Anaphylaxis is a life-threatening systemic allergic disease with sudden onset and rapid progression [1]. The estimated prevalence of anaphylaxis was reported in 2006 as 50 to 2000 attacks per 100,000 persons or a lifetime prevalence between 0.05% and 2% by the American College of Allergy, Asthma and Immunology Epidemiology of Anaphylaxis Working Group [2]. A recent United States study reported that 1.6% of the population manifested a history of anaphylaxis [3]. Studies from Europe find the incidence of anaphylaxis at 1.5–7.9/100,000 person-years [4]. Further research indicates that the incidence of anaphylaxis has increased in United States, Australia, and the United Kingdom [567]. The mortality rate ranges from 2% to 20% [8]. An anaphylaxis episode can be induced by drug, food, latex, venom or insect bites, but in some cases, the cause may be undetermined [1]. Most studies point to the leading causes of anaphylaxis as medications [9101112]. The diagnosis of anaphylaxis depends on clinical signs and symptoms; furthermore, accurate diagnosis criteria have been developed [1]. Management basically includes intramuscular epinephrine, intravenous fluid replacement, corticosteroids, and antihistamine [1]. Delayed or improper treatment, especially retarded epinephrine usage, increases mortality risk and can result in death [113]. Uncontrolled asthma is another risk factor defined for fatal anaphylaxis [14].

Anaphylaxis can be mild and spontaneously resolved by a rise in the endogen epinephrine level as compensatory but can also be very severe, resulting in respiratory or cardiovascular arrest, even death [15]. The major causes of mortality due to anaphylaxis are the asphyxia caused by obstruction of the upper and/or lower respiratory airways and cardiovascular collapse. Cardiovascular manifestations include hypotension, shock, arrhythmia, ventricular dysfunction, and cardiac arrest [16]. During anaphylaxis, impairment of the coronary blood flow can lead to acute ischemic vascular events such as angina and myocardial infarction.

Although cardiovascular involvement is the one of the major causes of mortality in anaphylaxis, no research to date examines the occurrence of cardiac dysfunction in every attack. The most frequently used method for the evaluation of the left ventricular function is to measure the left ventricular ejection fraction (leftV EF) with echocardiography (ECHO). This method provides an easy way to learn cardiac functions and offers prognostic information. However, the method does possess disadvantages including reproducibility, load dependency, technical problems, the influence of heart rate and translational motion [17]. Furthermore, the conditions leading to subclinical cardiac dysfunctions with limited structural changes in the heart cannot be recognized so the prognosis in such diseases could be poor [18].

In the early stages of myocardial diseases, longitudinal functions decrease but by radial and circumferential compensation, the leftV EF is preserved. Therefore, it is important to evaluate longitudinal functions in conditions that have led to cardiac dysfunction with preserved leftV EF. In this line of inquiry, a new technique evaluating myocardial deformation, namely global longitudinal strain (GLS) measurement, is a promising option which is not load dependent and may be used to detect early left ventricular dysfunction [19].

Strain denotes the percentage of the dimensional deformation occurring in the object (measure of the deformation). Myocardial deformation is the structural changes resulting from a combination of external and internal forces. Myocardial strain is regionally and globally calculated with ECHO and yields valuable information regarding systolic and diastolic functions [20]. The strain is only very slightly affected from passive myocardial movements. This sensitive method measures the cardiac functions in the conditions leading to subclinical dysfunction and detects myocardial involvement in noncardiac diseases which could not be recognized by the standard echocardiographic techniques [21].

The aim of the study is to define the impairment of the cardiac functions during anaphylaxis and assess the possible factors influencing the development of dysfunction.

Patients who experienced anaphylaxis due to any cause in our hospital were included in the anaphylaxis group and patients who experienced early urticaria without any cardiac complaints were included in the study's control group. Tryptase levels were measured on the third hour of the reaction and 6 weeks later. Left ventricular systolic functions were evaluated with the GLS measurement approximately 4 hours after reaction and repeated 6 weeks later.

Anaphylaxis was diagnosed according to the presence of one of the clinical criteria; (1) rapid onset (minutes to several hours) of an attack with involvement of the mucocutaneous tissue and respiratory compromise or reduced blood pressure or associated symptoms of end-organ dysfunction or both, (2) two or more of the clinical features that occur rapidly after exposure to a potential allergen including involvement of the mucocutaneous tissue, reduced blood pressure or associated symptoms, respiratory compromise, and persistent gastrointestinal symptoms, (3) reduced blood pressure after exposure to known allergen (for adults systolic blood pressure of less than 90 mmHg or greater than 30% decrease from that person's baseline) [22]. The reactions were graded according to severity which were mild (involvement of skin and subcutaneous tissues only), moderate (features suggesting respiratory, cardiovascular, or gastrointestinal involvement) and severe (hypoxia, hypotension, or neurologic compromise) as in the literature [23].

The present study is the first investigation which evaluated the cardiac function shortly after an anaphylaxis. The results of this study demonstrate that ventricular functions are affected due to an anaphylaxis attack independent of severity.

We used Speckle tracking ECHO to obtain a valuable parameter, namely GLS to evaluate cardiac function. Although a new method, GLS has been used in many published reports and routinely in many ECHO laboratories due to its superiority to other parameters [28]. In the setting of normal leftV EF, systolic dysfunction can be detected by Speckle tracking ECHO, a process/an application which assists in identifying rare causes of cardiac pathologies with normal EF including cardiac hypertrophy and amyloidosis as well as evaluating the future cardiac risk as a prognostic marker [27293031]. In our study, shortly after anaphylaxis, the leftV EF values were measured in the normal ranges in all patients. The major finding of our study is that the mean strain values were significantly lower shortly after the anaphylaxis than those measured 6 weeks later. The strain measures below -20 in 5 patients indicate myocardial dysfunction according to the cardiac guidelines [27] (Fig. 3). The pathologic strain values in those 5 patients were increased to normal levels after 6 weeks. In the other 5 patients, strain values were in the normal ranges during the postanaphylaxis period; however, strain values increased by at least 2 units. In another 2 patients no differences existed in strain measures during anaphylaxis and 6 weeks later. Furthermore, the mean strain value was lower during the reaction in the anaphylaxis group than in the urticaria group. These results demonstrate cardiac involvement in the systemic hypersensitivity reaction.

The effect of epinephrine to treat anaphylaxis on cardiac function can be considered as a matter of importance. It can be assumed that epinephrine may negatively influence cardiac function through the drug's vasospastic effect on coronary arteries. In our study no correlation was detected between the doses of epinephrine used to treat anaphylaxis and the strain values. A study evaluating left ventricular function and contractile reserve in a small animal model for type 1 diabetes showed that a positive inotropic agent dobutamine led to an increase in strain level [32]. Epinephrine as a positive inotropic agent is assumed to lead to an increase in strain measures as well. However, in the current study, the strain values were lower than those of the control levels (measured 6 weeks later) in most of the patients. We can hypothesize that the strain values probably would have been less if the patients had not been given epinephrine.

Although cardiac involvement in anaphylaxis patients was recovered 6 weeks later, it is not possible to predict the cardiac functions of these patients in the long term. Lower strain values have been recently associated with a higher long-term risk of cardiovascular morbidity and mortality in a low-risk general population [33]. Accordingly, it may be assumed that the patients for whom myocardial strains were affected due to an anaphylaxis and particularly those with recurrent anaphylaxis both require long term follow-up care in terms of cardiac function.

Another main finding of the study is that the cardiac dysfunction developed during anaphylaxis did not depend on the severity of the reaction or the baseline tryptase levels.

The studies evaluating the risk factors for the severe and fatal anaphylaxis demonstrate that the severity of the reaction can be associated with the type of the culprit drug, the personal level of sensitivity, genetic background, age, exercise, comorbidities including coinfections, asthma, cardiovascular diseases, and mastocytosis and also coadministration of some drugs, such as beta blockers and angiotensin converting enzyme inhibitors [822343536]. Unfortunately, we could not analyze the effects of these variables in our patient group because of the small sample size. However, our data indicated that basal tryptase levels and the increment of the tryptase during anaphylaxis were higher in severe anaphylaxis than in non-severe anaphylaxis. Other studies also report that severe anaphylaxis was associated with the increment of tryptase levels during anaphylaxis [373839]. Mirone et al. pointed out that basal tryptase levels were higher in severe anaphylaxis while some authors did not observe such an association [37394041].

Our study had an important limitation which was the small sample size made difficult to draw an exact conclusion. However, it gave a very crucial opinion about the cardiac functions during anaphylaxis providing a basis for the future studies in this field.

In conclusion, this study demonstrates that cardiac dysfunction may develop during anaphylaxis independent of the severity of the reaction and with proper treatment, may resolve after recovery from anaphylaxis. Higher baseline tryptase levels, even in normal ranges, may be associated with severe anaphylaxis episode, a finding which requires more attention and corroboration with a larger series. Lastly, the long-term cardiac effects of anaphylaxis should be evaluated as well.