International Journal of Medical Science and Health Research
Vol.8, No. 04; 2024
ISSN: 2581-3366
Correlation of Left Ventricular Diastolic Function with the Clinical Course
and Outcome of Acute Myocardial Infarction: A Brief Review
Beka Mikeladze 1,2,4, Nino Zhvania1,5, Giorgi Nikolaishvili 2,3,4 & Naira Kobaladze3,4
1
New Vision University, Georgia, Tbilisi
2
Avicenna Batumi Medical University, Georgia, Batumi
3
Batumi Shota Rustaveli State University, Georgia, Batumi
4
Medcenter – Batumi Referral Hospital, Georgia, Batumi
5
Ivane Javakhishvili Tbilisi State University, Georgia, Tbilisi
Correspondence: Beka Mikeladze, PhD Student, New Vision University, 11, Nodar Bokhua Str,
0159, Tbilisi, Georgia. Tel: +995 32 24 24 440
doi: 10.51505/ijmshr.2024.8405 URL: http://dx.doi.org/10.51505/ijmshr.2024.8405
Received: Aug 15, 2024 Accepted: Aug 16, 2024 Online Published: Aug 30, 2024
Abstract
Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality globally,
posing significant challenges in cardiology and internal medicine. AMI is characterized by the
sudden interruption of blood flow to a portion of the myocardium, resulting in ischemic injury
and myocardial necrosis. This condition presents a wide range of clinical manifestations, from
asymptomatic cases to severe complications. Advances in treatment underscore the need for a
comprehensive understanding of AMI's path physiology and prognostic indicators to improve
patient outcomes. One crucial aspect of myocardial function impacted by AMI is left ventricular
diastolic function (LVDF), which involves the heart's ability to relax and fill with blood during
diastole. Impaired LVDF can be an early sign of myocardial injury and is a significant
determinant of clinical outcomes post-AMI. Ischemic damage to the myocardium can lead to
changes in LVDF, affecting relaxation, ventricular filling, and myocardial stiffness, thereby
influencing the overall prognosis. Research links LV diastolic dysfunction (LVDD) with various
adverse clinical outcomes in AMI patients, including exacerbated heart failure symptoms,
adverse ventricular remodeling, and increased risk of chronic heart failure and cardiovascular
mortality. Echocardiography, particularly Doppler imaging, is vital for assessing LVDF, with the
E/A and E/e' ratios serving as key parameters. An abnormal E/A ratio suggests impaired LV
relaxation or increased stiffness, while an elevated E/e' ratio indicates increased LV filling
pressures (LVFP) and is associated with worse outcomes. Studies have shown that elevated E/e'
ratios predict higher left atrial pressures and increased heart failure risk, correlating with
prolonged hospitalization and higher mortality in AMI patients. Conversely, normalization of
diastolic parameters can indicate a positive response to therapy and improved recovery. In
conclusion, assessing LVDF through echocardiographic parameters like the E/A and E/e' ratios is
essential in managing AMI patients. These measures provide valuable insights into LVFP and
LVDF, crucial for understanding AMI's clinical course and optimizing patient care. Ongoing
www.ijmshr.com Page 51
International Journal of Medical Science and Health Research
Vol.8, No. 04; 2024
ISSN: 2581-3366
research and clinical application of these parameters are vital for enhancing prognostic accuracy
and treatment strategies for AMI.
Keywords: Left ventricular diastolic function, acute myocardial infarction, clinical outcomes,
echocardiography, prognosis
Introduction
Acute myocardial infarction (AMI) remains one of the leading causes of morbidity and mortality
worldwide, [1] representing a critical challenge in cardiology and internal medicine.
Characterized by the abrupt interruption of blood flow to a segment of the myocardium, AMI
results in ischemic injury and subsequent myocardial necrosis. [2] The clinical presentation of
AMI varies widely, from asymptomatic cases to those with life-threatening complications. As
advancements in treatment modalities continue to evolve, understanding the multifaceted aspects
of AMI, including its pathophysiology and prognostic indicators, is crucial for improving patient
outcomes.
Methods
A comprehensive literature search was conducted using the PubMed, Embase, and Cochrane
Library databases to identify relevant studies published up to the present date. The search
strategy was designed to capture studies that assess left ventricular diastolic function (LVDF) in
patients with acute myocardial infarction (AMI) and its association with clinical outcomes,
including heart failure, arrhythmias, and mortality. Keywords used in the search included "left
ventricular diastolic function," "acute myocardial infarction," "clinical outcomes,"
"echocardiography," “E/e′ ratio,” and "prognosis."
Selection Criteria
Studies were included if they met the following criteria:
1. Original research focused on AMI patients with documented LVDF assessment.
2. Utilization of echocardiographic parameters, particularly the E/A and E/e′ ratios, to evaluate
LVDF.
3. Reported clinical outcomes such as heart failure, mortality, or adverse ventricular remodeling.
4. Published in peer-reviewed journals with full-text availability in English.
LVDF and AMI
One critical dimension of myocardial function affected by AMI is LVDF. LVDF pertains to the
heart's ability to relax and fill with blood during diastole, the phase of the cardiac cycle when the
heart muscle is at rest. [3] The impairment of LVDF can be an early indicator of myocardial
injury and is increasingly recognized as a significant determinant of clinical outcomes following
AMI. [4]
Importance of LVDF
The left ventricle (LV) is responsible for pumping oxygenated blood to the systemic circulation.
[5] During diastole, the LV relaxes and expands, allowing blood to flow from the left atrium into
www.ijmshr.com Page 52
International Journal of Medical Science and Health Research
Vol.8, No. 04; 2024
ISSN: 2581-3366
the ventricle. This process is essential for maintaining adequate cardiac output and ensuring
efficient perfusion of vital organs. In the context of AMI, ischemic damage to the myocardium
can lead to altered LVDF, which may manifest as impaired relaxation, decreased ventricular
filling, or increased stiffness of the myocardial tissue. [6] Such alterations in LVDF can
influence the clinical trajectory of AMI and the patient's overall prognosis. [7]
Pathophysiology of LVDD in AMI
The pathophysiology of LVDD in AMI involves several interconnected mechanisms that impair
the heart's ability to relax and fill properly. During an ischemic event, myocardial injury leads to
impaired relaxation of the left ventricle, primarily due to disruptions in calcium handling within
cardiomyocytes. [8] Ischemia alters calcium uptake and release from the sarcoplasmic reticulum,
resulting in prolonged relaxation times and increased myocardial stiffness. [9] Additionally,
ischemic injury triggers inflammatory responses and neurohormonal activation, notably the
renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, which further
promote myocardial fibrosis and adverse remodeling. [10] This fibrosis increases ventricular
stiffness, [11] raising left ventricular filling pressures and exacerbating diastolic dysfunction
(DD). [12] Consequently, the impaired relaxation and increased stiffness of the myocardium lead
to elevated end-diastolic pressures, contributing to pulmonary congestion and heart failure
symptoms commonly observed in AMI patients. [13]
DD and Mortality in AMI
Today, it can be confidently stated that severe disturbance of the LVDF, particularly the
restrictive type, is a predictor of an unfavorable outcome in AMI. Nijland et al. [14] studied the
clinical outcomes of patients with AMI who had restrictive DD. Ninety-five patients were
included in the study during the first three days of AMI. In the restrictive type group, a 50%
mortality rate was observed one year after AMI, whereas in the non-restrictive group, no lethal
outcomes were detected. Thus, it was found that the restrictive type of DD is an independent
prognostic predictor of mortality after AMI.
Similar results were obtained by Poulsen S.H. et al, [15] who studied 58 patients with ST-
segment elevation myocardial infarction. Mortality 12 months after infarction was observed only
in the group of patients who had pseudo normal and restrictive DD. In the same group, the
mortality rate was 43%.
GISSI-3 [16] (effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-
week mortality and ventricular function after acute myocardial infarction) As part of the study,
an echocardiographic sub-study was conducted in which 571 patients participated and the
prognostic role of various echocardiographic parameters was studied. A substudy showed that
the best echocardiographic predictor of mortality after AMI at 4 years of follow-up was the
presence of irreversible restrictive DD during hospitalization. Overall mortality in this group of
patients was 2.9 times higher than in patients with reversible restrictive DD (p < 0.0003).
Sakata M. et al. [17] studied the prognostic role of various parameters of transmitral blood flow
www.ijmshr.com Page 53
International Journal of Medical Science and Health Research
Vol.8, No. 04; 2024
ISSN: 2581-3366
in patients with myocardial infarction. It was found that patients with fatal outcomes and those
who developed acute heart failure had a significantly higher peak transmitral blood flow E/A
ratio and a significantly lower left ventricular early diastolic filling blood flow deceleration time
than recovered patients without signs of heart failure.
Clinical Outcomes and LVDD
Research has shown that LVDD is closely linked to various clinical outcomes in patients with
AMI. DD can exacerbate symptoms of heart failure, such as shortness of breath, fatigue, and
exercise intolerance. [18] Furthermore, it may contribute to the development of adverse left
ventricular remodeling, which encompasses changes in ventricular geometry and function over
time. [19] Adverse remodeling is a well-established predictor of poor outcomes, including
increased risk of chronic heart failure and cardiovascular mortality. [20]
Echocardiographic Assessment of LVDF
Echocardiography, particularly Doppler imaging, is the primary tool for assessing diastolic
function. [21] Two key parameters derived from Doppler studies are the E/A ratio and the E/e'
ratio. The E/A ratio measures the velocities of early (E) and late (A) diastolic filling of the LV.
[22] Normally, the E wave, which represents early rapid filling, is larger than the A wave, which
represents late filling due to atrial contraction. An abnormal E/A ratio, such as a reduced E/A
ratio, may indicate impaired LV relaxation or increased stiffness. [23]
E/e' Ratio as an Indicator
The E/e' ratio, on the other hand, is a more nuanced indicator of DD and reflects the relationship
between the early diastolic filling velocity (E) and the early diastolic velocity of the mitral
annulus (e'). [24] Elevated E/e' ratios are indicative of increased LV filling pressures and have
been associated with worse outcomes in AMI patients. This parameter helps estimate LV filling
pressures indirectly and is particularly valuable in identifying patients at risk for heart failure and
other adverse events. [25,26]
Clinical Relevance and Research Findings
Research underscores the clinical relevance of these echocardiographic parameters in the context
of AMI. For instance, studies have shown that elevated E/e' ratios are predictive of higher left
atrial pressures and increased risk of heart failure. [27] In patients with AMI, an elevated E/e'
ratio has been linked to a greater likelihood of adverse clinical outcomes, including prolonged
hospitalization and increased mortality. [28,29] Conversely, normalization of diastolic
parameters over time may indicate a favorable response to therapy and better recovery. [30]
Data Extraction and Analysis
Data from selected studies were extracted independently by two reviewers. This included
information on study design, sample size, patient demographics, echocardiographic findings
(e.g., E/A and E/e′ ratios), and clinical outcomes. A third reviewer resolved any discrepancies.
www.ijmshr.com Page 54
International Journal of Medical Science and Health Research
Vol.8, No. 04; 2024
ISSN: 2581-3366
The extracted data were then synthesized into a summary table (Table 1) to facilitate comparison
of key parameters and outcomes across studies.
Table 1. Summary of Key Echocardiographic Parameters and Clinical Outcomes in AMI Patients
Study Sample Age Gende E/A Ratio E/e′ Ratio Clinical Follow-
Size (n) (Years) r Outcome up
(M/F) Duration
Nijland et al. 9 Mean: 63 62/33 Not Not 50% 1 year
[14] reported reported mortality in
restrictive
DD group
Poulsen et al. 58 Mean: 67 40/18 Reduced in Elevated in 43% 12
[15] restrictive restrictive mortality in months
DD DD pseudonorma
l and
restrictive
DD groups
GISSI-3 [16] 571 Median: 400/17 Irreversible Elevated in Irreversible 4 years
60 1 restrictive restrictive restrictive
DD: 2.9x DD DD: best
higher predictor of
mortality mortality
Sakata et al. 300 Mean: 65 210/90 Higher in Lower Higher risk Not
[17] fatal cases deceleration of acute specified
time in fatal heart failure
cases and fatal
outcomes
Critical Analysis
The studies were critically appraised for methodological quality, including aspects such as study
design (e.g., prospective vs. retrospective), sample size, and duration of follow-up. Particular
attention was paid to how well the studies controlled for confounding variables and the statistical
methods used to analyze the relationship between LVDF parameters and clinical outcomes.
The analysis included evaluating the consistency of findings across different studies and
assessing the strength of evidence supporting key statements made in this review. Studies with
higher methodological rigor and those demonstrating clear and statistically significant
associations between LVDF parameters and clinical outcomes were given greater weight in the
synthesis of evidence.
www.ijmshr.com Page 55
International Journal of Medical Science and Health Research
Vol.8, No. 04; 2024
ISSN: 2581-3366
Limitations
The review acknowledges potential limitations, including the variability in echocardiographic
techniques and measurements across studies, as well as differences in patient populations and
treatment regimens. The heterogeneity of the data was considered when drawing conclusions,
and the implications for clinical practice were discussed with caution.
Conclusion
In summary, the assessment of LVDF, particularly through parameters like the E/A ratio and E/e'
ratio, is a crucial component of evaluating and managing patients with AMI. These
echocardiographic measures offer valuable insights into LVFP and diastolic function, which are
integral to understanding the clinical course of AMI and optimizing patient care. Continued
research and clinical application of these parameters are essential for enhancing the prognostic
accuracy and treatment strategies for AMI.
References
Roth, G. A., Mensah, G. A., Johnson, C. O., Addolorato, G., Ammirati, E., Baddour, L. M.,
Barengo, N. C., Beaton, A. Z., Benjamin, E. J., Benziger, C. P., Bonny, A., Brauer, M.,
Brodmann, M., Cahill, T. J., Carapetis, J., Catapano, A. L., Chugh, S. S., Cooper, L. T.,
Coresh, J., Criqui, M., … GBD-NHLBI-JACC Global Burden of Cardiovascular Diseases
Writing Group (2020). Global Burden of Cardiovascular Diseases and Risk Factors,
1990-2019: Update From the GBD 2019 Study. Journal of the American College of
Cardiology, 76(25), 2982–3021. https://doi.org/10.1016/j.jacc.2020.11.010
Bhatt, D. L., Lopes, R. D., & Harrington, R. A. (2022). Diagnosis and Treatment of Acute
Coronary Syndromes: A Review. JAMA, 327(7), 662–675.
https://doi.org/10.1001/jama.2022.0358
Pollock JD, Makaryus AN. Physiology, Cardiac Cycle. [Updated 2022 Oct 3]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK459327/
Yoon, H. J., Kim, K. H., Kim, J. Y., Cho, J. Y., Yoon, N. S., Park, H. W., Hong, Y. J., Kim, J.
H., Ahn, Y., Jeong, M. H., Cho, J. G., & Park, J. C. (2015). Impaired Diastolic Recovery
after Acute Myocardial Infarction as a Predictor of Adverse Events. Journal of
cardiovascular ultrasound, 23(3), 150–157. https://doi.org/10.4250/jcu.2015.23.3.150
Pollock JD, Makaryus AN. Physiology, Cardiac Cycle. [Updated 2022 Oct 3]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK459327/
Ferreira-Martins, J., & Leite-Moreira, A. F. (2010). Physiologic basis and pathophysiologic
implications of the diastolic properties of the cardiac muscle. Journal of biomedicine &
biotechnology, 2010, 807084. https://doi.org/10.1155/2010/807084
Poulsen S. H. (2001). Clinical aspects of left ventricular diastolic function assessed by Doppler
echocardiography following acute myocardial infarction. Danish medical bulletin, 48(4),
199–210.
Lahiri, S. K., Aguilar-Sanchez, Y., & Wehrens, X. H. T. (2021). Mechanisms underlying
www.ijmshr.com Page 56
International Journal of Medical Science and Health Research
Vol.8, No. 04; 2024
ISSN: 2581-3366
pathological Ca2+ handling in diseases of the heart. Pflugers Archiv : European journal
of physiology, 473(3), 331–347. https://doi.org/10.1007/s00424-020-02504-z
Eisner, D. A., Caldwell, J. L., Trafford, A. W., & Hutchings, D. C. (2020). The Control of
Diastolic Calcium in the Heart: Basic Mechanisms and Functional Implications.
Circulation research, 126(3), 395–412.
https://doi.org/10.1161/CIRCRESAHA.119.315891
Sigurdsson A. (1995). Neurohormonal activation in patients with acute myocardial infarction or
chronic congestive heart failure. With special reference to treatment with angiotensin
converting enzyme inhibitors. Blood pressure. Supplement, 1, 1–45.
Frangogiannis N. G. (2021). Cardiac fibrosis. Cardiovascular research, 117(6), 1450–1488.
https://doi.org/10.1093/cvr/cvaa324
Moreo, A., Ambrosio, G., De Chiara, B., Pu, M., Tran, T., Mauri, F., & Raman, S. V. (2009).
Influence of myocardial fibrosis on left ventricular diastolic function: noninvasive
assessment by cardiac magnetic resonance and echo. Circulation. Cardiovascular
imaging, 2(6), 437–443. https://doi.org/10.1161/CIRCIMAGING.108.838367
Obokata, M., Reddy, Y. N. V., & Borlaug, B. A. (2020). Diastolic Dysfunction and Heart Failure
With Preserved Ejection Fraction: Understanding Mechanisms by Using Noninvasive
Methods. JACC. Cardiovascular imaging, 13(1 Pt 2), 245–257.
https://doi.org/10.1016/j.jcmg.2018.12.034
Nijland, F., Kamp, O., Karreman, A. J., van Eenige, M. J., & Visser, C. A. (1997). Prognostic
implications of restrictive left ventricular filling in acute myocardial infarction: a serial
Doppler echocardiographic study. Journal of the American College of Cardiology, 30(7),
1618–1624. https://doi.org/10.1016/s0735-1097(97)00369-0
Møller, J. E., Søndergaard, E., Poulsen, S. H., & Egstrup, K. (2001). The Doppler
echocardiographic myocardial performance index predicts left-ventricular dilation and
cardiac death after myocardial infarction. Cardiology, 95(2), 105–111.
https://doi.org/10.1159/000047355
GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week
mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per
lo Studio della Sopravvivenza nell'infarto Miocardico. (1994). Lancet (London, England),
343(8906), 1115–1122.
Sakata M., Kashiro M., Hirata M. Prognostic Value of Doppler Transmitral Flow Velocity
Patterns in Acute Myocardial Infarction The American Journal of Cardiology, 1997, 79 (
9), pp. 1165-1169
Ma, C., Luo, H., Fan, L., Liu, X., & Gao, C. (2020). Heart failure with preserved ejection
fraction: an update on pathophysiology, diagnosis, treatment, and prognosis. Brazilian
journal of medical and biological research = Revista brasileira de pesquisas medicas e
biologicas, 53(7), e9646. https://doi.org/10.1590/1414-431X20209646
French, B. A., & Kramer, C. M. (2007). Mechanisms of Post-Infarct Left Ventricular
Remodeling. Drug discovery today. Disease mechanisms, 4(3), 185–196.
https://doi.org/10.1016/j.ddmec.2007.12.006
Xu, L., Pagano, J., Chow, K., Oudit, G. Y., Haykowsky, M. J., Mikami, Y., Howarth, A. G.,
www.ijmshr.com Page 57
International Journal of Medical Science and Health Research
Vol.8, No. 04; 2024
ISSN: 2581-3366
White, J. A., Howlett, J. G., Dyck, J. R. B., Anderson, T. J., Ezekowitz, J. A., Thompson,
R. B., & Paterson, D. I. (2021). Cardiac remodelling predicts outcome in patients with
chronic heart failure. ESC heart failure, 8(6), 5352–5362.
https://doi.org/10.1002/ehf2.13626
Faggiano, P., Vizzardi, E., Pulcini, E., Maffeo, D., Fracassi, F., Nodari, S., & Dei Cas, L. (2007).
The study of left ventricular diastolic function by Doppler echocardiography: the
essential for the clinician. Heart international, 3(1), 42. https://doi.org/10.4081/hi.2007.42
Sharifov, O. F., Schiros, C. G., Aban, I., Denney, T. S., & Gupta, H. (2016). Diagnostic
Accuracy of Tissue Doppler Index E/e' for Evaluating Left Ventricular Filling Pressure
and Diastolic Dysfunction/Heart Failure With Preserved Ejection Fraction: A Systematic
Review and Meta-Analysis. Journal of the American Heart Association, 5(1), e002530.
https://doi.org/10.1161/JAHA.115.002530
Robinson, S., Ring, L., Oxborough, D. et al. The assessment of left ventricular diastolic function:
guidance and recommendations from the British Society of Echocardiography. Echo Res
Pract 11, 16 (2024). https://doi.org/10.1186/s44156-024-00051-2
Andersen, O. S., Smiseth, O. A., Dokainish, H., Abudiab, M. M., Schutt, R. C., Kumar, A., Sato,
K., Harb, S., Gude, E., Remme, E. W., Andreassen, A. K., Ha, J. W., Xu, J., Klein, A. L.,
& Nagueh, S. F. (2017). Estimating Left Ventricular Filling Pressure by
Echocardiography. Journal of the American College of Cardiology, 69(15), 1937–1948.
https://doi.org/10.1016/j.jacc.2017.01.058
Mitter, S. S., Shah, S. J., & Thomas, J. D. (2017). A Test in Context: E/A and E/e' to Assess
Diastolic Dysfunction and LV Filling Pressure. Journal of the American College of
Cardiology, 69(11), 1451–1464. https://doi.org/10.1016/j.jacc.2016.12.037
Park, J., Song, Y. J., Kim, S., Kim, D. K., Kim, K. H., Seol, S. H., Kim, D. I., & Ha, S. J. (2022).
The long-term prognostic value of E/e' in patients with ST segment elevation myocardial
infarction. Indian heart journal, 74(5), 369–374. https://doi.org/10.1016/j.ihj.2022.08.002
Harada, T., Obokata, M., Kagami, K., Sorimachi, H., Kato, T., Takama, N., Wada, N., & Ishii,
H. (2022). Utility of E/e' Ratio During Low-Level Exercise to Diagnose Heart Failure
With Preserved Ejection Fraction. JACC. Cardiovascular imaging, S1936-
878X(22)00666-0. Advance online publication.
https://doi.org/10.1016/j.jcmg.2022.10.024
Park, J., Song, Y. J., Kim, S., Kim, D. K., Kim, K. H., Seol, S. H., Kim, D. I., & Ha, S. J. (2022).
The long-term prognostic value of E/e' in patients with ST segment elevation myocardial
infarction. Indian heart journal, 74(5), 369–374. https://doi.org/10.1016/j.ihj.2022.08.002
Nallapati, S. N., Otikunta, A. N., Reddy, Y. V. S., & Srinivas, R. (2015). E/e’ as a Predictor of
Short-Term Survival Following ST-Elevation Myocardial Infarction. International
Journal of Clinical Medicine, 06(11), 831–837. https://doi.org/10.4236/ijcm.2015.611109
Kane GC, Karon BL, Mahoney DW, et al. Progression of Left Ventricular Diastolic Dysfunction
and Risk of Heart Failure. JAMA. 2011;306(8):856–863. doi:10.1001/jama.2011.1201
www.ijmshr.com Page 58
