IJC Heart & Vasculature 40 (2022) 101036 Contents lists available at ScienceDirect IJC Heart & Vasculature journal homepage: www.sciencedirect.com/journal/ijc-heart-and-vasculature “Impact of age on management and prognosis of resuscitated sudden cardiac death patients” Jordi Sans Roselló a, *, Maria Vidal-Burdeus b, Pablo Loma-Osorio c, Alexandra Pons Riverola d, Gil Bonet Pineda e, Nabil El Ouaddi f, Jaime Aboal c, Albert Ariza Solé d, Claudia Scardino e, Cosme García-García f, Estefanía Fernández-Peregrina g, Alessandro Sionis g, * a Cardiology Department. Parc Taulí Hospital Universitari. Sabadell, Spain b Acute and Intensive Cardiovascular Care Unit, Department of Cardiology, Hospital Universitari Vall d’Hebrón. Barcelona, Spain c Critical Cardiac Care Unit, Cardiology Department, Dr. Josep Trueta University Hospital, Girona, Spain d Acute and Intensive Cardiovascular Care Unit, Department of Cardiology, Hospital Universitario de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain e Department of Cardiology, Joan XXIII University Hospital, Pere Virgili Health Research Institute (IISPV), Rovira i Virgili University, Tarragona, Spain f Acute and Intensive Cardiovascular Care Unit, Department of Cardiology, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain g Acute and Intensive Cardiovascular Care Unit, Department of Cardiology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute IIB-Sant Pau, Barcelona, Spain A R T I C L E I N F O A B S T R A C T Keywords: Background: Sudden cardiac death (SCD) has a great impact on healthcare due to cardiologic and neurological Sudden cardiac death complications. Admissions of elderly people in Cardiology Intensive Care Units have increased. We assessed the Elderly patients impact of age in presentation, therapeutic management and in vital and neurological prognosis of SCD patients. Neurological outcomes Methods: We carried out a retrospective, observational, multicenter registry of patients who were admitted with a SCD in 5 tertiary hospitals from January 2013 to December 2020. We divided our cohort into two groups (pa­ tients < 80 years and ≥ 80 years). Clinical, analytical and hemodynamic variables as well as in-hospital man­ agement were registered and compared between groups. The degree of neurological dysfunction, vital status at discharge and the influence of age on them were also reviewed. Results: We reviewed 1160 patients admitted with a SCD. 11.3% were ≥ 80 years. Use of new antiplatelet agents, performance of a coronary angiography, use of pulmonary artery catheter and temperature control were less carried out in the elderly. Age, non-shockable rhythm, Killip class > 1 at admission, time to CPR initiation > 5 min, time to ROSC > 20 min and lactate > 2 mmol/L were independent predictors for in-hospital mortality. Non- shockable rhythm, Killip class > 1 at admission, time to CPR initiation > 5 min and time to ROSC > 20 min but not age were independent predictors for poor neurological outcomes. Conclusions: Age determined a less aggressive management and it was associated with a worse vital prognosis in patients admitted with a SCD. Nevertheless, age was not associated with worse neurological outcomes. 1. Introduction arrest due to a heart condition, that occurs within one hour of symptoms onset. Nowadays, it represents the third leading cause of death in Europe Sudden cardiac death (SCD) is defined as an unexpected cardiac (15–20%) and accounts for 50% of cardiovascular deaths in Western Abbreviations: SCD, Sudden cardiac death; CPR, Cardiopulmonary resuscitation; ROSC, Recovery of spontaneous circulation; CA, Cardiac arrest; ADL, Activities of daily living; EI-MV, Endotracheal intubation with mechanical ventilation; CAG, Coronary angiography; TC, Temperature control; NSE, Neuronal specific enolase; CPC, Cerebral performance category; CCI, Charlson Comorbidity Index. * Corresponding autor at: Intensive Cardiac Care Unit. Cardiology Department. Hospital de la Santa Creu i Sant Pau, C/Santa Maria Claret 167, Barcelona 08025, Spain (Alessandro Sionis) Cardiology Department. Parc Taulí Hospital Universitari. Sabadell, Spain. Parc Taulí, 1, 08208 Sabadell, Barcelona (Jordi Sans-Roselló). E-mail addresses: jordisansrosello@hotmail.com, jsansr@tauli.cat (J. Sans Roselló), m_vidal88@hotmail.com (M. Vidal-Burdeus), plomaosorio@gmail.com (P. Loma-Osorio), alexandraponsriverola@gmail.com (A. Pons Riverola), gil.bonet.p@gmail.com (G. Bonet Pineda), elouaddi@hotmail.com (N. El Ouaddi), jaime.aboal@gmail.com (J. Aboal), aariza@hotmail.com (A. Ariza Solé), claudia.scardino85@gmail.com (C. Scardino), cosmecg7@gmail.com (C. García-García), efernandezperegrina@gmail.com (E. Fernández-Peregrina), asionis@santpau.es (A. Sionis). https://doi.org/10.1016/j.ijcha.2022.101036 Received 20 January 2022; Received in revised form 27 March 2022; Accepted 18 April 2022 Available online 27 April 2022 2352-9067/© 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/). J. Sans Roselló et al. IJC Heart & Vasculature 40 (2022) 101036 societies [1,2]. to the initiation of CPR maneuvers (by health or non-health personnel). Pre-hospital care protocols for SCD patients and the spread of car­ Shockable rhythm was considered if ventricular fibrillation (VF), diopulmonary resuscitation (CPR) / automated external defibrillator pulseless ventricular tachycardia (VT), or shockable rhythm according (AED) training courses together with the progressive aging of the pop­ to AED were the first rhythms obtained. All these resuscitation param­ ulation have increased the number of elderly patients admitted to Car­ eters were collected from medical emergency services reports. First EKG diology Intensive Care Units (CICU) with an aborted SCD [3–5]. Impact post ROSC achieved and hemodynamic variables upon arrival at the of SCD patients on health care systems is high due to cardiologic and hospital were also analyzed. mainly neurologic complications that could lead to poor vital and Management during hospital admission was at the discretion of the functional prognosis of these patients [6]. This is especially relevant in treating physician and according to availability in each hospital. Per­ the elderly since morbidity and disability clearly increase with age, centage of endotracheal intubation with mechanical ventilation (EI- further worsening their vital and neurologic prognosis. MV), use of inotropes, intra-aortic balloon pump (IABP), pulmonary Even though the development of standardized protocols have artery catheter (PAC), renal replacement therapy (RRT) as well as cor­ improved the prognosis of patients hospitalized after SCD [7,8], their onary angiography (CAG) performance and emergency/urgent percu­ mortality and morbidity, especially in the older population, remain taneous coronary intervention (PCI) were reported. In patients who unacceptably high. Moreover, elderly patients are usually underrepre­ underwent CAG, number of affected vessels, culprit vessel and TIMI flow sented in clinical trials, so the evidence for some techniques or pro­ grade after PCI were also recorded. cedures in this setting is limited. For instance, they may not receive some Temperature control (TC) was performed using surface or endovas­ of the medical therapies that have been reported to improve the prog­ cular cooling devices according to availability in each hospital at a nosis based on the assumption of a per se poor prognosis [9,10]. temperature of 33 ◦ C. TC complications and reasons not to start or to Although cardiac arrest guidelines, ethical statements, and clinical stop it were examined. We also reviewed the presence of myoclonus or procedures do not propose age as a criterion for discrimination in SCD status epilepticus as well as the performance of an electroencephalo­ care [11], physicians are often faced with having to decide whether gram (EEG), use of anticonvulsant medication or the induction of a certain diagnostic tests or therapies may be beneficial or futile in older barbiturate coma. We registered the absence of brain stem reflexes and patients [12]. spontaneous mobilization at 72 h after SCD. Performance of somato­ The aim of this observational study is to assess whether the age could sensory evoked potentials N20 (SSEP-N20) and brain magnetic reso­ have an influence in the etiology, clinical presentation and therapeutical nance imaging (MRI) were also recorded. We registered neuronal management of patients admitted with a SCD in tertiary hospitals. specific enolase (NSE) at 24 h, 48 h and 72 h if available. To categorize Furthermore, we aimed to evaluate whether these possible differences neurological function at discharge, the Cerebral Performance Category could affect vital and neurological outcomes of these patients. (CPC) scale was used [15]. For patients who died from non-neurological causes, the last known previously achieved CPC category was consid­ 2. Methods ered. If the patient died from a non-neurological cause before a CPC category could be established (i.e., patients who died while still under 2.1. Study population sedation with no possibility of CPC assessment) it was categorized as unknown CPC. The population was divided into 2 groups: good neuro­ In this retrospective study, we reviewed all consecutive patients logical prognosis (CPC 1-CPC 2) and poor neurological prognosis (CPC admitted from January 2013 to December 2020 with an aborted SCD to 3-CPC 5). Patients with unknown CPC were excluded from neurological CICUs of 5 third-level hospitals in Catalonia, Spain (Hospital Uni­ prognosis analysis. Restriction of invasive procedures as well as in- versitario Dr. Josep Trueta, Hospital Universitario de Bellvitge, Hospital hospital mortality and causes of death were also registered. Universitario Joan XXIII, Hospital Universitario Germans Trias i Pujol and Hospital de la Santa Creu i Sant Pau). Inclusion criteria were: a) ≥ 2.3. Statistical analysis 18 years of age and b) diagnosis of SCD according to current guidelines [1,2]. Exclusion criteria were: a) patients not recovered from SCD prior Results are presented as the mean (standard deviation) for contin­ to hospital admission and b) cardiac arrest (CA) due to an extracardiac uous variables with a normal distribution, medians for continuous var­ condition. iables with a non-Gaussian distribution, and percentages for categorical The study was conducted in accordance with the standards set by the variables. The characteristics of patients with age < 80 years and age ≥ “Declaration of Helsinki” and was approved by the Clinical Research 80 years were compared using the x2 test or Fisher exact test for cate­ Ethics Committe. Informed consent was waived due to the retrospective gorical variables. For quantitative variables, they were analyzed by t-test nature of the study. in the case of normal distribution, or Mann-Whitney U test in the case of a non-normal distribution. 2.2. Study variables Multivariate analysis to evaluate the effect of variables on the inci­ dence of in-hospital mortality and neurologic prognosis at discharge Patient-related factors were collected from medical reports or by were performed using Cox proportional hazard modelling that included anamnesis to relatives at admission. We divided our cohort in two terms that showed p < 0.1 in the univariate analysis, as well as those groups as follows: the “younger” group refers to patients < 80 years previously reported to provide prognostic information [16]. Signifi­ while the “older” or “elderly” group refers to patients ≥ 80 years. This cance level was set at p < 0.05. All statistical analyses were performed cut-off age was chosen to achieve a better differentiation between the using Stata 13.0 for Windows. two groups. We identified those patients who were dependent for the basic activities of daily living (ADL) and we calculated the Charlson 3. Results Comorbidity Index (CCI) [13]. Biochemical and hematological param­ eters were measured by standard procedures in first blood test and The 5 participating centers recorded 1160 patients with an aborted arterial blood gas samples at admission; the estimated glomerular SCD between 2013 and 2020. One hundred and thirty-one patients function rate was calculated by the Modification of Diet in Renal Disease (11.3%) were ≥ 80 years and 27 patients (2.3%) were dependent for the Study equation (MDRD) [14]. basic ADL. We considered resuscitation parameters such as location of CA, witnessed CA, initial recorded rhythm, use of AED and resuscitation times. Time to CPR initiation was defined as the time from cardiac arrest 2 J. Sans Roselló et al. IJC Heart & Vasculature 40 (2022) 101036 3.1. Differences in baseline characteristics between groups Table 1 Differences between baseline characteristics at admission. Differences in baseline characteristics at admission of both groups Characteristic All cohort Patients < Patients ≥ P-value are detailed in Table 1. Patients aged ≥ 80 years were more frequently (n ¼ 1160) 80 years (n 80 years (n women, hypertensive, diabetic and dyslipidemic. In addition, there was ¼ 1029) ¼ 131) also a higher percentage of patients with a history of coronary artery BASELINE disease, respiratory disease, cerebrovascular disease and chronic kidney Age (years) 64.1 61.7 83.0 <0.001 disease in older patients. As expected, patients ≥ 80 years had a higher (53.9–73.6) (52.5–70.1) (81.6–85.5) Male gender, % 74.2 (861/ 75.7 (779/ 62.6 (82/ 0.001 CCI and they were in more percentage dependents for basic ADL. 1160) 1029) 131) Regarding the location of the CA, in elderly patients, it occurred Dependent for basic 2.3 (27/ 1.4 (14/ 10.0 (13/ <0.001 more frequently in a healthcare center and less frequently in a public ADL, % 1160) 1029) 131) place or at home. They had a lower percentage of a first shockable Charlston 3 (1–4) 2 (1–4) 5 (4–6) <0.001 comorbidity index rhythm and a shorter time to ROSC, but no differences were found in Hypertension, % 57.9 (672/ 54.8 (564/ 82.4 (108/ <0.001 percentage of witnessed SCD or in time to initiation of CPR. 1160) 1029) 131) When ROSC was achieved, elderly patients more frequently pre­ Diabetes mellitus, % 26.7 (309/ 25.7 (264/ 34.4 (45/ 0.035 sented a first EKG without repolarization alterations or with left bundle 1160) 1029) 131) branch block, while in younger patients a higher proportion of ST Dyslipidemia, % 49.5 (574/ 48.3 (497/ 58.8 (77/ 0.024 1160) 1029) 131) segment elevation was documented. Recovery of sinus rhythm was also Current smoker, % 35.8 (415/ 38.2 (393/ 16.9 (22/ <0.001 lower in the older group. 1159) 1029) 130) No differences were found in systolic blood pressure or LVEF upon Body mass index 25.4 25.4 25.0 0.194 hospital arrival. First arterial blood gases showed a better pH value in (kg/m2) (24.2–29.4) (24.2–29.4) (24.2–27.8) Previous coronary 22.8 (264/ 21.8 (224/ 30.5 (40/ 0.024 elderly patients, while no differences were recorded in lactate levels. artery disease, % 1160) 1029) 131) First blood test showed that older group had a lower glomerular filtra­ Respiratory disease, 13.1 (152/ 12.3 (127/ 19.1 (25/ 0.031 tion and a lower hemoglobin and white blood cells count. No other % 1160) 1029) 131) analytical or hemodynamic differences were found between groups. Chronic kidney 10.6 (123/ 8.6 (88/ 26.7 (35/ <0.001 disease, % 1160) 1029) 131) Cerebrovascular 7.8 (91/ 7.0 (72/ 14.5 (19/ 0.003 3.2. Differences in etiology and therapeutic management between groups disease, % 1160) 1029) 131) CARDIAC ARREST Differences in etiology of SCD and therapeutic management of both PARAMETERS groups are detailed in Table 2. In the elderly group, the percentage of Location of CA:, % <0.001 - Healthcare centre 22.0 (255/ 20.1 (207/ 36.6 (48/ SCD attributed to STEMI was lower while that attributed to bradyar­ 1160) 1029) 131) rhythmias and dilated ischemic cardiomyopathy was higher than in - Home 34.3 (398/ 35.1 (361/ 28.2 (37/ younger patients. 1160) 1029) 131) No differences were found in the percentage of either anterior STEMI - Public place 43.7 (507/ 44.8 (461/ 35.1 (46/ location or in Killip class > 1. Use of inotropes and IABP did not differ 1160) 1029) 131) Witnessed CA, % 91.3 (1059/ 91.5 (941/ 90.1 (118/ 0.600 between groups, but PAC was less used in elderly patients even after 1160) 1029) 131) excluding those patients dependent for basic ADL. ECMO was started in First shockable 70.4 (814/ 72.4 (743/ 54.2 (71/ <0.001 only 1.9% of the cases (21 patients), all of them < 80 years old. rhythm, % 1157) 1026) 131) An emergent CAG was performed less frequently in older patients. AEDs use, % 32.2 (364/ 32.4 (330/ 30.9 (34/ 0.453 1130) 1020) 110) Although there was a lower percentage of patients with ST segment Time until initiation 2 (0–5) 2 (0–5) 1 (0–3.5) 0.109 elevation in the elderly group, if we only included patients with elevated of CPR (min) ST on the baseline EKG, differences were still significant. Differences Time until ROSC 22 (13–33) 23 (13–35) 20 (9–30) 0.0016 were maintained despite excluding from the analysis patients who were (min) dependent for basic ADL. No differences were found in the percentage of BASELINE EKG & ECHO PCI performed or in the initial TIMI grade flow, but a significant lower VARIABLES use of new antiplatelet agents and a higher proportion of TIMI grade Sinus rhythm, % 71.0 (804/ 73.8 (745/ 48.4 (59/ <0.001 flow < 3 after PCI were shown in older patients. 1132) 1010) 122) The use of TC showed significant differences between groups. TC was First EKG abnormalities:, % induced in a smaller percentage of the elderly patients and significance - No abnormalities 12.1 (137/ 11.2 (113/ 19.7 (24/ 0.009 was maintained despite including only patients who had pulseless VT/ 1134) 1010) 122) VF as the first rhythm. After excluding patients who were dependent for - ST segment 46.8 (531/ 49.0 (495/ 29.5 (36/ <0.001 basic ADL, the differences remained significant. No differences were elevation 1134) 1010) 122) documented in the percentage of early withdrawal from TC in both - ST segment 15.7 (178/ 15.2 (154/ 19.7 (24/ 0.25 depression 1134) 1010) 122) groups. - Negative T waves 4.1 (47/ 4.3 (43/ 3.3 (4/122) 0.577 1134) 1010) 3.3. Differences in prognostic stratification and outcomes between groups - Left bundle 11.6 (131/ 10.6 (107/ 19.7 (24/ 0.004 branch block 1134) 1010) 122) - Right bundle 7.9 (90/ 7.9 (80/ 8.2 (10/122) 0.973 Clinical previously established indicators of poor outcome (status branch block 1134) 1010) myoclonus ≤ 72 h, absence of stem reflexes at ≥ 72 h and absence of LVEF:, % 0.981 spontaneous movements other than extension ≥ 72 h) did not differ - Preserved 29.0 (313/ 29.0 (279/ 28.8 (34/ between groups. Similarly, no differences were found in status epi­ 1079) 961) 118) lepticus, use of anticonvulsant medication or induction of barbiturate - Mildly depressed 16.1 (174/ 16.0 (154/ 17.0 (20/ 1079) 961) 118) coma percentage. A lower percentage of EEGs was performed in the - Moderately 41.1 (443/ 41.0 (394/ 41.5 (49/ group of elderly people. Moreover, a lower number of SSEP-N20 and depressed 1079) 961) 118) brain MRI tests were also requested in older patients even though no (continued on next page) differences in percentage of cerebral tomography were found between 3 J. Sans Roselló et al. IJC Heart & Vasculature 40 (2022) 101036 Table 1 (continued ) Table 2 Characteristic All cohort Patients < Patients ≥ P-value Differences in etiology and therapeutic management. (n ¼ 1160) 80 years (n 80 years (n Characteristic All Patients < Patients ≥ ¼ 1029) ¼ 131) cohort 80 years (n 80 years (n P- (n ¼ ¼ 1029) ¼ 131) value - Severely 13.8 (149/ 13.9 (134/ 12.7 (15/ 1160) depressed 1079) 961) 118) ANALYTICAL & ETIOLOGY HEMODYNAMIC Ischuemic etiology, % 68.2 69.1 (706/ 61.5 (80/ 0.085 VARIABLES (786/ 1022) 130) Systolic blood 106 107 (87–127) 105 0.950 1152) pressure (mmHg) (87–127) (85–126) STEMI, % 43.4 45.2 (463/ 29.2 (38/ 0.001 Heart rate (bpm) 84 (68–95) 85 (64–96) 79 (62–85) 0.356 (501/ 1024) 130) pH 7.23 7.22 7.27 0.008 1154) (7.10–7.31) (7.10–7.31) (7.09–7.36) - Anterior STEMI 50.9 50.5 (234/ 55.3 (21/ 0.576 Lactate (mmol/L) 5.2 5.2 (2.6–8.8) 5.2 (2.9–8.2) 0.618 location (255/ 463) 38) (2.7–8.7) 501) eGFR (ml/min/1.73 60.0 61.5 44.7 <0.001 NSTEMI, % 10.4 10.1 (103/ 13.1 (17/ 0.286 m2) (44.1–78.4) (46.0–79.1) (31.5–65.6) (120/ 1024) 130) AST (U/L) 106.5 107 (54–206) 96 (41–248) 0.988 1154) (53–209) Dilated ischemic 14.2 13.5 (138/ 20.0 (26/ 0.034 Hemoglobin (g/L) 135 136 121 <0.001 cardiomyopathy, % (164/ 1024) 130) (117–149) (119.5–151) (106–137) 1154) Leukocytes (x109/L) 14.4 14.6 12.5 0.002 Bradyarrhythmia, % 3.2 (37/ 1.8 (18/ 14.6 (19/ <0.001 (10.9–18.9) (11.0–19.1) (9.2–15.7) 1156) 1026) 130) Platelets (x103/ 208 211 198 0.085 Dilated non-ischemic 7.0 (81/ 7.3 (75/ 4.6 (6/130) 0.256 mm3) (169–261) (171–262) (148–247) cardiomyopathy, % 1157) 1027) C-reactive protein 9.5 8.5 13.0 0.215 Hypertrophic 1.1 (13/ 1.3 (13/ 0.0 (0/130) 0.197 (mg/dl) (2.5–62.2) (2.4–57.7) (4.1–69.7) cardiomyopathy, % 1156) 1026) Valvular heart disease, % 2.4 (28/ 2.2 (23/ 3.9 (5/128) 0.263 Continuous variables are expressed as median (IQR) and categorical data as % 1156) 1028) (n). Idiopathic, % 12.6 12.7 (130/ 11.5 (15/ 0.711 ADL: Activities of daily living; CPR: Cardiopulmonary resuscitation; CA: cardiac (145/ 1021) 130) arrest; AED: Automatic external defibrillator; EKG: Electrocardiogram; ROSC: 1151) Recovery-of-spontaneous-circulation; LVEF: Left ventricle ejection fraction; THERAPEUTIC eGFR: Estimated glomerular filtration rate; IQR: interquartile range. MANAGEMENT Inotropes, % 44.6 44.2 (448/ 47.9 (59/ 0.430 (507/ 1014) 123) groups. In addition, a NSE determination was carried out less frequently 1137) in patients ≥ 80 years. There were no differences in the percentage of Intra-aortic 8.5 (96/ 8.9 (90/ 4.9 (6/122) 0.130 neither pathological values of NSE (>33 ng/L) nor in positive Δ-NSE counterpulsation 1129) 1007) balloon, % between groups if repeated NSE determinations were performed. Pulmonary artery 11.6 (96/ 12.8 (94/ 2.1 (2/95) 0.002 In-hospital mortality was significantly higher in the elderly group. catheter, % 828) 733) Anoxic encephalopathy was more common in younger patients whilst - Excluding depenent for 11.9 (96/ 12.9 (94/ 2.5 (2/80) 0.006 cardiovascular death was more frequently the cause of death in older basic ADL 807) 727) patients. Restriction of invasive procedures was more commonly per­ Renal replacement 6.7 (56/ 7.3 (54/741) 2.1 (2/95) 0.056 theraphy, % 836) formed in the patients ≥ 80 years. Emergent CAG, % 69.6 72.8 (742/ 44.2 (57/ <0.001 There were no differences in the percentage of patients with a good (799/ 1019) 129) neurological prognosis between both groups. The percentage of patients 1148) with unknown CPC was higher in the elderly. Differences in prognostic - CAG if ST elevation 91.7 92.5 (457/ 80.6 (29/ 0.012 (486/ 494) 36) stratification and outcomes between groups are presented Table 3. 530) - CAG if ST elevation and 91.6 92.5 (455/ 78.8 (26/ 0.006 excluding depenent for (481/ 492) 33) 3.4. Predictors of in-hospital mortality basic ADL 525) Emergent PCI if CAG, % 55.5 55.1 (403/ 60.7 (34/ 0.411 A univariate analysis was performed to assess variables associated (437/ 731) 56) with in-hospital mortality. A Cox proportional hazard regression anal­ 787) ysis was performed including the well-known outcome predictors in SCD Deferred CAG, % 8.1 (92/ 8.2 (83/ 7.1 (9/127) 0.668 1136) 1009) patients and those variables found statistically significant in the uni­ Use of new antiplatelet 46.7 49.1 (506/ 27.4 (35/ <0.001 variate analysis. Age, non-shockable rhythm, time to to CPR initiation > agents, % (541/ 1030) 128) 5 min, time to ROSC > 20 min, a Killip class > 1 and lactate > 2 mmol/L 1158) at admission were independent predictors associated with in-hospital Culprit artery:, % - Left main 5.8 (30/ 6.1 (29/479) 2.6 (1/38) 0.370 mortality in these patients. Detailed results are shown in Table 4. 517) - Left anterior 42.5 45.1 (208/ 21.1 (12/ 0.075 descending (220/ 461) 36) 3.5. Predictors of poor neurologic outcome 518) - Left circumflex artery 19.7 18.4 (88/ 35.0 (14/ 0.008 We performed a univariate analysis to identify prognostic variables (102/ 478) 40) of poor neurologic outcomes among pacients in whom CPC assessment 518) was available. Based on the variables with p value < 0.1 in the uni­ - Right coronary artery 29.2 29.3 (140/ 28.2 (11/ 0.893 (151/ 478) 39) variate analysis those with a known prognostic value in the neurological 517) outcomes of patients with SCD, a Cox proportional hazard regression - Multivessel disease 0.002 analysis was performed. A non-shockable rhythm, time to CPR initiation (continued on next page) > 5 min, time to ROSC > 20 min and Killip class > 1 at admission were 4 J. Sans Roselló et al. IJC Heart & Vasculature 40 (2022) 101036 Table 2 (continued ) Table 3 Characteristic All Patients < Patients ≥ Differences in prognostic stratification and outcomes between groups. cohort 80 years (n 80 years (n P- All Patients < Patients ≥ (n ¼ ¼ 1029) ¼ 131) value Characteristic cohort 80 years (n 80 years (n P- 1160) (n ¼ ¼ 1029) ¼ 131) value 1160) 35.6 34.2 (279/ 54.0 (34/ (313/ 816) 63) 879) Status myoclonus ≥ 72 h, 19.8 20.2 (198/ 16.1 (19/ 0.293 Initial TIMI grade flow < 49.6 49.6 (385/ 50 (28/56) 0.940 % (1096) (217/ 978) 118) 3, % (413/ 776) 1096) 832) Absence of stem reflexes 17.9 17.7 (135/ 19.8 (16/ 0.867 Final TIMI grade flow < 10.4 (87/ 9.8 (76/781) 19.6 (11/ 0.020 ≥ 72 h, % (151/ 763) 81) 3, % 837) 56) 844) TC, % 53.4 56.5 (580/ 28.1 (36/ <0.001 Absence of spontaneous 30.5 31.2 (225/ 24.7 (20/ 0.233 (616/ 1026) 128) movements other than (245/ 722) 81) 1154) extension ≥ 72 h, % 803) TC if first shockable 59.3 61.3 (455/ 37.7 (26/ <0.001 EEG, % 39.9 41.1 (406/ 30.0 (36/ 0.019 rhythm, % (481/ 742) 69) (442/ 988) 120) 811) 1108) TC if first shockable 59.6 61.6 (453/ 37.5 (24/ <0.001 Status epilepticus, % 24.7 25.6 (112/ 16.3 (8/49) 0.152 rhythm excluding (477/ 736) 64) (120/ 437) depenent for basic 800) 486) ADL, % Use of anticonvulsant 17.9 18.5 (181/ 13.6 (16/ 0.189 TC early withdrawal, % 12.3 (75/ 12.6 (72/ 8.3 (3/36) 0.454 medication, % (197/ 982) 118) 610) 571) 1100) Induction of barbiturate 3.5 (23/ 3.8 (22/579) 1.3 (1/78) 0.279 coma, % 657) All variables are expressed as % (n). NSE determination, % 54.9 57.5 (567/ 34.1 (41/ <0.001 STEMI: ST-elevation myocardial infarction; NSTEMI: non-ST-elevation (608/ 987) 120) myocardial infarction; ADL: Activities daily living; CAG: coronary angiog­ 1107) raphy; OHCA: out-of-hospital cardiac arrest; PCI: percutaneous intervention; TC: NSE > 33 ng/L, % 45.0 44.6 (115/ 50 (10/20) 0.638 temperature management. (125/ 258) 278) Positive Δ-NSE, % 47.6 (88/ 46.8 (81/ 58.3 (7/12) 0.440 independent predictors of poor neurological outcome. Age was not a 185) 173) predictor of poor neurological prognosis in these patients. Detailed re­ SSEP-N20, % 28.8 30.1 (296/ 18.5 (22/ 0.009 sults are listed in Table 5. (318/ 985) 119) General management and predictors of in-hospital mortality and 1104) Brain magnetic 16.2 17.0 (156/ 9.3 (10/ 0.030 poor neurologic outcomes are illustrated in Fig. 1. resonance imaging, % (166/ 918) 107) 1025) 4. Discussion Cerebral tomography, % 45.7 46.2 (366/ 41.3 (38/ 0.377 (404/ 792) 92) 884) To the best of our knowledge this is the largest cohort addressing the CPC:, % impact of age on the management and prognosis of patients with an - 1 42.8 43.8 (451/ 35.1 (46/ 0.058 aborted SCD. Our study has shown the following main findings: 1) age (497/ 1029) 131) was an independent predictor for in-hospital mortality in patients 1160) admitted to hospital after an aborted SCD, 2) elderly patients were less - 2 6.1 (71/ 6.4 (66/ 3.8 (5/131) 0.243 1160) 1029) frequently offered therapies that are currently part of the standard of - 3 4.6 (53/ 4.9 (50/ 2.3 (3/131) 0.185 care in SCD patients and 3) neurological prognosis of elderly patients 1160) 1029) that suffered an aborted SCD appeared to be similar to that of younger - 4 21.4 21.7 (223/ 19.1 (25/ 0.496 patients. (248/ 1029) 131) First, advanced age seems to be an independent predictor of in- 1160) - 5 4.6 (55/ 4.9 (50/ 3.8 (5/131) 0.597 hospital mortality in patients admitted with a SCD. Our results are 1160) 1029) aligned with previous studies confirming a higher in-hospital mortality - Unknown 20.3 18.3 (189/ 35.9 (47/ <0.001 in SCD patients. As described in previous studies [17–20], we found that (236/ 1029) 131) younger patients had a higher likelihood of survival compared with 1160) CPC 1–2, % 61.5 61.6 (517/ 60.7 (51/ 0.881 elderly patients admitted after a SCD. Interestingly, the impact of age for (568/ 839) 84) increased mortality was lower with respect to other variables associated 923) with poorer prognosis such as an initial non-shockable rhythm or long Restriction of invasive 30.3 28.7 (189/ 42.0 (37/ 0.011 resuscitation times. This is supported by the results of previous studies procedures, % (226/ 658) 88) such as Hirlekar et al [21] who reported that despite the fact that the 30- 746) In-hospital mortality, % 44.2 42.2 (434/ 60.3 (79/ day survival of patients with SCD decreases with age, its OR was low, <0.001 (513/ 1029) 131) suggesting that age would be a weak predictor for the vital prognosis of 1160) these patients. For this reason, we looked for possible additional causes - Anoxic encephalopathy 55.4 57.4 (249/ 44.3 (35/ 0.032 that could explain this large difference in mortality between groups such (284/ 434) 79) 513) as a distinct diagnostic and therapeutic approach. - Cardiovascular death 30.2 27.6 (115/ 44.7 (34/ 0.003 The management of elderly patients admitted to hospital with a SCD (149/ 417) 76) was different from that of younger patients. Although the role of CAG 493) after a SCD is still debated, the guidelines propose that an emergent CAG All variables are expressed as % (n). should be indicated in those patients with the highest risk of a coronary EEG: Electroencephalogram; NSE: Neuron specific enolase; SSEP-N20: Somato­ occlusion (ST-segment elevation on the initial EKG, hemodynamic and/ sensory evoked potentials N20; CPC: Cerebral Performance Category STEMI: ST- 5 J. Sans Roselló et al. IJC Heart & Vasculature 40 (2022) 101036 elevation myocardial infarction; NSTEMI: non ST-elevation myocardial infarc­ performed less frequently in the elderly patients. This could be tion; ADL: Activities daily living; CAG: coronary angiography; PCI: percutaneous explained by a lower percentage of ST-elevation in this group, but when intervention; TC: temperature management. we analyzed only patients with ST-elevation, the percentage of emergent CAG in the elderly was still lower than in the younger group. Early CAG or electrical instability) [22] while in cases where there are no classical has been associated with better outcomes regardless of age in patients signs of STEMI in EKG, an immediate CAG strategy appears not to be who presented out-of-hospital SCD with a shockable rhythm [24] being superior to a delayed angiography strategy [23]. In our study, CAG was also less frequently performed in the elderly group in our cohort. Table 4 Predictors of in-hospital mortality. Univariate and multivariate analysis (n = 1160). UNIVARIATE ANALYSIS MULTIVARIABLE ANALYSIS Characteristic Alive (n ¼ 647) Dead (n ¼ 513) p-value Characteristic HR (95% CI) p-value Age (years) 61.3 (51.7–72.1) 67.1 (57.7–75.5) <0.001 Age 1.04 (1.01–1.08) 0.009 Male gender, % 74.7 (483/647) 73.7 (378/513) 0.708 Hypertension, % 54.7 (354/647) 62.0 (318/513) 0.013 Hypertension 0.63 (0.34–1.18) 0.149 Diabetes mellitus, % 23.8 (154/647) 30.3 (155/513) 0.013 Diabetes mellitus 2.28 (0.99–5.27) 0.054 Current smoker, % 61.4 (397/647) 67.5 (346/513) 0.031 Current smoker 1.78 (0.87–3.63) 0.114 Previous coronary artery disease, % 20.6 (133/647) 25.5 (131/513) 0.045 Previous coronary artery disease 0.55 (0.18–1.68) 0.292 Chronic kidney disease, % 8.0 (52/647) 13.8 (71/513) 0.001 Chronic kidney disease 1.12 (0.22–5.73) 0.895 Respiratory disease, % 9.9 (64/647) 17.2 (88/513) <0.001 Respiratory disease 1.84 (0.79–4.27) 0.158 Out-of-hospital SCD, % 78.1 (505/647) 78.0 (400/513) 0.974 Not-witnessed SCD, % 5.7 (37/647) 12.5 (64/513) <0.001 Not-witnessed SCD 1.65 (0.87–2.25) 0.163 Non-shockable rhythm, % 14.6 (94/644) 48.6 (249/512) <0.001 Non-shockable rhythm 3.05 (1.50–6.19) 0.002 STEMI, % 41.3 (267/647) 46.1 (234/508) 0.103 Time to CPR initiation (min) 1 (0–5) 3 (0–6) <0.001 Time to CPR initiation > 5 min 2.21 (1.14–4.27) 0.019 Time to ROSC (min) 17 (10–26) 30 (20–40) <0.001 Time to ROSC > 20 min 3.14 (1.30–7.60) 0.011 SBP < 90 mmHg, % 18.0 (106/589) 37.1 (163/439) <0.001 SBP < 90 mmHg 1.47 (0.71–3.03) 0.303 Emergent CAG 72.6 (470/647) 65.7 (329/501) 0.011 Emergent CAG 0.91 (0.55–1.35) 0.313 Multivessel disease, % 32.9 (179/544) 40.0 (134/335) 0.033 Multivessel disease 0.79 (0.42–1.48) 0.452 Final TIMI flow grade < 3, % 7.6 (39/513) 15.1 (48/318) <0.001 Final TIMI flow grade < 3 2.09 (0.90–4.82) 0.085 Killip class > 1, % 37.5 (100/267) 65.4 (153/234) <0.001 Killip class > 1 2.27 (1.9–4.73) 0.029 LVEF < 40%, % 36.1 (225/623) 46.3 (211/456) 0.001 LVEF < 40% 1.56 (0.77–3.16) 0.212 Lactate (mmol/L) 3.5 (1.9–6.1) 7.2 (4.6–11.4) <0.001 Lactate > 2 mmol/L 2.45 (1.02–5.92) 0.045 eGFR (ml/min/1.73 m2) 67.2 (51.7–82.7) 52.9 (37.8–67.9) <0.001 eGFR (ml/min/1.73 m2) 1.41 (0.66–2.99) 0.373 Hemoglobin (g/L) 137 (122–150) 132 (114–147) 0.005 Hemoglobin < 100 g/L 0.41 (0.06–1.1) 0.212 Leukocytes (x109/L) 14.1 (10.5–18.0) 15.1 (11.5–19.7) 0.003 Leukocytes > 11x109/L) 2.86 (0.99–8.13) 0.065 Continuous variables are expressed as median (IQR) and categorical data as % (n). SCD: Sudden cardiac death; STEMI: ST-elevation myocardial infarction; CPR: Cardiopulmonary resuscitation; ROSC: Recovery of spontaneous circulation; CAG: Coronary angiography; LVEF: Left ventricle ejection fraction; eGFR: Estimated glomerular filtration rate; IQR: interquartile range. Table 5 Predictors of poor neurological prognosis. Univariate and multivariate analysis (n = 1160). UNIVARIATE ANALYSIS MULTIVARIABLE ANALYSIS Characteristic CPC 1–2 (n ¼ 568) CPC 3–5 (n ¼ 356) p-value Characteristic HR (95% CI) p-value Age (years) 61.4 (51.7–72.3) 65.1 (54.8–73.4) 0.008 Age 1.01 (0.98–1.04) 0.383 Male gender, % 74.5 (423/568) 80.1 (285/356) 0.051 Male gender 0.99 (0.41–2.35) 0.974 Hypertension, % 55.5 (315/568) 59.3 (211/356) 0.255 Diabetes mellitus, % 24.5 (139/568) 27.8 (99/356) 0.259 Current smoker, % 36.3 (206/568) 38.3 (136/355) 0.165 Previous coronary artery disease, % 21.7 (123/568) 22.8 (81/356) 0.695 Chronic kidney disease, % 8.3 (47/568) 9.8 (35/356) 0.177 Respiratory disease, % 10.0 (57/568) 16.0 (57/356) 0.007 Respiratory disease 1.52 (0.54–4.26) 0.429 Out-of-hospital SCD, % 76.2 (433/568) 87.9 (313/356) <0.001 Out-of-hospital SCD 1.16 (0.40–3.42) 0.781 Not-witnessed SCD, % 4.9 (28/568) 11.0 (39/356) 0.001 Not-witnessed SCD 1.37 (0.38–4.87) 0.628 Non-shockable rhythm, % 12.4 (70/566) 43.9 (156/355) <0.001 Non-shockable rhythm 3.51 (1.85–6.64) <0.001 Time to CPR initiation (min) 1 (0–5) 3 (1–7) <0.001 Time to CPR initiation > 5 min 2.79 (1.44–5.41) 0.002 Time to ROSC (min) 15 (8–25) 29 (20–38) <0.001 Time to ROSC > 20 min 3.06 (1.31–7.12) 0.009 Ischemic etiology, % 68.1 (387/568) 65.6 (233/355) 0.431 Lactate (mmol/L) 3.3 (1.8–5.8) 6.8 (4.3–9.9) <0.001 Lactate > 4 mmol/L 1.42 (0.67–3.01) 0.361 eGFR (ml/min/1.73 m2) 68.7 (52.7–85.4) 54.8 (42.3–68.0) <0.001 eGFR (ml/min/1.73 m2) 1.49 (0.75–2.96) 0.255 Killip class > 1, % 38.2 (86/225) 49.0 (73/149) 0.039 Killip class > 1 2.26 (1.09–4.70) 0.029 Glucose (mmol/L) 11.3 (7.9–15.6) 14.9 (11.1–19.7) <0.001 Glucose > 10 mmol/L 1.40 (0.59–3.29) 0.443 Hemoglobin (g/L) 137 (122–150) 135 (117–149) 0.266 Leukocytes (x109/L) 14.0 (10.4–17.6) 15.0 (11.6–19.7) 0.003 Leukocytes > 11x109/L 1.83 (0.68–4.93) 0.231 SBP < 90 mmHg, % 18.2 (94/517) 25.2 (82/325) 0.015 SBP < 90 mmHg 1.16 (0.56–2.40) 0.691 LVEF < 40%, % 35.9 (195/543) 40.9 (140/342) 0.128 LVEF < 40% 0.93 (0.47–1.82) 0.826 Emergent CAG, % 71.7 (407/568) 68.5 (244/356) 0.312 Final TIMI grade flow < 3, % 6.4 (29/453) 10.4 (25/240) 0.065 Final TIMI flow grade < 3 0.78 (0.21–2.86) 0.707 Multivessel disease, % 32.7 (156/477) 35.9 (90/251) 0.393 No TC, % 53.1 (301/567) 68.3 (243/356) <0.001 No TC 1.30 (0.67–2.95) 0.361 Continuous variables are expressed as median (IQR) and categorical data as % (n). SCD: Sudden cardiac death; CPR: Cardiopulmonary resuscitation; ROSC: Recovery of spontaneous circulation; eGFR: Estimated glomerular filtration rate; SBP: systolic blood pressure; LVEF: Left ventricle ejection fraction; CAG: Coronary angiography; TC: Temperature control; IQR: interquartile range. 6 J. Sans Roselló et al. IJC Heart & Vasculature 40 (2022) 101036 Fig. 1. General management and predictors of in-hospital mortality and poor neurologic outcomes. SCD: sudden cardiac death; CAG: coronary angiography; OHCA: out-of-hospital cardiac arrest; PAC: Pulmonary artery catheter: CPR: Cardiopulmonary resuscitation; ROSC: Recovery of spontaneous circulation. However, our study probably lacked the power to demonstrate that it our study, after excluding patients with an unknown CPC, neurological was an independent predictor for good vital prognosis. prognosis appeared to be similar between groups, and age was not an Interestingly, among patients undergoing CAG, the rate of PCI was independent predictor for neurological outcomes. Only a non-shockable similar between groups, but even though they presented similar hemo­ rhythm, a worse hemodynamic status and longer CPR times were asso­ dynamic profile at admission, the percentage of final TIMI flow grade < ciated with poor neurological prognosis in our cohort. 3 was higher in elderly patients. TIMI flow grade < 3 after PCI has been TC is considered an effective therapy to improve neurological out­ related to poor outcomes in patients with acute coronary syndromes comes in patients with a SCD [35]. A recent update in the current [25]. In addition, as described in previous reports [26] age-related co­ guidelines on temperature control after cardiac arrest in adults [36] morbidity and a higher bleeding risk could conditioned a lower use of recommend actively preventing fever instead of temperature control at new antiplatelet agents in the elderly group. This fact along with that 32–36 ◦ C in these patients. In our study, we found that in the elderly age by itself can lead to an impaired coronary microcirculation state patients TC at 33 ◦ C was less performed than in the younger group. Older [27], could explain this higher rate of TIMI flow grade < 3 after PCI, and patients presented a lower percentage of shockable rhythms which could in turn, could also influence the outcomes. explain the lower use of TC in this group. However, when we analyzed We also observed that the use of PAC in our cohort was also lower in the use of TC only in patients with a shockable rhythm, its use in the elderly patients. Although Sionis et al [28], found that the use of PAC elderly was almost half that of younger patients. Even though in the was not associated with mortality in patients with cardiogenic shock, multivariate analysis, TC was not an independent predictor for neuro­ patients admitted with SCD may present hemodynamic instability not logical prognosis, it would have been interesting to know the neuro­ only secondary to myocardial dysfunction but also due to the effects of logical outcome of patients who died before CPC could be assessed since post-CA syndrome (ischemia–reperfusion damage) and the deleterious results could have been different [37]. effects of TC (arrhythmic alterations, volume depletion due to polyuria). Finally, the less invasive management in elderly patients admitted A better knowledge of the hemodynamic status of these patients may for SCD in our cohort could also influence their neurological prognosis, lead to a more adjusted and targeted management of their hemody­ since there are studies that show an increase in survival with a favorable namics and may also influence their prognosis [29]. neurological outcome in elderly patients admitted with SCD due to a Although our results did not allow us to establish a causal relation­ higher proportion of aggressive treatment [38]. ship between the lower rate of CAG, the worse results of PCI and the As a piece of real-world sample, our cohort represents the whole worse hemodynamic monitoring with the higher cardiovascular mor­ spectrum of SCD patients admitted at CICU. Despite the improvements tality in the elderly group, given that there is evidence that these vari­ in management and treatment of SCD patients, we found a high ables are associated with the outcomes of patients with SCD, we believe morbidity and mortality in these patients. Current therapies such as that they may have, at least partially, influenced it. Second, the influ­ extracorporeal cardiopulmonary resuscitation (ECPR) represent a ence of age on the neurological outcomes of SCD patients is still unclear. promising option to improve their prognosis in certain settings [39]. Some studies have shown that elderly patients with a SCD who survive However, in our environment, ECPR is not yet fully implemented. In our to discharge frequently have favorable neurological outcomes similar to cohort, age was associated with the vital prognosis of patients admitted that of the general population [19,21,30,31]. In our setting, a prospec­ after an aborted SCD, being also a determining factor in the management tive multicenter registry of patients with out-of-hospital SCD patients and treatment of these patients. Elderly patients received less invasive was carried out where age was not a predictor for neurological prognosis treatment even though they did not present a worse clinical profile upon [32]. In contrast, several other studies reported age as an independent arrival at the hospital, which could determine, at least in part, their predictor of poor neurological prognosis for SCD patients [17,33,34]. In worse prognosis. 7 J. Sans Roselló et al. IJC Heart & Vasculature 40 (2022) 101036 5. Study limitations References This is a multicenter retrospective observational study with a large [1] S.G. Priori, C. Blomström-Lundqvist, A. Mazzanti, N. Blom, M. Borggrefe, J. Camm, P.M. Elliott, D. Fitzsimons, R. Hatala, G. Hindricks, P. Kirchhof, K. Kjeldsen, K.- cohort of patients after aborted SCD. 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