Silent ischemia: clinical relevance

Myocardial ischemia can occur without overt symptoms. In fact, asymptomatic (or silent) ST-segment depression during ambulatory electrocardiogram monitoring occurs more often than symptomatic ST-segment depression in patients with coronary artery disease. Initial studies documented that silent ischemia provided independent prediction of adverse outcomes in patients with known and unknown coronary artery disease. The ACIP (Asymptomatic Cardiac Ischemia Pilot Study) enrolled patients in the 1990s and found that revascularization was better than medical therapy in reducing silent ischemic episodes and possibly cardiovascular (CV) events. However, the more recent COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial found similar CV event rates between patients treated with optimal medical therapy alone and those treated with optimal medical therapy plus percutaneous revascularization. Therefore, in the current era, medical therapy appears to be as effective as revascularization in suppressing symptomatic ischemia and preventing CV events. COURAGE was not designed to evaluate changes in the frequency of silent ischemia. Therefore, silent ischemia may persist despite current-era treatment and might still identify patients with increased risk of CV events. Also, silent ischemia is likely to occur frequently in heart transplant patients with denervated hearts and coronary allograft vasculopathy, and future study aimed at improving the management of silent ischemia in this population is warranted. Additionally, future research is warranted to study the effect of newer medical therapies such as ranolazine or selected use of revascularization (for example, guided by fractional flow reserve) in those patients with persistent silent ischemia despite optimal current-era medical therapy.     

Silent myocardial ischemia: diagnosis, clinical significance and management

With the inception of continuous ECG monitoring with high-fidelity reproduction of the ST-segment, silent myocardial ischemia has been regarded with increasing importance in the detection and management of coronary artery disease. With the aid of a variety of invasive and noninvasive methods, the validity of ST-segment depression as indicative of myocardial ischemia, even in the absence of symptoms, has been adequately documented. In completely asymptomatic subjects with positive evidence of silent ischemia in the exercise ECG or Holter monitoring, the risk of developing a future manifestation of coronary artery disease may be up to ten-fold higher than in individuals with negative tests In patients with established coronary artery disease, concomitant use of continuous ECG monitoring and exercise testing, methods which complement each other rather than being mutually exclusive, a substantial number of patients with otherwise typical angina pectoris may be found to have silent ischemic episodes. An adequate differentiation between those with symptomatic and those who are asymptomatic based on characterization with respect to age, sex, hypertension, coronary anatomy, etc., has not been successful. Patients with silent ischemia during exercise may also exhibit more episodes of silent ischemia during daily activities and up to 75% of ischemic episodes may be asymptomatic. In general, however, silent ischemia during exercise appears more common than silent ischemia only during daily activities. In the latter case, since there is usually no increase in heart rate, the pathophysiology is regarded as dissimilar from that associated with exercise-induced ischemia. While the presence of silent ischemia appears quite common in patients after acute myocardial infarction, its occurrence, to date, has not been confirmed to carry additional risk, whereas in unstable angina, the association of silent ischemia is indicative of a higher probability of subsequent cardiac events.     

Silent myocardial ischemia. A clinical perspective.

Silent myocardial ischemia has been shown to occur far more frequently than anginal episodes in patients with coronary artery disease. Both an increase in myocardial oxygen demand and abnormalities of coronary vasomotor tone appear to play a significant role in the genesis of silent ischemia. Recent data show that in excess of 40% of patients with stable angina have frequent episodes of silent ischemia. The presence of silent ischemia predicts an increased risk of coronary events and cardiac death. Based on these data, it has been proposed that anti-ischemic therapy should be directed toward control of total ischemic burden. Although several recent studies have demonstrated efficacy of various antianginal drugs in reducing the number and duration of silent ischemic episodes, none has demonstrated beneficial effect on the associated adverse prognosis.     

Silent myocardial ischemia

Silent myocardial ischemia seems a relatively frequent manifestation of coronary insufficiency. The practice of more and more sophisticated tests to detect myocardial ischemia shows that it is a relatively frequent pathological occurrence. It occurs in patients with an abnormality or a transient or constant failure of the alarm system, represented by pain during the ischemia. It is an heterogenous picture which may take the appearance of a completely silent ischemia (the metabolic, hemodynamic and electrical consequences of ischemia being the only symptoms of coronary insufficiency, demonstrated by the presence of severe, angiographic or anatomical, stenoses); of a silent transient ischemia (with alternance of symptomatic and silent episodes or with silent episodes after myocardial infarction); of myocardial necroses without pain or ischemic myocardiopathies. It is the consequences of either an ischemia which is too moderate to reach the pain threshold, or a severe ischemia in patients presenting alterations of the transmission system and of the perception of pain. It has metabolic, hemodynamic and anatomical consequences which may lead to necrosis or degeneration and fibrosis of the myocardium. The prognosis of a painless disease is difficult to make but it does not seem to be as poor as the one of the usual forms of ischemic cardiopathies. Medical treatment is mandatory, and surveillance of its efficacy must be systematic using the techniques of detection of the ischemia.     

Silent cardiac ischemia

Between the extremes of those who have no coronary disease and those limited by it are those with documented ischemia but no symptoms. Treating these patients in the "murky middle" generates some important questions. Should we treat patients with no symptoms solely on the basis of test abnormalities? Can we make the asymptomatic person better? What interventions would we use to treat such a disorder? How do we justify the risk, inconvenience, and cost of these interventions? How do we measure the efficacy of our intervention? Treating the asymptomatic person can only be justified if we prevent future events through our intervention. The management of silent ischemia can serve as a model for handling other preventative measures. The following article describes the issues around silent cardiac ischemia and some of the insights obtained in the Asymptomatic Cardiac Ischemia Pilot (ACIP) Study.     

Silent myocardial ischemia

Silent myocardial ischemia has emerged from a subject of mainly research interest to one with important clinical implications for practicing physicians. Although the pathophysiologic mechanisms responsible for the absence of pain are still not clear, it is apparent that episodes of silent myocardial ischemia are frequent and occur in many patients with coronary artery disease; episodes occur both in asymptomatic and symptomatic patients; episodes are detectable by various noninvasive and invasive techniques; and episodes appear to have important prognostic implications when combined with the extent of anatomic disease and degree of left ventricular dysfunction. It is expected the rapidly accumulating prognostic data, especially in patients after infarctions and patients with unstable angina, will have a profound effect on the way physicians treat their patients with coronary artery disease.     

Silent myocardial ischemia: Recent developments

Silent myocardial ischemia is now in its fourth decade of recognition as a clinical syndrome within the spectrum of coronary artery disease. Prior decades have seen important research into the pathophysiology, detection, prevalence, prognosis, and therapy of this syndrome. More recent developments have continued to add data to each of these areas, with particular emphasis on the comparative value of various diagnostic procedures and the effect of therapy on prognosis. While controversy still exists concerning proper screening guidelines for the asymptomatic population, there is a growing consensus that some form of stress testing in high-risk individuals (ie, those with multiple coronary risk factors) is appropriate.     

Silent somatotroph pituitary adenomas: an update

Silent growth hormone adenomas (SGHA) are a rare entity of non-functioning pituitary neuroendocrine tumors. Diagnosis is invariably made post-operatively of a tumor immunopositive for GH (and Pit-1 in selected cases) but without clinical acromegaly. Mainly young females are affected, and tumors are often uncovered by investigation for headaches or oligoamenorrhea. Integration of clinical, pathological and biochemical data is required for proper diagnosis. Beside normal IGF-1 levels, a third of SGHAs displays elevated GH levels and some will eventually progress to acromegaly. Almost two-thirds will be mixed GH-prolactin tumors and sparsely-granulated monohormonal GH tumors seems the more aggressive subtype. Recurrence and need for radiation is higher than other non-functioning tumors so close follow-up is warranted.     

Silent ischemia: a timely aspect in coronary artery disease

The phenomenon of silent myocardial ischemia is defined as a transient alteration in myocardial perfusion, function or electrical activity in the absence of chest pain or the usual anginal equivalents. Patients may be classified as having one of three types of silent ischemia: type 1-asymptomatic with no history of myocardial infarction or angina; type 2-asymptomatic with previous myocardial infarction; type 3-angina is present in addition to asymptomatic ischemic episodes. Based on exercise testing, silent ischemia has been found in 2.5% of asymptomatic middle-aged men; a substantial number of such subjects subsequently incur cardiac events. In patients with type 2 silent ischemia, post-infarction mortality appears markedly higher than in cohorts without silent ischemia. In type 3 patients, 75 to 80% can be found to have silent ischemic episodes in addition to typical anginal attacks, the frequency of which may be up to three or four times that of the latter counterpart. In persons with coronary artery disease who succumb to sudden cardiac death, 25% have never had clinical symptoms suggesting that there may be a great number of persons with silent disease in the population at large.     

Silent ischemia: to treat or not

As worded, the question "Should silent ischemia be treated?" needs to be examined carefully, assuming that silent ischemia is even the correct topic of the question. The way the question is phrased influences the answer. The more the question's permutations are examined, the clearer it becomes that the problem is one of definition. Our conceptualization of the ischemic process is still incomplete, and the question of whether to treat silent ischemia remains. Ultimately, the decision will depend on demonstrable benefit for prognosis. Every acute ischemic syndrome is indicative of poor prognosis, independent of other factors associated with adverse outcome and of the method of measurement. The true determinant of the need to treat is the total ischemic pattern, and how silent ischemia and angina fit within that context is not yet known.     

Silent myocardial ischemia: a problem in diagnosis and treatment

We tried to establish the incidence of silent myocardial ischemia (SMI) in the general population and also in patients with recognised ischemic heart disease. For this, purpose 2, 375 stress tests (ST) with Bruce protocol were reviewed, 364 were positive and those patients were divided in two groups: group I with SMI during the ST and group II with myocardial ischemia and angina during the ST. Coronary risk factors ergometric behaviour and angiographic factors were analysed. Group I had 263 patients with SMI (71%). Group II had 111 patients with ischemia and angina (29%) P less than 0.05; 90 patients had diabetes mellitus in group I and 19 in group II P less than 0.05. A previous myocardial infarction was registered in 157 patients from group I and 55 from group II P less than 0.05. The remaining coronary risks factors, ergometrics variables and significance and number of diseased coronary vessels were similar in both groups. We conclude that SMI is a frequent event in patients with ischemic heart disease. It represents probably the most frequent event in this disease. Previous myocardial infarction and diabetes mellitus may play an important role in the pathogenesis of SMI. The ST and Holter monitoring are dependable procedures for the identification of SMI and should be always performed specially in patients with high coronary risk factors. Once detecting SMI a therapeutic plan should be considered for medical, angioplastic or surgical procedures even in asymptomatic patients.     

Silent ischaemia: an update on current concepts

Angina pectoris is the cardinal symptom of coronary heart disease and is a symptom with which physicians are very familiar. The clinical diagnosis of ischaemic heart disease is often based largely on a history of typical chest or arm pain, and the major therapeutic endeavour in such patients is directed towards abolition or amelioration of angina. Indeed physicians have, at least up until recently, been confident in assuming that angina is a reliable marker of ongoing ischaemia and that success of medical or surgical treatment of coronary heart disease can be accurately gauged according to improvement or disappearance of anginal symptoms (Cohn & Braunwald, 1988). However, the results of a number of important clinical studies, reported over that last 10 to 15 years, appear to challenge these traditional medical assumptions. In many patients with coronary heart disease, acute episodes of myocardial ischaemia are frequently unaccompanied by angina, often referred to as "silent myocardial ischaemia" (Epstein et al., 1988; Fox, 1988; Cohn, 1985; Maseri, 1985). It has to be pointed out that not all painless ischaemic episodes are truly silent. Instead of experiencing pain during some episodes of acute myocardial ischaemia, patients may, on occasion, instead report symptoms such as dyspnoea or palpitations (these symptoms being known as "anginal equivalents") (Cohn & Braunwald, 1988). Nevertheless, the great majority of painless ischaemic episodes are, truly silent and not accompanied by "anginal equivalents", which has led to the trend in the recent literature to regard the terms "silent" and "painless" myocardial ischaemia as synonymous.