Mixed Carotid Sinus Syndrome Research Articles

Midodrine hydrochloride in the management of older adults with neurocardiogenic syncope and orthostatic hypotension: A prospective observational study

BackgroundMidodrine hydrochloride has been shown to be effective in the management of syncope in adults with reflex syncope, orthostatic hypotension and orthostatic intolerance syndromes; however, its use, tolerability and side effects have not been monitored specifically in the older old, particularly not over a prolonged period of time. ObjectivesWe aim to document changes in patients’ symptoms, drug dosages employed and adverse drug reactions to midodrine therapy in older adults with a diagnosis of neurocardiogenic syncope assessed and managed at a specialist falls and syncope outpatient unit. MethodsProspective observational study of 135 consecutive subjects with a mean age of 84 years started on midodrine after comprehensive geriatric assessment, structured falls evaluation, positive tilt table testing (TT) or a mixed/vasodepressor response to carotid sinus massage (CSM). ResultsNinety-seven individuals (71%) commenced on midodrine treatment and followed up for a mean of 2.7 years, reported either significant improvement or abolition of symptoms across all TT/CSM diagnosis. Forty-nine percent of individuals achieved sustained clinical improvement after an initial dosage of 2.5mg three times per day and only four patients required dosages above 7.5mg three times daily. One hundred and one individuals (75%) continued midodrine until the end of the monitoring period, and although 19 subjects developed adverse drug reactions, most were minor and only six resulted in drug withdrawal. ConclusionsMidodrine hydrochloride appears to be safe and well tolerated in older adults and should be considered, independent of age, in the management of patients with symptomatic orthostatic hypotension, vasovagal syncope and vasodepressor or mixed carotid sinus syndrome. This observation requires further confirmation by larger multicenter randomised control studies.

Carotid sinus syndrome is common in very elderly patients undergoing tilt table testing and carotid sinus massage because of syncope or unexplained falls

Although the incidence of falls and syncope increase with age, the underlying mechanisms are not fully understood, particularly in very old patients. We report diagnostic outcomes of tilt table and carotid sinus massage (TT/CSM) testing in a population of older old subjects (82% over 80 years of age) referred for TT/CSM from a falls clinic for assessment of syncope or unexplained falls. Prospective observational study between January 1, 2001 and January 1, 2005 involving 290 consecutive subjects undergoing TT/CSM testing according to European Society of Cardiology guidelines for the diagnosis and management of syncope. Combination of TT/CSM provided a positive result in 62% of subjects, and was significantly more likely to be positive in subjects over the age of 80 (68% vs 50%, p=0.001). Carotid sinus syndrome (CSS) was the most common diagnosis, and was significantly more common in subjects over 80 (48% vs 34%, p=0.022) particularly due to a higher incidence of mixed CSS (16% vs 7%, p=0.023). There was no significant difference in the diagnosis of subjects referred due to falls and those reporting syncope (p=0.93). No cardiovascular or neurological adverse events occurred. In our cohort of very elderly patients, the diagnostic accuracy of tilt testing and carotid sinus massage was high and adverse incidents absent when testing was indicated by a geriatrician experienced in the assessment of falls and syncope. We advocate the use of TT/CSM testing as part of a comprehensive falls/syncope assessment for the diagnostic evaluation of older patients presenting with unexplained falls and/or syncope in whom structured assessment has not identified a cause for their symptoms.

The role of pacemaker in hypersensitive carotid sinus syndrome

About 15% of patients with the hypersensitive carotid sinus syndrome (CSS) have no clinical improvement after permanent pacemaker implantation. We aimed to assess the outcome of patients with CSS treated with pacemaker and to determine predictors of symptoms' recurrence. A retrospective analysis of 138 patients in whom pacemaker was implanted for CSS was carried out from February 1990 to October 2008. Data were collected from clinical records. Mean age was 69 ± 10.7 years and 104 patients (75.4%) were men. Mean follow-up period was 4.9 ± 4.4 years. Twenty-one (15.2%) patients presented mixed CSS and 117 (84.8%) cardioinhibitory CSS. The head-up tilt test (HUTT) was performed in 93 patients (67.4%). After pacemaker implantation, 115 (83.3%) patients had no further symptoms, 8 (5.8%) presented minor symptoms and in 15 (10.9%), the symptoms remained unchanged. Among patients with symptoms' recurrence, 8 (38.1%) had mixed CSS and 15 (12.8%) cardioinhibitory CSS. Mixed CSS was the only independent predictor of symptoms' recurrence in total population {hazard ratio (HR) 2.84 [95% confidence intervals (CI) 1.20-6.71]; P = 0.017} and in patients who performed HUTT [HR 1.84 (95% CI 1.01-3.35); P = 0.045]. Although the HUTT result was not related to symptoms' recurrence, patients with mixed CSS were more likely to present a vasodepressor response (61.9 vs. 19.4%; P < 0.001) and a reproduction of spontaneous symptoms (28.6 vs. 2.8%; P = 0,001) on HUTT. Permanent pacemaker is an effective treatment for CSS. However, the recurrence of symptoms was two- to three-fold more frequent in patients with mixed CSS, probably due to the persistence of vasodepressor component.

MIDODRINE HYDROCHLORIDE IS SAFE AND EFFECTIVE IN OLDER PEOPLE WITH NEUROCARDIOGENIC SYNCOPE

To the Editor: Midodrine hydrochloride, an alpha 1-adrenergic receptor agonist that increases peripheral blood pressure by constricting arterial and venous beds, has been shown to be effective in the management of syncope in adults with orthostatic hypotension,1,2 vasovagal syncope,3–6 and vasodepressor carotid sinus syndrome,7 although its use, tolerability, and side effects have not been monitored specifically in older adults, particularly not over a prolonged period of time.8 Data are reported from a prospective registry of 135 consecutive elderly subjects (mean age 84) referred to a geriatric unit for assessment of syncope or unexplained falls from January 1, 2001, to January 1, 2005. All patients referred to the unit underwent investigation according to European Society of Cardiology guidelines.9 Patients who had a suspected diagnosis of neurally mediated syncope or had falls that remained unexplained and were severe or frequent underwent tilt table testing and carotid sinus massage maneuvers based upon a variation of a protocol established previously.10 Of 290 patients evaluated during the study period, 52 men and 83 women aged 64 to 97 who had a clinically significant tilt table test or carotid sinus massage and severe symptoms and remained symptomatic after standard treatments (e.g., patient education, physical counter-pressure maneuvers to abort imminent faints, advice on salt intake and hydration, avoidance of situational triggers, and standing training) were offered midodrine, initially at a dose of 2.5 mg three times a day. Dose was titrated up at clinic visits in increments of 2.5 mg, and patients were monitored for a median length of time of 2.7 years. Ninety-seven individuals (71%) reported cessation or significant reduction in their symptoms for all of the tilt table diagnoses (Figure 1), and 29% reported no benefit. Thirty-four subjects (25%) had stopped taking the drug by the end of follow-up: failure to maintain symptom control (n=14), inability to keep patient appointments (n=7), significant clinical deterioration unrelated to midodrine (n=7), and adverse drug reactions (n=6). Of the remaining 101 individuals taking midodrine until the end of follow-up, 49% received 2.5 mg three times per day, 30% required 5 mg three times daily, and 21% required higher dosages. Incidences of adverse drug reactions were assessed at each clinic visit, and although 19 patients reported drug-related side effects, only six ceased taking midodrine, whereas 13 continued treatment. Reasons for drug discontinuation were hypertension (n=3), lower urinary tract obstructive symptoms (n=1), palpitations (n=1), and nausea (n=1). Clinical improvement and tilt table and carotid sinus massage diagnoses. In conclusion, midodrine hydrochloride appears to be safe and well tolerated in older adults and should be considered in the management of patients with symptomatic orthostatic hypotension, vasovagal syncope, and vasodepressor or mixed carotid sinus syndrome independent of age after standard treatments have been tried. This observation requires further confirmation in randomized control studies. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: DP, AV, JS: concept and design, acquisition of subjects and data, analysis and interpretation of data, and preparation of manuscript. OA: acquisition of subjects, analysis and interpretation of data, and preparation of manuscript. EP: statistical design and analysis. QA: interpretation of data and preparation of manuscript. Sponsor's Role: No sponsor.

Randomized clinical trials of neurally mediated syncope.

Evidence for therapy of neurally mediated syncope is generally weak. Many drugs have been used for the treatment of vasovagal syncope (beta-blockers, disopyramide, scopolamine, clonidine, theophylline, fludrocortisone, ephedrine, dihydroergotamine, etilefrine, midodrine, clonidine, serotonin reuptake inhibitors, enalapril). In general, although the results have been satisfactory in uncontrolled trials or short-term controlled trials, the majority of long-term placebo-controlled prospective trials have not been able to show a benefit of the active drug over placebo. Only two well-designed double-blind placebo-controlled randomized trials have been performed-one for etilefrine and the other for atenolol-and both were unable to show a superiority of the active drug versus placebo. Four randomized clinical trials of pacing therapy-three positive and one negative-have been performed in patients affected by vasovagal syncope. The relationship between carotid sinus hypersensitivity and spontaneous, otherwise unexplained, syncope has been demonstrated. Cardiac pacing appears to be beneficial in carotid sinus syndrome; its efficacy has been demonstrated by two randomized controlled trials and confirmed by several pre-post comparative studies, one controlled trial, and one prospective observational study. There is evidence and general agreement that cardiac pacing is useful in patients with cardioinhibitory or mixed carotid sinus syndrome. Usefulness of the treatment is less well established and divergence of opinion exists with regard to cardiac pacing in patients with cardioinhibitory vasovagal syncope. The evidence fails to support the efficacy of beta-blocking drugs. As yet there are insufficient data to support the use of any other pharmacologic therapy for vasovagal syncope.

Contribution of a pacemaker bradycardia detection algorithm in the study of patients with carotid sinus syndrome.

While carotid sinus syndrome (CSS) is often suspected as a cause of syncope in the elderly, whether it represents an indication for cardiac pacing may remain uncertain. Bradycardia algorithms included in pacemakers are now able to establish a precise relationship between spontaneous asystole and occurrence of symptoms and strengthen the indication for permanent pacing. This study included seven men and three women (70.5 +/- 7.3 years of age) who, over an average period of 54.1 +/- 17 months, had suffered from syncope (12.6 episodes/patient) and presyncope (11.2 episodes/patient) attributed to pure cardioinhibition (2 patients) or mixed CSS (8 patients). Other sources of symptoms were excluded by thorough clinical evaluations, including Holter monitoring, echocardiography, and electrophysiological testing. All patients received a CHORUS 6234 pacemaker, the memory of which includes a dedicated bradycardia detection algorithm capable of storing atrial and ventricular chains, and date and time of the last ten pauses and/or bradycardic events. After a initial period of 14.7 +/- 8 months, during which symptoms were suppressed, the bradycardia algorithm was activated. From then on, a cumulative increase in the number of patients presenting with diurnal pauses was measured (1 month, n = 0; 3 months, n = 6; 9 months, n = 7; 2 years, n = 8). Fourteen episodes of diurnal asystole were recorded. The mean duration of the longest episodes of spontaneous ventricular standstill was 6,319 +/- 1,615 ms and was due to sinoatrial block (n = 7), atrioventricular block (n = 5), and a combination of both (n = 2). In conclusion, activation of the CHORUS bradycardia algorithm allowed confirmation of the appropriateness of permanent pacing in a majority of patients suffering from CSS.

B‐cell bradycardia: Carotid sinus massage by a high‐grade lymphoma

American Journal of HematologyVolume 64, Issue 3 p. 232-232 Letters and CorrespondenceFree Access B-cell bradycardia: Carotid sinus massage by a high-grade lymphoma Francisco F. Lopez, Francisco F. Lopez Department of Hematology/Oncology, The Miriam Hospital, Brown University School of Medicine, Providence, Rhode IslandSearch for more papers by this authorAbeel A. Mangi, Abeel A. Mangi Department of Hematology/Oncology, The Miriam Hospital, Brown University School of Medicine, Providence, Rhode IslandSearch for more papers by this authorRochelle Strenger, Rochelle Strenger Department of Hematology/Oncology, The Miriam Hospital, Brown University School of Medicine, Providence, Rhode IslandSearch for more papers by this authorFred J. Schiffman, Fred J. Schiffman Department of Hematology/Oncology, The Miriam Hospital, Brown University School of Medicine, Providence, Rhode IslandSearch for more papers by this authorRobert D. Meringolo, Robert D. Meringolo Department of Cardiology, The Miriam Hospital, Brown University School of Medicine, Providence, Rhode IslandSearch for more papers by this author Francisco F. Lopez, Francisco F. Lopez Department of Hematology/Oncology, The Miriam Hospital, Brown University School of Medicine, Providence, Rhode IslandSearch for more papers by this authorAbeel A. Mangi, Abeel A. Mangi Department of Hematology/Oncology, The Miriam Hospital, Brown University School of Medicine, Providence, Rhode IslandSearch for more papers by this authorRochelle Strenger, Rochelle Strenger Department of Hematology/Oncology, The Miriam Hospital, Brown University School of Medicine, Providence, Rhode IslandSearch for more papers by this authorFred J. Schiffman, Fred J. Schiffman Department of Hematology/Oncology, The Miriam Hospital, Brown University School of Medicine, Providence, Rhode IslandSearch for more papers by this authorRobert D. Meringolo, Robert D. Meringolo Department of Cardiology, The Miriam Hospital, Brown University School of Medicine, Providence, Rhode IslandSearch for more papers by this author First published: 15 June 2000 https://doi.org/10.1002/1096-8652(200007)64:3<232::AID-AJH19>3.0.CO;2-ACitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Strasberg B, Sagie A, Erdman S, et al. Carotid sinus hypersensitivity and the carotid sinus syndrome. Prog Cardiovasc Dis 1989; 31: 379. 2Patel AK, Yap VU, Fields J, et al. Carotid sinus syncope induced by malignant tumors in the neck. Arch Intern Med 1979; 139: 1281– 1284. 3Bauer CA, Redleaf MI, Gartlan MG, Tsue TT, McColloch TM. Carotid sinus syncope in head and neck cancer. Laryngoscope 1994; 104: 497. 4McIntosh SJ, Lawson J, Kenny RA. Clinical characteristics of vasodepressor, cardio-inhibitory and mixed carotid sinus syndrome in the elderly. Am J Med 1993; 95(2): 203– 208. Citing Literature Volume64, Issue3July 2000Pages 232-232 ReferencesRelatedInformation

Carotid sinus syncope: the most frequent neurally mediated syncope in the elderly.

The present work reviews current literature and the authors' experience of carotid sinus syndrome (CSS), which is considered to be the most common cause of neurally mediated acute disorders of consciousness in the elderly. Although no definitive consensus about its nosology has yet been reached, most groups agree that three features fulfill the diagnosis: anamnestic presence of syncope or its minor equivalents, and their reproduction by carotid sinus massage associated with defined values of cardioinhibition or vasodepression or both. The technique for performing carotid sinus massage used by the authors is described; this manoeuvre seems very safe and reproducible as long as simple rules are followed, and it allows the classification of CSS types. The treatment of CSS is varied, according to several factors. No pharmacological therapy has yet been demonstrated to be effective. While severe cardioinhibitory forms require an appropriate pacing, vasodepressive ones and types with only minor symptoms show a more favourable natural history. Pacing is advised in mixed CSS with either frequent and invalidating relapses, or 'high risk' attacks (severe, abrupt, with major traumas, etc.). Finally, the protocol for choosing the adequate mode of pacing is illustrated. In most cases VVI is sufficient, but the decision requires a careful individual examination.

Clinical characteristics of vasodepressor, cardioinhibitory, and mixed carotid sinus syndrome in the elderly

purpose: Carotid sinus syndrome (CSS) is frequently overlooked as a cause of syncope in the elderly. It is diagnosed when carotid sinus massage (CSM) produces asystole exceeding 3 seconds (cardioinhibitory CSS), a reduction in systolic blood pressure exceeding 50 mm Hg independent of heart rate slowing (vasodepressor CSS), or a combination of the two (mixed CSS). Most published data pertain to the cardioinhibitory subtype. The recent availability of noninvasive phasic blood pressure monitoring has allowed accurate routine assessment of the vasodepressor response to CSM. The aim of this study was to assess the clinical characteristics of vasodepressor, cardioinhibitory, and mixed CSS. patients and methods: CSM was carried out on 132 consecutive patients over 65 years referred for investigation of dizziness, falls, or syncope. Massage was performed both supine and upright with continuous electrocardiographic and phasic blood pressure monitoring. Patients exhibiting greater than 1.5-second asystole were given 600 pg of intravenous atropine to abolish heart rate slowing and allow assessment of the pure vasodepressor response. results: Carotid sinus hypersensitivity was documented in 64 patients (mean age 81 ± 7 years, 31 male). The response was vasodepressor in 37%, cardioinhibitory in 29%, and mixed in 34%. Thirty-six patients had recurrent syncope, 17 presented with unexplained falls, and the remainder had dizziness alone. Symptoms had been present for a median of 24 months, and the median number of syncopal episodes was four. Twenty-five percent had sustained a fracture and, of these, 93% had not experienced a prodrome. Head movement precipitated symptoms in 47% and vagal stimuli in 73%. Episodes were unwitnessed in two thirds of patients. Twelve patients who presented with falls denied syncope but had witnessed loss of consciousness during CSM. Mean cardioinhibition was 5 ± 2 seconds and mean vasodepression 61 ± 9 mm Hg. The blood pressure nadir occurred rapidly at 18 ± 3 seconds after massage, and baseline values were regained at 30 ± 6 seconds. The clinical characteristics of patients with vasodepressor, cardioinhibitory, and mixed responses were similar. conclusion: CSS is an underdiagnosed cause of dizziness, falls, and syncope in the elderly. The vasodepressor form occurs more frequently than previously reported and has clinical characteristics similar to those of the cardioinhibitory and mixed subtypes. Elderly patients with this condition may deny syncope and present with recurrent unexplained falls. CSM, ideally with noninvasive phasic blood pressure monitoring, should be routinely performed in elderly patients with unexplained bradycardic or hypotensive symptoms.

Validation of a Method for Choice of Pacing Mode in Carotid Sinus Syndrome With or Without Sinus Bradycardia

A new method for selection of the pacing mode in 60 consecutive patients with severe cardioinhibitory or mixed carotid sinus syndrome was prospectively validated. DDD pacing was preferred for 26 patients with: (1) the cardioinhibitory form and who had symptomatic pacemaker effect; (2) mixed type I form, (cardioinhibitory and vasodepressor) with symptomatic pacemaker effect, ventriculoatrial conduction or orthostatic hypotension; (3) mixed type II; or (4) severe bradycardia. VVI pacing was selected in the remaining 34 patients without these symptoms. During a 32 +/- 10 month follow-up period syncope and severe dizziness persisted in five patients in the VVI group (15%) and in three patients in the DDD group (12%). Symptomatic relief occurred in 87% (52/60) of patients. Minor symptoms persisted in 47% of the VVI group and 42% of the DDD group. No patient developed cardiac insufficiency or intolerance to pacing. During a 2-month duration a single-blind, randomized, cross-over study compared VVI and DDD pacing, 69% of the patients programmed from DDD to VVI suffered more frequent, severe, and intolerable symptoms. (1) Thirty four of 60 patients (57% of the entire group) in whom VVI pacing was satisfactory were identified prior to pacemaker implant. In the remainder, VVI pacing was contraindicated as it produced frequent side effects. (2) The preimplant predictive value that VVI pacing would be successful was 85% for those eventually receiving VVI pacemakers and the preimplant predictive value that VVI pacing would fail was 69% for those who underwent DDD implant.

Ventricular and Dual Chamber Pacing for Treatment of Carotid Sinus Syndrome

Thirty-nine consecutive patients with recurrent syncope and either cardioinhibitory or mixed type carotid sinus syndrome were studied to determine the efficacy of ventricular (VVI) pacing in 16, and dual chamber (DDD/DVI) in 23 patients. Only those patients affected by the isolated vasodepressor form were excluded. Follow-up lasted 12 +/- 5 months. Symptoms were totally eliminated in 67% of patients and ameliorated with persistence of minor symptoms in 33%. All patients underwent an initial 2-month follow-up in the VVI mode. Evaluation of the 19 patients who remained symptomatic and the 20 who became asymptomatic with VVI pacing demonstrated that factors observed prior to pacemaker implant were related to failure of the VVI mode. These included symptomatic pacemaker effect (42% vs 0%), mixed carotid sinus syndrome (95% vs 65%), orthostatic hypotension (47% vs 15%), or ventriculoatrial conduction (68% vs 38%). In the 23 patients with dual chamber pacing, random 2 month comparisons were performed between VVI and DVI/DDD pacing. The dual chamber mode was preferred by 14 patients, none preferred the VVI mode and nine noted no difference. Comparison of the two groups found that the factors linked to DVI/DDD preference were symptomatic pacemaker effect (50% vs 0%), ventriculoatrial conduction (78% vs 44%), or orthostatic hypotension (50% vs 11%). VVI pacing is efficacious in a high proportion of patients affected by cardioinhibitory or mixed carotid sinus syndrome. The identification of causes of VVI pacing failure allows determination of those who will benefit from VVI pacing and those who should have DVI/DDD. VVI pacing is suggested for the cardioinhibitory type with no symptomatic pacemaker effect and for the mixed type with no symptomatic pacemaker effect or orthostatic hypotension or ventriculoatrial conduction. Dual chamber pacing should be used in all other instances.

Is DDD Superior to VVI Pacing in Mixed Carotid Sinus Syndrome? An Acute and Medium‐Term Study

The aim of this study was to evaluate the importance of atrial synchronism for pacing therapy of patients with mixed carotid sinus syndrome. In 23 patients (21 m, two f; mean age 69 +/- 8 years) affected by symptomatic mixed carotid sinus syndrome we performed: (1) Research of ventriculo-atrial conduction, orthostatic hypotension and pacemaker effect; and (2) Carotid sinus massage in the standing position during VVI and DVI temporary pacing. Next, all patients received a permanent DDD pacemaker and entered a 2 month two period single-blind, randomized, cross-over study on DVI/DDD versus VVI mode. During the DVI/DDD period, no syncope occurred in any patients, minor symptoms persisted in 11 (48%) of them; during VVI period syncopes recurred in three patients, symptoms requiring the withdrawal of VVI pacing and premature DVI/DDD reprogramming in eight patients, minor symptoms in 17 (74%). A comparison between 14 patients, who preferred DVI/DDD period (Group A), and the remaining nine patients who noted no preference between DVI/DDD and VVI period (Group B) was performed on the basis of the preimplant evaluation. Group A patients had a greater pacemaker effect (-34 +/- 16 mmHg vs -16 +/- 14 mmHg) and a higher prevalence of symptomatic pacemaker effect (50% vs 0%), of ventriculo-atrial conduction (78% vs 44%) and of orthostatic hypotension (50% vs 11%), while the entity of the systolic pressure fall caused by carotid sinus massage was similar in the two groups either during VVI mode (Group A -51 +/- 16 mmHg vs Group B -56 +/- 27 mmHg) or DVI mode (Group A -38 +/- 17 mmHg vs Group B -45 +/- 17 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)