Congenitally corrected transposition of the great vessels (L-TGA) refers to a rare anomaly in which functionally correct circulation is preserved despite malposition of the great vessels and both atrioventricular and ventriculoarterial discordance.  In such cases, the left-sided systemic ventricle, triangular in shape, heavily trabeculated with a tricuspid valve for inlet, leading to the aorta.  The right-sided pulmonary ventricle is a morphological left ventricle, ovoid in shape, smooth, with a mitral valve for inlet, leading to the pulmonary valve.

Symptoms and survival depend on the presence of associated defects, e.g., ventricular septal defects and pulmonary stenosis.  If these anomalies are present, they may require surgical treatment in infancy or childhood.  Older patients are at risk for atrioventricular valve insufficiency and failure of the morphologic right ventricle.  "Survival into the sixth and seventh decades is uncommon, but not unknown."  Patients with corrected transposition are also at constant risk of developing a complete heart block - approximately 2 percent of patients per year.

The following patient is particularly remarkable for her longevity related to treatment of complete heart block.

Case Report

RR was 71 years old when seen in 1995 for a follow-up pacemaker evaluation.  She had a history of "corrected transposition of the great vessels" as well as multiple pacemaker implantations.  The patient reported longstanding mild extertional dyspnea with a mild increase in "puffiness" around the eyes and legs over the last several months.  The patient also reported intermittent chest discomfort.  Her medications included Diamox 500 mg b.i.d.

Her history was remarkable for having had three successful full-term pregnancies, the last at age 31.  She had one miscarriage.  Aortography in 1968 revealed coronary anatomy consistent with ventricular inversion without evidence of proximal coronary stenoses.  At age 50 she had developed syncope and "congestive heart failure secondary to complete heart block" and underwent placement of a permanent pacemaker at that time.

She had three subsequent pacemaker revisions, the last in 1993 utilizing a Medtronic Model 7108 DDD pulse generator.  An old lead was in the pulmonary ventricular apex. and two additional leads had been placed, presumably, in the coronary sinus and in the inflow tract of the pulmonary ventricle.

The patient weighed 155 pounds; her blood pressure was 130/70 mm Hg, and her pulse was regular at 80 beats per minute.  Her chest was clear to auscultation.  Her cardiac exam revealed normal first and prominent second heart sounds with no splitting appreciated.  There was a I/VI early systolic murmur at the left sternal border.  No diastolic murmurs were appreciated.  The extremities did not reveal any cyanosis, clubbing or edema.  An electrocardiogram revealed DDD pacing with 100 percent capture.  A chest x-ray revealed mesocardia as well as a CT ratio of 41 percent.  There was situs solitus.  The pulmonary vascularity was not prominent.

Three pacing wires were present.  There appeared to be an old nonfunctional wire in the apex of the right heart chamber.  An Accufix lead in what appeared to be the right atrium was, in fact, in the pulmonary ventricle inflow tract.  A third pacing wire was located well within the coronary sinus, presumably providing stable atrial pacing.  The X-ray findings were consistent with mixed mesocardia and ventricular inversion. (Figures 1 and 2)

Evaluation of the patient's Medtronic generator revealed a total of 2.5 volts which was equivalent to its end-of-life.  The patient's ventricular lead was an Accufix Atrial J Telectronics lead 33-801 which was subject to recall.  Documented extrusion of a fixation J wire through the insulation of this lead was felt to put patients at risk for cardiac perforation.  Pacemaker generator replacement and lead revision were deemed necessary.

Given the patient's recurrent chest complaints, progressive exercise intolerance and questionable location of her present pacing wires, cardiac catheterization was performed.  Catheterization revealed normal right heart pressures including a venous ventricular pressure of 32/9 mm Hg.  There was no evidence of intracardiac shunting.  The pulmonary ventricle (right-sided chamber) had a morphology of a normal left ventricle.  Its contractility was excellent.  The arterial ventricle (left-sided chamber) was heavily trabeculated and had the morphologic characteristics of a normal right ventricle.

Angiography conformed pacing wire positions within the pulmonary ventricle and coronary sinus.  The aorta remained left of the mid-line in an AP direction.  The pulmonary artery was posterior and to the right of the aorta.  There was no aortic insufficiency.  Selective injection of the coronary vessels documented the expected appearance of coronary anatomy in corrected transposition, i.e., the epicardial coronary vessels were concordant with the morphology of the ventricle.  No atherosclerotic disease was found.  Despite the use of only 150 cc of Isovue during angiography, the patient developed transient hyportension requiring low dose dopamine infusion.

The patient subsequently underwent a revision of her pacemaker.  Lead functions were confirmed intraoperatively.  The Accufix atrial lead was easily removed from the pulmonary ventricle (LV) using a telescoping (Bird) extraction set.  A new Medtronic 4058M lead was positioned in the LV apex utilizing the removal sheath for support expediting placement.  The coronary sinus lead was left in place for atrial pacing.  A new Medtronic Thera DR generator with an estimated life of seven years was placed in the original pocket.  Close inspection of the explanted Accufix lead revealed an insulation break not seen with fluoroscopy.

Comments

This case report illustrates remarkable long-term survival in a patient with congenitally corrected transposition.  The patient's course was complicated primarily by complete heart block and the need for multiple pacemaker replacements.  The lack of associated cardiac abnormalities and the unusual preservation of systemic ventricular function no doubt account for the patient's long-term survival.

References

1. Perloff J. The Clincial Recognition of Congenital Heart Disease, 4th Edition. WB. Saunders, CO., 1994; p.72.

2. Electronics pacing systems: product recall for active fixation Atrial J. Leans, Model 329-701, 330-801. Nov3. 1994, Englewood, Colorado.

3. Greenberg P, Castellanet M., Messenger J., Ellestad MH. Coronary sinus pacing. Circ. 1978; 57:98.

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Patients with hypertrophic cardiomyopathy represent a diverse group.  Many patients may be diagnosed easily and have a benign course; others may present particular diagnostic and therapeutic challenges.  The following case is a rare variant of apical hypertrophic disease that amply demonstrates these challenges.

A 40-year-old Filipino woman presented with a three-year history of intermittent substernal chest discomfort associated with dyspnea, marked light-headedness and diaphoresis.  Symptomatic episodes lasted five to 15 minutes, varied in intensity and occurred at rest as well as with exertion.  The patient had been seen in the emergency room three years prior to subsequent evaluation.  At that time, no specific abnormalities were appreciated.

The patient was a petite woman, weighing 104 pounds, with a moderate pectus deformity.  her blood pressure was 180/60 mm Hg.  her pulse was regular at 54 beats per minute.  The cardiac examination revealed a  prominent S4 at the apex, as well as a II/VI systolic ejection murmur at the left sternal border and apex, radiating to the axilla.  The murmur decreased markedly with Valsalva's maneuver.  Jugulovenous pulsations were normal.  The extremities did not reveal any cyanosis, clubbing or edema.

Laboratory data included a total cholesterol of 223 (LDL 163, HDL 46).  Her chest X-ray demonstrated cardiomegaly (CT ration 60 percent) as well as a pectus deformity.

Three prior electrocardiograms were available for review.  The 1986 electrocardiogram demonstrated voltage for LVH and normal R wave progression with upright T waves throughout the tracing.  The 1990 electrocardiogram revealed the development of a mild intraventricular conduction defect and new precordial T wave inversion.  The 1993 electrocardiogram showed a persistent intraventricular conduction defect and Q waves in V1 and V2, as well as deep T inversions in the inferolateral leads.

AN electrocardiographic study taken at rest revealed extensive apical akinesia as well as apical hypertrophy.  The base of the heart was not hypertrophic.  There was no evidence of abnormal systolic motion of the mitral leaflet.  The overall left ventricular ejection fraction was 40 percent.

During an exercise stress test, the patient exercised without complaint for nine minutes and achieved a heart rate of 127 beats per minute.  She was limited by leg fatigue but did not complain of any chest discomfort.  her blood pressure response was blunted with an increase in blood pressure from 108/60 to 114/68 mm Hg.  There was pseudonormalization of the T inversions during exercise.  The EKG returned to baseline at six minutes.  Rare premature ventricular contractions were present.

Subsequently, a right and left heart catheterization was performed.  The initial right heart pressures included a pulmonary capillary wedge pressure of 12 mm Hg, increasing to 20 mm Hg post angiography (V wave equaled 25 mm Hg).  The PA pressure was 35/15 mm Hg; the RV pressure was 45/10 mm Hg; the left ventricular end diastolic pressure was 28 mm hg.

There was no sign of obstruction at the valvular or subvalvular level in the left ventricular outflow tract.  Coronary cineangiography documented a conspicuous lack of motion of the left anterior descending, consistent with apical akinesia.  The circumflex system was normal.

Figure 1. Right anterior oblique coronary angiogram demonstrates large right coronary artery with prominent septal branches to the hypertrophic myocardium.

Figure 2A. Spade-like chamber with apical hypertrophy during diastole.

Figure 2B. Apical obliteration during systole.

Figure 2C. Repeat ventriculogram reveals a discrete apical chamber (x)

Figure 2D. Persistent contrast within the apical chamber several minutes after injection, consistent with outlet obstruction.

The right coronary artery was extremely large and gave rise to prominent septal branches.  

Figure 1.  Left ventriculography revealed a spade-like chamber at the base of the heart.  Figure 2A.  The ventricular cavity was nearly obliterated during systole.  Figure 2B.  A multipurpose A2 catheter was exchanged for the pigtail catheter and advanced well into the left ventricular apex.  Pressure readings were obtained.

The catheter was flushed and aspirated through the cardiac cycle to exclude catheter entrapment.  Contrast was injected selectively into an apical aneurysmal chamber.  A discrete apical aneurysm was connected to the base of the left ventricle through a mid-ventricular tunnel.  Figure 2C.  Dye remained in the aneurysmal chamber for several minutes after the catheter was removed but finally cleared.  Figure 2D.  There was moderate mitral insufficiency.  The overall ejection fraction was 75 percent.

The apex of the ventricle was hypertrophied as judged by the distance from the outline of the chamber and the position of the epicardial left anterior descending vessel.  Aortography was normal.  The right ventricle was heavily trabeculated, and there appeared to be encroachment hypertrophy of the septum.

Holter monitoring revealed two episodes of nonsustained ventricular tachycardia associated with the patient's symptoms.

An electrophysiologic study demonstrated an abnormal sinus node conduction time and AV nodal reentry tachycardia (cycle length 450 m.sec.) with retrograde conduction via a concealed accessory pathway in the right posterior septal area.  There was also inducible polymorphic ventricular tachycardia (cylce lengths 240 and 203) requiring countershock.

Both the AV nodal re-entry tachycardia and the ventricular tachycardia were prevented by procainamide.  The patient was started on sotalol 80 mg b.i.d.  Re-study revealed no repetitive ventricular response despite three driving rates and three extra stimuli from RV apex and RV outflow tract, even with Isuprel infusion.

The patient was lightheaded and fatigued on sotalol 80mg b.i.d.  The dose was reduced to 40 mg b.i.d. with improvement in the patient's bradycardia and hypotension.  The patient has remained asymptomatic, engaging in normal activities but avoiding vigorous exertion.

Follow-up exercise stress testing demonstrated preserved exercise tolerance.  Follow-up Holter monitoring did not reveal any sustained ventricular ectopy; however, isolated ventricular ectopic beats were present.

Discussion

This remarkable patient represents a rare variant of apical hypertrophic cardiomyopathy that is relatively uncommon outside of Japan.  Approximately 100 cases were reported in the world's literature as of 1990.  Criteria include a spade-like configuration of the left ventricular cavity, giant negative T waves, absence of an intraventricular pressure gradient, mild symptoms and, initially, a benign clinical course.

A apical hypertrophy, standard transthoracic echocardiographic examination may be inadequate.  Echocardiographic examination may miss a discrete apical chamber that may develop as a result of infarction.  Transesophageal echocardiography is  more sensitive technique; however, it is semi-invasive.  Consequently, MRI jas been utilized to assess these patients.

The precise pathophysiology of apical infarction remains speculative.  Ischemia may be caused by small vessel disease as well as by a supply-demand imbalance associated with hypertrophy.

Webb reported on 26 patients with apical hypertrophy who were followed for an average of seven years.  One patient with normal coronary arteries had an apical myocardial infarction with development of a discrete aneurysm.  Interestingly, the patient's EKG showed loss of giant T wave negativity. This patient also was the only one to have documented life-threatening ventricular dysrhythmias.

In the largest single series, Nakamura reported 20 patients with a diastolic paradoxic jet across the obliterated left ventricular apex, suggesting the presence of a discrete apical chamber.  Echocardiography did not demonstrate an apical chamber directly in 13 of these 20 patients; however, left ventriculography revealed a small apical outspouching in all patients.  This systolic bulging of the apex was followed by early diastolic shrinkage and persistent cavity narrowing between the two chambers.  Mid-ventricular obstruction varied between long and very localized tunnels, and the apical chambers were of various sizes.

Patients with apical outpouching, or aneurysmal chambers, should be differentiated from the "usual" patient with apical hypertrophic disease, as were those reported by Zoghbi.  In his early report, Zoghbi described patients who were predominantly male, had a history of hypertension, did not demonstrate ischemia and had a benign prognosis.

Patients with apical aneurysms and evidence of ischemia have a less favorable prognosis.  Such patients should be scrutinized carefully to exclude life-threatening dysrhythmias.  The true incidence and clinical outcome of this rare subgroup remains to be determined.

References

1. Wigle ED, Marquis Y, Auger P, Muscular subaortic stenosis: Initial left ventricular inflow tract pressure in the assessment of intraventricular pressure differences in man. Circulation 1967; 35:1100-1117.

2. Maron Barry. Apical hypertrophic cardiomyopathy: The continuing saga. J Am Coll Cardiol 1990; 15:91-92.

3. Koga Y, et al. Prognosis in hypertrophic cardiomyopathy, Am Heart J 1984; 108:351-359.

4. Suzuki II, et al.  New subtype of apical hypertrophic cardiomyopathy identified with nuclear magnetic resonance imaging as an underlying cause of markedly inverted  T waves. J Am Coll Cardiol 1993; 22:1175-1181.

5. Webb JG, Sasson Z., Rakowski, H, Liu P, Wigle ED. Apical hypertrophic cardiomyopathy: Clinical follow-up and diagnostic correlates. J Am Coll Cardiol 1990; 19:516-524.

6. Nakamura T, Matsubara K, Furukawa K, et al.  Diastolic jet flow in patients with hypertrophic cardiomyopathy: Evidence of concealed apical asynergy with cavity obliteration. J Am Coll Cardiol 1992; 19:516-524.

7. Zoghbi WA, Haichin RN, Quinones MA.  Mid-cavity obstruction in apical hypertrophy: Doppler evidence of diastolic intraventricular gradient with higher apical pressure. Am Heart J 1988; 116:1469-1474.

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Thyroid hormone has numerous direct and indirect effects on cardiac function, and alterations in thyroid status may complicate preexisting cardiac disease.  Ikram showed that cardiac failure may develop in thyrotoxic patients.  Although clinical evidence of underlying cardiac disease was excluded, the mean age of his patients was 60 years.  Several recent studies suggest that in middle-aged or older hyperthyroid^3-5 or hyperthyroid⁶ persons, cardiac reserve (determined by exercise radionuclide angiography) is impaired in the absence of underlying heart disease.  The present study was performed to determine whether younger adult patients also had evidence of a thyroid cardiomyopathy.

Fifteen patients with untreated hyperthyroidism were studied.  There were 10 women, mean age 30 years (range 19 to 39), and 5 men, mean age 24 years (range 19 to 31).  All patients had at least moderate symptoms and signs of hyperthyroidism and diffuse goiters.  Serum T₄ was elevated, at 19.2 + 4.3 ug/dl (normal 5.1 to 10.8), serum T₃ was increased, at 413 + 145 ng/dl (normal 115 to 220, and 24 hour radioactive iodine uptake was high, 35 to 90%, in all patients.  Four patients received proporanolol for brief periods before the initial study, but use of this drug was discontinued for at least 1 day.  Seven subjects were restudied after at least 3 months of euthyroidism.

Five hypothyroid patients were studied.  There were 2 women and 3 men, ages 20 to 48 years.  Four had low serum T4 and elevated thyrotropin levels; 1 patient had a normal T4 level but a slightly increased basal thyrotropin and a markedly exaggerated thyrotropin response to thyrotropin releasing hormone.  Three patients had at least moderate symptoms and signs of hypothyroidism.  All but 1 patient were restudied when euthyroid, 10 to 18 months after treatment was initiated.

No patients had systemic hypertension or symptoms or signs of clinical heart disease.  All subjects gave informed consent to participate in a protocol approved by the hospital human use committee.

Patients were exercised in a semisupine position.  Workload was initially 200 kg-m/ min, and this was increased every 3 minutes until fatigue developed.

Radionuclide gated blood pool ventriculography was performed at rest and during exercise after the patient's red blood cells were labeled with 20 to 25 mCi of technetium-99m pertechnetate.  Ejection fractions were calculated on a computer by a single observer.  A normal study was defined as a rest ejection fraction greater than 50%, an exercise ejection fraction at least 5% higher than during rest and normal wall motion.  Statistical methods used were Student t test for paired and unpaired data.

Hemodynamic measurements of the 15 untreated patients were listed in Table 1.  The results of the 7 patients studied before and after treatment of hyperthyroidism are also listed.  As a group, the untreated patients had rest tachycardia, although the range was wide.  All but 3 hyperthyroid patients reached the target rate during exercise, and all achieved a rate-pressure product greater than 23,000 beats mm Hg/min.  Wall motion was determined visually to be normal at rest in all 15 patients.

In 4 hyperthyroid patients ejection fraction (EF) failed to increase by more than 5% during exercise.  Compared with the 11 normal responders, these 4 patients had a higher serum T₄ (23.3 + 4.0 vs 17.7 + 3.4 ug/dl, p <0.02) andrest heart rate (115 + 11 vs 83 + 12 beats/min, p <0.0001).  Although the difference was not statistically significant, mean workload was 30% less (500 + 141 kg-m/min vs 709 + 247) in patients with abnormal EF responses, and mean exercise time was 26% less (8.2 + 1.9 vs 11.0 + 3.6 minutes).  The rate-pressure products were equivalent.  All 4 abnormal responders had a normal rest EF.  Two had a small increase (from 60% to 63% and from 65% to 69%) and 2 a small decrease (from 67% to 63% and from 63% to 62%) with exercise; in all cases EF remained greater than 60%.  One patient had some borderline hypokinesia of the inferior left ventricular (LV) wall with exercise, whereas all others had normal wall motion.

The effect of restoration of euthyroidism on cardiac function in 7 patients is shown in Table II.  Exercise time improved in all but 1 subject, whereas maximal workload increased only in the abnormal responders.  The 3 subjects who initially had a normal response to exercise maintained normal contractility when euthyroid; one showed an increase in contractile response as determined by the amount of change in EF.  The 4 abnormal responders, in contrast, all had considerable improvement in exercise EF after therapy.

The hemodynamic measurements in 5 hypothyroid patients are listed in Table I.  Four subjects were restudied after they were euthyroid.  Three of 5 patients did not reach the target heart rate during exercise when hypothyroid, but these 3 all achieved theri target rates when euthyroid.  Rate-pressure products were more than 22,000 beats mm Hg/min.  The effects of therapy in 4 patients are listed in Table II.  Return to a euthyroid state improved the exercise time in 3 patients but maximal workload in only 1 patient.  EF failed to increase by 5% in 2 patients, both when hypothyroid and later, after they became euthyroid.  Rest had normal wall motion during exercise.  Electrocardiograms were normal in every case.

We measured LVEF responses before and after therapy in young adults with thyroid abnormalities.  Previous reports purport to show impaired LV reserve, taking this as evidence for an early thyroid "cardiomyopathy."^3-5  Eleven of our 15 hyperthyroid patients had a normal EF response.  Four patients responded abnormally, that is, had less than a 5% increase in EF.  These latter patients differed from the former by having higher T4 levels, higher rest and exercise heart rates and shorter exercise time.  This constellation of findings suggests that they were more hyperthyroid chemically and physiologically.  Despite their relative exercise intolerance, the abnormal responders had generally preserved LV function, as evidenced by their high double product.  Moreover, their exercise EF was at least 62%.  Establishment of the euthyroid state in hyperthyroid patients improved exercise duration and maximal attainable EF.  After therapy, 3 normal responders had an increase in exercise time but the maximal workloads were unchanged.  After therapy, the 4 abnormal responders showed an increase in both exercise time and maximal workloads.  Although the rest EF was generally equivalent, exercise EF did increase after therapy.

Five hyperthyroid patients were studied before and after therapy.  Exercise duration was improved in all but 1 patient.  Maximal workload was similar before and after therapy.  Rest EF was not affected by thyroid hormone.  Three of the 5 patients had a higher EF after exercise while hyperthyroid.  The other 2 patients, both with an Ef of more than 70% at rest, either had no change or a slight decrease in EF with exercise.  As a group, establishment of the euthyroid state appeared to increase exercise tolerance.  These results differ from those of Forfar et al, who reported a reduced rest and exercise EF in hypothyroidism.  However, the mean age of his patients was 53 years.  Given the wide range of normal exercise EF responses, the present findings fail to document a significant effect of thyroid hormone deficiency on EF response in a younger adult population.

In conclusion, this study of young hyperthyroid and hypothyroid patients documents essentially normal cardiac reserve.  No patient had clinical evidence of cardiac dysfunction by history or physical examination.  Patients complained of decreased exercise tolerance related to their thyroid abnormality.  This was corrected with establishment of the euthyroid state.  Radioangiography documented good overall cardiac function before and after therapy.  Although a few hyperthyroid patients had a slight aberration in EF response, this was corrected with establishment of euthyroidism.  Although our findings are at variance with those of previous studies, the disparities may be explained in part by methodologic differences.  Moreover, mild changes in EF are believed to have low specificity.  Consequently, the findings noted in these patients do not support there being a primary aberration in myocardial function.

References

1. Smallridge RC. Thyroid hormone effects on the heart. In: Bourne G., ed. Hearts and Heart-Like Organs. New York: Academic Press, 1980;93-160.

2. Ikram H. The nature and prognosis of thyrotoxic heart disease. Q J Med 1985;54:19-28.

3. Shafer RB, Bianco JA. Assessment of cardiac reserve in patients with hyperthyroidism. Chest 1980;78:269-273.

4. Forfar JC, Muri AL, Sawers SA, Toft AD. Abnormal left ventricular function in hyperthyroidism: evidence for a possible reversible cardiomyopathy. N Engl J Med 1982;307:1165-1170.

5. Iskandrian AS, Rose L, Hakki A-H, Segal BL, Kane SA. Cardiac performance in thyrotoxicosis: analysis of 10 untreated patients. Am J Cardiol 1983;51:349-352.

6. Forfar JC, Muri AL, Toft AD. Left ventricular function in hypothyroidism: responses to exercise and beta adrenoceptor blockade. Br Heart J 1982;48:278-284.

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