A Specific Predictor of STSegment Elevation Myocardial Infarction Among the Symptoms of Acute Coronary Syndrome: Sweating In Myocardial Infarction (SWIMI) Study Group

A Specific Predictor of STSegment Elevation Myocardial Infarction Among the Symptoms of Acute Coronary Syndrome: Sweating In Myocardial Infarction (SWIMI) Study GroupA Specific Predictor of STSegment Elevation Myocardial Infarction Among the Symptoms of Acute Coronary Syndrome: Sweating In Myocardial Infarction (SWIMI) Study GroupA Specific Predictor of STSegment Elevation Myocardial Infarction Among the Symptoms of Acute Coronary Syndrome: Sweating In Myocardial Infarction (SWIMI) Study Group

Clinical Investigations Sweating: A Specific Predictor of ST-Segment Elevation Myocardial Infarction Among the Symptoms of Acute Coronary Syndrome: Sweating In Myocardial Infarction (SWIMI) Study Group Address for correspondence: Bhanwar Lal Ranwa, MD Department of Cardiology Jawaharlal Nehru Medical College and Hospital Ajmer, Rajasthan, India, Pin-305001 bhanwar.ranwa@gmail.com Rajendra K Gokhroo, MBBS, MD, FACC; Bhanwar L Ranwa, MBBS, MD; Kamal Kishor, MBBS, MD; Kumari Priti, MBBS, MD; Avinash Ananthraj, MBBS, MD; Sajal Gupta, MD; Devendra Bisht, MD Department of Cardiology, Jawaharlal Nehru Medical College and Hospital, Ajmer, Rajasthan, India Background: Today, cardiologists seek to minimize time from symptom onset to interventional treatment for the most favorable results Hypothesis: In the acute coronary syndrome (ACS) symptom complex, sweating can differentiate ST-segment elevation myocardial infarction (STEMI) from non–ST-segment elevation ACS (NSTE-ACS) during early hours of infarction Methods: This single-center, prospective, observational study compared symptoms of STEMI and NSTE-ACS patients admitted from August 2012 to July 2014 Results: Of 12 913 patients, 90.56% met ACS criteria Among these, 22.51% had STEMI Typical angina was the most common symptom (83.82%) On stepwise multiple regression, sweating (odds ratio: 97.06, 95% confidence interval [CI]: 82.16-114.14, P < 0.0001) and typical angina (odds ratio: 2.72, 95% CI: 2.18-3.38, P < 0.001) had significant association with STEMI For diagnosis of STEMI, positive likelihood ratio (LR) and positive predictive value (PPV) were highest for typical angina with sweating (LR: 11.17, 95% CI: 10.31-12.1; PPV: 76.09, 95% CI: 74.37-77.75), followed by sweating with atypical angina (LR: 3.6, 95% CI: 3.07-4.21; PPV: 50.61, 95% CI: 46.45-54.76), typical angina (LR: 1.05, 95% CI: 1.03-1.07; PPV: 22.97, 95% CI: 22.11-23.84), and atypical angina (LR: 0.77, 95% CI: 0.69-0.87; PPV: 18.09, 95% CI: 16.32-19.97) C statistic values of 0.859 for typical angina with sweating and 0.519 for typical angina alone reflected high discriminatory value of sweating for STEMI prediction Conclusions: Presence of sweating with ACS symptoms predicts probability of STEMI, even before clinical confirmation Sweating in association with typical or atypical angina is a much better predictor of STEMI than NSTE-ACS Introduction Failure to implement appropriate therapy in time is the major cause of increased cardiovascular morbidity and mortality in acute coronary syndrome (ACS) cases Inability to deliver any form of reperfusion therapy in about 30% of patients and failure to minimize delays in reperfusion reflect missed opportunities for improvement in care of acute ST-segment elevation myocardial infarction (STEMI).1 Only 25% of all patients presenting with suspected ACS in the emergency department (ED) have a confirmed diagnosis of ACS at discharge.2 Despite this, diagnosis of acute myocardial The authors have no funding, financial relationships, or conflicts of interest to disclose 90 Clin Cardiol 39, 2, 90–95 (2016) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22498 © 2015 Wiley Periodicals, Inc infarction (AMI) is missed in up to 11.1% of cases.3 Among AMI cases, 18% not have chest pain2 at presentation; an initial 12-lead electrocardiogram (ECG) has a sensitivity of only 20% to 60%; and a single set of biochemical markers also has poor sensitivity.4 – In this era of intervention, cardiologists around the globe seek to minimize time from first medical contact to device/needle time for the most favorable results The ‘‘time is muscle’’ concept for viable myocardium cannot be implemented unless patients present within a certain window of time So identification of event by patients and primary-care physicians is as important as is the golden hour of reperfusion We undertook this study to discover any ‘‘red flags’’ in the ACS symptom complex that could identify STEMI with precision during the early Received: August 20, 2015 Accepted with revision: November 1, 2015 hours of infarction This red flag might increase community awareness and clinical acumen of health care professionals, thereby improving event-to-reperfusion time (ie, time from event onset to reperfusion) Methods Study Patients This was a prospective, single-center, observational study that included 12–913 patients admitted to the coronary care unit from August 1, 2012, to July 31, 2014, with presumed diagnosis of ACS after meticulous screening in the ED (Figure 1) We included patients age ≥30 years who presented to the ED with a chief symptom of chest, arm, jaw, or epigastric pain or discomfort, shortness of breath, dizziness, palpitations, syncope, or other symptoms suggestive of ACS Cases with suspected pulmonary thromboembolism and known cases of coronary artery disease or heart failure were excluded from the study Clinical data was recorded by multiple on-duty cardiology fellows History was self-narrated and leading questions were asked according to a preset questionnaire Other data of interest included sociodemographic information, ECG findings, serial creatine kinase MB (CK-MB)/troponin T (TnT), and echocardiography Discharge diagnosis was made by the senior ward physician and confirmed by a senior cardiologist Analysis of Data Diagnosis was confirmed on the basis of ECG, serial CK-MB/TnT measurements, and echocardiography as per universal definition of myocardial infarction (MI) Unstable angina (UA) was defined as angina pectoris (or equivalent type of ischemic discomfort) with ≥1 out of features: (1) occurring at rest (or minimal exertion) and usually lasting >20 minutes (if not interrupted by the administration of a nitrate or an analgesic); (2) being severe and usually described as frank pain; or (3) occurring with a crescendo pattern (ie, pain that awakens the patient from sleep or that is more severe, prolonged, or frequent than previously).7 Non–ST-segment elevation myocardial infarction (NSTEMI) was as defined as ≥1 measurement of CK-MB >10 μg/L or TnT >0.1 μg/L in the context of UA with absent ECG criteria for STEMI.8 ST-segment elevation myocardial infarction was defined as a clinical syndrome with characteristic symptoms of myocardial ischemia in association with persistent ECG ST-segment elevation and subsequent release of biomarkers of myocardial necrosis Diagnostic ST-segment in the absence of left ventricular (LV) hypertrophy or left bundle branch block was defined as new ST-segment at the J point in ≥2 contiguous leads of ≥2 mm (0.2 mV) in men or ≥1.5 mm (0.15 mV) in women in leads V2 through V3 and/or of ≥1 mm (0.1 mV) in other contiguous chest leads or the limb leads New or presumably new left bundle branch block at presentation, ST-segment depression in ≥2 precordial leads (V1 through V4 ) diagnostic of posterior-wall STEMI, and multi-lead STsegment depression with coexistent ST-segment elevation in lead aVR were also included in the STEMI group.9 – 13 Symptoms were classified as typical angina and atypical Figure Flow of patients in SWIMI study Abbreviations: NSTE-ACS, non–ST-segment elevation acute coronary syndrome; STEMI, ST-segment elevation myocardial infarction; SWIMI, Sweating In Myocardial Infarction; USA, unstable angina angina/angina equivalent Typical angina was defined as substernal chest discomfort with a characteristic quality and duration that was provoked by exertion or emotional stress and relieved by rest or nitroglycerin.14 The rest of the symptoms suggestive of acute ischemia were grouped as atypical angina/angina equivalent Sweating was used as synonymous to diaphoresis, defined as profuse drenching sweats inappropriate to the physical and environmental state Statistical Analysis The statistical analyses were done using SPSS version 20 (IBM Corp., Armonk, NY) Odds ratios (OR) were calculated for the association between each potential risk factor and STEMI We considered 95% confidence intervals (CIs) that excluded unity, or, equivalently, P < 0.05, as statistically significant Univariate analysis was done to find statistically significant symptoms, which were then analyzed using multivariate logistic regression In the multivariable analysis, the probability of STEMI was predicted using multiple logistic regression All independent variables (symptoms) were entered in the regression models as categorical variables Starting with the full multivariable model with all independent variables included, we excluded insignificant independent variable at a time, starting with the variable with highest P value, until only significant and important predictors remained Likelihood ratios (LR) and predictive values (PV) of different symptoms for STEMI were also calculated The area under the receiver operating characteristic curve (ROC) was used as an overall measure of the discrimination abilities of different symptoms The area under ROC, measured in percent, can be interpreted as the probability that a randomly chosen patient with a particular symptom has a higher probability of STEMI than a randomly chosen patient without that symptom Results Among 12 913 patients, 11 695 (90.56%) were admitted with the diagnosis of ACS and 1218 (9.44%) patients had Clin Cardiol 39, 2, 90–95 (2016) R.K Gokhroo et al Sweating as a predictor of STEMI Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22498 © 2015 Wiley Periodicals, Inc 91 nonischemic chest pain Of the ACS patients, 2474 had STEMI and 9221 had non–ST-segment elevation acute coronary syndrome (NSTE-ACS) For 223 patients with STEMI, their history could not be elicited as they presented to the ED in a moribund state (due to cardiogenic shock, stroke, ventricular fibrillation, or sudden cardiac death); therefore, they were excluded from the analysis Six hundred five patients from the NSTE-ACS group could not be further evaluated and were excluded One hundred fifty-nine patients admitted with NSTE-ACS developed late ST-segment elevation and were included in the STEMI group Thus, the final cohort comprised 10 867 patients Of these, 2410 (22.18%) patients had STEMI, 6751 (62.12%) had UA, and 1706 (15.7%) patients had NSTEMI In our cohort, the majority of patients were in the age group of 51 to 70 years Out of all patients, 6781 (62.49%) were male and 4086 (31.6%) were female The NSTE-ACS group had more females than did the STEMI group (42.08% vs 21.87%; P < 0.0001) The NSTE-ACS patients had a higher prevalence of diabetes mellitus (32.43% vs 18.58%; P < 0.0001), hypertension (34.24% vs 27.30%; P < 0.0001), and dyslipidemia (38.61% vs 26.68%; P < 0.0001) than the STEMI group (Table 1) The site of infarction was anterior in 56.72%, inferior in 40.29%, posterolateral in 1.83%, lateral in 1.08%, and isolated right ventricular infarction in 0.08% In the study cohort, typical angina (83.82%) was the most common presenting symptom in the ACS population, with greater prevalence in the STEMI group than in the NSTEACS group (86.80% vs 82.97%, P < 0.0001; Table 1) Sweating was present in 90.95% of STEMI and 10.43% of NSTE-ACS patients (P < 0.0001) On univariate analysis, all symptoms except nausea (P = 0.225) and palpitations (P = 0.364) were found to have significant association with STEMI These significant independent variables were then analyzed using multivariate analysis Using backward stepwise multiple logistic regression, independent variables, typical angina (OR: 2.72, P < 0.0001) and sweating (OR: 97.06, P < 0.0001), were the only significant predictors of STEMI Sweating (28.29%) in the context of ACS had the highest odds (OR: 97.06, P < 0.0001) of favoring STEMI Arm pain (OR: 1.06, P = 0.437), back pain (OR: 1.03, P = 0.709), epigastric pain (OR: 1.01, P = 0.891), dyspnea (OR: 1.06, P = 0.57), nausea (OR: 1.05, P = 0.557), vomiting (OR: 1.17, P = 0.83), and vertigo (OR: 1.31, P = 0.487) favored STEMI over NSTEACS, whereas palpitations (OR: 0.99, P = 0.99), mouth dryness (OR: 0.82, P = 0.049), chest pain other than typical angina (OR: 0.70, P = 0.099), and throat pain (OR: 0.97, P = 0.656) favored NSTE-ACS over STEMI (Figure 2) The ROC curve was plotted to estimate the discriminatory performance of the logistic-regression model The C statistic value of typical angina with sweating for diagnosis of STEMI was 0.859, compared with 0.519 for typical angina alone To evaluate the impact of sweating for diagnosis of STEMI, all ACS symptoms were grouped into categories, typical angina and atypical angina or angina equivalents Atypical symptoms were more common in the NSTE-ACS group (17.03% vs 13.2%; P < 0.0001) Despite being the most common clinical presentation (86.8%), typical angina had a low PPV (22.97), low LR (0.05), and low OR (1.35) for diagnosis of STEMI (Table 2) 92 Clin Cardiol 39, 2, 90–95 (2016) R.K Gokhroo et al Sweating as a predictor of STEMI Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22498 © 2015 Wiley Periodicals, Inc Presence of sweating in the context of typical angina increased PPV from 22.97 to 76.09, LR from 1.05 to 11.17, and OR from 1.35 to 111.11 for STEMI Likewise, presence of sweating in the context of atypical angina improved PPV from 18.09 to 50.61, LR from 0.77 to 3.60, and OR from 0.74 to 45.45 Among all ACS symptoms, typical angina with sweating had the highest PPV (76.09), positive LR (11.17), and OR (111.11) for diagnosis of STEMI Presence of sweating markedly improved the statistical significance of anginal symptoms for diagnosis of STEMI (Table 2, Figure 3) On subgroup analysis, 159 STEMI patients initially did not meet the ECG criteria in the ED, and diagnostic ECG changes evolved after hospitalization The majority of them, 142 (89.3%), had sweating at presentation This implies the significance of symptoms for timely diagnosis and management of STEMI Discussion Diagnosis of STEMI with history has always been a clinical dilemma Its diagnosis is delayed due to lack of specificity of any symptom, delayed patient presentation, and temporal delay in obtaining supporting evidence of biochemical parameters, ECG, and echocardiography This study analyzed the symptoms of STEMI and NSTE-ACS patients to see if any emerged as potential indicators for early diagnosis of STEMI Typical angina was most common presentation in both groups In the STEMI group, 13.2% of patients, and 17.03% in the NSTE-ACS group, had complaints other than typical angina, which is on par with observations by Pope and colleagues.2 Chest-pain characteristics and duration are subjective and lack sound clinical evidence to pitch them for STEMI diagnosis In a meta-analysis by Chun and McGee15 and Panju et al,16 chest-pain characteristics such as pressure and the like were not enough to be independently useful in establishing a MI diagnosis Classic duration of pain lasting >30 minutes can be indicative of either an AMI or a nonischemic etiology, like gastroesophageal disease.17,18 In a meta-analysis of 64 studies, chest-pain duration >30 minutes suggested low likelihood of MI (LR+: 0.1).15 Several studies have examined the ability of associated symptoms such as nausea, vomiting, and diaphoresis to predict AMI Two meta-analyses discovered that nausea and diaphoresis predict AMI.15 Nattel et al noted sweating in 53% of AMI cases Diaphoresis was a more specific but less sensitive predictor of MI than prolonged chest pain.19 However, in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial, the association between diaphoresis and AMI disappeared on multivariable testing (OR: 1.1, P = 0.636).6 Underrepresentation of patients in older age groups and non–English-speaking ethnic groups probably underestimated the association of sweating In our Sweating In Myocardial Infarction (SWIMI) study cohort, sweating and typical angina were the only significant symptoms for STEMI prediction Sweating when added to angina, whether typical or atypical, improved the diagnostic accuracy of the symptom for STEMI in all statistical domains Typical angina with sweating had the highest PPV and LR for STEMI Table Baseline Characteristics and Symptom Profile of ACS Patients Total Patients, N = 10 867 STEMI Patients, n = 2410 NSTE-ACS Patients, n = 8457 P Value 989 (9.10) 221 (9.17) 768 (9.08) 0.925 41–50 1618 (14.89) 546 (22.66) 1072 (12.67)