Acute Effects of Coffee Consumption on Health among Ambulatory Adults.

BACKGROUND: Coffee is one of the most commonly consumed beverages in the world, but the acute health effects of coffee consumption remain uncertain. METHODS: We conducted a prospective, randomized, case-crossover trial to examine the effects of caffeinated coffee on cardiac ectopy and arrhythmias, daily step counts, sleep minutes, and serum glucose levels. A total of 100 adults were fitted with a continuously recording electrocardiogram device, a wrist-worn accelerometer, and a continuous glucose monitor. Participants downloaded a smartphone application to collect geolocation data. We used daily text messages, sent over a period of 14 days, to randomly instruct participants to consume caffeinated coffee or avoid caffeine. The primary outcome was the mean number of daily premature atrial contractions. Adherence to the randomization assignment was assessed with the use of real-time indicators recorded by the participants, daily surveys, reimbursements for date-stamped receipts for coffee purchases, and virtual monitoring (geofencing) of coffee-shop visits. RESULTS: The mean (±SD) age of the participants was 39±13 years; 51% were women, and 51% were non-Hispanic White. Adherence to the random assignments was assessed to be high. The consumption of caffeinated coffee was associated with 58 daily premature atrial contractions as compared with 53 daily events on days when caffeine was avoided (rate ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). The consumption of caffeinated coffee as compared with no caffeine consumption was associated with 154 and 102 daily premature ventricular contractions, respectively (rate ratio, 1.51; 95% CI, 1.18 to 1.94); 10,646 and 9665 daily steps (mean difference, 1058; 95% CI, 441 to 1675); 397 and 432 minutes of nightly sleep (mean difference, 36; 95% CI, 25 to 47); and serum glucose levels of 95 mg per deciliter and 96 mg per deciliter (mean difference, -0.41; 95% CI, -5.42 to 4.60). CONCLUSIONS: In this randomized trial, the consumption of caffeinated coffee did not result in significantly more daily premature atrial contractions than the avoidance of caffeine. (Funded by the University of California, San Francisco, and the National Institutes of Health; CRAVE ClinicalTrials.gov number, NCT03671759.).

Acute Impact of Fine Particulate Air Pollution on Cardiac Arrhythmias in a Population-Based Sample of Adolescents: The Penn State Child Cohort.

Background Fine particulate (fine particles with aerodynamic diameters ≤2.5 µm [PM2.5]) exposure has been associated with a risk of cardiac arrhythmias in adults. However, the association between PM2.5 exposure and cardiac arrhythmias in adolescents remains unclear. Methods and Results To investigate the association and time course between PM2.5 exposure with cardiac arrhythmias in adolescents, we analyzed the data collected from 322 adolescents who participated in the PSCC (Penn State Child Cohort) follow-up examination. We obtained individual-level 24-hour PM2.5 concentrations with a nephelometer. Concurrent with the PM2.5 measure, we obtained 24-hour ECG data using a Holter monitor, from which cardiac arrhythmias, including premature atrial contractions and premature ventricular contractions (PVCs), were identified. PM2.5 concentration and numbers of premature atrial contractions/PVCs were summarized into 30-minute-based segments. Polynomial distributed lag models within a framework of a negative binomial model were used to assess the effect of PM2.5 concentration on numbers of premature atrial contractions and PVCs. PM2.5 exposure was associated with an acute increase in number of PVCs. Specifically, a 10 µg/m3 increase in PM2.5 concentration was associated with a 2% (95% CI, 0.4%-3.3%) increase in PVC counts 0.5 to 1.0, 1.0 to 1.5, and 1.5 to 2.0 hours after the exposure. Cumulatively, a 10 µg/m3 increment in PM2.5 was associated with a 5% (95% CI, 1%-10%) increase in PVC counts within 2 hours after exposure. PM2.5 concentration was not associated with premature atrial contraction. Conclusions PM2.5 exposure was associated with an acute increased number of ventricular arrhythmias in a population-based sample of adolescents. The time course of the effect of PM2.5 on ventricular arrhythmia is within 2 hours after exposure.

Association between exposure to Efavirenz and substrates of dysrhythmia in HIV-infected young adults.

BACKGROUND: Dysrhythmia and sudden cardiac arrest occur more likely in HIV patients than healthy subjects. Thus, we need to examine dysrhythmias adverse effects of medications including Efavirenz as early as possible especially in young subjects. HYPOTHESIS: Efavirenz might have contributed to increased risk of developing common types of dysrhythmia in young HIV infected patients. METHODS: We performed a retrospective cohort study among 62 patients on Efavirenz and 38 controls. All participants were under 40 years old without cardiovascular disease. Total significant dysrhythmia in 24-hour ECG monitoring was the primary endpoint determined as the composite of high premature ventricular contraction (PVC) (>500 beats per 24 hours), high premature atrial contraction (PAC) (>500 bp24h), sinus pause, atrioventricular blocks, ventricular tachycardia, prolonged QTc, and low heart rate variability (HRV). Modified composite dysrhythmia consisted of low HRV (SD of normal-to-normal [SDNN]), high PVC and prolonged QT. RESULTS: Mean heart rate, Efavirenz regimen, male gender, and CD4 count predicted total dysrhythmia. Odds ratios were 1.108, 2.90, 4.36, and 0.96, respectively. The incidence of total dysrhythmia, high PVC, high PAC, low HRV(SDNN), and prolonged QTc were 54.8%, 41.85%, 9.71%, 45.2%, and 12.9% in patients on Efavirenz against 42.11%, 31.64%, 0%, 34.2%, and 7.91% in controls, respectively (p-values: .031, .001, <.0001, .063, and .043 respectively). Modified composite dysrhythmia was also more frequent in Efavirenz group than that of control group (69.42% vs. 52.60%, respectively p = .032). CONCLUSIONS: We found that patients with Efavirenz had higher prevalence of frequent PVC, frequent PAC, total significant dysrhythmia, Low HRV and prolonged QTc than controls.

Cardiotoxic Effects of Micrurus surinamensis (Cuvier, 1817) Snake Venom.

Micrurus surinamensis is a coral snake from the Elapidae family of wide distribution in Amazonia Forest. Its venom contains neurotoxins that induce muscular and respiratory paralysis; however, its cardiovascular action is not yet characterized. The aim of this study was to investigate the cardiotoxic effects caused by M. surinamensis poisoning in rodents. Twelve guinea pigs (Cavia porcellus) were distributed in two groups (n = 6) named as control and envenomed. The control group received 0.2 ml of PBS/BSA via intramuscular injection (IM), while envenomed animals received 0.75 µg of venom per g of body weight, also via IM. Electrocardiographic examination (ECG) and biochemical serum tests were conducted before and 2 h after inoculation. ECG of the envenomed animals revealed severe progressive arrhythmias including atrioventricular block, supraventricular, and ventricular extrasystoles. Serum biochemistry showed significant increase in CK, CK-MB, and LDH enzymes corroborating the skeletal and cardiac muscle damage. Myonecrosis and degeneration were observed in both skeletal and heart muscle; nevertheless, transmission electron microscopy revealed cardiac muscle fibers fragmentation. In conclusion, M. surinamensis venom has a potent cardiotoxic activity eliciting arrhythmogenic effects and heart damage after only 2 h of envenomation.

Betel-Quid Chewing, Heart Failure, and Premature Ventricular Contractions in Patients with Cardiopulmonary Symptoms.

Betel-quid (BQ) is a commonly used psychoactive substance that renders a specific cardiotoxicity. The purpose of this study was to investigate the association between BQ chewing and premature ventricular contractions (PVC) in patients with cardiopulmonary symptoms, and examine the potential influences of cardiovascular and chronic diseases on such relationship. Participants were 146 patients with cardiopulmonary symptoms who participated in 24-h Holter electrocardiogram monitoring during 2012-2018 in a hospital serving residents that lived in a BQ high prevalence area. Data on substance uses and medical histories for cardiovascular and chronic diseases were collected. Baron-Kenny method was employed to evaluate possible mediation. In patients with cardiopulmonary symptoms, 36.3% were BQ users and 63.7% were nonusers. Adjusting for covariates, BQ chewing was significantly associated with heart failure and diabetes mellitus (adjusted odds ratio (aOR) = 3.4 and 2.3, respectively), but only heart failure was significantly correlated with a low and high level of PVC. Additionally controlling for the effect of heart failure, the risk of high PVC for BQ users reduced from 3.60 to 2.88; however, the risk for BQ chewers remained significant (95% CI: 1.06-7.84). Heart failure was found to explain 27.7% of the excessive effect of BQ use on high PVC. In conclusion, BQ use is directly associated with an elevated risk of high PVC in patients with cardiopulmonary symptoms. The higher risk might be elevated among patients who suffered heart failure. Given several research limitations, the findings from this study offer future opportunities for validation.

Oral caffeine intake amplifies the effect of isoproterenol in patients with frequent premature ventricular contractions.

AIMS: Infrequent appearance and failed induction of premature ventricular contractions (PVCs) at catheter ablation make their localization difficult and are associated with a poor procedural outcome. This study aimed to assess the effect of preprocedural oral caffeine intake on induction of PVCs during catheter ablation. METHODS AND RESULTS: Seventy patients (age: 54 ± 14 years, 37 men) undergoing catheter ablation for monofocal PVCs were randomized to receive oral caffeine (5 mg/kg) or placebo. Before ablation, PVC counts for 5 min were performed at baseline and during isoproterenol infusion and the isoproterenol washout period. PVC count fluctuation was defined as the difference between the highest and lowest 5-min count among the three-time periods. The 5-min PVC counts during baseline and isoproterenol infusion were equivalent between the groups. However, those during the isoproterenol washout period and PVC count fluctuation were significantly higher in the caffeine group than the control group (73.1 ± 73.2 vs. 38.9 ± 28.9 beats/5 min, P = 0.012 and 69.3 ± 61.3 vs. 37.7 ± 30.9 beats/5 min, P = 0.008, respectively). The procedure and ablation times were significantly shorter in the caffeine group than the control group (105.0 ± 23.4 vs. 136.9 ± 43.2 min, P < 0.01 and 219.1 ± 104.7 vs. 283.5 ± 136.0 sec, P < 0.01, respectively). CONCLUSION: Oral caffeine intake amplified the effect of isoproterenol infusion on PVC induction during catheter ablation. The combined use of oral caffeine intake and isoproterenol infusion can be an option to increase intraprocedural PVCs.

A case report on clozapine-induced ventricular ectopics: a fatal adverse drug reaction.

Background Clozapine is one of the most efficacious antipsychotic drug used for the treatment-resistant schizophrenia; it is sometimes associated with serious adverse reactions like agranulocytosis, myocarditis, cardiac rhythm disturbances, etc. Case presentation A 30-year-old patient with a primary diagnosis of paranoid schizophrenia (ICD code - F20.05) was on regular prescription for 6 years. Due to refractoriness, the patient was initiated on tablet clozapine. After 45 days of clozapine therapy, he presented with the complaints of worsening of positive symptoms and sudden falls associated with a brief period of unresponsiveness for which the patient was admitted for evaluation. After stabilization of the patient, it was concluded that he was suffering from ventricular ectopics based upon cardiac investigations like electrocardiogram (ECG) and Holter monitoring. Upon causality assessment between the adverse drug reaction (ADR) and the suspected drug using Naranjo Scale and WHO causality assessment scale, the ADR was found to be probable. Conclusions This case report will help to keep physicians vigilant about the rare cardiac side effects of clozapine and to do regular ECG monitoring of the patients who are on clozapine. Moreover, this case report generates the evidence of clozapine-induced arrhythmia, which is needed to be quantified with aggressive study design and there is a need to study the dose-dependent relationship of clozapine-induced arrhythmia.

Stepwise approach to induce infrequent premature ventricular complex using bolus isoproterenol and epinephrine infusion.

BACKGROUND: Paucity of a premature ventricular complex (PVC) during ablation procedures may occur and be associated with a lower success rate. Isoproterenol (ISP) injections are commonly used to induce PVC; however, the induced tachycardia sometimes prevents the appearance of PVC. Epinephrine (EPI) administration may be an alternative strategy to induce PVC due to its smaller effect on heart rate (HR). This study sought to examine the electrophysiological impact of EPI injection, with a stepwise induction protocol, for infrequent intraprocedural PVC. METHODS: We studied 78 consecutive patients who underwent catheter ablation of idiopathic frequent PVC. If no PVC was observed at the beginning of the procedure, ISP (10 µg) was injected. If clinical PVC was not induced by ISP administration, EPI (10 µg) was injected. RESULTS: Of 18 patients without PVC at baseline, ISP injection induced PVC in five patients. Of the remaining 13 patients, EPI injection successfully induced PVC in seven patients (53%). The maximum HR and increments of HR after EPI injection were significantly lower than those after ISP injection (99 ± 15 vs 137 ± 15 bpm, P = .001; 22 ± 10 vs 53 ± 12 bpm, P < .001, respectively). There were no complications related to the induction protocol. CONCLUSION: EPI injection following ISP injection is an effective and safe stepwise approach for the induction of infrequent PVC in the electrophysiology laboratory. It is hypothesized that α- and ß-adrenergic receptor stimulation by EPI injections, with reduced HR acceleration compared to that with ISP injections, may result in the successful induction of PVC.

Cannabidiol Interacts Significantly with Everolimus-Report of a Patient with Tuberous Sclerosis Complex.

A 6.5-year-old female patient with a TSC2 mutation had been given everolimus (EVE) for 3 years for pharmacoresistant focal epilepsy and for life-threatening, severe ventricular dysrhythmia. EVE had been started with daily dose of 0.15 mg/kg/day and was increased up to 0.6 mg/kg/day. Target blood trough levels of around 9 µg/L had been documented. Although EVE therapy revealed no effect on seizure activity, cardiac rhythm normalized completely. Thus, EVE was reduced to a dose of 0.3 mg/kg/day leading to stable blood trough levels of 4 to 5 µg/L. Due to refractory tonic seizures with a frequency of 1 to 4 per day, we initiated cannabidiol (CBD) treatment, raising it to a daily dose of 200 mg. After 6 weeks, the EVE blood trough levels rose to 12.0 µg/L. Although we halved the EVE dose, her EVE blood trough level continued increasing up to 16.0 µg/L.The CBD dose was increased to 500 mg/day (20.4 g/kg/day), but EEG parameters and seizures failed to respond. Serum concentrations of EVE were unstable under the co-medication with CBD. Depending on the CBD dose, they varied between 1.7 and 12.3 µg/L, while EVE was always administered at the same dose.Although never before reported, CBD and EVE appear to interact, due to the metabolic pathway through CYP 450 3A4. Although we detected no side effects in our patient, we strongly recommend drug monitoring using the combination of CBD with EVE to prevent harmful overdosing.

Ambient fine particulate matter (PM2.5) exposure is associated with idiopathic ventricular premature complexes burden: A cohort study with consecutive Holter recordings.

BACKGROUND: Epidemiological evidence has shown an association between ambient fine particulate matter (PM2.5) exposure and cardiovascular mortality. Increased ventricular premature complex (VPC) burden can cause left ventricular dilatation and dysfunction. We aimed to investigate the relationship between acute PM2.5 exposure and VPC burden in patients without structural heart disease. METHODS: We reviewed 26 820 patients who underwent 24-hour Holter electrocardiogram (ECG) recordings between 1 Jan 2013 and 1 Dec 2016. We enrolled patients with significant idiopathic (structurally normal heart) VPC burden defined as ≥30 VPCs/h (Lown grade 2) who had at least two Holter ECG recordings. The VPC burden between the studies on high and low PM2.5 exposure dates was compared in 24 and 12 hours time periods. RESULT: Sixty-seven patients (31 men, 56.49 ± 18.35 years) were enrolled. Patients were exposed to 25.63 ± 11.47 and 14.66 ± 7.51 µg/m 3 of PM2.5 during the high and low study dates, respectively. The overall VPC counts (10,490.69 ± 10,681.63/day) and burden (10.22% ± 10.17%) were significantly higher on the days with higher PM2.5 exposure compared with low PM2.5 exposure dates (8293.31 ± 9009.09; P = 0.014% and 9.14% ± 12.73%, P = 0.012, respectively). Compared with low PM2.5 exposure dates, the VPC burden on high exposure dates was significantly higher from 9 am to 9 pm (5.85% ± 6.41% vs 4.84% ± 6.97%; P = 0.025) but not at nocturnal periods. CONCLUSION: Our study demonstrated a significantly higher VPC burden on high PM2.5 exposure date. The burden was increased in the daytime but not at nighttime. This result suggests that daytime PM2.5 exposure may be associated with ventricular arrhythmia burden in the healthy population.

Premature ventricular contractions as a side effect of filgrastim in a child with B-thalassaemia.

Premature ventricular contractions are a rare side effect of filgrastim, reported mainly in elderly men. Here we report the case of a 9-year-old child with thalassaemia who developed frequent premature ventricular contractions after three doses of filgrastim were given for deferiprone-induced agranulocytosis. The arrhythmia resolved 3 weeks after discontinuation of filgrastim. Children treated with filgrastim should be carefully monitored for potentially serious arrhythmia.

Case report: electrical storm during induced hypothermia in a patient with early repolarization.

BACKGROUND: Population based studies showed an association of early repolarization in the electrocardiogram (ECG) and a higher rate of sudden cardiac death presumably due to ventricular fibrillation. The triggers for ventricular fibrillation in patients with early repolarization are not fully understood. CASE PRESENTATION: We describe the case of a young patient with a survived ventricular fibrillation arrest while asleep followed by multiple episodes of recurrent ventricular fibrillation. The admission ECG showed an early repolarization pattern with substantial J-point elevation in most of the ECG-leads. After initiation of a hypothermia protocol, the patient developed an electrical storm with multiple ventricular fibrillation episodes requiring multiple cardioversions. Intravenous isoproterenol infusion successfully suppressed the malignant arrhythmia. CONCLUSION: Hypothermia appears proarrhythmic in patients with early repolarization and may trigger ventricular fibrillation. This knowledge is particularly important when initiating temperature management protocols in patients after a survived cardiac arrest. During the acute phase of an early repolarization associated electrical storm, isoproterenol is the most effective treatment suppressing the ventricular fibrillation-inducing premature ventricular complexes at higher heart rates.

Ventricular Extrasystoles after First Dose of Sofosbuvir in a Patient Treated with Propranolol but not with Amiodarone: A Case Report.

BACKGROUND: Sofosbuvir is a direct-acting antiviral drug used to treat chronic hepatitis C infection. In 2015, Gilead Sciences, the manufacturer of sofosbuvir, warned that bradycardia could occur when sofosbuvir is administered in combination with amiodarone. Interestingly, among the reported cases of patients with sofosbuvir and amiodarone related bradycardia, some of them were also treated with propranolol. OBJECTIVE: We herein report a case of ventricular extrasystoles within three hours after the coadministration of sofosbuvir-containing regimen with propranolol. This patient had never been treated with amiodarone. After the sofosbuvir-containing regimen was stopped, ventricular extrasystoles disappeared within 24 hours. This observation suggests that the association of sofosbuvir with propranolol may have a role in the emergence of cardiac arrhythmia. CONCLUSION: Patients treated with amiodarone and/or propranolol should be continuously monitored within the early hours following the initiation of sofosbuvir.

Sleep Medications Containing Melatonin can Potentially Induce Ventricular Arrhythmias in Structurally Normal Hearts: A 2-Patient Report.

Idiopathic ventricular arrhythmias (IVAs) are relatively common in the general population and usually have a good prognosis. However, frequent premature ventricular contractions (PVCs) can lower the quality of life (in symptomatic cases) and can cause cardiomyopathy and sudden cardiac death. In this report, we demonstrate a novel trigger for IVAs. Melatonin use for treating sleep disorders has increased significantly in recent years. We provide here the first human evidence of its proarrhythmic effect by presenting 2 patients (with normal myocardium) with symptomatic PVCs, while on melatonin. Discontinuation of melatonin stopped PVCs in both patients. Our findings highlight the importance of identifying precipitating factors for IVAs.

Diospyros rhodocalyx (Tako-Na), a Thai folk medicine, associated with hypokalemia and generalized muscle weakness: a case series.

INTRODUCTION: Diospyros rhodocalyx (Tako-Na) is a Thai folk medicine purported to promote longevity, treat impotence, etc. We present patients with hypokalemia, weakness and hypertension after consuming Tako-Na tea. CASE SERIES: Case 1: A 61-year-old man was brought in nine hours after drinking 400-500 mL of Tako-Na tea. One handful of Tako-Na bark was boiled in water to make tea. He had vomiting and watery diarrhea six hours after drinking it. He took no medications and had no history of hypertension. The only remarkable vital sign was BP 167/90 mmHg. Physical examination revealed generalized muscle weakness. Laboratory findings were potassium 2.7 mmol/L, bicarbonate 24 mmol/L, and transtubular potassium gradient (TTKG) 5.6. He was discharged the next day with a BP 140/90 mmHg and potassium 4.2 mmol/L. Case 2: A 78-year-old man, a friend of case 1, also drank Tako-Na tea from the same pot at the same time as case 1. He also had vomiting and diarrhea six hours later. He took no medications despite past history of hypertension (baseline SBP 140-160). Initial BP was 230/70 mmHg. He also had muscle weakness. Laboratory findings were potassium 3.3 mmol/L, bicarbonate 24 mmol/L, TTKG 7.37 and normal thyroid function. He was also discharged the next day with a BP 148/70 mmHg and potassium 4.2 mmol/L. Case 3-7: These were patients reported to a poison center and their potassium concentrations were 1.4, 1.4, 3.3, 1.3 and 1.2 mmol/L, respectively. Three of them were intubated and case 3 died. CONCLUSIONS: Tako-Na contains betulin, betulinic acid, taraxerone, lupeol, and lupenone. Their structures are similar to glycyrrhetic acid, the active metabolite of glycyrrhizic acid found in licorice which is well known to cause pseudoaldosteronism. Glycyrrhetic acid is potent in inhibiting 11-beta-hydroxysteroid dehydrogenase, and causes pseudoaldosteronism. We hypothesize that the compounds in Tako-Na act in the same way as glycyrrhetic acid in producing pseudoaldosteronism.

Premature ventricular contractions associated with isotretinoin use

Abstract Isotretinoin has been considered a unique drug for acne treatment. However, it is associated with numerous adverse effects. Isotretinoin can trigger premature ventricular contractions. This report describes a 33-year-old-woman who presented with palpitations for 1 week while undergoing 1-month isotretinoin treatment for mild-moderate facial acne. An electrocardiogram and Holter monitoring showed premature ventricular contractions during isotretinoin (Roaccutane, Roche) treatment. Isotretinoin-related premature ventricular contractions were strongly suggested in this case due to the existence of documented premature ventricular contractions on electrocardiograms and the disappearance of these premature ventricular contractions two weeks after termination of the treatment To the authors' knowledge, there has been 1 reported case of premature ventricular contractions linked to isotretinoin use; this report describes a second such case.