Year : 2021 | Volume
: 9 | Issue : 2 | Page : 102--107
Clinical presentation, management and in-hospital outcomes of Acute coronary syndrome patients in real world scenario in developing countries: Insight from a high volume tertiary care center in North India
Akhil Kumar Sharma1, Diwakar Goel2, Gaurav Cahaudhary1, Ashish Tiwari1,
1 Department of Cardiology, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Brij Healthcare and Research Center, Mathura, Uttar Pradesh, India
Dr. Ashish Tiwari
Department of Cardiology, King George's Medical University, Lucknow - 226 003, Uttar Pradesh
Background: With the introduction of a huge armamentarium of invasive and noninvasive therapeutic strategies, the mortality related to acute coronary syndrome (ACS) has decreased across the world over the past 20 years, but the mortality remains high among Indian patients due to limited resource settings. Even in India, there is significant difference in health infrastructure in different part of country. This study was performed to evaluate the presentation, management and outcomes of ACS patients admitted in a high volume tertiary center of north India. Enrolment of the study done prior to covid pandemic.
Materials and Methods: 3511 ACS patients >18 year of age were included for this prospective observational study. All patients were evaluated with detailed clinical history and examination, ECG, Troponin, and detailed echocardiography. Patients were treated as per current guideline recommendation which included primary percutaneous coronary intervention (PCI), pharmacoinvasive therapy, thrombolysis or medical management only. Data was analysed for age, sex, risk factors, type of ACS, treatment given and complications if any. Those patients who underwent invasive approach also evaluated for coronary anatomy pattern and variables.
Results: Study population had younger mean age of 57.2 years, male preponderance (67%) and very high tobacco intake (46%). Out of all ACS patients 39% were STEMI (55% anterior wall myocardial infarction, 43% inferior wall myocardial infarction) and 61% were NSTEMI/USA. In STEMI subgroup, only 18% had primary PCI, while 42% received thrombolytic therapy as primary management. Nearly half of the patients who received thrombolytic therapy underwent pharmacoinvasive treatment (47.5%). A large number of late presenters (32% of all STEMI) did not receive any reperfusion therapy in index admission while few of them (6%) underwent invasive revascularization. Coronary anatomy evaluation showed multivessel disease in 53.1%. Left anterior descending artery was most common vessel involved (69.3%) among all ACS patients underwent coronary angiography. Most of the STEMI patients who underwent invasive route received PCI while very low rate for referral for CABG (2.1%). Major complications noted in study included left ventricular failure/cardiogenic shock (11.7%), advance AV blocks (8.2%), VT/VF (2.8%), Ventricular septal rupture (0.7%) and stent thrombosis (0.5%). In hospital mortality remained high (11.5%) mainly due to late presenters.
Conclusion: ACS management specially STEMI care is still needs a boost in north India. With primary PCI rate of only 18% and more than one third being late presenters not receiving any reperfusion therapy, there is urgent need of robust primary and referral health care system. As compared to other part of India, tobacco intake is alarmingly high (46%) and needs widespread health awareness in community of tobacco ill effects.
|How to cite this article:|
Sharma AK, Goel D, Cahaudhary G, Tiwari A. Clinical presentation, management and in-hospital outcomes of Acute coronary syndrome patients in real world scenario in developing countries: Insight from a high volume tertiary care center in North India.Heart India 2021;9:102-107
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Sharma AK, Goel D, Cahaudhary G, Tiwari A. Clinical presentation, management and in-hospital outcomes of Acute coronary syndrome patients in real world scenario in developing countries: Insight from a high volume tertiary care center in North India. Heart India [serial online] 2021 [cited 2021 Dec 3 ];9:102-107
Available from: https://www.heartindia.net/text.asp?2021/9/2/102/324617
According to WHO estimate, 29% of total deaths in India are due to cardiovascular disease (CVD). It has increased by 7% in the last five decades, 1960-2010 (from 4% to 11%). There is a sharp rural-urban divide and 20% have precocious coronary artery disease (CAD) (below 40 years). With the introduction of a huge armamentarium of invasive and non-invasive therapeutic strategies, the mortality related to ACS has decreased across the world over the past 20 years, but the mortality remains high among Indian patients due to limited resource settings., Only few studies exist in literature on the presentation, management and outcomes of ACS patients in India in present day scenario (Create and Kerala ACS Registry).
Uttar Pradesh, the largest state of India, is distinct from other states due to scarcity of health care manpower especially among rural areas, lower literacy rate and lack of health awareness, higher prevalence of diabetes mellitus and tobacco consumption in various forms and food habits in the form of increased carbohydrate consumption.
Ischemic heart disease may be manifested clinical as either chronic stable angina or an acute coronary syndrome (ACS). The latter, in turn, can be subdivided into STEMI, NSTEMI or UA.
A combination of criteria is required to meet the diagnosis of acute MI, namely the detection of an increase and/or decrease of a cardiac biomarker, preferably high-sensitivity cardiac troponin, with at least one value above the 99th percentile of the upper reference limit and at least one of the following: (1) Symptoms of ischemia. (2) New or presumed new significant ST-T wave changes or left bundle branch block on 12-lead ECG. (3) Development of pathological Q waves on ECG. (4) Imaging evidence of new or presumed new loss of viable myocardium or regional wall motion abnormality. (5) Intracoronary thrombus detected on angiography or autopsy.
Unstable angina (UA) is described as myocardial ischemia at rest or minimal exertion in the absence of myocardial infarction. Among unselected patients presenting with suspected ACS, the introduction of high-sensitivity cardiac troponin measurements has replaced standard troponin assays and it resulted in an increase in the detection of myocardial infarction and a reciprocal decrease in the diagnosis of UA.,,,
India is undergoing a rapid health transition with rising burden of coronary heart disease (CHD).
Among adults over 20 years of age, the estimated prevalence of CHD is around 3%–4% in rural areas and 8%–10% in urban areas, representing a two-fold rise in rural areas and a six-fold rise in urban areas between the years 1960 and 2000. Studies among Indian migrants in various parts of the world have documented an increased susceptibility to CHD in comparison to the native population studied.,
The INTERHEART study showed that 90% of population attributable to risk of a first myocardial infarction (MI) was accounted for by nine modifiable risk factors. These included smoking, dyslipidemia, hypertension, diabetes, abdominal obesity, psychological stress, daily consumption of fruits and vegetables, regular alcohol use, and physical activity.
India is the second largest consumer of tobacco with more than one-third of adults (35%) using tobacco in some forms or other and of which 21% using smokeless form exclusively.
INTERHEART study not only showed that smoking increases the risk of AMI by three times irrespective of the type of smoking form (Cigarette, bidi, pipe, etc.) but also demonstrated the ill effects of non-smoking forms of tobacco.
Chewing tobacco is known to increase the risk of AMI two-fold but when combined with smoking the risk increases four fold. Unselected ACS patients who are smokers are twice as likely to present with a STEMI, compared with nonsmokers, indicating a strong prothrombotic effect of smoking.
Diabetes mellitus patients are at 2–4 fold greater risk of developing cardiovascular events.
In the Jaipur Heart Watch (JHW) studies conducted over a 20-year period, the prevalence of metabolic syndrome has been progressively increasing in urban Indian population.,
While benefit has been documented with glycemic control on delaying or preventing microvascular disease, the relationship between hyperglycemia and macrovascular disease has been a subject of constant debate (UKPDS).,
The in-hospital mortality of unselected STEMI patients in the national registries of the ESC countries varies between 6% and 14%. Mortality is greater in patients experiencing anterior wall STEMI than in those with inferior wall STEMI, even when corrected for infarct size. Patients with right ventricular MI (RVMI) complicating inferior infarction have greater mortality rates. Cardiogenic shock complicates 6%–10% of all cases of STEMI and remains a leading cause of death, with hospital mortality rates approaching 50%. Baseline and follow-up stroke volume index and follow-up stroke work index appear to be the most powerful hemodynamic predictors of 30-day mortality in patients in cardiogenic shock and are more useful than traditional haemodynamic variables.
Early mortality risk with NSTEMI is lower than in patients with STEMI but, long-term outcomes with respect to both mortality and non-fatal events are worse.
Arrhythmias and conduction disturbances are common during the early hours after myocardial infarction. According to recordings from cardiac monitors implanted within 11 + 5 days of an acute myocardial infarction, the incidence is 28% for new-onset atrial fibrillation, 13% for non-sustained ventricular tachycardia, 10% for high-degree atrioventricular block (≤30 beats per minute lasting for ≥ 8 s), 7% for sinus bradycardia (≤30 beats per minute lasting for ≥ 8 s), 5% for sinus arrest (≥5 s), 3% for sustained ventricular tachycardia, and 3% for ventricular fibrillation.
Approximately 85% of patients with a clinical diagnosis of NSTE-ACS have significant coronary obstruction (i. e., >50% stenosis of the luminal diameter) in at least one major coronary artery. Most have obstructive disease involving multiple epicardial arteries (~10% with left main (LM) coronary artery, ~ 35% with three-vessel diseases, and ~ 20% with two-vessel disease), whereas only approximately 20% have isolated single vessel disease (SVD). The remaining 15% have no evidence of significant coronary obstruction on angiography; this finding occurs more frequently in women and is related to microvascular coronary obstruction, endothelial dysfunction, or spasm.
The prognosis of patients after AMI depends on infarct size and left ventricular (LV) dysfunction. LV ejection fraction (LVEF) lesser than 40% was an independent mortality predictor in the multicentre Postinfarction Research Group in 1980s. LV failure is the single most important predictor of mortality following STEMI. According to a study from US on 13,600 patients, mortality was 65% in patients with cardiogenic shock as compared to 10.5% in patients who did not develop cardiogenic shock after an AMI. This study was performed to evaluate the presentation, treatment, and outcomes of ACS patients admitted in a high volume tertiary center of north India.
Materials and Methods
In a prospective registry study, all 3511 successive patients >18 years presenting with ACS to the Emergency Department were included for over a year and analyzed for various factors. All STEMI patients were treated by primary percutaneous coronary intervention (PCI)/thrombolysis/conservative management depending on their time of presentation, risk profile and affordability. Patients who could not undergo primary PCI due to any reason, were offered for pharmacoinvasive approach (within 48 h). Intention to treat was to revascularize the culprit vessel first in the index setting and the remaining vessels as a staged procedure in the next hospital setting (except in rare circumstances, when critical stenosis of nonculprit vessel was also opened up).
Drug eluting stent was the mainstay of treatment as a part of invasive strategy, with Everolimus, Zotarolimus, and Sirolimus being the major stents.
Recent ACC and ESC guidelines were practiced and use of periprocedural drugs-Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Gp IIb-IIIa inhibitors, heparin, statins, β-blockers, and ACEIs and techniques used such as IVUS-guided optimization and FFR guided decisions whenever required were as per latest guidelines and recommendations. All uncomplicated patients were discharged from hospital on Day 3 on optimal medical therapy.
Thus, in hospital stay of 2–3 days in uncomplicated patients and longer stay in case of complicated ones, was the duration studied for all the outcomes and complications of the ACS patients. Data was analyzed for age, sex, risk factors, type of ACS, management strategy, and complications. Those underwent invasive strategy also evaluated for coronary anatomy and variables.
Study included 3511 patients presenting with ACS within 48 h of chest pain/equivalent symptoms when uncomplicated and irrespective of day of presentation (with in 4 week of index event) if complicated. Demographic profile included 67% male with mean age of 57.2 years. Among risk factors, tobacco consumption was alarming high to 46%, with the next other two commonest risk factors being diabetes mellitus (28%) and hypertension (33%).
Of all ACS patients, in our study, 39% were STEMI patients and 61% were USA/NSTEMI patients. The relative proportion of various STEMIs was as follows: Anterior wall myocardial infarction 55%, inferior wall myocardial infarction 5.5%, Inferior wall and right ventricular myocardial infarction 16.7%, inferior wall and posterior wall myocardial infarction (IWPWMI) 11.3%, inferior, right ventricular and posterior (IWRVPWMI) 9.3%, Isolated RVMI 0.1%, posterolateral MI 0.4%, and lateral MI 1.7%.
Of all STEMIs admitted, 42% were thrombolysed, 18% were taken up for primary PCI, 20% were treated using pharmacoinvasive approach. No reperfusion therapy could be provided to around 32% patients, mainly due to delayed reach to the hospital or financial constraints in uninsured patients. In NSTEMI group, 58% underwent invasive management, while 42% remained on medical therapy only. Of all ACS patients in our study, patients with LV EF <40 was 15.2%, while >40% was 84.8%.
On invasive coronary angiography, SVD was found in 46.9% of patients while multivessel disease (MVD) involvement seen in 53.1% of patients. Among major epicardial coronary artery disease, LM disease was involved in 4.7%, left anterior descending (LAD) in 69.3%, right coronary artery in 47.2%, and left circumflex in 35.9%.
The various complications were as follows: advanced AV blocks 8.2%, ventricular septal rupture 0.7%, cerebrovascular accident 0.5%, LV failure or cardiogenic shock 11.7%, stent thrombosis (during in-hospital course) 0.5%, and ventricular tachycardia/VF in 2.8% of study population. In-hospital mortality still remains high to 11.5% due to delayed presentation of MI patients.
CVDs are an important cause of mortality and morbidity in India. With Uttar Pradesh population over 225 million, there are only scant data available regarding real world scenario of ACS patients – their presentation, demographics, prevailing treatment practices, and in-hospital course and complications. The present study was conducted with similar aim in one of the largest tertiary care centers of Northern India.
“Kerala ACS Registry” of year 2007–2009 done by Mohannan et al. of 25,748 patients published in European Heart Journal 2013 and “CREATE Registry” of 20,000 ACS patients published in LANCET 2008 are two such studies conducted in the past.
Of all ACS patients admitted, 67% were males as compared to Kerala ACS registry males constituted 77.4%. It is a known fact that CHD events in women occur on average approximately 10 years after those in men, and women are less likely to be recognized and treated than men with ACS because of atypical symptoms. As per Merz CN in “The Yentl syndrome is alive and well,” “female-pattern IHD” characterized by a relatively lower obstructive CAD burden and preserved LVEF represents a “Yentl Syndrome” whereby women are relatively less likely to be recognized and treated than men with “male-pattern” IHD.
Diabetes constituted 28% of patients of all ACS patients in our study, while 37.6% in Kerala ACS registry and 30.4% in create registry. Giraldez et al. in “Prevalence and clinical outcomes of undiagnosed diabetes mellitus and prediabetes among patients with high-risk NSTE-ACS,” concluded that 20%–30% of European patients with NSTE-ACS have known diabetes mellitus.
Hypertensives were 29% patients in our study, while 40.4% in Kerala ACS registry and 37.7% in CREATE registry. As per prior studies, HTN is directly responsible for 57% of all stroke deaths and 24% of all coronary heart disease deaths in India.
Tobacco intake in the form of chewable tobacco or bidi or cigarette smoking was in 46% patients in our study, while 34.4% in Kerala ACS registry and 40.2% in CREATE registry.
Of all ACS patients, 39% were STEMI patients and 61% were USA/NSTEMI patients. Similarly in Kerala ACS registry 37% patients were STEMI patients. In create registry 60.6% were STEMI patients. Yeh et al., in their study titled, “Population trends in the incidence and outcomes of AMI,” found that the proportion of patients with ACS events who have STEMI various across observational studies from 29% to 47% of patients admitted with ACS.
MVD was seen in 53.1% of all ACS patients who underwent coronary angiogram (whether they were NSTEMI or STEMI). LM was diseased in 4.7% of our population. As per Cannon et al., most of the NSTEMI patients (55%) have MVD and 10% have LM coronary artery involvement. Similarly 50% of STEMI patients have significant MVD in previous studies.
LAD was diseased in 69.3% of all ACS patients who underwent coronary angiogram and anterior wall MI constituted 55% of all STEMI patients. As far as individual coronary arteries are concerned, LAD artery is the most frequent culprit vessel in both STEMI and NSTEMI-ACS in up to 40% of patients as per studies done by Ndrepepa et al. titled “Patterns of presentation and outcomes of patients with ACS.”
Of all STEMI admitted 42% were thrombolyzed and 18% were taken up for primary PCI.
Of those thrombolyzed, nearly half of them were taken up for pharmacoinvasive approach within 24 h. Similarly, around 6% patients were those who underwent PCI but not as a part of primary PCI strategy or pharmacoinvasive approach mostly as they reached us after 48 h with PMIA (Post Myocardial Infarction Angina), arrhythmia, shock, or any mechanical complication. Similar to our data, as per NIC database, primary angioplasty comprises 17% (24,375) of all interventional procedures in India. No reperfusion therapy, mainly due to delayed reach to the hospital or financial constraints, could be provided to around 32% patients.
In create registry, thrombolysis with streptokinase was done in 58.5% patients, while PCI was done in 8% STEMI patients. Similarly in Kerala ACS registry, thrombolysis was done in 41% STEMI patients and PCI in 11.9% patients. Kumar et al. in their study enrolled 1905 acute STEMI patients from whom 65% received STK, 10% used TNK-tPA, and 11% received primary PCI. Among NSTEMI-UA patients, 58% patients in our study underwent coronary angiogram out of which 45% underwent PCI and 13% were referred for CABG to CTVS department. Whereas in Create registry 6.7% underwent PCI. Ranasinghe et al. in their study-'Risk stratification in the setting of non-ST elevation ACS s' found that approx. 10% of NSTE-ACS patients may require CABG during their index hospitalization. In our study, of all ACS patients who underwent coronary angiogram, around 13% were referred for CABG.
As per the studies done by Bloch et al., long-term recording of cardiac arrhythmias with an implantable cardiac monitor in patients with reduced ejection fraction after acute myocardial infarction: the CARISMA study's during early hours after myocardial infarction arrhythmias and conduction disturbances are common. During early days (11 ± 5 days) after acute myocardial infarction, advanced AV blocks were seen in 10% of MI patients as compared to 8.2% in our study and sustained ventricular tachycardia or fibrillation was seen in 6% of MI patients, as compared to 2.8% in our study. In the APEX-AMI study, which included patients treated with primary PCI, sustained VT/VT developed in 5.7%.
As per prior studies, cardiogenic shock complicates 6%–10% of all cases of STEMI. Recent data suggest that the incidence of cardiogenic shock is reduced from 7% in 1970–1990s to approximately 5.5%–6% in the past two decades. Incidence of ventricular septal rupture in acute MI patients as per prior studies is said to be 1%–3% without reperfusion therapy and 0.2–0.34% with fibrinogen therapy, while in our study overall incidence of VSR was 0.7% among all ACS patients.
Finally, in-hospital mortality, out of all ACS patients admitted in our hospital was 11.5%. In create registry, it was around 8.6%, while in Kerala ACS registry it was 8.2%. The in-hospital mortality of unselected STEMI patients in the national registries of the ESC countries varies between 6% and 14% (“The second Euro Heart Survey on ACS: characteristics, treatment and outcome of patients with ACS in Europe and the Mediterranean Basin in 2004”, study done by Mandelzweig et al.).
Thus, for a developing country like ours, the major challenge in the field of ACS management is minimizing time delay from symptom onset to first medical contact and then to reperfusion. Community awareness programs, proper referral systems and development of regional centers with PCI capability are key areas of thrust. A lot more systemic and infrastructure improvisation are required to bring down the mortality and morbidity from ACS.
The important point to note is that 42% of the population which presented to the emergency department with ACS is young (35–55 years) and in the productive years of their life. Smoking and tobacco chewing contributed to the major chunk (46%) of the risk factors. Importantly 15% tend to have no conventional risk factor leading us to the area of research into newer risk factors responsible in the young population. Furthermore, the large majority (89%) has no known coronary artery disease. About 40% present with STEMI with a mostly half-half distribution between anterior and inferior MI. In our center, we were able to do primary PCI in 17.8% being centrally located.
This leaves scope for increasing the opportunity to those, who could not get primary PCI primarily because of presenting in off hours and socio-economic reasons. However, we were able to apply, the pharmacoinvasive approach in 20.1% cases, and this we believe is a strategy that should be encouraged, in developing countries to achieve long-term benefits in those who for some reason cannot get a PAMI. Unfortunately, we also had a large group, almost one third of the patients (32.1%) who could not get any reperfusion. This was primarily because of very late presentation (beyond 24 h), and other socioeconomic reasons. Our referral for CABG in the STEMI was very low (2.1%). In the NSTEMI group, there was a tilt toward conservative management primarily due to patients' preference (42%). One SAT rate was 0.5%. Since we have a lot of late presenters, where treatment delays are unescapable and patient complications high (11.7% were in shock), our in hospital mortality rate was also a little high standing at 11.5%.
There was a half-half distribution of single and MVD (SVD-46.9%, MVD 53.1%). In those who underwent PCI, the largest majority had a single stent implanted (80.6%).
The information gained from this registry, therefore, helps in reinforcing lifestyle modification in the young, who are struck by ACS in the prime of their life. Primary angioplasty is feasible with timely reporting to the hospital, with a low cost single stent strategy. In case, that is not possible, a strategy of pharmacoinvasive approach also seems to reduce in-hospital mortality. The nearly one-third presenters, who get no reperfusion therapy, may be taken into the umbrella of therapy via public awareness, of the benefits of such treatment and in-hospital mortality reduced. We need to look into the long term outcomes of those received reperfusion therapy and those who receive no therapy at all.
Limitation of study includes single center study, less number of patients and observational study. Many other factors such as socioeconomic status, dietary habits, door to needle time, etc., were not studied in the present study.
Dr. Akhil was consultant incharge of the research work, Dr. Diwakar and Dr. Ashish did research work and prepared manuscript, Dr. Gaurav did the literature review and prepared manuscript.
Manuscript has been read and approved by all the authors that the requirements for authorship as stated earlier in this document have been met and that each author believes that the manuscript represents honest work.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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