158 SA MEDIESE TYDSKRIF DEEL 63 29 JANUARIE 1983 Acute coronary secondary to industrial nitroglycerin withdrawal

A case presentation and review

J. Z. PRZYBOJEWSKI, M. H. HEYNS

Clinical presentation Summary The patient, a Black man, was apparently quite healthy Ilntil July A Black employee exposed to industrial nitrogly­ 1977 when he' noted the onset ofdyspnoea on moderate exertion cerin (NG) in an explosives factory presented with and nonspecific . A chest radiograph then showed severe precordial pain. The clinical presentation 'bilateral basal segment pleuropneumonitis with pleural effu­ was that of significant transient anteroseptal and sions', and pulmonary congestion. Therapy for anterolateral transmural myocardial ischaemia cardiac failure was begun but the patient's clinical condition did which responded promptly to sublingual isosorbide not improve significantly and he began experiencing dyspnoea dinitrate. Despite being removed from exposure to on minimal exertion, orthopnoea, paroxysmal cardiac dyspnoea, industrial NG and receiving therapy with long­ swelling of the ankles, and some abdominal distension. At this acting oral nitrates and calcium antagonists, the time he was 41 years old and had been employed atan explosives patient continued to experience repeated attacks of factory for many years whe:re he came into contact with indus­ severe retrosternal pain, although transient myo­ trial nitroglycerin (NG). cardial ischaemia was not demonstrated electro­ There was no past history of or any other cardiographically during these episodes. Cardiac cardiac disease; he did not indulge in the consumption ofalcohol catheterization revealed cl normal myocardial hae­ and his diet was normal. Since his condition was not improving modynamic sy~tem and selective coronary arterio­ he was referred for admission to another university hospital, graphy delineated coronary arteries free from any where a diagnosis of significant constrictive was obstructive lesions. An ergonovine (ergometrine) made. The treatment for cardiac failure was increased with maleate provocative test failed to elicit coronary apparent good effect, and he was discharged a week later. artery spasm, although this was undertaken while Approximately I month after discharge he was readrnirred the patient was on nitrate and calcium-blocker the­ because of the recurrence of symptoms of severe right heart rapy. Clinical records of previous significant con-. failure. Examination revealed gross hepatomegaly, a marked strictive pericarditis (probably due to tuberculosis) pulsus paradoxus, a soft, apical mid-systolic murmur, a diastolic with resultant abnormalities on the ECG compli­ parasternal lift associated with instantaneous splining of the cated the diagnosis. Evaluation was further hin­ second heart sound at the pulmonary area, and a markedly dered by the known 'variant pattern' seen on the elevated jugular venous pressure exhibiting a positive hepato­ ECGs of members of the Black population. jugular reflux and Kussmaul's sign. Blood pressure readings We postulate that this patient's clinical features were repeatedly normal. A chest radiograph showed a slightly were a direct result of severe vasospasm affecting' increased cardiothoracic ratio with evidence of hilar blunting, the left coronary artery; it is also strongly suggested interstitial pulmonary oedema, and bilateral pleural effusions. that withdrawal from contact with industrial NG The ECG displayed sinus rhythm, 'low voltage and some T­ precipitated this potentially lethal coronary vaso­ wave changes'. Cardiological consultation resulted·in a diagnosis .spasm. The role played by industrial NG in ischae­ of constrictive pericarditis, probably a result of tuberculosis. mic heart disease is reviewed, as well as the impor­ Antituberculosis therapy was commenced and the possibility of tance of the 'normal variant pattern' in the assess­ performing a pericardiectomy contemplated, but at follow-up ment of cardiac disease in Black patients. there was a significant decrease in the signs of pericardial con­ As far as we are aware this is the first timethat the striction. The patient was last seen at that hospital in June 1978 use of the ergonovine maleate provocative test has when he was asymptomatic with sinus rhythm, left atrial en­ been documented in the industrial NG withdrawal largement and 'diffuse T -wave inversion in keeping with peri­ syndrome. ' (Fig. la). A chest radiograph showed a normal-sized heart with clear lung fields but small bilateral pleural effusions. S AIr Med J 1983: 63: 158-165. The final diagnosis of 'healed ' was then made and surgery was considered unnecessary. He was dis­ charged to continue with antituberculosis treatment, digoxin and diuretics for a further 3-month period. An ECG taken in July 1979 demonstrated quite a dramatic change: the T waves Cardiac Clinic, Department ofInternal Medicine, Univer­ were now upright and the only abnormality was increased left sity of Stellenbosch and Tygerberg Hospital, Parowvallei, ventricular voltage in the absence ofsystemic hypertension (Fig. CP lb). J. Z. PRZYBOJEWSKI, M.B. CHB., FCP (SA) The patient was admitted to the Intensive Coronary Care Unit Department of Occupational Medicine, PO Dynamite Fac­ (ICCU) ofTygerberg Hospital, Parowvallei, CP, on the morning tory, Somerset West, CP M. H. HEYNS, M.B. CH.B., DIP. OCC MED. of Monday 17 December 1979, having been woken up at 04h30 by sudden, severe retrosternal pain such as he had never expe­ Dale received: 27 July 1982. rienced before. On examination he appeared healthy, was nor- SA MEDICAL JOURNAL VOLUME 63 29 JANUARY 1983 159

l~Y;~-V~-1

~~-~'~~k--'~~jJJ l -k -k

Fig. 1. Twelve-lead resting ECG recorded on full (normal) stan­ dardization (10 mm = 1 mV):a - sinus 53 beats/min, Fig. 2. Twelve-lead resting ECG recorded on full (normal) stan­ 1st degree (PR interval 0,20 second), mean dardization (10 mm = 1 mY): a - recurrence of ST-segment CRS axis + 50°, diffuse upward-coved ST segments and asym­ changes, unifocal ventricular extrasystoles (arrowed) in leads metric T-wave inversion; b - ST segments now normal with V4-V6 portray significant ST-segment elevation not revealed in upright T waves, increased CRS voltage in all precordial leads; c sinus complexes; b - after sublingual isosorbide dinitrate and - recorded during : of 30°, marked relief of angina. Less severe ST-segment displacement; c - deep ST-segment elevation in anteroseptal/anterolateralleads, recip­ asymmetrical T-wave inversion in anteroseptal/anterolateralleads rocal ST-segment depression in inferior leads; d - recorded raising possibility of non-transmural . Pos­ after administration of sublingual isosorbide dinitrate and relief sible Grusin pattern 1 variant; d - ST segment and T waves now of angina, mean CRS axis now normal, some early ventricular normal. Early ventricular repolarization and increased CRS vol­ repolarization in anteroseptal leads. tage in precordia! leads.

motensive and not in cardiac failure. A soft, grade 1/6 ejection Serological tests for syphilis were negative, as were investiga­ systolic murmur was heard along the left sternal border with tions for a collagen disorder. A chest radiograph revealed a poor radiation to the axilla; a prominent fourth heart sound was normal cardiac silhouette and clear lung fields. Ventricular present, but no clicks or diastolic murmurs could be heard. An ectopic activity ceased and the patient had no further chest pain. ECG recorded on admission, while the patient was in pain, In view of the electrocardiographic findings a 99mTc pyrophos­ showed most impressive abnormalities (Fig. lc). Very marked phate scan ('hot-spot scan') was carried out on the 5th day of ST-segment elevation was visualized in the anteroseptal and hospitalization, but this failed to establish a diagnosis of infarc­ anterolateral leads, this being as much as 10 mm in leads V2 and tion; a repetition on the 8th day again did not show an increase in V3. In addition, marked reciprocal ST-segment depression was isotope uptake. M-mode echocardiography excluded a possible present in standard leads 11, III and aVF, but no Qwaves could prolapse (Barlow's syndrome), as well as hypertro­ be seen. There was left axis deviation of 30°. The diagnosis of phic obstructive . Left ventricular function was possible hyperacute anteroseptallanterolateral myocardial also within normal limits. The patient was discharged on 24 infarction or coronary artery spasm with severe transmural December 1979 with a diagnosis of coronary vasospasm due to myocardial ischaemia was made. He was immediately given industrial NG withdrawal, and the remaining T -wave changes sublingual isosorbide dinitrate; within a few minutes the retro­ seen on the ECGs were attributed to the 'normal variant pattern' sternal pain subsided and a repeat resting ECG demonstrated a encountered in the Black population. remarkable change (Fig. Id). There was no longer any ST­ Therapy with isosorbide dinitrate 10 mg 3 times daily and segment elevation, apart from some early ventricular repolariza­ nifedipine at the same dosage was continued, and the patient was tion in the anteroseptallanterolateralleads. A diagnosis of tran­ withdrawn from exposure to NG. On 7 January 1980 a resting sient severe transmural myocardial ischaemia secondary to ECG showed that the previously inverted T waves were now significant vasospasm ofthe left coronary artery (LCA) was then upright; the only abnormality was increased voltage over the made, and was thought to have been provoked by NG withdra­ precordial leads (Fig. 2d). The patient went to his place of wal. Frequent sublingual isosorbide dinitrate, as well as the oral employment a few days later (10 January), complaining of con­ preparation was prescribed, and heparin was also given. stricting left-sided chest pain radiating down his left arm. He was Within about an hour of his chest pain having subsided he immediately given sublingual isosorbide dinitrate 5 mg, with again complained of severe retrosternal pain associated with rapid relief. After this emergency treatment an ECG was taken palpitations, sweating and dyspnoea. A further resting ECG (Fig. 3a), but proved to be no different from that taken a few days demonstrated recurrence of significant ST-segment elevation previously. It was then decided to readmit the patient to the and depression changes as in the initial episode.However, several ICCD at Tygerberg Hospital on 11 January for observation. The unifocal ventricular extrasystoles were also recorded during only abnormal finding was a persistent soft ejection systolic chest pain, with marked ST-segment elevation in leads V4 - V6 murmur at the lower left sternal border. Daily resting ECGs not evident in the sinus complexes (Fig. 2a). The patient was showed no change. A submaximal-treadmill effort test demon­ given more sublingual isosorbide dinitrate with prompt reliefof strated no myocardial ischaemia, no and no angina. pain as well as gradual subsidence of the ST-segment changes In view of the uncertainty ofthe underlying pathophysiology it (Fig. 2b). Treatment with oral nifedipine 10 mg 3 times daily was was decided to undertake full . The nitrate commenced. On the following day an ECG (Fig. 2c) showed and nifedipine medication was not discontinued for fear of pre­ deep asymmetrical T -wave inversion in the anteroseptal and cipitating further episodes of coronary artery spasm. anterolateral leads, raising the possibility of acute non­ transmural myocardial infarction.. However, daily ECGs remained unchanged and serial enzyme estimations failed to Cardiac catheterization show any elevation to support this diagnosis. Baseline haemato­ This procedure was undertaken on 17 January 1980. The logical and biochemical investigations were within normal limits. Seldinger technique via the right femoral artery and vein was 160 SA MEDIESE TYDSKRIF DEEL 63 29 JANUARIE 1983

employed using 7F Goodale-Lubin and pigtail catheters. All the intracardiac pressures and indices of cardiac contractility were normal. A left ventricular cine angiogram in the right anterior oblique (RAO) projection delineated a normally contracting left ventricle with no evidence ofany mitral insufficiency or prolapse (Fig. 4). Selective coronary angiography demonstrated that both the right coronary artery (RCA) (Fig. 5) and the LCA (Fig. 6) were normal. In view of the possibility of underlying coronary vaso­ spasm in anatomically normal coronary arteries, it was decided to carry out an ergonovine (ergometrine) maleate provocation test. A 12-lead ECG was set up and standard lead II and lead V2 were monitored on the oscilloscope, as well as the aortic pressure. Ergonovine maleate was initially given as a bolus of 0,025 mg injected into the main pulmonary artery; 12-lead ECGS were recorded every minute. Since the patient did not complain of angina and there were no features ofmyocardial ischaemia on the Fig. 3. Twelve-lead resting ECG recorded on full (standard) stan­ ECGs, a further bolus of ergonovine 0,025 mg was injected 4 dardization (10 mm = 1 mV): a - after relief of angina with sublingual isosorbide dinitrate, tracing similar to that seen in Fig. minutes after the initial injection. The provocative drug was then 2d; b - precordial T waves flatter than seen on 10 January, still administered every 4 minutes at doses of0,05 mg, 0,05 mg, 0,10 increased ORS voltage in precordial leads; c - precordial T mg ;'md 0,15 mg to a total dose of 0,40 mg: Again, there was no waves now taller than seen on 28 January; d - most recent change on the ECG and the patient did not experience angina. tracing showing early repolarization and increased ORS voltage in precordial leads. Repeat cine angiograms of the LCA (Fig. 7) and RCA (Fig. 8)

Fig. 4. Left ventricular cine angiograms in RAO projection showing normal contractility and mitral valve: a - left ventricle in end­ diastole; b - left ventricle in end-systole.

Fig. 5. Before ergonovine (ergometrine) maleate provocation. RCA cine angiograms in the (a) leftanterior oblique (LAO) and (b) RAO views. The vessel is dominant and normal. SA MEDICAL JOURNAL VOLUME 63 29 JANUARY 1983 161

Fig. 6. Before ergonovine (ergometrine) maleate provocation. LCA cine angiograms in the (a) LAO and (b) RAO views. Normal vessels are seen.

Fig. 7. After ergonovine maleate provocation. LCA cine angiograms in the (a) LAO and (b) RAO views. No coronary vasospasm could be provoked.

Fig. 8. After ergonovine maleate provocation. RCA cine angiograms in the (a) LAO and (b) RAO views. No coronary vasospasm could be provoked. 162 SA MEDIESE TYDSKRIF DEEL 63 29 JANUARIE 1983

failed to document coronary vasospasm. The procedure was then problem even more intriguing. These aspects will now be consi­ completed without complication. de:ed in more detail, as will the therapeutic implications.

The patient was discharged on 18 January and was advised to continue his medication. A resting ECG taken on 28 January (Fig. 3b) showed that the T-wave amplitude in the precordial leads was now much smaller than previously seen, despite the The electrocardiographic 'normal variant increased QRS voltage in these leads. He remained asympto­ pattern' in the Black matic and a routine ECG taken on 25 August (Fig. 3c) recorded As regards ECGs, differences do exist between races, sexes T waves of larger amplitude in the precordial leads. Repeated and at different stages ofmaturation (taken from infaacy through 'checking' resting ECGs subsequently demonstrated no change. adolescence to senescence).J7 This fact is of particular impor­ A routine submaximal treadmill effort test carried out on 8 June tance in South Africa in view of the multiracial population. The 1981 was negative. 'early repolarization variant'18 has been variously termed: 'pre­ mature repolarization',!9 'unusual RT-segment deviation',20 The patient remained asymptomatic over the ensuing months 'normal RS-T elevation variant',2! 'early repolari;::afion syn­ and continued working away from industrial NG. However, on drome',22 and the 'juvenile pattern of adult Negro:males'.23 17 November 1981 he was admitted to the factory hospital with These changes have been attributed to such conditions as exces­ severe precordial pam radiating down the left arm; sublingual sive vagotonia (such as is seen in athletes, i:e. 'the athletic heart isosorbide. dinitrate 5 mg gave effective relief. A resting ECG syndrome', infantile bodily habitus, the electrical position ofthe showed no change from that taken on 25 August 1980. Several heart, some metabolic factors and an increase in-myocardial days of hospitalization ensued with no further chest pain, serial mass. ECGs showing no new features. Since that episode the patient 24 25 has continued to remain asymptomatic on a combination of Brink . was the first to document T -wave inversion in the isosorbide dinitrate and nifedipine. The most recent resting right ventricular (VI - V3) precordial leads (reporting an inci­ ECG taken (13 July 1982) demonstrated increased voltage and dence of 5% in healthy Black adults), and attributed these repo­ early ventricular repolarization changes in the precordial leads, larization changes to excessive vagotonia. Grusin26 -then pub­ but nothing else of significance (Fig. 3d). lished his findings in 159 Black patients without heart disease and in 50 healthy Black nurses; some 63% of the former group and 20% ofthe latter exhibited some form ofthe 'normal variant pattern'. He recognized three basic 'patterns'. The first pattern (the most common of the three) was characterized by ST­ Discussion segment depression associated with asymmetrical, deeply inverted Twaves, mostly in the right ventricular precordial leads Atheromatous has always been accepted (V 1-V3). The second pattern (the next most frequent) consisted as beingextremely uncommon in South African Blacks,1-5 butan of marked ST-segment elevation associated with tall T waves increasing incidence is being seen in urbanized or 'westernized' 6 and large-amplitude R waves primarily in the left ventricular Blacks. The symptom ofangina pectoris in a Black patient must precordial leads (V4-V6). The third panernwas characterized by therefore be considered seriously and a definite cause sought. rounded or 'flat' T waves in the precordial leads. Some of his Syphilitic coronary ostial stenosis is a well-known cause of both subjects displayed a combination of the first two patterns. A .angina and acute myocardial infarction in this population most striking feature documented by Grusin was the sponta­ group.7 Other non-atheromatous causes such as the collage­ neous fluctuation seen to occur in many of his patients over a 8 lO noses ,9 and aortic arteritis (Takayasu's disease ) must also be 12-month period. He preferred to incriminate some influence of . considered. malnutrition or a persistence ofthe 'juvenile pattern' rather than to attribute this to auto-immune nervous system imbalance. The explosives industry is particularly important in this coun­ try, especially since mining is such a dominant economic force. PowelJ27 found a ~normal variant' incidence of 39% in 100 Industrial NG is usually employed in this field and for many Black patients without cardiac disease, in 22% of50 healthy Black years 'withdrawal' symptoms have been experienced by workers male nurses and 37% of 100 Black males suffering from amoebic exposed to industrial NG.II The most frequent complaint is that of 'Monday morning headache',12,13 which follows withdrawal dysentery. He found that the second pattern previously de­ scribed by Grusin predominated, and concluded that the cause from NG over the previous weekend. Precordial pain,!4 acute of the variant pattern was a 'biochemical change in the myocar­ myocardial infarction15 and sudden death16 have also been dial cell due to unknown factors'. Woods and Laurie28 were most thought to be secondary to industrial NG withdrawal. Our critical of Grusin's publication, mainly because only about 20% patient presented with the classic features of coronary artery ofhis subject's 'were in good health'. These workers claimed that spasm, seriously considered to have been a direct result of the the ECG of the healthy Black was similar to that seen in other withdrawal syndrome; yet selective coronary arteriography de­ racial groups, and that the 'Grusin normal variant' was usually lineated normal coronary arteries, and an ergonovine (ergome­ due to some underlying cardiac abnormality, apart from those trine) maleate provocative test for coronary artery spasm was cases of functional aetiology. negative. However, it is important to note that this provocative measure was applied while the patient was on maintenance long­ 29 3o acting nitrates and calcium-antagonist drugs which were not Fleishman • investigated 573 apparently healthy Black male discontinued for fear of the very real danger of precipitating an subjects and found an incidence of ST-segment and T-wave acute myocardial infarction. Analysis of .the patient's clinical changes of 23%, supporting the work of previous researchers. picture was further complicated by the previous documentation Walker and Walker!7 documented interesting data on the elec­ ofconstrictive pericarditis (probably tuberculous in nature) with trocardiographic differences encountered in young South Afri­ ensuing electrocardiographic abnormalities. Furthermore, the can Blacks and Whites, highlighting the influence of race, sex, presence of the 'normal variant panern' on the ECGs, well esta­ age and the state of nutrition. They confirmed the findings of blished in Black South Africans, made unravelling ofthe clinical Grusin and noted a general diminution in the degree of ST-T SA MEDICAL JOURNAL VOLUME 63 29 JANUARY 1983 163 segment changes with increasing age. Furthermore, an unduly compared with a pseudo-myocardial infarction pattern in the bad prognosis was not related to the existence of these variant latter. patterns. Myocardial infarction. The hyperactive phase ofan antero­ Reiley el al. 31 carried out a similar survey in the USA, and septal myocardial infarction may be confused with the ST-T found the greatest incidence of the variant among Black males, wave changes seen in the Grusin pattern I variant. An acute who were also noted to have the most marked increase in precor­ non-transmural anteroseptal infarction can likewise be confused dial QRS amplitude. A smaller incidence was found in White with the Grusin pattern 2 variant. Previous non-transmural men, but this was higher than those found in Black or White anteroseptal and lateral myocardial infarctions can quite easily women. The variant pattern has also been documented in mimic the third Grusin pattern of the normal variant. healthy East Africans. 32 . This condition, irrespective of the cause, can Our patient displayed a combination of ST-segment elevation quite easily be mistaken for a Grusin pattern 3 variant. The and intermittent biphasic T waves and tented precordial T picture is further complicated by the frequent existence of an waves, as well as deep, asymmetrical T -wave inversion in the associated pericarditis (i.e. ). However, the Black precordial leads and markedly increased precordial QRS voltage. patient often has an underlying in association Thus, a combination of Grusin's pattern I and pattern 2 was with the normal variant pattern, whereas is usual encountered. The difficulty in interpreting the electrocardiogra­ with myocarditis. phic changes in this patient in the light of his previous history Cardiomyopathy. The wide spectrum of restrictive,46-4s will be discussed shortly. congestive (dilated, cryptogenic, idiopathic) and hypertrophic (obstructive49 and non-obstructiveSO,51) cardiomyopathy must be considered in the differential diagnosis of the normal variant pattern, but the clinical characteristics usually allow for quite ECG tracings mimicked the 'normal accurate diagnosis. Left secondary to by systemic hypertension may be especially problematic when variant pattern' (Table I) 'decapitated' hypertension gives rise to . The spectrum of electrocardiographic or is associated with it. changes caused by various forms of pericarditis are of particular Athletic heart syndrome. Virtually identical repolarization 52 importance in the differential diagnosis. Acute pericarditis, changes are seen in the athlete. ,53 These features ar'e thought to especially durinJ? its very early phase (said to be caused by an be an expression of the electrophysiological and anatomical epimyocarditis3 -35) when seen on ECGs, has proved the most effects ofregular exercise on the heart, especially that induced by difficult to distinguish from the normal variant pattern, and increased vagal tone. Thus, apart from varying degrees of atrio­ these two conditions have been claimed to be indistinguish­ ventricular , tall and peaked T waves with ST­ able.21,36,37 However, differentiation has been aided by the fact segment elevation are common in the anteroseptal leads. Deep that the changes caused by pericarditis tend to evolve over a asymmetrical T -wave inversions may be evident in all precordial period of hours, days or even weeks,3s,39 whereas those of the leads, as well as increased QRS voltage. normal variant can last many years, albeit with numerous fluc­ Miscellaneous conditions. The hyperventilation syn­ tuations. The injury current ofthe former condition is thought to drome54 is a well-known cause of ventricular repolarization alte­ be secondary to subepicardial inflammation ofvarying duration. rations, as has been experienced in the interpretation of stress Spodick33 was the first to demonstrate that the ST- ECGs. Hyperkalaemia, apart from mimicking acute anteroseptal alterations always occurred in the limb leads in acute pericardi­ myocardial infarction,55 may well be confused with the normal tis, but that in some 30% of the normal variants these changes variant pattern. Acute cor pulmonale could present difficulty in were confined to the precordial leads. He also showed that differentiation from the Grusin pattern I normal variant. Like­ ST-segmentelevation in lead V6and depression in lead VI were wise, the electrocardiographic manifestations of acute pulmo­ far commoner in acute pericarditis, and that the two conditions nary embolism and primary pulmonary hypertension56 could be could be further differentiated by vector cardiographic analysis. mimicked, apart from the obvious changes in P-wave morphology. Ginzton and Laks40 attempted to distinguish acute pericarditis' from the normal variant pattern by quantitative electrocardio­ graphic analysis. These researchers found that an ST wave IT TABLE I. ECG TRACINGS MIMICKED BY THE 'NORMAL 2': ratio of 0,25 in lead V6 was specific for acute pericarditis, and VARIANT PATTERN' that ifthis lead was not available the same ratio value in leads V4, VS and I was most suggestive of this condition. Furthermore, a 1. Acute pericarditis T-wave amplitude of :::;0,3 mV in lead V6 was highly suggestive 2. Chronic constrictive pericarditis of acute pericarditis. 3. Myocardial infarction Chronic constrictive pericarditis. The T -wave deviations Acute non-transmural in this condition are usually widespread, and consist of either Old non-transmural flattened, upright T waves or inverted T waves which are either 4. Myocarditis (myopericarditis) deep or ofsmall amplitude. These findings would be consistent A(;ut~ with those found on the initial ECG of our patient (Fig. la). Cl1ronic However, that was the only ECG tracing which revealed such 5. Cardiomyopathy extensive changes, and probably indicated that the patient had, Restrictive (dila~ed) most likely, almost passed the constrictive phase ofhis presumed Congestive tuberculous pericarditis. In fact, serial ECGs taken before and Hypertrophic (obstructive and non-obstructive) after radical pericardiectomy for chronic constrictive pericarditis 6. Athletic heart syndrome have demonstrated the persistence of diffuse T -wave inversion 7. Miscellaneous despite normal haemodynamic findings. 41 These T -wave changes Hyperventilation syndrome may be caused by myocardial atrophy, myocardial fibrosis,42 Hyperkalaemia cardiac constriction,43 myocardial calcification or a reduction in Acute cor pulmonale Acute pulmonary embolism myocardial blood flow. 44 Lewis el al.45 differentiated the electro­ cardiographic changes of constrictive pericarditis from 'Bantu Primary pulmonary hypertension myocardiopathy'; the former had a typical ST-T wave pattern 164 SA MEDIESE TYDSKRIF DEEL 63 29 JANUARIE 1983

Pathophysiology of coronary vasospasm in employees, his angina decreased in frequency with removal from industrial NG withdrawal syndrome the explosives environment. HogstedteT a/. 62 first utilized 48-hour ambulatory ECGs (Hol­ The pathophysiological.concept ofcoronary artery spasm was ter monitoring) on explosives workers, attemptingto demonstrate revived during the I970s,,7.58 and its importance in atheroscle­ an increasing incidence of dangerous ventricular arrhythmias rotic coronary artery disease has been emphasized by several 59 61 during the withdrawal period; this would explain the symptoms researchers. - More frequent use ofselective coronary arterio­ as due to acute myocardial ischaemia on the basis of coronary graphy in patients presenting \vith chest pain, as well as the fairly vasospasm. They were only able to detect recent introduction of the ergonovine (ergometrine) maleate on a Monday morning in a single worker, and some ventricular provocation test to detect possible underlying coronary vaso­ ectopic beats in both control workers and exposed workers. In spasm, has increased the frequency of its documentation as well addition, they postulated that increased sympatheticactivity was as its firm acceptance. It is therefore not surprising that this mecha­ more pronounced during the withdrawal period, and that the nism has been postulated as being of vital importance in the myocardium was more vulnerable to ventricular , spectrum of non-atheromatous coronary artery disease reported secondary to coronary vasospasm. Thus, a hypoth~sis of the in employees working with explosives. cause of sudden death in explosives workers was made more G alone, or in combination with ethylene glycol dinitrate attractive. evertheless, it has been shown that sudq.en cardiac (nitroglycol), has been utilized in the manufacturing ofdynamite death in men not known to have underlying cardiac disease is for several decades. This usually involves open techniques, and a statistically more frequent on a Monday ~orning.63 substantial level ofnitrates is therefore detected in the surround­ Our patient almost certainly suffered from the NG withdrawal ing atmosphere. Nitrates are particularly volatile and thus easily syndrome as evidenced by severe intermittent non-exertional absorbed via the skin and lungs, especially ifadequate protective angina associated with electrocardiographic features oftransient clothing is not worn. An 'acute toxic response' is therefore most myocardial ischaemia, relieved by nitrate therapy. Coronary common, and is characterized by such symptoms as head­ angiography gave the usual negative results. The fact that the ache,12,13 orthostatic hypotension, palpitations, gastro-intestinal patient was taking oral nitrates and nifedipine while undergoing disturbance, a fall in diastolic blood pressure and rise in systolic coronary angiography and the ergonovine maleate provocative pressure. This clinical picture is usually present for approxi­ test may well have accounted for the fact that spontaneous or matelya week. Once the subject has been exposed to NG for a induced coronary vasospasm was not documented.64 As far as we' period of longer than 12 months a different 'adaptation' are aware, this is the first time that the ergonovine maleate response, consisting of a rise in diastolic and a fall in systolic provocative test has been employed in the industrial NG with­ blood pressure with resultant smaller pulse pressure and accom­ drawal syndrome. panying bradycardia, occurs. This is the period in the employee's A further interesting finding was the occurrence of ST­ ll life when a 'withdrawal response' may OCCUr. segmentelevation in ventricular ectopic beats (Fig. 2a) butnot in Some 30 years ago the effects of withdrawal from industrial sinus beats. A similar finding has been documented by Scham­ NG was first documented in the German, Swedish and Italian roth6S in a patient experiencing episodes ofvariant (Prinzmetal's) literature. Symptoms ofsevere angina not related to exertion or angina. Several authors have previously reported on this charac­ emotion were commonly encountered within I - 3 days of teristic in the diagnosis of acute myocardial infarction. 66 non-exposure, and relief was subsequently experienced upon re-exposure. Sudden death was far less common. l6 Another typical clinical presentation was that of acute myocardial infarc­ Therapeutic implications tion, autopsy revealing no evidence of significant obstructive coronary atherosclerosis. In an attempt to explain the with­ It would seem clear that any subject who has underlying drawal reaction various theories have been proposed. The sugges­ ischaemic heart disease should not be exposed to industrial NG. tion of alternating coronary vasodilation (occurring during TJ1e intriguing possibility ofthe use ofprophylactic oral isosor­ periods of exposure) and vasoconstriction (during periods of bide dinitrate administration during the withdrawal period can­ withdrawal), involving the nutrient arterioles and resulting in not be ignored entirely, much as this drug is used in the prophy­ deposition of hyaline material in the arterial wall was put for­ laxis of angina pectoris due to atherosclerotic coronary artery ward. Another theory was that ofsevere peripheral vasodilation disease. Furthermore, if coronary vasospasm is the mechanism giving rise to cardiovascular collapse due to inadequate venous of this withdrawal syndrome, administration of long-term pro­ return. However, the most attractive postulate, first propo~ed by phylactic calcium-blocking drugs may entirely prevent angina at Carmichael and Lieben,l6 would appear to be that of acute rest, acute myocardial infarction and sudden death in this spe­ cific working population. coronary artery spasm. Lange eT al. ls were the first to document spontaneous coronary vasospasm by coronary arteriography du­ A further important implication of the experience derived ring a period of withdrawal. Their patient also responded quite from the industrial NG withdrawal syndrome concerns the dramatically to the sublingual administration ofnitrates, although treatment of ischaemic heart disease. Much has been written no electrocardiographic features of vasospasm were noted. A about the dangers of abrupt withdrawal of propranolol in further 8 patients had symptoms ofnon-atheromatous ischaemic patients given this drug for angina pectoris. Perhaps sudden heart disease, I dying suddenly; a further 4 underwent selective cessation of the commonly prescribed oral long-acting nitrates coronary angiography. One ofthe subjects who underwent coro­ may be just as potentially lethal; prescribing doctors should nary angiography developed complete left bundle-branch block probably warn their patients of this danger. Sudden death is and had a late sudden death. almost certainly the most common and frustrating single presen­ tation in the spectrum ofsymptomatic atherosclerotic ischaemic l4 Klock was the second to demonstrate spontaneous vaso­ heart disease and its incidence might well be dramatically spasm of the RCA at the time of coronary arteriography in a reduced by ~pplying such basic clinical principles in the patient who developed frequent episodes of non-exertional management. angina during the withdrawal period. This vasospasm was rapidly relieved by sublingual nitrates, but again no electrocar­ diographic features of myocardial ischaemia could be detected. We wish to sincerely thank Miss H. Weymar of the Cardiology The patient had several more episodes of angina after cardiac Unit, Tygerberg Hospital, for preparing the manuscript and electro­ catheterization, but his condition stabilized on high doses of cardiographic illustrations. Sister P. Goldsmith of the Department isosorbide dinitrate. In common with all the previous affected of Occupational Medicine, AECI Ltd, Somerset West, is thanked SA MEDICAL JOURNAL VOLUME 63 29 JANUARY 1983 165 for her invaluable technical assistance. Appreciation is also shown 32. Somers K, Rankin AM. The electrocardiogram in healrhy East African (Bantu towards Mrs 1. BickJe of the Department of Photography, Univer­ and Nilotic) men. Br Heart J 1962; 24: 542-548. 33. Spodick OH. Differential characrerisrics of the electrocardiogram in early sit\" ofSteUenbosch Medical School, for her painstaking preparation repolarization and acure pericarditis. N Engl J Med 1976; 295: 523-526. o(the photographs. Finally, due appreciation is shown towards Dr 34. Surawicz B, Lasserer KC. Electrocardiogram in pericardiris. Am J Cardiol C. Vivier, ChiefMedical SuperintendentofTygerberg Hospital, for 1970; 26: 471-474. 35. Spodick OH. Parhogenesis and clinical correlations of elecrrocardiographic permis ion to publish. abnormalities of pericardial disease. Cardiovasc Chn 1977; 8: 201-248. 36. Parisi AF, Beckmann CH, Lancaster MC. The spe"rrum of ST-segmeOl elevarion in the electrocardiogram of healthy adult men.J Electrocardiol1971; 4: 137-144. REFERENCES 37. Goldman MJ. RS-T segmeOl elevarion in mid and left precordial leads as a normal variant. Am Heart J 1953; 46: 817-820. I. Seftel HC. The rarir\" of coronar\" heart disease in Sourh African Blacks. 5 Afr 38. Spodick OH. Diagnosric electrocardiographic sequences in acure pericardiri : MedJ 1978; 54: 99-105. . significance of PR segmeOl and PR vector changes. Circulation 1973; 48: 2. Chesler E, Mitha AS, Weir EK, Matisonn RE, Hirchcock PJ. Myocardial 575-580. infarction in the Black population of South Africa: coronary aneriographic 39. Spodick OH. DiffereOlial diagnosis of acute pericarditis. Prog Cardio'1'Osc Dis findings. Am Heart J 1978; 95: 691-696. 1971; 14: 192-209. 3. Schire V, Uys Cl, Cardiac infarction in the Banru. Am J Cardiol 1958; 2: 40. Giozton LE, Laks MM. The differential diagnosis of acure peticarditis from 453-463. the normal variant: new electcocardiographic criteria. Cir:cu[acioll 1982; 65: 4. Lowenrhal MN. Coronary !;lean disease diagnosed as cardiomyoparhy in 1004-1009. Blacks: a report of four cases. 5 Afr Med J 1978; 53: 948-949. 41. Avgoustakis 0, Lazarides 0, Athanasiades 0, Michaelides G. The electrocar­ 5. Seedat YK, Pillay N. Myocardial infarction in rhe African hyperrensive diogram in constrictive pericarditis before and after radical pericardiectomy. patienr. Am Heart J 1977; 94: 388-390. Chest 1970; 57: 460-467. 6. Isaacson C. The changing panern of heart disease in Sourh African Blacks. 5 42. Hull E. The electrocardiogram in pericardiris. Am J Cardiol 1961; 7: 21-32. Afr Med J 1977; 52: 793-798. 43. Scheepers G WHo Tuberculous pericarditis. Am J Cardiol 1962; 9: 248-276. 7. Scharfman WB, Wallach JB, Angrist A. Myocardial infarction due ro syphiliric 44. Burwell CS. Constricrive pericarditis. CirClllation 1957; 15: 161-163. coronarv ostial stenosis. Am Heart J 1950; 40: 603-613. . 45. Lewis BS, Van der Horsr RL and Gotsman MS. Diagnostic electrocardiogra­ 8. Bonfiglio TA, Boni RE, Hagstrom JWc. Coronary arreritis, occlusion, and phic parterns in Banru myocardiopathy and constrictive pericarditis. 5 AfrMed mvocardial infarction due ro lupus erythematosus. Am Heart J 1972; 83: J 1971;45: 1110-1118. 153-158. 46. Benorri JR, Grossman W, Cohn PF. Clinical profile of resrrictive cardio- 9. Przvbojewski JZ. Polyarreritis nodosa in rhe adult: reporr of a case wirh myoparhy. Cimrlalion 1980; 61: 1206-1212. .. repeated myocardial infarction and review ofcardiac involvement. 5 AfrMedJ 47. Przyhojewski JZ, Daniels AR, Van der Wait Jj. Primary cardiac : a 1981; 60: 512-518. ca e presenrarion. 5 Afr MedJ 1980; 57: 774-780. 10. Cipriano PR, Silverman JF, Perlrorh MG, Griepp RB, Wexler L. Coronary 48. Przybojewski JZ, Daniels AR, Van der Wait Jj. Primary : a arrerial narrowing in Takayasu's aortiris. Am J Cardiol 1977; 39: 744-750. review of rhe lirerarure. 5 Afr Med J 1980; 57: 831-837. 11. Lund RP, Haggendal J, Johnsson G. Withdrawal symptoms in workers 49. Savage DD, Seides SF, Clark CE et al. E1ecrrocardiographic findings in exposed ro nitroglycerine. BrJ Industr Med 1968; 25: 136-138. patients with obstructive and nonobsIrucrive hypertrophic cardiomyopathy_ 12. Trainor DC, Jones RC. Headaches in explosive magazine workers. Arch Circulation 1978; 58: 402-408. Em·iron Health 1966; 12: 231-234. 50. Chen CH, Tobuyoshi M, Kawai C. ECG parrern of left veOlricular hyper­ 13. McGuinness BW, Harris EL. 'Monday head': an inreresring occupational trophy in nonobstrucrive hyperrrophic cardiomyopathy: the significance ofthe disorder. Br MedJ 1961; 2: 745-747. . . mid-precordial changes. Am Heart J 1979; 97: 687-695. 14. Klock JC Nonocclusive coronary disease after chromc exposure ro mtrares: 51. Przybojewski JZ, Hoffman H, de Graaf AS et al. A study of a family wirh ..·idence for physiologic nirrare dependence. Am Heatl J 1975; 89: 510-513. inherired disease ofcardiac and skeletal mu cle. Part I: Clinical, electrocardio­ 15. Lange RL, Reid MS, Tresch DD, Keelan MH, Bernhard VM, Coolidge G. graphic, echocardiographic, haemodynamic, electrophysiological and electron ~ona[heromatousischaemic hean disease following withdrawal from chronic microscopic studies. 5 Afr ,tIedJ 1981; 59: 363-373. industrial nitroglycerine exposure. Cirwlarion 1972; 46: 666-678. 52. Lichtman J, 0 Rourke RA, Klein A, Karliner JS. Elecrrocardiogram of rhe 16. Carmichael P, Lieben J. Sudden death in explosive workers. Arch Em.ron arhlete: alterations simulating those of organic heart disease. Arch Imern Med Health 1963; 7: 424-439. 1973; 132: 763-770. 17. Walker ARP, Walker BF. The bearing ofrace, sex, age, and nutritional srate on 53. Roeske WR, 0 Rourke RA, Klein A, Leopold G, Karliner JS. Non-invasive the precordial electrocardiogram ofyoung Sourh African Banru and Caucasian evaluarion ofveOlricular hyperrrophy in professional athleres. Circulation 1976; subjecrs. Am Heart J 1969; 77: 441-459. 53: 286-292. 18. Alimurung BN, Gilbert CA, Felner JM, Schlanr RC The influence of early 54. Biberman L. Sarma RN, Surawicz E. T-wave abnormalities during hyperven­ repolariz3rion variant on the exercise electrocardiogram: a correlation with tilation and isoprorerenol infusion. Am Heart J 1977; 81: 166-174. coronary arteriograms. Am Heatl J 1980; 99: 739-745. 55. Chawla KK, Cruz J, Kramer NE, Towne WO. Elecrrocardiographic changes 19. GOllschalk CW, Craig E. A comparison of the precordial S-T and T waves in simularing acure myocardial infarcrion caused by hyperkalemia: report of a the electrocardiogram of 600 healrhy young Negro and White adulrs. 50ruh parient with normal coronary arreriograms. Am Heart J 1978; 95: 637-640. Med J 1956; 49: 453-457. 56. Factor SM, Reichel J. Primary pulmonary hypertension. Am Heart J 1980; 99: 20. Chelton LG, Burchel HE. Unusual RT segmenr deviation in electrocardio­ 789-798. grams of normal persons. AmJ Med 5ci 1955; 230: 54-60. 57. Maseri A. Pathogenetic mechanisms of angina pectoris: expanding views. Br 21. Wasserburger RH, Alt WJ, Lloyd C. The normal RS-T segmenr elevarion Heart J 1980; 43: 648-660. varianr. AmJ Cardia/1961; 8: 184-192. 58. CoOli CR, Curry RC. Coronary artery spasm and myocardial ischaemia. Mad 22. Kambara H, Phillips J. Long-rerm evaluation ofearly repolarization syndrome Concepts Cardiovasc Dis 1980; 69: 1-6. (normal variant RS-T segmenr elevarion). AmJ Cardial 1976; 38: 157-166. 59. Brown BG. Coronary vasospasm: observarions linking the clinical spectrum of 23. Wasserburger RH. Observations on rhe 'juvenile parrern' ofadult Negro males. ischaemic heart disease ro rhe dynamic parhology ofcoronary arherosclerosis. AmJ Med 1955; 18: 428-437. Arch Imern Med 1981; 141: 716-722. , 24. Brink AJ. An investigation of factors influencing repolarization in rhe human 60. Maseri A, Chierchia S, L'Abbare A. Pathogenetic mechanisms underlying rhe heart. 5 AIrJ Clin 5ci 1951; 2: 288-297. clinical events associated with atherosclerotic heart disease. CirculatIOn 1980; 25. Brink AJ. The normal electrocardiogram in rhe adult South African Banru. S 62: suppl V, 3-13. AfrJ Lab Clin Med 1956; 2: 97-123. .' 61. Hellstrom HR. Evidence in favor of the vasospasric cause of coronary artery 26. Grusin H. Peculiarities of rhe African's elecrrocardlogram and the changes thrombosis. Am Heart J 1979; 97: 449-452. observed in serial srodies. Circulalian 1954; 9: 860-867. 62. Hogstedt C, SOderholm B, Bodin L 48-hour ambulatory electrocardiography 27. Powell SJ. Unexplained electrocardiograms in the African. BrHeartJ 1959; 21: in dynamite workers and controls. BrJ Industr Med 1980; 37: 299-306. 263-268. 63. Rabkin SW, Mathewson FAL, Tate RE. Chronobiology of cardiac sudden 28. Woods JD, Laurie W. The elecrrocardiogram of rhe South African Banru. dearh in men .JAMA 1980; 244: 1357-1358. Circulation 1959; 19: 251-256. 64. Waters DD, Szlachcic J, Theroux P, Dauwe F, Mizgala HP. Ergonovine 29. Fleishman SJ. Observations ofrhe electrocardiogram ofthe apparenrly healrhy testing (0 detect spontaneous remissions of variant angina during long-term African (M. D. rhesis). Johannesburg: Universiry ofrhe Wirwarersrand, 1962. trearment wirh calcium antagonist drugs. AmJ Cardial 1981; 47: 179-184. 30. Fleishman SJ. The normal electrocardiogram in the African. S AfrMedJ 1965; 65. Schamrorh L. The Elecrrocardiology of Coronary Artery Disease. Oxford: 39: 177-179. BlackwelI Scienrific Publicarions, 1981: 288. 31. Reiley MA, Su Jj, Guller B. Racial and sexual differences in rhe srandard 66. Bisteni A, Medrano GA, Sodi-Pallares D. Ventricular premarure bears in the electrocardiogram in Black vs Whire adolescents. Chest 1979; 75: 474-480. diagnosis of myocardial infarction. Br Heart J 1961; 23: 521-532.