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ORIGINAL ARTICLE
Year : 2021  |  Volume : 31  |  Issue : 1  |  Page : 6-10

Assessment of pulmonary arterial hemodynamic and vascular changes by pulmonary pulse transit time in patients with human immunodeficiency virus infection


1 Department of Cardiology, University of Health Sciences, Ankara City Hospital, Ankara, Turkey
2 Department of Cardiology, Kocaeli University, Kocaeli, Turkey
3 Department of Infectious Diseases and Clinical Microbiology, Hacettepe University, Ankara, Turkey
4 Department of Infectious Diseases and Clinical Microbiology, Ankara Training and Research Hospital, Ankara, Turkey
5 Department of Infectious Diseases and Clinical Microbiology, Atilim University, Ankara, Turkey

Date of Submission10-Sep-2020
Date of Decision21-Nov-2020
Date of Acceptance08-Dec-2020
Date of Web Publication20-May-2021

Correspondence Address:
Mehmet Akif Erdol
Üniversiteler Mahallesi 1604, Cadde No: 9 Çankaya/Ankara, University of Health Sciences, Ankara City Hospital, Ankara 06800
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcecho.jcecho_103_20

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  Abstract 


Introduction: Pulmonary arterial hypertension and human immunodeficiency virus (HIV) infection is a well-known association. Pulmonary pulse transit time (pPTT) is a recent echocardiographic marker that might be used for evaluation of pulmonary arterial stiffness (PAS) in patients with HIV infection. We aimed to investigate whether pPTT elevated in patients with HIV infection compared to healthy controls and its association with echocardiographic indices of right ventricular functions. Materials and Methods: Fifty HIV (+) patients from infectious disease outpatient clinics and fifty age- and sex-matched HIV (−) healthy volunteers were enrolled in this study. pPTT was measured from pulmonary vein flow velocity as the time interval between the R-wave in the electrocardiography and corresponding peak late systolic was then calculated as the mean from two separate pw-Doppler measurements. Results: pPTT, tricuspid annular peak systolic excursion (TAPSE) and right ventricle fractional area change (FAC) were significantly lower in patients with HIV than control patients (177.1 ± 34.9 vs. 215.7 ± 35.7 msn, P < 0.001; 2.33 ± 0.28 vs. 2.19 ± 0.22, P = 0.039; 45 [4.25] vs. 41.1 [4.0], P = 0.032, respectively). pPTT was positively correlated with FAC, TAPSE and cluster of differentiation 4 count (r = 0.210; P = 0.036, r = 0.256; P = 0.041, r = 0.304; P = 0.044, respectively). Conclusion: Our study showed that pPTT, TAPSE, and right ventricle FAC levels were lower in patients with HIV infection. pPTT is an important predictor in patients with HIV expected to develop pulmonary vascular pathology.

Keywords: Echocardiography, HIV infection, pulmonary hypertension, pulmonary pulse transit time


How to cite this article:
Erdol MA, Acar B, Ertem AG, Karanfil M, Yayla Ç, Demirtas K, Aladag P, Sönmezer MÇ, Kiliç EK, Hatipoglu ÇA, Erdinc FS, Tulek N, Akcay AB. Assessment of pulmonary arterial hemodynamic and vascular changes by pulmonary pulse transit time in patients with human immunodeficiency virus infection. J Cardiovasc Echography 2021;31:6-10

How to cite this URL:
Erdol MA, Acar B, Ertem AG, Karanfil M, Yayla Ç, Demirtas K, Aladag P, Sönmezer MÇ, Kiliç EK, Hatipoglu ÇA, Erdinc FS, Tulek N, Akcay AB. Assessment of pulmonary arterial hemodynamic and vascular changes by pulmonary pulse transit time in patients with human immunodeficiency virus infection. J Cardiovasc Echography [serial online] 2021 [cited 2021 Jun 25];31:6-10. Available from: https://www.jcecho.org/text.asp?2021/31/1/6/316509




  Introduction Top


Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance (PVR), leading to right ventricular (RV) failure and premature death.[1],[2] One of the causes of PAH is human immunodeficiency virus (HIV) infection , and survival is worse in patients with HIV-PAH, compared with either HIV-infected patients without PAH or patients with idiopathic PAH.[3] In this subset, early detection of PAH is essential, as it could be provide early treatment and improvement of the survival for patients.[4]

Transthoracic echocardiography represents an important diagnostic tool to diagnose PAH; various studies have been done to evaluate RV function in HIV-infected patients.[4],[5] Most of the studies included traditional RV function parameters such as tricuspid annular peak systolic excursion (TAPSE), myocardial performance index.[6] Pulmonary pulse transit time (pPTT) is a surrogating echocardiographic marker for pulmonary hypertension[7] and might give valuable information about the stiffness of pulmonary vascular disease.[8],[9] The objective of this study was to assess whether the pPTT level was different in HIV-infected patients and its relation with RV function.


  Materials and Methods Top


Study population

Fifty, HIV (+) patients from infectious disease outpatient clinic and fifty age- and sex-matched HIV (−) healthy volunteers were enrolled in this study. The exact diagnosis of HIV infection was established after documenting medical history and positive HIV antibody testing. The subjects with moderate-severe heart valve disease, heart failure (left ventricular [LV] ejection fraction [EF] below 50%), autoimmune disorders, malignancy, moderate-severe pulmonary disease, active infection, pregnancy, diabetes mellitus, hypertension, thyroid disorders, severe chronic obstructive pulmonary disease, rheumatologic disease, abnormal serum electrolyte values, kidney failure, incomplete/complete bundle branch block, atrial fibrillation, and paced rhythm were excluded. All patients underwent respiratory function tests to exclude subtle lung disease. Patients with concomitant hepatitis C and hepatitis B infection were also excluded. Duration of disease and duration of treatment was calculated for each patient. All patients were on highly active anti-retroviral (HAART) therapy and none of the patients was not AIDS. The study protocol was approved by the local ethics committee, and a written informed consent was obtained from each subject before the study.

Laboratory measurements

Blood samples were obtained from all participants in the morning after 8 h of fasting. The biochemical tests included the complete blood count and cluster of differentiation 4 (CD4) count. The weight and height of the participants were measured, and their body mass index (BMIs) (kg/m2) was calculated.

Transthoracic echocardiography

Transthoracic echocardiographic was performed with patients in the standard left lateral decubitus position using General Electric Vivid E95 echocardiographic imaging system (Horten, Norway) with a 2.5–5 MHz transducer. Examinations were performed by a two-experienced cardiologist who were blind to the characteristics of individuals. Pulmonary vein flow was obtained by Doppler of the right superior pulmonary vein from the apical four-chamber view according to guidelines of the American Society of Echocardiography.[10] Twelve patients whose right upper pulmonic vein flow Doppler cannot be obtained excluded from the study. Study patients had good enough images for analysis of pulmonary venous flow for the measurement. All patients were examined in the sinus rhythm and asymptomatic in terms of cardiac symptoms. The Nyquist limit was adjusted to 15–20 cm/s and the sweep speed was set to 50–100 mm/s to optimize the spectral display of myocardial velocities. pPTT was defined as the time interval between the R-wave in the electrocardiogram (ECG) and corresponding peak late systolic pulmonary vein flow velocity (R-PVs2 interval), was then calculated as the mean from 2 separate pw-Doppler measurements taken during the same examination.[7] A continuous one-lead ECG was obtained during all examinations. The blood pressure of all participants was measured before the examination. LV EF was estimated using the Simpson's rule. Basic echocardiographic measurement such as left atrium antero-posterior diameter, LV end-systolic, end-diastolic dimensions, diastolic ventricular septal, and diastolic LV posterior wall thickness were performed in the parasternal long-axis view. systolic pulmonary artery pressure (sPAP) was measured as the sum of caval breathing index using the Bernoulli equation and right atrial pressure value attained from the tricuspid valve pressure gradient. We performed sPAP, tricuspid annular peak systolic excursion (TAPSE), fractional area change (FAC), and tricuspid systolic annular velocity.

Statistical analysis

Continuous variables were expressed as mean ± standard deviation or median with interquartile range, and categorical variables were expressed as percentages and numbers. The normality of distributions of the parameters was assessed using the Kolmogorov–Smirnov test. Comparison between continuous variables was made by use of independent samples t-test for normally distributed variables, and Mann–Whitney U-test when the distribution was skewed. Pearson's correlation coefficients were used to assess the strength of the relationship between continuous variables, and Spearman correlation analysis was performed for non-continuous and categorical variables. All statistical procedures were performed using SPSS software version 20.0 (SPSS Inc., Chicago, IL, USA). A P < 0.05 was considered statistically significant.


  Results Top


Baseline clinical characteristics of the study groups are shown in [Table 1]. Gender, mean age, body mass index, lymphocyte count, and neutrophil count were not statistically different between the control and the HIV (+) patients. Hemoglobin levels were slightly higher but not statistically significant in HIV-positive patients than HIV negative patients (14.8 ± 1.3 vs. 13.9 ± 1.41 mg/dL, P = 0.055). Echocardiographic image and parameters are shown in [Table 2] [Figure 1]. There were no significant differences between the control and the HIV (+) patients in terms of heart rate, LV end-diastolic dimension, LV end-systolic dimension, EF, diameter of the left atrium, diastolic interventricular septum diameter, and diastolic LV posterior wall diameter. RV functions and pPTT between HIV positive and control group are shown in [Table 3]. There were no differences between the control group and HIV-positive group in terms of basal RV diameter and pulmonary artery systolic pressure. pPTT, TAPSE, FAC were significantly lower in patients with HIV than control patients (177.1 ± 34.9 vs. 215.7 ± 35.7 msn, P < 0.001; 2.33 ± 0.28 vs. 2.19 ± 0.22, P = 0.039; 45 (4.25) vs. 41.1 (4.0), P = 0.032, respectively). pPTT was positively correlated with FAC, TAPSE, and CD4 count (r = 0.210; P = 0.036, r = 0.256; P = 0.041, r = 0.304; P = 0.044, respectively) [Table 4].
Table 1: Baseline clinical characteristics of patients and control subjects

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Table 2: Echocardiographic features of the study and healthy subjects

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Figure 1: pPTT was defined as the time interval between the R-wave in the electrocardiogram (ECG) and corresponding peak late systolic pulmonary vein flow velocity (R PVs2 interval)

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Table 3: Right ventricular functions and pulmonary pulse transit time between HIV positive and control group

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Table 4: Correlation analysis between pulmonary pulse transit time and variables

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  Discussion Top


Our study demonstrated that a noninvasive and simple Doppler-derived marker called pPTT is a possible surrogate marker of pulmonary hemodynamic alterations and vascular stiffening in HIV-infected patients. pPTT was found significantly lower in patients with HIV-infected patients than in controls. On the other hand, pPTT was positively correlated with FAC, TAPSE, and CD 4 count.

HIV-related cardiac involvement is represented by asymptomatic right ventricle dysfunction (detectable only by advanced echocardiography), PAH and left ventricle dysfunction.[11] PAH caused by chronic obstruction of small pulmonary arteries and it eventually leads to RV failure and death. One of the established risk factors for the development of PAH is HIV infection.[12],[13] HIV-PAH is a rare entity; however, the prevalence was estimated to be approximately 0.5% in HIV-infected patients before the HAART therapy[14] but indicating that HAART has not made a great impact on the prevention of HIV-PAH.[3]

Diagnoses of HIV-related PAH are often beside on clinical doubt because of the main symptom of the disease is dyspnea and requires multidisciplinary approach. Recent studies have reported that >35%–57% of HIV-positive patients had systolic pulmonary arterial pressure (SPAP) >30 mmHg.[15],[16] Most of the HIV-positive patients with PAH are mostly diagnosed in the final stages of the disease.[17] It seems too important to diagnose HIV-related PAH in the early stages. The median time of diagnosis to death in these patients is approximately equal to 6 months; therefore, early diagnosis of PAH may provide to timely treatment and decrease in symptoms and rate of mortality.[4]

Previous studies have showed that pulse wave velocity (PWV) and the inversely related pulse transit time are physiologic measures and they have been identified as clinically important parameters in the evaluation of increased arterial stiffness in high blood pressure.[18],[19] PWV is a speed marker, and the pulse pressure wave travels along an arterial segment; however, pPTT refers to the time it takes the pulse pressure wave to travel from one arterial site to another.[7],[18] While arterial stiffness and blood pressure increasing, PWV increases and pPTT shortens.[18],[20] It has been suggested that alterations in pulmonary vascular impedance resulting from vascular stiffening might have the potential to be a better predictor of prognosis and outcome than PVR.[21],[22] Wibmer et al. showed that a shortening of the interval between the R-wave in the ECG and the peak late systolic pulmonary vein flow velocity (R-PVs2) in patients with pulmonary hypertension.[7] In addition to these findings, Cerik et al. showed correlation between pulmonary arterial stiffness (PAS) and pulmonary acceleration time with HIV-infected patients.[23]

In the European Society of Cardiology/European Respiratory Society pulmonary hypertension guideline published in 2015, HIV infection and connective tissue disorder are included both in Group 1 (PAH) and in Group 1' pulmonary veno-occlusive disease as an etiopathological factor for PH.[24] There are similar pathological findings in patients with PAH. Intima, media and adventitia include hypertrophy, proliferation, and plexiform lesions. In the present study, pPTT levels in patients with HIV infection were lower than controls. SPAP was slightly higher in the HIV group, but it did not reach statistical significance. RV dysfunction can be seen in HIV-positive patients.[25] Virus-induced myocarditis, drug side effects, autonomic system disorders, and oxidative stress are some of them. In our study, the parameters associated with RV dysfunction (pPTT, TAPSE, RV FAC) were found to be statistically significantly lower in the HIV-positive arm, but no difference was found in sPAP. The sPAP calculation measured from the tricuspid regurgitation jet is based on the RV and right atrium (RA) gradient. In RV dysfunction, RA pressure rises. Consequently, the RV-RA gradient decreases and sPAP can be underestimated as in severe tricuspid regurgitation. This may explain why significant changes in pTT, TAPSE and RV FAC are not observed in the sPAP parameter. Recent study reported by Efe et al. has shown that TAPSE was positively correlated with pPTT and they found lower pPTT values in the patients with lupus.[26] Dogan et al. showed that pPTT and TAPSE were shorter in patients with systemic sclerosis as compared to the controls.[27] Our study showed that patients with HIV had shorter pPTT and its correlation with TAPSE. We also found that pPTT was positively correlated with FAC of the right ventricle. FAC is a relatively simple method for evaluating RV function and it is used as a quantitative method for estimating RV function via transthoracic echocardiography.[28] FAC reflects both the longitudinal and transverse movement of the RV and it might be more valuable than TAPSE in the assessment of RV functions.[28],[29]


  Conclusion Top


pPTT is a simple and easily calculated echocardiographic marker for the evaluation of pulmonary hemodynamics. pPTT seems to be able to predict the possible development of pulmonary vascular disease in patients with HIV even when their pulmonary arterial pressure is still within the normal range.

Limitations

Main limitation of this study was absence of long-term follow-up data. We did not know whether the patients were developed PAH. The number of patients with HIV infection was relatively small. Non-HAART regimen patients were not included in this study, because of that we did not know the relation between HAART regimen and pulmonary hypertension.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Araújo I, Enjuanes-Grau C, Lopez-Guarch CJ, Narankiewicz D, Ruiz-Cano MJ, Velazquez-Martin T, et al. Pulmonary arterial hypertension related to human immunodeficiency virus infection: A case series. World J Cardiol 2014;6:495-501.  Back to cited text no. 1
    
2.
Park JH, Kusunose K, Kwon DH, Park MM, Erzurum SC, Thomas JD, et al. Relationship between right ventricular longitudinal strain, invasive hemodynamics, and functional assessment in pulmonary arterial hypertension. Korean Circ J 2015;45:398-407.  Back to cited text no. 2
    
3.
Alp S, Schlottmann R, Bauer TT, Schmidt WE, Bastian A. Long-time survival with HIV-related pulmonary arterial hypertension: A case report. AIDS 2003;17:1714-5.  Back to cited text no. 3
    
4.
Schwarze-Zander C, Pabst S, Hammerstingl C, Ohlig J, Wasmuth JC, Boesecke C, et al. Pulmonary hypertension in HIV infection: A prospective echocardiographic study. HIV Med 2015;16:578-82.  Back to cited text no. 4
    
5.
Rasoulinejad M, Moradmand Badie S, Salehi MR, Seyed Alinaghi SA, Dehghan Manshadi SA, Zakerzadeh N, et al. Echocardiographic assessment of systolic pulmonary arterial pressure in HIV-positive patients. Acta Med Iran 2014;52:827-30.  Back to cited text no. 5
    
6.
Correale M, Palmiotti GA, Lo Storto MM, Montrone D, Foschino Barbaro MP, Di Biase M, et al. HIV-associated pulmonary arterial hypertension: From bedside to the future. Eur J Clin Invest 2015;45:515-28.  Back to cited text no. 6
    
7.
Wibmer T, Rüdiger S, Scharnbeck D, Radermacher M, Markovic S, Stoiber KM, et al. Pulmonary pulse transit time: A novel echocardiographic indicator of hemodynamic and vascular alterations in pulmonary hypertension and pulmonary fibrosis. Echocardiography 2015;32:904-11.  Back to cited text no. 7
    
8.
Hunter KS, Lammers SR, Shandas R. Pulmonary vascular stiffness: Measurement, modeling, and implications in normal and hypertensive pulmonary circulations. Compr Physiol 2011;1:1413-35.  Back to cited text no. 8
    
9.
Lammers S, Scott D, Hunter K, Tan W, Shandas R, Stenmark KR. Mechanics and function of the pulmonary vasculature: Implications for pulmonary vascular disease and right ventricular function. Compr Physiol 2012;2:295-319.  Back to cited text no. 9
    
10.
Quinones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA, Doppler Quantification Task Force of the N, et al. Recommendations for quantification of Doppler echocardiography: A report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr 2002;15:167-84.  Back to cited text no. 10
    
11.
Deidda M, Dessalvi CC, Campus S, Ortu F, Piano P, Bassareo PP, et al. Early right ventricular dysfunction in highly selected (totally free from cardiovascular risk factors and other comorbidities) human immunodeficiency virus patients: A Pilot study with advanced echocardiography. J Cardiovasc Echogr 2018;28:228-32.  Back to cited text no. 11
    
12.
Heron E, Laaban JP, Capron F, Quieffin J, Brechot JM, Rochemaure J, et al. Thrombotic primary pulmonary hypertension in an HIV+ patient. Eur Heart J 1994;15:394-6.  Back to cited text no. 12
    
13.
Speich R, Jenni R, Opravil M, Jaccard R. Regression of HIV-associated pulmonary arterial hypertension and long-term survival during antiretroviral therapy. Swiss Med Wkly 2001;131:663-5.  Back to cited text no. 13
    
14.
Opravil M, Pechère M, Speich R, Joller-Jemelka HI, Jenni R, Russi EW, et al. HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV cohort study. Am J Respir Crit Care Med 1997;155:990-5.  Back to cited text no. 14
    
15.
Prendergast BD. HIV and cardiovascular medicine. Heart 2003;89:793-800.  Back to cited text no. 15
    
16.
Morris A, Gingo MR, George MP, Lucht L, Kessinger C, Singh V, et al. Cardiopulmonary function in individuals with HIV infection in the antiretroviral therapy era. AIDS 2012;26:731-40.  Back to cited text no. 16
    
17.
Cicalini S, Chinello P, Petrosillo N. HIV infection and pulmonary arterial hypertension. Expert Rev Respir Med 2011;5:257-66.  Back to cited text no. 17
    
18.
Smith RP, Argod J, Pépin JL, Lévy PA. Pulse transit time: An appraisal of potential clinical applications. Thorax 1999;54:452-7.  Back to cited text no. 18
    
19.
Laurent S. Arterial stiffness in arterial hypertension. Curr Hypertens Rep 2006;8:179-80.  Back to cited text no. 19
    
20.
Hirata K, Kawakami M, O'Rourke MF. Pulse wave analysis and pulse wave velocity: A review of blood pressure interpretation 100 years after Korotkov. Circ J 2006;70:1231-9.  Back to cited text no. 20
    
21.
Champion HC, Michelakis ED, Hassoun PM. Comprehensive invasive and noninvasive approach to the right ventricle-pulmonary circulation unit: State of the art and clinical and research implications. Circulation 2009;120:992-1007.  Back to cited text no. 21
    
22.
Wang Z, Chesler NC. Pulmonary vascular wall stiffness: An important contributor to the increased right ventricular afterload with pulmonary hypertension. Pulm Circ 2011;1:212-23.  Back to cited text no. 22
    
23.
Cerik IB, Meric M, Gulel O, Ozturk Cerik H, Coksevim M, Soylu K, et al. Echocardiographic assessment of pulmonary arterial stiffness in human immunodeficiency virus-infected patients. Echocardiography 2019;36:1123-31.  Back to cited text no. 23
    
24.
Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J 2016;37:67-119.  Back to cited text no. 24
    
25.
Simon MA, Lacomis CD, George MP, Kessinger C, Weinman R, McMahon D, et al. Isolated right ventricular dysfunction in patients with human immunodeficiency virus. J Card Fail 2014;20:414-21.  Back to cited text no. 25
    
26.
Efe TH, Doğan M, Özişler C, Çimen T, Felekoğlu MA, Ertem AG, et al. Pulmonary arterial hemodynamic assessment by a novel index in systemic lupus erythematosus patients: Pulmonary pulse transit time. Anatol J Cardiol 2017;18:223-8.  Back to cited text no. 26
    
27.
Dogan M, Efe TH, Cimen T, Ozisler C, Felekoglu MA, Ertem AG, et al. Pulmonary arterial hemodynamic assessment by a novel index in systemic sclerosis patients: Pulmonary pulse transit time. Lung 2018;196:173-8.  Back to cited text no. 27
    
28.
Imada T, Kamibayashi T, Ota C, Carl Shibata S, Iritakenishi T, Sawa Y, et al. Intraoperative right ventricular fractional area change is a good indicator of right ventricular contractility: A retrospective comparison using two-and three-dimensional echocardiography. J Cardiothorac Vasc Anesth 2015;29:831-5.  Back to cited text no. 28
    
29.
Anavekar NS, Gerson D, Skali H, Kwong RY, Kent Yucel E, Solomon SD. Two-dimensional assessment of right ventricular function: An echocardiographic – MRI correlative study. Echocardiography 2007;24:452-6.  Back to cited text no. 29
    


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