CE: Tripti; JCM-D-14-00310; Total nos of Pages: 5;
JCM-D-14-00310
Original article
Enhanced platelet activity in atrial septal defect Mehmet Gungor Kayaa, Deniz Elcika, Bekir Calapkorura and Yat-Yin Lamb Aims Enhanced platelet activity assessed by mean platelet volume (MPV) was observed in pulmonary arterial hypertension. This study examined the presence of platelet activation in adults with atrial septal defect (ASD), its relationship with pulmonary vascular disease and its changes following device closure of the defects. Methods A total of 76 consecutive patients received transcatheter ASD closure and 40 matched healthy volunteers were prospectively enrolled for blood tests and transthoracic echocardiography (patients: aged 36 W 13, 37% men; controls: aged 36 W 8, 38% men). MPV, systolic pulmonary arterial pressures (PAP), and right ventricular end-diastolic diameters were collected before and after ASD closure in patients. Results The mean MPV levels were significantly higher in patients than in controls (10.1 W 1.3 to 8.6 W 0.9 fl; P < 0.001) at baseline. A moderate, positive correlation was also observed between baseline MPV levels and systolic PAP (r U 0.542, P < 0.001) in patients. Both MPV levels, systolic PAP and right ventricular end-diastolic diameters reduced
Introduction Atrial septal defect (ASD) accounts for 7–10% of all forms of congenital heart diseases,1,2 and the common causes of morbidity and mortality in adult patients with ASD are the development of pulmonary vascular disease, right heart failure and pulmonary thromboembolism in the fourth and fifth decades.3,4 Published data showed increased platelet activation and aggregation in other causes of pulmonary hypertension.5–9 Moreover, such enhanced platelet activity was associated with worse functional status and survival in patients with pulmonary hypertension.7,8 Mean platelet volume (MPV) is an easily measured hematological marker which increases during platelet activation.10–12 Increased MPV levels were found in patients with progression of pulmonary vascular disease.5,13 There is a lack of studies to explore the relationship of MPV and the development of pulmonary vascular disease in ASD patients. The study, therefore, examined the presence of platelet activation in adults with ASD, its relationship with pulmonary vascular disease and its changes after transcatheter closure of the defects.
Methods Study population
A total of 76 consecutive patients received transcatheter closure of a secundum-type ASD and 40 matched healthy 1558-2027 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
significantly 6 months following ASD closure. The 6-month MPV and systolic PAP values were comparable to those of the normals. Conclusion Enhanced platelet activity was present in ASD and associated with the presence of pulmonary vascular disease. This phenomenon was largely reversible following device closure of the defects. J Cardiovasc Med 2015, 16:000–000 Keywords: atrial septal defect, mean platelet volume, pulmonary hypertension
a Department of Cardiology, Erciyes University School of Medicine, Kayseri, Turkey and bDivision of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR
Correspondence to Professor Yat-Yin Lam, Division of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR Tel: +852 2632 1299; fax: +852 2637 3852; e-mail: [email protected] Received 29 May 2013 Revised 13 August 2014 Accepted 20 August 2014
volunteers. The inclusion criteria for the ASD group required the presence of a secundum-type ASD with left-to-right shunt and right ventricular volume overloading (Qp/Qs ratio 1.5 : 1 and/or right ventricular dilation). The exclusion criteria included a Qp/Qs ratio below 1.5 : 1, the presence of a sinus venosus or primum-type defect and/or the development of Eisenmenger syndrome. Previous medical history was recorded from patients’ medical records. Office blood pressure was measured 10 min before transthoracic echocardiography (TTE) with a random-zero sphygmomanometer by trained observers. Informed consent was obtained from all patients, and the protocol was approved by the Ethics Committee and the Institutional Review Board of Erciyes University Medical School. Echocardiographic evaluation
All patients were evaluated by TTE. Patients with ASD were evaluated also by transesophageal echocardiography (TEE) before the procedure and additional TTE 6 months after ASD closure. TTE was performed with the patient in a left lateral decubitus position, using a 2.5-MHz and 5-MHz transducer of a Vivid 7 (GEVingmed Ultrasound AS, Horten, Norway) echocardiographic machine. The TEE evaluation was performed with the patient under sedation using a 6-MHz and 9-MHz TEE probe. Left ventricular ejection fraction DOI:10.2459/JCM.0000000000000217
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: Tripti; JCM-D-14-00310; Total nos of Pages: 5;
JCM-D-14-00310
2 Journal of Cardiovascular Medicine 2015, Vol 00 No 00
(LVEF) was assessed by two-dimensional (2D) Simpson’s method.14 Systolic pulmonary arterial pressure (PAP) was calculated by Doppler interrogation of tricuspid regurgitation flow using the formula: PAP ¼ RAP þ 4V2, where RAP and V are the right atrial pressure and the peak velocity of tricuspid valve regurgitant flow, respectively. RAP was assessed with reference to the inferior venal caval size and the degree of collapse during respiratory cycle. Right ventricular end-diastolic diameter (RVEDD) was obtained by M-mode echocardiography at parasternal long-axis view. Transcatheter atrial septal defect closure procedure
All procedures were performed under general anesthesia and TEE guidance. Before the procedure, hemodynamic evaluation was performed for the patient. The Qp/Qs ratio was assessed by the oximetry method. A sizing balloon was inflated across the defect until there was no Doppler flow seen across the defect. The waist of the balloon was then measured by both TEE and fluoroscopy. An Amplatzer Septal Occluder (AGA Medical Corp., Golden Valley, Minnesota, USA) 1–2 mm larger than the measured balloon waist diameter would be chosen to close the defect by the techniques previously reported.15–17 During the procedure, 100 IU/kg of heparin and 30–40 mg/kg of cefazolin for endocarditis prophylaxis were administered intravenously to all patients, and daily use of 3–5 mg/kg of aspirin was recommended for 6 months after the procedure. Laboratory measurements
All blood samples were drawn at antecubital veins in the morning after 20 min rest following a fasting period of 12 h. Blood glucose, creatinine, lipid profile and all routine biochemical tests were carried out on an autoanalyzer (Roche Diagnostic Modular Systems, Tokyo, Japan). Blood samples for MPV analyses were collected into the tripotassium EDTA-based, anticoagulated tubes and stored at 48C. The samples were assessed using a Sysmex K-1000 auto analyzer within 30 min of sampling in order to avoid platelet swelling. Statistical analysis
All statistical analyses were performed using the SPSS Statistical Package for Windows, version 15.0 (SPSS Inc, Chicago, Illinois, USA). Continuous variables were tested for normal distribution by the Kolmogorov–Smirnov test and reported as mean SD. We compared continuous variables using Student’s t test or Mann–Whitney U test between the groups. The changes of continuous variables before and after treatment were compared using twotailed paired t test. Categorical variables were summarized as percentages and compared with the chi-square test. Pearson correlation coefficients examined the degree of association between the examined variables. P value less than 0.05 was considered significant.
Results Table 1 shows the baseline characteristics of patients and normal controls. Both groups had comparable age, sex prevalence, cardiovascular risk factors, biochemical indices and blood pressure findings. Systolic PAP was significantly higher in the ASD population than in healthy volunteers (45.9 11.9 vs. 27.3 6.1 mmHg; P < 0.001). Hemostatic parameters are shown in Table 2. MPV levels were significantly higher in ASD patients than in healthy volunteers (10.1 1.3 vs. 8.6 0.9 fl; P < 0.001), whereas hemoglobin, hematocrit, white blood cell and platelet counts did not differ between the groups. There was a significant, positive correlation between MPV levels and systolic PAP values in the pretreatment ASD population (r ¼ 0.542, P < 0.001) (Fig. 1). At 6 months following ASD closure, the systolic PAP (45.9 11.9–30.2 7.6 mmHg; P < 0.001) and RVEDD (4.4 1.3 vs. 8.6 0.9 cm; P < 0.001) decreased, whereas LVEF and RA diameter remained similar (Table 3). For hemostatic parameters, the MPV levels also significantly decreased at 6 months (10.1 1.3–8.6 0.7 fl; P < 0.001), whereas the hemoglobin levels and the platelet counts did not change. The post-treatment MPV levels and systolic PAP became similar to those of the healthy volunteers (8.6 0.7 vs. 8.6 0.9 fl and 30.2 7.6 vs. 28.9 3.7 mmHg; P ¼ 0.941 and P ¼ 0.057, respectively; Tables 2 and 3).
Discussion Congenital heart defects are detected in 8/1000 of all newborns,18 and ASD accounts for 7–10% of them.1,2 Most patients are asymptomatic in first and second decades. However, some patients can develop severe pulmonary hypertension and right heart failure, which leads to significant morbidity, if not mortality.19–21 Enhanced Table 1
Baseline characteristics of study population
Age (years) Sex (M/F) BMI (kg/m2) Diabetes mellitus Hypertension Smoking status Creatinine (mg/dl) Glucose (mg/dl) Total cholesterol (mg/dl) LDL (mg/dl) HDL mg/dl) Triglyceride (mg/dl) Hemodynamic parameters Heart rate (beats/min) LVEF (%) Systolic PAP (mmHg) SBP (mmHg) DBP (mmHg)
ASD population (n ¼ 76)
Healthy volunteers (n ¼ 40)
36 13 51/85 24.8 2.6 5 (7%) 6 (8%) 8 (11%) 1.0 0.2 98 23 177.6 38.9 107.7 31.2 45.7 9.2 120.9 82.4
36 8 15/25 24.2 2.9 3 (8%) 5 (13%) 6 (15%) 0.8 0.1 95 19 183.2 41.5 114.0 35.2 47.0 9.3 110.8 47.6
0.976 0.944 0.258 0.852 0.421 0.482 0.190 0.649 0.470 0.323 0.459 0.474
74 14 62.6 5.7 45.9 11.9 121.6 16.8 79.2 11.6
76 21 61.6 5.2 27.3 6.1 125.7 19.9 82.7 13.1
0.818 0.360
JCM-D-14-00310
Original article
Enhanced platelet activity in atrial septal defect Mehmet Gungor Kayaa, Deniz Elcika, Bekir Calapkorura and Yat-Yin Lamb Aims Enhanced platelet activity assessed by mean platelet volume (MPV) was observed in pulmonary arterial hypertension. This study examined the presence of platelet activation in adults with atrial septal defect (ASD), its relationship with pulmonary vascular disease and its changes following device closure of the defects. Methods A total of 76 consecutive patients received transcatheter ASD closure and 40 matched healthy volunteers were prospectively enrolled for blood tests and transthoracic echocardiography (patients: aged 36 W 13, 37% men; controls: aged 36 W 8, 38% men). MPV, systolic pulmonary arterial pressures (PAP), and right ventricular end-diastolic diameters were collected before and after ASD closure in patients. Results The mean MPV levels were significantly higher in patients than in controls (10.1 W 1.3 to 8.6 W 0.9 fl; P < 0.001) at baseline. A moderate, positive correlation was also observed between baseline MPV levels and systolic PAP (r U 0.542, P < 0.001) in patients. Both MPV levels, systolic PAP and right ventricular end-diastolic diameters reduced
Introduction Atrial septal defect (ASD) accounts for 7–10% of all forms of congenital heart diseases,1,2 and the common causes of morbidity and mortality in adult patients with ASD are the development of pulmonary vascular disease, right heart failure and pulmonary thromboembolism in the fourth and fifth decades.3,4 Published data showed increased platelet activation and aggregation in other causes of pulmonary hypertension.5–9 Moreover, such enhanced platelet activity was associated with worse functional status and survival in patients with pulmonary hypertension.7,8 Mean platelet volume (MPV) is an easily measured hematological marker which increases during platelet activation.10–12 Increased MPV levels were found in patients with progression of pulmonary vascular disease.5,13 There is a lack of studies to explore the relationship of MPV and the development of pulmonary vascular disease in ASD patients. The study, therefore, examined the presence of platelet activation in adults with ASD, its relationship with pulmonary vascular disease and its changes after transcatheter closure of the defects.
Methods Study population
A total of 76 consecutive patients received transcatheter closure of a secundum-type ASD and 40 matched healthy 1558-2027 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
significantly 6 months following ASD closure. The 6-month MPV and systolic PAP values were comparable to those of the normals. Conclusion Enhanced platelet activity was present in ASD and associated with the presence of pulmonary vascular disease. This phenomenon was largely reversible following device closure of the defects. J Cardiovasc Med 2015, 16:000–000 Keywords: atrial septal defect, mean platelet volume, pulmonary hypertension
a Department of Cardiology, Erciyes University School of Medicine, Kayseri, Turkey and bDivision of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR
Correspondence to Professor Yat-Yin Lam, Division of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR Tel: +852 2632 1299; fax: +852 2637 3852; e-mail: [email protected] Received 29 May 2013 Revised 13 August 2014 Accepted 20 August 2014
volunteers. The inclusion criteria for the ASD group required the presence of a secundum-type ASD with left-to-right shunt and right ventricular volume overloading (Qp/Qs ratio 1.5 : 1 and/or right ventricular dilation). The exclusion criteria included a Qp/Qs ratio below 1.5 : 1, the presence of a sinus venosus or primum-type defect and/or the development of Eisenmenger syndrome. Previous medical history was recorded from patients’ medical records. Office blood pressure was measured 10 min before transthoracic echocardiography (TTE) with a random-zero sphygmomanometer by trained observers. Informed consent was obtained from all patients, and the protocol was approved by the Ethics Committee and the Institutional Review Board of Erciyes University Medical School. Echocardiographic evaluation
All patients were evaluated by TTE. Patients with ASD were evaluated also by transesophageal echocardiography (TEE) before the procedure and additional TTE 6 months after ASD closure. TTE was performed with the patient in a left lateral decubitus position, using a 2.5-MHz and 5-MHz transducer of a Vivid 7 (GEVingmed Ultrasound AS, Horten, Norway) echocardiographic machine. The TEE evaluation was performed with the patient under sedation using a 6-MHz and 9-MHz TEE probe. Left ventricular ejection fraction DOI:10.2459/JCM.0000000000000217
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: Tripti; JCM-D-14-00310; Total nos of Pages: 5;
JCM-D-14-00310
2 Journal of Cardiovascular Medicine 2015, Vol 00 No 00
(LVEF) was assessed by two-dimensional (2D) Simpson’s method.14 Systolic pulmonary arterial pressure (PAP) was calculated by Doppler interrogation of tricuspid regurgitation flow using the formula: PAP ¼ RAP þ 4V2, where RAP and V are the right atrial pressure and the peak velocity of tricuspid valve regurgitant flow, respectively. RAP was assessed with reference to the inferior venal caval size and the degree of collapse during respiratory cycle. Right ventricular end-diastolic diameter (RVEDD) was obtained by M-mode echocardiography at parasternal long-axis view. Transcatheter atrial septal defect closure procedure
All procedures were performed under general anesthesia and TEE guidance. Before the procedure, hemodynamic evaluation was performed for the patient. The Qp/Qs ratio was assessed by the oximetry method. A sizing balloon was inflated across the defect until there was no Doppler flow seen across the defect. The waist of the balloon was then measured by both TEE and fluoroscopy. An Amplatzer Septal Occluder (AGA Medical Corp., Golden Valley, Minnesota, USA) 1–2 mm larger than the measured balloon waist diameter would be chosen to close the defect by the techniques previously reported.15–17 During the procedure, 100 IU/kg of heparin and 30–40 mg/kg of cefazolin for endocarditis prophylaxis were administered intravenously to all patients, and daily use of 3–5 mg/kg of aspirin was recommended for 6 months after the procedure. Laboratory measurements
All blood samples were drawn at antecubital veins in the morning after 20 min rest following a fasting period of 12 h. Blood glucose, creatinine, lipid profile and all routine biochemical tests were carried out on an autoanalyzer (Roche Diagnostic Modular Systems, Tokyo, Japan). Blood samples for MPV analyses were collected into the tripotassium EDTA-based, anticoagulated tubes and stored at 48C. The samples were assessed using a Sysmex K-1000 auto analyzer within 30 min of sampling in order to avoid platelet swelling. Statistical analysis
All statistical analyses were performed using the SPSS Statistical Package for Windows, version 15.0 (SPSS Inc, Chicago, Illinois, USA). Continuous variables were tested for normal distribution by the Kolmogorov–Smirnov test and reported as mean SD. We compared continuous variables using Student’s t test or Mann–Whitney U test between the groups. The changes of continuous variables before and after treatment were compared using twotailed paired t test. Categorical variables were summarized as percentages and compared with the chi-square test. Pearson correlation coefficients examined the degree of association between the examined variables. P value less than 0.05 was considered significant.
Results Table 1 shows the baseline characteristics of patients and normal controls. Both groups had comparable age, sex prevalence, cardiovascular risk factors, biochemical indices and blood pressure findings. Systolic PAP was significantly higher in the ASD population than in healthy volunteers (45.9 11.9 vs. 27.3 6.1 mmHg; P < 0.001). Hemostatic parameters are shown in Table 2. MPV levels were significantly higher in ASD patients than in healthy volunteers (10.1 1.3 vs. 8.6 0.9 fl; P < 0.001), whereas hemoglobin, hematocrit, white blood cell and platelet counts did not differ between the groups. There was a significant, positive correlation between MPV levels and systolic PAP values in the pretreatment ASD population (r ¼ 0.542, P < 0.001) (Fig. 1). At 6 months following ASD closure, the systolic PAP (45.9 11.9–30.2 7.6 mmHg; P < 0.001) and RVEDD (4.4 1.3 vs. 8.6 0.9 cm; P < 0.001) decreased, whereas LVEF and RA diameter remained similar (Table 3). For hemostatic parameters, the MPV levels also significantly decreased at 6 months (10.1 1.3–8.6 0.7 fl; P < 0.001), whereas the hemoglobin levels and the platelet counts did not change. The post-treatment MPV levels and systolic PAP became similar to those of the healthy volunteers (8.6 0.7 vs. 8.6 0.9 fl and 30.2 7.6 vs. 28.9 3.7 mmHg; P ¼ 0.941 and P ¼ 0.057, respectively; Tables 2 and 3).
Discussion Congenital heart defects are detected in 8/1000 of all newborns,18 and ASD accounts for 7–10% of them.1,2 Most patients are asymptomatic in first and second decades. However, some patients can develop severe pulmonary hypertension and right heart failure, which leads to significant morbidity, if not mortality.19–21 Enhanced Table 1
Baseline characteristics of study population
Age (years) Sex (M/F) BMI (kg/m2) Diabetes mellitus Hypertension Smoking status Creatinine (mg/dl) Glucose (mg/dl) Total cholesterol (mg/dl) LDL (mg/dl) HDL mg/dl) Triglyceride (mg/dl) Hemodynamic parameters Heart rate (beats/min) LVEF (%) Systolic PAP (mmHg) SBP (mmHg) DBP (mmHg)
ASD population (n ¼ 76)
Healthy volunteers (n ¼ 40)
36 13 51/85 24.8 2.6 5 (7%) 6 (8%) 8 (11%) 1.0 0.2 98 23 177.6 38.9 107.7 31.2 45.7 9.2 120.9 82.4
36 8 15/25 24.2 2.9 3 (8%) 5 (13%) 6 (15%) 0.8 0.1 95 19 183.2 41.5 114.0 35.2 47.0 9.3 110.8 47.6
0.976 0.944 0.258 0.852 0.421 0.482 0.190 0.649 0.470 0.323 0.459 0.474
74 14 62.6 5.7 45.9 11.9 121.6 16.8 79.2 11.6
76 21 61.6 5.2 27.3 6.1 125.7 19.9 82.7 13.1
0.818 0.360
