Management strategies for vasovagal syncope.

Vasovagal syncope (VVS) (or neurocardiogenic syncope) is a common clinical condition that is challenging to both physicians and patients alike. Severe episodes of recurrent syncope can result in physical injury as well as psychological distress. This article provides a brief overview of current management strategies and a detailed overview of therapeutic modalities such as closed loop stimulation (CLS) and cardioneuroablation (CNA).

Risks of adverse events in patients with orthostatic intolerance undergoing surgery with general anesthesia.

INTRODUCTION: Orthostatic intolerance (OI) is a group of disorders characterized by symptoms that occur upon standing and resolve with recumbence. Although well established but not widely recognized, these diagnoses may create uncertainty for clinicians dealing with a patient affected by OI and requiring a surgical procedure. OBJECTIVES: To determine the rate of intra- and postoperative major adverse events in patients with OI undergoing surgery with general anesthesia. METHODS: The study was a retrospective study of patients with orthostatic intolerance who underwent surgery requiring general anesthesia from 1 January 2000 to 31 December 2018. RESULTS: A total 171 patients with OI underwent 190 surgeries. In patients with POTS and orthostatic-induced VVS, there were no major significant adverse events. There was one episode of AVNRT in a patient with POTS and one episode of bradycardia secondary to vasovagal reflex in a patient with orthostatic-induced VVS. Moreover, there were 13 (6.8%) episodes of postoperative hypotension. However, the majority of these episodes were related to bleeding, volume depletion or sepsis. All cases of hypotension responded well to appropriate therapy. In patients with OH, the rate of postoperative major adverse cardiac events was 4.7%, and the 30-day mortality rate was 6.1%. This is not significantly different from the calculated risk for patients without OH. There were no myocardial infarctions or deaths at 30 days in patients with POTS or orthostatic-induced VVS. CONCLUSION: Patients with OI may not experience higher rates of perioperative complications compared with patients without OI syndromes.

The benefit of closed loop stimulation in patients with cardioinhibitory vasovagal syncope confirmed by head-up tilt table testing: a systematic review and meta-analysis.

PURPOSE: A proportion of patients with vasovagal syncope (VVS) experience recurrence despite appropriate management. Closed loop stimulation (CLS) pacing is a promising treatment for a subgroup of patients with cardioinhibitory response on head-up tilt table test (HUTT). Nonetheless, its efficacy remains uncertain. We sought to assess the efficacy of CLS pacing in patients with cardioinhibitory VVS. METHODS: We searched PubMed, Google Scholar, and the Cochrane Central Register of controlled trials for relevant studies (last search date April 23, 2018). Data were pooled using the Mantel-Haenszel fixed-effects model. For cohort studies, we used a Freeman-Tukey transformation to calculate the weighted summary proportion. Primary outcomes are syncope and presyncope. RESULTS: Eight studies were included in the final analyses (two single-blinded and one double-blinded RCT, two prospective observational studies, and three retrospective observational studies). Two hundred ninety-one patients included, with an average age of 57 years. Quality of evidence is moderate. Use of CLS pacing was associated with reduced risk of syncope (OR 0.08; 95% CI 0.03-0.18; I2 32%) and presyncope (OR 0.34; 95% CI 0.18-0.63; I2 0.00%). Using proportion meta-analysis, the summary estimate of the proportion of cases that developed syncope during CLS pacing was similar between RCTs and prospective studies (3.2% and 3.1%), respectively. This is much lower than the rate of recurrence in the control arm of RCTs at 33.7%. Sensitivity analyses yielded similar results. CONCLUSION: CLS pacing is beneficial for patients with recurrent vasovagal syncope who demonstrate a cardioinhibitory response on HUTT.

Role of implantable loop recorders in patients with postural orthostatic tachycardia syndrome.

INTRODUCTION: We previously reported on a subgroup of postural orthostatic tachycardia syndrome (POTS) patients who may also have features of neurocardiogenic syncope as well. In this subgroup of patients, we found syncope and presyncope were predominant clinical features. To understand the mechanism of syncope in this subgroup, we identified 39 patients who underwent loop recorder insertion. METHODS: We reviewed charts of 450 patients who had POTS and syncope seen at the University of Toledo Medical Center from 2003 to 2017. Thirty-nine patients had at least four episodes of syncope in the last 6 months and were included for this study. All of these patients had a prior evaluation with a Holter and an event monitor which were inconclusive. RESULTS: Thirty-nine patients, 33 (85%) women, aged 20-46 years, were included in this study. All patients demonstrated prolonged asystole (>6 seconds) or severe bradycardia (heart rate < 30 beats/min) during their syncope on implantable loop recorder (IRL). Fifteen patients demonstrated an asystole of >10 seconds and also had prolonged and convulsive syncope. All patients had abrupt syncope without any warning sign. All patients underwent dual-chamber pacemaker implantation using a closed loop stimulation algorithm. Syncope were completely eliminated in all patients following pacemaker implantation; however, they continued to have orthostatic tachycardia. CONCLUSION: POTS patients with unusually frequent syncope should be considered for ILR implantation if other monitoring modalities like 48-hour Holter monitor or event recorder are inconclusive. ILR may identify a subgroup of POTS patients who may benefit from pacemaker implantations.

Vasovagal syncope-role of closed loop stimulation pacing.

The benefit of conventional pacing in vasovagal syncope remains controversial and is currently recommended for patients with recurrent syncope and documented asystole. In the last two decades, a growing body of evidence has emerged supporting the use of a new sensing technique called closed loop stimulation or CLS, to treat refractory vasovagal syncope. CLS uses a sensing algorithm that can detect variation in cardiac contractility and respond to drop in blood pressure by increasing the heart rate. Multiple observational and randomized studies have assessed its efficacy and showed its superiority to conventional pacing in reducing the burden of syncopal attacks in patients with cardio-inhibitory vasovagal syncope.

Pediatric Disorders of Orthostatic Intolerance.

Orthostatic intolerance (OI), having difficulty tolerating an upright posture because of symptoms or signs that abate when returned to supine, is common in pediatrics. For example, ∼40% of people faint during their lives, half of whom faint during adolescence, and the peak age for first faint is 15 years. Because of this, we describe the most common forms of OI in pediatrics and distinguish between chronic and acute OI. These common forms of OI include initial orthostatic hypotension (which is a frequently seen benign condition in youngsters), true orthostatic hypotension (both neurogenic and nonneurogenic), vasovagal syncope, and postural tachycardia syndrome. We also describe the influences of chronic bed rest and rapid weight loss as aggravating factors and causes of OI. Presenting signs and symptoms are discussed as well as patient evaluation and testing modalities. Putative causes of OI, such as gravitational and exercise deconditioning, immune-mediated disease, mast cell activation, and central hypovolemia, are described as well as frequent comorbidities, such as joint hypermobility, anxiety, and gastrointestinal issues. The medical management of OI is considered, which includes both nonpharmacologic and pharmacologic approaches. Finally, we discuss the prognosis and long-term implications of OI and indicate future directions for research and patient management.

Syncope as an initial manifestation of atypical lipomatous hypertrophy of the interatrial septum.

Lipomatous hypertrophy of the interatrial septum (LHIS) is an incidental echocardiographic abnormality characterized by dumb-bell configuration of the interatrial septum from excess fat deposition. We report a case of syncope in a patient with LHIS obstructing the superior vena cava at the right atrial junction.

Use of octreotide in the treatment of refractory orthostatic intolerance.

There have been reports on the use of octreotide in patients with orthostatic hypotension, postural tachycardia syndrome, and orthostatic syncope. However, there are little if any data on the use of octreotide in patients who have failed multiple other medications. This study was a retrospective chart analysis and was approved by our Institutional Review Board. A total of 12 patients were identified for inclusion in this study. The diagnosis of orthostatic intolerance was based on patient history, physical examination, and response to Head Up Tilt Table testing. These patients had failed multiple medications and were ultimately treated with octreotide. In a retrospective chart review, we collected data, including demographic information, presenting symptoms, laboratory data, tilt-table response, standing heart rate, standing blood pressure before and after treatment (wherever available), and treatment outcomes. Twelve patients aged 33 ± 18 years, eight (66.7%) females, were found to have symptoms of refractory orthostatic intolerance and failed multiple regimens of medication and were ultimately treated with octreotide administration. Five patients (41.7%) had demonstrated a postural tachycardia syndrome pattern, five (41.7%) a neurocardiogenic, and two (16.6%) a dysautonomic response on a Head Up Tilt Table. Symptoms of syncope and orthostatic palpitations improved in six (50%) of the patients. Standing heart rate was significantly reduced after octreotide administration (80 ± 8 versus 108 ± 13; P < 0.05). The standing systolic blood pressure was increased after octreotide administration (107 ± 26 versus 116 ± 22). Three patients (25%) reported complete elimination of syncope, whereas another three had reduction in the frequency of their syncope. However, symptoms of fatigue improved only in two (29%) of the seven patients. Octreotide may improve symptoms in some patients with refractory orthostatic intolerance.

Erythropoietin in the treatment of postural orthostatic tachycardia syndrome.

Erythropoietin has been reported to improve symptoms of orthostatic intolerance in patients suffering from orthostatic hypotension. Previous reports on the use of erythropoietin in patients with postural orthostatic tachycardia (POTS) have included only a very small number of patients. In the current study, we report on the use of erythropoietin in patients with refractory POTS. The study was approved by the institutional review board. A retrospective nonrandomized analysis was performed on 39 patients evaluated at our autonomic center for POTS from 2003 to 2010. The diagnosis of POTS was based on patient history, physical examination, and response to head-up tilt-table testing. The mean follow-up period was 6 months. The patients were included in the current study if they had a diagnosis of POTS with severe symptoms of orthostatic intolerance and were refractory to the commonly used medications. All these patients were started on erythropoietin, and the response to therapy was considered successful if it provided symptomatic relief. We screened 200 patients with POTS and found 39 patients (age 33 ± 12, 37 females) to be eligible for inclusion in the current study. The response to the treatment was assessed subjectively in each patient and was obtained in a retrospective fashion from patient charts and physician communications. Eight (21%) patients demonstrated no improvement in symptoms after administration of erythropoietin. Three (8%) patients showed an improvement in symptoms of orthostatic intolerance of <3 months. Twenty-seven (71%) patients demonstrated sustained improvement in their symptoms of orthostatic intolerance at the mean follow-up of 6 months. Erythropoietin significantly improved sitting diastolic blood pressure but had no effect on other hemodynamic parameters. In a select group of POTS patients who are refractory to commonly used medications, erythropoietin may help improve symptoms of orthostatic intolerance.

Neurocardiogenic syncope coexisting with postural orthostatic tachycardia syndrome in patients suffering from orthostatic intolerance: a combined form of autonomic dysfunction.

INTRODUCTION: There is anecdotal evidence that one or more forms of orthostatic intolerance (OI) subgroups may coexist in the same patients. However, there is a paucity of published data on the clinical features and management of patients who suffer from coexisting features of postural tachycardia syndrome (POTS) and neurocardiogenic syncope (NCS). We herein present our experience of 18 patients who we found displayed evidence of coexisting NCS and POTS. METHODS: We reviewed charts of 300 POTS patients seen at the University of Toledo Syncope and Autonomic Disorders Center from 2003 to 2010 and found 18 patients eligible for inclusion in this study. Patients were included in this study if they reported clinical symptoms consistent with both POTS and NCS and then demonstrated a typical POTS pattern (a rise in heart rate without change in blood pressure [BP]) on head up tilt table (HUTT) within the first 10 minutes of upright posture followed by a neurocardiogenic pattern (a sudden fall in heart rate and/or fall in blood pressure) reproducing symptoms that were similar to the patients spontaneous episodes. RESULTS: We found 18 patients, mean age (30 ± 12), with 15 (84%) women and three (16%) men, who met the inclusion criterion for this study. Each of these 18 patients demonstrated a typical POTS pattern within the first 10 minutes on initial physical exam and on a HUTT. Continued tilting beyond 10 minutes resulted in a sudden decline in heart rate (which in some patients manifested as an asystole that lasted anywhere between 10 and 32 seconds [mean of 18 seconds]) and/or a fall in BP in each of these patients demonstrating a pattern consistent with neurocardiogenic subtype of OI. The mean time to the NCS pattern of a fall in BP and heart was 15 minutes with a range of 13-20 minutes. This group of patients was highly symptomatic and reported frequent clinical symptoms that were suggestive of OI. Recurrent presyncope, syncope, orthostatic palpitations, exercise intolerance, and fatigue were the principal symptoms reported. CONCLUSION: NCS may coexist with POTS in a subgroup of patients suffering from OI.

Autonomic dysfunction presenting as orthostatic intolerance in patients suffering from mitochondrial cytopathy.

BACKGROUND: Disturbances in autonomic nervous system function have been reported to occur in patients suffering from mitochondrial cytopathies. However, there is paucity of literature on the occurrence of orthostatic intolerance (OI) in these patients. We report on a series of patients diagnosed with mitochondrial cytopathy who developed features of autonomic dysfunction in the form of OI. METHODS: This was a single-center report on a series of 6 patients who were followed in our clinic for orthostatic intolerance. All of these patients had a diagnosis of mitochondrial cytopathy on the basis of muscle biopsy and were being followed at a center specializing in the treatment of mitochondrial disorders. This study was approved by our local institutional review board. Each of the patients had suffered from symptoms of fatigue, palpitations, near syncope, and syncope. The diagnosis of OI was confirmed by head-up tilt test. Collected data included demographic information, presenting symptoms, laboratory data, tilt-table response, and treatment outcomes. RESULTS: Six patients (3 females) were identified for inclusion in this report. The mean age of the group was 48 ± 8 years (range, 40-60 years). All of these patients underwent head-up tilt table testing and all had a positive response that reproduced their clinical symptoms. Among those having an abnormal tilt-table pattern, 1 had a neurocardiogenic response, 1 had a dysautonomic response, and 4 had a postural orthostatic tachycardia response. All but 1 patient reported marked symptom relief with pharmacotherapy. The patient who failed pharmacotherapy received a dual-chamber closed-loop pacemaker and subsequently reported marked improvement in her symptoms with elimination of her syncope. CONCLUSIONS: Orthostatic intolerance might be a significant feature of autonomic nervous system dysfunction in patients suffering from mitochondrial cytopathy.

Comparative clinical profile of postural orthostatic tachycardia patients with and without joint hypermobility syndrome.

BACKGROUND: Autonomic dysfunction is common in patients with the joint hypermobility syndrome (JHS). However, there is a paucity of reported data on clinical features of Postural orthostatic tachycardia syndrome (POTS) in patients suffering from JHS. METHODS: This retrospective study was approved by our local Institutional Review Board (IRB). Over a period of 10 years, 26 patients of POTS were identified for inclusion in this study. All these patients had features of Joint Hypermobility Syndrome (by Brighton criterion). A comparison group of 39 patients with other forms of POTS were also followed in the autonomic clinic during the same time. We present a descriptive report on the comparative clinical profile of the clinical features of Postural Orthostatic Tachycardia patients with and without Joint Hypermobility syndrome. The data is presented as a mean+/-SD and percentages wherever applicable. RESULTS: Out of 65 patients, 26 patients (all females, 20 Caucasians) had POTS and JHS. The mean age at presentation of POTS was 24+/-13 (range 10-53 years) vs 41+/-12 (range 19-65 years), P=0.0001, Migraine was a common co morbidity 73 vs 29% p=0,001. In two patients POTS was precipitated by pregnancy, and in three by surgery, urinary tract infection and a viral syndrome respectively. The common clinical features were fatigue (58%), orthostatic palpitations (54%), presyncope (58%), and syncope (62%). CONCLUSIONS: Patients with POTS and JHS appear to become symptomatic at an earlier age compared to POTS patients without JHS. In addition patients with JHS had a greater incidence of migraine and syncope than their non JHS counterparts.

Underutilization of implantable cardioverter defibrillators post coronary artery bypass grafting in patients with systolic dysfunction.

BACKGROUND: Evaluation of the need for prophylactic internal cardiac defibrillators among patients with ischemic cardiomyopathies should be deferred until at least 3 months after revascularization procedures to allow adequate time for recovery of ventricular function. METHODS: Among patients with left ventricular systolic dysfunction (LVSD) who undergo coronary artery bypass grafting (CABG), the proportion of patients who are risk stratified postoperatively with reassessment of left ventricular ejection fraction (LVEF) is unknown. RESULTS: One hundred and six patients with LVSD (LVEF < 40%) who underwent CABG during 2004-2006 and survived 3 months post CABG were evaluated. Follow-up was assessed by chart review and telephone contact. LVEF was not reassessed in 24% (25/106) of the population, none of whom underwent internal cardioverter defibrillator (ICD) implantation. Of those with LVEF reassessed, persistent LVSD was present in 20/81 (25%), 12 of whom were referred for prophylactic ICD placement. CONCLUSION: One-fourth of patients with LVSD who undergo CABG do not have LVEF reassessed postoperatively which may lead to underutilization of ICDs.

Preliminary observations on the use of closed-loop cardiac pacing in patients with refractory neurocardiogenic syncope.

BACKGROUND: In many patients with recurrent neurocardiogenic syncope (NCS), a significant fall in blood pressure precedes any appreciable decline in heart rate. Closed-loop pacing (CLS) employs a sensing system that measures myocardial contractility, thereby providing a potential way to detect the onset of NCS at a much earlier point in time than that provided by standard pacing systems. METHODS: Patients were included in the study if they suffered from recurrent NCS and met all of the following criteria: (1) They had suffered at least two syncopal episodes in the preceding 6 months. (2) Patients were refractory to (or intolerant of) all conventional, non-pharmacological, or pharmacological treatments. (3) They had evidence of asystole (>10 s) or severe bradycardia (heart rate <30 bpm) on implantable loop recorder or during head-up tilt test (HUTT). RESULTS: Thirty five patients meeting the above criterion received 44 devices. Twelve patients received a standard unit (with rate drop or rate hysterisis response) and 32 patients received a CLS unit (Cylos, Biotronik). The pacemaker implantation was termed successful if there was no recurrence of syncope, if the syncope burden decreased by > or =50%, if only presyncope occurred, or if the syncope occurred but with significant warning symptoms. Thirty-five patients, 29 females and six males, age 41 +/- 11, with refractory NCS underwent pacemaker implantation. Mean follow-up was 9 +/- 3 months. Out of 32 patients who received CLS, nine had a conventional pacemaker implanted in the past. Recurrence (59% vs 83%), reduction in syncope burden and pacemaker success (84% vs 25%, P = 0.002), and occurrence prodrome/warning signs (40% vs 16%) were much better in the closed-loop group. CONCLUSION: These preliminary observations suggest that dual-chamber CLS pacing may be promising therapy for refractory NCS. Further randomized trials will be needed to better determine the role of this therapy in refractory NCS.

New-onset orthostatic intolerance following bariatric surgery.

BACKGROUND: As bariatric surgery has become an increasingly popular treatment for obesity, we have seen an increasing number of patients present after bariatric surgery with new-onset syncope, near-syncope, and lightheadedness. METHODS: We retrospectively reviewed patients who had had bariatric surgery referred to our institution for evaluation of orthostatic intolerance. We reviewed history, physical examination, type of bariatric surgery procedure, and tilt table test results in these patients. There were 14 women and one man with mean age 42 +/- 6 years, preoperative body mass index was 49.3 +/- 6.0 kg/m(2), and mean postoperative weight loss was 55.9 kg. Mean onset of symptoms was 5.2 +/- 3.9 months after surgery. Presenting symptoms were lightheadedness in 15 (100%), near-syncope in 11 (73%), and syncope in nine (60%). All but one patient had a positive tilt table test with eight (53%) having a neurocardiogenic response, three (20%) having a dysautonomic response, and (20%) having a postural tachycardia response. The likely mechanism of orthostatic intolerance is autonomic insufficiency in combination with reverse course of obesity-related hypertension. The majority of the patients (12 out of 15) responded to standard therapy for autonomic insufficiency. CONCLUSION: Some patients may develop significant orthostatic intolerance due to autonomic insufficiency following bariatric surgery, and awareness of the potential association between bariatric surgery and new orthostatic intolerance is important for providing timely care.

Evaluation of syncope.

Syncope is not an uncommon condition. The evaluation can be as frustrating as the treatment. The role of a detailed history and physical examination cannot be underestimated and both remain a cornerstone in the evaluation of syncope. A systematic approach may not only lead to correct diagnosis in most cases, but also ultimately will be cost effective. This review emphasizes the systematic approach for the evaluation of this challenging problem.