Vasodepressor Syncope Due to Subclinical Myocardial Ischemia

Vasodepressor Syncope. Introduction: Vasodepressor syncope is a common cause of syncope, but the initiating event that triggers the vasodepressor response remains incompletely understood. Although ischemia due to acute right coronary occlusion may precipitate hypotension and bradycardia through the Bezold-Jarisch reflex, an ischemic precipitant for the common vasodepressor faint has not been previously identified. In the present study, we present evidence for a causal relationship between myocardial ischemia and vasodepressor syncope. Methods and Results: Two patients referred for evaluation of syncope underwent upright tilt table testing with either ST segment monitoring, sestamibi scintigraphy and echocardiography during the tilt test, or coronary angiography. Both patients had positive tilt table tests during the control study. Patient 1 was documented to have reproducible ischemic ECG changes during atypical chest pressure induced by upright tilt, despite a normal coronary angiogram with ergonovine provocation. Subsequent tilt testing with simultaneous sestamibi perfusion imaging and echocardiography revealed reversible anterolateral hypoperfusion corresponding with anterolateral hypokinesis during upright tilt that preceded syncope. Ischemic ECG changes during incremental rapid atrial pacing further suggested ischemia on the basis of microvascular disease. Follow-up tilt testing on verapamil was negative. Patient 2 developed ischemic ECG changes during the recovery phase of an exercise stress test, which was followed by a vasodepressor response and frank syncope. Coronary angiography revealed a 90% distal right coronary artery stenosis that was successfully dilated, after which follow-up tilt table testing off all other medication was negative. Conclusions: These two cases illustrate a previously unrecognized causality between myocardial ischemia and clinical vasodepressor syncope, and demonstrate that subtle manifestations of myocardial ischemia, associated with either atypical angina or silent ischemia, can provoke syncope.     

Idiopathic hypertrophic subaortic stenosis presenting as cough syncope.

In a patient with idiopathic hypertrophic subaortic stenosis, syncope developed as a result of a sustained decrease in aortic pressure induced by severe cough paroxysms. Treatment with propranolol was effective in abolishing the syncopal episodes, by reducing the post-tussive gradient and facilitating a more rapid return to normal of aortic pressure. Post-tussive syncope in IHSS may result from both an unusually strong cough paroxysm and augmented left ventricular outflow obstruction consequent to reflex sympathetic stimulation.     

Torsade de pointes

The evaluation of syncope in severe aortic stenosis usually requires intense work-up. Mechanical obstruction should not always be implicated as the underlying cause of syncope. Syncope at rest may be rarely associated with ventricular arrhythmias. We present a patient with severe aortic stenosis who experienced syncopal events due to torsade de pointes.     

The antiarrhythmic effect and clinical consequences of ischemic preconditioning

Potentially hazardous short ischemic episodes increase the tolerance of myocardium to ischemia paradoxically. This condition decreases the infarct area markedly caused by a longer duration of coronary occlusion. This phenomenon is known as 'ischemic preconditioning' and its powerful cardioprotective effect has been shown in experimental and clinical studies. Ischemic preconditioning decreases cardiac mortality markedly by preventing the development of left ventricular dysfunction and ventricular and supraventricular arrhythmias after acute myocardial infarction. Ischemia-induced opening of ATP-sensitive potassium channels and synthesis of stress proteins via activation of adenosine, bradykinin and prostaglandin receptors seem to be the possible mechanisms. By understanding the underlying mechanisms of ischemic preconditioning, it may be possible to develop new pharmacologic agents that cause ischemic preconditioning with antiischemic and antiarrhythmic properties without causing myocardial ischemia.     

A standardized conventional evaluation of the mechanism of syncope in patients with bundle branch block.

BACKGROUND: The finding of bundle branch block in patients with syncope suggests that paroxysmal AV block may be the cause of syncope, even though its prevalence is unknown. METHODS: We evaluated 55 consecutive patients with syncope and bundle branch block (mean age 75 +/- 8 years; median of two syncopal episodes per patient) referred to three Syncope Units. The hierarchy and appropriateness of diagnostic tests and the definitions of the final diagnoses followed standardized predefined criteria. RESULTS: Cardiac syncope was diagnosed in 25 patients (45%): AV block in 20, sick sinus syndrome in 2, sustained ventricular tachycardia in 1, aortic stenosis in 2. Neurally mediated syncope was diagnosed in 22 (40%): carotid sinus syndrome in 5, tilt-induced syncope in 15, adenosine-sensitive syncope in 2. Syncope remained unexplained in 8 (15%). CONCLUSIONS: Less than half of the patients with bundle branch block have a final diagnosis of cardiac syncope; in these patients, paroxysmal AV block is the most frequent but not the only mechanism supposed.     

Left ventricular apical aneurysm as a consequence of diffuse type congenital nonfamilial supravalvular aortic stenosis in a 30-year-old female

Congenital nonfamilial supravalvular aortic stenosis (SVAS) is relatively rare, its diffuse type being the least common. We present a 30-year-old woman with diffuse SVAS complicated with left ventricular apical aneurysm. We believe that subtle left ventricular myocardial ischemia or infarction and long-lasting severe pressure overload to the apical chamber caused LV apical aneurysm in our case. Acquired LV apical aneurysm secondary to supravalvular aortic stenosis, in the absence of atherosclerotic coronary artery disease and hypertrophic obstructive cardiomyopathy, has not been described before.     

Frequent occurrence of postbreakfast syncope due to carotid sinus syndrome after surgery for hypopharyngeal cancer: A case report

Rationale:Syncope often occurs in patients with advanced head and neck cancers due to the stimulation of the autonomic nervous system by the tumor. Here, we describe a case of frequent syncopal episodes after laryngopharyngectomy for hypopharyngeal cancer. As all syncopal episodes were observed during the forenoon, we also evaluated the heart rate variability using ambulatory electrocardiography to determine why the syncopal episodes occurred during a specified period of the day.Patient concerns:A 73-year-old Japanese man who underwent laryngopharyngectomy for recurrent hypopharyngeal cancer started experiencing frequent episodes of loss of consciousness that occurred during the same time period (10:00–12:00). He had never experienced syncopal episodes before the operation. From 23 to 41 days postoperatively, he experienced 9 syncopal episodes that occurred regardless of his posture.Diagnoses:Pharyngo-esophagoscopy revealed an anastomotic stricture between the free jejunum graft and the upper esophagus. Swallowing videofluoroscopy confirmed the dilatation of the jejunal autograft and a foreign body stuck on the oral side of the anastomosis. Contrast-enhanced computed tomography revealed that the carotid artery was slightly compressed by the edematous free jejunum. The patient was diagnosed with carotid sinus syndrome (CSS) as the free jejunum was dilated when consuming breakfast, which may have caused carotid sinus hypersensitivity and induced a medullary reflex.Interventions:Administration of disopyramide was effective in preventing syncope. Heart rate variability analysis using ambulatory electrocardiography showed that parasympathetic dominancy shifted to sympathetic dominancy during 10:00 to 12:00. The significant time regularity of the syncopal episodes may have been affected by modified diurnal variation in autonomic tone activity.Outcomes:After the surgical release and re-anastomosis of the pharyngoesophageal stenosis via an open-neck approach, no recurrent episodes of syncope were reported.Lessons:We reported a case of frequent syncopal episodes limited to the forenoon due to CSS after surgery for hypopharyngeal carcinoma. The patient was treated with anticholinergics followed by the release and re-anastomosis of the pharyngoesophageal stenosis. When syncope occurs after surgery for head and neck lesions, CSS due to postoperative structural changes should be considered as a differential diagnosis of syncope.     

The DDDR closed loop stimulation for the prevention of vasovagal syncope: results from the INVASY prospective feasibility registry.

BACKGROUND: The contraction dynamics of the ventricular myocardium are affected before and during vasovagal fainting suggesting that the Closed Loop Stimulation (CLS) pacemaker could be useful for the treatment of these patients. CLS is a new concept of heart rate modulation in cardiac pacing. The pacemaker INOS(2) CLS (Biotronik, Germany) derives its information for heart rate optimization from myocardial contraction dynamics, by measuring right ventricular intracardiac impedance. The pacemaker becomes an integral part of the circulatory regulation and, therefore, reacts appropriately to different cardiovascular demands. METHODS: In a prospective registry, 34 patients with a history of recurrent vasovagal syncopal events were implanted with INOS(2) DDDR CLS pacemakers. The aim of the study was to evaluate both long term clinical outcome, including the first recurrence of syncope, with DDDR-CLS pacing and acute precipitation of vasovagal fainting with DDDR-CLS mode compared with DDD during head up tilt testing. RESULTS: During a follow up period of 12-50 months, 30 patients experienced no further syncopal events in daily life; 1 patient had no syncope but night palpitations, which were eliminated by pacemaker reprogramming; 2 patients had presyncopal episodes but not syncopes; 3 syncopal recurrences occurred in one patient in chronic atrial fibrillation, possibly not an ideal candidate for implantation. CONCLUSIONS: Further studies for detailed understanding of the preventive mechanism of DDDR-CLS pacing in vasovagal syncope are warranted. A randomized multicentre prospective new study (INotropy controlled pacing in VAsovagal SYncope: INVASY) is now in progress to confirm the beneficial effect of DDDR-CLS pacing in a larger group of patients with recurrent vasovagal syncope.     

Myocardial ischemia in aortic stenosis

In hypertensive heart disease without coronary artery disease it has been proposed that the presence of ischemia of myocardial tissue is due to an inadequate increment of myocardial mass or to an increase in coronary artery resistance. In this study, 18 patients with aortic stenosis, without coronary artery disease were included. It was demonstrated that the existence of myocardial ischemic, induced by atrial pacing and manifested by ST segment depression, had direct association to increased myocardial mass, and it had no relation with left ventricular telediastolic pressure nor with transvalvular gradient. The results support the hypothesis that an inappropriate increment of the myocardial mass is the main cause of myocardial ischemia in these type of cardiopathies.     

Neural Control Mechanisms and Vasovagal Syncope

Vasovagal Syncope, Patients with recurrent unexplained syncope may have cardioinhibitory and vasodepressor responses provokable with head-up tilt with or without exogenousbeta-adrenergic stimulation. Although these responses are believed to be neurally mediated, the neural mechanisms involved are pourly understood. Numerous studies have documentedperipheral vasodilation, hypotension, and bradycardia at the time of syncope and several casereports have shown sudden withdrawal of vasoconstrictor sympathetic neural outflow to skeletal muscle in human subjects. In cats and rats, a similar response can be provoked with hemorrhage and is prevented by interruption of cardiac vagal C-fiber afferents. In dogs, however, section of these fibers does not prevent the development of a vasodepressor response. Theprovocation of vasodepressor syncope during nitroprusside infusion in a heart transplantrecipient with presumed ventricular denervation also suggests that cardiac afferent nerves maynot be required for the development of vasodepressor responses in humans. Other potentialmechanisms include release of endogenous opioids or nitric oxide that may inhibit sympatheticnerve firing, and primary central nervous system activation (as in partial seizures) that triggerscardioinhibitory and vasodepressor responses. This article reviews our current understandingof the mechanisms involved in the development of neurally mediated syncope.     

Improved myocardial ischemic response and enhanced collateral circulation with long repetitive coronary occlusion during angioplasty: a prospective study.

OBJECTIVES. The goal of the study was to evaluate the progressive increase in ischemic threshold with multiple sequential transient coronary occlusions and to assess the role of the collateral circulation in adaptation to ischemia. BACKGROUND. It has been observed that the duration of balloon inflations during coronary angioplasty can be gradually prolonged during subsequent dilations with a reduction in patient symptoms and diminished ischemic electrocardiographic (ECG) changes. Although the mechanism has not been fully explained, recruitment of coronary collateral circulation induced by repeated coronary occlusion has been reported. The stimuli for recruitment and the natural history of coronary collateral circulation are not understood. METHODS. Seventeen patients with isolated stenosis of the left anterior descending coronary artery and a normal left ventricle were enrolled. Angioplasty consisted of five successive prolonged inflations. Sequential changes in clinical, intracoronary ECG and left ventricular indexes of myocardial ischemia were examined. Coronary collateral channels were evaluated during balloon inflations by ipsilateral and contralateral injections of contrast medium and hemodynamically by occlusion pressure. RESULTS. An improved tolerance to myocardial ischemia with repetitive coronary occlusions was demonstrated by a significant reduction of angina, ST segment deviation, left ventricular filling pressure and less impairment of ejection fraction. Left ventricular wall motion abnormalities remained unchanged. Collateral angiographic grade did not change in 7 patients and increased in 10. CONCLUSIONS. This study confirms a progressive adaptation of myocardial ischemia to repetitive coronary occlusions and supports the concept that sequential episodes of myocardial ischemia are a stimulating factor for the recruitment of collateral channels in humans. These results also suggest that enhancement of recruitable collateral circulation might be an underlying mechanism of myocardial ischemic preconditioning.     

Exertional syncope in a patient with aortic stenosis and right coronary artery disease

A female with advanced aortic valvular stenosis and moderateright coronary artery disease experienced an exertional syncopeduring 24-h ambulatory electrocardiographic monitoring. A progressivebradycardia with 90-s sinus node arrest (cardio-inhibitory response)and premonitory angina pectoris with significant ST segmentchanges were demonstrated. Our report supports the concept of a neurocardiogenie (vasovagal)mechanism of exertional syncope in patients with aortic stenosis.The predominant left ventricular inferior-wall myocardial iscliaemiain our patient might be an additional stimulus to left ventricularmechanoreceptors, resulting in a profound cardio-inhibitoryresponse.     

Sinus and A-V nodal dysfunction following myocardial infarction.

A patient in whom syncopal episodes occurred following an inferior myocardial infarction is described. Electrocardiographic monitoring revealed periods of profound sinus bradycardia and AV block during syncope. In addition, transient spontaneous prolongations of the PR interval due to AV nodal delay and episodes of atrial fibrillation also occurred. Sinus node recovery time following atrial overdrive was within normal limits. Symptoms disappeared following the insertion of a permanent, demand pacemaker. The onset of symptoms following myocardial infarction suggests that dysfunction of the sino-atrial and AV nodes may have been the result of ischemic damage during the infarction.     

Clinical characteristics and possible role of coronary artery spasm in syncope and/or aborted sudden death

We investigated the clinical and pathophysiologic characteristics in patients with vasospastic angina who developed syncope and/or experienced aborted sudden death (SD). Vasospastic angina was diagnosed using the methylergonovine test. Syncope was found in 32 (10.4%) patients among 309 who were admitted to our institute in a one-year period. The most frequent cause of syncope was ventricular tachycardia which was found in 10 (31.2%) of the 32 patients. The next important cause of syncope was vasospastic angina which was found in 7 patients (21.8%). Among the 7 patients with vasospastic angina who experienced one or more syncopal episodes, there were 3 patients with aborted SD, 3 with syncope and one with shock. Cardiovascular collapse was observed in 4. Interior wall ischemia was found in 5 and anterior wall ischemia in 2 during the methylergonovine test. None of the 7 patients had significant coronary stenosis. Two patients had no prodromal symptom such as chest pain. Our results suggest that coronary artery spasm may be one of the most frequent cardiovascular diseases that causes syncope which is not always accompanied by a prodromal symptom. Therefore, coronary spasm should be distinguished in patients with unexplained syncope or aborted SD.     

Syncopal monomorphic ventricular tachycardia with pleomorphism, sensitive to antitachycardia pacing in a patient with Brugada syndrome.

Polymorphic ventricular tachycardia and ventricular fibrillation are the most common arrhythmias in Brugada syndrome, causing syncope or sudden death. Sustained monomorphic ventricular tachycardias are rare in this context. We report the case of a 41-year-old man with repetitive syncopal episodes and an ajmaline-induced characteristic Brugada ECG pattern, in whom episodes of monomorphic ventricular tachycardia with pleomorphism and response to ventricular pacing were documented.     

Significance of spasm in the pathogenesis of ischemic heart disease.

The role of coronary arterial vasospasm in the pathogenesis of ischemic heart disease is reviewed on the basis of investigations carried out in our laboratory. Patients were selected because they had angina either at rest or both at rest and during exercise. With continuous hemodynamic and electrocardiographic monitoring of these patients, as well as thallium-201 scintigraphy and coronary arteriography during ischemic episodes, we were able to demonstrate a vasospastic origin for the attacks. During anginal episodes, electrocardiographic changes were variable, with S-T segment elevation, S-T segment depression, a rise in T wave potential and pseudonormalization of inverted T waves corresponding to various distributions of myocardial ischemia in different patients and even in the same patient at different times. Increases in hemodynamic variables that control myocardial oxygen consumption never preceded the onset of ischemic episodes, which challenges the theory that the limitation of a possible increase in flow caused by critical organic stenosis is the only cause of myocardial ischemia. In some patients in whom myocardial infarction developed, the lesion was always found in the same area in which the vasospastic phenomena had been seen angiographically. Vasospasm led to serious arrhythmias in some patients. We therefore believe that independent of atherosclerosis or superimposed on it, vasospasm plays an important role in producing myocardial ischemia—angina, myocardial infarction and possibly sudden death. Elucidation of its mechanisms will lead to more appropriate therapy.     

Effects of afterload elevation on the ischemic myocardium in isolated, paced canine heart with partial coronary stenosis

The effect of afterload elevation on the ischemic myocardium was examined in an isolated, paced canine heart with a partial coronary stenosis. The coronary blood flow of the left circumflex coronary artery was reduced to approximately one-third of the values before stenosis. The left circumflex coronary stenosis produced a decrease in global ventricular function, a decrease in systolic shortening and deviation of the ST-segment of the epicardial electrocardiogram and an increase in myocardial carbon dioxide (CO2) tension of the ischemic region. Then, afterload elevation with constant preload decreased the myocardial CO2 tension and improved the ST-segment deviation of the ischemic myocardium. Mechanical function, estimated by the relation between mean aortic pressure and systolic shortening, also improved with elevation of mean aortic pressure. In contrast, afterload elevation combined with preload elevation did not improve ischemic injury, as estimated by myocardial CO2 tension, and did not improve ST-segment deviation or mechanical function despite an increase in left circumflex coronary flow. These results suggest that the elevation of afterload pressure under constant preload improves ischemia produced by a partial coronary stenosis due to increased coronary blood supply; however, the preload elevation counterbalances the beneficial effects of afterload elevation.     

"Warm-up" phenomenon detected by electrocardiographic ambulatory monitoring in adult and older patients.

OBJECTIVE: Inducing tolerance to myocardial ischemia by repeated brief episodes of ischemia has been called "ischemic preconditioning." "Warm-up" phenomenon refers to patients with coronary heart disease improving performance after a first exertion and may represent a clinical counterpart to ischemic preconditioning. The goal of this study was to assess whether the severity of myocardial ischemia would be attenuated by two repeated walking-induced ischemic episodes in adult and older patients. SUBJECTS: Thirty-eight adults (51 +/- 5 years) and 39 older patients (76 +/- 4 years) with stable angina and angiographic evidence of coronary stenosis. MEASUREMENTS: Holter monitoring was performed in adult and older patients walking on two consecutive occasions, with a 5-minute rest between walks, a distance known to have previously caused myocardial ischemia. RESULTS: Computer-assisted analysis recorded by ambulatory Holter monitoring revealed that the mean maximal ST-segment depression (P < .001) and ischemia duration decreased (P < .001), whereas the ischemic threshold increased (P < .001), from the first to the second walk in the adult but not in the older group. CONCLUSIONS: Myocardial ischemia is attenuated and ischemic threshold is increased between two brief ischemic episodes in adult but not in older patients. These results indicate that the "warm-up" phenomenon, involved in increasing myocardial ischemic tolerance, is absent in the aging heart.     

Benefits of fludrocortisone in the treatment of symptomatic vasodepressor carotid sinus syndrome.

OBJECTIVE--To assess treatment with fludrocortisone in vasodepressor carotid sinus syndrome. PATIENTS AND METHODS--Eleven patients, mean (SD) age 83 (5) years, with daily dizzy episodes and a median of five (range two to 20) syncopal episodes over a median of one year were studied. All had vasodepressor carotid sinus syndrome (> 50 mm Hg fall in systolic blood pressure during carotid sinus massage independent of bradycardia). Carotid sinus massage was carried out while the patient was supine and upright (tilt table) before and after 600 micrograms intravenous atropine. Phasic heart rate and blood pressure recordings were monitored throughout. The study was repeated after 100 micrograms of fludrocortisone daily by mouth for two weeks. Patients continued to take fludrocortisone for a six month follow up period. RESULTS--Baseline systolic blood pressure was (mean (SD)) 169 (31) mm Hg and the RR interval was 770 (150) ms. After carotid sinus massage, systolic blood pressure fell to 113 (27) mm Hg (p < 0.01) and RR was 1060 (210) ms (NS). The vasodepressor response was 56 (12) mm Hg. Baseline systolic blood pressure after two weeks of fludrocortisone treatment was 171 (37) mm Hg (NS); but the fall in systolic blood pressure during carotid sinus massage was significantly reduced (32 (14) mm Hg; p < 0.01). At six months follow up, two patients complained of intermittent dizziness and no patients had syncope. CONCLUSION--Fludrocortisone effectively reduces the vasodepressor response and relieves the symptoms of vasodepressor carotid sinus syndrome.     

The effect of regional myocardial ischemia on Doppler echocardiographic indexes of left ventricular performance: influence of heart rate, aortic blood pressure, and the size of the ischemic zone

Doppler echocardiographic indexes of ascending aortic blood flow velocity have been found to be an effective method of assessing changes in left ventricular performance induced by myocardial ischemia in both experimental animal preparations and in patients. In eight opened-chest anesthetized dogs, we investigated the influence of heart rate, aortic blood pressure, and size of the ischemic zone on Doppler indexes during regional myocardial ischemia. With control of mean aortic blood pressure and heart rate, transient coronary artery occlusion resulted in a statistically significant decline in peak velocity and mean velocity when as little as 24% of left ventricular myocardium was rendered ischemic. However, when heart rate and mean aortic blood pressure were not controlled, significant declines in peak velocity and mean velocity occurred only with simultaneous two-vessel occlusions involving greater than 47% of left ventricular myocardium. Although transient coronary artery occlusions generally produced no significant change in heart rate in the absence of atrial pacing, significant declines in aortic blood pressure were observed. We conclude that Doppler indexes of left ventricular performance obtained during myocardial ischemia are influenced not only by the extent of myocardium rendered ischemic, but also by changes in mean aortic blood pressure.