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.).

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.

Consumption of Caffeinated Products and Cardiac Ectopy.

BACKGROUND: Premature cardiac contractions are associated with increased morbidity and mortality. Though experts associate premature atrial contractions (PACs) and premature ventricular contractions (PVCs) with caffeine, there are no data to support this relationship in the general population. As certain caffeinated products may have cardiovascular benefits, recommendations against them may be detrimental. METHODS AND RESULTS: We studied Cardiovascular Health Study participants with a baseline food frequency assessment, 24-hour ambulatory electrocardiography (Holter) monitoring, and without persistent atrial fibrillation. Frequencies of habitual coffee, tea, and chocolate consumption were assessed using a picture-sort food frequency survey. The main outcomes were PACs/h and PVCs/hour. Among 1388 participants (46% male, mean age 72 years), 840 (61%) consumed ≥1 caffeinated product per day. The median numbers of PACs and PVCs/h and interquartile ranges were 3 (1-12) and 1 (0-7), respectively. There were no differences in the number of PACs or PVCs/h across levels of coffee, tea, and chocolate consumption. After adjustment for potential confounders, more frequent consumption of these products was not associated with ectopy. In examining combined dietary intake of coffee, tea, and chocolate as a continuous measure, no relationships were observed after multivariable adjustment: 0.48% fewer PACs/h (95% CI -4.60 to 3.64) and 2.87% fewer PVCs/h (95% CI -8.18 to 2.43) per 1-serving/week increase in consumption. CONCLUSIONS: In the largest study to evaluate dietary patterns and quantify cardiac ectopy using 24-hour Holter monitoring, we found no relationship between chronic consumption of caffeinated products and ectopy.

[Establishment of biological assess for quality control of Fuzi based on determination of premature ventricular contractions in rats].

Aconiti Lateralis Radix (Fuzi) is a toxic traditional Chinese medicine with definite efficacy. In order to improve the quality control of its different prepared products and ensure the security in clinic, it is significant to establish a method of quality evaluation related to clinic adverse effects. Aiming at the important biological marker of early cardiac toxicity reaction, there was no method to detect it. In this manuscript, a novel approach for measuring the minimal toxic dose (MTD) of premature ventricular contractions (PVC) poisoning of rats was established. Then, the determination methodology and conditions were optimized to meet the needs of the quality and biological assessment, including animal sex, weight, stability of standards and test solutions. Using this method, the MTD value of different Fuzi products were determined, such as Heishunpian, Baifupian, Zhengfupian, Baofupian, and Paotianxiong. The results showed that the MTD of Fuzi was significantly decreased after detoxification processed (P<0.05) and the MTD of Heishunpian, Zhengfupian, Baofupian and Baifupian was as much as 15.76, 22.36, 19.65 and 20.97 times to that of unprocessed Shengfuzi. In addition, Paotianxiong could not induce PVC in rats, which indicated that Paotianxiong was nontoxic and safe.This method could appropriately reflects the cardiotoxity of Fuzi and its prepared samples. Together with the chemical composition analysis, the contents of diester alkaloids were explored including aconitine, mesaconitine and hypaconitine as well as monoester alkaloids in Fuzi and its prepared products were significantly associated with PVC. Furthermore, there may be some components undetermined facilitating arrhythmia to be worth exploring. This research provides an overall and comprehensive approach to diagnose early clinical cardiotoxity and control the quality of Fuzi, which could not only be a complementary solution for the chemical evaluation, but a new method to ensure its efficacy and security of clinical application.

Right coronary cusp as a new window of ablation for pilsicainide-induced ventricular premature contractions in a patient with Brugada syndrome.

A previous study demonstrated that ventricular premature contractions (VPCs) and ventricular fibrillation (VF) are provoked during sodium channel blocker challenge tests in Brugada syndrome (BrS) patients (Morita et al., J Am Coll Cardiol 42:1624-1631, 2003). The right ventricular outflow tract (RVOT) is a major arrhythmogenic focus and isolated VPCs originating from that area have been shown to initiate VF (Kakishita et al., J Am Coll Cardiol 36:1646-1653, 2000). Here, we describe a case report of a BrS patient with VPCs arising from the posterior aspect of the RVOT epicardium which was provoked by a low-dose of pilsicainide, a pure sodium channel blocker, and was successfully ablated from the right coronary cusp.

Ventricular arrhythmias induced by long-term use of ephedrine in two competitive athletes.

Ephedrine is a sympathomimetic substance used by sportsmen as a doping substance because of its stimulating and slimming effects. We report two cases of ventricular arrhythmias induced by abuse of ephedrine in two competitive athletes. Endomyocardial biopsies guided by electroanatomic mapping revealed contraction-band necrosis, a myocardial injury frequently observed in cases of catecholamine excess. Our cases suggest that long-term abuse of ephedrine may result in myocardial damage, and that these structural alterations may promote areas of slow conduction favoring re-entrant ventricular tachyarrhythmias and a long-lasting risk of ventricular arrhythmias.

Local ß-adrenergic stimulation overcomes source-sink mismatch to generate focal arrhythmia.

RATIONALE: ß-Adrenergic receptor stimulation produces sarcoplasmic reticulum Ca(2+) overload and delayed afterdepolarizations in isolated ventricular myocytes. How delayed afterdepolarizations are synchronized to overcome the source-sink mismatch and produce focal arrhythmia in the intact heart remains unknown. OBJECTIVE: To determine whether local ß-adrenergic receptor stimulation produces spatiotemporal synchronization of delayed afterdepolarizations and to examine the effects of tissue geometry and cell-cell coupling on the induction of focal arrhythmia. METHODS AND RESULTS: Simultaneous optical mapping of transmembrane potential and Ca(2+) transients was performed in normal rabbit hearts during subepicardial injections (50 µL) of norepinephrine (NE) or control (normal Tyrode's solution). Local NE produced premature ventricular complexes (PVCs) from the injection site that were dose-dependent (low-dose [30-60 µmol/L], 0.45±0.62 PVCs per injection; high-dose [125-250 µmol/L], 1.33±1.46 PVCs per injection; P<0.0001) and were inhibited by propranolol. NE-induced PVCs exhibited abnormal voltage-Ca(2+) delay at the initiation site and were inhibited by either sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase inhibition or reduced perfusate [Ca(2+)], which indicates a Ca(2+)-mediated mechanism. NE-induced PVCs were more common at right ventricular than at left ventricular sites (1.48±1.50 versus 0.55±0.89, P<0.01), and this was unchanged after chemical ablation of endocardial Purkinje fibers, which suggests that source-sink interactions may contribute to the greater propensity to right ventricular PVCs. Partial gap junction uncoupling with carbenoxolone (25 µmol/L) increased focal activity (2.18±1.43 versus 1.33±1.46 PVCs per injection, P<0.05), which further supports source-sink balance as a critical mediator of Ca(2+)-induced PVCs. CONCLUSIONS: These data provide the first experimental demonstration that localized ß-adrenergic receptor stimulation produces spatiotemporal synchronization of sarcoplasmic reticulum Ca(2+) overload and release in the intact heart and highlight the critical nature of source-sink balance in initiating focal arrhythmias.

Direct effects of arsenic trioxide on action potentials in isolated cardiac tissues: importance of the choice of species, type of cardiac tissue and perfusion time.

INTRODUCTION: The aim of the present study was to evaluate direct/acute effects of arsenic trioxide on action potentials (APs) in isolated cardiac tissues, and to investigate if the choice of species and tissue and the duration of the perfusion play a role in arsenic-induced acute/direct prolongation of AP/QT. METHODS AND RESULTS: Direct electrophysiological effects of arsenic trioxide were measured in cardiac tissues isolated from four different species using micro-electrode recording. Arsenic (after 30 to 95 min perfusion at 10 µM) significantly prolonged APD(90), increased triangulation of the AP and elicited early afterdepolarizations (EADs) only in isolated guinea-pig and dog Purkinje fibers but not in rabbit and porcine (minipig) Purkinje fibers. Arsenic induced a prolongation of the APD(90) and increases in triangulation and the occurrence of EADs was not observed in papillary muscles of guinea-pigs and rabbits. Arsenic at 4 increasing concentrations from 0.1 µM to 10 µM at the standard perfusion-time of 15 min per concentration, and after a continuous 90-min perfusion at 1 µM and 1 Hz did not induce these direct effects on APD(90), triangulation and EADs in isolated guinea-pig Purkinje fibers, but it at 1 µM elicited EADs in 2 out of 7 preparations after 90 min at 0.2 Hz. DISCUSSION: The present study demonstrates that the choice of species and cardiac tissue as well as perfusion-time play important roles in arsenic-induced direct/acute effects on APD(90) and induction of EADs in vitro.

Five cases of aconite poisoning: toxicokinetics of aconitines.

Aconite poisoning was examined in five patients (four males and one female) aged 49 to 78 years old. The electrocardiogram findings were as follows: ventricular tachycardia and ventricular fibrillation in case 1, premature ventricular contraction and accelerated idioventricular rhythm in case 2, AIVR in case 3, and nonsustained ventricular tachycardia in cases 4 and 5. The patient in case 1 was given percutaneous cardiopulmonary support because of unstable hemodynamics, whereas the other patients were treated with fluid replacement and antiarrhythmic agents. The main aconitine alkaloid in each patient had a half-life that ranged from 5.8 to 15.4 h over the five cases, and other detected alkaloids had half-lives similar to the half-life of the main alkaloid in each case. The half-life of the main alkaloid in case 1 was about twice as long as the half-lives in the other cases, and high values for the area under the blood concentration-time curve and the mean residence time were only observed in case 1. These results suggest that alkaloid toxicokinetics parameters may reflect the severity of toxic symptoms in aconite poisoning.

Clinical features and management of herb-induced aconitine poisoning.

STUDY OBJECTIVE: We define the potential sources, clinical manifestations, and treatment of aconitine poisoning. METHODS: The database of the National Poison Center in Taiwan was retrospectively searched for the diagnosis of aconitine poisoning for 1990 to 1999. The reasons for taking the aconite roots, the clinical features, management, and possible predisposing factors were noted. RESULTS: A total of 17 cases occurred and consisted of 9 men and 8 women aged 30 to 70 years. Thirteen patients ingested aconite roots as treatment for rheumatism and wounds. Two patients volunteered to test the effects of aconite roots in a drug study. Two patients accidentally ingested the aconite roots. After a latent period of 10 to 90 minutes, patients developed a combination of neurologic (n=17), cardiovascular (n=14), gastrointestinal (n=9), and other (n=5) features typical of aconitine poisoning. Four patients developed ventricular tachycardia. All patients received supportive treatment. Patients with ventricular tachycardia were also treated with charcoal hemoperfusion. All patients made a complete recovery. CONCLUSION: Life-threatening ventricular tachycardia can occur after the consumption of aconite roots. The risk is higher with inadequately processed aconite roots, large doses, or tincture preparations. With increasing popularity of herbal medicines, herb-induced aconitine poisoning may also be seen in Western countries.

Ginkgo biloba-induced frequent ventricular arrhythmia.

The use of herbal medications is becoming ever more widespread, but data for them are not yet as robust as for conventional drugs. The available safety information indicates that potential side effects of such use can be due to allergic reactions and bleeding. In this report, a case of frequent ventricular arrhythmias probably due to Ginkgo biloba is presented. The patient complained of palpitations twice in a month and on both occasions symptoms and electrocardiographic evidence of ventricular arrhythmias resolved with discontinuation of Ginkgo biloba. This case underlines that continuing research is needed to elucidate the pharmacological activities of the many herbal remedies now being used.

Hydroxychloroquine overdose: toxicokinetics and management.

BACKGROUND: The management and toxicokinetics of hydroxychloroquine overdose are poorly described. CASE REPORT: We report a case of an 18-year-old girl who ingested 20 g of hydroxychloroquine. She developed marked hypokalemia, hypotension, and ventricular tachyarrhythmias but survived with treatment including intubation, adrenaline infusion, high-dose diazepam, and aggressive potassium replacement. Plasma hydroxychloroquine level was 29.40 mumol/L (9.87 mg/L) 2 hours after ingestion and the elimination half-life of hydroxychloroquine was 22 hours. CONCLUSIONS: The clinical manifestations of this hydroxychloroquine overdose were similar to those reported for chloroquine overdose and the management principles recommended for chloroquine overdose appeared to be efficacious in this case.