment with angiotensin-converting enzyme inhibitors reduces post-infarction morbidity and mortality in patients with left ventricular (LV) systolic dysfunction or symptomatic heart failure. Until recently, the effect of such treatment in patients with preserved LV function has not been known. The results from the Heart Outcome Prevention Evaluation trial have indicated that long-term treatment with ramipril leads to a significant reduction in cardiovascular events in patients with atherosclerotic disease, including those with prior myocardial infarction and preserved LV function. These results suggest that long-term angiotensin-converting enzyme inhibition should also be considered in post-infarction patients with normal cardiac function.     

Statement of the ad hoc committee on the laboratory diagnosis of infectious and serum hepatitis.

A prospective study was carried out to determine the prognostic factors in patients with second-degree and complete heart block following acute myocardial infarction and to re-examine the indications for artificial transvenous pacing. Of the 117 consecutive patients with proved acute myocardial infarction, 15 developed advanced heart block (second degree and complete). The presence of the following factors, either alone or in combinations, were attended with poor prognosis: preceding Stokes-Adams syndrome, cardiogenic shock, congestive heart failure, complications secondary to cardiac arrest, anterior infarction and wide QRS complex. In the nine cases requiring artificial transvenous pacemaker because of Stokes-Adams attacks, congestive heart failure or frequent multifocal ventricular ectopic beats, there were five deaths. The remaining six patients, who were without complications and were not paced, all survived; these patients had normal QRS duration with heart rates above 60 per minute. This study indicates that prophylactic transvenous catheter insertion in acute heart block does not appear justified unless specific indication(s) arise. Postmortem studies revealed significant narrowing of all the major coronary vessels in all five fatalities. The overall mortality in this series of cases of acute heart block was 33%.     

Cardiac predictors of death after non-cardiac surgery evaluated by intention to treat.

Cardiac risk factors were studied among patients who were admitted to hospital with appendicitis or a fracture of the proximal femur less than one year after being admitted with myocardial infarction. Of 99 patients with myocardial infarction and appendicitis, 87 underwent appendicectomy; and of 221 with myocardial infarction and hip fracture, 179 were operated on. The patients were studied on an intention to treat basis. The mortality within one month was 9% and 16% respectively. A history of congestive heart failure was the dominating risk factor, while ischaemic heart disease (recent myocardial infarction or angina pectoris) had no independent association with mortality. If the ventricular function is known additional preoperative information about the heart is of negligible value when estimating the mortality of non-cardiac surgery.     

Hemodynamic monitoring in acute myocardial infarction.

The main cause of in-hospital death in patients with acute myocardial infarction is the "power failure syndrome". Hemodynamic monitoring provides precise and current data on the filling and output status of the left ventricle and, when indicated, the right ventricle. The information obtained is used to determine the hemodynamic status more precisely than is possible from conventional clinical assessment. It permits categorization of patients by hemodynamic status; the hemodynamic subset classification of Forrester, Diamond and Swan is a powerful tool in guiding therapy and establishing prognosis in individual patients. In addition to guiding the initiation of therapy, hemodynamic monitoring is useful in the continuing assessment of potent and complex treatment. This therapy is directed at resolving hemodynamic derangements without unfavourably altering the myocardial oxygen supply-demand relationship. Specific clinical indications for hemodynamic monitoring may include confusing or complicated clinical situations in which diagnostic problems exist, complicating mechanical derangements, severe congestive heart failure, cardiogenic shock and clinical research in acute myocardial infarction.     

Cardiac Monitoring in a Community Hospital—Analysis of 18 Months' Experience

Cardiac monitoring facilities have been present in teaching hospital centers for over five years. A substantial decrease in mortality has been observed in monitored patients with acute myocardial infarction. The community hospital system offers a challenge to effective monitoring since many physicians care for patients and often many kinds of therapy are used.After 18 months of operation mortality from myocardial infarction was only 16.6 percent in a community hospital monitoring unit where the majority of the emergency care and resuscitation was carried out by nurses. Vital to this success was the use of standing orders for nurses, requirement of privilege to practice within the monitoring facility and acceptance of the nurse as a therapist in emergency situations.Fourteen patients were successfully resuscitated and were later discharged from the hospital. Four of them had ventricular fibrillation from digitalis intoxication.Patients with shock and severe congestive heart failure continue to be a major unsolved clinical problem. The results indicate that the potentially viable patient with serious electrical disturbances can almost invariably be salvaged.     

Central sleep apnoea syndrome in chronic heart failure: an underestimated and treatable comorbidity

Chronic heart failure is a clinical syndrome with a high mortality and morbidity. Despite optimal therapy, five-year survival is still only 50%. Central sleep apnoea syndrome is seen in approximately 40% of patients with congestive heart failure. Sleep apnoea syndrome can be divided into two forms in these patients: obstructive sleep apnoea syndrome (OSAS) and central sleep apnoea syndrome (CSAS, Cheyne-Stokes respiration), of which CSAS is the most common. CSAS is a form of sleep apnoea in congestive heart failure which is driven by changes in pCO₂. As a consequence of apnoea-hypopnoea an imbalance in myocardial oxygen delivery/consumption ratio will develop, sympathetic and other neurohormonal systems will be activated and right and left ventricular afterload will be increased. Sleep apnoea is associated with an increased mortality in patients with systolic heart failure. Treatment of sleep apnoea increases left ventricular ejection fraction and transplant-free survival. Because of its high prevalence, poor quality of life, poor outcome, and the beneficial effects of treatment, physicians treating patients with heart failure should be aware of central sleep apnoea. There are different treatment options, but the exact effects and indications of each option have not yet been fully determined. Further studies should be done to further investigate its prevalence, and to establish the most adequate therapy for the individual patient. (Neth Heart J 2010;18:260-3.)     

Improvements in clinical outcomes with the use of angiotensin-converting enzyme inhibitors: cross-fertilization between clinical and basic investigation

The expanding clinical indications for the use of angiotensin-converting enzyme (ACE) inhibitors during the past three decades to reduce cardiovascular morbidity and mortality across a broad spectrum of cardiovascular diseases have been the consequence of impressively productive interchanges between basic science and clinical medicine. In some areas, the initial discovery from animal investigations produced the hypotheses that were confirmed and expanded in patients with specific disease processes. In the development of ACE inhibitors, there are also important examples where an unexpected discovery from clinical trials spurred a host of laboratory investigations that uncovered novel mechanisms to underpin the clinical observations. Although developed as an antihypertensive agent, these effective interchanges, termed "translational research," have collectively produced convincing data to demonstrate that ACE inhibitors can and should be used to slow progression of renal disease, prevent and treat heart failure, attenuate adverse left ventricular remodeling after myocardial infarction and improve prognosis, reduce atherosclerotic complications in patients with coronary artery disease, and, even more recently, reduce the incidence of Type II diabetes.     

Mechanical circulatory support

Currently, almost five million Americans and 23 million people worldwide are living with congestive heart failure (CHF), with 2 million new cases diagnosed each year. The etiology is mostly ischemic, idiopathic, or viral, and more than $36 billion is spent each year on the care of congestive heart failure patients. Treatment of advanced CHF takes three forms: medical therapy, surgical therapy and cardiac replacement. Medical therapy, including inotropes and vasodilators, relieves symptoms by reducing cardiac work and increasing myocardial contractility. This has helped improve quality of life, but mortality remains unaffected. Surgical therapy, including revascularization, ventricular restoration and valve replacement/repair, relieves symptoms and improves function, but in most cases does not stop the underlying disease process from progressing. When conventional medical or surgical therapies are exhausted, cardiac assist or replacement, including ventricular assist device (VAD), heart transplant or a total artificial heart (TAH) may become the only therapeutic options. This article will not discuss the use of extracorporeal membrane oxygenation for cardiac support that is described in an additional article in this issue of Organogenesis.     

Specificity of Serum Creatine Kinase Isoenzymes in Diagnosis of Acute Myocardial Infarction

A study of the diagnostic value of serum creatine kinase (CK) isoenzymes showed that MB isoenzyme, which characterizes heart tissue, was a specific and sensitive indicator of acute myocardial infarction. In cases where the clinical picture was complicated by ventricular tachycardia, severe congestive failure, shock, or resuscitation procedures heart, liver, and muscle enzymes were increased. There was also an increase in lactate dehydrogenase isoenzyme values in these cases; indeed, the only enzyme test that correlated well with electrocardiographic and necropsy findings was the MB isoenzyme.     

Mechanical Complications of Myocardial Infarction—Radiologic Aspects

Left ventricular aneurysm, interventricular septal defect and acute mitral valve incompetence due to papillary muscle damage are three mechanical complications which cause intractable heart failure following myocardial infarction. In each case surgical intervention can result in dramatic improvement of congestive heart failure.A hemodynamically significant left ventricular aneurysm enlarges the cardiac silhouette and frequently causes a localized protrusion as seen radiographically. Cardiac fluoroscopy will disclose an abnormal pulsation of the left ventricular border. The left ventricular angiogram establishes the diagnosis, reveals the extent of the aneurysm and may disclose a filling defect in the aneurysmal sac due to the presence of mural thrombus. Coronary arteriography shows occlusion of a major vessel, most commonly the anterior descending branch of the left coronary artery.Ischemic perforation of the interventricular septum and acute mitral incompetence due to severe papillary muscle damage both cause severe heart failure shortly after myocardial infarction. A similar pansystolic murmur accompanies both conditions, and differentiation between the two is rarely possible on the basis of the electrocardiogram or x-ray film of the chest. Ventricular cardiac catheterization and left ventricular angiocardiography are required for a correct diagnosis.     

Role of echocardiography in diagnosis and risk stratification in heart failure with left ventricular systolic dysfunction

Congestive heart failure with preserved left ventricular systolic function has emerged as a growing epidemic medical syndrome in developed countries, which is characterized by high morbidity and mortality rates. Rapid and accurate diagnosis of this condition is essential for optimizing the therapeutic management. The diagnosis of congestive heart failure is challenging in patients presenting without obvious left ventricular systolic dysfunction and additional diagnostic information is most commonly required in this setting. Comprehensive Doppler echocardiography is the single most useful diagnostic test recommended by the ESC and ACC/AHA guidelines for assessing left ventricular ejection fraction and cardiac abnormalities in patients with suspected congestive heart failure, and non-invasively determined basal or exercise-induced pulmonary capillary hypertension is likely to become a hallmark of congestive heart failure in symptomatic patients with preserved left ventricular systolic function. The present review will focus on the current clinical applications of spectral tissue Doppler echocardiography used as a reliable noninvasive surrogate for left ventricular diastolic pressures at rest as well as during exercise in the diagnosis of heart failure with preserved left ventricular systolic function. Chronic congestive heart failure, a disease of exercise, and acute heart failure syndromes are characterized by specific pathophysiologic and diagnostic issues, and these two clinical presentations will be discussed separately.     

Angiotensin II contributes to arterial compliance in congestive heart failure

Arterial compliance is determined by structural factors, such as collagen and elastin, and functional factors, such as vasoactive neurohormones. To determine whether angiotensin II contributes to decreased arterial compliance in patients with heart failure, this study tested the hypothesis that administration of an angiotensin-converting enzyme inhibitor improves arterial compliance. Arterial compliance and stiffness were determined by measuring carotid artery diameter, using high-resolution duplex ultrasonography, and blood pressure in 23 patients with heart failure secondary to idiopathic dilated cardiomyopathy. Measurements were made before and after intravenous administration of enalaprilat (1 mg) or vehicle. Arterial compliance was inversely related to both baseline plasma angiotensin II (r = -0.52; P = 0.015) and angiotensin-converting enzyme concentrations (r = -0.45; P = 0.041). During isobaric conditions, enalaprilat increased carotid artery compliance from 3.0 +/- 0.4 to 5.0 +/- 0.4 x 10(-10) N(-1). m(4) (P = 0.001) and decreased the carotid artery stiffness index from 17.5 +/- 1.8 to 10.1 +/- 0.6 units (P = 0.001), whereas the vehicle had no effect. Thus angiotensin II is associated with reduced carotid arterial compliance in patients with congestive heart failure, and angiotensin-converting enzyme inhibition improves arterial elastic properties. This favorable effect on the pulsatile component of afterload may contribute to the improvement in left ventricular performance that occurs in patients with heart failure treated with angiotensin-converting enzyme inhibitors.     

Biventricular stimulation therapy in patients with heart failure and tachycardic arrhythmias. Indications--results--prospects]

Biventricular pacing (BV-P) therapy is a new therapeutic approach in patients (pts) with drug refractory congestive heart failure; the beneficial effects of implantable cardioverter defibrillator (ICD) without BV-P therapy in patients (pts) with life-threatening ventricular tachyarrhythmias and impaired left ventricular (LV) function is associated with a relatively high cardiac and total mortality. We studied the follow-up of 410 pts (368 males, 42 females, mean age 57 +/- 11 years) after ICD implant. The LV function was assessed by the New York Heart functional class of heart failure (NYHA). Fifty pts (12%) were in NYHA I-II, 151 pts (37%) in NYHA II, 117 pts (29%) in NYHA II-III and 92 pts (22%) in NYHA III. Epicardial ICD implantation was performed in 209 pts (51%) and 201 pts (49%) received nonthoracotomy ICDs. Perioperatively (within 30 days after implant), 12 pts (3%) died, significantly more frequent after epicardial (11 of 209 pts, 5%) than after transvenous ICD implant (1 of 201 pts, < 1%)(p < 0.05). During a mean follow-up of 28 + 24 months (range < 1 to 114 months), 90 pts (23%) died: 9 pts (2%) died from sudden arrhythmic death and 5 pts (1%) suddenly, but probably not from arrhythmic causes; 55 pts (14%) died from cardiac causes (congestive heart failure, myocardial reinfarction) and 21 pts (5%) from noncardiac causes. 338 pts (82%) received ICD shocks (mean incidence 21 +/- 43 shocks per pt). Our data show that pts with LV dysfunction benefit from ICD therapy and that these pts survive for a considerable time after the first shock. However, survival is clearly influenced by the degree of left ventricular dysfunction and, in addition to ICD therapy, aggressive treatment of heart failure is necessary. Therefore, BV-P is a very promising concept to improve the worse prognosis in pts with moderate or severe congestive heart failure.     

The isolated working heart model in infarcted rat hearts

Congestive heart failure (CHF) is one of the most common causes of death in western countries. The aim of this study was to establish and validate the working heart model in rat hearts with CHF. In the rat model the animals show parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure. The focus of attention was the evaluation of cardiodynamics (e.g.contractility) in the isolated 'working heart' model. The geometric properties of the left ventricle were measured by planimetry (stereology). Formulae available in the past for determining certain parameters in the working heart model (e.g.external heart work) have to be fitted to the circumstances of the infarcted rat hearts with its different organ properties.CHF was induced in Wistar Kyoto (WKY/NHsd) and spontaneously hypertensive rats (SHR/NHsd) by creating a permanent (8 week) occlusion of the left coronary artery, 2 mm distal to the origin from the aorta, by a modified technique (Itter et al. 2004). This resulted in a large infarction of the free left ventricular wall.We were able to establish and adapt a new and predictive working heart model in spontaneously hypertensive rat hearts with myocardial infarction (MI) 8-12 weeks after coronary artery ligation. At this stage the WKY rat did not show any symptoms of CHF. The SHR rat represented characteristic parameters and symptoms that could be extrapolated to the clinical situation of patients with end-stage heart failure (NYHA III-IV). Upon inspection, severe clinical symptoms of CHF such as dyspnoea, subcutaneous oedema, palebluish limbs and impaired motion were prominent. On necropsy the SHR showed lung oedema, hydrothorax, large dilated left and right ventricular chambers and hypertrophy of the septum. In the working heart model the infarcted animals showed reduced heart power, diminished contractility and enhanced heart work, much more so in the SHR/NHsd than in the Wistar Kyoto rat (WKY/NHsd).The aim for the future is to find a causal therapy of heart failure treatment. At present, only palliative therapy is possible for patients with heart failure. For this reason the working heart model in CHF rat hearts should provide a valuable method for early testing of new therapeutic approaches for patients with CHF.     

Clinical observations and echocardiographic features of mural thrombi in the left ventricle during myocardial infarction]

The incidence and changes in the mural thrombi in left ventricle in ECHO-2D in the acute myocardial infarction as well as relationship between clinical parameters and echocardiographic indices of the left cardiac ventricle contractability asynergy and dynamics of changes in mural thrombi have been investigated. The studies included 137 consecutive patients (98 males and 39 females) treated for the acute myocardial infarction. Patients' age ranged from 35 to 87 years (mean 62 years). Infarction of the anterior and/or lateral wall was diagnosed in 67 patients, and infarction of the inferior and/or posterior wall in 70 patients. Mural thrombi were diagnosed in 42 (31%) patients. Eighteen thrombi (43%) were liquefied during hospitalization. Comparative analysis of patients in whom mural thrombi underwent liquefaction in the hospital and a group of patients with myocardial infarction and persisting mural thrombi showed that return of left ventricle movements with subsequent contractability facilitate liquefaction of mural thrombi. Higher mortality rate in the group of patients with myocardial infarction with mural thrombi is due to extension of the infarction accompanied by marked asynergy of left ventricular contractions which does not decrease in sequential examinations, and increasing congestive heart failure.     

Pacing in congestive heart failure

Despite the major advances in medical drug therapy, heart failure remains a syndrome associated with high mortality and morbidity. Biventricular or left ventricular (LV) short atrioventricular (AV) delay pacing is being tested in congestive heart failure patients with left bundle branch block. The aim is to resynchronise the dyscoordinate LV contraction. A number of studies are underway, but it is clear that while some patients respond remarkably, this is highly variable. Accurate identification of patients likely to benefit will be crucial. The mechanism of benefit is unclear. A greater understanding of the physiological consequences of pacing will be necessary to accurately identify these patients.     

The therapeutic potential of stem cells in heart disease

Abstract.  Coronary heart disease and chronic heart failure are common and have an increasing frequency. Although interventional and conventional drug therapy may delay ventricular remodelling, there is no basic therapeutic regime available for preventing or even reversing this process. Chronic coronary artery disease and heart failure impairs quality of life and are associated with subsequent worsening of the cardiac pump function. Numerous studies within the past few years have been demonstrated, that the intracoronary stem cell therapy has to be considered as a safe therapeutic procedure in heart disease, when destroyed and/or compromised heart muscle must be regenerated. This kind of cell therapy with autologous bone marrow cells is completely justified ethically, except for the small numbers of patients with direct or indirect bone marrow disease (e.g. myeloma, leukaemic infiltration) in whom there would be lesions of mononuclear cells. Several preclinical as well as clinical trials have shown that transplantation of autologous bone marrow cells or precursor cells improved cardiac function after myocardial infarction and in chronic coronary heart disease. The age of infarction seems to be irrelevant to regenerative potency of stem cells, since stem cells therapy in old infarctions (many years old) is almost equally effective in comparison to previous infarcts. Further indications are non-ischemic cardiomyopathy (dilative cardiomyopathy) and heart failure due to hypertensive heart disease.     

High mortality in obese women diabetics with acute myocardial infarction.

The factors associated with mortality in 89 diabetics and 793 non-diabetics with acute myocardial infarction who were initially admitted to a coronary care unit were analysed retrospectively. During their stay in hospital diabetics had twice the mortality of non-diabetics. The higher mortality among diabetics was largely accounted for by obese women, who had a hospital mortality of 43%. There was an increased incidence of congestive heart failure in such patients. A therapeutic trial should be performed in such patients to assess whether insulin has an effect on infarct size.     

Sarcoplasmic reticulum Ca2+ transport and gene expression in congestive heart failure are modified by imidapril treatment

This study was designed to test the hypothesis that blockade of the renin-angiotensin system improves cardiac function in congestive heart failure by preventing changes in gene expression of sarcoplasmic reticulum (SR) proteins. We employed rats with myocardial infarction (MI) to examine effects of an angiotensin-converting enzyme inhibitor, imidapril, on SR Ca(2+) transport, protein content, and gene expression. Imidapril (1 mg.kg(-1).day(-1)) was given for 4 wk starting 3 wk after coronary artery occlusion. Infarcted rats exhibited a fourfold increase in left ventricular end-diastolic pressure, whereas rates of pressure development and decay were decreased by 60 and 55%, respectively. SR Ca(2+) uptake and Ca(2+) pump ATPase, as well as Ca(2+) release and ryanodine receptor binding activities, were depressed in the failing hearts; protein content and mRNA levels for Ca(2+) pump ATPase, phospholamban, and ryanodine receptor were also decreased by approximately 55-65%. Imidapril treatment of infarcted animals improved cardiac performance and attenuated alterations in SR Ca(2+) pump and Ca(2+) release activities. Changes in protein content and mRNA levels for SR Ca(2+) pump ATPase, phospholamban, and ryanodine receptor were also prevented by imidapril treatment. Beneficial effects of imidapril on cardiac function and SR Ca(2+) transport were not only seen at different intervals of MI but were also simulated by another angiotensin-converting enzyme inhibitor, enalapril, and an ANG II receptor antagonist, losartan. These results suggest that blockade of the renin-angiotensin system may increase the abundance of mRNA for SR proteins and, thus, may prevent the depression in SR Ca(2+) transport and improve cardiac function in congestive heart failure due to MI.     

DNA enzyme targeting TNF-alpha mRNA improves hemodynamic performance in rats with postinfarction heart failure

Tumor necrosis factor-alpha (TNF-alpha) probably affects the pathogenesis of heart failure. Here we have investigated the therapeutic potential of a nuclease-resistant DNA enzyme that specifically cleaves TNF-alpha mRNA. A phosphorothioate-modified DNA enzyme was designed to retain similar cleavage activity as its unmodified version, and that inhibited the expression of TNF-alpha in vitro. To test its efficacy in vivo, postinfarction congestive heart failure was induced in anesthetized rats by ligation of the left coronary artery. A 4-wk treatment with the DNA enzyme induced a substantial reduction in left ventricular end-diastolic pressure and lung weight concomitant with an increase in arterial blood pressure and myocardial blood flow compared with controls. The concentration of TNF-alpha in coronary sinus blood was markedly lowered on treatment, and myocardial TNF-alpha mRNA was substantially reduced. Recovery studies showed that the DNA enzyme cleavage activity was present within the myocardium throughout the observation period and had no apparent toxic effects. Our findings indicate that DNA enzyme-based therapy may hold promise in the treatment of this debilitating disease.