-
Annals of Internal Medicine Jan 2021Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH).
PURPOSE
To examine the effects of intensive BP-lowering treatment on OH in hypertensive adults.
DATA SOURCES
MEDLINE, EMBASE, and Cochrane CENTRAL from inception through 7 October 2019, without language restrictions.
STUDY SELECTION
Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) that involved more than 500 adults with hypertension or elevated BP and that were 6 months or longer in duration. Trial comparisons were groups assigned to either less intensive BP goals or placebo, and the outcome was measured OH, defined as a decrease of 20 mm Hg or more in systolic BP or 10 mm Hg or more in diastolic BP after changing position from seated to standing.
DATA EXTRACTION
2 investigators independently abstracted articles and rated risk of bias.
DATA SYNTHESIS
5 trials examined BP treatment goals, and 4 examined active agents versus placebo. Trials examining BP treatment goals included 18 466 participants with 127 882 follow-up visits. Trials were open-label, with minimal heterogeneity of effects across trials. Intensive BP treatment lowered risk for OH (odds ratio, 0.93 [95% CI, 0.86 to 0.99]). Effects did not differ by prerandomization OH ( for interaction = 0.80). In sensitivity analyses that included 4 additional placebo-controlled trials, overall and subgroup findings were unchanged.
LIMITATIONS
Assessments of OH were done while participants were seated (not supine) and did not include the first minute after standing. Data on falls and syncope were not available.
CONCLUSION
Intensive BP-lowering treatment decreases risk for OH. Orthostatic hypotension, before or in the setting of more intensive BP treatment, should not be viewed as a reason to avoid or de-escalate treatment for hypertension.
PRIMARY FUNDING SOURCE
National Heart, Lung, and Blood Institute, National Institutes of Health. (PROSPERO: CRD42020153753).
Topics: Antihypertensive Agents; Blood Pressure; Blood Pressure Determination; Humans; Hypertension; Hypotension, Orthostatic
PubMed: 32909814
DOI: 10.7326/M20-4298 -
The American Journal of Medicine Dec 2020Guidelines recommend increased salt intake as a first-line recommendation in the management of symptomatic orthostatic hypotension and recurrent syncope. There have been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Guidelines recommend increased salt intake as a first-line recommendation in the management of symptomatic orthostatic hypotension and recurrent syncope. There have been no systematic reviews of this intervention. We sought to summarize the evidence for increased salt intake in patients with orthostatic intolerance syndromes.
METHODS
We conducted a systematic review and meta-analysis of studies in PubMed, EMBASE, and CINAHL. Interventional studies that increased salt intake in individuals with orthostatic intolerance syndromes were included. Primary outcome measures included incidence of falls and injuries, and rates of syncope and presyncope. Secondary outcome measures included other orthostatic intolerance symptoms, blood pressure, and heart rate.
RESULTS
A total of 14 studies were eligible, including participants with orthostatic hypotension, syncope, postural orthostatic tachycardia syndrome, and idiopathic orthostatic tachycardia (n = 391). Mean age was 35.6 (± 15) years. All studies were small and short-term (<60 mins-90 days). No study reported on the effect of increased salt intake on falls or injuries. Meta-analysis demonstrated that during head-up tilt, mean time to presyncope with salt intake increased by 1.57 minutes (95% confidence interval [CI], 1.26-1.88), mean systolic blood pressure increased by 12.27 mm Hg (95% CI, 10.86-13.68), and mean heart rate decreased by -3.97 beats per minute (95% CI, -4.08 to -3.86), compared with control. Increased salt increased supine blood pressure by 1.03 mm Hg (95% CI, 0.81 to 1.25). Increased salt intake resulted in an improvement or resolution of symptoms in 62.3% (95% CI, 51.6 to 72.6) of participants in short-term follow-up studies (mean follow-up of 44.3 days, 6 studies; n=91). Methodological quality of studies were low with high statistical heterogeneity in all meta-analyses.
CONCLUSIONS
Our meta-analysis provides low-quality evidence of a short-term improvement in orthostatic intolerance with increased salt intake. There were no clinical trials demonstrating the efficacy and safety of increased salt intake on long-term clinical outcomes. Overall, there is a paucity of clinical trial evidence to support a cornerstone recommendation in the management of orthostatic intolerance syndromes.
Topics: Adult; Humans; Middle Aged; Orthostatic Intolerance; Sodium Chloride, Dietary; Young Adult
PubMed: 32603788
DOI: 10.1016/j.amjmed.2020.05.028 -
Cureus Jun 2020Chronic myeloid leukemia (CML) represents a common condition in the spectrum of myeloproliferative disorders (MPD). It classically exhibits leukocytosis, but rarely... (Review)
Review
Chronic myeloid leukemia (CML) represents a common condition in the spectrum of myeloproliferative disorders (MPD). It classically exhibits leukocytosis, but rarely presents with isolated thrombocytosis. This paper is designed to review the clinicopathologic features, treatment, and outcomes of patients with CML who present with isolated thrombocytosis. We searched PubMed, MEDLINE®, ScienceDirect, and Scopus for English-language articles about case series and case reports for the period 2000-2020 with the terms "chronic myeloid leukemia" and "thrombocytosis" and pooled them with a case from our institution. Cases were also incorporated from the reference list and screened for inclusion. A total of 20 cases were included in the final cohort. The male-to-female ratio was 1:1.86. The mean age of the patients at the time of initial diagnosis was 40.5 years (range: 9-77 years). Out of 17 cases with available data, seven (41%) were asymptomatic and found to have thrombocytosis incidentally upon routine blood work. Five cases (29.4%) either had a history of thrombotic events or presented with severe thrombotic complications, including ischemic cerebrovascular accidents (CVA), myocardial infarction (MI), pulmonary embolism (PE), and/or miscarriages. Four cases (23.5%) had more than one symptom at presentation, including headache, syncope, and bruising. The average platelet count was 1,923 × 10/L (range: 584-8,688 × 10/L), and one case (5%) had anemia. The bone marrow (BM) examination showed normal cellularity and normal myeloid to erythroid (M/E) ratio in seven (50%) and 11 (84.6%) out of the 14 and 13 cases with reported data, respectively. Moreover, megakaryocytes in the BM were small in 10 cases (71.4%), pleomorphic in three cases (21.4%), and dysplastic in one case (7.1%). Accurate differentiation among MPD subtypes and the exclusion of CML is critical in reaching a proper diagnosis to decide on proper therapy and eventually modify outcomes. Prompt evaluation for the precise diagnosis of patients presenting with isolated marked thrombocytosis will help expedite their diagnosis and initiation of a specific tyrosine kinase inhibitor (TKI) therapy, thereby promptly inducing remission, preventing thrombotic complications, and avoiding adverse drug events, which would eventually improve outcomes.
PubMed: 32596094
DOI: 10.7759/cureus.8788 -
Pediatric Emergency Care Sep 2020The aims of the study were to perform the first systematic review of pediatric syncope etiologies and to determine the most common diagnoses with credible intervals...
OBJECTIVES
The aims of the study were to perform the first systematic review of pediatric syncope etiologies and to determine the most common diagnoses with credible intervals (CredIs).
METHODS
Review was performed within Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and used Embase, Scopus, PubMed, and the Cochrane Controlled Trial databases. The following inclusion criteria for the articles were used: minimum of 10 patients, standard definition of syncope used, subjects who were 21 years or younger, and subjects who were either a consecutive retrospective group or a prospective group. No restrictions were made regarding language of the studies, but an English abstract was required. The following information was collected: purpose of the study, definition of syncope, number of patients, patient age range, inclusion/exclusion criteria, and etiologies of syncope.
RESULTS
Of the 500 articles initially identified, 11 studies met the inclusion criteria and were the basis for this review. Three thousand seven hundred patients were included, ranging in age from 3 months to 21 years. The most common etiologies identified were vasovagal (52.2%; 95% CredI, 50.6-53.9), postural orthostatic tachycardia syndrome (13.1%; 95% CredI, 12.1-14.2), and cardiac causes (4.0%; 95% CredI, 3.39-4.65). A total of 18.3% (95% CredI, 17.0-19.5) of patients were found to have syncope of unknown cause.
CONCLUSIONS
Syncope is a common pediatric complaint. Most cases seen are a result of benign causes, with only a small percentage because of serious medical conditions. In addition, most syncopal episodes in the pediatric population are diagnosed clinically or with minimally invasive testing, emphasizing the importance of a detailed history and physical examination.
Topics: Child; Diagnosis, Differential; Humans; Medical History Taking; Physical Examination; Syncope
PubMed: 32530839
DOI: 10.1097/PEC.0000000000002149 -
Archives of Cardiovascular Diseases 2020The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK)... (Meta-Analysis)
Meta-Analysis
Cardiovascular safety of rapidly accelerated fibrosarcoma B-type and/or mitogen-activated extracellular signal-regulated kinase inhibitors: A mixed approach combining a meta-analysis and a pharmacovigilance disproportionality analysis.
BACKGROUND
The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is not fully characterized.
AIM
To evaluate the cardiovascular adverse events risks related to BRAF and/or MEK inhibitors in randomized placebo-controlled clinical trials and in the real-life setting.
METHODS
We used two approaches. First, we conducted a systematic review and meta-analysis of randomized placebo-controlled clinical trials reporting the incidence of cardiovascular adverse events for BRAF and/or MEK inhibitors in cancer patients. Second, we performed a disproportionality analysis, using age- and sex-adjusted reporting odds ratios (arORs) and their 95% confidence intervals (CIs) from the World Health Organization's pharmacovigilance database (VigiBase®) of anticancer drug-associated reports, to investigate real-life data.
RESULTS
MEK inhibitors increased the risk of ejection fraction decrease (odds ratio [OR] 3.35, 95% CI 1.58-7.07), peripheral oedema (OR 2.87 95% CI 1.93-4.27) and syncope (OR 6.71, 95% CI 3.00-14.99) compared with placebo in randomized placebo-controlled clinical trials. BRAF and MEK inhibitor combination therapy further increased the risk of ejection fraction decrease. In the disproportionality analysis, we found over-reporting of ejection fraction decrease (arOR 8.42, 95% CI 7.03-10.09), peripheral oedema (arOR 1.39, 95% CI 1.17-1.66), syncope (arOR 1.56, 95% CI 1.22-1.99), torsade de pointes/QT prolongation (arOR 6.13, 95% CI 5.04-7.47) and supraventricular arrhythmias (arOR 1.50, 95% CI 1.21-1.85) for BRAF and MEK inhibitors. BRAF and MEK inhibitors were not associated with hypertension in either approach.
CONCLUSIONS
In conclusion, MEK inhibitors increase the risk of ejection fraction decrease, peripheral oedema and syncope in randomized placebo-controlled clinical trials. Real-life data confirm these findings, and suggested additional risks of torsade de pointes/QT prolongation and supraventricular arrhythmias with BRAF/MEK inhibitors.
Topics: Adverse Drug Reaction Reporting Systems; Aged; Antineoplastic Agents; Cardiovascular Diseases; Databases, Factual; Female; Fibrosarcoma; Humans; Male; Middle Aged; Mitogen-Activated Protein Kinase Kinases; Patient Safety; Pharmacovigilance; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 32418884
DOI: 10.1016/j.acvd.2020.03.014 -
Heart Rhythm Jul 2020Vasovagal syncope (VVS) significantly reduces quality of life, yet lacks effective medical therapies. Pharmacological norepinephrine transporter (NET) inhibition... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vasovagal syncope (VVS) significantly reduces quality of life, yet lacks effective medical therapies. Pharmacological norepinephrine transporter (NET) inhibition increases synaptic norepinephrine reuptake, which may be able to prevent hypotension, bradycardia, and syncope.
OBJECTIVE
The objective of this systematic review was to evaluate the ability of 3 NET inhibitors-reboxetine, sibutramine, and atomoxetine-to prevent head-up tilt-induced vasovagal outcomes in healthy participants and patients with VVS.
METHODS
Relevant studies were identified from Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature without language restriction from database inception to August 2019. All randomized controlled trials comparing the benefit of a NET inhibitor vs placebo in adult populations were selected for review and meta-analysis.
RESULTS
Four studies (101 participants) met inclusion criteria. The mean study size was 25 (range 11-56) participants. NET inhibition reduced the likelihood of vasovagal reactions marked by hypotension and bradycardia in healthy participants during head-up tilt testing (relative risk 0.15; 95% confidence interval 0.04-0.52; P = .003). This relative risk reduction also occurred in patients with VVS during head-up tilt when given atomoxetine (relative risk 0.49; 95% confidence interval 0.28-0.86; P = .01). This was achieved through heart rate compensation with NET inhibition toward the end of tilt testing (106 ± 32 beats/min vs 60 ± 22 beats/min; P < .001), which in turn preserved cardiac output and mean arterial pressure (71 ± 20 mm Hg vs 43 ± 13 mm Hg; P < .001) in the absence of significantly increased systemic vascular resistance.
CONCLUSION
NET inhibition prevents severe vasovagal reactions and syncope induced by head-up tilt testing in both healthy participants and patients with VVS. Pharmacological NET inhibition is a promising potential treatment of recurrent syncope.
Topics: Adult; Cardiac Output; Heart Rate; Humans; Norepinephrine Plasma Membrane Transport Proteins; Quality of Life; Reboxetine; Syncope, Vasovagal; Young Adult
PubMed: 32151742
DOI: 10.1016/j.hrthm.2020.02.033 -
Frontiers in Genetics 2019Short QT syndrome (SQTS) is a rare syndrome and affects different types of genes. However, data on differences of clinical profile and outcome of different SQTS types...
BACKGROUND
Short QT syndrome (SQTS) is a rare syndrome and affects different types of genes. However, data on differences of clinical profile and outcome of different SQTS types are sparse.
METHODS
We conducted a pooled analysis of 110 SQTS patients. Patients have been diagnosed between 2000 and 2017 at our institution (n = 12) and revealed using a literature review (n = 98). 29 studies were identified by analysing systematic data bases (PubMed, Web of Science, Cochrane Libary, Cinahl).
RESULTS
67 patients with genotype positive SQTS origin and 43 patients with genotype negative origin were found. A significant difference is documented between the sex with a higher predominance of male in genotype negative SQTS patients and predominance of females in genotype positive SQTS patients (male 52% versus 84%, female 45% versus 14%; p = 0.0016). No relevant difference of their median age (genotype positive 27 ± 19 versus genotype negative 29 ± 15; p = 0.48) was found. Asymptomatic patients and patients reporting symptoms such as syncope, sudden cardiac death, atrial flutter and ventricular fibrillation documented in both groups were similar except atrial fibrillation (genotype positive 19% versus genotype negative 0%; p = 0.0055). The QTc interval was not significantly different in both groups (genotype positive 315 ± 32 versus genotype negative 320 ± 19; p = 0.30). The treatments (medical treatment and ICD implantation) in both groups were comparable. Electrophysiology studies were not significantly higher documented in patients with genotype positive and negative origin (24% versus 9%; p = 0.075). Events at follow up such as VT, VF, and SCD were not higher presented in patients with genotype positive (13% versus 9%) (p = 0.25). 54% of genotype positive SQTS patients showed SQTS 1 followed by STQS 2 (21%) and SQTS 3 (10%).
CONCLUSIONS
The long-term risk of a malignant arrhythmic event is not higher in patients with genotype positive. However, patients with genotype positive present themselves more often with AF with a female predominance. Also, other events at follow up such as syncope, atrial flutter and palpitation were not significantly higher (9% versus 0%; p = 0.079).
PubMed: 32010184
DOI: 10.3389/fgene.2019.01312 -
Frontiers in Pediatrics 2019Postural tachycardia syndrome (POTS) is a severe health problem in children. Short-term β-blockers are recommended for pharmaceutical treatment. However, there have...
Postural tachycardia syndrome (POTS) is a severe health problem in children. Short-term β-blockers are recommended for pharmaceutical treatment. However, there have been contradictory data about its efficacy among pediatric patients. Eight studies comparing β-blockers to conventional treatments for children with POTS were selected, where 497 cases of pediatric POTS were included. The efficacy of β-blockers was evaluated using the effective rate, the change of symptom score, the change of heart rate difference and adverse events. The results were stated as relative ratio (RR) and mean difference (MD) with a 95% confidence interval (95% CI). A random-effects meta-analysis for the effective rate indicated that β-blockers were more effective in treating pediatric POTS than controlled treatment (79.5 vs. 57.3%, RR = 1.50, 95%CI: 1.15-1.96, < 0.05). A fixed-effects model analysis showed that β-blockers were more effective in lowering the symptom score and the heart rate increment during standing test than controlled treatment with a mean difference of 0.81 (95% CI: 0.44-1.18, < 0.05) and 3.78 (95% CI: 2.10-5.46, < 0.05), respectively. There were no reported severe adverse events in included studies. β-blockers are effective in treating POTS in children and adolescents, alleviating orthostatic intolerance, and improving hemodynamic abnormalities.
PubMed: 31788462
DOI: 10.3389/fped.2019.00460 -
Journal of Arrhythmia Aug 2019Risk stratification in patients with asymptomatic Brugada Syndrome is challenging, and despite recent advances, there is no clear evidence. The first-degree...
BACKGROUND
Risk stratification in patients with asymptomatic Brugada Syndrome is challenging, and despite recent advances, there is no clear evidence. The first-degree atrioventricular block was hypothesized to be a predictor of arrhythmic events. Measurement of the PR interval and diagnosing atrioventricular block from surface ECG is easy, noninvasive, and cost-effective. We aimed to assess the latest evidence on PR interval or first-degree atrioventricular block and major arrhythmic events related to Brugada Syndrome.
METHODS
We performed a comprehensive search in PubMed for "atrioventricular block" OR "PR interval" and "Brugada syndrome." We included studies that have a component of PR interval and/or first-degree atrioventricular block and major arrhythmic events related to Brugada Syndrome including syncope/VT/VF/appropriate ICD shocks/ICD implantation.
RESULTS
We included 1526 subjects from 7 studies. Pooled mean difference of PR interval in 4 studies showed a significant difference [MD 10.77 ms (2.97-18.57) = 0.007, moderate-high heterogeneity I = 53% = 0.08]. On sensitivity analysis by removing a study, it became MD 6.50 ms [1.97-11.03], = 0.005, heterogeneity I = 0% = 0.52. Indicating that PR interval was prolonged by small margin. Pooled analysis of the association between a first-degree atrioventricular block and major arrhythmic events was significant [OR 3.33 (2.02-5.50) < 0.001, low heterogeneity I = 0% = 0.57].
CONCLUSION
First-degree AV block is associated with more frequent major arrhythmic events in Brugada syndrome patients. PR interval seemed to be prolonged but is yet to be determined whether the PR interval association is still significant if it did not cross the first-degree AVB threshold.
PubMed: 31410227
DOI: 10.1002/joa3.12188 -
BMC Cardiovascular Disorders Aug 2019Swallow or deglutition syncope is an unusual type of neurally-mediated syncope associated with life-threatening bradyarrhythmia and hypotension. It is a difficult...
BACKGROUND
Swallow or deglutition syncope is an unusual type of neurally-mediated syncope associated with life-threatening bradyarrhythmia and hypotension. It is a difficult condition to diagnose with commonly delayed diagnosis and management. There is lack of review articles that elucidate the basic demographics, clinical characteristics and management of this rare condition. This publication systematically reviews the 101 case reports published since 1793 on swallow syncope.
CASE PRESENTATION
A 59-year-old man presented with the complaint of recurrent dizziness associated with meals. A 24-h ambulatory ECG recording confirmed an episode of p-wave asystole at the time of food intake. Oesophagogastroduodenoscopy with balloon inflation in the mid to lower oesophagus resulted in a 5.6 s sinus pause. The patient's symptoms resolved completely following insertion of a permanent dual chamber pacemaker.
CONCLUSIONS
Swallow syncope is extremely rare, but still needs to be considered during diagnostic workup. It is commonly associated with gastro-intestinal disease. Permanent pacemaker implantation is the first line treatment.
Topics: Blood Pressure; Cardiac Pacing, Artificial; Deglutition; Eating; Heart Rate; Humans; Male; Middle Aged; Pacemaker, Artificial; Syncope; Treatment Outcome
PubMed: 31391000
DOI: 10.1186/s12872-019-1174-4