Bachmann's Bundle's Unique Physiology: Reviewing How it Made an Atypical Flutter Even More Atypical.

A 69-year-old man with a history of previous ablation and cardiac surgery was found on cardiac electrophysiology study to have a macro-re-entrant left atrial flutter initially misdiagnosed as a micro-re-entrant right atrial tachycardia resulting from the unique conduction properties of Bachmann's bundle. (Level of Difficulty: Advanced.).

Challenges and opportunities for integrating genetic testing into a diagnostic workflow: heritable long QT syndrome as a model.

BACKGROUND: An increasing number of diagnostic evaluations incorporate genetic testing to facilitate accurate and timely diagnoses. The increasing number and complexity of genetic tests continue to pose challenges in deciding when to test, selecting the correct test(s), and using results to inform medical diagnoses, especially for medical professionals lacking genetic expertise. Careful consideration of a diagnostic workflow can be helpful in understanding the appropriate uses of genetic testing within a broader diagnostic workup. CONTENT: The diagnosis of long QT syndrome (LQTS), a life-threatening cardiac arrhythmia, provides an example for this approach. Electrocardiography is the preferred means for diagnosing LQTS but can be uninformative for some patients due to the variable presentation of the condition. Family history and genetic testing can augment physiological testing to inform a diagnosis and subsequent therapy. Clinical and laboratory professionals informed by peer- reviewed literature and professional recommendations constructed a generalized LQTS diagnostic workflow. This workflow served to explore decisions regarding the use of genetic testing for diagnosing LQTS. SUMMARY AND OUTLOOK: Understanding the complexities and approaches to integrating genetic testing into a broader diagnostic evaluation is anticipated to support appropriate test utilization, optimize diagnostic evaluation, and facilitate a multidisciplinary approach essential for achieving accurate and timely diagnoses.

Walk the Line-The Importance of Well-Informed Interpretation of QT Prolongation.

Acute care pharmacists play an integral role in identifying drug-drug interactions that may predispose patients to QT prolongation. Although most pharmacists are equipped with a baseline understanding of drug interactions and the risks of QTc prolongation, few understand the limitations of QTc calculation and interpretation. In this commentary, we put forth the notion that at times health care providers, including pharmacists, place an overemphasis on the QTc interval. In the context of using the QTc to guide pharmacotherapy decisions, unintended consequences may include a cascade of effects leading to delays in treatment, suboptimal medication selection, alert fatigue, and overutilization of resources.

KCNQ1 and Long QT Syndrome in 1/45 Amish: The Road From Identification to Implementation of Culturally Appropriate Precision Medicine.

BACKGROUND: In population-based research exome sequencing, the path from variant discovery to return of results is not well established. Variants discovered by research exome sequencing have the potential to improve population health. METHODS: Population-based exome sequencing and agnostic ExWAS were performed 5521 Amish individuals. Additional phenotyping and in vitro studies enabled reclassification of a KCNQ1 variant from variant of unknown significance to pathogenic. Results were returned to participants in a community setting. RESULTS: A missense variant was identified in KCNQ1 (c.671C>T, p.T224M), a gene associated with long QT syndrome type 1, which can cause syncope and sudden cardiac death. The p.T224M variant, present in 1/45 Amish individuals is rare in the general population (1/248 566 in gnomAD) and was highly associated with QTc on electro-cardiogram (P=5.53E-24, ß=20.2 ms/allele). Because of the potential importance of this variant to the health of the population, additional phenotyping was performed in 88 p.T224M carriers and 54 noncarriers. There was stronger clinical evidence of long QT syndrome in carriers (38.6% versus 5.5%, P=0.0006), greater history of syncope (32% versus 17%, P=0.020), and higher rate of sudden cardiac death in first degree relatives

Clinical Pharmacology-Driven Translational Research to Optimize Bedside Therapeutics of Sotalol Therapy.

Oral sotalol, used in adults for sinus rhythm control, is initiated at 80 mg b.i.d. and titrated to a maximum safe dose. The US Food and Drug Administration recommends monitoring the corrected QT interval (QTc ) for at least 3 days, until steady-state exposure of the drug is reached, before patient discharge, which can significantly impact the total cost of treatment. The objectives of this research were to design an accelerated intravenous sotalol loading and maintenance therapy that will reduce the hospital length of stay and to also evaluate the pharmacoeconomic impact in a hospital setting. Pharmacokinetic simulations of sotalol plasma concentrations vs. times profiles were performed to determine the optimal intravenous/oral transition regimen. A cost minimization analysis from the health sector perspective was conducted to assess the cost savings for these proposed accelerated regimens. For a chosen target dose of 120 mg b.i.d., two infusions of 40 mg over 1 hour and 20 mg over 0.5 hour, each followed up by an evaluation of QTc , can be administered followed immediately by the target oral maintenance dose of 120 mg at the end of the second infusion. Consequently, steady-state exposure and, therefore, steady-state QTc are obtained on the first day of therapy, facilitating an earlier hospital discharge. Two and 1-day mean total cost of -$3,123 (95% confidence interval (CI), -$3,640, -$2,607) -$4,820 (95% CI, -$5,352, -$4,288) were observed for this strategy, respectively. We are proposing an intravenous to oral transition strategy for sotalol that has the potential to significantly reduce cost and increase patient convenience.

Ventricular Tachycardia (VT) Substrate Characteristics: Insights from Multimodality Structural and Functional Imaging of the VT Substrate Using Cardiac MRI Scar, 123I-Metaiodobenzylguanidine SPECT Innervation, and Bipolar Voltage.

Postischemic adaptation results in characteristic myocardial structural and functional changes in the ventricular tachycardia (VT) substrate. The aim of this study was to compare myocardial structural and functional adaptations (late gadolinium enhancement/abnormal innervation) with detailed VT mapping data to identify regional heterogeneities in postischemic changes. Methods: Fifteen patients with ischemic cardiomyopathy and drug-refractory VT underwent late gadolinium enhancement cardiac MRI (CMR), 123I-metaiodobenzylguanidine SPECT, and high-resolution bipolar voltage mapping to assess fibrosis (>3 SDs), abnormal innervation (<50% tracer uptake), and low-voltage area (<1.5 mV), respectively. Three-dimensional reconstructed CMR/123I-metaiodobenzylguanidine models were coregistered for further comparison. Results: Postischemic structural and functional adaptations in all 3 categories were similar in size (reported as median [quartile 1-quartile 3]: CMR scar, 46.1 cm2 [33.1-86.9 cm2]; abnormal innervation, 47.8 cm2 [40.5-68.1 cm2]; and low-voltage area, 29.5 cm2 [24.5-102.6 cm2]; P > 0.05). However, any single modality underestimated the total VT substrate area defined as abnormal in at least 1 of the 3 modalities (76.0 cm2 [57.9-143.2 cm2]; P < 0.001). Within the total VT substrate area, regions abnormal in all 3 modalities were most common (25.2%). However, significant parts of the VT substrate had undergone heterogeneous adaptation (abnormal in <3 modalities); the most common categories were "abnormal innervation only" (18.2%), "CMR scar plus abnormal innervation only" (14.9%), and "CMR scar only" (14.6%). All 14 VT channel/exit sites (0.88 ± 0.74 mV) were localized to myocardium demonstrating CMR scar and abnormal innervation. This specific tissue category accounted for 68.3% of the CMR scar and 31.2% of the total abnormal postischemic VT substrate area. Conclusion: Structural and functional imaging demonstrated regional heterogeneities in the postischemic VT substrate not appreciated by any single modality alone. The coexistence of abnormal innervation and CMR scar may identify a particularly "proarrhythmic" adaptation and may represent a potential novel target for VT ablation.

Outcomes following implantable cardioverter-defibrillator generator replacement in patients with recovered left ventricular systolic function: The National Cardiovascular Data Registry.

BACKGROUND: Some patients with heart failure (HF) experience recovery of left ventricular (LV) systolic function by the end of their implantable cardioverter-defibrillator (ICD) generator battery life. Outcomes following generator replacement in this setting are poorly understood. OBJECTIVE: We sought to describe outcomes following ICD generator replacement associated with recovery of LV systolic function. METHODS: We evaluated 26,197 Medicare beneficiaries enrolled in the American College of Cardiology's National Cardiovascular Data Registry ICD Registry who underwent primary prevention ICD generator replacement between 2006 and 2009, stratified by LV ejection fraction (LVEF): reduced (LVEF ≤35%), partially recovered (LVEF >35% and ≤50%), and recovered (LVEF >50%). RESULTS: At the time of generator replacement, 1915 (7.3%) patients had recovered LVEF and 4576 (17.5%) had partially recovered LVEF. Periprocedural events were rare (<1%) in all patients. In patients with reduced LVEF, the incidence of HF readmission and mortality at 3 years was 27.5% and 32.7%, respectively. In comparison, the rates of HF readmission and mortality were lower for patients with partially recovered LVEF (readmission: 15.9%; hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.61-0.72; mortality: 23.0%; HR 0.82; 95% CI 0.76-0.87) and those with recovered LVEF (readmission: 12.2%; HR 0.55; 95% CI 0.48-0.63; mortality: 18.2%; HR 0.72; 95% CI 0.64-0.80). CONCLUSION: Patients with partially recovered and recovered LVEF have lower risks of mid-term adverse outcomes than do those with reduced LVEF following ICD generator replacement. Approximately 3 in 4 patients continue to have reduced LVEF at the time of generator replacement and are at high risk of HF readmission and mortality. These data highlight the prognostic associations of LVEF in patients undergoing generator replacement as well as the clinical encounter for generator replacement as an opportunity to identify those at increased risk of adverse outcomes.

A Tale of 2 Hearts: Simultaneous Dual Tachycardias Occurring 22 Years After Orthotopic Heart Transplantation.

At 22 years following heart transplantation, a patient presented with incessant atrial flutter. During electrophysiologic study, 2 simultaneous atrial arrhythmias were mapped, 1 from the donor and 1 from the recipient's heart. High-density mapping allowed for rapid identification of electrically abnormal areas, which were successfully ablated, thus restoring sinus rhythm. (Level of Difficulty: Advanced.).

Antithromboembolic Strategies for Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

We set out to synthesize available data on antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), with a focus on triple antithrombotic therapy (triple therapy [TT]; dual antiplatelet therapy plus an anticoagulant) versus dual therapy (DT; one antiplatelet agent and an anticoagulant). We searched OVID MEDLINE and PubMed from January 2005 to September 2017 using the search terms oral anticoagulant, triple therapy, dual therapy, acute coronary syndrome, percutaneous coronary intervention, and atrial fibrillation (limited to randomized controlled trials, observational studies, English language, minimum 6-12 months of follow-up, minimum 100 human patients). We excluded surveys, literature reviews, articles not directly related to TT versus DT, incomplete studies, and short-term in-hospital studies. All eligible studies were reviewed to evaluate possible antithrombotic management strategies for patients with AF undergoing PCI. Extracted studies were categorized according to the specific anticoagulant (vitamin K antagonist vs. direct-acting oral anticoagulant) and P2Y12 inhibitor used. Each category review was followed by a discussion providing insight into the quality of evidence and implications for practice. We found that the risk of bleeding with TT was higher than with DT, without demonstrated added benefit of reducing major adverse cardiovascular events. TT use should be minimized in patients with high bleeding risk, and patient-specific factors should be critically analyzed to select appropriate antiplatelet and anticoagulant agents.

Left atrial thrombus two years after placement of a left atrial appendage closure device: Unexplored area of the Watchman.

A 72-year-old man who underwent a left atrial appendage (LAA) closure device 2 years ago presented with atrial flutter with rapid ventricular rate and was referred for cardioversion. Precardioversion transesophageal echocardiogram showed left atrial thrombus and therefore the procedure was aborted. Currently, there is no guideline on imaging surveillance or anticoagulation in patients with LAA closure device who develop intracardiac thrombus after the initial 6-month surveillance period.

A review of the LARIAT device: insights from the cumulative clinical experience.

Atrial fibrillation (AF) is the most common arrhythmic disorder world-wide, accounting for 15 % of all strokes. Management of stroke risk in AF is complicated by intolerance of anti-coagulation (AC) therapy and difficulty maintaining therapeutic range in patients treated with warfarin. The left atrial appendage (LAA) is a source of thrombus in AFrelated thrombo-embolic events and surgical LAA exclusion (LAAO) is commonly performed during cardiac surgery in AF patients. Surgical approaches are limited by a high incidence of incomplete closure with a potential for consequent thrombo-embolic events as well as the morbidity of an open-heart procedure. More recently, percutaneous approaches to LAAO have been developed. The LARIAT device is an epicardial LAA exclusion system that enables percutaneous suture ligation of the LAA via combined, pericardial and trans-septal access. The device has 510k Federal Drug Administration (FDA) clearance for soft-tissue ligation and has been studied in canine models in pre-clinical studies as well as published series of clinical experience with LARIAT LAAO. The history, patient selection, procedural technique and complications of LARIAT LAAO are reviewed here. Additionally, insights and procedural improvements that have been elucidated from clinical series and outcomes from the collective experience are discussed. The LARIAT's epicardial approach to LAA ligation is unique compared with other percutaneous LAA exclusion devices, however more data regarding device safety and efficacy is needed for the LARIAT to emerge as an established therapy for stroke prevention in AF.