EARLY VERSUS LATE PRESENTATION OF PATIENTS WITH CARDIOGENIC SHOCK IN ST-ELEVATION MYOCARDIAL INFARCTION – COMPARISON OF CLINICAL FEATURES AND OUTCOMES

Title  of  the  project**:**  â€˜EARLY  VERSUS  LATE  PRESENTATION  OF  PATIENTS  WITH CARDIOGENIC SHOCK IN ST-ELEVATION MYOCARDIAL INFARCTION – COMPARISON OF CLINICAL FEATURES AND OUTCOMES’

Type of Study: Prospective, Single-Center, Clinical Observational Study.

Aims & objectives:

Aim

·      To study the clinical features and outcomes of patients with cardiogenic shock (CS) in ST –Elevation myocardial infarction (STEMI) presenting early versus lat

Objective

a)  To compare the major adverse cardiovascular events (MACE) in patients presenting early with those presenting late with cardiogenic shock due to STEMI in hospital and at one month follow up.

b)   To compare the differences in the clinical profile, angiographic features and mechanisms of shock in early versus late presenters of cardiogenic shock with STEMI*.*

4.  Justification for study (whether of national significance with rationale): Mortality in STEMI complicated by cardiogenic shock is high. Most common cause of CS-STEMI is LV systolic failure. Other causes include mechanical complications like ventricular septal rupture, free wall rupture and mitral regurgitation. Patients who present to the hospital within 24 hours of symptom onset are characterized as early presenters of CS-STEMI and those presenting after 24 hours of symptom onset are characterized as late presenters of CS-STEMI. Our aim in this study is to study the outcomes in these two groups and study the differences in clinical profile, angiographic features and mechanism of shock in them. In developed countries, most of the patients with STEMI receive early medical attention and hence late presentation is rare in such scenario. As a result, data related to the late presentation and the differences in this group from that presenting early are lacking. In our country, as most of the patients do not have access to the tertiary centers, patients are unable to recognize the symptoms and hence late presentation of CS-STEMI is common compared to developed countries. Hence it is important to have study which focuses on the two different set of groups and compare them. There are very few studies differentiating these two groups. This study is therefore important especially in developing country like India, where the access to the healthcare resources are limited. By studying the clinical features and angiographic profile we can arrive at an in depth understanding of underlying mechanisms and outcomes which will help in improving treatment strategies.

Departments involved: Department of Cardiology

Study period: OCTOBER 2020 TO DEC 2021

Sample size: Time bound

Materials and methods:

a)  Inclusion and exclusion criteria:

Inclusion criteria

All Patients aged > 18 years presenting to ER with chest pain and ECG diagnosis of STEMI and Cardiogenic shock

·       Patients with ECG diagnosis of STEMI defined as new ST segment elevation at J point in at least 2 contiguous leads of >= 2mm (0.2mV) in men >40 years and >=1.5mm (0.15mV )I n women > 40 years in leads V2-V3 &/or > 1mm (0.1)mV in other contiguous chest /limb leads) and CS as defined by SCAI

-          SBP <90mmHg for MAP < 60 mmHg or > 30mmHg drop from the baseline and drugs/device to maintain the BP

-          Evidence of cardiac dysfunction – based on Echocardiographic findings

-         Evidence of end organ hypoperfusion (urine output < 30ml/hr or Lactate >2 or altered mental status.)

·       Time to Hospitalisation since the onset of symptoms <24 hours for early presenters of cardiogenic shock and >24 hours for late presenters of cardiogenic                                       shock

Exclusion criteria

·       Patients not giving informed written consent

·       Patients who are unable to document the symptom onset time

·       Shock due to causes other than STEMI

·       Patients with cardiac arrest before hospitalisation

·       Pregnant women, terminal illness and advanced malignancy.

b)Biological materials required (type - blood, tissue etc. and quantity): None. Reports from standard blood test will be collected. No additional blood sample for the purpose of this study.

c)   Statistical methods:Univariate and multivariate logistic regression will be used to assess outcomes.Mean and standard deviations will be used to describe continuous variables. Categorical variables will be expressed as frequencies and percentages along with medians and interquartile ranges. Chi square test and student t-test will be used to compare categorical variables and continuous variables respectively. P value of <0.05 will be considered statistically significant.

Detailed description of procedure/processes: The study will be conducted in the Department of Cardiology, Kasturba Hospital, Manipal after IEC clearance and CTRI registration during June 2020 to Dec 2021. Eligible patients will be explained in detail about the study in their own language and given the participant information sheet. An informed consent will be taken from patients who are willing to participate in the study after fully understanding the nature of the study and risk/benefits involved.This is an observational study in which data will be collected from the patients who are willing to participate. Baseline characteristics of the patients, presenting symptoms, time to hospitalization since onset of symptoms, vital signs at hospitalization, laboratory evidence for CS (lactate level if any), echocardiographic details (LVEF, mechanical complications if present) is collected and documented. The angiographic details in case the patient undergoes coronary angiography is also collected and entered in the data collection form. Major adverse cardiovascular events – all cause death, nonfatal MI, stroke, resuscitated cardiac arrest and renal failure will be noted during in hospital stay and at 1 month follow up

Outcome measures:

1.  MACE – All cause death, resuscitated cardiac arrest, nonfatal MI, Target Vessel Revascularization (TVR) and stroke during in hospital stay and one month follow up.

2.    Renal Failure – in hospital and at one month follow up

Review of literature :

Myocardial infarction (MI) complicated by cardiogenic shock (CS) remains a major problem in cardiovascular medicine. Although outcomes have improved over the last 2 decades with early revascularization and modern intensive care, morbidity and mortality remain high**.** Five to 10% of patients with myocardial infarction develop cardiogenic shock and 2/3 of these patients are expected to die within a few weeks.(1,2)

CS is caused by severe impairment of myocardial performance that results in diminished cardiac output, endâ€organ hypoperfusion, and hypoxia (3, 4) .The hallmark is peripheral vasoconstriction and vital endâ€organ damage, which stems from ineffective stroke volume and insufficient circulatory compensation (3,4,5).Clinically this presents as hypotension refractory to volume resuscitation with features of endâ€organ hypoperfusion requiring pharmacological or mechanical intervention.(6)

Acute myocardial infarction (MI) accounts for 81% of patient in CS (7, 4). STâ€segment–elevation myocardial infarction (STEMI) is associated with a 2â€fold increased risk for development of CS compared with non–STâ€segment–elevation myocardial infarction (NSTEMI) (4). The incidence of CS has increased in recent years, while the reason for increasing incidence is unclear, improved diagnosis and better access to care are both likely contributory(4,8)

The time of onset of CS has a potential role in influencing its prognosis. Limited contemporary data exist on this complication (9). In a study done by Lindholmand Køberet al.,showed that the time interval between myocardial infarction and development of cardiogenic shock is a major determinant of mortality in patients with cardiogenic shock complicating myocardial infarction. Thirty-day mortality was 45% in patients with early shock as compared to more than 80% in patients developing cardiogenic shock more than 48h after a myocardial infarction(2). A study done by John G. et al., concluded that shock onset after acute MI occurred within 24 h in 74% of the patients with predominant LV failure. Mortality was slightly higher in patients developing shock early rather than later. Many factors influence when shock develops, which has implications for its management.In a Danish study of 444 patients with CS in MI from the thrombolytic era, the majority (59%) had shock within 48 hours of presentation, 11% developed shock on days 3–4, and 30% developed shock after day 4. Late shock was a significant predictor of 30-day mortality compared to early shock (mortality 87% versus 45%). Those with late shock were more likely to be female, a lower proportion received thrombolytics, and a higher proportion had in-hospital reinfarction.(11) It is intuitive to suspect that shock might occur early after MI due to occlusion of a major coronary arteryand very extensive myocardial damage.Early shock was more often associated with ST-segment elevationin multiple leads and with multiple ECGinfarct locations.(10) The LAD coronary artery was the most common culprit vessel regardless of the time of shock onset. Nevertheless, patients in whom the right coronary artery was the culprit, or who had inferior MI on clinical grounds, were relatively more likely to develop shock early. Mortality in these patients may be reduced with aggressive medical support and reperfusion strategies (10) More than 25% of patients who developed shock did so relatively late (≥24 h) after MI. With a median delay of 51 h after MI onset in this group, the implications for aetiology and treatment may differ from those for patients developing shock early . Several factors may favour the delayed appearance of shock. Infarct expansion may progressively reduce mechanical efficiency, particularly after large anterior MIs .This relationship may underlie the frequent association between a culprit LAD artery, multiple new Q wavesand late shock (10).

Cardiogenic shock is a devastating complication of acute myocardial infarction (AMI) and remains the most common cause of mortality in patients hospitalized with AMI. (12,6,1,13,14). Despite high clinical acuity at presentation, many MI-CS patients can have excellent long-term outcomes with some recovery of contractile function and physiologic accommodation. Therefore, a focus on improvement in early mortality via the thorough understanding of the inflammatory response and prevention or early reversal of end-organ dysfunction may provide these critically ill patients with improved quality and longer duration of life.(15)Early and aggressive revascularization for cardiogenic shock in the setting of AMI, in conjunction with the use of mechanical approaches to counter left ventricular pump failure in cardiogenic shock, has been shown to improve the short-term survival of these high-risk patients (12).

Limited data exist on comparing the difference in the outcome of early versus late cardiogenic shock. Present literature lacks sufficient data and also each study has different results from the others. Most of these studies are based on western data. Hence it is important to have a study in India which focuses on the time of presentation of cardiogenic shock and its outcome.

References:

1.GoldbergRJ, Samad NA, Yarzebski J, et al.Temporal trends in cardiogenic shock complicating acute myocardial infarction. .N Engl J Med. 1999;340:1162–1168

2.M.G Lindholm, L Køber, S Boesgaard, C Torp-Pedersen, J Aldershvile.Cardiogenic shock complicating acute myocardial infarction: Prognostic impact of early and late shock development.European Heart Journal, Volume 24, Issue 3, 1 February 2003, Pages 258–265, https://doi.org/10.1016/S0195-668X(02)00429-3

3.  van Diepen S, Katz JN, Albert NM, Henry TD, Jacobs AK, Kapur NK, Kilic A, Menon V, Ohman EM, Sweitzer NK, Thiele H, Washam JB, Cohen MG. .Contemporary management of cardiogenic shock: a scientific statement from the American Heart Association. Circulation. 2017; 136:e232–e268.

4.  Cyrus Vahdatpour , David Collins , and Sheldon Goldberg.Cardiogenic Shock.Journal of the American Heart Association. 2019;8:e011991.doi.org/10.1161/JAHA.119.011991

5.  Hochman JS. Cardiogenic shock complicating acute myocardial infarction: expanding the paradigm. Circulation. 2003; 107:2998–3002

6.R Goldberg, J Gore, J Alpert, et al.Cardiogenic shock after acute myocardial infarction. Incidence and mortality from a community-wide perspective, 1975–1988.N Engl J Med, 325 (1991), pp. 1117-1122

7.Harjola Vâ€P, Lassus J, Sionis A, Køber L, Tarvasmäki T, Spinar J, Parissis J, Banaszewski M, Silvaâ€Cardoso J, Carubelli V, Di Somma S, Tolppanen H, Zeymer U, Thiele H, Nieminen MS, Mebazaa A; for the CardShock study investigators and the GREAT network . Clinical picture and risk prediction of shortâ€term mortality in cardiogenic shock: clinical picture and outcome of cardiogenic shock. Eur J Heart Fail. 2015; 17:501–509

8.  Kolte D, Khera S, Aronow WS, Mujib M, Palaniswamy C, Sule S, Jain D, Gotsis W, Ahmed A, Frishman WH, Fonarow GC.

Trends in incidence, management, and outcomes of cardiogenic shock complicating STâ€elevation myocardial infarction in the United States. J Am Heart Assoc. 2014; 3:e000590. DOI:10.1161/JAHA.113.000590

9 Hoa L. Nguyen, MD, MS, PhD; Jorge Yarzebski, MD, MPH; Darleen Lessard , et al.Ten-Year (2001–2011) Trends in the Incidence Rates and Short-Term Outcomes of Early Versus Late Onset Cardiogenic Shock After Hospitalization for Acute Myocardial Infarction.J Am Heart Assoc . 2017 Jun 7;6(6):e005566. DOI: 10.1161/JAHA.117.005566

10.  John G. Webb, MD, FACC,* Lynn A. Sleeper, SCD,† Christopher E. Buller, MD, FACC ,et al.Implications of the timing of onset of cardiogenic shock after acute myocardial infarction: a report from the SHOCK Trial Registry.Journal of the American College of Cardiology.Volume 36, Issue 3, Supplement 1, September 2000, Pages 1084-1090

11.  Lindholm MG, Køber L, Boesgaard S, et alTrandolapril Cardiac Evaluation study group.Cardiogenic shock complicating acute myocardial infarction; prognostic impact of early and late shock development. Eur Heart J. 2003;24:258–265

12.  Robert J. Goldberg , Raghavendra Charan P. Makam , Jorge Yarzebski , David D. McManus , Darleen Lessard , and Joel M. Gore.Decade-Long Trends (2001–2011) in the Incidence and Hospital Death Rates Associated with the In-Hospital Development of Cardiogenic Shock after Acute Myocardial Infarction.Circulation: Cardiovascular Quality and Outcomes. 2016;9:117–125.https://doi.org/10.1161/CIRCOUTCOMES.115.002359

13.  Goldberg RJ, Spencer FA, Gore JM, Lessard D, Yarzebski J.Thirty-year trends (1975 to 2005) in the magnitude of, management of, and hospital death rates associated with cardiogenic shock in patients with acute myocardial infarction: a population-based perspective.Circulation. 2009; 119:1211–1219. doi: 10.1161/CIRCULATIONAHA.108.814947

14. Reynolds HR, Hochman JS.Cardiogenic shock: current concepts and improving outcomes.Circulation. 2008; 117:686–697.  doi: 10.1161/CIRCULATIONAHA.106.613596

15 Deepak Acharya, MD, MSPH.Predictors of Outcomes in Myocardial Infarction and Cardiogenic Shock.Cardiol Rev. 2018 Sep-Oct; 26(5): 255–266.