Prevention and Treatment of Atrial Fibrillation via Risk Factor Modification.

Atrial fibrillation (AF) is the most common clinically significant arrhythmia, and it increases stroke risk. A preventive approach to AF is needed because virtually all treatments such as cardioversion, antiarrhythmic drugs, ablation, and anticoagulation are associated with high cost and carry significant risk. A systematic review was performed to identify effective lifestyle-based strategies for reducing primary and secondary AF. A PubMed search was performed using articles up to March 1, 2021. Search terms included atrial fibrillation, atrial flutter, exercise, diet, metabolic syndrome, type 2 diabetes mellitus, obesity, hypertension, stress, tobacco smoking, alcohol, Mediterranean diet, sodium, and omega-3 fatty acids. Additional articles were identified from the bibliographies of retrieved articles. The control of hypertension, ideally with a renin-angiotensin-aldosterone system inhibitor, is effective for preventing primary AF and recurrence. Obstructive sleep apnea is a common cause of AF, and treating it effectively reduces AF episodes. Alcohol increases the risk of AF in a dose-dependent manner, and abstinence reduces risk of recurrence. Sedentary behavior and chronic high-intensity endurance exercise are both risk factors for AF; however, moderate physical activity is associated with lower risk of AF. Recently, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 agonists have been associated with reduced risk of AF. Among overweight/obese patients, weight loss of ≥10% is associated with reduced AF risk. Lifestyle changes and risk factor modification are highly effective for preventing AF.

Takotsubo Syndrome: Cardiotoxic Stress in the COVID Era.

Takotsubo syndrome (TTS), also known as stress cardiomyopathy and broken heart syndrome, is a neurocardiac condition that is among the most dramatic manifestations of psychosomatic disorders. This paper is based on a systematic review of TTS and stress cardiomyopathy using a PubMed literature search. Typically, an episode of severe emotional or physical stress precipitates regions of left ventricular hypokinesis or akinesis, which are not aligned with a coronary artery distribution and are out of proportion to the modest troponin leak. A classic patient with TTS is described; one who had chest pain and dyspnea while watching an anxiety-provoking evening news program on the coronavirus disease 2019 (COVID-19) pandemic. An increase in the incidence of TTS appears to be a consequence of the COVID-19 pandemic, with the TTS incidence rising 4.5-fold during the COVID-19 pandemic even in individuals without severe acute respiratory syndrome coronavirus 2 infection. Takotsubo syndrome is often mistaken for acute coronary syndrome because they both typically present with chest pain, electrocardiographic changes suggesting myocardial injury/ischemia, and troponin elevations. Recent studies report that the prognosis for TTS is similar to that for acute myocardial infarction. This review is an update on the mechanisms underlying TTS, its diagnosis, and its optimal management.

Physicians' opinions following pharmacogenetic testing for psychotropic medication.

Pharmacogenetics seeks to improve patient drug response and decrease side effects by personalizing prescriptions using genetic information. Since 2012, by one estimate, the number of patients who have had pharmacogenetic testing has doubled and this number is expected to double again by 2015. Given the increasing evidence for genetic influences on treatment response, we deemed it important to study physicians' opinions of pharmacogenetic testing. Surveys were completed by 168 Canadian physicians who had ordered at least one pharmacogenetic test (in particular for CYP2D6 or CYP2C19) for the prescription of psychiatric medication. Our results indicated that 80% of respondents believe genetic testing would become common standard in psychiatric drug treatment and 76% of respondents reported satisfactory or higher than satisfactory understanding of the pharmacogenetic report provided. Significantly more male physicians believed they had a higher understanding of the pharmacogenetic report compared to female physicians. To our knowledge, this is the only study that has assessed physicians' opinions of pharmacogenetic testing for psychotropic medication after they had received a pharmacogenetic report. Our results demonstrate a positive opinion of physicians on pharmacogenetics and indicate great potential for future clinical application.

The AmpliChip® CYP450 test and response to treatment in schizophrenia and obsessive compulsive disorder: a pilot study and focus on cases with abnormal CYP2D6 drug metabolism.

AIM: Genetic factors can result in variance in drug metabolism enzyme function, which is one major mechanism impacting on interindividual variability in response and side effects. We therefore performed a pilot study to investigate genetic variants in the drug metabolizing enzymes CYP2D6 and CYP2C19. METHODS: We evaluated 35 schizophrenic and 39 obsessive compulsive disorder (OCD) patients treated with various antipsychotics and antidepressants. Patients were assessed for treatment response and side effects. Genotyping for CYP2D6 and CYP2C19 was performed using the AmpliChip(®). Statistical analysis was performed using analysis of variance and Fisher's exact test. Cases of poor metabolizers (PMs) or ultrarapid metabolizers (UMs) were examined in further detail to assess medication outcomes. RESULTS: Statistical analysis identified no overall significant association of CYP2D6 metabolizer status with treatment response or occurrence of side effects. Nonetheless, case reports of PM and UM individuals indicated lack of response and/or occurrence of side effects in most of these patients. A secondary analysis comparing OCD subjects with impaired 2D6 function to extensive metabolizers was significant (p=0.021). CONCLUSION: Although not conclusive, there was some association between CYP2D6 impaired metabolic status and medication response. Our case reports suggest a potential clinical benefit of CYP genotyping for specific patients. Further validation of CYP2D6 and CYP2C19 testing in prospective, randomized trials is warranted.

Pharmacogenetics of alcohol, nicotine and drug addiction treatments.

The numerous premature deaths, medical complications and socio-economic repercussions of drug and alcohol addiction suggest that improvements in treatment strategies for addictive disorders are warranted. The use of pharmacogenetics to predict response to medication, side effects and appropriate dosages is relatively new in the field of drug addiction. However, increasing our understanding of the genetic factors influencing these processes may improve the treatment of addiction in the future. We examined the available scientific literature on pharmacogenetic advancements in the field of drug addiction with a focus on alcohol and tobacco to provide a summary of genes implicated in the effectiveness of pharmacotherapy for addiction. In addition, we reviewed pharmacogenetic research on cocaine and heroin dependence. Thus far, the most promising results were obtained for polymorphisms in the OPRM1 and CYP2A6 genes, which have been effective in predicting clinical response to naltrexone in alcoholism and nicotine replacement therapy in smoking, respectively. Opinions differ as to whether pharmacogenetic testing should be implemented in the clinic at this time because clinical utility and cost-effectiveness require further investigation. However, the data summarized in this review demonstrate that pharmacogenetic factors play a role in response to addiction pharmacotherapy and have the potential to aid in the personalization of addiction treatments. Such data may lead to improved cessation rates by allowing physicians to select medications for individuals based, at least in part, on genetic factors that predispose to treatment success or failure rather than on a trial and error basis.

Adenosine A1 and A2A receptors are not upstream of caffeine's dopamine D2 receptor-dependent aversive effects and dopamine-independent rewarding effects.

Caffeine is widely consumed throughout the world, but little is known about the mechanisms underlying its rewarding and aversive properties. We show that pharmacological antagonism of dopamine not only blocks conditioned place aversion to caffeine, but also reveals dopamine blockade-induced conditioned place preferences. These aversive effects are mediated by the dopamine D(2) receptor, as knockout mice showed conditioned place preferences in response to doses of caffeine that C57Bl/6 mice found aversive. Furthermore, these aversive responses appear to be centrally mediated, as a quaternary analog of caffeine failed to produce conditioned place aversion. Although the adenosine A(2A) receptor is important for caffeine's physiological effects, this receptor seems only to modulate the appetitive and aversive effects of caffeine. A(2A) receptor knockout mice showed stronger dopamine-dependent aversive responses to caffeine than did C57Bl/6 mice, which partially obscured the dopamine-independent and A(2A) receptor-independent preferences. Additionally, the A(1) receptor, alone or in combination with the A(2A) receptor, does not seem to be important for caffeine's rewarding or aversive effects. Finally, excitotoxic lesions of the tegmental pedunculopontine nucleus revealed that this brain region is not involved in dopamine blockade-induced caffeine reward. These data provide surprising new information on the mechanism of action of caffeine, indicating that adenosine receptors do not mediate caffeine's appetitive and aversive effects. We show that caffeine has an atypical reward mechanism, independent of the dopaminergic system and the tegmental pedunculopontine nucleus, and provide additional evidence in support of a role for the dopaminergic system in aversive learning.

A test of the opponent-process theory of motivation using lesions that selectively block morphine reward.

The opponent-process theory of motivation postulates that motivational stimuli activate a rewarding process that is followed by an opposed aversive process in a homeostatic control mechanism. Thus, an acute injection of morphine in nondependent animals should evoke an acute rewarding response, followed by a later aversive response. Indeed, the tegmental pedunculopontine nucleus (TPP) mediates the rewarding effects of opiates in previously morphine-naive animals, but not other unconditioned effects of opiates, or learning ability. The aversive opponent process for acute morphine reward was revealed using a place-conditioning paradigm. The conditioned place aversion induced by 16-h spontaneous morphine withdrawal from an acute morphine injection in nondependent rats was abolished by TPP lesions performed prior to drug experience. However, TPP-lesioned rats did show conditioned aversions for an environment paired with the acute administration of the opioid antagonist naloxone, which blocks endogenous opioids. The results show that blocking the rewarding effects of morphine with TPP lesions also blocked the opponent aversive effects of acute morphine withdrawal in nondependent animals. Thus, this spontaneous withdrawal aversion (the opponent process) is induced by the acute rewarding effects of morphine and not by other unconditioned effects of morphine, the pharmacological effects of morphine or endogenous opioids being displaced from opiate receptors.