ST-elevation myocardial infarction due to coronary thrombus in a young patient with diabetic ketoacidosis and a new diagnosis of type 2 diabetes

Abstract

The association between cardiovascular disease and diabetes is increasingly understood and shared therapeutic targets are emerging. We describe the presentation and successful management of ST-elevation myocardial infarction (STEMI) secondary to coronary thrombus in a young patient with a new diagnosis of type 2 diabetes and diabetic ketoacidosis.

Background

This case emphasises the importance of considering aetiology of myocardial infarction other than coronary atherosclerotic plaque rupture, particularly in young patients presenting with acute coronary syndrome. The cardiovascular sequelae of severe metabolic derangement can be life-threatening and diabetic ketoacidosis (DKA) should be considered in the context of acute illness with metabolic acidosis.

Case presentation

A 24-year-old man was admitted as an emergency via the ambulance service to our regional cardiology centre with a view to percutaneous coronary intervention (PCI). He presented with chest pain on a background of schizophrenia, intermittent alcohol excess, cigarette smoking, obesity (BMI 32 kg/m²) and a family history of premature cardiovascular disease, his mother having died of an acute myocardial infarction in her 40’s. The patient denied illicit drug use and there was no documented history of this. Regular prescribed medication were olanzapine 15 mg once daily and fluoxetine 80 mg once daily and had been established for over a year.

Symptoms included a 24-hour history of vomiting and diarrhoea following excess alcohol consumption and a 6-hour history of severe central chest pain radiating to the left arm with associated autonomic symptoms. There was no polyuria or excessive thirst and weight had been stable.

On arrival the patient was in discomfort, diaphoretic and tachycardic with a heart rate of 110 bpm. Initial blood pressure was 134/86 mm Hg and there was no subsequent haemodynamic compromise. On physical examination, lungs were clear to auscultation and heart sounds were normal with no cardiac murmur or gallop. Jugular venous pressure was not elevated and there was no peripheral oedema. The abdomen was soft and non-tender to palpation throughout with no organomegaly.

12-Lead ECG demonstrated ST-segment elevation in leads II, III and aVF with reciprocal ST-segment depression in lead I and aVL (figure 1). Emergency coronary angiography performed 12 minutes following the ECG in figure 1 demonstrated preserved flow (‘Thrombolysis in Myocardial Infarction’ Grade III) in the right coronary artery (RCA) but occlusion of the distal posterior left ventricular (PLV) branch. Coronary intravascular ultrasound (IVUS) identified thrombus burden throughout the RCA but did not demonstrate atherosclerotic plaque rupture (figure 2). The left coronary system was normal in appearance. Following coronary intervention chest pain resolved. However, the patient remained tachycardic and diaphoretic.

Figure 1.

12-Lead ECG at presentation demonstrating inferior STEMI.

Figure 2.

(A) Angiographic appearance of thrombus in proximal right coronary artery (RCA) and reduced flow in posterior left ventricular branch. (B) Coronary thrombosis confirmed on intravascular ultrasound in proximal RCA.

Investigations and differential diagnosis

Routine laboratory investigations revealed hyperglycaemia (blood glucose 20.4 mmol/L), a raised anion gap metabolic acidosis (lactate 10.9 mmol/L, bicarbonate 15 mmol/L) and ketonuria (3+) in keeping with DKA. Liver enzymes were mildly elevated in the context of recent alcohol excess. White blood cell count was elevated at 25.9 (10⁹/L) with neutrophilia and C reactive protein (CRP) was normal. High sensitivity troponin T was elevated at 1212 ng/L and total serum cholesterol was 6.2 mmol/L with low-density lipoprotein 3.9 mmol/L. Prothrombin time and partial thromboplastin time were normal. Thrombophilia screen was not undertaken as results would be influenced by acute thrombosis and anticoagulant therapy. Complete admission laboratory results are presented in table 1.

Table 1.

Admission laboratory test results

Haematology
White blood cells	25.9 (109 /L)
Red blood cells	4.7 (1012 /L)
Haemoglobin	158 g/L
Haematocrit	0.4 l/L
Mean cell volume	92.9 fL
Platelets	352 (109 /L)
Neutrophils	22.4 (109 /L)
Renal function and electrolytes
Sodium	134 mmol/L
Potassium	3.2 mmol/L
Chloride	94 mmol/L
Bicarbonate	15 mmol/L
Urea	1.2 mmol/L
Creatinine	76 umol/L
Estimated glomerular filtration rate	>60 mL/min
Liver function
Bilirubin	9 umol/L
Aspartate aminotransferase	74 IU/L
Alanine aminotransferase	152 IU/L
Gamma-glutamyl transferase	145 IU/L
Bone profile
Adjusted calcium	2.2 mmol/L
Phosphate	1.2 mmol/L
Magnesium	0.59 mmol/L
Albumin	43 g/L
Alkaline phosphatase	99 IU/L
Lipid profile
Cholesterol	6.2 mmol/L
Triglyceride	3.1 mmol/L
High-density lipoprotein	0.9 mmol/L
Low-density lipoprotein	3.9 mmol/L
Cholesterol/HDL ratio	7
Other
Lactate	10.9 mmol/L
High sensitivity troponin T	1212 ng/L
Serum osmolality	290 mOsm/kg

HDL, High-density lipoprotein.

Transthoracic echocardiography demonstrated impaired left ventricular systolic function (estimated left ventricular ejection fraction 49%) with inferior wall hypokinesis. There was no evidence of atrial or ventricular septal defect, and no evidence of intracardiac thrombus.

The primary diagnosis was inferior STEMI in the context of a new diagnosis of diabetes complicated by DKA. Significant lactataemia contributed to a mixed acidosis picture secondary to tissue hypoperfusion in the setting of acute cardiac ischaemia and catecholamine surge. Clinical examination and investigations did not support systemic infection or sepsis syndrome. Specifically, chest radiograph was normal, CRP <1 mg/L and nasopharyngeal swab PCR testing for SARS-CoV-2 was negative.

Further investigations were undertaken to clarify the underlying metabolic diagnosis. Glycosylated haemoglobin (HbA1c) was 64 mmol/mol. C peptide level was elevated at 996 pmol/L with concomitant random serum glucose of 12.6 mmol/L suggesting significant endogenous insulin production and insulin resistance. Both glutamic acid decarboxylase antibodies (anti-GAD) and islet antigen 2 antibodies (anti-IA2) were undetectable. Consensus opinion on the underlying metabolic diagnosis considering the patient’s body habitus and absence of autoimmunity is type 2 diabetes. Ketoacidosis in the setting of type 2 diabetes is uncommon and recent alcohol excess is likely to have led to an enhanced state of physiological stress and contributed to metabolic decompensation.¹

Treatment

Acute coronary syndrome was treated with oral antiplatelet agents and intravenous unfractionated heparin and morphine in a prehospital setting. This was followed by emergency primary PCI using low pressure balloon angioplasty to the occluded PLV branch, then aspiration thrombectomy yielding large amounts of macroscopic red thrombus from the RCA. Persisting intracoronary thrombus was confirmed on IVUS following coronary intervention and intravenous glycoprotein IIb/IIIa inhibitor was subsequently administered. Secondary prevention medications including angiotensin-converting enzyme inhibitor, beta-blocker and statin were initiated. Previous case reports have highlighted recurrent STEMI in the setting of type 2 diabetes, DKA and coronary artery thrombus and we advised a 3 month treatment period with dual antiplatelet therapy.²

DKA was treated with intravenous fluids, variable rate intravenous insulin infusion and electrolyte replacement. Metabolic disturbance resolved quickly, within 6 hours of presentation blood glucose had reduced to 10 mmol/L and lactate to 3.1 mmol/L. By 15 hours, acid base status had normalised, ketonuria resolved and minimal doses (0–0.5 units/hour) of intravenous insulin were needed to maintain blood glucose levels within normal range. Insulin was discontinued after 24 hours. Following specialist review, metformin and dapagliflozin were initiated as oral hypoglycaemic agents.

Outcome and follow-up

ST-segment changes persisted for approximately 24 hours following PCI, likely related to distal thrombus embolisation. 12-Lead ECG 3 days following initial presentation demonstrated inferior Q waves and T-wave inversion (figure 3). Blood glucose levels remained within normal range on oral hypoglycaemic agents without ketonuria. The patient was discharged from hospital after 4 days. Through lifestyle measures he has achieved 6 kg of weight loss and HbA1c has reduced to 51 mmol/mol. There is outpatient follow-up in place with cardiology, cardiac rehabilitation including smoking cessation counselling and specialist diabetes clinical teams.

Figure 3.

12-Lead ECG 3 days following presentation demonstrating inferior Q waves and T-wave inversion.

Discussion

The association between diabetes and cardiovascular disease is well recognised. Underpinning pathophysiological processes include vascular endothelial dysfunction, accelerated atherosclerosis, increased platelet activation and impaired fibrinolysis leading to a prothrombotic state.^{3 4} In a large population-based cohort study in patients with STEMI, diabetes was associated with a 72% excess risk of death.⁵ DKA further promotes a prothrombotic state with increased Von Willebrand factor and decreased free protein S and protein C activity.⁶ Arterial thrombosis in this setting has been recognised for over 50 years.⁷

Symptom chronology in this case suggests that metabolic disturbance was followed by myocardial ischaemia. Combined with evidence of thrombotic coronary occlusion in otherwise normal coronary arteries in a 24-year-old patient we believe that DKA was responsible for the acute coronary syndrome (ACS). Myocardial infarction due to a primary coronary atherosclerotic event can also precipitate DKA and our patient had multiple risk factors for atherosclerosis including a family history of premature cardiovascular disease, cigarette smoking, obesity, dyslipidaemia and type 2 diabetes of uncertain duration. However, intracoronary imaging did not identify plaque rupture and metabolic decompensation following a cardiac event typically occurs in individuals with established type 1 diabetes. A temporal illustration of the possible underlying physiological mechanisms in this case is presented in figure 4.

Figure 4.

Temporal illustration of possible mechanisms of myocardial infarction and diabetic ketoacidosis (DKA).

Shared therapeutic pathways between diabetes and cardiovascular disease continue to emerge. Dapagliflozin is a potent and reversible, selective sodium-glucose cotransporter-2 inhibitor (SGLT2i) which reduced the rate of hospitalisation for heart failure and cardiovascular death relative to placebo in patients with multiple risk factors for cardiovascular disease. SGLT2i’s while designed as oral hypoglycaemic agents are advantageous in cardiovascular secondary prevention therapy, reducing major adverse cardiovascular events, heart failure admissions and progression of renal disease.⁸

Patient’s perspective.

I phoned an ambulance because I had chest pain. I was told by the ambulance crew that I was having a heart attack, so I was rushed to hospital where I had an emergency procedure. After that I was taken to the ward and started on tablets and drip medications. It was explained that I had diabetes and would need some new medications. After a couple of days, I started to feel better.

Learning points.

• Aetiology of myocardial infarction other than coronary atherosclerotic plaque rupture should be considered in young patient groups presenting with acute coronary syndrome.

• Cardiovascular sequelae of severe metabolic derangement can be life-threatening.

• Acute coronary syndrome and other physiological stressors such as excess alcohol consumption can lead to metabolic decompensation in susceptible individuals. Recognition of cardiac risk factors in these patients is important.

• Diabetic ketoacidosis should be a differential diagnosis in the context of acute illness with metabolic acidosis regardless of previously established endocrine pathology.

• Emerging shared therapeutic pathways in cardiovascular and endocrine disease provide the opportunity for individualised treatment approaches, and underline the benefits of collaborative, cross-speciality care.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).