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Atrial fibrillation (AF) represents the most common cardiac arrhythmia with significant morbidity and mortality implications. It is a common cause of hospital admissions, significantly impacts quality of life, increases morbidity and decreases life expectancy. Despite advancements in treatment options, prevalence of AF remains exceptionally high. AF is a challenging disease to manage, not just clinically but also financially. Evidence suggests lifestyle modification, including dietary changes, plays a significant role in the treatment of AF. This review aims to analyze the existing literature on the effects of dietary modifications on the incidence, progression, and outcomes of atrial fibrillation. It examines various dietary components, including alcohol, caffeine, omega-3 polyunsaturated fatty acids and minerals, and their impact on AF incidence, progression, and outcomes. The evidence surrounding the effects of dietary patterns, such as the Mediterranean and low carbohydrate diets, on AF is also evaluated. Overall, this review underscores the importance of dietary interventions as part of a comprehensive approach to AF management and highlights the need for further research in this emerging field., Competing Interests: PC and AT have ownership interest in AlfredAI Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Nabil, Rychlik, Nicholson, Cheung, Olsovsky, Molden, Tripuraneni, Hajivandi and Banchs.)

Competing Interests: Dr Widmer is an advisor to Abbott, Medtronic, and Philips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Competing Interests: No potential conflict of interest was reported by the author(s).

Temporary cardiac pacing is commonly used in patients with life-threatening bradycardia and serves as a bridge to implantation of a permanent pacemaker (PPM). For years, passive fixation leads have been used for this purpose, offering the advantage of that they can be placed at bedside. The downside, however, is that patients must remain on telemetry and bed rest until lead removal due to the risk of displacement and failure to capture. Even then, the latter cannot always be prevented. Temporary cardiac pacing with passive fixation leads has also been related to a higher incidence of infection and venous thrombosis, delayed recovery, and increased length of stay. Thus, over the last couple of decades, pacemaker leads with an active fixation mechanism have become increasingly used. This is known as a temporary PPM (TPPM) approach, which carries a very low risk of lead dislodgement and allows patients to ambulate, among other advantages. Here, we performed a review of the literature on the use of TPPMs and their advantages over temporary pacemakers with passive fixation leads and in order to evaluate the advantages and disadvantages of active and passive fixation leads in temporary cardiac pacing. Most articles found were case reports and case series, with few prospective studies. We excluded documents such as editorials and image case reports that provided little to no useful information for the final analysis. The literature search was performed in PubMed, Google Scholar, and other databases and articles written in English and Spanish were considered. Articles were screened up to January 2017. The search keywords used were "temporary permanent pacemaker," "external permanent pacemaker," "active fixation lead," "explantable pacemaker," "hybrid pacing," "temporary permanent generator," "prolonged temporary transvenous pacing," and "semipermanent pacemaker." A total of 24 studies with 770 patients were ultimately included in our review. The age group was primarily above the sixth decade of life, with the exception of one that included pediatric patients. Indications for pacing included device infection, sick sinus syndrome, atrioventricular block, ventricular tachycardia, and bradyarrhythmias associated with systemic illness. The duration of TPPM usage varied from a few days up to 336 days. A total of 18 (2.3%) TPPM-related infections were reported, in which the duration of TPPM use was less than 30 days in at least 15 patients. Loss of capture was documented in only eight patients (1.0%). Complication rates varied from 0% to 30%, with the highest event rates being present in studies that used femoral venous access. In conclusion, although no high-quality studies were identified in our literature search, we found the data retrieved suggest the association of overall favorable outcomes with the use of TPPMs. Device placement and removal typically involve a simple procedure, although fluoroscopy, usually applied in the cardiac catheterization laboratory, is necessary for implantation, which could represent an additional risk in a patient who is already hemodynamically unstable. When possible, a screw-in-lead pacemaker should be used for temporary pacing., Competing Interests: The authors report no conflicts of interest for the published content., (Copyright: © 2019 Innovations in Cardiac Rhythm Management.)

Cardiac resynchronization therapy device implantation is complicated by a significant rate of failure to place a left ventricular lead via the coronary sinus. The present case describes one such failure ironically leading to resynchronization. The patient's QRS narrowing subsequent to postimplant atrial pacing alone suggests that bradycardia-dependent phase 4 block was the indirect but exclusive cause of the patient's intraventricular conduction delay. Thus, phase 4 block should be considered when atrial pacing at a faster rate resolves a wide QRS interval., (© 2018 Wiley Periodicals, Inc.)

Background: In 2012, the Food and Drug Administration issued Drug Safety Communications on several drugs associated with QT prolongation and fatal ventricular arrhythmias. Among these was citalopram, a selective serotonin reuptake inhibitor (SSRI) approved for depression and commonly used for posttraumatic stress disorder (PTSD). Evaluation of the risk for QT prolongation among other psychotropic drugs for individuals with PTSD remains limited., Objective: Explore psychotropic drugs associated with QT prolongation among veterans with PTSD., Methods: Patients in the Veterans Health Administration in 2006-2009 with PTSD and QT prolongation (176 cases) were matched 1:4 on age, gender, visit date and setting, and physical comorbidity. Classification trees assessed QT prolongation risk among prescribed medications (n=880)., Results: Receipt of any drug with known risk of QT prolongation varied by group (23% QT cases vs 15% control, p<0.01). Psychotropic medications conferring significant risks included ziprasidone (3% vs 1%, p=0.02) and buspirone (6% vs 2%, p=0.01). Increased risk was not observed for the SSRIs, citalopram and fluoxetine. Classification trees found that sotalol and amitriptyline carried greater risk among cardiac patients and methadone, especially if prescribed with quetiapine, among noncardiac patients. Per adjusted survival model, patients with QT prolongation were at increased risk for death (hazard ratio=1.60; 95% CI=1.04-2.44)., Conclusions: Decision models are particularly advantageous when exploring nonlinear relationships or nonadditive interactions. These findings may potentially affect clinical decision-making concerning treatment for PTSD. For patients at higher risk of QT prolongation, antidepressants other than amitriptyline should be considered. Medications for comorbid conditions should also be closely monitored for heightened QT prolongation risk.

Background: The role of intracardiac echocardiography (ICE) to detect thrombus within left atrium (LA) before atrial fibrillation (AF) ablation despite a recent transesophageal echocardiogram (TEE) is not well defined. We examined the prevalence of LA/left atrial appendage (LAA) thrombus using ICE immediately prior to AF ablation in patients in whom anticoagulation was not withheld., Methods: We analyzed 122 consecutive patients (62.6 ± 10.8 years, 90 males, CHA(2)DS(2) -VASc score 2.4 ± 1.5, persistent AF 29.5 %) who underwent an ICE-guided AF ablation 1 day after a negative (n = 120) or inconclusive (n = 2) TEE for LA thrombus. LA was imaged with ICE from the right atrium, coronary sinus, and right ventricular inflow tract (RVIT). ICE and TEE images were compared for LAA area, thrombus, and spontaneous echo contrast (SEC)., Results: LAA was adequately visualized in 99 and 100 % of patients with TEE and ICE, respectively. RVIT was the best ICE view for LAA visualization. The LAA 2-D-area measured by TEE was 4.9 ± 0.5 vs. 5 ± 0.5 cm(2) by ICE (P = NS). ICE identified a thrombus in seven patients with a previous negative TEE, leading to cancellation of ablation. It ruled out a thrombus in two patients with an inconclusive TEE. Thrombi were found in the LAA (n = 4), atrial septum (n = 2), and left superior pulmonary vein (n = 1). SEC during TEE was more frequent in patients with thrombus on ICE than those without (85.7 vs. 17.4 %; p = 0.03; positive predictive value 23.1 %, negative predictive value 98.9 %)., Conclusions: The results of our staged imaging approach suggest that ICE has a complimentary value in re-screening the LA/LAA for thrombus after a recent negative or equivocal TEE. The presence of SEC during TEE increases the probability of finding a thrombus with ICE, which could potentially be dislodged during catheter manipulation.

Current available mobile health technologies make possible earlier diagnosis and long-term monitoring of patients with cardiovascular diseases. Remote monitoring of patients with implantable devices and chronic diseases has resulted in better outcomes reducing health care costs and hospital admissions. New care models, which shift point of care to the outpatient setting and the patient's home, necessitate innovations in technology., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Most cardiovascular implantable electronic devices (CIEDs) require a ventricular lead to be placed across the tricuspid valve. Tricuspid regurgitation (TR) is an understudied clinical complication of right ventricular lead implantation and its clinical significance is unknown. We review the incidence, predictors, and current management of TR as a complication of ventricular lead implantation. Emerging technologies, including leadless pacing devices and subcutaneous systems, offer the benefit of little or none tricuspid valve disruption.

Background: The anatomical reconstruction of the left atrium (LA) and pulmonary veins with fast anatomical mapping (FAM) and intracardiac echocardiography (ICE) using the Carto 3 system (Biosense Webster, Inc) provides real-time guidance to catheter manipulation during ablation of atrial fibrillation (AF). The present study compared real-time LA volume reconstruction using FAM and ICE. In addition, the contribution of respiratory gating was assessed., Methods: LA reconstruction was created using FAM and ICE in 60 consecutive patients (mean age 63 ± 9 years; 38 males) undergoing AF ablation. In the first 30 patients, FAM and ICE were performed without respiratory gating. In the last 30 patients, FAM and ICE were performed with respiratory gating., Results: LA volumes determined by FAM were larger than those obtained with ICE in the absence of respiratory gating (n = 30; 129.5 ± 44 vs 110 ± 39.7 cm(3); p = 0.001). However, respiratory gating reduced LA volume determined with FAM by 17.7 ± 6.6% resulting in similar LA volumes to those obtained using ICE [n = 30; 100 ± 29.7 (61-154) vs 101.53 ± 40.1 (56-212) cm(3), p = 0.7, NS]., Conclusions: In the absence of respiratory gating, LA volumes determined by FAM are larger than those obtained with ICE. In contrast, with the addition of respiratory gating, both FAM and ICE provide similar real-time LA volumes.

Importance: AliveCor ECG is an FDA approved ambulatory cardiac rhythm monitor that records a single channel (lead I) ECG rhythm strip using an iPhone. In the past few years, the use of smartphones and tablets with health related applications has significantly proliferated., Objective: In this initial feasibility trial, we attempted to reproduce the 12 lead ECG using the bipolar arrangement of the AliveCor monitor coupled to smart phone technology., Methods: We used the AliveCor heart monitor coupled with an iPhone cellular phone and the AliveECG application (APP) in 5 individuals., Results: In our 5 individuals, recordings from both a standard 12 lead ECG and the AliveCor generated 12 lead ECG had the same interpretation., Conclusions: This study demonstrates the feasibility of creating a 12 lead ECG with a smart phone. The validity of the recordings would seem to suggest that this technology could become an important useful tool for clinical use. This new hand held smart phone 12 lead ECG recorder needs further development and validation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Atrial tachyarrhythmias (AT) including atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia represent a clinical challenge in the adult with congenital heart disease (CHD). Dofetilide (D) is a rapidly activating delayed rectifier potassium channel (IKr) blocker effective in pharmacological conversion and maintenance of normal sinus rhythm in patients with AF and AFL. There is limited knowledge regarding the role of D in adults with CHD., Methods: Safety and efficacy of D was evaluated in a consecutive group of thirteen adult patients (age 40 ± 11; six women) with CHD and refractory AT., Results: Ten patients had persistent (four AFL, one AF, and five atrial tachycardia) and three paroxysmal (one AF and two atrial tachycardia) AT. All patients were symptomatic during tachycardia, 12 patients had previously failed 2 ± 1 antiarrhythmic drugs. Mean systemic ventricular ejection fraction was 55 ± 9%; baseline QRS complex duration was 129 ± 45 ms (>120 ms in six patients). Patients were followed on D for 33 ± 39 months (median 16). Among 10 patients with persistent AT, seven patients (70%) pharmacologically converted to sinus rhythm on D and three patients (30%) required direct current cardioversion. Two patients (15.4%) experienced complete arrhythmia suppression, and seven (53.8%) experienced significant clinical improvement with sporadic recurrences; average time to recurrence was 5.5 ± 3.5 months. One patient developed torsade de pointes during loading, and the drug was discontinued. D was discontinued in five (38.5%) other patients due to recurrence of AT (n = 4) and renal failure (n = 1). Corrected QT interval (QTc) increased from 452 ± 61 to 480 ± 49 ms (P = .04) and corrected JT interval (JTc) from 323 ± 39 to 341 ± 33 ms (P = .09)., Conclusions: D should be considered a pharmacologic alternative when adult patients with CHD develop AT. D does not depress conduction, sinus node, or ventricular function but needs close monitoring for potential ventricular pro-arrhythmia., (© 2013 Wiley Periodicals, Inc.)

Purpose: Cardiac rhythm management devices (CRMD) require a ventricular lead to be placed across the tricuspid valve. Tricuspid regurgitation (TR) is an under-recognized clinical complication of lead implantation and its clinical significance is unknown. We studied the incidence of hospitalizations for congestive heart failure (CHF) exacerbation among patients with worsening TR after ventricular lead implantation., Methods: We reviewed 148 patients (age 68 ± 15) that received a CRMD. TR and pulmonary artery systolic pressure (PASP) measured by Doppler echocardiography before and after CRMD implantation were analyzed. Hospitalizations for CHF exacerbation post-implantation were counted., Results: Follow-up was 32 ± 14 months. Ninety-nine (67%) patients had no change, 24 (16%) slight, and 9 (6%) significant increase in TR after CRMD implantation, while 13 (9%) patients had slight and 3 (2%) significant improvement. Patients with a significant increase in TR had higher incidence of hospitalizations (1.7 ± 0.5) compared to patients with slight (0.8 ± 1; p = 0.006) or no increase (0.5 ± 1; p = 0.0002) in TR. Patients with significant increase in TR had a greater change in PASP (25 mmHg; p = 0.002) after device implantation compared to those with a slight (10 mmHg; p = 0.002) or no increase (0.7 mmHg; p = 0.17)., Conclusion: Increased TR following CRMD implantation is relatively common (33%) and correlated with subsequent risk of hospitalization for heart failure. A preventive strategy and close monitoring for development or worsening of CHF after CRMD implantation may help prevent hospital admissions.

Isolated left ventricular noncompaction is a rare form of cardiomyopathy characterized by prominent left ventricular trabeculations and intertrabecular recesses. The typical clinical manifestations are severe systolic and diastolic dysfunction, conduction abnormalities, and cardiac embolic events theorized to result from thrombus formation within the intertrabecular recesses. Evidence-based recommendations for preventing thromboembolic events in isolated left ventricular noncompaction have not been established. We report the case of a woman who, at 10 years of age, had been diagnosed with hypertrophic cardiomyopathy without systolic dysfunction. At age 30, she presented with left hemiparesis consequent to a large right-hemispheric ischemic stroke, and she was diagnosed with isolated left ventricular noncompaction. In addition to discussing the patient's case, we review the medical literature that pertains to isolated left ventricular noncompaction.

Background: Patients with an implanted cardioverter defibrillator (ICD) and ventricular arrhythmias leading to ICD therapies have poor clinical outcomes and quality of life. Antiarrhythmic agents and catheter ablation are needed to control these arrhythmias. Dofetilide has only been approved for the treatment of atrial fibrillation. The role of dofetilide in the control of ventricular arrhythmias in patients with an ICD has not been established., Objective: Evaluate the safety and efficacy of dofetilide in a consecutive group of patients with an ICD and recurrent ventricular tachycardia (VT) and/ or ventricular fibrillation (VF) after other antiarrhythmic drugs have failed to suppress these arrhythmias., Methods: We studied 30 patients (age 59 ± 11; 5 women) with symptomatic VT or VF and ICDs for secondary prevention of sudden cardiac death. These patients had an average of 1.8 ± 4.5 episodes of VT/VF per month despite antiarrhymic therapy. Twenty-one patients (70%) had recurrent appropriate ICD therapies prior to initiation of dofetilide, and 9 (30%) VTs below the programmed detection rate of the ICD. Twenty-three patients (77%) had coronary artery disease. Mean ejection fraction was 30 ± 14% and 26/30 (87%) had congestive heart failure. All patients had previously failed 2 ± 1 antiarrhythmic drugs including amiodarone (n = 19) and sotalol (n = 10)., Results: During the first month of treatment, 25 patients (83%) had complete suppression of VT/VF and of the 21 patients with ICD therapies 16 (76%) had no therapies during the first month of treatment. During a follow-up period of 32 ± 32 months, dofetilide reduced the monthly episodes of VT/VF from 1.8 ± 4.5 to 1.0 ± 3.5 (P = 0.006). Monthly ICD therapies decreased from 0.9 ± 1.4 to 0.4 ± 1.7 (P = 0.037). In 9 patients that presented with slow VTs under the ICD detection zone, dofetilide reduced monthly VT/VF episodes from 0.7 ± 0.6 to 0.1 ± 0.1 (P = 0.01) and 6 (67%) had no further ICD therapies. Dofetilide was discontinued in 13 patients (43%) after 24 ± 30 months due to failure to control VT/VF (n = 7), placement of a left ventricular assist device (n = 3), catheter ablation (n = 1), heart transplantation (n = 1), and left ventricular restoration surgery (n = 1). There were 7 documented deaths (2 patients died suddenly; 3 patients of progressive heart failure; and 2 of non-cardiac causes)., Conclusions: In patients with an ICD and ventricular arrhythmias, dofetilide decreases the frequency of VT/VF and ICD therapies even when other antiarrhythmic agents, including amiodarone, have previously been ineffective. Recurrences still occur in some patients requiring catheter ablation, mechanical support, or heart transplantation., (© 2011 Wiley Periodicals, Inc.)

Dronedarone is an amiodarone analog but differs structurally from amiodarone in that the iodine moiety was removed and a methane-sulfonyl group was added. These modifications reduced thyroid and other end-organ adverse effects and makes dronedarone less lipophilic, shortening its half-life. Dronedarone has been shown to prevent atrial fibrillation/flutter (AF/AFl) recurrences in several multi-center trials. In addition to its rhythm control properties, dronedarone has rate control properties and slows the ventricular response during AF. Dronedarone is approved in Europe for rhythm and rate control indications. In patients with decompensated heart failure, dronedarone treatment increased mortality and cardiovascular hospitalizations. However, when dronedarone was used in elderly high risk AF/AFl patients excluding such high risk heart failure, cardiovascular hospitalizations were significantly reduced and the drug was approved in the USA for this indication in 2009 by the Food and Drug Administration. Updated guidelines suggest dronedarone as a front-line antiarrhythmic in many patients with AF/Fl but caution that the drug should not be used in patients with advanced heart failure. In addition, the recent results of the PALLAS trial suggest that dronedarone should not be used in the long-term treatment of patients with permanent AF.

Dronedarone is a multichannel blocker with electrophysiologic effects similar to amiodarone. Dronedarone has been documented to prevent atrial fibrillation recurrences and also has efficacy in slowing the ventricular response during episodes of atrial fibrillation. However, in the ANDROMEDA trial, dronedarone was associated with increased mortality when tested in New York Heart Association (NYHA) III/IV patients with left ventricular ejection fractions of less than 35%, who also had a recent hospitalization for decompensated heart failure. When such high-risk patients with heart failure were excluded in the ATHENA trial, dronedarone treatment resulted in a statistical reduction in the composite primary end point of all-cause mortality or cardiovascular hospitalization. In ATHENA, dronedarone reduced cardiovascular hospitalizations even though in the DIONY-SOS trial dronedarone had less effect than amiodarone on suppressing atrial fibrillation recurrences. The most appropriate patients for treatment with dronedarone would be patients with a recent history of paroxysmal or persistent atrial fibrillation/atrial flutter (AF/AFL) that have associated risk factors per the inclusion criteria of ATHENA. Inappropriate patients would be those with class IV heart failure or recently hospitalized for heart failure within the last month from an acute decompensation, the main inclusion criteria in ANDROMEDA. Dronedarone is a novel, multichannel blocking antiarrhythmic agent that may have some pleiotropic effects in addition to its ability to suppress and maintain sinus rhythm and control the rate during AF/AFL recurrences.

Cardiac resynchronization therapy (CRT) is an established treatment modality for systolic heart failure. Aimed to produce simultaneous biventricular stimulation and correct the lack of ventricular synchrony in selected patients with congestive heart failure, CRT has shown to improve mortality and reduce hospital admissions when compared to medical treatment. At present, the indication criteria for the implantation of a CRT device include an ejection fraction of less than 35%, heart failure symptoms consistent with NYHA functional class III-IV and a QRS complex duration equal or longer than 120 milliseconds. It has been reported that 30% of patients who meet those criteria still may not derive clinical benefit from CRT. Due to the existing diversity of imagin modalities and resources for their process and analysis, a great expectation in terms of more accurate diagnosis of ventricular dyssynchrony has been raised. Reilable identification of dyssynchrony could allow us to better predict the favorable response of an individual patient to CRT and therefore offer this procedure to those individuals most likely to benefit. We review the available techniques for the study of ventricular dyssynchrony for CRT patient selection and the results of its application in clinical trials. Despite tremendous progress in the imaging technology available for the assessment and diagnosis of ventricular dyssynchrony, an ideal method has not been identified and the duration of QRS complex in the surface ECG remains the accepted criteria of dyssynchrony in the selection of patients for CRT.

With the availability of catheter ablation for the elimination of complex cardiac arrhythmias, new imaging tools have enhanced the safety and efficacy of procedures performed in the electrophysiology laboratory. We review the use of intracardiac ultrasound (ICE) as the modality that allows real-time monitoring and reconstruction of cardiac anatomy. Practical technical information related to the use of ICE in ablation procedures in general and particular aspects related to ablation of atrial fibrillation, atrial flutter, ventricular tachycardia, and arrhythmias in adults with congenital heart disease are discussed in this manuscript.

Cardiac resynchronization therapy (CRT) is a well established treatment modality in heart failure. Using standard techniques, placement of the left ventricular (LV) lead is usually successful; however LV lead placement failure remains a clinical problem. In the present report, the standard over-the-wire technique was not successful due to absence of the necessary support to place the lead into a tortuous vein. This was achieved using balloon occlusion of the great cardiac vein distal to the target vessel. An 81 year old female candidate for CRT presented for biventricular pacemaker implantation. After placement of the right ventricular lead, the CS was cannulated and an occlusive venogram was performed. A lateral branch was selected as the target vessel. Initial attempts at cannulating the vessel were unsuccessful due to the guidewire and telescoping delivery system prolapsing into the great cardiac vein. The acute angle prevented instrumentation of the branch with the tools available. A second parallel CS sheath was advanced to drive a balloon catheter used to occlude the great cardiac vein distal to the target vessel. This provided support for the guidewire and lead allowing their advancement through the tortuous vessel. Consecutive traction on the balloon during also helped to reflect the lead towards the vessel. The lead remained stable in its final position on the lateral wall of the LV with appropriate thresholds and no diaphragmatic stimulation. We report a case where balloon occlusion of the great cardiac vein distal to the target branch aided in advancing the LV lead into the desired position. This approach can be used in navigating lead placement to branches thought to be unreachable. Techniques such as this can decrease the failure rate of CRT implants.

Background: Dofetilide, an I(Kr) blocker has been demonstrated to be effective in terminating persistent atrial fibrillation and flutter (AF/AFL), and in maintaining sinus rhythm after direct current cardioversion (CV). It is not known, however, whether pharmacological conversion with dofetilide predicts maintenance of sinus rhythm. In addition, there is limited information comparing the efficacy of dofetilide in persistent versus paroxysmal AF/AFL., Methods and Results: Eighty consecutive patients with AF/AFL (51 persistent, 29 paroxysmal) admitted for initiation of dofetilide were studied. Termination of persistent AF/AFL occurred in 61% of patients while 39% required CV. After 21 +/- 19 months of follow-up, 37% of patients with persistent AF/AFL were free of recurrence. Acute conversion with dofetilide did not predict long term efficacy. Dofetilide was more effective in maintaining sinus rhythm in patients with AFL (65%) than in those with AF (25%) (p < 0.05). Dofetilide was more likely to maintain sinus rhythm in patients with persistent than paroxysmal AF/AFL (37 vs. 14%; p < 0.05). Torsades de Pointes developed in two patients despite careful dosing and monitoring of QT changes., Conclusions: Dofetilide is more effective in patients with persistent than in those with paroxysmal AF/AFL. Importantly, short-term response does not necessarily predict long-term efficacy. Significant proarrhythmia can occur even with careful in-hospital monitoring.

The development of new antiarrhythmic agents for the treatment of atrial fibrillation is advancing simultaneously on several fronts. The molecular structure of existing agents such as amiodarone is being modified in an attempt to improve safety and reduce adverse effects. Similarly, atrial-selective antiarrhythmic drugs are being developed to minimize the occurrence of ventricular proarrhythmia. One of these atrial-selective compounds is vernakalant, which has demonstrated efficacy in terminating atrial fibrillation when given intravenously. In addition, preliminary data suggest that it could also suppress recurrences when used orally. This paper reviews the pharmacology, electrophysiology, efficacy and safety of intravenous and oral vernakalant., (Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.)

Background: This paper reviews the pharmacology, electrophysiology, efficacy and safety of intravenous and oral vernakalant hydrochloride (RSD-1235), a novel antiarrhythmic drug that has relative atrial selectivity by blocking potassium channels that are present in the atria and not the ventricle. In addition, this drug has important rate-dependent sodium channel blocking properties., Methods: Currently, there few commercially approved intravenous antiarrhythmic agents for the conversion of atrial fibrillation. Intravenously, vernakalant has been demonstrated to be useful in terminating over 50% of recent-onset atrial fibrillation (< 7 days duration) with minimal ventricular proarrhythmic effects. Intravenous vernakalant is not effective in terminating atrial flutter. Oral vernakalant is currently undergoing study and appears to be effective in suppressing atrial fibrillation recurrences after cardioversion of persistent atrial fibrillation., Results/conclusion: Intravenous vernakalant has the potential to be an important agent in the conversion of atrial fibrillation and oral vernakalant may be a useful drug for the suppression of atrial fibrillation recurrences.

Antiarrhythmic pharmaceutical development for the treatment of atrial fibrillation (AF) is moving in several directions. The efficacy of existing drugs, such as carvedilol, for rate control and, possibly, suppression of AF, is more appreciated. Efforts are being made to modify existing agents, such as amiodarone, in an attempt to ameliorate safety and adverse effect concerns. This has resulted in promising data from the deiodinated amiodarone analog, dronedarone, and further work with celivarone and ATI-2042. In an attempt to minimize ventricular proarrhythmia, atrial selective drugs, such as intravenous vernakalant, have demonstrated efficacy in terminating AF in addition to promising data in suppression recurrences when used orally. Several other atrial selective drugs are being developed by multiple manufacturers. Other novel therapeutic mechanisms, such as drugs that enhance GAP junction conduction, are being developed to achieve more effective drug therapy than is offered by existing compounds. Finally, nonantiarrhythmic drugs, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, high-mobility group coenzyme A enzyme inhibitors and omega-3 fatty acids/fish oil, appear to have a role in suppressing AF in certain patient subtypes. Future studies will clarify the role of these drugs in treating AF.

Explanted hearts from patients with chronic left ventricular assist device (LVAD) support have shown the presence of aortic cusp fusion, which results in valvular stenosis and may complicate weaning of a LVAD. This is the first report of aortic cusp fusion diagnosed solely by transesophageal echocardiography (TEE) in vivo in a patient on chronic LVAD support. Under intraoperative TEE guidance, a 41-year-old woman underwent an attempted explantation of a LVAD, which had been implanted 8 months before for dilated cardiomyopathy. When LVAD support was discontinued, previously normal left ventricular function deteriorated, and aortic stenosis from aortic valve cusp fusion was documented by TEE. The explantation procedure was abandoned. This case demonstrates the utility of intraoperative TEE in the evaluation of aortic valvular anatomy and function in patients wtih chronic LVAD support.

Background: Vascular endothelial functions, other than nitric oxide (NO)-mediated control of vasomotor tone, are poorly characterized in patients with chronic heart failure (CHF). Veins and arteries are exposed to the same circulating proinflammatory mediators in patients with CHF. The present study tested whether endothelial cell activation occurs in veins of patients with decompensated CHF and whether activation, if present, subsides with return to a clinically compensated state., Methods and Results: Fifteen patients with decompensated CHF requiring transient inotropic support and 6 age-matched, healthy controls were studied. Endothelial cells and blood were collected from a forearm vein, and brachial artery flow-mediated dilation (FMD) was measured before and 24 hours after discontinuation of short-term inotropic therapy, when patients had returned to a steady compensated state. Nitrotyrosine immunoreactivity (an intracellular marker of oxidative stress), cyclooxygenase-2 (COX-2), and inducible NO synthase (iNOS) expression were significantly higher in venous endothelial cells of patients in clinical decompensation when compared with healthy subjects. Return to a compensated state resulted in a significant reduction in nitrotyrosine immunoreactivity, COX-2, and iNOS expression. Concomitantly, a significant increase in FMD and a decline in plasma total 8-isoprostane and bicycloprostaglandin E2 levels were observed. Venous endothelial NOS expression was unaffected by clinical decompensation., Conclusions: Clinical decompensation in CHF is associated with activation of the venous endothelium. Return to a compensated state after short-term inotropic therapy results in a significant reduction in endothelial nitrotyrosine formation, COX-2, and iNOS expression.

Limited availability of endothelial tissue is a major constraint when investigating the cellular mechanisms of endothelial dysfunction in patients with metabolic and cardiovascular diseases. We propose a novel approach that combines collection of 200-1,000 endothelial cells from a superficial forearm vein or the radial artery, with reliable measurements of protein expression by quantitative immunofluorescence analysis. This method was validated against immunoblot analysis in cultured endothelial cells. Levels of vascular endothelial cell activation, oxidative stress, and nitric oxide synthase expression were measured and compared in five patients with severe chronic heart failure and in four healthy age-matched subjects. In summary, vascular endothelial biopsy coupled with measurement of protein expression by quantitative immunofluorescence analysis provides a novel approach to the study of the vascular endothelium in humans.