Ivabradine in children with postural orthostatic tachycardia syndrome: a retrospective study.

BACKGROUND: Ivabradine is a unique medication that reduces the intrinsic heart rate by specifically blocking the inward funny current that controls the pacemaker activity of the sinus node. We conducted a retrospective cohort study to assess the efficacy of ivabradine in children suffering from postural orthostatic tachycardia syndrome. METHODS: A chart review was conducted of patients less than 18 years of age who were diagnosed with postural orthostatic tachycardia syndrome who had received ivabradine as treatment from January 2015 to February 2019 at our institution. Twenty-seven patients (25 females, 92.5%) were identified for the study. The outcomes which were assessed included a change in the severity and frequency of symptoms, heart rate, and blood pressure before and after starting ivabradine. RESULTS: There was an improvement in the symptoms of 18 (67%) out of 27 patients. The most notable symptom affected was syncope/presyncope with a reduction in 90%, followed by lightheadedness (85%) and fatigue (81%). The vital signs of the patients showed an overall significant lowering of the heart rate during sitting (89.7 ± 17.9 versus 73.2 ± 12.1; p-value <0.05) and standing (100.5 ± 18.1 versus 80.9 ± 10.1; p-value <0.05) without a significant change in the blood pressure. Two patients had visual disturbances (luminous phenomena). Severe bradycardia and excessive flushing were seen in two patients, respectively. Another one patient reported joint pain and fatigue. CONCLUSION: This study indicates that 67% of children treated with ivabradine report an improvement in symptoms.

Droxidopa in the Treatment of Postural Orthostatic Tachycardia Syndrome.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a constellation of signs and symptoms that occur when a patient is upright and relieved by recumbence. Currently, no drugs are labeled for the treatment for POTS. Droxidopa is an orally administered amino acid that is converted to norepinephrine and thought to improve both blood pressure and symptoms in patients with orthostatic intolerance. STUDY QUESTION: To appraise the effect of Droxidopa in a clinical setting in patients with POTS refractory to other forms of treatment. STUDY DESIGN: A retrospective study of patients with POTS at our Syncope and Autonomic Disorders Center. Three hundred fifty-two patients were screened, 54 of them were prescribed Droxidopa and found to be eligible to include in our study. MEASURES AND OUTCOME: Symptoms of orthostatic intolerance, side effects of therapy and response to treatment. Statistical analyses were done using SPSS software. Thirty-seven patients were included in data analysis. Patients who failed to follow up, didn't obtain Droxidopa due to insurance and cost concerns, had hypertensive response to therapy or had allergic reaction were excluded from data analysis. RESULTS: The most frequently reported symptom was dizziness in 91.9% of patients, followed by syncope and fatigue in 70.3% and 67.6% of patients, respectively. Symptoms of dizziness, syncope and fatigue were reported less after treatment; 75.7%, 51.4% and 40.5%, respectively. There was no statistically significant difference in standing or sitting blood pressure before and after treatment. Despite the improvement in some symptoms. Only 27% of patients reported improved quality of life after treatment. Of total, 40.5% of patients stopped the treatment either due to side effects or ineffectiveness. CONCLUSION: Droxidopa appears to improve some symptoms of orthostatic intolerance in patients with POTS but has diminutive impact on quality of life and blood pressure. Further assessment in large clinical trials is needed to evaluate its efficacy.

Ivabradine in the treatment of postural tachycardia syndrome (POTS), a single center experience.

BACKGROUND: Ivabradine is a selective If  channel blocker that reduces heart rate without affecting other cardiovascular functions. In case reports and case series, it was shown to improve symptoms in patients with postural tachycardia syndrome (POTS). METHODOLOGY AND RESULTS: This retrospective study examined patients who were diagnosed with POTS and received ivabradine as part of their treatment. Forty-nine patients (47 females, 95.9%) received ivabradine. The average age was 35.1 ± 10.35 years. The most common symptoms were palpitations and lightheadedness and both improved significantly, 88.4% and 76.1% response rate, respectively. A total of 38 patients reported improvement in their symptoms. In addition, ivabradine resulted in an objective decrease in sitting and standing heart rate (78.1 ± 10.7 vs 72.5 ± 7.6, P-value: 0.01) and (107.4 ± 14.1 vs 95.1 ± 13.7, P-value: < 0.001), respectively, with no significant change in blood pressure. The most common reported side effect was luminous phenomena/visual brightness occurring in nine patients. However, none of the patients stopped ivabradine due to side effects. CONCLUSION: Our study shows that ivabradine is likely to be effective in treating patients with POTS. Nearly 78% of our cohort reported a significant improvement in symptoms with no major adverse effects reported. A future randomized, placebo-controlled trial is warranted.

Use of methylphenidate in the treatment of patients suffering from refractory postural tachycardia syndrome.

Methylphenidate has been shown to be an effective therapy in patients with refractory neurocardiogenic syncope. However, the role of methylphenidate in patients suffering from postural orthostatic tachycardia (POTS) has not been reported. The study was approved by the institutional review board. A retrospective nonrandomized analysis was preformed on 24 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 9 ± 3 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 of these patients were started on methylphenidate and the response to therapy was considered successful if it provided symptomatic relief. Twenty-four patients (age 28 ± 12, 20 women) met inclusion criterion for this study. The response to treatment was assed subjectively in each patient and was collected in a retrospective fashion from patient charts and physician communications. Four patients reported side effects in the form of nausea and 2 ultimately had to discontinue the treatment. Another 4 patients had a follow-up of less than 6 months. Thus, only 18 patients who received methylphenidate completed the follow-up of 6 months. Out of these 18 patients, 14 (77%) patients reported marked improvement in their symptoms. Nine out of 12 patients who had recurrent episodes of syncope reported no syncope at 6 months of follow-up. Fourteen (77%) patients reported marked improvement in their symptoms of fatigue and presyncope. Four patients continue to have symptoms of orthostatic intolerance and 3 continued to have recurrent episodes of syncope. Methylphenidate may be beneficial in patients with otherwise refractory postural tachycardia syndrome.

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.

Initial experience with a technique for wound closure after cardiac device implantation designed to reduce infection and minimize tissue scar formation.

Infection is a well-recognized complication that can occur after the implantation of cardiac devices such as pacemakers and implantable cardioverter defibrillators (ICDs). Reported infection rates after new device implantation are reported to be around 1%, while infection rates after device generator replacements are higher with a reported average of up to 4-5% per year. Here we report our experience using a modified plastic surgical technique for cardiac device wound closure designed to both reduce infections and enhance cosmetic outcomes. Patients were recruited from among those individuals undergoing routine cardiac device implantation (either new or replacement) at our institution. A total of 124 patients were included in the study. There were 74 women and 48 men, mean age 58 ± 16 years. There were 74 new pacemaker implants and 27 pacemaker generator replacements. There were 17 new ICD generator implants and 6 ICD generator reimplants. Mean follow-up time was 15 ± 16 months. During the follow-up period, there have been no device infections nor any wound dehiscences observed. Each patient felt that the scar was cosmetically acceptable. Two patients developed mild rashes to the clear plastic adhesive that resolved after removal. The modified wound closure technique described above appears to minimize cardiac device wound infections while facilitating cosmetically acceptable wound scar formation.

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.

Platelet Storage Pool Deficiency and Elevated Inflammatory Biomarkers Are Prevalent in Postural Orthostatic Tachycardia Syndrome.

A significant number of postural orthostatic tachycardia syndrome (POTS) patients have platelet delta granule storage pool deficiency (δ-SPD). The etiology of POTS is unknown but a number of laboratories, including ours, have reported elevations of G-protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies in POTS patients, detected by a variety of techniques, suggesting that the disorder is an autoimmune condition. Thus, it could also be considered an inflammatory disease. In a pilot study, we investigated a limited number of platelet-related cytokines and chemokines and discovered many that were elevated. This case−control study validates our pilot study results that POTS patients have an activated innate immune system. Plasma of 35 POTS patients and 35 patients with unexplained bleeding symptoms and categorized as "non-POTS" subjects was analyzed by multiplex flow cytometry to quantify 16 different innate immune system cytokines and chemokines. Electron microscopy was used to quantify platelet dense granules. Ten of 16 biomarkers of inflammation were elevated in plasma from POTS patients compared to non-POTS subjects, with most of the differences extremely significant, with p values < 0.0001. Of particular interest were elevations of IL-1ß and IL-18 and decreased or normal levels of type 1 interferons in POTS patients, suggesting that the etiology of POTS might be autoinflammatory. All POTS patients had δ-SPD. With a growing body of evidence that POTS is an autoimmune disease and having elevations of the innate immune system, our results suggest a potential T-cell-mediated autoimmunity in POTS characteristic of a mixed-pattern inflammatory disease similar to rheumatoid arthritis.

Preliminary observations suggesting that treatment with modafinil improves fatigue in patients with orthostatic intolerance.

Many patients who suffer from orthostatic intolerance (OI) may also have severe fatigue and extreme exercise intolerance. In some of these patients, fatigue may be so severe that they are unable to maintain employment. In some, even the activities of the daily living may be compromised. We report on the use of modafinil in a subgroup of patients who failed therapy with commonly used medication for fatigue in patients with OI. The study was approved by the institutional review board. A retrospective nonrandomized analysis was preformed on 60 patients evaluated at our autonomic center for OI from 2003 to 2010. The diagnosis of OI was based on patient history, physical examination, and reponse to head up tilt table testing. All these patients had fatigue as their predominant symptom. Multiple trials of stimulants including methylphenidate, amphetamine, or dextroamphetamine failed to provide symptomatic relief of fatigue in these patients. Each patient received modafinil (100-200 mg daily). The mean follow-up period was 9 ± 3 months. A treatment was considered successful if it provided symptomatic relief from fatigue for the patient. Sixty patients, age 29 ± 15, 52 women were included in the analysis. Migraine (57%) and joint hypermobility syndrome (33%) were common comorbidities. Out of 60 patients, 40 patients reported initial improvement with initiation of modafinil therapy. Twenty patients reported no change in their symptoms of fatigue. Of the 40 patients who showed initial improvement in their symptoms 4 had eventual recurrence of fatigue after 3 months of modafinil therapy. Thirty-six patients continued to demonstrate symptom relief from fatigue for more than 6 months. In a selective group of patients of OI, modafinil may improve fatigue.

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.

Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience.

BACKGROUND: The long-term efficacy of pyridostigmine, a reversible acetyl cholinesterase inhibitor, in the treatment of postural orthostatic tachycardia syndrome (POTS) patients remains unclear. We report our retrospective, single-center, long-term experience regarding the efficacy and adverse effect profile of pyridostigmine in the treatment of POTS patients. METHODS: This retrospective study included an extensive review of electronic charts and data collection in regards to patient demographics, orthostatic parameters, side-effect profile, subjective response to therapy, as well as laboratory studies recorded at each follow-up visit to our institution's Syncope and Autonomic Disorders Center. The response to pyridostigmine therapy was considered successful if patient had both symptom relief in addition to an objective response in orthostatic hemodynamic parameters (heart rate [HR] and blood pressure). Three hundred patients with POTS were screened for evaluation in this study. Of these 300, 203 patients with POTS who received pyridostigmine therapy were reviewed. Of these 203 patients, 168 were able to tolerate the medication after careful dose titration. The mean follow-up duration in this group of patients was 12 ± 3 (9-15) months. Pyridostigmine improved symptoms of orthostatic intolerance in 88 of 203 (43%) of total patients or 88 of 172 (51%) who were able to tolerate the drug. The symptoms that improved the most included fatigue (55%), palpitations (60%), presyncope (60%), and syncope (48%). Symptom reduction correlated with a statistically significant improvement in upright HR and diastolic blood pressure after treatment with pyridostigmine as compared to their baseline hemodynamic parameters (standing HR 94 ± 19 vs 82 ± 16, P < 0.003, standing diastolic blood pressure 71 ± 11 vs 74 ± 12, P < 0.02). Gastrointestinal problems were the most common adverse effects (n = 39, 19%) reported. The overall efficacy of pyridostigmine in our study was seen in 42% of total patients or 52% of patients who could tolerate taking the drug. CONCLUSION: The subgroup of POTS patients who can tolerate oral pyridostigmine may demonstrate improvement in their standing HR, standing diastolic blood pressure, and clinical symptoms of orthostatic intolerance.

Ethical Dilemmas and End-of-Life Choices for Patients with Implantable Cardiac Devices: Decisions Regarding Discontinuation of Therapy.

OPINION STATEMENT: It is our belief that a well-designed cardiac device management program should include end-of-life patient and family planning, addressing potential decisions regarding withdrawal of pacemaker and/or implantable cardioverter defibrillator therapy. Guided by the basic ethical and legal principles outlined in the article, it is the responsibility of the electrophysiologist and other involved health care providers to introduce this topic to patients, provide guidance and resources for decision making, and honor both patient and family requests.

Inflammatory Biomarkers in Postural Orthostatic Tachycardia Syndrome with Elevated G-Protein-Coupled Receptor Autoantibodies.

A growing body of evidence suggests that postural orthostatic tachycardia syndrome (POTS) may be an autoimmune disorder. We have reported in a previous manuscript that 89% of POTS patients (n = 55) had elevations in G-protein-coupled adrenergic A1 receptor autoantibodies and 53% had elevations in muscarinic acetylcholine M4 receptor autoantibodies, as assessed by ELISA. Patients with autoimmune disorders have been reported with a variety of elevated cytokines and cytokines (such as rheumatoid arthritis); thus, we evaluated a limited number of cytokines/chemokines in POTS patients with elevated adrenergic and muscarinic receptor autoantibodies. We utilized the plasma of 34 patients from a previous study; all of the patients (100%) had autoantibodies against the A1 adrenergic receptor and 55.9% (19/34) had autoantibodies against the M4 muscarinic acetylcholine receptor. In particular, the plasma cytokine/chemokine levels were measured as biomarkers of inflammation by Quantibody® technology (Raybiotech, Peachtree Corners, GA, USA). We also evaluated the platelet dense granule numbers, as these patients frequently complain of symptoms related to platelet dysfunction. Patients were predominantly young females who displayed a multitude of co-morbidities but generally reported viral-like symptoms preceding episodes of syncope. Eighty five percent (29/34) had platelet storage pool deficiency. Patients had elevations in five of ten cytokine/chemokines biomarkers (IL1ß, IL21, TNFα, INFγ, and CD30), whereas two biomarkers had decreased levels (CD40L and RANTES). Our observations demonstrate that POTS patients known to have autoantibodies against the G-protein-coupled adrenergic A1 receptor have abnormal plasma concentrations of inflammatory cytokines.

Supraventricular Tachycardia and Postural Orthostatic Tachycardia Syndrome Overlap: A Retrospective Study.

Postural orthostatic tachycardia syndrome (POTS) and supraventricular tachycardia (SVT) are disease states with distinctive features but overlapping clinical manifestations. Currently, studies on the presence of underlying SVT in patients with POTS are lacking. This retrospective study analyzed 64 patients [mean age: 43 years; 41 (61%) women] who had a POTS diagnosis and were found to have concomitant SVT during rhythm monitoring from September 1, 2013 to September 30, 2019 at our Syncope and Autonomic Disorders Clinic. The outcomes assessed were changes in disease severity, frequency of symptoms, heart rate, and blood pressure between before and after SVT ablation. The most frequent types of SVT noted on the electrophysiologic study were atrioventricular nodal reentrant tachycardia (57.81%), atrial flutter (29.68%), atrioventricular reentrant tachycardia (9.37%), atrial tachycardia (1.56%), and junctional tachycardia (1.56%). After SVT ablation, all 64 patients experienced an improvement in symptoms. Palpitations and lightheadedness experienced the most improvement after the procedure (72% vs. 31%; p < 0.001 and 63% vs. 22%; p < 0.001, respectively). There was a significant improvement in the resting heart rate (81.1 ± 12.8 vs. 75.8 ± 15.6 bpm; p < 0.002), but the orthostatic tachycardia on standing persisted (93.6 ± 16.5 vs. 77.3 ± 19.8 bpm; p = 0.14). Underlying SVT in patients with POTS can be missed easily. A strong suspicion and long-term ambulatory cardiac rhythm monitoring can help in diagnosing the condition.

Postural orthostatic tachycardia syndrome: a rare complication following electrical injury.

We report on two previously healthy patients who developed severe form of postural orthostatic tachycardia syndrome (POTS) following an electric injury. Both the patients developed symptoms of orthostatic intolerance in the form of dizziness, fatigue, lightheadedness, and palpitations, weeks to months after electrical injury. Orthostatic intolerance produced considerable functional impairment in these patients. Early recognition of POTS when it occurs after an electrical injury allows for prompt evaluation and management to occur.