May 2009
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A Case of Menstrual Cycle-Related Ventricular Arrhythmias
This case illustrates the need for further study of gonadal hormones and their effect on cardiac arrythmias.
By David Lam, MD; Christina Mitchell, MD; and Intekhab Ahmed, MD, FACP, FACE
Gender differences in cardiac electrophysiology and the prevalence of specific arrhythmias have been identified by several investigators. In vivo and in vitro studies have evaluated the role estradiol 17-beta has on cardiac electrophysiology and catecholamines.1,2 The role of gonadal hormones and the effects of fluctuations during menstrual cycles on exacerbations of cardiac arrhythmias, however, is a topic of research that has not been well studied. There are conflicting studies regarding this issue.3,4 This article presents we present a case of a patient with recurrent ventricular arrhythmia seemingly exacerbated by initiation of menses and the role of hormonal therapy.
CASE REPORT
A 50-year-old nulligravid white female with a history of arrhythmogenic right ventricular dysplasia status post-automatic implantable cardioverter defibrilator (AICD) placement and mild exercise-induced asthma presented to the endocrinology clinic with symptoms of palpitations around the time of menses as well as a documented history of AICD firings and subsequent hospital admissions also around the time of menses (Table 1). After AICD placement and administration of several oral antiarrhythmic drugs and beta-blocker therapy, the patient continued to experience symptoms of palpitations 1 to 2 days prior to initiation of menses as well as up to 7 days after initiation of menses. She was referred to our endocrinology clinic for possible cessation of menses using hormonal treatment.
The patient's cardiac history began at age 35 years with reports of ventricular tachycardia and cardiac arrest after running a half-marathon. Subsequent to this event, an electrophysiology study failed to reveal inducible ventricular tachycardia, and she was discharged without AICD placement. At age 39 years, the patient experienced another episode of ventricular tachycardia leading to cardiac arrest also after running a half-marathon. She was successfully resuscitated with bolus and infusion of lidocaine and treated for possible asthma exacerbation. After uncomplicated extubation, she was transferred to our institution for further workup of ventricular tachycardia. This workup included transthoracic echocardiogram, which demonstrated normal ejection fraction, left ventricular wall thickness, wall motion, and trace mitral regurgitation. The patient's persantine thallium cardiac stress test result was normal, and her left heart cardiac catheterization was negative for significant coronary disease or evidence of hypertrophic obstructive cardiomyopathy.
ELECTROPHYSIOLOGY TESTING
Electrophysiology testing revealed inducible ventricular tachycardia, which resolved with direct-current cardioversion. The patient underwent successful placement of AICD on this same hospital admission. Subsequent to this admission, she had four hospitalizations for ventricular tachycardia with revisions to AICD programming and trials of sotalol, mexiletine, quinidine, and finally amiodarone for arrhythmia control. Since amiodarone loading 4 months prior to being seen in our clinic, she had not experienced any AICD firings, however, she continued to have symptoms of palpitations.
The patient's other past medical history included gastroparesis, gastroesophageal reflux disease, and exercise-induced asthma. Her surgical history included AICD placement with four revisions and two ablations for ventricular tachycardia. Her family history was positive for coronary artery disease and hypertension but negative for sudden cardiac death. She was nulligravid with irregular menses for the last 2 years and she denied any history of alcohol, tobacco, or substance use. Current medications included amiodarone, metoprolol, enalapril, occasional multivitamin, and polyethylene glycol as needed for constipation.
On physical examination, the patient was afebrile and normotensive with a resting heart rate of 66 beats per minute. She was a healthy-appearing female with normal body habitus, normocephalic atraumatic, no evidence of thyromegaly, normal cardiac exam with no murmurs, lungs were clear to auscultation bilaterally, benign abdominal exam, no lower extremity clubbing, cyanosis or edema. Her laboratory studies included a basic metabolic panel with normal electrolytes, hepatic function panel within normal limits, a complete blood count, which revealed a microcytic anemia with hemoglobin 11.2 g/dL, free thyroxine 1.2 ng/mL, thyroid-stimulation hormone 1.25 µIU/mL, and total triiodothyronine 51 ng/dL.
Due to our suspicion of symptoms and their correlation with her menstrual cycle, the patient was started on ethinyl estradiol/levonorgestrel 0.03 mg/0.15 mg for 84 consecutive days followed by 7 days of inert tablets.
There have been few case reports regarding ventricular arrhythmias and their association with menstrual cycles. In 1973, Gorfinkel and O'Driscoll described a 46-year-old patient with paroxysmal ventricular tachycardia without any evidence of structural heart disease who had failed multiple antiarrhythmic therapies.4 Correlation of symptoms of palpitations with the menstrual cycle led to a trial of norethinodrone and mestranol, which resulted in rapid cessation of symptoms. Withdrawal of hormonal therapy during hospitalization led to an almost immediate return of palpitations.
DISCUSSION
Gender differences in cardiac electrophysiology have been documented in several publications, and there are well-known differences in the prevalence of certain arrhythmias with respect to gender. Women have been observed to have a higher resting heart rate despite autonomic blockade leading investigators to believe there may be an intrinsic sinus node difference in women. Women on average are also noted to have a longer corrected QT interval compared to men, a difference that becomes apparent after men enter puberty when their QTc shortens and then gradually increases with age. The prevalence of atrioventricular reentrant tachycardia shows a 2:1 predominance for women, and the prevalence of congenital long QT syndrome is also higher in women.2
The role of gonadal hormones with cardiac electrophysiology has also been described in animal models by Chen et al.1 Estradiol 17-beta in dog models lengthened the atrial effective refractory period and increased the incidence of torsades de pointes after rapid atrial pacing. These findings were confirmed in vivo by Rosano et al in a study of 16 menopausal women following treatment with estradiol
17-beta.5 In addition, estrogen has been observed to have a calcium antagonistic effect on cardiac myocytes and an inhibitory effect on epinephrine release. Because of the effects of estrogen on the sympathetic nervous system and cardiac myocytes, it is thought that variations in estrogen and progesterone in the luteal and follicular phase may have an effect on cardiac arrhythmias.
To date, however, there have been few small studies published regarding the correlation of arrhythmias and menstrual cycle with differing conclusions. Fuenmayor et al studied 25 women with normal menstrual cycles and normal cardiac anatomy.3 Thirteen were patients in an arrhythmia clinic, all of whom had complaints of arrhythmia aggravation preceding and during time of menses and 12 age-matched controls with no history of cardiac arrhythmia. Twenty-four hour Holter monitoring was done 7 days after initiation of menses and 3 days before the next menstruation. The investigators found no evidence by means of Holter monitor of sustained arrhythmia in either group. In addition, no significant differences in heart rate or frequency of supraventricular or ventricular premature beats were observed in either group when comparing the different stages of the menstrual cycle. The only difference was a note that the arrhythmic group had more premature supraventricular and ventricular beats than the control.
Rosano et al published data specifically examining the frequency of paroxysmal supraventricular tachycardia (SVT) in women with relation to menstrual cycle.6 In a study group of 26 women with known paroxysmal SVT and normal menses, 48-hour Holter monitoring and serial measurements of estradiol 17-beta and progesterone at day 7, 14, 21, and 28 of the menstrual cycle was completed. There was an increase at day 28 in frequency and duration of SVT. Biochemical analysis noted a positive correlation with progesterone levels and a negative correlation with 17-beta estradiol with respect to frequency and duration of SVT in the study group. Rosano et al therefore concluded that the changes in plasma levels of gonadal hormones may be important in determining the frequency of arrhythmias.
Our case illustrates documented ventricular arrhythmia that was seemingly exacerbated by intiation of menses. With the AICD, we have the advantage of very accurate correlation of symptoms with incidents of arrhythmia and menses. We are limited by the fact that we did not have estradiol or progesterone levels from her previous episodes before initiation of hormonal therapy. This case, however, illustrates the need for further study of gonadal hormones and their effect on cardiac arrythmias. It also raises the issue regarding the potential benefit of hormone replacement therapy in a select group of patients with life-threatening arrhythmias particularly in the perimenopausal age group.
David Lamb, MD, is a second-year resident in internal medicine and Christina Mitchell, MD, is a first-year fellow in the Division of Diabetes, Endocrinology, and Metabolism, both at Thomas Jefferson University. Intekhab Ahmed, MD, FACP, FACE, is the Program Director, Endocrine Fellowship at Thomas Jefferson Medical College and University in Philadelphia. Dr. Ahmed may be reached at Intekhab.Ahmed@jefferson.edu or phone: 215-955-5104. The authors have no conflicts of interest to disclose.
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