The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.

BACKGROUND: Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data. METHODS AND FINDINGS: This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out. CONCLUSIONS: Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.

Randomised controlled trials of antihypertensive therapy: does exclusion of orthostatic hypotension alter treatment effect? A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Management of antihypertensive therapy is challenging in patients with symptomatic orthostatic hypotension, a population often excluded from randomised controlled trials of antihypertensive therapy. In this systematic review and meta-analysis, we sought to determine whether the association of antihypertensive therapy and adverse events (e.g. falls, syncope), differed among trials that included or excluded patients with orthostatic hypotension. METHODS: We performed a systematic review and meta-analysis of randomised controlled trials comparing blood pressure lowering medications to placebo, or different blood pressure targets on falls or syncope outcomes and cardiovascular events. A random-effects meta-analysis was used to estimate a pooled treatment-effect overall in subgroups of trials that excluded patients with orthostatic hypotension and trials that did not exclude patients with orthostatic hypotension, and tested P for interaction. The primary outcome was fall events. RESULTS: 46 trials were included, of which 18 trials excluded orthostatic hypotension and 28 trials did not. The incidence of hypotension was significantly lower in trials that excluded participants with orthostatic hypotension (1.3% versus 6.2%, P < 0.001) but not incidences of falls (4.8% versus 8.8%; P = 0.40) or syncope (1.5% versus 1.8%; P = 0.67). Antihypertensive therapy was not associated with an increased risk of falls in trials that excluded (OR 1.00, 95% CI; 0.89-1.13) or included (OR 1.02, 95% CI; 0.88-1.18) participants with orthostatic hypotension (P for interaction = 0.90). CONCLUSIONS: The exclusion of patients with orthostatic hypotension does not appear to affect the relative risk estimates for falls and syncope in antihypertensive trials.

Treatment of drop attacks: Anti-seizure drug choices of pediatric neurologists in Saudi Arabia.

OBJECTIVES: To evaluate Epileptic drop attacks (EDAs) treatment options among pediatric neurologists in Saudi Arabia (SA) and to develop a recommendation scheme for the management of EDAs in SA. Epileptic drop attacks are one of the most pharmaco-resistant epileptic seizures. The different approaches to EDA treatment are influenced by a variety of factors, including pharmaceutical availability, costs, side effects, treating physicians' experience and personal preferences. METHODS: This cross-sectional study was conducted online. A structured questionnaire that aimed to measure the therapeutic options for patients with EDA was electronically distributed to pediatric neurologists across SA. It contained 21 questions, and the data were collected in Excel sheets and analyzed. RESULTS: Our study included a cohort of 71 pediatric neurologists from SA, of which male doctors represented 60%. Most of the participating pediatric neurologists had more than 10 years of experience in the field. We found that 77% of the included pediatric neurologists used valproic acid as a first-line drug in patients with EDA. Further, in the different case scenarios provided to participants, levetiracetam, clobazam, topiramate, and rufinamide were included in the initial management protocol for EDA. CONCLUSION: The majority of pediatric neurologists in Saudi Arabia chose valproic acid and/or levetiracetam as the first line of treatment for EDA. These results highlight the need for an evidence-based clinical guidelines to treat EDA.

Theophylline in patients with syncope without prodrome, normal heart, and normal electrocardiogram: a propensity-score matched study verified by implantable cardiac monitor.

AIMS: Syncope without prodromes in subjects with normal heart and normal electrocardiogram (ECG) is classified as non-classical neurally mediated syncope and is characterized by low adenosine plasma levels (APLs) and frequent asystolic syncope. We assessed the efficacy of theophylline, a non-selective adenosine receptor antagonist, in preventing syncopal events. METHODS AND RESULTS: Participants received an implantable cardiac monitor, underwent APL measurement, and received oral theophylline at maximum tolerated dose (starting dose 300 mg b.i.d.). They were compared with a historical cohort of untreated patients with implantable cardiac monitor who had the same inclusion criteria and were balanced with the propensity score (PS) method as regard age, sex, lifetime syncopal episodes, APL, and antihypertensive drugs. Primary endpoint was time to first syncopal recurrence at 24 months. There were 76 patients in the theophylline group and 58 in the control group. Syncope recurred in 25 (33%) patients in the theophylline group and in 27 (47%) patients in the control group, with an estimated 2-year recurrence rate of 33% and 60%, respectively, and a hazard ratio of 0.53 [95% confidence interval (CI), 0.30-0.95; P = 0.034]. Most of the benefit of theophylline is derived from reduction of syncope due to asystolic atrioventricular (AV) block (hazard ratio of 0.13; 95% CI, 0.03-0.58; P = 0.008). Thirty (39%) patients discontinued theophylline after a median of 6.4 (interquartile range 1.7-13.8) months due to side effects. CONCLUSION: Theophylline was effective in preventing recurrences in patients with syncope without prodromes, normal heart, and normal ECG. The benefit was greater in patients with syncope due to asystolic AV block. CLINICALTRIALS.GOV IDENTIFIER: NCT03803215.

Clinical features and management of Meniere's disease patients with drop attacks.

PURPOSE: The aims of the present study are to investigate the variations in clinical features, including medical history, hearing function, vestibular function, and degree of endolymphatic hydrops (EH), in Meniere's disease (MD) patients with and without drop attacks (DAs), and to examine the efficacy of intratympanic gentamicin (ITG) treatment in alleviating DAs. METHODS: In total, 177 unilateral definite MD patients, including 16 patients with DAs and 161 patients without DAs, were enrolled. The results of hearing test, vestibular-evoked myogenic potentials (VEMPs), and magnetic resonance imaging (MRI) were analyzed. Thirteen patients with DAs received a single ITG treatment and were followed up. RESULTS: The disease course of MD in the DA group was significantly longer than that in the control group (p = 0.007). MD patients with DAs had significantly greater hearing loss and worse EH than MD patients without DAs (p < 0.05). However, there was no between-group difference in vestibular function. In the study, 92.31% of refractory definite MD patients with DAs achieved satisfactory control of DAs after ITG treatment. CONCLUSIONS: MD patients with DAs tend to suffer from severe hearing loss and a significant degree of EH in the inner ear. However, the vestibular function of MD patients with DAs may not be completely abolished, but be sensitive to stimulating signals. ITG treatment, which helps to decrease vestibular sensitivity, was an effective treatment to control DAs.

Repetitive ventricular tachycardia in a syncopal child: Cause or incidental finding ?

A 15-year-old girl suffered recurrent syncopal episodes during 7 years. Events were precipitated by exercise or emotional stress, leading to the diagnosis of reflex syncope. Exercise testing induced recurrent salvos of nonsustained right ventricular outflow tract tachycardia. This arrhythmia is often asymptomatic, reflex syncope is very frequent and both causes are related to the same triggering situations. It was therefore essential to obtain recordings during syncopal events and to observe the clinical evolution under effective treatment in order to make the right diagnosis.

Dysphagia, Hyperglycemia, and Presyncope.

There have been over 80 documented cases of swallow syncope-a rare form of reflex or neurally mediated syncope-with most cases associated with an underlying esophageal disorder. Here, we describe the first reported case of swallow syncope or presyncope caused by an infectious esophagitis. Our 65-year-old patient initially developed dysphagia, odynophagia, and presyncope with swallowing. This lead to nutrition and medication avoidance behavior, which was followed by the development of diabetic ketoacidosis. The diagnosis of swallow presyncope was confirmed with a provocative swallow study demonstrating 8 s sinus arrest, and an underlying cause of Candida esophagitis was found by upper endoscopy. Symptoms completely resolved after treatment with micafungin.

Different clinical features of anaphylaxis according to cause and risk factors for severe reactions.

BACKGROUND: Anaphylaxis is a life-threatening allergic reaction. Several studies reported different anaphylactic reactions according to the causative substances. However, a comparison of anaphylaxis for each cause has not been done. This study was conducted to identify common causes of anaphylaxis, characteristics of anaphylactic reaction for each cause and to analyze the factors related to the severity of the reaction. METHODS: Medical records of patients who visited the emergency room of Ewha Womans University Mokdong Hospital from March 2003 to April 2016 and diagnosed with anaphylactic shock were retrospectively reviewed. We compared the clinical features of anaphylaxis according to the cause. In addition, the severity of anaphylaxis was analyzed and contributing factors for severe anaphylaxis were reviewed. RESULTS: A total of 199 patients with anaphylaxis were analyzed. Food was the most common cause (49.7%), followed by drug reaction (36.2%), bee venom (10.1%), and unknown cause (4.0%). Cardiovascular symptoms of syncope and hypotension were more common in drug-induced anaphylaxis. The incidence of severe anaphylaxis was the highest in anaphylaxis due to drugs (54.2%). Urticaria and other skin symptoms were significantly more common in food-induced anaphylaxis. Risk factors for severe anaphylaxis included older age, male, and drug-induced one. Epinephrine treatment of anaphylaxis was done for 69.7% and 56.9% of patients with food-induced and drug-induced anaphylaxis, respectively. CONCLUSIONS: More severe anaphylaxis developed with drug treatment and in males. Low rate of epinephrine prescription was also observed. Male patients with drug induced anaphylaxis should be paid more attention.

Clinical Aspects of Type 3 Long-QT Syndrome: An International Multicenter Study.

BACKGROUND: Risk stratification in patients with type 3 long-QT syndrome (LQT3) by clinical and genetic characteristics and effectiveness of ß-blocker therapy has not been studied previously in a large LQT3 population. METHODS: The study population included 406 LQT3 patients with 51 sodium channel mutations; 391 patients were known to be event free during the first year of life and were the focus of our study. Clinical, electrocardiographic, and genetic parameters were acquired for patients from 7 participating LQT3 registries. Cox regression analysis was used to evaluate the independent contribution of clinical, genetic, and therapeutic factors to the first occurrence of time-dependent cardiac events (CEs) from age 1 to 41 years. RESULTS: Of the 391 patients, 118 (41 males, 77 females) patients (30%) experienced at least 1 CE (syncope, aborted cardiac arrest, or long-QT syndrome-related sudden death), and 24 (20%) suffered from LQT3-related aborted cardiac arrest/sudden death. The risk of a first CE was directly related to the degree of QTc prolongation. Cox regression analysis revealed that time-dependent ß-blocker therapy was associated with an 83% reduction in CEs in females (P=0.015) but not in males (who had many fewer events), with a significant sex × ß-blocker interaction (P=0.04). Each 10-ms increase in QTc duration up to 500 ms was associated with a 19% increase in CEs. Prior syncope doubled the risk for life-threatening events (P<0.02). CONCLUSIONS: Prolonged QTc and syncope predispose patients with LQT3 to life-threatening CEs. However, ß-blocker therapy reduces this risk in females; efficacy in males could not be determined conclusively because of the low number of events.

Insight into specific pro-arrhythmic triggers in Brugada and early repolarization syndromes: results of long-term follow-up.

The pro-arrhythmic triggers in Brugada and early repolarization syndromes (BrS, ERS) have not been analyzed systematically except for case reports. We clinically investigated the circumstances which precede/predispose to arrhythmic events in these syndromes during long-term follow-up. A detailed history from the patients/witnesses was taken to investigate the antecedent events in the last few hours that preceded syncope/ventricular fibrillation (VF); medical records, ECG and blood test from the emergency room (ER) were reviewed. 19 patients that fulfilled the investigation criteria were followed up for 71 ± 49 months (34-190 months). Prior to the event (syncope/VF), the patients were partaking different activities in the following decreasing order; drinking alcoholic beverage, having meal, and getting up from sleep, exercise. 3 patients reported mental/physical stress prior to the event and 2 patients developed VF several days after starting oral steroid for treatment of bronchial asthma. In the ER, elevated J-wave amplitude (0.27 ± 0.15 mV) was found with 58 % of the patients having hypokalemia. After electrolyte correction and cessation of steroids, the following day plasma K+ (4.2 ± 0.3 mEq/L, P < 0.001) was significantly increased and J-wave amplitude (0.13 ± 0.1 mV, P < 0.001) was remarkably reduced. Three patients were kept on oral spironolactone/potassium supplements. During follow-up for 71 ± 49 (34-190) months, among 4 patients with VF recurrence, one patient developed VF after taking oral steroid. In ERS and BrS, hypokalemia and corticosteroid therapy add substantial pro-arrhythmic effects, but potentially treatable. Stopping steroid therapy and avoiding hypokalemia had excellent long-term outcome.

Is the thrombus truly free-floating? A case report.

A free-floating thrombus in the left atrium is very rare in mitral stenosis. Such a thrombus can lead to sudden circulatory arrest and syncope or can cause severe cerebral or peripheral thromboembolic events. Clinical diagnosis is difficult, but left atrial thrombus should be suspected if patients with mitral stenosis and atrial fibrillation have intermittent or changing murmurs, emboli, or syncope. We describe the case of a patient with mild mitral stenosis under warfarin therapy, and a left atrial pedunculated thrombus discovered during the investigation for syncope attacks.

New-onset syncope in diabetic patients treated with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors: a Chinese population-based cohort study.

BACKGROUND AND AIMS: Syncope is a symptom that poses an important diagnostic and therapeutic challenge, and generates significant cost for the healthcare system. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated beneficial cardiovascular effects, but their possible effects on incident syncope have not been fully investigated. This study compared the effects of SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i) on new-onset syncope. METHODS AND RESULTS: This was a retrospective, territory-wide cohort study enrolling type 2 diabetes mellitus (T2DM) patients treated with SGLT2i or DPP4i between 1 January 2015 and 31 December 2020, in Hong Kong, China. The outcomes were hospitalization of new-onset syncope, cardiovascular mortality, and all-cause mortality. Multivariable Cox regression and different approaches using the propensity score were applied to evaluate the association between SGLT2i and DPP4i with incident syncope and mortality. After matching, a total of 37 502 patients with T2DM were included (18 751 SGLT2i users vs. 18 751 DPP4i users). During a median follow-up of 5.56 years, 907 patients were hospitalized for new-onset syncope (2.41%), and 2346 patients died from any cause (6.26%), among which 471 deaths (1.26%) were associated with cardiovascular causes. Compared with DPP4i users, SGLT2i therapy was associated with a 51% lower risk of new-onset syncope [HR 0.49; 95% confidence interval (CI) 0.41-0.57; P < 0.001], 65% lower risk of cardiovascular mortality (HR 0.35; 95% CI 0.26-0.46; P < 0.001), and a 70% lower risk of all-cause mortality (HR 0.30; 95% CI 0.26-0.34; P < 0.001) in the fully adjusted model. Similar associations with syncope were observed for dapagliflozin (HR 0.70; 95% CI 0.58-0.85; P < 0.001), canagliflozin (HR 0.48; 95% CI 0.36-0.63; P < 0.001), and ertugliflozin (HR 0.45; 95% CI 0.30-0.68; P < 0.001), but were attenuated for empagliflozin (HR 0.79; 95% CI 0.59-1.05; P = 0.100) after adjusting for potential confounders. The subgroup analyses suggested that, compared with DPP4i, SGLT2i was associated with a significantly decreased risk of incident syncope among T2DM patients, regardless of gender, age, glucose control status, Charlson comorbidity index, and the association remained constant amongst those with common cardiovascular drugs and most antidiabetic drugs at baseline. CONCLUSION: Compared with DPP4i, SGLT2i was associated with a significantly lower risk of new-onset syncope in patients with T2DM, regardless of gender, age, degree of glycaemic control, and comorbidity burden.

Mediastinal choriocarcinoma presenting with syncope.

Mediastinal choriocarcinomas are rare germ-cell tumors that occur almost exclusively in young males. These tumors grow rapidly, causing compression of mediastinal structures, and are usually associated with a poor prognosis. We report herein a unique case documenting syncope as initial clinical presentation of a mediastinal choriocarcinoma causing a superior vena cava (SVC) syndrome. The patient was treated with a standard chemotherapy triplet, with normalization of the tumor markers after the first chemotherapy cycle. He remains with no evidence of disease relapse 18 months later. Clinicians should consider the diagnosis of a mediastinal germ-cell tumor in a younger male patient presenting with a syncopal episode.

[Alleviation of carotid sinus syncope and removal of cardiac pacing after regression of cervical malignant lymphoma].

A 68-year-old man developed a rapidly-growing right cervical tumor, a biopsy of which allowed for the diagnosis of diffuse large B-cell lymphoma, not otherwise specified. Magnetic resonance imaging demonstrated a right cervical mass lesion of 80 mm in diameter that extended from the medial region of the parotid gland to the posterior region of the neck. While undergoing a chest X-ray in an upright position, he lost consciousness and briefly fell. A transient loss of consciousness recurred while changing his position on the bed, and an electrocardiogram at that time revealed sinus arrest of a seven second duration. This syncope was considered to be a carotid sinus syncope (CSS) induced by the compression of the carotid sinus by his cervical bulky lymphoma. Temporary cardiac pacing was immediately started and rituximab was administered. Three days later, CHOP therapy was started. As his cervical tumor rapidly shrank, the frequency of sensed sinus arrests decreased to zero per day by day 9 of CHOP therapy, resulting into the removal of the pacemaker. In certain cases with CSS due to cervical lymphoma, cardiac pacing, if needed at the onset, is considered to become removable early after chemotherapy in association with tumor shrinkage.

Safety Signal Evaluation of a Risk of Syncope and Dizziness Not Related to Bleeding or Stroke in Direct Oral Anticoagulant-treated Patients.

PURPOSE: In clinical studies, rivaroxaban treatment has been associated with increased incidence of syncope not related to bleeding, anemia, or stroke. The study objective was to evaluate the occurrence of dizziness and/or syncope not related to bleeding, anemia, or stroke in patients treated with direct oral anticoagulants (DOACs). METHODS: A retrospective, observational, comparative study of adult patients diagnosed with atrial fibrillation and treated with DOACs was conducted using digital retrieval of medical records. Primary outcomes were an emergency department (ED) visit or hospitalization due to syncope, fall, or dizziness. Cases related to bleeding, anemia, or stroke were excluded. Separate examination of a sample of records validated the data. FINDINGS: Of 6467 eligible patients, 256 (4%) were hospitalized or referred to the ED due to fall, syncope, or dizziness during a mean observation period of 20.1 months. After multivariate regression analysis, statistically independent risk factors were found to be age (hazard ratio [HR] = 1.04, P < 0.0001) and benzodiazepine use (HR = 1.33, P = 0.03). No statistically significant difference was found among the different DOAC types regarding the primary outcome (apixaban and rivaroxaban HR = 0.97, P = 0.85; dabigatran and rivaroxaban HR = 1.2, P = 0.386). IMPLICATIONS: The study results failed to confirm the claimed association between the use of a DOAC and syncopal symptoms unrelated to bleeding, anemia, or stroke in this relatively large Israeli patient population. Age and benzodiazepine treatment were significant independent risk factors of these events.

Ventricular fibrillation in loop recorder memories in a patient with early repolarization syndrome.

We report the first documentation of spontaneous ventricular fibrillation by a loop recorder in a patient with an ECG pattern of early repolarization (ER) in the inferior leads and presenting with syncope.