Patterns of comorbidities in patients with atrial fibrillation and impact on management and long-term prognosis: an analysis from the Prospective Global GLORIA-AF Registry.

BACKGROUND: Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk of major outcomes. METHODS: From the prospective GLORIA-AF Registry, we performed a latent class analysis based on 18 diseases, encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed. RESULTS: 32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes: (i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv) thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49-2.09] and 1.57 [1.35-1.81], respectively); similar results were observed for beta-blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity groups (hazard ratio and 95%CI: 1.37 [1.13-1.67] and 1.47 [1.24-1.75], respectively). CONCLUSIONS: Comorbidities influence management and long-term prognosis of patients with AF. Patients with complex phenotypes may require comprehensive and holistic approaches to improve their prognosis.

Cardiovascular dysautonomia in postacute sequelae of SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) has led to a worldwide pandemic that continues to transform but will not go away. Cardiovascular dysautonomia in postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection has led to persistent symptoms in a large number of patients. Here, we define the condition and its associated symptoms as well as potential mechanisms responsible. We provide a careful and complete overview of the topic addressing novel studies and a generalized approach to the management of individuals with this complex and potentially debilitating problem. We also discuss future research directions and the important knowledge gaps to be addressed in ongoing and planned studies.

Sleep-Disordered Breathing and Cardiac Arrhythmias in Adults: Mechanistic Insights and Clinical Implications: A Scientific Statement From the American Heart Association.

Sleep-disordered breathing (SDB), characterized by specific underlying physiological mechanisms, comprises obstructive and central pathophysiology, affects nearly 1 billion individuals worldwide, and is associated with excessive cardiopulmonary morbidity. Strong evidence implicates SDB in cardiac arrhythmogenesis. Immediate consequences of SDB include autonomic nervous system fluctuations, recurrent hypoxia, alterations in carbon dioxide/acid-base status, disrupted sleep architecture, and accompanying increases in negative intrathoracic pressures directly affecting cardiac function. Day-night patterning and circadian biology of SDB-induced pathophysiological sequelae collectively influence the structural and electrophysiological cardiac substrate, thereby creating an ideal milieu for arrhythmogenic propensity. Cohort studies support strong associations of SDB and cardiac arrhythmia, with evidence that discrete respiratory events trigger atrial and ventricular arrhythmic events. Observational studies suggest that SDB treatment reduces atrial fibrillation recurrence after rhythm control interventions. However, high-level evidence from clinical trials that supports a role for SDB intervention on rhythm control is not available. The goals of this scientific statement are to increase knowledge and awareness of the existing science relating SDB to cardiac arrhythmias (atrial fibrillation, ventricular tachyarrhythmias, sudden cardiac death, and bradyarrhythmias), synthesizing data relevant for clinical practice and identifying current knowledge gaps, presenting best practice consensus statements, and prioritizing future scientific directions. Key opportunities identified that are specific to cardiac arrhythmia include optimizing SDB screening, characterizing SDB predictive metrics and underlying pathophysiology, elucidating sex-specific and background-related influences in SDB, assessing the role of mobile health innovations, and prioritizing the conduct of rigorous and adequately powered clinical trials.

Initial heart rate score predicts new-onset atrial tachyarrhythmias in pacemaker patients.

AIMS: Heart rate score (HRSc), the per cent of atrial paced and sensed event in the largest 10 b.p.m. rate histogram bin of a pacemaker, predicts survival in patients with cardiac devices. No correlation between HRSc and development of atrial fibrillation (AF) has been reported. In this study, we evaluated the relationship between pacemaker post-implantation HRSc and the incidence of newly developed atrial tachyarrhythmias (ATAs). METHODS AND RESULTS: Patients with dual-chamber pacemakers, implanted 2013-17, with the LATITUDE remote monitoring data with ≥600 000 beats of histogram data collected at baseline were included (N = 34 543). Heart rate score was determined from the initial 3-month post-implantation histogram data. Patients were excluded if they had ATAs, defined as atrial high-rate episodes >5 min or >1% of right atrial beats >170 b.p.m. during the initial 3 months post-implantation. New ATAs, after the baseline period, were defined by each of the following: >1, >10, or >25% of atrial beats >170 b.p.m. or atrial tachycardia response (ATR) events >24 h. Patients were followed a median of 2.8 (1.0-4.0) years. The incidence of ATAs increased in proportion to HRSc (log-rank P-value <0.001), and the initial HRSc ≥70% was associated with increased ATAs by all definitions. Patients with initial HRSc ≥70% were older, had a higher percentage of right atrium pacing (%RA pacing), had a lower percentage of right ventricular pacing (%RV pacing), and were more likely programmed with rate-response vs. subjects with HRSc <70%. Initial HRSc (hazard ratio: 1.07, 95% confidence interval: 1.05-1.09; P < 0.0001) independently predicted ATAs after adjusting for age, gender, %RV pacing, and rate-response programming. The %RA pacing and initial HRSc were correlated. CONCLUSION: Heart rate score independently predicts any subsequent duration of ATAs in pacemaker patients.

Combined atrial fibrillation ablation and left atrial appendage occlusion procedure in the United States: a propensity score matched analysis from 2016-2019 national readmission database.

AIMS: The safety and feasibility of combining percutaneous catheter ablation (CA) for atrial fibrillation with left atrial appendage occlusion (LAAO) as a single procedure in the USA have not been investigated. We analyzed the US National Readmission Database (NRD) to investigate the incidence of combined LAAO + CA and compare major adverse cardiovascular events (MACEs) with matched LAAO-only and CA-only patients. METHODS AND RESULTS: In this retrospective study from NRD data, we identified patients undergoing combined LAAO and CA procedures on the same day in the USA from 2016 to 2019. A 1:1 propensity score match was performed to identify patients undergoing LAAO-only and CA-only procedures. The number of LAAO + CA procedures increased from 28 (2016) to 119 (2019). LAAO + CA patients (n = 375, mean age 74 ± 9.2 years, 53.4% were males) had non-significant higher MACE (8.1%) when compared with LAAO-only (n = 407, 5.3%) or CA-only patients (n = 406, 7.4%), which was primarily driven by higher rate of pericardial effusion (4.3%). All-cause 30-day readmission rates among LAAO + CA patients (10.7%) were similar when compared with LAAO-only (12.7%) or CA-only (17.5%) patients. The most frequent primary reason for readmissions among LAAO + CA and LAAO-only cohorts was heart failure (24.6 and 31.5%, respectively), while among the CA-only cohort, it was paroxysmal atrial fibrillation (25.7%). CONCLUSION: We report an 63% annual growth (from 28 procedures) in combined LAAO and CA procedures in the USA. There were no significant difference in MACE and all-cause 30-day readmission rates among LAAO + CA patients compared with matched LAAO-only or CA-only patients.

Impact of chronic obstructive pulmonary disease in patients with atrial fibrillation: an analysis from the GLORIA-AF registry.

AIMS: Chronic obstructive pulmonary disease (COPD) may influence management and prognosis of atrial fibrillation (AF), but this relationship has been scarcely explored in contemporary global cohorts. We aimed to investigate the association between AF and COPD, in relation to treatment patterns and major outcomes. METHODS AND RESULTS: From the prospective, global GLORIA-AF registry, we analysed factors associated with COPD diagnosis, as well as treatment patterns and risk of major outcomes in relation to COPD. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). A total of 36 263 patients (mean age 70.1 ± 10.5 years, 45.2% females) were included; 2,261 (6.2%) had COPD. The prevalence of COPD was lower in Asia and higher in North America. Age, female sex, smoking, body mass index, and cardiovascular comorbidities were associated with the presence of COPD. Chronic obstructive pulmonary disease was associated with higher use of oral anticoagulant (OAC) [adjusted odds ratio (aOR) and 95% confidence interval (CI): 1.29 (1.13-1.47)] and higher OAC discontinuation [adjusted hazard ratio (aHR) and 95% CI: 1.12 (1.01-1.25)]. Chronic obstructive pulmonary disease was associated with less use of beta-blocker [aOR (95% CI): 0.79 (0.72-0.87)], amiodarone and propafenone, and higher use of digoxin and verapamil/diltiazem. Patients with COPD had a higher hazard of primary composite outcome [aHR (95% CI): 1.78 (1.58-2.00)]; no interaction was observed regarding beta-blocker use. Chronic obstructive pulmonary disease was also associated with all-cause death [aHR (95% CI): 2.01 (1.77-2.28)], MACEs [aHR (95% CI): 1.41 (1.18-1.68)], and major bleeding [aHR (95% CI): 1.48 (1.16-1.88)]. CONCLUSION: In AF patients, COPD was associated with differences in OAC treatment and use of other drugs; Patients with AF and COPD had worse outcomes, including higher mortality, MACE, and major bleeding.

EHRA expert consensus document on the management of arrhythmias in frailty syndrome, endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA).

There is an increasing proportion of the general population surviving to old age with significant chronic disease, multi-morbidity, and disability. The prevalence of pre-frail state and frailty syndrome increases exponentially with advancing age and is associated with greater morbidity, disability, hospitalization, institutionalization, mortality, and health care resource use. Frailty represents a global problem, making early identification, evaluation, and treatment to prevent the cascade of events leading from functional decline to disability and death, one of the challenges of geriatric and general medicine. Cardiac arrhythmias are common in advancing age, chronic illness, and frailty and include a broad spectrum of rhythm and conduction abnormalities. However, no systematic studies or recommendations on the management of arrhythmias are available specifically for the elderly and frail population, and the uptake of many effective antiarrhythmic therapies in these patients remains the slowest. This European Heart Rhythm Association (EHRA) consensus document focuses on the biology of frailty, common comorbidities, and methods of assessing frailty, in respect to a specific issue of arrhythmias and conduction disease, provide evidence base advice on the management of arrhythmias in patients with frailty syndrome, and identifies knowledge gaps and directions for future research.

COVID-19 Vaccination and Cardiac Arrhythmias: A Review.

PURPOSE OF REVIEW: In this review, we aim to delve into the existing literature, seeking to uncover the mechanisms, investigate the electrocardiographic changes, and examine the treatment methods of various cardiac arrhythmias that occur after administration of the COVID-19 vaccine. RECENT FINDINGS: A global survey has exposed an incidence of arrhythmia in 18.27% of hospitalized COVID-19 patients. Furthermore, any type of COVID-19 vaccine - be it mRNA, adenovirus vector, whole inactivated, or protein subunit - appears to instigate cardiac arrhythmias. Among the cardiac adverse events reported post-COVID-19 vaccination, myocarditis emerges as the most common and is thought to be a potential cause of bradyarrhythmia. When a patient post-COVID-19 vaccination presents a suspicion of cardiac involvement, clinicians should perform a comprehensive history and physical examination, measure electrolyte levels, conduct ECG, and carry out necessary imaging studies. In our extensive literature search, we uncovered various potential mechanisms that might lead to cardiac conduction abnormalities and autonomic dysfunction in patients who have received the COVID-19 vaccine. These mechanisms encompass direct viral invasion through molecular mimicry/spike (S) protein production, an escalated inflammatory response, hypoxia, myocardial cell death, and the eventual scar/fibrosis. They correspond to a range of conditions including atrial tachyarrhythmias, bradyarrhythmia, ventricular arrhythmias, sudden cardiac death, and the frequently occurring myocarditis. For treating these COVID-19 vaccination-induced arrhythmias, we should incorporate general treatment strategies, similar to those applied to arrhythmias from other causes.

Recognition, Prevention, and Management of Arrhythmias and Autonomic Disorders in Cardio-Oncology: A Scientific Statement From the American Heart Association.

With the advent of novel cancer therapeutics and improved screening, more patients are surviving a cancer diagnosis or living longer with advanced disease. Many of these treatments have associated cardiovascular toxicities that can manifest in both an acute and a delayed fashion. Arrhythmias are an increasingly identified complication with unique management challenges in the cancer population. The purpose of this scientific statement is to summarize the current state of knowledge regarding arrhythmia identification and treatment in patients with cancer. Atrial tachyarrhythmias, particularly atrial fibrillation, are most common, but ventricular arrhythmias, including those related to treatment-induced QT prolongation, and bradyarrhythmias can also occur. Despite increased recognition, dedicated prospective studies evaluating true incidence are lacking. Moreover, few studies have addressed appropriate prevention and treatment strategies. As such, this scientific statement serves to mobilize the cardio-oncology, electrophysiology, and oncology communities to develop clinical and scientific collaborations that will improve the care of patients with cancer who have arrhythmias.

Inappropriate sinus tachycardia: an examination of existing definitions.

AIMS: Inappropriate sinus tachycardia (IST) is a syndrome characterized by an elevated sinus rate unassociated with known physiological, pathological, or pharmacological causes. Despite published consensus documents, IST definitions appear to vary in the literature. In this study, we reviewed IST publications to evaluate IST definition variability and ascertain the degree to which consensus definitions are being adopted. METHODS AND RESULTS: English-language articles in PubMed, Ovid MEDLINE, Ovid Embase, and Google Scholar published from 1 January 1970 to 1 June 2021 with the title terms 'inappropriate sinus tachycardia,' 'non-paroxysmal sinus tachycardia,' or 'permanent sinus tachycardia' were searched. In each, the IST definition used, qualifying characteristics, and publications cited to support each definition were recorded. We identified 138 publications meeting the search criteria. Inappropriate sinus tachycardia definitions were provided in 114 of 138 articles (83%). A majority of definitions (92/114, 81%) used distinct heart rate (HR) thresholds. Among these, the most common threshold was ≥100 beats per minute (BPM) (75/92, 82%), mainly measured at rest (54/92, 59%). Most definitions (47/92, 51%) included a second criterion to qualify for IST; these were most often an HR threshold of 90 BPM measured over 24 h by ambulatory electrocardiogram (37/47, 79%). Diagnosis of exclusion was a common criterion (75/92, 82%) but symptom status was not (41/92, 45%). The 2015 Heart Rhythm Society IST consensus was commonly cited but adopted in only 37% of definitions published after 2015. CONCLUSIONS: Inappropriate sinus tachycardia definitions in current literature are inconsistent, and professional society consensus IST definitions have, to date, had limited impact.

Tilt testing remains a valuable asset.

Head-up tilt test (TT) has been used for >50 years to study heart rate/blood pressure adaptation to positional changes, to model responses to haemorrhage, to assess orthostatic hypotension, and to evaluate haemodynamic and neuroendocrine responses in congestive heart failure, autonomic dysfunction, and hypertension. During these studies, some subjects experienced syncope due to vasovagal reflex. As a result, tilt testing was incorporated into clinical assessment of syncope when the origin was unknown. Subsequently, clinical experience supports the diagnostic value of TT. This is highlighted in evidence-based professional practice guidelines, which provide advice for TT methodology and interpretation, while concurrently identifying its limitations. Thus, TT remains a valuable clinical asset, one that has added importantly to the appreciation of pathophysiology of syncope/collapse and, thereby, has improved care of syncopal patients.

REDUCE-IT USA: Results From the 3146 Patients Randomized in the United States.

BACKGROUND: Some trials have found that patients from the United States derive less benefit than patients enrolled outside the United States. This prespecified REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial) subgroup analysis was conducted to determine the degree of benefit of icosapent ethyl in the United States. METHODS: REDUCE-IT randomized 8179 statin-treated patients with qualifying triglycerides ≥135 and <500 mg/dL and low-density lipoprotein cholesterol >40 and ≤100 mg/dL and a history of atherosclerosis or diabetes mellitus to icosapent ethyl 4 g/d or placebo. The primary composite end point was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary composite end point was cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. A hierarchy was prespecified for examination of individual and composite end points. RESULTS: A total of 3146 US patients (38.5% of the trial) were randomized and followed for a median of 4.9 years; 32.3% were women and 9.7% were Hispanic. The primary composite end point occurred in 24.7% of placebo-treated patients versus 18.2% of icosapent ethyl-treated patients (hazard ratio [HR], 0.69 [95% CI, 0.59-0.80]; P=0.000001); the key secondary composite end point occurred in 16.6% versus 12.1% (HR, 0.69 [95% CI, 0.57-0.83]; P=0.00008). All prespecified hierarchical end points were meaningfully and significantly reduced, including cardiovascular death (6.7% to 4.7%; HR, 0.66 [95% CI, 0.49-0.90]; P=0.007), myocardial infarction (8.8% to 6.7%; HR, 0.72 [95% CI, 0.56-0.93]; P=0.01), stroke (4.1% to 2.6%; HR, 0.63 [95% CI, 0.43-0.93]; P=0.02), and all-cause mortality (9.8% to 7.2%; HR, 0.70 [95% CI, 0.55-0.90]; P=0.004); for all-cause mortality in the US versus non-US patients, Pinteraction=0.02. Safety and tolerability findings were consistent with the full study cohort. CONCLUSIONS: Whereas the non-US subgroup showed significant reductions in the primary and key secondary end points, the US subgroup demonstrated particularly robust risk reductions across a variety of individual and composite end points, including all-cause mortality. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01492361.

Guidance for Cardiac Electrophysiology During the COVID-19 Pandemic from the Heart Rhythm Society COVID-19 Task Force; Electrophysiology Section of the American College of Cardiology; and the Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, American Heart Association.

Coronavirus disease 2019 (COVID-19) is a global pandemic that is wreaking havoc on the health and economy of much of human civilization. Electrophysiologists have been impacted personally and professionally by this global catastrophe. In this joint article from representatives of the Heart Rhythm Society, the American College of Cardiology, and the American Heart Association, we identify the potential risks of exposure to patients, allied healthcare staff, industry representatives, and hospital administrators. We also describe the impact of COVID-19 on cardiac arrhythmias and methods of triage based on acuity and patient comorbidities. We provide guidance for managing invasive and noninvasive electrophysiology procedures, clinic visits, and cardiac device interrogations. In addition, we discuss resource conservation and the role of telemedicine in remote patient care along with management strategies for affected patients.

Predictors of myocardial recovery in arrhythmia-induced cardiomyopathy: A multicenter study.

BACKGROUND: Arrhythmia-induced cardiomyopathy (AIC) is characterized by improvement in left ventricular ejection fraction (LVEF) following arrhythmia treatment. Predictors of recovery in LVEF are not well understood. OBJECTIVE: We evaluated predictors of AIC recovery in a large multicenter cohort. METHODS: In total, 243 patients (age 65 ± 11, 73% male) with AIC caused by atrial fibrillation (49%), atrial tachycardia (20%), and premature ventricular contractions (PVCs; 31%) were treated and included. LVEF was assessed before and after treatment. Patients were stratified by arrhythmia duration (known [KN, n = 132] vs. unknown [UKN, n = 111]), arrhythmia type, LVEF, and presence of structural heart disease (SHD). RESULTS: Arrhythmia treatment was rhythm control in 95%. Median arrhythmia duration in the KN group was 47 months (25-75th percentile, 24-80 months). Post treatment LVEF was higher in KN group (55.9 ± 7 vs. 46.2 ± 12%; p < .0001) but the degree of LVEF improvement was similar (21.2 ± 9 vs. 19.4 ± 11; p = .16). Comparing highest quartile (longest arrhythmia duration) versus the rest of the KN group, the extent of LVEF improvement was similar (21.5 ± 8 vs. 21 ± 9%; p = .1). Patients in lowest index LVEF quartile (n = 74) had more PVC-induced AIC, greater EF improvement after treatment (24 ± 17 vs. 19 ± 7%; p < .0001) but lower post treatment EF (45 ± 14 vs. 54 ± 8%; p < .0001) versus other patients. Patients with SHD had lower index EF (28 ± 8 vs. 34 ± 8%; p < .0001) and lower final EF (47 ± 12 vs. 56 ± 7; p ≪ .0001). In multivariate regression, low index LVEF predicted myocardial recovery (odds ratio, 11.4; p < .005). CONCLUSIONS: In this AIC cohort, LVEF improved regardless of arrhythmia duration or type but those with PVCs had lower index LVEF and had less recovery. Low index LVEF predicted LVEF recovery following arrhythmia treatment.

Outcomes and predictors of readmission after implantation of a percutaneous left atrial appendage occlusion device in the United States: A propensity score-matched analysis from The National Readmission Database.

BACKGROUND: Left atrial appendage occlusion (LAAO) devices have become a favorable alternative option among nonvalvular atrial fibrillation (AF) patients with long-term contraindication to anticoagulation. Real-world experience with postprocedural readmission rates and predictors of readmission in LAAO patients is limited. OBJECTIVE: To assess all-cause 30-day readmission rate and predictors of readmission after LAAO procedure in the United States. METHOD: This retrospective observational study included all AF patients undergoing percutaneous LAAO procedures in the United States from January 1, 2016, and December 31, 2017, in the National Readmission Database. The primary outcome measure was all-cause 30-day readmission. A propensity score-matched analysis compared outcomes with a non-LAAO AF cohort. RESULT: Among 14 024 LAAO procedures (age: 76 ± 8 years; 60.5% males), 9.4% were readmitted within 30-days and, 0.2% died during their index hospitalization. The most frequent primary diagnosis during readmission among LAAO was gastrointestinal bleeding (12%). The incidence of LAAO procedures increased by 102%. In the multivariate model, gender and CHA2 DS2 -VASc failed to predict readmission. Age 55-64 years had lower odds (adjusted odds ratios [aOR]: 0.41; 95% confidence interval [CI]: 0.18-0.94), while drug abuse (aOR: 4.1; 95% CI: 1.34-12.54), and deficiency anemia (aOR: 1.88; 95% CI: 1.12-3.18) had higher odds of readmission. In propensity-matched cohort, compared to non-LAAO AF, LAAO patients had lower 30-day readmission (9.4% vs. 10.98%, p = .002) and all-cause in-hospital mortality (0.19% vs. 0.57%, p < .001). CONCLUSION: The readmission rate following the LAAO procedure is substantial (approximately 10%), and largely attributable to gastrointestinal bleeding. Factors such as drug abuse and anemia must be explored further to minimize readmission risk.

Mineral oil: safety and use as placebo in REDUCE-IT and other clinical studies.

Mineral oil is often used as a clinical trial placebo. Pharmaceutical-grade mineral oil consists of a mixture of saturated hydrocarbons, with a purity and chemical structure that differs substantially from food-grade or technical-/industrial-grade mineral oils. Interest in mineral oil was piqued by suggestions that a portion of the substantially positive results of the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) might be attributable to the theoretical negative effects of mineral oil rather than being due to the clinical benefits of icosapent ethyl. The objective of this review was to explore possible mineral oil safety and efficacy effects and contextualize these findings in light of the REDUCE-IT conclusions. A literature search identified studies employing mineral oil placebos. Eighty studies were identified and relevant data extracted. Adverse events associated with mineral oil were generally gastrointestinal and consistent with use as a lubricant laxative. Changes in triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and other biomarkers were inconsistent and generally not statistically significant, or clinically meaningful with mineral oil, as were changes in blood pressure. There was no consistent evidence that mineral oil in the amounts used in the REDUCE-IT or Effect of Vascepa on Progression of Coronary Atherosclerosis in Patients With Elevated Triglycerides on Statin Therapy (EVAPORATE) trials affects absorption of essential nutrients or drugs, including statins. These results were then considered alongside publicly available data from REDUCE-IT. Based on available evidence, mineral oil does not appear to impact medication absorption or efficacy, or related clinical outcomes, and, therefore, does not meaningfully affect study conclusions when used as a placebo at the quantities used in clinical trials.

Inappropriate sinus tachycardia.

Inappropriate sinus tachycardia (IST) is a clinical syndrome, oftentimes debilitating, defined by fast sinus rates (>100 b.p.m. at rest or >90 b.p.m. on average over 24 h and not due to underlying causes) associated with symptoms that may include palpitations, as described in some guidelines and consensus documents. While heart rates may vary by patient, especially based upon gender and age, some individuals experience sinus tachycardia or persistent fast sinus rates with no symptoms; these individuals would not necessarily be considered to have the syndrome of IST. Various explanations for IST have been considered but a definitive common mechanism is not yet known; the true aetiology may be multifactorial. A thorough evaluation of secondary causes of tachycardia is required in the work-up of all cases and if found, must be treated before a diagnosis of IST can be made. Finally, effective treatments vary but can include ivabradine, beta-blockers, or calcium channel antagonists; ablation is seldom advised.