Acute pancreatitis-induced takotsubo cardiomyopathy and cardiogenic shock treated with a percutaneous left ventricular assist device

Abstract

A 63-year-old man was admitted for severe acute pancreatitis. On day 3 of hospitalisation, he developed shortness of breath and acute pulmonary oedema. Echocardiogram revealed global hypokinesis with a left ventricular ejection fraction of 20%, and he was diagnosed with takotsubo cardiomyopathy. He developed cardiogenic shock which was treated successfully with a percutaneous left ventricular assist device. His left ventricular ejection fraction improved by hospital follow-up 3 weeks later.

Background

Acute pancreatitis is a common inflammatory condition of the pancreas which can range from a mild, self-limited illness to severe disease with complications such as pancreatic necrosis and multiorgan failure.^{1 2} Through release of inflammatory mediators, acute pancreatitis has important systemic effects on other organ systems. Cardiovascular manifestations include ECG changes, decreased myocardial contractility and haemodynamic alterations secondary to the systemic inflammatory response syndrome.^{3 4}

Rarely, acute pancreatitis can induce takotsubo cardiomyopathy (TCM), a condition characterised by the sudden onset of reversible left ventricular dysfunction with a presentation similar to acute coronary syndrome. Only six prior cases of acute pancreatitis-induced TCM have been reported in the literature.^{5 6} We present a patient with severe acute pancreatitis who developed TCM and cardiogenic shock, treated with a percutaneous left ventricular assist device.

Case presentation

A 63-year-old man presented to the emergency department with 5 hours of acute epigastric pain, nausea, vomiting and diaphoresis. His medical history included type 2 diabetes mellitus, chronic obstructive pulmonary disease, permanent atrial fibrillation, hypertension, hypothyroidism and gastro-oesophageal reflux disease. His medications included apixaban, carvedilol, insulin and gabapentin. He had a smoking history of 20 packs/year and did not consume alcohol. On presentation, the patient was in atrial fibrillation with a rapid ventricular rate of 140 bpm and blood pressure of 130/80 mm Hg. On physical examination, we found hypoactive bowel sounds and epigastric abdominal tenderness without rebound or guarding. Laboratory studies revealed a white cell count of 11.5×10⁹ cells/L, haemoglobin 16.5 g/dL, blood urea nitrogen 13 mg/dL, creatinine 1.3 mg/dL and lactate 3.8 mmol/L. Liver studies were remarkable for aspartate aminotransferase 418 U/L, alanine transaminase 228 U/L, alkaline phosphatase 155 U/L, total bilirubin 2.6 mg/dL, direct bilirubin 1.4 mg/dL, lipase 3680 U/L, triglyceride level 222 mg/dL and calcium 9.1 mg/dL. CT of the abdomen revealed oedema of the pancreatic head and body with peripancreatic fat stranding, consistent with acute pancreatitis (figure 1). There were small bilateral pleural effusions, with no evidence of pancreatic necrosis or focal fluid collection. Magnetic resonance cholangiopancreatography demonstrated small gallstones within the common bile duct without dilation, the presumed cause of acute pancreatitis.

Figure 1.

CT of the abdomen in the axial plane demonstrating oedema of the pancreatic head and body with fat stranding. These findings are consistent with acute pancreatitis.

The patient was admitted to the hospital and treated for acute pancreatitis with intravenous fluid resuscitation with Ringer lactate. He received intravenous narcotics and antiemetics for his symptoms of pain and nausea and diltiazem infusion for atrial fibrillation with rapid ventricular rate. During day 2 of hospitalisation, the patient had continued epigastric pain and developed hypotension and oliguria, despite fluid resuscitation. The diltiazem infusion was stopped, and he was treated empirically with piperacillin–tazobactam in the setting of hypotension. Creatinine and blood urea nitrogen increased to 1.6 mg/dL and 14 mg/dL, respectively. The patient received 7 L intravenous fluids after the second day. On day 3, he continued to have clinical manifestations of severe acute pancreatitis with epigastric pain and multiorgan dysfunction with oliguria and hypotension. He received a total of 12 L intravenous fluids over the course of hospitalisation. He developed new-onset shortness of breath requiring 10 L/min of supplemental oxygen.

Investigations

The patient’s B-type natriuretic peptide was 444 pg/mL and troponin level was 0.02 ng/mL, increased from less than 0.01 ng/mL at hospital admission. ECG showed non-specific T-wave changes in the inferior and lateral leads. Chest radiography was remarkable for diffuse bilateral pulmonary interstitial infiltrates with worsening pleural effusions, concerning for pulmonary oedema. Echocardiography revealed new-onset cardiomyopathy and global hypokinesis with left ventricular ejection fraction of 20%–25% and mild to moderate mitral regurgitation (figure 2). The left ventricular ejection fraction from an echocardiogram the year prior was 65%.

Figure 2.

Echocardiogram with an apical four-chamber view demonstrating dilation of the left ventricle. V indicates ventricle.

Differential diagnosis

The differential diagnosis included causes of acute heart failure, such as acute coronary syndrome, TCM, myocarditis and sepsis-related myocardial dysfunction.⁷ Other causes of acute dyspnoea with bilateral pulmonary infiltrates included acute respiratory distress syndrome secondary to AP or iatrogenic heart failure from aggressive intravenous fluid resuscitation.

Treatment

The patient had sudden worsening of hypoxaemia with bradycardia and suffered cardiac arrest with pulseless electrical activity. He had spontaneous return of circulation after 1 min of cardiopulmonary resuscitation. He was intubated and required pressor support with dobutamine, norepinephrine, vasopressin and epinephrine. Right heart catheterisation was consistent with cardiogenic shock, with pulmonary capillary wedge pressure of 31 mm Hg and cardiac index of 1.4 L/min/m². Systemic vascular resistance was 4800 dyn∙s/cm⁵, and SVO2 was 60%. Left-sided cardiac catheterisation demonstrated 50% stenosis of the left anterior descending artery, with otherwise no obstructive coronary artery disease (figure 3A,B). An Impella 2.5 device (Abiomed) was placed with immediate improvement in haemodynamics and urine output.

Figure 3.

(A and B) Cardiac catheterisation demonstrating non-obstructive coronary artery disease in the right (3A) and left (3B) coronary artery distributions.

The following morning, the patient had improvement in his oxygenation and haemodynamics; inotropes and vasopressors were discontinued. Chest radiography showed improvement in bilateral pulmonary oedema, and the Impella 2.5 device was removed after 24 hours due to bleeding at the insertion site in the right groin.

Outcome and follow-up

The patient was successfully extubated on hospital day 7. He had diffuse anasarca secondary to acute cardiogenic shock and fluid resuscitation, and was treated with intravenous bumetanide and discharged to a rehabilitation facility. During follow-up 3 weeks later, he reported continued improvement in his functional status with shortness of breath only after climbing multiple flights of stairs. Repeat echocardiogram revealed an improvement in left ventricular ejection fraction to 40%.

Discussion

To our knowledge, this is the seventh reported case of acute pancreatitis-induced TCM in the English literature, and the first such case of a patient with cardiogenic shock requiring mechanical support with a left ventricular assist device. Our case highlights the effects of acute pancreatitis on the cardiovascular system, and specifically, on development of TCM.

TCM derives its name from the Japanese word takotsubo (octopus pot) to describe the characteristic ballooning of the left ventricular apex in this condition.⁸ The disease is characterised by transient systolic and diastolic dysfunction of the left ventricle. TCM is generally associated with physical or emotional stress, and although the exact cause remains unknown, the most widely accepted hypotheses are catecholamine toxicity and microvascular dysfunction.⁸ The diagnostic standard for TCM is the Mayo criteria, which includes transient left ventricular dysfunction, absence of obstructive coronary artery disease, new ECG abnormalities and absence of secondary causes, including pheochromocytoma and myocarditis.⁹ Chest pain and dyspnoea are the most common presenting symptoms, and up to 10% of cases are complicated by cardiogenic shock.^{8 9}

Acute pancreatitis is a significant physical stressor with exaggerated sympathetic stimulation, which could explain the pathophysiological mechanism for development of TCM.⁶ Six prior cases of acute pancreatitis-induced TCM have been reported.^{5 6} Five of the reported cases are females, and one is a male.^{5 6}

In addition to TCM, sepsis-related myocardial dysfunction is an important consideration in patients with shock and infection. Sepsis-related myocardial dysfunction can present as left or right ventricular dysfunction alone or in combination.⁷ Although sepsis was considered in this patient and he was treated empirically with antibiotics in the setting of shock, he did not otherwise have clinical evidence of infection such as fever, significant leucocytosis, positive blood cultures or evidence of infected pancreatic necrosis.

Although the majority of patients with TCM recover quickly over a period of days to weeks, some patients experience severe cardiac dysfunction with fulminant heart failure and cardiogenic shock, as in our patient. There are no randomised controlled trials for the optimal treatment of TCM, which is primarily supportive care and conventional heart failure therapy in milder cases.¹⁰ In patients with fulminant heart failure and severe haemodynamic instability, management can be challenging. In severe cases of TCM, mechanical circulatory support can be considered as a bridge to recovery, especially since ventricular dysfunction generally completely resolves.¹⁰ Short-term ventricular assist devices have become a widely accepted treatment for acute cardiogenic shock. Prior cases of TCM treated with the Impella 2.5 left ventricular assist device have been reported with good outcomes.^11–13

Acute pancreatitis is a common gastrointestinal condition with considerable morbidity, mortality and healthcare costs.^{1 2} Diagnosis of acute pancreatitis requires two of the following three features: characteristic abdominal pain, elevated serum lipase or amylase at least three times greater than the upper limit of normal and characteristic findings on abdominal imaging.¹⁴ Severe acute pancreatitis occurs in 20% of cases and is defined by organ failure and complications, such as pancreatic necrosis, abscess or pseudocyst.¹⁴

Similar to sepsis, the mechanism of myocardial suppression in acute pancreatitis is thought to be secondary to inflammatory mediators, although no specific myocardial depressant has been identified.¹⁵ High levels of proinflammatory cytokines are released in acute pancreatitis, including interleukins IL-1, IL-6 and tumor necrosis factor-α. Other inflammatory mediators include bradykinin, nitric oxide, substance P and complement.¹⁵ ECG changes are common, including T-wave and ST-segment changes. The mechanism of these changes is not well understood but thought to be secondary to metabolic disturbances, including hypocalcaemia, hypophosphataemia and hyperkalaemia. New-onset ST-segment elevation may occur, which can mimic acute myocardial infarction.¹⁶ Experimental studies in rats with acute pancreatitis have demonstrated changes in the myocardium, including interstitial oedema and cardiomyocyte hypoxia, overcontracted myofibrils, intracellular oedema, cardiomyocyte hypertrophy and collagenation of the stroma.¹⁷

In summary, acute pancreatitis is a common inflammatory condition of the pancreas with notable effects on the cardiovascular system. We present a rare case of acute pancreatitis-induced TCM and cardiogenic shock treated with a percutaneous left ventricular assist device. Clinical providers should be familiar with the cardiac complications of acute pancreatitis and the diagnosis and management of TCM. Patients with TCM generally have complete resolution of left ventricular dysfunction, and aggressive treatment interventions can be lifesaving.

Patient’s perspective.

Transcribed verbatim from patient consent form:

Before presenting myself to the ER on 09-10-2017, I had been exerting myself excessively in preparing for hurricane Irma which impacted our area on 09-10-2017. At first I thought I had dehydrated myself or had a heat related illness, but as time went on, I began feeling worse and could not keep liquids down. My left side felt like I had been wounded with a sharp object and at that point I decided I needed to go to the ED.

I recall being placed in a wheelchair and being rolled into the ED. From that point, I have no recollection of any of the events that occurred from the 10^th to the 15^th of September. I was extremely disoriented when I awoke with my wife talking to me. I did have hallucinations of being ‘beamed up’ to a space ship and aliens were probing. Also my (ICU) room was a strip mall store front and there was an ATM machine outside my door.

At the time I was transferred to the rehab hospital I had retained fluids to the point that my scrotum was the size of a large grapefruit and the rest of my body looked like the (Michelin Man). As I went through rehab, the fluid I had retained abated, blood pressure/pulse was good and I was on a minimum insulin schedule.

Everything was doing well until 02-21-2018 when I had to go back to the ED with tachycardia; my heart rate was 150 bpm. This had been going on for approximately 4 days. At that time, I was also being treated with a descending steroid dose for COPD episode which was also resulting in high blood sugar results. During the hospital stay, a cardioversion resolved the heart issue, however the glucose results continued to be high and I was finally put on insulin drip. I was released 02-24-2018 and have been managing the COPD and blood sugars nicely at home. In conclusion, I feel I am a very blessed and lucky man. All the medical personnel that I have come in contact with have been professional, knowledgeable and kind to me and my wife. The only irony is that my 15 min of fame will be in anonymity.

Learning points.

• Acute pancreatitis has well-known effects on the cardiovascular system secondary to the systemic inflammatory response.

• Takotsubo cardiomyopathy generally occurs in the context of acute physical or emotional stress, including acute pancreatitis.

• Patients with cardiogenic shock secondary to takotsubo cardiomyopathy may benefit from short-term treatment with a left ventricular assist device, which can be placed quickly.