Difficult Atrial Fibrillation Rate-Control and Digitalis Toxicity in Mitral-Valve Prolapse Patient with Hyperthyroidism

Rate-control is important management in patient with atrial fibrillation. The optimum rate control provides a decrease of symptoms, improves hemodynamics and prevents tachycardiainduced cardiomyopathy. Rate-control could be difficult to achieve because of patient's comorbidities and special treatment strategy is needed to resolve it. A-46-yo. male, came to ER with palpitation. Holosystolic murmur was heard at apex, radiating to axilla. ECG showed atrial fibrillation, with rapid ventricular response 180 bpm. Echocardiography showed dilated LA and LV, false-normal LV function with EF 59% and anterior mitral-valve prolapse with moderate mitral regurgitation. Acute treatment was administration of digoxin and beta blockers, but ventricular rate wasn’t controlled, until 1.5 mg doses of digoxin was administered. Then patient develops acute digitalis intoxication. After toxicity management, rapid ventricular rate recurs. Patient reevaluation showed hyperthyroidism with low TSH and high T4. Methimazole and propranolol was given and rate-control was achieved shortly after euthyroid state, in 2 months treatment. This patient suffered difficult rate-control despite guidelines-based management. Digitalis intoxication was developed after administration of several therapeutic doses. The diagnosis of hyperthyroidism is central in management of this case. Coexistent of hyperthyroidism and mitral-valve prolapse may be explained by genetic, autoimmune, and thyroid hormone effects in myocardium. Case Report Difficult Atrial Fibrillation Rate-Control and Digitalis Toxicity in Mitral-Valve Prolapse Patient with Hyperthyroidism S. A. Hutomo1* and A. Subagjo1,2 1 Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. 2 Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

Rate control can be done loosely or strictly. The

Rate Control Study of Efficacy in Permanent Atrial
Fibrillation (RACE) II shows that the control rate is strictly not better than a loose rate control. But sometimes the control rate cannot be achieved with standard rate control, commonly called "difficult atrial fibrillation". In this case a special strategy is needed in its management [3].
We reported one patient with mitral regurgitation caused by mitral valve prolapse, and experienced rapid ventricular atrial fibrillation which was difficult to control for heart rate. During treatment, the patient also experienced acute digitalis intoxication and was found to have comorbid hyperthyroidism.

Case Presentation
Mr. S, male, 46 years old came to emergency room with palpitation. Palpitation was felt since 7 days ago, worsening in the last 4 days. It felt especially during heavy activity and fatigue, and improves with rest. In these 2 days it felt even after resting. There is no shortness of breath, chest pain, or swollen feet. History of diabetes mellitus, hypertension, dyslipidemia is denied.
The patient does not smoke. The patient had never been hospitalized before. On physical examination, irregular-irregular S1-S2 heart sounds were obtained. Holosystolic murmur at cardiac apex  Trans-thoracic echocardiography was performed with the following results: (1) valves: there was moderate mitral regurgitation due to anterior mitralvalve prolapse, restricted posterior mitral valve (carpentier type 2) and trivial tricuspid regurgitation.
(2) Dilated left atrium (LA) with LA major 6.2 cm, LA minor 6.0 cm; dilated left ventricle (LV) with end diastolic diameter (LVEDD) 5  Hyperthyroidism is also associated with shortening of action potential duration which is a substrate of AF [12,14].
Because hyperthyroidism is quite common in AF

c. Digitalis intoxication
Digitalis intoxication is one of the most frequent drug adverse reactions in clinical practice [19,20], although the use of digitalis has declined since 1990 21 . This is related to the narrow therapeutic range of digitalis (0.8-2.0 ng/mL) [19]. According to the clinical setting, digitalis intoxication is differentiated into acute and chronic intoxication, where conditions in these two conditions are very different. Acute intoxication occurs due to overdosing, which usually occurs in younger individuals, with sudden and severe symptoms. While chronic intoxication is caused by accumulation of digoxin levels due to the use of long time digitalis, appearance of symptoms was slow.

Diagnosis of digitalis intoxication is something that
is not easy, this is caused by several factors, namely non-specific symptoms and signs, nonspecific electrocardiographic findings, and digoxin concentrations in the blood also do not always correlate with the level of toxicity [19,21,22].
Signs and symptoms of digitalis intoxication can manifest in cardiac or extracardiac [19,23,24]. The intoxication, which is as much as 50%. ECG images caused by the mechanism of the conduction system include 1st degree to total AV blocks. Normalization of the ventricular response in AF can also be categorized as one of the characteristics of digitalis intoxication [22].
In addition to the above manifestations, there are changes in laboratory parameters that must be watched out for digitalis intoxication. These parameters are serum electrolytes, kidney function, glucose and also digoxin concentrations in serum.
In acute intoxication hyperkalemia can occur (K level> 5.1) which can be caused by excessive blocking of the Na-K-ATPase pump. Hyperkalemia is a prognosis factor that can predict outcomes in patients. Acute intoxication also causes a decrease in kidney function [25,26].   [28,29]. However, in a 2015 study, found conflicting results, that there was no association between mitral-valve prolapse and autoimmune thyroid disease. In contrast, these two opinions certainly require further research to determine the relationship between mitral-valve prolapse and hyperthyroidism [30]. September 2020 | Vol 1 | Article 5

Conclusion
We have reported one case of a patient with difficult AF rate-control and also experiencing acute digitalis intoxication. Patients have several factors triggering AF, namely mitral-valve prolapse with moderate mitral regurgitation (causing dilatation of the left atrium as a substrate of AF) and hyperthyroidism.
Rate-control cannot be done with standard digoxin and beta blockers therapy. It was obtained after administration of anti-thyroid drugs and propranolol for two months.
Hyperthyroidism plays a central role in the problem of these patients. Hyperthyroidism causes difficulty in controlling the rate of AF through a mechanism for increasing atrial ectopic activity, shortening the duration of potential action and increasing left atrial pressure. Hyperthyroidism also plays a role in the occurrence of digitalis intoxication by causing tolerance and decreasing the sensitivity of myocytes to digoxin. Thyroid function therefore must be evaluated in patients with AF suffering difficult rate-control as well as first-detected AF.