Prognosis of Left Ventricular Systolic Dysfunction Based on Early Assessment of Patients with ST-Segment Elevation Myocardial Infarction on ECG

The dissertation addresses the problem of prognosis of left ventricular systolic dysfunction in patients with ST-segment elevation myocardial infarction on ECG. It examines the processes of post-infarction myocardial remodeling, factors determining its adaptive or maladaptive character, and the role of echocardiographic and clinical parameters measured during the first day of hospitalization in predicting the maintenance of impaired cardiac contractile function at six months of follow-up. The author identifies independent predictors of the development of left ventricular systolic dysfunction in the acute and post-infarction periods, evaluates the influence of reperfusion therapy on long-term functional outcomes, and demonstrates the relationship of early clinical and instrumental characteristics to the frequency of in-hospital complications and recurrent coronary events.

Relevance of the Problem.

The process of LV remodeling in patients who have suffered AMI is triggered by the death of a significant portion of cardiomyocytes and continues after the cessation of the damaging effect on the myocardium (Yu.N. Belenkov, 2000). This process is adaptive in character and directed toward preserving adequate cardiac output and appropriate myocardial stress. At the same time, it is known that a substantial proportion of patients who have suffered AMI subsequently develop CHF. The cause of this complication is that the remodeling process assumes a maladaptive character, with progressive LV dilation, disturbance of its geometry, and ultimate decline of pump function (M. Sutton et al., 1997; Yu.I. Buziashvili et al., 1999).

According to the Framingham Study data, CHF develops within 5 years in 14% of patients who have survived acute MI, and the risk of developing CHF in patients with LV dilation is significantly higher than in patients with a normal LV cavity size (W.B. Kannel et al., 1979; R.G. Oganov et al., 2007).

A prognostically unfavorable outcome of maladaptive LV remodeling is the development of chronic post-infarction cardiac aneurysms (V. Dor, 1990; L.A. Bockeria et al., 2002).

In addition to the risk of developing CHF, patients with AMI also have a significantly increased risk of developing arrhythmias and sudden death. All of this attests to the importance of early detection and prevention of maladaptive LV remodeling (Yu.A. Karpov, 2006).

Echocardiography is the method most frequently used to assess systolic cardiac function. This is due primarily to the non-invasive nature of the investigation, the absence of ionizing radiation, the speed of execution, the accessibility, and the wide availability. Therefore, in accordance with the current recommendations of the European Society of Cardiology, echocardiography is considered the method of choice for assessing cardiac systolic function (M.N. Alekhin et al., 2007).

The dynamics of echocardiographic parameters in the acute and subacute phases of MI have been studied quite thoroughly (U. Marzoll et al., 1991; I.V. Persiyanov-Dubrov et al., 2004; R. Hoffman et al., 2005). It has been established that during these two phases dynamic changes occur in the indices characterizing LV geometry and function. According to a number of investigators, LV EF declines substantially in the acute phase of MI (E. Agricola et al., 2005). Thereafter, in the majority of patients a gradual increase in this parameter of LV contractile function takes place (H.-O. Lee et al., 1995; N.N. Mikheev, 2008). According to U. Marzoll et al. (1991), LV EF during the first 24 h from the onset of acute MI amounted to 45.7% and increased prior to patient discharge to 49.6%. According to H.-O. Lee et al. (1995), LV EF in patients with acute MI changed as follows: 45.11% (first 48 h), 50.8% (1st week), 53.9% (2nd week), 52.11% (3rd week). G. Lamas et al. (1989) established that, of the multitude of echocardiographic indices, only the sphericity index (SI) independently predicted a decrease in exercise tolerance and the appearance of CHF symptoms. Data are also available indicating that LV EDV and ESV measured 1 month after acute MI are the best predictors of long-term survival of patients in comparison with LV EF and the degree of coronary artery occlusion (D.E. Habash-Bseiso et al., 2005; V.V. Chestukhin et al., 2005).

The GISSI-3 clinical trial (L. Tavazzi et al., 1997) demonstrated that an LV EDV greater than 112 ml doubled mortality at 6 months after AMI, while with an ESV greater than 57.6 ml mortality increased nearly 3-fold (S.A. Boldueva et al., 2008).

By the beginning of the scar formation period, as a rule, either a certain stabilization of the indices characterizing LV geometry and function is achieved, or their dynamics slow considerably. This makes it possible to regard the parameter values measured at that point in time as convenient baselines for observation of the further process of late LV remodeling (D.M. Aronov et al., 2007). However, the decline in LV systolic function is insignificant. This is due to the fact that the Frank–Starling mechanism comes into play during the observed period, i.e., adequate cardiac output and LV EF are maintained through an increase in LV end-diastolic volume (EDV) (Yu.V. Parkhomenko et al., 2008). LV dimensions grow considerably, its eccentric hypertrophy progresses, and ventricular sphericity increases. This leads to an increase in LV filling pressure, a rise in pulmonary artery pressure, and the appearance of the first signs of congestive heart failure (M. Sutton et al., 2000; E.P. Pavlikova et al., 2006).

Another manifestation of maladaptive LV remodeling in patients who have suffered AMI is a tendency toward the development of a restrictive type of LV diastolic filling. Such a type of diastolic dysfunction is a powerful predictor of cardiovascular mortality (S.M. Yu et al., 1996; S.H. Poulsen et al., 1997; V.V. Kalyuzhin et al., 2006).

Thus, observation of the late remodeling process in the MI scar formation period and beyond has shown that this process may assume either an adaptive or a maladaptive character (N.B. Lyapkovich et al., 2007). An important point is that in patients with maladaptive cardiac remodeling the unfavorable dynamics of increasing myocardial stress is preserved. Myocardial stress rises despite the increase in myocardial mass. Consequently, in this category of patients the stimulus for further development of maladaptive LV remodeling is maintained (V. Dor et al., 1997; J. Kjekshus et al., 2007).

The unfavorable consequences of maladaptive post-infarction LV remodeling are well known. According to the Framingham Study data, progressive dilation of the LV cavity after acute MI has an unfavorable prognostic significance (M.J. Cziraky et al., 2006).

The reasons for which the process of cardiac remodeling assumes a maladaptive character are not entirely clear. It has been suggested that this may be associated with excessive activation of various neurohumoral systems (S. Julius et al., 2006). Such activation, in turn, develops predominantly in those with large-focal acute MI and in patients with impaired LV contractile function. Data have been obtained that patients with elevated levels of neurohormones in the acute phase of MI have a higher risk of developing dilation and a decrease in LV systolic function at 6 months of follow-up (J. Schrader et al., 2005).

The importance of early identification of AMI patients who are at elevated risk of unfavorable consequences (development of CHF, sudden cardiac death) is evident (Yu.N. Belenkov et al., 2008). Early detection of the maladaptive character of cardiac remodeling and adequate pharmacological correction during both the early and late phases of LV remodeling can prevent the development of unfavorable long-term sequelae of AMI that determine patient survival (W.E. Boden et al., 2007).

Aim of the Study.

To identify parameters, based on early (during the first day of hospitalization) assessment of patients with myocardial infarction whose symptom onset occurred less than 6 hours before presentation, that allow prognosis of the development of left ventricular systolic dysfunction at 6 months after the survived myocardial infarction.

Objectives of the Study:

1. To evaluate left ventricular myocardial systolic function in patients with ST-segment elevation myocardial infarction and symptom duration <6 h during the first day of hospitalization and at 6 months after the survived myocardial infarction.

2. To study the influence of left ventricular systolic dysfunction on the clinical course and outcomes of the survived myocardial infarction (over 6 months of follow-up).

3. To evaluate the factors associated with the development of left ventricular systolic dysfunction from the first day of myocardial infarction and with its persistence over the subsequent 6 months of follow-up.

4. To identify predictors of the development of left ventricular systolic dysfunction during the first day of myocardial infarction and in the post-infarction period (at 6 months after the survived myocardial infarction) based on early (during the first day of hospitalization) assessment of patients with acute ST-segment elevation myocardial infarction and symptom duration <6 h.

Scientific Novelty.

For the first time it has been established that age >62 years, recurrent myocardial infarction, and ST-segment elevation >4.5 mm in the most informative ECG lead at admission are predictors of the development of left ventricular systolic dysfunction during the first day of hospitalization in patients with myocardial infarction whose symptom onset occurred less than 6 hours before presentation.

For the first time it has been shown that in patients with myocardial infarction with disease duration <6 h the independent predictors of the development of left ventricular systolic dysfunction at 6 months after the survived infarction are anterior infarct location, recurrent myocardial infarction, a "new" pathological Q wave on ECG, troponin T level >0.1 ng/ml during the first 6 hours, TIMI risk score >4 points, and left ventricular myocardial asynergy size >40% at admission.

Practical Significance of the Work.

In the overwhelming majority of patients with acute ST-segment elevation myocardial infarction and symptom duration <6 h, a decrease in left ventricular ejection fraction <40% has been detected during the first day of hospitalization.

At the same time, the left ventricular ejection fraction value during the first 6 h from the onset of myocardial infarction symptoms is not a predictor of the development of left ventricular systolic dysfunction at 6 months after the survived myocardial infarction.

It has been revealed that the presence of left ventricular systolic dysfunction in the post-infarction period in patients with acute ST-segment elevation myocardial infarction and symptom duration <6 h is associated with an increased frequency of in-hospital complications of the infarction as well as recurrent infarctions and recurrent angina over 6 months of follow-up.

It has been shown that the administration of reperfusion treatment (thrombolytic therapy and primary angioplasty of the infarct-related artery) within the first 6 h of ST-segment elevation myocardial infarction symptom development is associated with the absence of left ventricular systolic dysfunction at 6 months after the survived myocardial infarction.

Main Statements Defended.

1. Left ventricular systolic dysfunction (EF <40%) during the first day of hospitalization develops in 78% of patients with ST-segment elevation myocardial infarction and symptom duration <6 h. The independent predictors of left ventricular systolic dysfunction development during the first day of hospitalization are age >62 years, recurrent myocardial infarction, and ST-segment elevation >4.5 mm in the most informative ECG lead at admission.

2. In 28% of cases in which systolic dysfunction develops during the first day of hospitalization it persists at 6 months after the survived myocardial infarction. The presence of left ventricular systolic dysfunction during the first day of hospitalization and its persistence over 6 months after the survived infarction are associated with age >65 years, anterior infarct location, recurrent myocardial infarction, heart rate on ECG >80 beats/min at admission, total ST elevation on ECG >14 mm, ST elevation >5 mm in the most informative ECG lead, number of ECG leads with ST elevation >5 at admission, troponin T level >0.1 ng/ml during the first 6 hours, and TIMI risk score >4 points at admission.

3. At 6 months after the survived ST-segment elevation myocardial infarction, left ventricular systolic dysfunction develops in 31% of patients hospitalized no later than 6 h from symptom onset. The independent predictors of its development in patients with ST-segment elevation myocardial infarction and disease duration <6 h are anterior infarct location, recurrent myocardial infarction, a "new" pathological Q wave on ECG, troponin T level >0.1 ng/ml during the first 6 h, TIMI risk score >4 points, and left ventricular myocardial asynergy size >40% at admission.

The work was approved on 29 October 2008. The main statements of the dissertation were presented and discussed at the I Interregional Conference "Current Problems of Hemostasiology and Endotheliology" (Omsk, 28–29 October 2003), the Russian National Congress of Cardiologists (Tomsk, 12–14 October 2004), and the III Congress of Cardiologists of the Ural Federal District (19–20 February 2008).

Implementation into Practice.

The results and methods of the present investigation have been implemented into the practical work of Cardiology Department No. 1 of the Tyumen Regional Clinical Hospital. The results of the study are used in teaching the section "Emergency Cardiology" at the Department of Cardiology of the Faculty of Advanced Training and Professional Retraining of Specialists of the State Educational Institution of Higher Professional Education Tyumen State Medical Academy of Roszdrav.

Publications. On the topic of the dissertation, 8 printed works have been published, including 1 article in a journal refereed by the Higher Attestation Commission.

Structure and Scope of the Dissertation.

The dissertation consists of an introduction, a literature review, a chapter on the material and methods of the study, a chapter presenting the results of the author's own investigations and their discussion, a conclusion, conclusions, and practical recommendations. The reference list includes 65 Russian and 117 foreign sources. The dissertation is presented on 107 pages of typewritten text, contains 32 tables, and 3 figures.