ESC HEART FAILURE SHORT COMMUNICATION ESC Heart Failure 2020; 7: 768–773 Published online 12 March 2020 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/ehf2.12637 Prognostic impact of angiographic findings, procedural success, and timing of percutaneous coronary intervention in cardiogenic shock Tuija Sabell1*†† , Marek Banaszewski2††, Johan Lassus1††, Markku S. Nieminen1††, Heli Tolppanen1††, Toni Jäntti1††, Anu Kataja3††, Mari Hongisto3††, Lars Køber4, Alessandro Sionis5††, John Parissis6††, Tuukka Tarvasmäki1††, Veli-Pekka Harjola3†† and Raija Jurkko1†† 1 Heart and Lung Center, Helsinki University Hospital, Helsinki University, Helsinki, Finland; 2Intensive Cardiac Therapy Clinic, Institute of Cardiology, Warsaw, Poland; 3 Department of Emergency Medicine and Services, Helsinki University Hospital, Helsinki University, Helsinki, Finland; 4Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 5Cardiology Department, Hospital de la Santa Creu i Sant Pau, IIB-SantPau, CIBER-CV, Universitat Autònoma de Barcelona, Barcelona, Spain; 6ER and Heart Failure Clinic, Attikon University Hospital, Athens, Greece Abstract Aims Urgent revascularization is the mainstay of treatment in acute coronary syndrome (ACS) related cardiogenic shock (CS). The aim was to investigate the association of angiographic results with 90-day mortality. Procedural complications of percu- taneous coronary intervention (PCI) were also examined. Methods and results This CardShock (NCT01374867) substudy included 158 patients with ACS aetiology and data on coro- nary angiography and complications during PCI procedure. Survival analysis was conducted with Kaplan–Meier curves and Cox regression analysis. Median age was 67 ± 11 years, and 77% were men. During 90-day follow-up, 66 (42%) patients died. Pa- tients with one-vessel disease (n = 49) had lower mortality than patients with two-vessel (n = 59) or three-vessel (n = 50) dis- ease (25% vs. 48% vs. 52%, P = 0.011). Successful revascularization [Thrombolysis in Myocardial Infarction (TIMI) Flow 3 post- PCI) was achieved more often in survivors than non-survivors (81% vs. 60%, P = 0.019). The median symptom-to-balloon time was 340 (196–660) minutes, with no difference between survivors and non-survivors. In multivariable mortality analysis, multivessel disease (HR 2.59, CI95% 1.29–5.18) and TIMI flow <3 post-PCI (HR 2.41, CI95% 1.4–4.15) were associated with 90-day mortality. Procedural PCI complications were recorded in 51 (35%) patients, arrhythmic complications being the most common (n = 32, 63%). The incidence of complications was similar between survivors and non-survivors (31% vs. 42%, P = 0.21). Conclusions Multivessel disease is associated with worse survival in ACS-related CS. In patients undergoing PCI, arrhythmic complications were common, but not associated with excess mortality. Successful revascularization of the IRA had positive ef- fect on outcome despite delay from symptom onset. Keywords Cardiogenic shock; Acute coronary syndrome; Percutaneous coronary intervention Received: 10 October 2019; Revised: 15 January 2020; Accepted: 21 January 2020 *Correspondence to: Tuija Sabell, MD, Heart and Lung Center, Helsinki University Hospital, PO Box 340, 00029 HUS, Helsinki, Finland. Email: tuija.sabell@outlook.com †This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. Background multivessel2–4 and three-vessel coronary artery disease (CAD),5–8 unsuccessful revascularization,3–5,7–11 and left main Urgent coronary angiography and revascularization are the (LM) CAD3,5,7 have been associated with poor outcomes in mainstay of treatment in acute coronary syndrome (ACS) re- ACS-related CS. However, many of these studies lated cardiogenic shock (CS).1 In previous studies, predate the primary percutaneous coronary intervention © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Prognostic impact of angiographic findings, procedural success, and timing of percutaneous coronary intervention in cardiogenic shock 769 (PCI) era,5–7 were of retrospective nature10,12 or examined (NT-proBNP) at baseline, left ventricular ejection fraction registry data.3,8,11 Furthermore, data on procedural PCI com- (LVEF), multivessel CAD (significant stenosis in more than plications in ACS-related CS are scarce. one main coronary vessel or major side branch), stenosis of LM, infarct related artery (IRA), thrombolysis prior to angiog- raphy, intra-aortic balloon pump (IABP), CABG during hospital Aims stay, PCI, symptom-to-balloon time, number of stents, drug- eluting stent, metal stent, amount of contrast agent, pre- The aim of this study was to explore coronary angiographic procedural Thrombolysis in Myocardial Infarction (TIMI) findings in a prospective multicentre cohort of ACS-related grade 0/1 flow, TIMI flow <3 post-PCI, and PCI complications. CS. The primary objective was to investigate the association The variables with P value <0.10 in univariate analysis were of angiographic results and 90-day mortality. In addition, pro- included in the multivariable analysis. The final model was cedural PCI complications were examined. built with backward stepwise method with Cox regression analysis. A two-tailed P value of <0.05 was considered statis- tically significant. The statistical analyses were performed using R statistical software version 3.4.3 (The “R” Foundation Methods for Statistical Computing, Vienna, Austria). The CardShock study (NCT01374867) is a prospective multi- national study on CS conducted in nine centres in eight Euro- pean countries between October 2010 and December 2012. Results The description of the study cohort has been reported previ- ously.13 Briefly, consecutive patients aged over 18 years were In total, 177 CardShock patients had ACS aetiology. Of these enrolled within 6 h from detection of CS. The criteria for patients, 10 did not undergo angiographic evaluation, six pa- shock were systolic blood pressure <90 mmHg for 30 min de- tients did not have data on angiographic findings, and three spite adequate fluid therapy or need for vasoactive therapy, were lost to follow-up. Finally, 158 patients were included in and ≥1 signs of inadequate organ perfusion: confusion or al- this study. Median age was 67 ± 11 years, and 121 (77%) tered mental status, cool extremities, oliguria <0.5 mL/kg/h were male. During the 90-day follow-up, 66 (42%) patients for the previous 6 h, or blood lactate >2 mmol/L. died. Baseline characteristics are described in Table 1. Survi- Patients’ characteristics, medical history, clinical signs, and vors were younger (66 ± 12 vs. 70 ± 9 years, P = 0.029), had laboratory measurements were registered. Echocardiogram fewer comorbidities, and had higher LVEF (38% ± 14 vs. 29% was performed at study baseline. Patients were treated ac- ± 12, P < 0.001) than non-survivors (Table 1). cording to local practise. Information on angiographic find- Patients with one-vessel CAD (n = 49, 31%) had lower 90- ings and revascularisation procedures were collected. day mortality than patients with two- (n = 59, 37%) or three- This sub-study included patients with ACS aetiology and (n = 50, 32%) vessel CAD (25% vs. 48% vs. 52%, respectively; data on coronary angiography. The primary endpoint was P = 0.011, Figure 1A). Mortality was numerically higher in all-cause mortality at 90 days. The vital status was confirmed patients with LM or left anterior descending (LAD) as the by the patient or next of kin, or through hospital or popula- culprit artery when compared to right coronary artery tion registers. The study was approved by local ethics com- (RCA) or LCX, but the difference was not statistically signifi- mittees and conducted in accordance with the Declaration cant. Successful revascularization (TIMI Flow 3 post-PCI) of Helsinki. was achieved more often in survivors than in non-survivors Data are presented as means and standard deviations (81% vs. 60%, P = 0.019, Table 1, Figure 1C), whereas there (SDs), medians and interquartile ranges (IQRs), or as counts were no differences in the rate of successful revasculariza- and percentages. Comparisons between groups were tion between different IRAs: 72% in LM, 70% in LAD, 59% analysed by Student’s t-test or Mann–Whitney U-test for con- in LCX, 77% in RCA, and 80% in saphenous vein graft (SVG) tinuous variables and χ 2 test or Fisher’s exact test for categor- (P = 0.67). The median symptom-to-balloon time was 340 ical variables, as appropriate. (196-660) minutes, with no difference between groups Survival was analysed using Kaplan–Meier curves and log- (Table 1). One-third of the patients (n = 49, 36%) developed rank tests. The association with 90-day mortality was shock only after the PCI procedure, but there was no differ- assessed by univariate Cox regression for the following vari- ence in the rate of successful revascularization, if shock de- ables selected a priori: age, gender, comorbidities [prior myo- veloped before or after the procedure (32% vs. 24%, P = cardial infarction or coronary artery bypass grafting (CABG), 0.41). diabetes, hypertension, and smoking], estimated glomerular In multivariable analysis, multivessel CAD (HR 2.59, CI95% filtration rate (eGFR), levels of lactate, high sensitivity tropo- 1.29–5.18, P = 0.007), TIMI flow <3 post-PCI (HR 2.41, CI95% nin T (hs-TnT) and N-terminal pro brain natriuretic peptide 1.4–4.15, P = 0.001), increasing lactate (HR 1.17, CI95% 1.11– ESC Heart Failure 2020; 7: 768–773 DOI: 10.1002/ehf2.12637 770 T. Sabell et al. Table 1 Baseline and angiographic characteristics All patients (n = 158) Survivors (n = 92) Non-survivors (n = 66) P Age 67 ± 11 66 ± 12 70 ± 9 0.029 Male gender 121 (77) 75 (82) 46 (70) 0.12 ACS type: STEMI 139 (88) 80 (87) 59 (89) 0.83 Medical history Known coronary artery disease 49 (31) 21 (23) 28 (42) 0.014 Prior myocardial infarction 36 (23) 14 (15) 22 (33) 0.013 Prior PCI 22 (14) 10 (11) 12 (18) 0.28 CABG 9 (6) 1 (1) 8 (12) 0.009 Chronic heart failure 10 (6) 2 (2) 8 (12) 0.03 Clinical characteristics CardShock risk score 4±2 4±2 5±1 <0.001 Systolic blood pressure 78 ± 14 80 ± 15 75 ± 12 0.025 LVEF 34 ± 14 38 ± 14 29 ± 12 <0.001 Laboratory tests Lactate (mmol/L) 3 [2-5] 2 [1-4] 4 [3-8] <0.001 2 eGFR (mL/min/1.73 m ) 63 [44-87] 71 [51-96] 49 [33-70] <0.001 hs-TnT (ng/L) 3205 [1167-8907] 2614 909-6940] 4010 [1628-10993] 0.08 NT-proBNP (ng/L) 1751 [374-8602] 1077 [252-5029] 3769 [648-12249] 0.01 Characteristics of CAD Number of diseased vessels 0.011 One-vessel disease 49 (31) 37 (40) 12 (18) Two-vessel disease 59 (37) 31 (34) 28 (42) Three-vessel disease 50 (32) 24 (26) 26 (39) IRA 0.005 LAD 63 (40) 33 (36) 30 (47) LCX 21 (14) 16 (17) 5 (8) LM 19 (12) 9 (10) 10 (16) RCA 48 (31) 34 (37) 14 (22) SVG 5 (3) 0 (0) 5 (8) Treatment PCI 144 (91) 82 (89) 62 (94) 0.44 Thrombolysis 17 (11) 13 (14) 4 (6) 0.18 IABP 103 (65) 55 (60) 48 (73) 0.13 CABG 8 (5) 7 (8) 1 (2) 0.18 Procedural characteristics n = 144 n = 82 n = 62 Symptom-to-balloon time (min) 340 [196–660] 335 [210–641] 340 [190–660] 0.70 Bare metal stent 66 (46) 39 (48) 27 (44) 0.76 Multivessel PCI 38 (26) 21 (26) 17 (27) 0.96 PCI of LM 21 (15) 8 (10) 13 (21) 0.11 Total occlusion (pre-procedural TIMI 0/1) 119 (84) 65 (80) 54 (89) 0.27 Post-procedural TIMI 0.027 0/1 15 (11) 6 (7) 9 (15) 2 25 (18) 10 (12) 15 (25) 3 102 (72) 66 (81) 36 (60) Amount of contrast agent (mL) 160 [120-220] 170 [120-210] 160 [124-250] 0.66 Shock after PCI 49 (36) 33 (41) 16 (28) 0.16 Complications Any PCI complication 51 (35) 25 (31) 26 (42) 0.21 Ventricular tachycardia or fibrillation 27 (19) 11 (13) 16 (26) 0.10 Bradycardia 21 (15) 7 (9) 14 (23) 0.034 Dissection 8 (6) 5 (6) 3 (5) 1.00 Tamponade 1 (1) 1 (1) 0 (0) 1.00 Re-occlusion 4 (3) 1 (1) 3 (5) 0.43 Re-coronary angiography 12 (9) 10 (13) 2 (3) 0.10 Re-PCI 10 (7) 8 (10) 2 (3) 0.22 ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; CAD, coronary artery disease, CRP, C reactive protein; eGFR, esti- mated glomerular filtration rate; hs-TnT, high-sensitive troponin T; IABP, intra-aortic balloon pump; IRA, infarct related artery; LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; LM, left main coronary artery; LVEF, left ventricular ejection frac- tion; MAP, mean arterial pressure; NT-proBNP, N-terminal pro brain natriuretic peptide; PCI, percutaneous coronary intervention; RCA, right coronary artery; STEMI, ST-segment elevation myocardial infarction; SVG, saphenous vein graft; TIMI, Thrombolysis in Myocardial Infarction. Data are presented as means ± standard deviation, medians (interquartile range) or counts (%). 1.23, P < 0.001), and decreasing LVEF (HR 1.03, CI95% 1.01– Any procedural complication was recorded in 35% of the 1.06, P = 0.002) were independently associated with 90-day patients who underwent PCI with no difference between sur- mortality. vivors and non-survivors (31% vs. 42%, P = 0.21, Table 1). ESC Heart Failure 2020; 7: 768–773 DOI: 10.1002/ehf2.12637 Prognostic impact of angiographic findings, procedural success, and timing of percutaneous coronary intervention in cardiogenic shock 771 Figure 1 Kaplan–Meier 90-day survival curves in different patient groups divided by (A) severity of coronary artery disease, (B) the infarct related ar- tery, and (C) the Thrombolysis in Myocardial Infarction flow post-percutaneous coronary intervention. (A) Patients with one-vessel disease had lower 90-day mortality rates than patients with two-vessel or three-vessel disease. (B) Patients with left anterior descending coronary artery or left main coronary artery as the infarct related artery had high mortality rates. (C) Patients with successful revascularization, i.e. TIMI Flow 3, had lower mortality rates than patients with TIMI Flows 0–2. Arrhythmia was the most common complication: 19% had numerically higher in LM and LAD in comparison to RCA and ventricular tachycardia or fibrillation, and bradycardia was re- LCX. In other studies, LM as the culprit artery has been asso- corded in 15% of patients. Bradycardia was more frequent in ciated with worse survival,3,5,7,11 whereas RCA as the culprit non-survivors than survivors (23% vs. 9%, P = 0.034), but in artery has been associated with better prognosis.6,12 The pro- adjusted mortality analysis, bradycardia was not associated portion of patients with successful revascularization was sim- with the risk of 90-day death (HR 1.09, CI95% 0.51–2.35, P = ilar irrespective of the culprit artery, which suggests that high 0.82). mortality rates of LM and LAD were not related to procedural failure. Indeed, the culprit vessel may only play minor role in survival in CS, especially when revascularization is successful, Conclusion as mortality may be more strongly associated with haemody- namic instability and multi-organ damage. In this study, multivessel CAD and TIMI flow <3 post-PCI Our study confirms that successful revascularization of the were associated with poor prognosis in ACS-related IRA is associated with good prognosis.3,5,7–11 In our study, the CS. Among patients undergoing PCI, arrhythmic median symptom-to-balloon time was suboptimal with a me- complications were common but not associated with excess dian delay of 6 h. Nevertheless, there was no difference in PCI mortality. timing between survivors and non-survivors. As we examined Multivessel CAD was associated with worse survival in ACS- symptom-to-balloon time and not contact-to-balloon time, related CS, as previously shown.2,3,5–8 No difference in mor- our results are not directly comparable to the FITT-ST- tality between different IRAs was discovered, similar to one segment elevation myocardial infarction (STEMI) trial,14 yet previous study,4 even though mortality rates were our results show that in CS, even delayed successful ESC Heart Failure 2020; 7: 768–773 DOI: 10.1002/ehf2.12637 772 T. Sabell et al. revascularization is associated with improved prognosis. examination of angiograms was not centralized, but the pa- However, some factors should be taken in consideration. tients were treated, and the results were reported, by expe- We did not record specific reasons for the delay in rienced interventional cardiologists. symptom-to-balloon time, such as patient-related delays to In conclusion, multivessel disease is associated with worse first medical contact, or transfer times. In addition, not all pa- survival in ACS-related CS. In patients undergoing PCI, ar- tients were in shock on arrival to the hospital but developed rhythmic complications were common, but not associated shock only after the revascularisation procedure. In patients with excess mortality. Successful revascularization of the with ACS, delayed revascularisation may predispose to later IRA had a positive effect on outcome despite delay from development of shock,15 but the timing of PCI was similar be- symptom onset. Thus, in CS, even late PCI seems to be tween survivors and non-survivors, and there was no differ- feasible. ence in the rate of successful revascularisation if shock developed before or after PCI. Despite prolonged symptom- to-balloon time, TIMI Flow 3 post-PCI was still associated with better outcome, indicating that successful revascularization Conflict of interest may be a more important driver for improved prognosis than None declared. timing of the procedure. We found no difference in survival with culprit-vessel only or multivessel PCI, in contrary to the CULPRIT-SHOCK trial.16 The evident difference between our study and the CULPRIT- Funding SHOCK trial is that our study was of prospective nature, which enabled the treating physician to select the most suitable pa- This study was supported by grants from the Finnish Founda- tients to the multivessel PCI. In addition, some of the patients tion for Cardiovascular Research, and Aarne Koskelo Founda- included in this study did not have CS during the PCI tion, Helsinki, Finland. Roche Diagnostics provided kits for the procedure. analysis of NT-proBNP and TnT. The funding sources had no The rate of procedural PCI complications was higher than role in the design and conduct of the study; collection, man- reported in STEMI,17 and slightly higher than in a registry agement, analysis, and interpretation of the data; prepara- study of ACS-related CS11. However, the rate of ventricular tion, review, or approval of the manuscript; or decision to arrhythmias was similar to previously reported STEMI-related submit the manuscript for publication. CS10. In this critically ill population, arrhythmic events were Tuija Sabell (néeJavanainen) received following personal most likely related to the severity of the disease and not to research grants: Acute Coronary Syndromes and secondary the revascularisation procedure itself. Indeed, procedural prevention grant from the Finnish Cardiac Society, grant sup- complications did not associate with mortality, suggesting ported by Astra Zeneca and grants from Paavo Nurmi Foun- that they are transient and treatable. During PCI in CS, imme- dation and Paavo Ilmari Ahvenaisen säätiö. diate actions, such as defibrillation and cardiac pacing, should Dr Lassus has served on an advisory board for Boehringer be readily available for management of arrhythmic Ingelheim, Medix Biochemica, Novartis, Servier, and Vifor complications. Pharma and received lecture fees from Bayer, Boehringer There are limitations to be acknowledged. Though this Ingelheim, Pfizer, Novartis, Orion Pharma, and Vifor Pharma. study is considerable for a prospective study of CS, the num- Dr Parissis has received honoraria from Novartis and Orion ber of patients in some groups was low. In addition, the Pharma. References 1. Ponikowski P, Voors AA, Anker SD, diagnosis and treatment of acute and ST-elevation myocardial infarction pa- Bueno H, Cleland JGF, Coats AJS, Falk chronic heart failure of the European So- tients with and without cardiogenic V, González-Juanatey JR, Harjola V-P, ciety of Cardiology (ESC). Eur Heart J shock. 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ESC Heart Failure 2020; 7: 768–773 DOI: 10.1002/ehf2.12637