CC BY
6
International Heart and Vascular Disease Journal • Volume 7, № 22, June 2019
Journal of the Cardioprogress Foundation
OriginaL articLes
Assessment of the relation between
pulmonary hypertension severity and left ventricular diastolic dysfunction in patients with ischemic heart disease
Author
Mahmoud Shawky Abd-El moneum, M.D., Cardiology Department, Benha University Hospital, Benha city, Egypt.
Background. Association between pulmonary hypertension and left ventricular (L.V.) diastolic dysfunction in pa- tients with ischemic heart disease has been observed. However, the relation between the severity of pulmonary hypertension and left ventricular diastolic dysfunction is still unclear.
Objectives. To explore the relationship between pulmonary hypertension severity and L.V. diastolic dysfunction in patients with ischemic heart disease.
Patients and methods. 200 symptomatic patients with ischemic heart disease were included in this study. History taking, clinical examination, and echocardiography were performed to all patients, LV dimensions, systolic and diastolic function, and systolic pulmonary artery pressure (SPAP) were measured. We characterized the patients into two groups as indicated by the presence or absence of diastolic dysfunction. Results. Patients with diastolic dysfunction had significantly higher SPAP (p < 0.00001), and significantly higher incidence of severe pulmonary hypertension (p = 0.034). Autonomous indicators for the presence of severe pulmonary hypertension were E/Ex > 15, E/A< 1 and E-wave DT < 160.
Conclusion. patients with ischemic heart disease in addition to left ventricular diastolic dysfunction had a higher systolic pulmonary artery pressure and a higher incidence of severe pulmonary hypertension. Systolic pulmonary artery pressure was essentially connected with LV diastolic dysfunction. Key Words: left ventricular diastolic dysfunction, pulmonary hypertension.
* Corresponding author. Tel.: +2001223723050. E-mail: [email protected]
Mahmoud Shawky Abd-El moneum
Cardiology Department, Benha University Hospital, Benha city, Egypt.
conflicts of interest: nothing to declare.
Received: 06.04.2019 Accepted: 06.05.2019
Introduction
Elevated pulmonary artery pressure in patients with ischemic heart disease has been observed a long time ago. Oliver and his partners in 1978 have discov- ered a relationship between the increase in both pul- monary artery pressure and ischemic heart disease [1]. LV diastolic dysfunction however are at increased risk of developing heart failure [2] and it is seen that the incidence of heart failure with preserved ejec- tion fraction (HFpEF) is particularly higher among ischemic patients [3-4]. When present in ischemic patients with diastolic dysfunction and/or HFpEF, pulmonary hypertension has a deleterious effect on mortality and morbidity [5]. Beside the presence of diastolic dysfunction, other factors were found to be associated with the presence of pulmonary hyperten- sion in patients with ischemic heart disease like el- evated pulmonary vascular resistance, declined renal function, and increased pro-Brain Type Natriuretic Peptide (pro-BNP) levels [6]. However, the severity of pulmonary hypertension in patients with ischemic heart disease and its relation to different indices of diastolic function has not been yet studied. Along these lines, the point of this work was to investigate the relationship between pulmonary hypertension severity and different indices of LV diastolic function in patients with ischemic heart disease.
Patients and methods
This study was performed in the Cardiology Department, Benha University during the period from January 2017 till November 2018. This study included 200 symptomatic patients with ischemic heart
disease.
Patients were barred from this study if one or more of the following were present:
• Severe pulmonary disease «identified as forced vital capacity < 50 %» [7-9].
• LV systolic dysfunction with ejection fraction (EF) <50 %.
• Known hypertension.
• More than mild aortic or pulmonary stenosis, mitral or aortic regurgitation > grade 2, or severe tricuspid regurgitation.
• Significant congenital heart disease that may affect pulmonary pressure.
• Atrial fibrillation.
We made the following to every patient after obtaining a written informed consent:
1) History taking and clinical examination.
2) Pulmonary function test with measuring of forced vital capacity for exclusion.
3) Echocardiography: Standard transthoracic echocardiographic and Doppler studies were performed for all patients using GE VIVID E9 machine with 2.5 MHz transducers. The following measures were taken:
• M-mode measures: Left atrial (LA) diameter, left ventricular end diastolic (LVEDD) and systolic dimensions (LVESD), ejection fraction (EF) and fraction of shortening (FS).
• Left atrial volume (LAV) was determined by measuring LA area in apical four, and apical two chamber views.
• Mitral valve (MV) flow velocities by pulsed Doppler; E-wave, A-wave E/A ratio and E-wave decel- eration time (DT).
• Tissue Doppler of the septal segment of MV an-nulus was done from the apical 4 chamber view with measuring of the peak systolic wave (Sx), early (Ex), late diastolic waves (A) and E/Ex were calculated.
• Diastolic function was evaluated by combining all measured parameters. The diastolic function was considered normal if E/A > 1, DT between 160 and 240 ms, E/A > 1, and E/Ex < 15.
• Grade 1 diastolic dysfunction (impaired relaxation pattern) was diagnosed when E/A < 1, and DT > 240 ms, plus either E/A < 1, or E/D <8.
• Grade 2 diastolic dysfunction (pseudo normal pattern) was diagnosed when E/A between 1 and 2, and DT between 160 and 240 ms, plus either E/A < 1, or E/E\ 8-15.
• Grade 3 diastolic dysfunction (restrictive fill- ing pattern) was diagnosed when E/A > 2, and DT < 160 ms, plus either E/A < 1, or E/D > 15 [10-11].
• As all our patients had mild or moderate tri-cuspid regurgitation, systolic pulmonary artery pressure (SPAP) was calculated from the peak continuous wave Doppler signal of tricuspid regurgitant jet veloc- ity and adding a constant value for right atrial pres- sure to it (10 mmHg). Patients with SPAP > 40 mmHg
14
International Heart and Vascular Disease Journal. Volume 7, № 22, June 2019. Original
were considered as having pulmonary hypertension, and patients with SPAP > 80 mmHg were considered as having severe pulmonary hypertension [12].
4) Statistical analysis: All data were analyzed using the SPSS for Windows package program (Version 20.0; Armonk, NY, USA:IBM Corp.). Differences between patients' group and control group were analyzed using x2 test and Student's t-test. Relationsships between different variables were investigated by Pearson cor- relation analysis. The logistic regression analysis was evaluated by the Hosmer -Lemeshow goodness-of-fit test.p value < 0.05 was regarded as being statisti- cally significant. We repeated the echocardiographic measures in 30 patients within 7 days from the first measure for assessing the intraobserver variability. The interobserver and intraobserver variability were calculated by dividing the difference between the two sets of measurements, by the mean of the two observations.
Results
Patients were divided into two groups as indicated by the presence or absence of LV diastolic dysfunction:
Group 1: Included 100 patients without diastolic dysfunction.
Group 2: Included 100 patients with diastolic dysfunction.
There was no significant difference between the two groups regarding clinical data of the two groups as the mean age of patients in group A was 54.46±
Table 1. Comparison of clinical data among studied groups
7.55 years and the mean age of patients in group B was 55.02 ± 6.80 years (p-value = 0.582), and regard- ing sex distribution, 57 % of patients in group A were males and 43 % of the same group were females and group B included males constituting 55 % of the group and females representing 45 % of the group (p-value= 0.776), the mean value of BMI in group A was 26.22 ± 1.82 and was 28.86 ± 1.82 and in group B (p-value= 0.325), hypertension was in 60 % of pa- tients in group A and 51 % of patients in group B (pvalue= 0.200), also diabetes mellitus was in 53 % of patients in group A and 50 % of patients in group B (p-value= 0.671), 43 patients in group A were smok- er and 42 smoker were in group B (p-value= 0.9), and dyslipidemia was in 37 % of patients in group A versus 40 % of patients in group B (p-value= 0.7) (Table 1).
As shown in Table 2, patients with diastolic dysfunction had significantly higher LA diameter (31.1 ±5.8 mm in group 1, versus 33.8 ± 4.9 mm in group 2, p = 0.013), higher LAV (36.2 ± 8.61 ml in group 1, versus 42.1 ±9.64 ml in group2, p = 0.0011), lower septal E\ velocity (11.3 ± 3.58 cm/s in group 1, versus
8.1 ±4.87 cm/s in group 2, p = 0.0071), higher septal E/E^ ratio (9.7 ± 3.11 in group 1, versus 14.2 ± 4.65 in group 2, p < 0.00001), higher SPAP (25.3 ± 7.12 mmHg in group 1, versus 33.4 ±14.34 mmHg in group 2, p < 0.00001), and significantly higher incidence of se- vere pulmonary hypertension (0 % in group 1, versus 7 %, p = 0.034). There was no significant difference
Table 2. Comparison of echocardiographic data among studied groups
Group A Group B p. value
LAD (mm) 31.1 ± 5.8 33.8 ± 49 0.013
LAV (ml) 36.2 ± 8.61 42.1 ± 9.64 0.0011
Septal E\ (cm/s) 11.3 ± 3.58 8.1 ± 4.87 0.007
Septal E/E\ 9.7 ± 3.11 14.2 ± 4.65 0.00001
LVEDD (mm) 46.8 ± 7.82 48.2 ± 9.17 0.408
LVESD (mm) 31.3 ± 6.51 33.4 ± 7.23 0.116
FS (%) 32.4 ± 7.42 30.1 ± 8.16 0.129
EF (%) 62.40 ± 6.95 62.16 ± 7.01 0.808
SPAP (mmHg) 25.3 ± 7.12 33.4 ± 14.34 <0.0000 1
severe pulmonary hypertension 0 (0 %) 7 (10 %) 0.034
LAD = left atrial dimension, LAV = left atrial volume, LAV = left atrial volume index, septal the early diastolic tissue Doppler wave of septal segment of mitral annulus, E: the early diastolic Doppler wave of mitral valve flow, LVEDD = left ventricular end diastolic dimension, LVESD = left ventricular end systolic dimension, FS = fraction of shortening, EF = ejection fraction, SPAP = systolic pulmonary artery pressure.
Group A Group B p. value
Age (years) Mean ± S. 54.46 ± 55.02 ± 0.582
D 7.55 6.80
BMI Mean ± S. 26.22 ± 28.86 ± 0.325
D 1.82 1.82
Sex Male (%) 57 (57 %) 55 (55 %) 0.776
Female (%) 43 (43 %) 45 (45 %)
+ve 60 51
HTN 60.0 % 51 % 0.200
- ve 40 49
40.0 % 49 %
+ve 53 50
DM 53 % 50.0 % 0.671
- ve 47 50
47 % 50.0 %
+ve 43 42
Smoking 43.0 % 42.0 % 0.9
- ve 57 58
57.0 % 58.0 %
+ve 37 40
Hyperlipidemia 37.0 % 40.0 % 0.7
- ve 63 60
63.0 % 60.0 %
between the two study groups regarding other echo-cardiographic data.
Discussion
This study furnishes a complete correlation between patients with ischemic heart disease with and without diastolic dysfunction regarding the prevalence and severity of pulmonary hypertension. Left atrial diameter was seen to be higher in patients with dia-stolic dysfunction compared to those without. This was concordant with Mukherjee and his partners who defined two groups of patients with ischemic heart disease as indicated by presence or absence of pulmonary hypertension. They discovered that left atrial area was larger among ischemic heart patients with PH. This perception, bolster the idea that ischemic heart disease leads to both pulmonary venous as well as arterial hypertension. This can be demonstrated through the mechanism of pulmonary remodeling and increase pulmonary vascular resistance [6].
Furthermore Gerdts et al. in 2002 studied LA indices in patients with ischemic heart disease and sealed that patients with LA enlargement were older, more obese, had elevated systolic blood pressure and pulse pressure. Regarding indices of LV diastolic function, our results disclosed that a restrictive pattern obtained by E/Ex> 15 was the strongest predictor of the presence of pulmonary hypertension this was followed by E/A < 1, and E-wave DT < 160 ms [13].
The prognostic importance of a restrictive filling pattern after acute myocardial infarction (AMI) was initially declared by Oh et al.in 1992 [14]. They considered the prognostic ramifications of this pattern in post AMI patients in a cohort of 62 patients. They discovered that restrictive filling pattern was related to a high occurrence of in-hospital congestive heart failure.
This was confirmed by Poulsen et al. in an age-selected population with a first AMI in which Doppler echocardiography was done within 1 hour of hospital admission and they found that deceleration of E-wave of MV flow < 130 ms was able to identify patients at risk of development of congestive heart failure fol- lowing AMI [15].
In 1997, Nijland et al. declared in a study of 95 patients with first AMI that DT < 140 ms was related to a 22 % survival rate at 3 years compared with 100 % in the nonrestrictive group [16].
Although the study was limited by a small number of deaths, this finding has subsequently been confirmed in several studies [17-20].
In these studies, patients with a restrictive filling pattern have been characterized by higher age, more advanced LV systolic dysfunction, and a high risk of in-hospital heart failure.
The relation between ischemic heart disease and pulmonary hypertension was a matter of concern a long time ago, [1] but the debate continues about the exact mechanism of this relationship. However, the association of diastolic dysfunction and increased pulmonary resistance with pulmonary hypertension in patients with ischemic heart disease aroused the attention about their possible mechanism in the development of pulmonary hypertension in these patients [6]. The results support the relationship between LV diastolic dysfunction and pulmonary hypertension in patients with ischemic heart disease as we have found that severe pulmonary hypertension was more prevalent among with ischemic heart patients with diastolic dysfunction (10 % of patients with diastolic dysfunction had severe pulmonary hypertension versus 0 % of patients without). Also we have discovered that LV diastolic dysfunction indices (E/Ex) ratio, E/A ratio, and (E-wave DT) were significantly correlated with SPAP.
Conclusion
• Ischemic heart patients with diastolic dysfunction had an elevated systolic pulmonary artery pressure and a higher incidence of severe pulmonary hypertension.
• Systolic pulmonary artery pressure was significantly correlated with different indices of LV diastolic function. — In patients with ischemic heart disease, E/E\ > 15, E/A 0 < 1, E-wave DT < 160 ms were independent predictors for pulmonary hypertension.
• Looking for pulmonary hypertension in patients with ischemic heart disease, currently when associated with LV diastolic dysfunction, may help in managing them and in predicting their prognosis.
Conflict of interest: None declared.
References
1. Olivari MT, Fiorentini C, Polese A, Guazzi MD. Pulmonary hemodynamics and right ventricular function in hypertension. Circulation. 1978;57:1185-1190.
2. Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK. The progression from hypertension to congestive heart failure. JAMA. 1996;275:1557-1562.
3. Lam CS, Roger VL, Rodeheffer RJ, Borlaug BA, Enders FT, Redfield MM. Pulmonary hypertension in heart failure with
16
International Heart and Vascular Disease Journal. Volume 7, № 22, June 2019. Original
preserved ejection fraction: acommunity-based study. J Am Coll Cardiol. 2009;53:1119-1126.
4. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251-259.
5. Mukherjee M, Mehta NK, Connolly JJ, et al. Pulmonary hypertension in hypertensive patients: association with diastolic dysfunction and increased pulmonary vascular resistance. Echocardiography. 2014;31:442-448.
6. Chobanian AV, Bakris GL, Black HR, et al. National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-2572.
7. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-520.
8. Morris JF, Koski A, Breese JD. Normal values and evaluation of forced endexpiratory flow. Am Rev Respir Dis. 1975; 111:755- 762.
9. Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28: 1-39.e14.
10. Nagueh SF, Appleton CP, Gillebert TC, et al. Recommendations for the evaluation of left ventricular diastolic function by echo- cardiography. J Am Soc Echocardiogr. 2009;22:107-133.
11. Bossone E, D'Andrea A, D'Alto M, et al. Echocardiography in pulmonary arterial hypertension: from diagnosis to prognosis. J Am Soc Echocardiogr. 2013;26:1-14.
12 Gerdts E, Oikarinen L, Palmieri V, et al. Correlates of left atrial size in hypertensive patients with left ventricular hypertrophy: the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) Study. Hypertension. 2002;39:739-743.
13. Oh JK, Ding ZP, Gersh BJ, Bailey KR, Tajik AJ. Restrictive left ventricular diastolic filling identifies patients with heart fail- ure after acute myocardial infarction. J Am Soc Echocardiogr. 1992;5:497-503.
14. Poulsen SH, Jensen SE, G0tzsche O, Egstrup K. Evaluation and prognostic significance of left ventricular diastolic function as- sessed by Doppler echocardiography in the early phase of a first acute myocardial infarction. Eur Heart J. 1997;18:1882-1889.
15. Nijland F, Kamp O, Karreman AJ, van Eenige MJ, Visser CA. Prognostic implications of restrictive left ventricular filling in acute myocardial infarction: a serial Doppler echocardiograph-ic study. J Am Coll Cardiol. 1997;30:1618-1624.
16. Temporelli PL, Giannuzzi P, Nicolosi GL, et al. Dopplerderived mitral deceleration time as a strong prognostic marker of left ventricular remodeling and survival after acute myocar- dial infarction: results of the GISSI-3 echo substudy. J Am Coll Cardiol. 2004;43:1646-1653.
17. Beinart R, Boyko V, Schwammenthal E, et al. Long-term prognostic significance of left atrial volume in acute myocardial infarction. J Am Coll Cardiol. 2004;44:327-334.
18. Cerisano G, Bolognese L, Buonamici P, et al. Prognostic implications of restrictive left ventricular filling in reperfused anterior acute myocardial infarction. J Am Coll Cardiol. 2001;37:793-799.
19. Schwammenthal E, Adler Y, Amichai K, et al. Prognostic value of global myocardial performance indices in acute myocardial infarction: comparison to measures of systolic and diastolic left ventricular function. Chest. 2003;124:1645-1651.
20. Farag EM, Al-Daydamony MM, Gad MM. What is the association between left ventricular diastolic dysfunction and 6min-ute walk test in hypertensive patients? J Am Soc Hypertens. 2017;11:158-164.
