1. O'Keefe-McCarthy, Sheila PhD, RN
  2. Ready, Linda MN, RN(EC)
  3. Francis, Sara-Lynn MD, BSc, FRCPC

Article Content

Prodromal symptoms indicative of myocardial ischemia are often not recognized as cardiac in nature. Prodromal symptoms are transitory symptoms that may occur days to months prior to an adverse cardiac event.1-3 This case study illustrates a routine follow-up of a 65-year-old female with type 2 diabetes mellitus (T2DM). She presented with a 1-month history of recurrent, unprovoked nausea and vomiting, intermittent chest discomfort, and a 3-week history of insomnia. Differential diagnoses included cholecystitis, gastroesophageal reflux disease (GERD), and/or diabetic gastroparesis.


The internal medicine consult suggested that symptoms were likely gastrointestinal (GI) in nature and recommended an exercise stress test and echocardiogram. The echocardiogram revealed normal systolic function with mild diastolic dysfunction. The exercise stress test indicated moderate anteroseptal and apical ischemia. Diagnostic cardiac catheterization revealed 99% stenosis of the left anterior descending artery and 70% stenosis of the proximal right coronary artery. A percutaneous coronary intervention with drug-eluting stents was emergently performed.


Warning signs

Prodromal symptoms are warning signs of an impending cardiac event related to development of coronary artery disease (CAD) and remain a challenge for primary care providers to recognize, screen, and treat. Prodromal symptoms may include the following: chest and arm pain, shortness of breath (SOB), unusual fatigue, dizziness, nausea and vomiting, headaches, sleep disturbances, and anxiety.1-3 Prodromal symptoms may occur weeks to months before an actual cardiac-related event and typically dissipate after the cardiac event occurs.1-4


As individuals survive with CAD, the prevalence of prodromal symptoms also increases. Average estimated prevalence rates for prodromal symptoms have ranged from 49% to 92%.1,3 A lack of prodromal symptom recognition may increase cardiac-related morbidity and mortality. Delayed symptom recognition may be attributed to the elusive nature of symptoms that are frequently experienced by individuals prior to their ischemic event.


Moreover, symptoms are experienced among a myriad of other competing conditions and comorbidities, confounding the presentation. Primary care providers need to recognize the variable, prehospital warning signs of CAD to help provide a thorough cardiac workup and ensure proactive screening for evidence of possible prodromal symptoms.


This case illustrates a clinical follow-up of a patient seen in a family healthcare clinic for cardiac-related prodromal symptoms. This article describes the assessment, treatment, and interventions provided and highlights clinical challenges to assist in the identification of patients' elusive and subjective prodromal symptoms.


Case report

Ms. S, a 65-year-old woman returning for her scheduled follow-up clinic visit for T2DM, had relevant medical history for T2DM, hypertension, obesity, depression, and dyslipidemia. Functional inquiry revealed the ability to perform instrumental activities of daily living, no decrease in exercise tolerance, and an intentional 44-lb (19.9-kg) weight loss in the last year. Current medications include enteric-coated aspirin, ramipril, lantus insulin, sitagliptin, metformin hydrochloride, and escitalopram. Family history revealed both parents and a sibling had confirmed CAD.


Ms. S reported a 1-month history of recurrent, unprovoked nausea and vomiting accompanied occasionally by chest discomfort and a 3-week history of insomnia. When asked about the duration, Ms. S stated, "It is relieved on its own within a few minutes and occurs every 2 days or so." Ms. S was assessed twice in the ED for episodes of nausea and vomiting and associated chest discomfort. Results of a routine cardiac workup and metabolic profile were unremarkable.


Physical exam revealed that she was in no apparent acute distress. Her BP was 120/60, and her heart rate was 70 and regular. Chest auscultation revealed normal vesicular breath sounds. Cardiac assessment indicated normal S1 and S2 heart sounds with no identification of S3 or S4; no rubs or murmurs were elicited. Her abdomen was round, soft, slightly tender in the epigastric area with no organomegaly or abdominal rebound present; bowel sounds were evident in all four quadrants. Ms. S's peripheral pulses were palpable in both upper and lower extremities; no peripheral edema was noted; integument, musculoskeletal, and neurologic exams were normal.


Cholecystitis, GERD, or diabetic gastroparesis were considered as possible differential diagnoses. Ms. S was started on pantoprazole 40 mg orally once daily for GERD, and an abdominal ultrasound (that was suspicious for fatty infiltrates with otherwise unremarkable results) was done. ECG findings indicated normal sinus rhythm with nonspecific T-wave changes in the anterior leads. Routine blood work was done (complete blood cell count, blood urea nitrogen, electrolytes, creatinine, random glucose, creatine kinase, troponin 1, international normalized ratio, and partial thromboplastin time), and she was referred to internal medicine.


The internal medicine physician suspected that the cause of Ms. S's symptoms was likely GI in nature. However, considering her comorbidities, risk factors, and strong family history of cardiovascular disease, it was decided that Ms. S needed an exercise stress test and an echocardiogram. The echocardiogram revealed normal systolic function with grade I/IV left ventricle and mild diastolic dysfunction. The exercise myocardial perfusion study results revealed a moderate size region of ischemia across the anteroseptum and apex, corresponding to the left anterior descending (LAD) coronary artery territory.


Coronary artery disease was confirmed by a definitive ECG-positive stress test. Ms. S was sent for emergent diagnostic cardiac catheterization. A percutaneous coronary intervention (PCI) with drug-eluting stents was emergently performed.



Prodromal symptoms may present a challenge to primary care providers, as these symptoms are often overlooked or incorrectly recognized as noncardiac in nature. As a result, screening for CAD is not initiated and diagnosis is delayed, which may lead to increased risk of CAD-related morbidity and mortality. A recent systematic review examined whether cardiac-related prodromal symptoms were predictive of acute coronary syndrome (ACS) symptom presentation, cardiac event, or treatment intervention.


Across seven studies of 6,716 individuals with confirmed CAD, prodromal symptoms were predictive of patients' acute cardiac symptom presentation and associated cardiac events and interventions (acute myocardial infarction [AMI], PCI, and coronary artery bypass grafting) from 3 to 24 months.3 In this case, Ms. S described transient episodes of nonspecific GI symptoms along with chest discomfort that were unprovoked by stress, exertion, or food. These symptoms, which are transient in nature, are cardinal signs and are reflective of suspicious prodromal symptomology.3


Although Ms. S was protected against incurring a fatal AMI with immediate treatment via angiogram and reperfusion with PCI, evidence documents that myocardial ischemia leading to infarction, specifically within the diabetic-cardiovascular population, may occur in the absence of pain.5,6 In fact, up to 30% of episodes of myocardial ischemia have been silent or painless.5-7


Silent ischemia within this diabetic-cardiovascular population is thought to be attributed to development of diabetic autonomic neuropathy.8 It is not unexpected that patients with diabetes who also have CAD describe a myriad of unusual or anginal equivalent symptoms, such as SOB, dizziness, fatigue, and nausea, prior to and during their myocardial infarction.5,7-10


Convincing current evidence suggests individuals who experience cardiac-related prodromal symptoms are more likely to report the same or similar symptomology during their ACS presentation.1,3 Moreover, women are less likely than men to present with chest pain and may report unusual AMI symptoms.4 In addition, diabetes mellitus was found to be an independent predictor of atypical presentation of AMI in women.9


Interpretation of cardiac-related prodromal symptoms in the context of patients' multiple comorbidities, symptoms, and other chronic conditions is a definite challenge. Prodromal symptoms of fatigue, anxiety, SOB, sleep disturbances, or nausea may not be recognized as cardiac in origin because of other concurrent conditions. Within clinical practice, it may be prudent to incorporate the use of psychometrically robust prodromal screening tools.


To date, one tool is published and available that may be used in practice to screen for prodromal symptoms: The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey. This instrument assesses 37 acute and 33 prodromal symptoms and has established content validity and acceptable test-retest reliability.10


Preemptive screening

Both men and women may experience prodromal warning symptoms months, weeks, or days prior to a cardiac event.1,2,11-14 Routine preemptive screening of prodromal symptoms in clinical practice should be considered when obtaining a patient medical history. This may serve to identify patients at increased risk for CAD. It may provide evidence-based rationale that would support preemptive, individualized cardiac risk factor modification and diagnostic cardiac workup in order to decrease cardiovascular-related disability, poor health-related quality of life, and reduce early death.


Key points


* Preemptive recognition of prodromal symptoms is imperative for effective targeting, screening, diagnosis, and timely treatment to identify those at risk for future CAD-related events.


* Cardiac-related prodromal symptoms are both subjective and variable in nature and may include the following: chest pain/discomfort, anxiety, fatigue, sleep disturbances, GI complaints, dizziness, headaches, and/or SOB.


* Prodromal symptoms are often transient in nature, may occur in clusters (two or more symptoms together), and are cardinal signs to be aware of that may indicate prodromal symptomology.


* Those who experience prodromal symptoms are more likely to report the same or similar symptoms during the acute phase of an ACS episode.




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