Acute Pancreatitis and Myocardial Infarction: A Narrative Review

Acute pancreatitis, which is sudden inflammation of the pancreas, is caused by multiple etiologies with gallstone (38%) and alcohol use (36%) among the most common [1, 2]. Most patients with mild pancreatitis recover with conservative management but 20% of acute pancreatic cases advance to severe disease [3]. Complications of acute pancreatitis may range from pancreatic pseudocyst, acute peripancreatic fluid collection, pancreatic necrosis, abdominal compartment syndrome, splanchnic venous thrombosis to systemic complications like deep venous thrombosis, acute respiratory distress syndrome (ARDS), acute kidney injury, shock, and worsening of underlying acute cardiovascular disease such as heart failure and ischemic heart disease [4‒6]. Studies have shown that regardless of the severity of acute pancreatitis, it can be associated with myocardial injury [7], although sometimes it only mimics acute coronary syndrome (ACS) in the absence of obstructive coronary artery disease. Electrocardiographic (ECG) changes involving T-wave and ST segment abnormalities have been seen in 25% of cases of acute pancreatitis [8] but one presenting as an ST-elevation myocardial infarction (STEMI) is very rare. This rare but serious association of pancreatitis with ischemic ECG changes presents as a diagnostic dilemma as treating it as a true ACS may unnecessarily expose patients to thrombolytic therapy and/or invasive procedures like cardiac catheterization and its side effects if no underlying ischemic cardiac disease is present. On the other hand, attributing ischemic ECG changes to mere manifestations of electrical modifications caused by pancreatitis may result in missing real ACS with fatal consequences. This literature review was conducted to better understand the association of acute pancreatitis with ACS, identify different strategies being deployed worldwide for its management, and suggest areas for possible improvement.

The incidence of myocardial infarction (MI) in acute pancreatitis is very rare. According to a retrospective cohort study done in Taiwan [9], higher incidence of acute atherosclerotic cardiovascular disease (ASCVD) was found in patients with acute (11.8 per 1,000 person-years) and chronic (17.7 per 1,000 person-years) pancreatitis than those without pancreatitis (6.81 per 1,000 person-years, p < 0.0001) during follow-up period of 13 years. This study also showed that significantly higher proportions of comorbidities such as hypertension, end-stage renal disease requiring dialysis, chronic obstructive pulmonary disease, cholecystitis, mental disorders, alcohol-related illness, liver cirrhosis, hyperlipidemia, and diabetes were found in pancreatitis patients than in subjects without pancreatitis. Pancreatitis was associated with increased risk of acute ASCVD (i.e., acute MI or stroke) among people with 1 (HR 2.01, 95% CI 1.49–2.71) and ≥2 (HR 2.02, 95% CI 1.53–2.67) of those comorbid conditions [9]. Per 2019 review study by Yu et al. [10] since 1954 only 36 cases of acute pancreatitis mimicking myocardial ischemia where underlying ACS was excluded either with cardiac catheterization or autopsy have been reported in literature.

The exact mechanism of myocardial injury in acute pancreatitis is not known but several hypotheses have been proposed. Severe pancreatitis can cause severe hypotension, which can decrease coronary perfusion and lead to myocardial ischemia, especially in patients with coronary artery disease [11]. Pancreatic proteolytic enzymes (i.e., trypsin, etc.) may lead to cellular necrosis as well as electrolyte disturbance by directly damaging the membrane of the myocyte [12]. These enzymes may also lead to coronary thrombosis by changing platelet adhesiveness properties [13, 14]. One study showed that increased comorbidity burden seen in patients with pancreatitis may predispose them to increased risk of ASCVD [8]. Vagal reflexes via parasympathetic nervous system stimulation may cause cardiac damage by acting directly on myocardium, increased secretion of pancreatic proteolytic enzymes, or via alteration of coronary blood flow [15, 16]. Electrolyte abnormalities sometimes seen with acute pancreatitis may evoke ischemic ECG changes [17]. Takotsubo cardiomyopathy occurring as a complication of pancreatitis may cause ischemic ECG changes from catecholamine excess as reported by Cheezum and Rajani [18, 19]. Acute pancreatitis may result in coronary vasospasm leading to ECG changes [20]. Pleural and pericardial effusions have been observed transiently in acute pancreatitis cases [21]. It has been postulated that digestive enzymes in those fluids may injure the myocardium through lymphatic drainage via the thoracic duct [22, 23]. Transdiaphragmatic passage of inflammation from pancreatitis may also contribute to epicardial cardiac inflammation [24]. Moreover, inflammation of the pancreas releases inflammatory cytokines such as interleukin (IL)-6, IL, tumor necrosis factor-alpha, and platelet-derived growth factor and may cause endothelial dysfunction which contributes to initiation and progress of atherosclerosis [25‒27]. A narrative review study by Luo et al. [7] summarized the pathological mechanism of severe acute pancreatitis (SAP) associated myocardial injury into three main categories as shown in Table 1.

As discussed below, review of reported cases of AMI related to pancreatitis suggests that most patients initially presented with retrosternal chest pain, epigastric pain, or abdominal pain with or without radiation to the back. Lipase and amylase are elevated in most of the reported cases. Troponin elevation is also a common finding, noticed in almost 54% of cases where values were reported, as shown in Table 2. ECG changes like ST elevations and T-wave inversions are most commonly seen in inferior, inferolateral, or anterior regions. Peaked T waves, ST depressions, pathological Q waves, and QT prolongation are some other ECG abnormalities typically observed. In 2019, Yu et al. [10] comprehensive summary of cases where acute pancreatitis simulated acute myocardial injury, inferior wall STEMI pattern was the most common presentation. Electrolytic abnormalities such as hypokalemia, hypocalcemia, hypomagnesemia, and hyponatremia are common in acute pancreatitis and can contribute to ECG changes [17]. Transthoracic echocardiogram (TTE) may be normal or show reduced ejection fraction with or without regional wall abnormalities of the left ventricle. Of the 34 total reported cases of pancreatitis presenting with STEMI pattern, as shown in Table 2, incidence of true MI remained very low, with overwhelming majority of cases demonstrating normal coronary angiography or nonobstructive coronary artery disease.

A standard management protocol for AMI associated with acute pancreatitis does not exist due to its rare occurrence. As there are multiple causes that can lead to acute ST segment elevation in acute pancreatitis, it is essential to identify the underlying mechanism. It is important to establish whether it is real or pseudo myocardial infarction since treatment options are different for both. Misdiagnosing pseudo myocardial infarction as real and treating it with thrombolytics can have serious hemorrhagic consequences, especially if it is associated with pancreatitis [90]. When a patient with acute pancreatitis presents with symptoms concerning for acute MI, it is important to evaluate and treat electrolyte abnormalities, especially hyperkalemia, as it can induce ST segment changes [93]. Troponin and brain natriuretic peptide (BNP) levels should also be checked. TTE can be obtained if there is suspicion of stress cardiomyopathy, which is characterized by elevated troponin, high BNP, and/or transient left ventricular wall abnormalities on TTE. This can have the same clinical presentation as ACS [98]. Coronary angiography or CT coronary angiogram may be performed after weighing the risks and benefits to rule out true MI and assess for antithrombotic need, especially if risk of ACS is moderate to high and cannot otherwise be excluded with certainty. Coronary angiography can be done without heparin and antithrombotics can be initiated once the culprit coronary artery is identified. Culprit vessel(s) with significant stenosis are treated with revascularization. If thrombus is present, aspiration via catheter followed by plain old balloon angioplasty can be done [11]. As acute pancreatitis is an absolute contraindication to emergent percutaneous coronary intervention, conservative treatment with antithrombotic and lipid-lowering drugs can be chosen in certain scenarios [99]. Overall, it is important to keep in mind that pseudo-myocardial infarction associated with pancreatitis or “pancreatitis-related ECG and biomarker abnormalities” is a diagnosis of exclusion and coronary artery disease needs to be excluded even in cases when the patient does not present with chest pain or tightness [100].

Drummond first noted ECG changes related to acute pancreatitis in 1934 [89]. Since then, it has been noted that ECG abnormalities are present in approximately 50% of patients with acute pancreatitis [17]. Majority of these changes include arrhythmias, intraventricular conduction disturbances, and nonspecific ST and T wave changes [89]. Instances of acute myocardial infarction complicating acute pancreatitis have also been reported. Rarer, however, is acute pancreatitis presenting with an ECG distribution consistent with acute myocardial infarction without true coronary artery thrombosis. In 2019, Yu et al. [10] conducted a review of 36 cases of acute pancreatitis mimicking myocardial infarction where ACS was excluded. We will evaluate those cases along with new cases from 2019 to present.

Of the 36 cases identified by Yu et al., we have excluded seven for not meeting diagnostic ECG criteria for STEMI. Three cases had normal troponin with T-wave inversions but no ST elevation. Four cases had isolated new LBBB, which was used as a sign of STEMI equivalent. The 2013 American College of Cardiology Foundation/American Heart Association Guideline for the Management of STEMI recommends that new or presumably new LBBB should not be considered diagnostic of acute myocardial infarction in isolation [101]. Given that the aforementioned cases had no chest pain or elevated cardiac markers to support acute MI, these cases were excluded from our evaluation.

We have now identified a total of 34 instances of acute pancreatitis mimicking acute myocardial infarction on ECG. Two-thirds of the patients were male (64.7% or 22/34). Of risk factors reported, 87% (21/24) had at least one cardiovascular risk factor and 25% (6/24) only had a history of severe alcohol abuse. Chest pain was reported as the presenting symptom in 32% (11/34) of cases. Two cases had mixture of ST depression and T-wave inversions and one had a posterior infarction pattern. Troponin was reported in 71% (24/34) of cases, of which 54% (13/24) were classified as elevated. Twenty-three (67.6% or 23/34) patients had TTE performed, of which 48% (11/23) identified wall motion abnormalities with four consistent with Takotsubo cardiomyopathy. Seventeen (50% or 17/34) patients had a coronary angiography performed while inpatient. One case showed evidence of acute myocarditis on cardiac MRI in a patient with fulminant diabetes type 1 and acute pancreatitis [72]. There were four (11.7% or 4/34) cases where thrombolytics were administered. Seven patients (21% or 7/34) were reported to have died, most from necrotizing pancreatitis, and one in particular a few hours after receiving thrombolytics, with significant intraperitoneal hemorrhaging noted on autopsy. Of the patients who were discharged, the majority (63% or 17/27) had resolution of ECG and/or echocardiogram findings either prior to discharge or on follow-up, and three (11% or 3/27) cases reported no normalization but had no follow-up after discharge.

It is well known that acute pancreatitis has the potential to have a wide array of complications, both local and systemic, affecting many organ systems. However, thus far, it has been rare to see acute pancreatitis associated with acute myocardial infarction. Since 1954, when reporting 12-lead ECGs became standard practice [89], there have only been 34 such cases. Although the frequency of such presentations may be low, the acuity is high and typically leads to high-risk invasive testing or treatment and carries high morbidity and mortality.

Recently, great strides have been made to better understand the association of acute pancreatitis and its effect on the heart. Luo et al. [7] in 2021 published the first comprehensive report on pathological mechanisms, in which they noted three broad contributing categories. The most insight can be gained from the pathogenesis of myocardial injury caused by sepsis; however, scientific data are still limited. This study serves as a much-needed stepping stone for further research focused on specific molecular areas as targets of potential drug treatment, as current strategies are focused on symptomatic support rather than preventative interventions.

It is imperative that clinicians are aware that acute pancreatitis can mimic an acute myocardial infarction and that they keep this in their differential when evaluating patients with ST-segment and T-wave changes. The full clinical picture should be taken into account when deciding how to pursue further with medical care. Careful evaluation of cardiovascular risk factors, symptoms, cardiac markers, and wall motion changes on TTE can be highly indicative of the presence of a thrombotic event and should be performed prior to exposing patients to thrombolytic therapy and/or invasive procedures like cardiac catheterization. That being said, presentation can vary significantly, and a missed acute myocardial infarction can be fatal. Moving forward, a larger data pool and more focused molecular research are needed to effectively examine associations of pancreatitis and its effect on the heart.

Authors have no conflicts of interest to declare.

This work did not receive any funding.

Umair Khan was involved in writing of the manuscript. Oksana Petrechko was involved in writing of the manuscript and formatting. Shazib Sagheer helped with revision and editing. Harris Majeed and Syeda Hamna Zaidi performed data collection, tabulation, and formatting. Najam Wasty was involved in revision of the manuscript. Abu Baker Sheikh oversaw and edited the manuscript and provided clinical input.

Umair Khan and Oksana Petrechko contributed equally to this work.