Recommendations regarding dietary intake and caffeine and alcohol consumption in patients with cardiac arrhythmias: what do you tell your patients to do or not to do?

OPINION STATEMENT: The etiology of arrhythmias including atrial fibrillation is multifactorial. Most arrhythmias are associated with comorbid illnesses like hypertension, diabetes, thyroid disease, or advanced age. Although it is tempting to blame a stimulant like caffeine as a trigger for arrhythmias, the literature does not support this idea. There is no real benefit to having patients with arrhythmias limit their caffeine intake. Caffeine is a vasoactive substance that also may promote the release of norepinephrine and epinephrine. However, acute ingestion of caffeine (as coffee or tea) does not cause atrial fibrillation. Even patients suffering a myocardial infarction do not have an increased incidence of ventricular or other arrhythmias after ingesting several cups of coffee. Large epidemiologic studies have also failed to find a connection between the amount of coffee/caffeine used and the development of arrhythmias. As such, it does not make sense to suggest that patients with palpitations, paroxysmal atrial fibrillation, or supraventricular tachycardia, abstain from caffeine use. Energy drinks are a new phenomenon on the beverage market, with 30-50 % of young adults and teens using them regularly. Energy drinks are loaded with caffeine, sugar, and other chemicals that can stimulate the cardiac system. There is an increasing body of mainly anecdotal case reports describing arrhythmias or even sudden death triggered by exercise plus using energy drinks. Clearly, there must be more study in this area, but it is wise to either limit or avoid their use in patients with arrhythmias. Moderate to heavy alcohol use seems to be associated with the development of atrial fibrillation. The term "holiday heart" was coined back in 1978, to describe patients who had atrial fibrillation following binge alcohol use. Thus, it is reasonable to recommend to patients with arrhythmias that they limit their alcohol use, although unfortunately this treatment will likely not completely resolve their arrhythmia.

History of the Plague: An Ancient Pandemic for the Age of COVID-19.

During the fourteenth century, the bubonic plague or Black Death killed more than one third of Europe or 25 million people. Those afflicted died quickly and horribly from an unseen menace, spiking high fevers with suppurative buboes (swellings). Its causative agent is Yersinia pestis, creating recurrent plague cycles from the Bronze Age into modern-day California and Mongolia. Plague remains endemic in Madagascar, Congo, and Peru. This history of medicine review highlights plague events across the centuries. Transmission is by fleas carried on rats, although new theories include via human body lice and infected grain. We discuss symptomatology and treatment options. Pneumonic plague can be weaponized for bioterrorism, highlighting the importance of understanding its clinical syndromes. Carriers of recessive familial Mediterranean fever (FMF) mutations have natural immunity against Y. pestis. During the Black Death, Jews were blamed for the bubonic plague, perhaps because Jews carried FMF mutations and died at lower plague rates than Christians. Blaming minorities for epidemics echoes across history into our current coronavirus pandemic and provides insightful lessons for managing and improving its outcomes.

Inductionless or limited shock testing is possible in most patients with implantable cardioverter- defibrillators/cardiac resynchronization therapy defibrillators: results of the multicenter ASSURE Study (Arrhythmia Single Shock Defibrillation Threshold Testing Versus Upper Limit of Vulnerability: Risk Reduction Evaluation With Implantable Cardioverter-Defibrillator Implantations).

BACKGROUND: Implantable cardioverter-defibrillators and cardiac resynchronization therapy defibrillators have relied on multiple ventricular fibrillation (VF) induction/defibrillation tests at implantation to ensure that the device can reliably sense, detect, and convert VF. The ASSURE Study (Arrhythmia Single Shock Defibrillation Threshold Testing Versus Upper Limit of Vulnerability: Risk Reduction Evaluation With Implantable Cardioverter-Defibrillator Implantations) is the first large, multicenter, prospective trial comparing vulnerability safety margin testing versus defibrillation safety margin testing with a single VF induction/defibrillation. METHODS AND RESULTS: A total of 426 patients receiving an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator underwent vulnerability safety margin or defibrillation safety margin screening at 14 J in a randomized order. After this, patients underwent confirmatory testing, which required 2 VF conversions without failure at < or = 21 J. Patients who passed their first 14-J and confirmatory tests, irrespective of the results of their second 14-J test, had their devices programmed to a 21-J shock for ventricular tachycardia (VT) or VF > or = 200 bpm and were followed up for 1 year. Of 420 patients who underwent 14-J vulnerability safety margin screening, 322 (76.7%) passed. Of these, 317 (98.4%) also passed 21-J confirmatory tests. Of 416 patients who underwent 14-J defibrillation safety margin screening, 343 (82.5%) passed, and 338 (98.5%) also passed 21-J confirmatory tests. Most clinical VT/VF episodes (32 of 37, or 86%) were terminated by the first shock, with no difference in first shock success. In all observed cases in which the first shock was unsuccessful, subsequent shocks terminated VT/VF without complication. CONCLUSIONS: Although spontaneous episodes of fast VT/VF were limited, there was no difference in the odds of first shock efficacy between groups. Screening with vulnerability safety margin or defibrillation safety margin may allow for inductionless or limited shock testing in most patients.

Functional roles of Cav1.3(alpha1D) calcium channels in atria: insights gained from gene-targeted null mutant mice.

BACKGROUND: Previous data suggest that L-type Ca2+ channels containing the Cav1.3(alpha(1D)) subunit are expressed mainly in neurons and neuroendocrine cells, whereas those containing the Cav1.2(alpha1C) subunit are found in the brain, vascular smooth muscle, and cardiac tissue. However, our previous report as well as others have shown that Cav1.3 Ca2+ channel-deficient mice (Cav1.3(-/-)) demonstrate sinus bradycardia with a prolonged PR interval. In the present study, we extended our study to examine the role of the Cav1.3(alpha1D) Ca2+ channel in the atria of Cav1.3(-/-) mice. METHODS AND RESULTS: We obtained new evidence to demonstrate that there is significant expression of Cav1.3 Ca2+ channels predominantly in the atria compared with ventricular tissues. Whole-cell L-type Ca2+ currents (I(Ca,L)) recorded from single, isolated atrial myocytes from Cav1.3(-/-) mice showed a significant depolarizing shift in voltage-dependent activation. In contrast, there were no significant differences in the I(Ca,L) recorded from ventricular myocytes from wild-type and null mutant mice. We previously documented the hyperpolarizing shift in the voltage-dependent activation of Cav1.3 compared with Cav1.2 Ca2+ channel subunits in a heterologous expression system. The lack of Cav1.3 Ca2+ channels in null mutant mice would result in a depolarizing shift in the voltage-dependent activation of I(Ca,L) in atrial myocytes. In addition, the Cav1.3-null mutant mice showed evidence of atrial arrhythmias, with inducible atrial flutter and fibrillation. We further confirmed the isoform-specific differential expression of Cav1.3 versus Cav1.2 by in situ hybridization and immunofluorescence confocal microscopy. CONCLUSIONS: Using gene-targeted deletion of the Cav1.3 Ca2+ channel, we established the differential distribution of Cav1.3 Ca2+ channels in atrial myocytes compared with ventricles. Our data represent the first report demonstrating important functional roles for Cav1.3 Ca2+ channel in atrial tissues.

Implantable cardioverter-defibrillators: a new preventive medical option.

Implantable cardioverter-defibrillator (ICD or defibrillator) therapy has revolutionized the fields of cardiology and electrophysiology. Hundreds of thousands of patients at risk for sudden cardiac death receive them each year. The devices are not much larger than a pacemaker, and they have full pacemaker capabilities in addition to being able to shock patients out of life-threatening ventricular arrhythmias. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) in 1996 was a landmark trial that showed for the first time a mortality benefit of ICD therapy over medications in patients at high risk for sudden death. Multicenter Automatic Defibrillator Implantation Trial II, published in 2002, extended these results to all patients with ischemic heart failure with depressed heart function. Candidates for ICD implantation include most patients with an ejection fraction of <30%, especially those with coronary artery disease. More work needs to be done to define those patients with nonischemic cardiomyopathies who will benefit from ICDs and biventricular pacing for heart failure.

Use of ibutilide in cardioversion of patients with atrial fibrillation or atrial flutter treated with class IC agents.

OBJECTIVES: We sought to assess the efficacy and safety of ibutilide cardioversion for those with atrial fibrillation (AF) or atrial flutter (AFL) receiving long-term treatmentwith class IC agents. BACKGROUND: Attenuation of ibutilide-induced QT prolongation has been observed in a small number of patients pretreated with class IC agents. The clinical significance of the interaction between ibutilide and class IC agents is unknown. METHODS: Seventy-one patients with AF (n = 48) or AFL (n = 23), receiving propafenone 300 to 900 mg/day (n = 46) or flecainide 100 to 300 mg/day (n = 25), presented for ibutilide (2.0 mg) cardioversion. RESULTS: The mean durations of arrhythmia episode and arrhythmia history were 25 +/- 48 days and 4.4 +/- 6.4 years, respectively. Sixty-five patients (91.5%) had normal left ventricular systolic function. Twenty-three of 48 patients (47.9%; 95% confidence interval, 33.3% to 62.8%) with AF and 17 of 23 patients (73.9%; 95% confidence interval, 51.6% to 89.8%) with AFL converted with mean conversion times of 25 +/- 14 min and 20 +/- 12 min, respectively. There was a small increase in corrected QT interval after ibutilide (from442 +/- 61 ms to 462 +/- 59 ms, p = 0.006). One patient developed non-sustained polymorphous ventricular tachycardia and responded to intravenous magnesium. Another developed sustained torsade de pointes and was treated effectively with direct-current shock and intravenous dopamine. CONCLUSIONS: Our observations suggest that the use of ibutilide in patients receiving class IC agents is as successful in restoring sinus rhythm and has a similar incidence of adverse effects as the use of ibutilide alone.

Effectiveness of sotalol treatment in symptomatic Brugada syndrome.

We describe a 53-year-old man with recurrent syncopal events and a malignant family history who was treated for 13 years with sotalol drug therapy with no further occurrence of Brugada syndrome symptoms. Genetic testing revealed that he carried a Brugada syndrome sodium channel SCN5A mutation (4189delT). This finding suggests that sotalol may be of therapeutic benefit in such patients.

Mechanism of conversion of atypical right atrial flutter to atrial fibrillation.

The purpose of this study was to explore the mechanisms of conversion from atypical atrial flutter (AFL) to atrial fibrillation (AF), and the long-term results of cavotricuspid isthmus ablation in these patients. We retrospectively reviewed the records of 221 patients with typical AFL referred to our hospital for ablation. A total of 25 patients had atypical AFL, and cavotricuspid isthmus ablation was performed in 23 with isthmus-dependent atypical AFL, as well as in 180 patients with typical counterclockwise and/or clockwise AFL. In all, 13 spontaneous transitions from atypical AFL to AF were documented in 11 of 17 patients. Before AF, a pattern of lower loop reentry was observed in 11 of 13 patients (85%) and upper loop reentry in 3 (1 had both). Multiple early breaks along the tricuspid annulus during AFL were noted in 6 of 13 patients (46%). Among the 13 transitions, discrete atrial premature complexes before AF were found in 5 patients with lower loop reentry and in 1 with upper loop reentry (46%). In the remaining patients, a more rapid atrial rhythm was involved in the development of AF with a pulmonary venous focus in 2. In some cases, additional "breaks" in the functional line of block occurred before the development of AF. There was a significant increased incidence of AF (68%) in those with atypical AFL compared with those with typical AFL (38%) (p = 0.004). After a mean follow-up of 28 +/- 9 months for the atypical group and 18 +/- 11 months for the typical group, the AF recurrence rate was similar (57% vs 48%, p = 0.4). Discrete atrial premature complexes or atrial tachycardia may initiate AF either directly or by producing further breaks in lines of functional block. Bidirectional cavotricuspid isthmus block is associated with cure or control of AF in approximately 50% of patients with AFL.

Short-term secondhand smoke exposure decreases heart rate variability and increases arrhythmia susceptibility in mice.

Exposure to secondhand smoke (SHS), a major indoor air pollutant, is linked to increased cardiovascular morbidity and mortality, including cardiac arrhythmias. However, the mechanisms underlying the epidemiological findings are not well understood. Impaired cardiac autonomic function, indexed by reduced heart rate variability (HRV), may represent an underlying cause. The present study takes advantage of well-defined short-term SHS exposure (3 days, 6 h/day) on HRV and the susceptibility to arrhythmia in mice. With the use of electrocardiograph telemetry recordings in conscious mice, HRV parameters in the time domain were measured during the night after each day of exposure and 24 h after 3 days of exposure to either SHS or filtered air. The susceptibility to arrhythmia was determined after 3 days of exposure. Exposure to a low concentration of SHS [total suspended particle (TSP), 2.4 +/- 3.2; and nicotine, 0.3 +/- 0.1 mg/m(3)] had no significant effect on HRV parameters. In contrast, the exposure to a higher but still environmentally relevant concentration of SHS (TSP, 30 +/- 1; and nicotine, 5 +/- 1 mg/m(3)) significantly reduced HRV starting after the first day of exposure and continuing 24 h after the last day of exposure. Moreover, the exposed mice showed a significant increase in ventricular arrhythmia susceptibility and atrioventricular block. The data suggest that SHS exposure decreased HRV beyond the exposure period and was associated with an increase in arrhythmia susceptibility. The data provide insights into possible mechanisms underlying documented increases in cardiovascular morbidity and mortality in humans exposed to SHS.

Ratio of late to early T-wave peak amplitude in 24-h electrocardiographic recordings as indicator of symptom history in patients with long-QT Syndrome types 1 and 2.

UNLABELLED: We reviewed 24-h electrocardiographic recordings from 214 genotyped subjects--97 with long-QT syndrome type 1 (LQT1), 62 with LQT2, and 55 unaffected--to record maximal diurnal amplitude ratios between late and early T-wave peaks. Maximal amplitude ratios between late and early T-wave peaks were higher in symptomatic than in asymptomatic patients both in LQT1 (3.2 +/- 1.0 vs. 2.3 +/- 0.8; p < 0.001) and in LQT2 patients (2.6 +/- 1.0 vs. 1.7 +/- 0.5; p < 0.001). The maximal amplitude ratio between late and early T-wave peaks was independently associated with symptom history in both LQT1 and LQT2 patients. OBJECTIVES: We tested the hypothesis that in long-QT syndrome types 1 (LQT1) and 2 (LQT2), the diurnal maximal ratio between late and early T-wave peak amplitudes correlates with a history of symptoms better than QT interval durations. BACKGROUND: Genotype and phenotype studies have delineated clinical profiles of the most prevalent LQT1 and LQT2 subtypes of inherited LQT, but prediction of arrhythmia risk remains uncertain, the baseline QTc interval being the best predictor. In experimental long-QT syndrome models, the ratio between late and early T-wave peak amplitude predicts onset of torsade de pointes. METHODS: We reviewed 24-h electrocardiographic recordings from 214 genotyped subjects--97 with LQT1, 62 with LQT2, and 55 unaffected-to record maximal amplitude ratios between late and early T-wave peaks by use of a computer-assisted program. RESULTS: Maximal amplitude ratios between late and early T-wave peaks were higher in symptomatic than in asymptomatic patients both in LQT1 (3.2 +/- 1.0 vs. 2.3 +/- 0.8; p < 0.001) and LQT2 patients (2.6 +/- 1.0 vs. 1.7 +/- 0.5; p < 0.001). Although the QTc interval also was longer in symptomatic patients, only the maximal amplitude ratio between late and early T-wave peaks was independently associated with symptoms in both LQT1 and LQT2 patients. CONCLUSIONS: Maximal diurnal ratio between late and early T-wave peak amplitude improves noninvasive risk assessment both in LQT1 and LQT2 syndromes. We propose this new indicator in clinical evaluation of arrhythmia risk in LQT1 and LQT2.

Pregnancy in postural orthostatic tachycardia syndrome.

INTRODUCTION: Postural orthostatic tachycardia syndrome (POTS) is a rare disease characterized by syncope, sinus tachycardia, and orthostasis due to autonomic dysfunction. METHODS AND RESULTS: Two women aged 26 and 24 years with severe POTS became pregnant. Both women experienced hyperemesis gravidarum with subsequent marked improvement in their POTS symptoms until 6 months gestation, when their syncope and sinus tachycardia caused clinical decompensation. Both patients delivered healthy babies at 37 weeks by elective cesarean section. CONCLUSION: In long-term follow-up, both women reported improvement in their prepartum symptoms. We describe the first report, to our knowledge, of two successful pregnancy outcomes in severe POTS, including the first report of midodrine use in pregnant women.

Differential expression of small-conductance Ca2+-activated K+ channels SK1, SK2, and SK3 in mouse atrial and ventricular myocytes.

Small-conductance Ca2+-activated K+ channels (SK channels, KCa channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca2+ with membrane potential. We recently reported for the first time the functional existence of SK2 (KCa2.2) channels in human and mouse cardiac myocytes. Here, we report cloning of SK1 (KCa2.1) and SK3 (KCa2.3) channels from mouse atria and ventricles using RT-PCR. Full-length transcripts and their variants were detected for both SK1 and SK3 channels. Variants of mouse SK1 channel (mSK1) differ mainly in the COOH-terminal structure, affecting a portion of the sixth transmembrane segment (S6) and the calmodulin binding domain (CaMBD). Mouse SK3 channel (mSK3) differs not only in the number of polyglutamine repeats in the NH2 terminus but also in the intervening sequences between the polyglutamine repeats. Full-length cardiac mSK1 and mSK3 show 99 and 91% nucleotide identity with those of mouse colon SK1 and SK3, respectively. Quantification of SK1, SK2, and SK3 transcripts between atria and ventricles was performed using real-time quantitative RT-PCR from single, isolated cardiomyocytes. SK1 transcript was found to be more abundant in atria compared with ventricles, similar to the previously reported finding for SK2 channel. In contrast, SK3 showed similar levels of expression in atria and ventricles. Together, our data are the first to indicate the presence of the three different isoforms of SK channels in heart and the differential expression of SK1 and SK2 in mouse atria and ventricles. Because of the marked differential expression of SK channel isoforms in heart, specific ligands for Ca2+-activated K+ currents may offer a unique therapeutic opportunity to modify atrial cells without interfering with ventricular myocytes.

Retrograde cycle length alternans during supraventricular tachycardia: an unusual tachycardia mechanism.

Cycle length alternans is occasionally seen during supraventricular tachycardia due to oscillations in the antegrade atrioventricular nodal (AVN) refractoriness. However, alternans due to retrograde variation in AVN conduction has not been reported. This report describes the case of a 36-year-old man with atypical AVN reentry tachycardia (AVNRT) whose episodes of tachycardia were characterized by continuous oscillations in retrograde AVN conduction. Ablation at one spot eliminated the tachycardia. Cycle length alternans due to oscillations in retrograde AVN conduction, although rare, can be seen during atypical AVNRT and should be considered.

Molecular identification and functional roles of a Ca(2+)-activated K+ channel in human and mouse hearts.

The repolarization phase of cardiac action potential is prone to aberrant excitation that is common in cardiac patients. Here, we demonstrate that this phase is markedly sensitive to Ca2+ because of the surprising existence of a Ca2+-activated K+ currents in cardiac cells. The current was revealed using recording conditions that preserved endogenous Ca2+ buffers. The Ca2+-activated K+ current is expressed differentially in atria compared with ventricles. Because of the significant contribution of the current toward membrane repolarization in cardiac myocytes, alterations of the current magnitude precipitate abnormal action potential profiles. We confirmed the presence of a small conductance Ca2+-activated K+ channel subtype (SK2) in human and mouse cardiac myocytes using Western blot analysis and reverse transcription-polymerase chain reaction and have cloned SK2 channels from human atria, mouse atria, and ventricles. Because of the marked differential expression of SK2 channels in the heart, specific ligands for Ca2+-activated K+ currents may offer a unique therapeutic opportunity to modify atrial cells without interfering with ventricular myocytes.