Predicting cardiac index using the electrocardiogram in pulmonary hypertension patients
Marzieh Mirtajaddini1, Nasim Naderi1, Khadije Mohammadi2, Sepideh Taghavi1, Maryam Maharloo1, Saeideh Mazloomzadeh1, Ahmad Amin1
1 Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
2 Cardiovascular Research Center, Kerman University of Medical Sciences, Kerman, Iran
Correspondence Address:
Dr. Marzieh Mirtajaddini
Rajaie Cardiovascular Medical and Research Center, Valiasr Ave, Hashemi Rafsanjani Blvd, Tehran
Iran
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/rcm.rcm_11_22
Background: Pulmonary hypertension (PH) is a fatal disease where on-time treatment can change the prognosis. The selection of treatment is dictated by the severity of PH. The cardiac index (CI) is a robust indicator of PH severity. This trial aimed to find out the association between electrocardiogram (ECG) data and CI as a prognostic factor of PH. Methods: Ninety-five patients with precapillary PH were included in the study. The cardiac output of patients was calculated using the right heart catheterization and the Fick formula. Patients were categorized into low- and high-risk groups based on the CI. Their ECGs were interpreted by an expert cardiologist. The association between ECG parameters and severity of PH was evaluated based on the CI. Results: The median age of patients was 36 years. The mean of CI was 2.35 L/min/m2 with a standard deviation of 0.74. About 36% of patients were in the high-risk category based on the CI. Among ECG parameters, ST segment depression in V1-V6 and R/S ratio ≥1 in V1 were found significantly correlated with CI for high-risk category (P = 0.026). Conclusion: ST segment depression in V1-V6 and R/S ratio ≥1 in V1 had a significant association with CI in the range lower than 2 L/min/m2, which is an indicator of poor PH prognosis. Therefore, these variables can be used as an inexpensive and available prognostic factor in patients with precapillary PH.
Keywords: Electrocardiogram, heart catheterization, pulmonary hypertension
Pulmonary hypertension (PH) is a serious disease which is categorized into five clinical groups based on the World Health Organization (WHO) classification. This classification demonstrates the underlying causes of PH.[1],[2] Regardless of the PH causes, a well-timed detection of PH progression is necessary to decide on appropriate treatment and improvement of the prognosis.[3] As clinical signs of PH are mild until the end-stage disease, several methods are used for screening and evaluation of PH severity.[4] The measured cardiac index (CI) using the right heart catheterization (RHC) is a strong predictor of the right ventricular (RV) function. Hence, it is a useful and confirmed approach for the evaluation of the PH prognosis.[1] RHC is an invasive and expensive method which may not be available in all medical centers. Nowadays, more efforts are carried out to find available and cost-effective techniques.[5] Electrocardiogram (ECG) is a cost-effective and noninvasive method which is available in all medical centers. ECG can be used as a prognostic factor if the association between ECG and CI is proved. Several studies have evaluated ECG as an indicator of PH hemodynamic and prognostic factor;[6],[7],[8],[9],[10] however, trials related to the association of ECG data and CI are rare and limited to R-wave and S-wave amplitude.[11],[12] In this study, the association among CI, as a prognostic factor of PH and QRS changes, ST depression (STD) and T-wave inversion (TI) were evaluated.
MethodsThis study was a retrospective trial performed on patients with precapillary PH (Groups 1, 3, and 4 PH based on the WHO classification) who had been referred to our center, a tertiary center of PH, for 5 years. The study protocol was approved by the Research and Ethics Committee of Rajaie Cardiovascular Medical and Research Center, and all methods were undertaken in accordance with relevant guidelines and regulations. Patients with diabetes mellitus, systemic hypertension, coronary artery disease, congenital heart disease, severe left valvular heart disease, ejection fraction <45%, significant electrolyte abnormality, and uninterpretable ECG were excluded from the study. In addition, two of the patients with left bundle branch block and secondary ST-T changes were also excluded. Finally, 95 patients were remained in the trial.
Right heart catheterization
RHC was done using femoral, jugular, subclavian, and brachial vein accesses through the guide of fluoroscopy. The cardiac output (CO) was calculated based on the Fick method. CI was determined by dividing CO to patient's body surface area. Patients' PH can be categorized based on CI into low-, moderate-, and high-risk groups [Table 1].[1] In this study, patients were divided into two groups of high-risk patients (CI <2 L/min/m2) and nonhigh-risk patients (CI ≥2 L/min/m2).
Electrocardiogram
A 12-lead ECG was done in supine and standard positions with paper speed of 25 mm/s and sensitivity 10 mm/millivolt. The ECGs of patients were performed with a delay of maximum of 3 days from RHC. The ECGs were analyzed manually by an expert cardiologist without an orientation about patient's characteristics and their RHC data. The evaluated ECG variables included cardiac rhythm, QRS complex axis, STD in inferior leads (Inf), STD in V1-V3, STD in V4-V6, STD in V1-V6, T-wave TI in Inf, TI in V1-V3, TI in V4-V6, TI in V1-V6, R-wave amplitude in V1 (R in V1), S-wave amplitude in V1 (S in V1), R-wave amplitude in aVR (R in aVR), S-wave amplitude in aVR (S in aVR), R-wave amplitude in V6 (R in V6), S-wave amplitude in V6 (S in V6), the ratio of R/S (R/S) in V1 ≥1, R/S in aVR ≥1, S/R in V6 ≥1, R-S wave (R-S) in V1, R-S in aVR, and S-R in V6. Depression of ST segment more than 1 mm, based on the next TP segment, was defined as STD. Each variable was measured in three beats and the mean value was recorded. According to the induction of ST-segment depression by digoxin usage and its resolution by diltiazem,[13],[14] the association between two drugs and ST segment changes was evaluated.
Statistical analysis
Statistical analysis was performed using the SPSS software 19 for Windows (IBM SPSS Statistics for Windows, Version 19.0). Numerical variables with normal distribution are reported as mean ± standard deviation (SD), and variables with abnormal distribution are presented as minimum, maximum, and median. Categorical variables are reported as percentage. The association among CI categories, digoxin usage, diltiazem usage, and ECG variables was evaluated using binary logistic regression. Independent-samples t-test was used for comparison of patients with and without ECG variables.
ResultsAs explained earlier, 95 patients were entered in this study. The maximum, minimum, and median age of the patients were 84, 17, and 36 years, respectively. The majority of patients were female (64.2% or 61 patients). In medical history, 5.3% of patients underwent treatment with diltiazem and 11.6% of them had a history of digoxin usage. About 78% of cases were in Group 1, 5% in Group 3, and 17% in Group 4 PH. The mean of CI was 2.35 with an SD of 0.74. About 36% (34 patients) were in high-risk category based on CI and 64% (61 patients) categorized in nonhigh-risk group [Table 2].
The analysis of ECG data showed that most of PH patients had sinus rhythm (96.8%). Only 2.1% of patients had atrial fibrillation and 1.1% of them had multifocal atrial tachycardia. 68.4% of patients had right axis deviation and 30.5% had normal sinus rhythm. STD in Inf was seen in 64.2% (61 patients). 75.8% (72 patients) of patients had R/S in aVR ≥1 and 57.9% (55 patients) had R/S in V1 ≥1. The summary of the ECG parameters is summarized in [Table 3].
Association between ECG parameters and patients' categories based on CI was evaluated. Among ECG variables, STD in V1-V6 and R/S ≥1 in V1 had a significant association with high-risk category (P = 0.026). P values of TI in Inf and TI in V1-V6 were borderline (P = 0.070 and 0.077). The analyses of the association between ECG data and high-risk category are summarized in [Table 4]. Furthermore, the analysis shows that CI in patients with STD V1-V6 and R/S ≥1 in V1 was significantly greater than those without this variable (P = 0.002 and 0.005) [Figure 1]. [Figure 2] shows the receiver-operating characteristic curve of STD V1-V6, R/S ≥1 in V1 and CI.
No patient had Salvador Dali sagging sign and digoxin effect on the ECG. Nevertheless, the association between STD in V1-V6 and digoxin usage was not significant (P = 0.951). Some studies have shown that diltiazem can resolve ST changes, especially ST changes due to ischemia.[13],[14] Therefore, the relationship between the absence of STD in V1-V6 and diltiazem usage was assessed, which was not statistically significant (P = 0.254).
DiscussionPH is a fatal disease which is treated based on its severity and prognosis. Several techniques are used for PH severity detection; however, little attention has been paid to ECG, despite its availability and cost-effectiveness. This study aimed to find the ability of ECG as a prognostic factor of PH.
Stroke volume and heart rate are two factors which can determine CO and CI. Stroke volume is influenced by myocardial contraction force, preload and afterload. During PH progression, stroke volume reduces due to afterload elevation. Thus, CI is decreased despite an increase in the heart rate. Therefore, CI is an indicator of the RV function and a robust prognostic factor in PH.[1] In the current study, the association between CI and QRS complex as well as ST-T changes was evaluated. The analysis showed that R/S in V1 ≥1 has an association with CI <2 L/min/m2. The findings of the Kanemoto study have a controversy with the findings of this study. Kanemoto showed the association between CI <2.8 L/min/m2 and R in V6, R/S ≤2 in V6 and RVH, but no correlation was found between R/S in V1 and CI.[11] Furthermore, Cheng et al. demonstrated that S in V6 correlates with CI and the R wave in aVR has an association with survival.[12] Association between R/S in V1 and PH mortality was reported in Tonelli's study, while the correlation between R/S in V1 and CI was not observed.[15]
The other finding of this study was the correlation between STD in V1-V6 and CI, which has not been evaluated in other trials. RV has a greater sensitivity to afterload changes in comparison with the left ventricle; hence, a mild increase in the RV afterload can induce a severe decrease in stroke volume and CI.[16],[17] Chronic pressure overload due to an increase in wall stress can lead to RV hypertrophy. As the RV cannot be adapted to the increase in the afterload in most of these cases, it may result in RV dilation, RV failure, and vascular remodeling.[18],[19] RV dilation reduces the RV blood flow in diastole and decreases the RV perfusion.[20] Therefore, PH due to RV hypertrophy, RV ischemia and RV failure can produce ST-T changes.[21]
TI was less evaluated in PH prognosis and was more considered in acute pulmonary thromboembolism. Some researchers have reported that TI in precordial leads has a correlation to RV dysfunction and severity of acute pulmonary thromboembolism,[22],[23] while the other study by Petruzzelli et al. rejected this idea.[24] However, in the current study, based on the P values of TI in Inf and TI in V1-V6 (P = 0.070 and 0.077), further investigation with greater sample size is recommended for future studies.
Despite undertaking this study in patients with precapillary PH, most of the patients were in the PH Group of 1, where the ECG changes may be different in other PH groups. Therefore, other studies in well-populated groups of PH are recommended.
ConclusionSTD in V1-V6 and R/S ≥1 in V1 had a significant association with CI <2 L/min/m2, which is an indicator of PH prognosis. Therefore, STD in V1-V6 and R/S ≥1 in V1 is recommended to use as a prognostic factor in patients with precapillary PH.
Ethical clearance
The study was approved by the research and ethics committee of Rajaie Cardiovascular Medical and Research Center.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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