BRIEFCLINICALOBSERVATIONS SYSTEMIC ARTERIAL VASOSPASTICSYNDROME: FAMILIAL OCCURRENCEWITH VARIANT ANGINA The observation that migraine headaches and Raynaud’s phenomenon are occasionally associated with variant angina has raised the possibility of a systemic arterial vasospastic (SAV) syndrome [l]. A familial basis for this syndrome, however, remains uncertain. We report a family in which three generations have developed manifestations of a SAV disorder. Case Reports. Mother. An apple orchard owner with a history of classical migraine headaches since childhood developed, at age 48, intermittent substernal chest pain at rest. Coronary angiography revealed only minor luminal irregularities, but diffuse coronary artery spasm and her typical symptoms developed after the intravenous administration of 0.15 mg of ergonovine maleate. Subsequently, with discontinuation of her P-blocker and an increased dose of isosorbide dinitrate, her symptoms abated. Daughter. An animal researcher with a history of Raynaud’s disease and classical migraine headaches since her early teen years developed intermittent chest pain and shortness of breath at age 37. During an exercise treadmill test, the patient developed l- to 2-mm ST elevation and hyperacute T waves in leads Va, Vq, and Vg (Figure l), consistent with coronary vasospasm [2]. Coronary angiography revealed normal arteries. Ergonovine was not administered because the patient required continuous intravenous nitroglycerin to control her symptoms. The patient finally achieved relief of her symptoms on a regimen of diltiazem, isosorbide dinitrate, and terazosin. Neither her brother nor sister has a history of chest pain, but her sister has had classical mi334
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1992
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EXERCISE
t 15 secl
IMMEDIATE
B EXERCISE
Figure 1. At rest (left panels), the electrocardiogram was normal. Within 15 seconds after beginning treadmill exercise (middle panels), the patient developed substernal chest discomfort with lateral lead ST-segment elevations and increased T-wave positivity. After exercise (right panels), the ST elevations then returned to normal.
graine hood.
headaches
since child-
Granddaughter. A 14-year-old high school student has a 6-year history of Raynaud’s disease. She currently has no other symptoms. None of her three other siblings have a history of Raynaud’s disease, chest pain, or migraine headaches. Comments. There is controversy about whether a hereditary form of variant angina exists [3-61. Yoshino and colleagues [4] reported two brothers with left anterior descending coronary arterial spasm, demonstrated with the use of ergonovine maleate during cardiac catheterization. Madias and O’Connor [5] also reported two brothers with variant angina, diagnosed by typical chest pain, transient ST elevation, insignificant fixed coronary artery disease, and response to nitroglycerin. The possibility of a genetic susceptibility is further supported by one study demonstrating a low frequency of HLADQw3 in patients with variant .of Medicine
Volume
92
angina as compared with patients with normal and atherosclerotic arteries [7]. In 1981, Miller and colleagues [l] reported the association of migraine headaches and Raynaud’s phenomenon in patients with variant angina. The clinical entity of systemic arterial vasospasm has also been previously reported within a family. Fournier and associates [6] reported two siblings with a familial history of migraine and coronary artery spasm. We extend these previous observations by reporting a family in which a mother, daughter, and granddaughter have manifestations of a SAV syndrome, raising the possibility of a genetic predisposition. The basis of the vasospastic diathesis in these patients remains poorly defined, although a role for altered ol-adrenergic tone is suggested. The familial association of this syndrome, nevertheless, may be more common than previously recognized, and a careful family history should be
BRIEF CLINICAL
part of the evaluation of all patients who present with variant angina. HARLAN M. KRUMHOLZ, M.D. ARY L. GOLDBERGER,M.D. Beth Israel Hospital Boston, Massachusetts 1. Miller D, Waters DD. Warnica W. Szlachcic J, Kreef J, Theroux P. Is variant angina the coronary manifestation of a generalized vasospastic disorder? N Engl J Med 1981; 304: 763-6. 2. Specchia G, de Servi F. Falcone C. et al. Significance of exercise-induced S-T segment elevation in patients without myocardial infarction. Circulation 1981; 63: 46-53. 3. Mauritson D, Peshock R, Winniford M, Stern L, Johnson S, Hillis L. Prinzmetal’s variant angina: is it transmitted genetically? Am Heart J 1983; 105: 1049. 4. Yoshino F. Sakuma N, Unoki T, et al. Variant angina in two brothers with left anterior descending coronary arterial spasm. Am J Cardiol 1989; 63: 379-80. 5. Madias J, O’Connor W. Variant angina in siblings with mild coronary artery disease. Am J Cardiol 1984; 53: 956-7. 6. Fournier J, Fernandez-Cortacero J, Granado C, Gascon D. Familial migraine and coronary artery spasm in two siblings. Clin Cardiol 1986; 9: 121-5. 7. Numano F. Nomura S, Yajima M, et al. Human leukocyte antigen in variant angina. Int J Cardiol 1987; 14: 47-53. Submitted
April 19, 1991, and accepted in revised form June 19, 1991
ACKNOWLEDGMENT: This work was supported in part by a grant from the G. Harold and Leila Y. Mathers Charitable Foundation and by the National Heart, Lung, and Blood Institute Grant ROl Hl42172 and Grant HL-07374. We thank Patricia Daly, M.D., and Lewis Landsberg, M.D., who participated in the patient’s care.
HIGH-TECHARREST The prognosis for the individual who sustains a cardiac arrest outside the hospital and is not resuscitated in the field remains dismal [1,2]. Despite major recent advances in our understanding of the pathophysiology of cardiac arrest, most physicians still approach cardiac arrests the same way they did in the 1970s: compressions, ventilation, and blind drug administration until the patient has remained pulseless for an extended time. Two new devices, disposable qualitative endtidal carbon dioxide (ETCOs) detectors and portable real-time ul-
trasound equipment, now allow physicians to make more rational decisions about the underlying etiology and prognosis in individuals who have a cardiac arrest. A 42-year-old man recovering from a thrombotic stroke had 6 weeks earlier developed sudden dyspnea and pleuritic chest pain. On arrival at the emergency department, he was tachypneic (78 breaths/minute) with tachycardia (126 beats/minute) and a blood pressure of 140/120 mm Hg. Hemoglobin saturation was 81% despite assisted ventilation with 100% oxygen. Orotracheal intubation was emergently performed. The qualitative ETCOa detector revealed the presence of CO2 on expiration. Streptokinase was administered but the patient became progressively hypoxic, ultimately resulting in ventricular fibrillation. After immediate defibrillation, an organized rhythm without pulses was noted at rates between 50 and 140/minute. During this period of electromechanical dissociation (EMD), the ETC02 detector indicated the absence of expired CO2 despite confirmation of correct endotracheal tube position by direct laryngoscopy. Bedside ultrasonography immediately performed in the emergency department confirmed the absence of any ventricular wall motion and the absence of pericardial tamponade. Resuscitation was terminated 16 minutes after initiation of thrombolysis. Disposable qualitative ETCOs detectors, which are small and inexpensive (Fenem Co., New York, NY), have been used mainly to document correct placement of an endotracheal tube. Detection of expired CO2 confirms that the tube is in communication with the pulmonary tree where COz is eliminated, thereby confirming intratracheal placement [3,4]. The device is connected between the adaptor on the endotracheal tube and the ventilation March
1992
The American
OBSERVATIONS
port of the manual ventilating bag. The COz-sensitive paper of the detector remains purple if less than 0.5% CO2 is detected and turns bright yellow on expiration if greater than 2.0% CO2 is expired (Figure 1). Detection of ETCOs is also dependent on the peripheral production of CO2 and its delivery to the lungs. After endotracheal tube insertion, failure to detect ETCOz implies: (1) incorrect tube placement in the esophagus, (2) the development of such profound circulatory impairment that pulmonary CO2 delivery has ceased, or (3) some form of interference with CO2 elimination (e.g., massive pulmonary embolism) [3,5]. In our patient, in whom correct tube placement was confirmed, the absence of ETCOz implied that massive pulmonary embolism and/or profound circulatory impairment was present. Such profound circulatory impairment in the setting of EMD is an indication of futility of further resuscitation efforts [5]. If return of ETCOs detection had occurred, this would have implied return of circulation or possibly successful thrombolysis of a massive pulmonary embolus. Small portable ultrasound machines are now available (weight 2.5 kg) (Scan-Mate Ultrasound Scanner, Damon Corp., Needham Heights, MA) and have sufficient scan quality to evaluate the presence of cardiac activity, the presence of pericardial effusion, and even the diameter of the abdominal aorta (all visible from a four-chamber subxiphoid approach). The subxiphoid approach can be rapidly and unobtrusively performed even while cardiopulmonary resuscitation is underway (Figure 2). In the setting of EMD, documenting the .presence or absence of pericardial fluid may guide treatment, and the absence of any myocardial contractility strongly implies fuJournal
of Medicine
Volume
92
335
March
1992
The American
Journal
BASELINE
(STANDING)
EXERCISE
t 15 secl
IMMEDIATE
B EXERCISE
Figure 1. At rest (left panels), the electrocardiogram was normal. Within 15 seconds after beginning treadmill exercise (middle panels), the patient developed substernal chest discomfort with lateral lead ST-segment elevations and increased T-wave positivity. After exercise (right panels), the ST elevations then returned to normal.
graine hood.
headaches
since child-
Granddaughter. A 14-year-old high school student has a 6-year history of Raynaud’s disease. She currently has no other symptoms. None of her three other siblings have a history of Raynaud’s disease, chest pain, or migraine headaches. Comments. There is controversy about whether a hereditary form of variant angina exists [3-61. Yoshino and colleagues [4] reported two brothers with left anterior descending coronary arterial spasm, demonstrated with the use of ergonovine maleate during cardiac catheterization. Madias and O’Connor [5] also reported two brothers with variant angina, diagnosed by typical chest pain, transient ST elevation, insignificant fixed coronary artery disease, and response to nitroglycerin. The possibility of a genetic susceptibility is further supported by one study demonstrating a low frequency of HLADQw3 in patients with variant .of Medicine
Volume
92
angina as compared with patients with normal and atherosclerotic arteries [7]. In 1981, Miller and colleagues [l] reported the association of migraine headaches and Raynaud’s phenomenon in patients with variant angina. The clinical entity of systemic arterial vasospasm has also been previously reported within a family. Fournier and associates [6] reported two siblings with a familial history of migraine and coronary artery spasm. We extend these previous observations by reporting a family in which a mother, daughter, and granddaughter have manifestations of a SAV syndrome, raising the possibility of a genetic predisposition. The basis of the vasospastic diathesis in these patients remains poorly defined, although a role for altered ol-adrenergic tone is suggested. The familial association of this syndrome, nevertheless, may be more common than previously recognized, and a careful family history should be
BRIEF CLINICAL
part of the evaluation of all patients who present with variant angina. HARLAN M. KRUMHOLZ, M.D. ARY L. GOLDBERGER,M.D. Beth Israel Hospital Boston, Massachusetts 1. Miller D, Waters DD. Warnica W. Szlachcic J, Kreef J, Theroux P. Is variant angina the coronary manifestation of a generalized vasospastic disorder? N Engl J Med 1981; 304: 763-6. 2. Specchia G, de Servi F. Falcone C. et al. Significance of exercise-induced S-T segment elevation in patients without myocardial infarction. Circulation 1981; 63: 46-53. 3. Mauritson D, Peshock R, Winniford M, Stern L, Johnson S, Hillis L. Prinzmetal’s variant angina: is it transmitted genetically? Am Heart J 1983; 105: 1049. 4. Yoshino F. Sakuma N, Unoki T, et al. Variant angina in two brothers with left anterior descending coronary arterial spasm. Am J Cardiol 1989; 63: 379-80. 5. Madias J, O’Connor W. Variant angina in siblings with mild coronary artery disease. Am J Cardiol 1984; 53: 956-7. 6. Fournier J, Fernandez-Cortacero J, Granado C, Gascon D. Familial migraine and coronary artery spasm in two siblings. Clin Cardiol 1986; 9: 121-5. 7. Numano F. Nomura S, Yajima M, et al. Human leukocyte antigen in variant angina. Int J Cardiol 1987; 14: 47-53. Submitted
April 19, 1991, and accepted in revised form June 19, 1991
ACKNOWLEDGMENT: This work was supported in part by a grant from the G. Harold and Leila Y. Mathers Charitable Foundation and by the National Heart, Lung, and Blood Institute Grant ROl Hl42172 and Grant HL-07374. We thank Patricia Daly, M.D., and Lewis Landsberg, M.D., who participated in the patient’s care.
HIGH-TECHARREST The prognosis for the individual who sustains a cardiac arrest outside the hospital and is not resuscitated in the field remains dismal [1,2]. Despite major recent advances in our understanding of the pathophysiology of cardiac arrest, most physicians still approach cardiac arrests the same way they did in the 1970s: compressions, ventilation, and blind drug administration until the patient has remained pulseless for an extended time. Two new devices, disposable qualitative endtidal carbon dioxide (ETCOs) detectors and portable real-time ul-
trasound equipment, now allow physicians to make more rational decisions about the underlying etiology and prognosis in individuals who have a cardiac arrest. A 42-year-old man recovering from a thrombotic stroke had 6 weeks earlier developed sudden dyspnea and pleuritic chest pain. On arrival at the emergency department, he was tachypneic (78 breaths/minute) with tachycardia (126 beats/minute) and a blood pressure of 140/120 mm Hg. Hemoglobin saturation was 81% despite assisted ventilation with 100% oxygen. Orotracheal intubation was emergently performed. The qualitative ETCOa detector revealed the presence of CO2 on expiration. Streptokinase was administered but the patient became progressively hypoxic, ultimately resulting in ventricular fibrillation. After immediate defibrillation, an organized rhythm without pulses was noted at rates between 50 and 140/minute. During this period of electromechanical dissociation (EMD), the ETC02 detector indicated the absence of expired CO2 despite confirmation of correct endotracheal tube position by direct laryngoscopy. Bedside ultrasonography immediately performed in the emergency department confirmed the absence of any ventricular wall motion and the absence of pericardial tamponade. Resuscitation was terminated 16 minutes after initiation of thrombolysis. Disposable qualitative ETCOs detectors, which are small and inexpensive (Fenem Co., New York, NY), have been used mainly to document correct placement of an endotracheal tube. Detection of expired CO2 confirms that the tube is in communication with the pulmonary tree where COz is eliminated, thereby confirming intratracheal placement [3,4]. The device is connected between the adaptor on the endotracheal tube and the ventilation March
1992
The American
OBSERVATIONS
port of the manual ventilating bag. The COz-sensitive paper of the detector remains purple if less than 0.5% CO2 is detected and turns bright yellow on expiration if greater than 2.0% CO2 is expired (Figure 1). Detection of ETCOs is also dependent on the peripheral production of CO2 and its delivery to the lungs. After endotracheal tube insertion, failure to detect ETCOz implies: (1) incorrect tube placement in the esophagus, (2) the development of such profound circulatory impairment that pulmonary CO2 delivery has ceased, or (3) some form of interference with CO2 elimination (e.g., massive pulmonary embolism) [3,5]. In our patient, in whom correct tube placement was confirmed, the absence of ETCOz implied that massive pulmonary embolism and/or profound circulatory impairment was present. Such profound circulatory impairment in the setting of EMD is an indication of futility of further resuscitation efforts [5]. If return of ETCOs detection had occurred, this would have implied return of circulation or possibly successful thrombolysis of a massive pulmonary embolus. Small portable ultrasound machines are now available (weight 2.5 kg) (Scan-Mate Ultrasound Scanner, Damon Corp., Needham Heights, MA) and have sufficient scan quality to evaluate the presence of cardiac activity, the presence of pericardial effusion, and even the diameter of the abdominal aorta (all visible from a four-chamber subxiphoid approach). The subxiphoid approach can be rapidly and unobtrusively performed even while cardiopulmonary resuscitation is underway (Figure 2). In the setting of EMD, documenting the .presence or absence of pericardial fluid may guide treatment, and the absence of any myocardial contractility strongly implies fuJournal
of Medicine
Volume
92
335
