The Impact of COVID-19 Infection Control Measures on End-Stage Renal Disease Patients in a Community Hemodialysis Setting.

INTRODUCTION: Several non-pharmaceutical infection control measures have been implemented at community-based hemodialysis centers to reduce the risk of Coronavirus Disease of 2019 (COVID-19) transmission, caused by the SARS-CoV-2 virus. However, there have been concerns that such measures may disrupt the routine and timely care required by patients, with adverse effects on their health outcomes. This cross-sectional study aims to determine the unintended consequences of COVID-19 infection control measures on hemodialysis patients. METHODS:  Electronic medical records were extracted from patients enrolled in community-based hemodialysis centers in Singapore. A baseline group prior of patients consisted of those enrolled in 2017, which was three years prior to the SARS-CoV-2-related pandemic (n = 548). This was compared with the study group of patients enrolled in 2019 (n = 426), just before the COVID-19 pandemic started. Medical records for these two groups were extracted from January to July 2018 for the baseline group and from January to July 2020, respectively. Three regression models were built to study dialysis adherence, kidney disease biomarkers, and hospitalization episodes. RESULTS:  There was no statistically significant difference in hospitalization and mortality outcomes, adherence to dialysis management, laboratory results for dialysis-related clearance, and anemia outcomes. There was a higher proportion of patients hospitalized for vascular access-related reasons in the study group as compared to the baseline group (OR 1.6, 95% CI: 1.10 to 2.29, P = 0.014). Patients in the study group had albumin levels 2.13% higher (95% CI: 0.88 to 3.39, P < 0.001) and alkaline phosphatase levels 7.3% lower (95% CI: 1.17 to 13.02, P = 0.020) than those in the baseline group. CONCLUSIONS:  From this community-based hemodialysis study in Singapore, it was shown that the COVID-19 pandemic did not disrupt regular healthcare services for these patients. With strategies instituted for a coordinated health delivery workflow, ensuring sufficient capacity in the various healthcare delivery sites and overall pandemic preparedness, the patient clinical outcomes measures continued to be met with no adverse consequences noted. Some improvements in dialysis-related laboratory values and quality of care targets may be due to more stringent measures instituted to protect these vulnerable patients in the community.

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.).

Limited Left Thoracoscopic Sympathectomy Effectively Silences Refractory Electrical Storm.

BACKGROUND: An electrical storm (ES) is a life-threatening condition that affects up to 20% of patients with implantable cardioverter defibrillators. In this small retrospective study, we report our results with left video-assisted thoracoscopic sympathectomy/ganglionectomy (VATSG) to treat refractory ES in low-ejection fraction patients who were not candidates for catheter ablation. METHODS: We identified 12 patients who presented with ES and underwent a total of 14 video-assisted thoracoscopic sympathectomy/ganglionectomy, including 3 patients on venoarterial extracorporeal membrane oxygenation. We reviewed demographic data, survival to discharge, number of cardioversions (before and after VATSG), need for readmissions, and need for right-sided procedures. RESULTS: In the 30 days before a left VATSG, mean number of shocks was 22.67 for all patients. For the patients who survived to discharge, the mean was 3.55 since surgery and the median was zero shocks after a median follow-up of 358 days. Six patients did not experience further cardioversions since the last VATSG and 5 were not readmitted for ventricular tachycardia. Two patients had staged bilateral procedures owing to recurrences; of those, 1 did not require further cardioversions. CONCLUSIONS: Limited left VATSG is an appropriate and effective initial treatment for ES patients who are not candidates for catheter ablation, including those on venoarterial extracorporeal membrane oxygenation for hemodynamic support.

Dominant vector changes during early wavebreak/spiral wave (Wiggers stage 1) in ventricular fibrillation: insights from the analysis of 100 electrophysiology studies.

PURPOSE: To describe electrocardiographic vector patterns during early VF transition (Wiggers stage 1). METHODS: In 100 electrophysiology studies with VF induction, the first 3 beats of VF were analyzed in lead I for left/right axis (LA/RA), V1 for left/right bundle (LB/RB), and aVF for superior/inferior axis (SA/IA). Correlation with demographic/clinical factors was performed using regression analyses and mixed effect modeling. RESULTS: VF initiated more likely with LA than RA (P < 0.001) and LB than RB (P = 0.04) suggesting original wavebreak in the right ventricle. The 3-dimensional morphology changed in 69% of VF during the first 3 beats, with predominant increase in RB, suggesting a transition of QRS-originating vector to septum/left ventricle. Conservation of morphology (31%) was favored by initial RB (P = 0.002) and LA morphology (P = 0.01). Initiation of VF with LA vs RA was more likely in African-Americans (P = 0.016) and increasing age (P = 0.032). Ischemic cardiomyopathy favored VF initiation with RB 6.7-fold (P = 0.025), possibly linking LV myocardial scar to initial VF wavebreak location. Male gender and ischemic cardiomyopathy prolonged time-to-loss of predominant vector by 119% (P = 0.002) and 71% (P = 0.017), respectively, suggesting more preserved anatomic/functional reentry. CONCLUSION: The predominant QRS vectors during early Wiggers stage 1 VF are not random and suggest an initial wavebreak more commonly in the right ventricle, followed by a transitional shift to the septum/left ventricle. Ethnicity, male gender, age, and co-morbidities result in directional preservation of initiating VF vectors possibly due to myocardial mass/fibrosis. Findings may allow new treatment/ablation approaches.

Metabolic heterogeneous zone assessed by 18 FDG-PET is predictive of postablation mortality in patients with ventricular tachycardia.

PURPOSE: We sought to study the predictive value of the metabolic heterogeneous zone (HZ) as determined by 18 Fluorodeoxyglucose (18 FDG) positron emission tomography (PET) viability studies in ventricular tachycardia (VT) patients. METHODS: PET studies utilizing 82 Rubidium (82 Rb) tracer for perfusion and 18 FDG tracer for viability were analyzed using PMOD (PMOD Technologies) and further analyzed using 684-segment plots. 18 FDG uptake was normalized to the area with maximal perfusion on the rest 82 Rb study. Metabolic scar, HZ, and healthy segments were defined with perfusion-normalized 18 FDG uptake between 0%-50%, 50%-70%, and >70%, respectively. RESULTS: Thirty-four VT patients (age, 63 ± 12 years) were evaluated with 18 FDG-PET viability study. Most (n = 31) patients underwent VT ablation. Patients were categorized to HZ < median versus HZ ≥ median based on a median HZ area size of 21.0 cm2 . HZ size was significantly larger in the deceased group than the alive group (35.2 cm2 vs. 18.1 cm2 , p = .01). Deaths were significantly higher in HZ ≥ 21 cm2 group than HZ < 21 cm2 group (58.8% vs. 11.8%, p = .005). Survival analysis showed significantly higher mortality in the HZ ≥ 21 cm2 group than the HZ < 21 cm2 group (HR = 4.1, 95% CI: 1.3-12.6, p = .016). In a multivariable analysis, HZ was found to be an independent predictor for all-cause mortality (HR = 1.07, 95% CI: 1.02-1.12, p = .01) CONCLUSIONS: Increased HZ size of myocardium was associated with increased mortality. Metabolic HZ quantification may be of value in risk stratification and management of ischemic and nonischemic patients with VT.

Metabolic Scar Assessment with18F-FDG PET: Correlation to Ischemic Ventricular Tachycardia Substrate and Successful Ablation Sites.

The functional and molecular imaging characteristics of ischemic ventricular tachycardia (VT) substrate are incompletely understood. Our objective was to compare regional 18F-FDG PET tracer uptake with detailed electroanatomic maps (EAMs) in a more extensive series of postinfarction VT patients to define the metabolic properties of VT substrate and successful ablation sites. Methods: Three-dimensional (3D) metabolic left ventricular reconstructions were created from perfusion-normalized 18F-FDG PET images in consecutive patients undergoing VT ablation. PET defects were classified as severe (defined as <50% uptake) or moderate (defined as 50%-70% uptake), as referenced to the maximal 17-segment uptake. Color-coded PET scar reconstructions were coregistered with corresponding high-resolution 3D EAMs, which were classified as indicating dense scarring (defined as voltage < 0.5 mV), normal myocardium (defined as voltage > 1.5 mV), or border zones (defined as voltage of 0.5-1.5 mV). Results: All 56 patients had ischemic cardiomyopathy (ejection fraction, 29% ± 12%). Severe PET defects were larger than dense scarring, at 63.0 ± 48.4 cm2 versus 13.8 ± 33.1 cm2 (P < 0.001). Similarly, moderate/severe PET defects (≤70%) were larger than areas with abnormal voltage (≤1.5 mV) measuring 105.1 ± 67.2 cm2 versus 56.2 ± 62.6 cm2 (P < 0.001). Analysis of bipolar voltage (23,389 mapping points) showed decreased voltage among severe PET defects (n = 10,364; 0.5 ± 0.3 mV) and moderate PET defects (n = 5,243; 1.5 ± 0.9 mV, P < 0.01), with normal voltage among normal PET areas (>70% uptake) (n = 7,782, 3.2 ± 1.3 mV, P < 0.001). Eighty-eight percent of VT channel or exit sites (n = 44) were metabolically abnormal (severe PET defect, 78%; moderate PET defect, 10%), whereas 12% (n = 6) were in PET-normal areas. Metabolic channels (n = 26) existed in 45% (n = 25) of patients, with an average length and width of 17.6 ± 12.5 mm and 10.3 ± 4.2 mm, respectively. Metabolic channels were oriented predominantly in the apex or base (86%), harboring VT channel or exit sites in 31%. Metabolic rapid-transition areas (>50% change in 18F-FDG tracer uptake/15 mm) were detected in 59% of cases (n = 33), colocalizing to VT channels or exit sites (15%) or near these sites (85%, 12.8 ± 8.5 mm). Metabolism-voltage mismatches in which there was a severe PET defect but voltage indicating normal myocardium were seen in 21% of patients (n = 12), 41% of whom were harboring VT channel or exit sites. Conclusion: Abnormal 18F-FDG uptake categories could be detected using incremental 3D step-up reconstructions. They predicted decreasing bipolar voltages and VT channel or exit sites in about 90% of cases. Additionally, functional imaging allowed detection of novel molecular tissue characteristics within the ischemic VT substrate such as metabolic channels, rapid-transition areas, and metabolism-voltage mismatches demonstrating intrasubstrate heterogeneity and providing possible targets for imaging-guided ablation.

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.

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.

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

Ventricular arrhythmia ablation lesions detectability and temporal changes on cardiac magnetic resonance.

BACKGROUND: Cardiac magnetic resonance (CMR) characteristics of ventricular radiofrequency ablation (RFA) lesions have only been incompletely defined. AIM: To determine the detectability and imaging characteristics of ventricular RFA lesions in an unselected patient cohort undergoing ventricular arrhythmia ablation. METHODS AND RESULTS: A retrospective chart review (n = 249) identified 36 patients with either pre-/postablation CMR (n = 14) or only postablation CMR (n = 22). Ablation lesions could be identified in 50% (n = 18) of patients. Nonvisualized lesions had more preexisting transmural late gadolinium enhancement (LGE) >75% at the ablation sites (21% vs 0.0%, P = .042), more prevalent ICD artifact (50% vs 0%, P = .001), and lower ejection fraction (35.8 ± 14.2% vs 45.3 ± 13.4%, P = .048). Early CMR imaging demonstrated a central "black" signal void (microvascular obstruction [MVO], n = 12, 67%) up to 32 days post-RFA, whereas late imaging showed a homogenously "white" gadolinium enhancement pattern (n = 6, 33%). MVO was only observed in nonfibrotic myocardium without preexisting LGE (n = 12) but was not observed in the scar with preexisting LGE (n = 3, P = .002) suggesting different wash-in/wash-out kinetics in scar/nonscar myocardium. Signal intensity (1909 vs 2534, P = .009) and contrast-to-noise ratio (-7.8 vs 16.3, P = .009) were significantly different between MVO and LGE lesions, respectively. CONCLUSION: Ventricular ablation lesions visualization is negatively affected by preexisting transmural scar, ICD artifact, and low ejection fraction. The transition of "black" MVO appearance to "white" LGE appearance on CMR occurs around 1 month following ablation, suggesting a change in histological characteristics of ablation lesions. This may affect the utility of CMR in the evaluation of the ventricular lesions, when undergoing real-time or repeat VT ablations.

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.

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.).