We prospectively analyzed the clinical data of 400 children with PDA from the Cardiovascular Surgical Department and the Heart Disease Center at the Union Hospital, Fujian Medical University from January 2017 until December 2019. Patients were diagnosed with PDA through transthoracic echocardiography (TTE). All experimental protocols of this study were approved by the ethics committee of Union Hospital of Fujian Medical University.
Criteria for Patients’ Enrollment
Patients enrolled in the study covered the following standards for the conventional surgical groups. These were patients diagnosed with types of PDA like window, tube and funnel, patients who refused device closing as well as those who were unqualified for device closing. The inclusion criteria of the device group were covered by patients with isolated PDA or PDA combined with other minor cardiovascular malformations that did not require a surgical correction and residual shunts after PDA surgery.
For a more precise selection of the patients, we also formulated exclusion criteria. Specifically, patients with cardiac malformations that relied on PDA or those with thrombus at the occluder placement and with thrombosis at the place of venous catheter insertion (which prevents thrombosis from falling off) were excluded. Patients with active endocarditis or other infections that caused bacteremia and those with complicated catheter-associated physiological conditions (such as severe anaemia, acute heart failure, active tuberculosis, and severe hepatopathy) were further excluded. Moreover, patients with a history of considerably intensified pre- and postoperative inflammation and infection markers were further disqualified from the investigation.
Specific criteria for the surveillance of infection were additionally formulated and they were: 1) fever body T°C ≥ 38.5; 2) lung infection diagnosed with chest-radiography imaging; 3) detection of evident moist rales by pulmonary auscultation; 4) development of purulent sputum and 5) presence of bacteria in mucus and plasma cultures 21. All patients’ medical and clinical results were documented in their medicinal records.
The PDA width in the five groups was measured by colour Doppler echocardiography before surgery and was evaluated by angiography during the device closure procedure in the device group. Pulmonary artery pressure and LVEF were only evaluated with colour Doppler echocardiography. The cardiothoracic ratio was evaluated with the use of chest radiography. In addition, all patients underwent common preoperative tests, like an electrocardiogram, complete blood picture, biochemical analyses and quantitative assessment of blood serum indicators for myocardial injury (CK-MB and troponin I) and inflammation (WBC, CRP, PCT, and IL-6). We did not detect medical or laboratory indications for myocardial injury or infection before the surgery.
Regarding the patients from the other four groups, the surgery technique used on them was introduced in 1938 by Dr Robert Gross at Boston Children’s Hospital. he conducted the first successful closing of PDA 22. The thoracic cavity of the patients was accessed via an incision in the left fourth or fifth intercostal space. After adequate dissection for the insertion of the catheter, it was completely ligated with double-thick silk thread or clamped with clips of an appropriate size, or ligated and then sutured, or even ligated and then clamped. The chest wall was then closed layer by layer. (see Figuer. 1A)
The percutaneous device closing in group E was done following protocols reported in other studies 23,24. Briefly, the femoral vein was initially punctured and sheathed. A guidewire catheter technique was applied to traverse the PDA along the inferior vena cava, the right atrium and ventricle, down to the connection of the pulmonary artery with the descending aorta. The occluder determined the delivery sheath, which was then advanced along the guidewire down to the descending aorta. After removal of the guidewire, the PDA occluder was inserted along the delivery sheath for complete occlusion of the PDA. Moreover, we planned a three-month antiplatelet therapy as a consequent patient handling. (see Figuer. 1B)
Patients’ Outcome Measures
We collected and analyzed the data concerning the surgery time, intraoperative blood loss, length of hospital stay (LOS). We also examined the selected myocardial damage blood serum indicators. They were analyzed before the surgery (designated as the preOP time), on the 6th, 24th, and 48th hour as well as on the 5th day postoperatively. These post-operative time points were designated as POH6, POH24, POH48, and POH120, respectively. Similarly, we investigated the levels of the inflammatory markers on a preOP day, as well as on the POH24, POH48, POH72, and POH120, respectively. None of the patients did have difficulties in breathing and thus there was no need in using a ventilator. On the day of surgery, all the subjects were transferred to the general ward. For those patients whose stay was less than 5 days, the examinations were completed at the outpatient department.
The Shapiro-Wilk test was applied to assess the normal distribution of the registered data. The analysis of the continuous variables was done by the use of one-way ANOVA and data are presented as means ± standard deviations. The Kruskal-Wallis analysis was used for the continuous variables with non-normal distribution and data are presented as median [first quartile (Q1); third quartile (Q3)]. Moreover, the categorical variables were studied via the chi-squared or Fisher’s exact tests and were expressed as percentages. In the case of a statistically significant difference, the Bonferroni test was utilized for multiple comparisons. The analysis of levels of the selected markers of myocardial injury and inflammation was performed with the use of Levene's test for equality of variances. If the collected data suggested that the homogeneity of variance could serve as a precondition, then we performed an analysis of variance on repeated measures to evaluate the significance of the trends of changes in markers. P < 0.05 determined the significance of the obtained results. The software SPSS 26.0 was applied for the realization of all analyses used.