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CTRI Number  CTRI/2020/10/028222 [Registered on: 05/10/2020] Trial Registered Prospectively
Last Modified On: 02/10/2020
Post Graduate Thesis  Yes 
Type of Trial  Observational 
Type of Study   Cohort Study 
Study Design  Other 
Public Title of Study   COMPARING THE CLINICAL FEATURES AND OUTCOME IN PATIENTS WITH HEART ATTACK AND LOW BP, WHO COME TO THE HOSPITAL EARLY VERSUS THOSE WHO COME LATE. 
Scientific Title of Study   EARLY VERSUS LATE PRESENTATION OF PATIENTS WITH CARDIOGENIC SHOCK IN ST-ELEVATION MYOCARDIAL INFARCTION – COMPARISON OF CLINICAL FEATURES AND OUTCOMES  
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  NAGARATHNA SHENOY 
Designation  Cardiology Registrar 
Affiliation  Kasturba Medical College , Manipal  
Address  Department Of Cardiology, 3rd floor, Kasturba Medical College and Hospital, Madhav Nagar, Manipal, Karnataka. PIN: 576104

Udupi
KARNATAKA
576104
India 
Phone  8197361377  
Fax    
Email  nagarathna.shenoy2@learner.manipal.edu  
 
Details of Contact Person
Scientific Query  
Name  Dr Ganesh P 
Designation  Associate Professor 
Affiliation  Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 
Address  Department Of Cardiology, 3rd floor, Kasturba Medical College and Hospital, Madhav Nagar, Manipal, Karnataka. PIN: 576104

Udupi
KARNATAKA
576104
India 
Phone    
Fax    
Email  ganeshbmc@gmail.com  
 
Details of Contact Person
Public Query  
Name  Dr Ganesh P 
Designation  Associate Professor 
Affiliation  Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 
Address  Department Of Cardiology, 3rd floor, Kasturba Medical College and Hospital, Madhav Nagar, Manipal, Karnataka. PIN: 576104

Udupi
KARNATAKA
576104
India 
Phone    
Fax    
Email  ganeshbmc@gmail.com  
 
Source of Monetary or Material Support  
KASTURBA MEDICAL COLLEGE, MANIPAL, MANIPAL ACADEMY OF HIGHER EDUCATION, MANIPAL 
 
Primary Sponsor  
Name  KASTURBA MEDICAL COLLEGE MANIPAL MANIPAL ACADEMY OF HIGHER EDUCATION MANIPAL 
Address  DEPARTMENT OF CARDIOLOGY, 3RD FLOOR, KASTURBA MEDICAL COLLEGE AND HOSPITAL, MADHAV NAGAR, MANIPAL, UDUPI, KARNATAKA. PIN - 576104 
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Ganesh P  Kasturba Medical College, Manipal  Department of Cardiology, 3rd floor, Kasturba Medical college and hospital, Madhav Nagar, Manipal, Udupi. PIN - 576104
Udupi
KARNATAKA 		 9914204224

ganeshbmc@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethics Committee, Kasturba Medical College and Kasturba Hospital   Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: I210||ST elevation (STEMI) myocardial infarction of anterior wall, (2) ICD-10 Condition: I211||ST elevation (STEMI) myocardial infarction of inferior wall, (3) ICD-10 Condition: I212||ST elevation (STEMI) myocardial infarction of other sites, (4) ICD-10 Condition: I213||ST elevation (STEMI) myocardial infarction of unspecified site,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  NIL  NIL 
Intervention  NIL  NIL 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  All Patients aged more than 18 years presenting to ER with chest pain and ECG diagnosis of STEMI and Cardiogenic shock

1. Patients with ECG diagnosis of STEMI defined as new ST segment elevation at J point in at least 2 contiguous leads of more than or equal to 2mm in
men more than 40 years and more than or equal to 1.5mm in women more than 40 years in leads V2-V3, and or more than 1mm in other contiguous chest /limb leads and

2. CS as defined by SCAI
- SBP less than 90mmHg or MAP less than 60 mmHg or more than 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

3. Time to Hospitalisation since the onset of symptoms less than 24 hours for early presenters of cardiogenic shock and more than 24 hours for late presenters of cardiogenic shock. 
 
ExclusionCriteria 
Details  1. Patients not giving informed written consent
2. Patients who are unable to document the symptom onset time
3. Shock due to causes other than STEMI
4. Patients with cardiac arrest before hospitalisation
5. Pregnant women, terminal illness and advanced malignancy.
 
 
Method of Generating Random Sequence   Not Applicable 
Method of Concealment   Not Applicable 
Blinding/Masking   Not Applicable 
Primary Outcome  
Outcome  TimePoints 
Major adverse cardiovascular events (MACE) defined as a composite of all cause death, resuscitated cardiac arrest, nonfatal MI, stroke  1. End of hospital stay
2. 1 month 
 
Secondary Outcome  
Outcome  TimePoints 
1. All cause death
2. Resuscitated cardiac arrest
3. Nonfatal MI
4. Stroke
5. Renal failure 		 1. End of hospital stay
2. 1 month 
 
Target Sample Size   Total Sample Size="300"
Sample Size from India="300" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   N/A 
Date of First Enrollment (India)   05/10/2020 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   No publication yet on this study 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  



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

 Â·      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.)

                              Â·       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, end‐organ hypoperfusion, and hypoxia (3, 4) .The hallmark is peripheral vasoconstriction and vital end‐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 end‐organ hypoperfusion requiring pharmacological or mechanical intervention.(6)

Acute myocardial infarction (MI) accounts for 81% of patient in CS (7, 4). ST‐segment–elevation myocardial infarction (STEMI) is associated with a 2‐fold increased risk for development of CS compared with non–ST‐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 Lindholm and Køber et 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 artery and very extensive myocardial damage. Early shock was more often associated with ST-segment elevation in multiple leads and with multiple ECG infarct 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 waves and 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 V‐P, Lassus J, Sionis A, Køber L, Tarvasmäki T, Spinar J, Parissis J, Banaszewski M, Silva‐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 short‐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 ST‐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.


 
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