Dilated cardiomyopathy in acromegaly: Case report and anesthesia management.

Patients who are diagnosed having acromegaly develop a lot of cardiovascular Complications such as hypertension, arrhythmias, systolic and diastolic dysfunction, valvular dysfunction and heart failure. Dilated cardiomyopathy (DCM) with systolic and diastolic dysfunction is relatively rare but is associated with an increased mortality. We report a case of acromegaly diagnosed at 52 years of age in a known diabetic, non-hypertensive male who had DCM with severe left ventricular dysfunction, global hypokinesia, moderate mitral regurgitation, and grade II diastolic dysfunction who was treated with diuretics, digitalis, and vasodilators. He was diagnosed with a growth hormone secreting pituitary macroadenoma and underwent endoscopic excision of the pituitary tumor under general anesthesia.

INTRODUCTION

Acromegalic cardiomyopathy has a very high mortality (up to 60%). In cardiomyopathy heart muscle gets dilated progressively and the dysfunction that develops is irreversible. Therefore, even after the removal of the tumor, which secretes growth hormone or insulin like growth factor-1 (IGF-1), the myocardium doesn’t return to its normal state. In order to prevent this irreversible state, early diagnosis is important and medical management in the form of anti-failure medications and surgical removal of growth hormone and IGF-1 secreting tumor is necessary. In situations where even tumor resection and anti-failure medications doesn’t help, orthotopic heart transplant is the only available option. Our patient ignored the progressive enlargement of limbs and face and didn’t get investigated. He presented with heart failure and was diagnosed with pituitary macroadenoma. He had dilated cardiomyopathy (DCM) on 2D echocardiogram and was started on anti-failure drugs by the cardiologist. To summarize, early diagnosis and prompt treatment will at least slow down the progression of cardiomyopathy by pharmacotherapy and surgery.

Review of literature

Clayton[1] described in detail how cardiomyopathy develops in acromegaly and progresses in patients with increased GH and IGF-1. They concluded mentioning that early diagnosis and prompt medical management can prevent the progression to irreversible cardiomyopathy. Saccà et al.[2] described the relationship of growth hormone, acromegaly, and heart failure. Lombardi et al.[3] described in their article that the problem is more if cardiomyopthy is associated with other comorbidities such as hypertension and diabetes mellitus. Sue et al.[4] described a case in which a 22-year-old male with acromegaly who was admitted with palpitations and shortness of breath.

On further investigation, the patient was found to have to diastolic cardiomyopathy, which lead to congestive heart failure. The patient didn’t improve even after tumor resection and on anti-failure medications.

CASE REPORT

Our patient was a 52 years male, weighing 84 kg and height of 178 cm with a history of type II diabetes mellitus on oral hypoglycemic agents (Tab Metformin 500 mg twice daily). Glycemic control was fair with a glycosylated hemoglobin of 6.6%. He noticed progressive enlargement of his face, hands and feet over several years (5 years according to relatives), but didn’t take any medical advice. He was admitted to an Intensive care unit when he experienced palpitations, heaviness of the chest and orthopnea. A provisional diagnosis of acute coronary syndrome was made on the basis of his presenting history, but differential diagnosis of acromegalic cardiomyopathy was considered looking at the habitus of the patient. He had crepitation's on auscultation hence was started on diuretics, IV nitroglycerin, oxygen by nasal prongs and IV morphine. 12 lead ECG revealed sinus tachycardia, poor progression of R wave from V2 to V6 and inverted T waves in V3-V6.

A 2D ECHO was carried out. The findings were as follows: Ejection fraction-29%, severe left ventricular dysfunction, grade II diastolic dysfunction, moderate mitral regurgitation, global hypokinesia, dilated left atrium and ventricle, no vegetations/clot.

To rule out coronary artery disease, a coronary angiogram (CAG) was planned the next day. The CAG was normal and was reported as the presence of normal major epicardial arteries. He was started on tab Frussemide 40 mg once daily, tab spironolactone 25 mg once daily, tab digoxin 0.125 mg once daily (5 days a week), tab isosorbide mononitrate 30 mg once daily, and tab Aspirin 150 mg once daily by the cardiologist.

After ruling out coronary artery disease and based on 2D ECHO findings, a diagnosis of acromegalic DCM was made.

Following are the details of other investigations that he underwent as a part of the evaluation:

Growth hormone level was >35 ng/ml by chemiluminescence (biological reference range in males: 0.003-0.97 ng/ml)

IGF-1: 34.6 ng/ml (87-238 ng/ml is the value for his age). Literature describes that IGF-1 can be normal in 5-10% of acromegaly patients

Serum cortisol- 7.3 ug/dl for 8 am sample (5-23 ug/dl)

Serum prolactin- 12.1 ng/ml (2-15 ng/ml in males)

Serum testosterone- 0.9 ng/ml (2.8-8 ng/ml)

Free T4- 1.2 ng/dl (0.93-1.7 ng/dl)

Serum electrolytes, renal and liver function tests were normal

Magnetic resonance imaging revealed a pituitary macroadenoma [Figures 1 and 2]

Figure 1

Magnetic resonance imaging 1 showing pituitary macroadenoma

Figure 2

Magnetic resonance imaging 2 showing pituitary macroadenoma

Lipid profile was normal.

The final diagnosis made in this patient was: Acromegaly due to growth hormone secreting pituitary macroadenoma leading to dilated cardiomyopathy (DCM). (Figure 3 shows comparison of a acromegalic hand with a normal one).

Figure 3

Comparison between hands of an acromegalic patient and a normal adult

After 15 days of optimization, he was posted electively for endoscopic excision of pituitary macroadenoma under general Anesthesia. A detailed pre-anesthesia check-up was carried out. Airway was Mallampatti class III due to large beefy tongue.

Anticipated difficult airway was highlighted on the Anesthesia form. Tab Aspirin was stopped 5 days prior to surgery so as to reduce the risk of bleeding. Rest of medication are continued as scheduled until the day of surgery. High-risk consent for surgery was taken from the patient and his attenders regarding the existing issues. Patient was explained about the possibility of major adverse cardiovascular events such as congestive heart failure, ventilator support (invasive/non-invasive), ICU stay etc., In Operation room (OR), a 16 G peripheral line and an arterial line was placed in the left radial artery for real time monitoring of blood pressure along with Lead II and V5 electrocardiogram and pulse oximeter. As an endoscopic pituitary surgery is not associated with blood loss or fluid shifts, we decided to defer a central venous catheter. Pulmonary artery catheterization is a very invasive procedure associated with several problems, which are beyond the scope of discussion here. Hence, we didn’t consider it. A transesophageal echocardiography can give real time monitoring of cardiac function, but as this was a transnasal surgery, with a throat pack in situ we didn’t consider it. Anesthesia was induced with IV 250 mg Thiopentone (titrated to loss of eyelash reflex), 2 mg midazolam, 150 ug of Fentanyl, 80 mg of IV lignocaine and 8 mg of vecuronium bromide after premedication with injection ondansetron 8 mg. Airway was secured with 8.5 sized cuffed endotracheal tube and a throat pack was placed to prevent microaspiration of blood from the surgical site into the airway. There was no hypertensive response to orotracheal intubation. There was no difficulty in mask ventilation or intubation. We monitored lead II and lead V5 intraoperatively. There were no changes observed throughout the surgery. Anesthesia was maintained with 1 l oxygen, 1 l medical air and Sevoflurane titrated to an end tidal of 1.5-1.6 by adjusting dial concentration. 500 ml of normal saline was infused intraoperatively. After 2 h of surgery, patient was successfully extubated after reversing neuromuscular blockade with 0.5 mg glycopyrollate and 2.5 mg neostigmine. Blood loss was negligible. There was negligible cerebrospinal fluid (CSF) leak after tumor resection; hence, a lumbar intrathecal catheter to drain CSF was not considered. He was kept in surgical intensive care unit overnight. Post-operatively the 12 lead ECG had no fresh ECG changes. For post-operative analgesia, he was prescribed 100 mg of Tramadol intravenously 8th hourly and tablet paracetamol 1 g orally 4 times a day. Blood glucose was monitored 6th hourly and sliding scale was followed accordingly. He was made to resume his scheduled cardiac medications and shifted to room the next day. There was no evidence of diabetes insipidus in the post-operative period.

DISCUSSION

A patient with acromegaly presents with a lot of cardiovascular manifestations like hyperdynamic states, hypertension, valvular dysfunction, systolic dysfunction, diastolic dysfunction, arrhythmias, heart failure.[5] DCM is a rare complication of acromegaly which develops due to prolonged and excessive exposure of the myocardium to excess of growth hormone and IGF-1.[6] DCM is a state of irreversible dilatation and hypertrophy of heart, which makes the prognosis poor even after surgical removal of the tumor. Therefore, acromegalic DCM is associated with a poor outcome and has an increased mortality rate.[7]

Pathogenesis of a cardiovascular involvement

Sustained increased levels of growth hormone and IGF-1 leads to derangement of cardiomyocytes, which leads to structural changes in cardiac muscles leading progressively to cardiomyopathy. Early phase is characterized by a hyperdynamic state, which leads to increased heart rate and increased cardiac output. If the disease is not addressed at this time, there is biventricular hypertrophy followed by diastolic dysfunction.[12] The cardiomyopathy further progresses leading to the development of valvular disorders and arrhythmias, which makes the situation worse and makes treatment more difficult. DCM due to acromegaly has a poor prognosis just such as DCM due to any other cause (Post MI, alcoholic, infectious, inflammatory, drug induced, muscular dystrophiesetc).[78]

Histopathologic finding in myocardium due to acromegalic DCM is that of myofibrillosis and interfascicular fibrosis.

Treatment

Once DCM develops its unlikely to improve even after tumor resection because myocardium has suffered irreversible insult. In young patients who have the disease of short duration, they have a reasonably better outcome as compared to elderly patients in whom the diagnosis is made late especially after the irreversible changes have developed or once heart failure manifests.

Treatment is usually supportive in the form of diuretics, Angiotensin converting enzyme (ACE) inhibitors, Beta blockers, and nitrates. If arrhythmias develop, anti-arrhythmics can be started. Somatostatin analogues (especially subcutaneous octreotide) has been used in these patients. It works by reducing the left ventricular and interventricular septum thickness.

However, data on the long-term follow-up with this regime is lacking. Only definitive treatment described in the literature in this situation is a heart transplant.

Management of a patient with DCM in acromegaly

They are anticipated difficult airways in view of big jaw due to mandibular hypertrophy, large tongue and epiglottis, difficult bag and mask ventilation. They may have glottis or subglottic stenosis, turbinate enlargement, vocal cord thickening and recurrent laryngeal nerve involvement. Hence, difficult airway cart should be complete with all necessary gadgets like fiberoptic bronchoscope, laryngeal mask airways, different types and sizes of blades.[89] A lot has been described in the literature about the management of cardiovascular complications in a patient with DCM. The principles remain same with acromegaly as well.

They are:

Avoid myocardial depression (Propofol is best avoided)[8]

Patient should be euvolemic

Avoid precipitous fall in blood pressure

Avoid tachycardia, which can precipitate heart failure. Good depth of anesthesia, analgesia, maintain euvolemia, use of lignocaine/beta blockers/dexmedetomidine during induction and extubation to avoid unnecessary tachycardia.

Prevent increase in afterload maintain adequate preload[89]

Maintain sinus rhythm, electrolytes should be optimized

Use inotropic support whenever there is a suspicion of myocardial depression in the form of noradrenaline, dobutamine, dopamine, phosphodiesterase inhibitors, levosimendan

Use of Pulmonary artery catheter for judicious fluid management is described by many, but its use can be justified in major surgeries where there's a lot of fluid shifts/blood loss expected. Also using a PA catheter may not necessarily change the outcome. A central venous catheter can be used, but it won’t give information about left heart pressures. However, the catheter can be used for using inotropes. An Intraoperativetrans esophageal ECHO can give a lot of information about the myocardial function during anesthesia.

CONCLUSION

Patient with acromegaly and DCM have a compromised airway and an impaired heart. One can manage the airway by a detailed airway examination, having a well-equipped difficult airway cart and by following difficult airway algorithm. If we follow the principles of management of anesthesia for a patient with DCM, one can prevent heart failure or worsening of myocardial function perioperatively. The anesthesiologist, surgeon, Cardiologist, and Endocrinologist should coordinate among themselves when they deal with a surgical situation for this patient.