External Counterpulsation Improves Angiogenesis by Preserving Vascular Endothelial Growth Factor-A and Vascular Endothelial Growth Factor Receptor-2 but Not Regulating MicroRNA-92a Expression in Patients With Refractory Angina.

Objective: External counterpulsation (ECP) provides long-term benefits of improved anginal frequency and exercise tolerance in patients with refractory angina (RA). This is postulated as a result of improved angiogenesis and endothelial function through an increase in shear stress. Angiogenesis is mainly represented by vascular endothelial growth factor-A (VEGF-A) and its receptor, vascular endothelial growth factor receptor-2 (VEGFR-2). The microRNA-92a (miR-92a) is a flow-sensitive miRNA that regulates atherosclerosis and angiogenesis in response to shear stress. Thus, ECP beneficial effect might be achieved through interaction between VEGF-A, VEGFR-2, and miR-92a. This study aims to evaluate the ECP effect on VEGF-A, VEGFR-2, and miR-92a in patients with RA in a sham-controlled manner. Methods: This was a randomized sham-controlled trial, enrolling 50 patients with RA who have coronary artery disease (CAD). Participants were randomized (1:1 ratio) to 35 sessions of either ECP (n = 25) or sham (n = 25), each session lasting for 1 h. Plasma levels of VEGF-A and VEGFR-2 were assayed by the ELISA technique. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to measure miR-92a circulating levels in plasma. Result: External counterpulsation significantly preserved VEGF-A and VEGFR-2 level compared to sham [ΔVEGF-A: 1 (-139 to 160) vs.-136 (-237 to 67) pg/ml, p = 0.026; ΔVEGFR-2: -171(-844 to +1,166) vs. -517(-1,549 to +1,407) pg/ml, p = 0.021, respectively]. Circulating miR-92a increased significantly in ECP [5.1 (4.2-6.4) to 5.9 (4.8-6.4), p < 0.001] and sham [5.2 (4.1-9.4) to 5.6 (4.8-6.3), p = 0.008] post-intervention. The fold changes tended to be higher in ECP group, although was not statistically different from sham [fold changes ECP = 4.6 (0.3-36.5) vs. sham 2.8 (0-15), p = 0.33)]. Conclusion: External counterpulsation improved angiogenesis by preserving VEGF-A and VEGFR-2 levels. Both ECP and sham increased miR-92a significantly, yet the changes were not different between the two groups. (Study registered on www.clinicaltrials.gov, no: NCT03991871, August 8, 2019, and received a grant from the National Health Research and Development of Ministry of Health of Indonesia, No: HK.02.02/I/27/2020).

Performance of Primary Angioplasty for STEMI during the COVID-19 Outbreak.

There has been concern whether the declining cases of ST-segment elevation myocardial infarction (STEMI) during the coronavirus disease 2019 (COVID-19) outbreak associate with primary angioplasty performance. We assessed the performance of primary angioplasty in a tertiary care hospital in Jakarta, Indonesia, by comparing the door-to-device (DTD) time and thrombolysis in myocardial infarction (TIMI) flow after angioplasty between two periods of admission: during the outbreak of COVID-19 (March 1 to May 31, 2020) and before the outbreak (March 1, to May 31, 2019). Overall, there was a relative reduction of 44% for STEMI admission during the outbreak ( n = 116) compared with before the outbreak ( N = 208). Compared with before the outbreak period ( n = 141), STEMI patients who admitted during the outbreak and received primary angioplasty ( n = 70) had similar median symptom onset-to-angioplasty center admission (360 minutes for each group), similar to radial access uptake (90 vs. 89.4%, p = 0.88) and left anterior descending infarct-related artery (54.3 vs. 58.9%, p = 0.52). The median DTD time and total ischemia time were longer (104 vs. 81 minutes, p < 0.001, and 475.5 vs. 449 minutes, p = 0.43, respectively). However, the final achievement of TIMI 3 flow was similar (87.1 vs. 87.2%), and so was the in-hospital mortality (5.7 vs. 7.8%). During the COVID-19 outbreak, we found a longer DTD time for primary angioplasty, but the achievement of final TIMI 3 flow and in-hospital mortality were similar as compared with before the outbreak. Thus, primary angioplasty should remain the standard of care for STEMI during the COVID-19 outbreak.

"Door-In to Door-Out" Delay in Patients with Acute ST-Segment Elevation Myocardial Infarction Transferred for Primary Percutaneous Coronary Intervention in a Metropolitan STEMI Network of a Developing Country.

Background Routine performance measures of primary percutaneous coronary intervention (PCI) within an ST-segment elevation myocardial infarction (STEMI) network are needed to improve care. Objective We evaluated the door-in to door-out (DI-DO) delays at the initial hospitals in STEMI patients as a routine performance measure of the metropolitan STEMI network. Patients and Methods We retrospectively analyzed the DI-DO time from 1,076 patients with acute STEMI who were transferred by ground ambulance to a primary PCI center for primary PCI between 4 October 2014 and 1 April 2019. Correlation analysis between DI-DO times and total ischemia time was performed using Spearman's test. Logistic regression analyses were used to find variables associated with a longer DI-DO time. Results Median DI-DO time was 180 minutes (25th percentile to 75th percentile: 120-252 minutes). DI-DO time showed a positive correlation with total ischemia time ( r = 0.4, p < 0.001). The median door-to-device time at the PCI center was 70 minutes (25th percentile to 75th percentile: 58-88 minutes). Multivariate analysis showed that women patients were independently associated with DI-DO time > 120 minutes (odds ratio 1.55, 95% confidence interval 1.03 to 2.33, p = 0.03). Conclusion The DI-DO time reported in this study has not reached the guideline recommendation. To improve the overall performance of primary PCI in the region, interventions aimed at improving the DI-DO time at the initial hospitals and specific threat for women patients with STEMI are possibly the best efforts in improving the total ischemia time.

Hospital outcomes in STEMI patients after the introduction of a regional STEMI network in the metropolitan area of a developing country.

Aims: Data on the long-term outcomes of STEMI patients treated via a network in Asian countries are very limited. We aimed to evaluate the characteristics and outcomes of STEMI patients at two different periods, before and five years after the establishment of a regional STEMI network in Jakarta, Indonesia. Methods and results: Out of 6,291 patients with STEMI admitted to hospital between January 2008 to January 2016, we compared the characteristics and outcomes of STEMI patients from two different periods, January 2008 to July 2009 (before instalment of the STEMI network, N=624), and from January 2015 to January 2016 (five years after the start of the network, N=1,052). The PCI hospital is an academic tertiary care cardiac hospital and initiated the regional STEMI network in 2010. Logistic regression was used to determine the adjusted association between treatment in the latter period and mortality. Compared with data from 2008/2009, in the 2015/2016 period, more primary PCI procedures were performed (N=589 [56%] vs. N=176 [28%], p<0.001), fewer patients did not receive reperfusion therapy (37% vs. 59%, p<0.001), and median door-to-device (DTD) times were shorter (82 vs. 94 minutes, p<0.001). Overall in-hospital mortality decreased from 9.6% to 7.1% (adjusted odds ratio 0.72, 95% CI: 0.50 to 1.03, p=0.07). Conclusions: Half a decade after the implementation of the STEMI network in Jakarta, Indonesia, the result is better and faster care for patients with STEMI and this has been associated with lower in-hospital mortality.