Pulsed Field or Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation.

BACKGROUND: Catheter-based pulmonary vein isolation is an effective treatment for paroxysmal atrial fibrillation. Pulsed field ablation, which delivers microsecond high-voltage electrical fields, may limit damage to tissues outside the myocardium. The efficacy and safety of pulsed field ablation as compared with conventional thermal ablation are not known. METHODS: In this randomized, single-blind, noninferiority trial, we assigned patients with drug-refractory paroxysmal atrial fibrillation in a 1:1 ratio to undergo pulsed field ablation or conventional radiofrequency or cryoballoon ablation. The primary efficacy end point was freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation. The primary safety end point included acute and chronic device- and procedure-related serious adverse events. RESULTS: A total of 305 patients were assigned to undergo pulsed field ablation, and 302 were assigned to undergo thermal ablation. At 1 year, the primary efficacy end point was met (i.e., no events occurred) in 204 patients (estimated probability, 73.3%) who underwent pulsed field ablation and 194 patients (estimated probability, 71.3%) who underwent thermal ablation (between-group difference, 2.0 percentage points; 95% Bayesian credible interval, -5.2 to 9.2; posterior probability of noninferiority, >0.999). Primary safety end-point events occurred in 6 patients (estimated incidence, 2.1%) who underwent pulsed field ablation and 4 patients (estimated incidence, 1.5%) who underwent thermal ablation (between-group difference, 0.6 percentage points; 95% Bayesian credible interval, -1.5 to 2.8; posterior probability of noninferiority, >0.999). CONCLUSIONS: Among patients with paroxysmal atrial fibrillation receiving a catheter-based therapy, pulsed field ablation was noninferior to conventional thermal ablation with respect to freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation and with respect to device- and procedure-related serious adverse events at 1 year. (Funded by Farapulse-Boston Scientific; ADVENT ClinicalTrials.gov number, NCT04612244.).

Pulmonary vein narrowing after pulsed field versus thermal ablation.

AIMS: When it occurs, pulmonary vein (PV) stenosis after atrial fibrillation (AF) ablation is associated with significant morbidity. Even mild-to-moderate PV narrowing may have long-term implications. Unlike thermal ablation energies, such as radiofrequency (RF) or cryothermy, pulsed field ablation (PFA) is a non-thermal modality associated with less fibrotic proliferation. Herein, we compared the effects of PFA vs. thermal ablation on PV narrowing after AF ablation. METHODS AND RESULTS: ADVENT was a multi-centre, randomized, single-blind study comparing PFA (pentaspline catheter) with thermal ablation-force-sensing RF or cryoballoon (CB)-to treat drug-refractory paroxysmal AF. Pulmonary vein diameter and aggregate cross-sectional area were obtained by baseline and 3-month imaging. The pre-specified, formally tested, secondary safety endpoint compared a measure of PV narrowing between PFA vs. thermal groups, with superiority defined by posterior probability > 0.975. Among subjects randomized to PFA (n = 305) or thermal ablation (n = 302), 259 PFA and 255 thermal ablation (137 RF and 118 CB) subjects had complete baseline and 3-month PV imaging. No subject had significant (≥70%) PV stenosis. Change in aggregate PV cross-sectional area was less with PFA (-0.9%) than thermal ablation (-12%, posterior probability > 0.999)-primarily driven by the RF sub-cohort (-19.5%) vs. CB sub-cohort (-3.3%). Almost half of all PFA PV diameters did not decrease, but the majority (80%) of RF PVs decreased, regardless of PV anatomic location. CONCLUSION: In this first randomized comparison of PFA vs. thermal ablation, PFA resulted in less PV narrowing-thereby underscoring the qualitatively differential and favourable impact of PFA on PV tissue.

Impact of age and comorbidities on the effect of transcatheter versus surgical mitral valve repair on inpatient outcomes.

BACKGROUND: Transcatheter mitral valve repair (TMVR) has shown to be a safe and effective treatment option for symptomatic severe mitral regurgitation (MR) in patients who are at prohibitive surgical risk. Whether age and comorbidities impact the inpatient safety outcomes of TMVR versus surgical mitral valve repair (SMVR) is unknown. METHODS: Using the national inpatient sample, patients undergoing either elective TMVR or SMVR between 2012 and 2015 were analyzed. Logistic, generalized logistic, and linear regression were used to compare inpatient complications, discharge disposition, and length of stay (LOS). Heterogeneity in the effect of TMVR versus SMVR across Charlson comorbidity index (CCI, categorized as <2 and ≥2) and age (categorized as <75 years old and ≥75 years old) were assessed for effect modification. RESULTS: Overall, 8,716 hospitalizations were included, 7,950 (91%) SMVR and 766 (9%) TMVR. Compared with SMVR, patients undergoing TMVR were older (median age 79 vs. 62 years) and more likely to be female (45% vs. 40%) with a higher CCI score (median CCI 2 vs. 1). Despite being older with a higher comorbidity burden, patients undergoing TMVR had a lower incidence of permanent pacemaker implantation (OR 0.23, 95% CI: 0.11, 0.50), cerebrovascular accidents (OR 0.37, 95% CI: 0.15, 0.92), and major bleeding (OR 0.39, 95% CI: 0.32, 0.47). TMVR patients were also discharged 3 days earlier (CIE -3.26; 95% CI: -3.72, -2.80) and were less likely to be discharged to a skilled nursing facility (OR 0.72, 95% CI 0.55, 0.93). Additionally, the relative reduction in complications after TMVR versus SMVR was significantly higher in older (age ≥75 years) and more comorbid (CCI ≥2) patients (p for interaction <.05 for both). CONCLUSION: Patients treated with TMVR, as compared with SMVR, were older and had more comorbidities, but had a lower incidence of inpatient complications, shorter LOS, and better discharge disposition. Therefore, TMVR may be a safer option than SMVR in older patients and those with a higher burden of comorbidities.

Spontaneous clearance of hepatitis B surface antigenemia after long-term hemodialysis.

Persistent infection with the hepatitis B virus (HBV) [as indicated by chronic HBV surface antigenemia (HBsAg)] continues to be an important problem in end-stage renal disease (ESRD) patients and specifically in those receiving maintenance hemodialysis (HD). Patients on HD who are HBsAg-positive for a year have little chance of ever eliminating the virus; hence, clearance of HBsAg is a rare event in long-term HD patients. We report the case of a 62-year-old diabetic woman who was HBsAg-positive at the time she started HD and remained so until 10 years later when she became HBsAg-negative followed by the development of hepatitis B surface antibody (anti-HBs). Prior to her seroconversion, she suffered a persistent infection of her HD arteriovenous graft (AVG) that required prolonged antibiotics and several surgical procedures. We speculate that this immune stimulation contributed to her seroconversion.

Point-of-Care Ultrasound in the Emergency Department: Training, Perceptions, Applications, and Barriers from Different Healthcare Professionals.

Background: Point-of-care ultrasound (POCUS) is a valuable tool that assists in diagnosis and management of patients in the emergency department (ED) while being cost-efficient and without the use of ionizing radiation. To discern the opinions and perceptions of ED staff about POCUS applications and barriers, we conducted a cross-sectional survey of employees of 12 EDs in North Texas. Methods: Participants completed a 20-item online survey about POCUS with questions pertaining to four domains: (1) employee and training information, (2) perceived benefits, (3) common applications, and (4) barriers to use. Out of 805 eligible ED employees, 103 completed the survey (16.1% response rate). Results: The results indicated a generally positive perception of POCUS among all employee types. Physician had significant exposure and training of POCUS than non-physician group ( p < 0.001). Physicians tend to find cardiac assessments more useful for clinical management than non-physicians (47% vs. 23%, p = 0.01), while non-physicians find soft tissue/abscess assessments more useful (27% vs. 9%, p = 0.01). Conclusion: The most significant barriers to POCUS use were time constraints for physicians and a lack of training for non-physician employees. Our study provides valuable insights into the perceptions of multiple ED professionals, serving as a foundation for promoting POCUS use in the ED.

Comparison of cerebral safety after atrial fibrillation using pulsed field and thermal ablation: Results of the neurological assessment subgroup in the ADVENT trial.

BACKGROUND: Atrial fibrillation (AF) ablation carries the risk of silent cerebral event (SCE) and silent cerebral lesion (SCL). Although "silent," these may have long-term clinical implications and are challenging to study as postprocedural magnetic resonance imaging (MRI) is not standard of care. OBJECTIVE: The neurological assessment subgroup (NAS) of ADVENT compared cerebral effects of pulsed field ablation (PFA) with standard-of-care thermal ablation. METHODS: The NAS included consecutive randomized PFA and thermal ablation patients who received postprocedural brain MRI 12-48 hours after ablation. Patients with apparent SCE or SCL findings underwent a modified Rankin scale assessment. MRI images were subsequently reviewed by a blinded brain imaging core laboratory. RESULTS: In total, 77 patients with paroxysmal AF were enrolled at 6 centers; 71 had analyzable scans (34 PFA; 37 thermal ablation). Through individual center review, 6 PFA and 4 thermal scans were identified as SCE/SCL positive, of which 3 PFA and 0 thermal SCE/SCL findings were confirmed by a blinded core laboratory. MRI findings revealed 1 patient with 2- to 4-mm SCEs, 1 patient with a 3-mm SCE, and 1 patient with 2 SCLs (5.5 mm and 11 mm). All modified Rankin scale and National Institutes of Health Stroke Scale scores were 0 before discharge and at 90-day follow-up. There were only 2 neurological safety events (1 transient ischemic attack [PFA] and 1 stroke [thermal ablation]) in the ADVENT study, neither of which was part of the NAS. CONCLUSION: The ADVENT trial provides the first prospective, randomized data on the cerebral impact of PFA and thermal ablation of AF. Incidence of SCE/SCL after ablation in the NAS was low.

Broadening Perspectives of Artificial Intelligence in Echocardiography.

Echocardiography frequently serves as the first-line treatment of diagnostic imaging for several pathological entities in cardiology. Artificial intelligence (AI) has been growing substantially in information technology and various commercial industries. Machine learning (ML), a branch of AI, has been shown to expand the capabilities and potential of echocardiography. ML algorithms expand the field of echocardiography by automated assessment of the ejection fraction and left ventricular function, integrating novel approaches such as speckle tracking or tissue Doppler echocardiography or vector flow mapping, improved phenotyping, distinguishing between cardiac conditions, and incorporating information from mobile health and genomics. In this review article, we assess the impact of AI and ML in echocardiography.

Echocardiography is the most common test in cardiovascular imaging and helps diagnose multiple different diseases. Machine learning, a branch of artificial intelligence (AI), will reduce the workload for medical professionals and help improve clinical workflows. It can rapidly calculate a lot of important cardiac parameters such as the ejection fraction or important metrics during different phases of the cardiac cycle. Machine learning algorithms can include new technology in echocardiography such as speckle tracking, tissue Doppler echocardiography, vector flow mapping, and other approaches in a user-friendly manner. Furthermore, it can help find new subtypes of existing diseases in cardiology. In this review article, we look at the current role of machine learning and AI in the field of echocardiography.

Longitudinal predictors of uremic pruritus.

OBJECTIVE: Pruritus is a common problem among hemodialyzed patients. Its causes are poorly understood, and, as a result, itching is often attributed to elevated serum phosphorus and other disorders of bone and minerals. The primary purpose of this study was to analyze the relationship between pruritus and common tests of bone and mineral disease. METHODS: This study was a post hoc analysis of data from a randomized controlled trial of 3 months of ergocalciferol versus placebo treatment in 50 hemodialysis patients with uremic pruritus. A pruritus survey was administered at baseline and then every 2 weeks for 12 weeks. Concurrent serum phosphorus, intact parathyroid hormone (PTH), serum calcium, and calcium-phosphate product were measured. RESULTS: Pruritus score was not found to be associated or correlated with serum phosphate, intact PTH, serum calcium, or calcium-phosphate product at each time interval or over time. Likewise, when analyzed by original study group (placebo or ergocalciferol), no association or correlation between the mineral and bone indicators and itching were found. CONCLUSION: Neither serum phosphate nor other tests of bone and mineral status were found to be significant predictors of pruritus at any point in time or over time.

Long-term response to peginterferon in hepatitis C virus-associated nephrotic syndrome from focal segmental glomerulosclerosis.

Hepatitis C virus (HCV) infection is a global public health problem. Chronic HCV infection is an important cause of chronic liver disease. Since the first reported association between HCV and membranoproliferative glomerulonephritis (MPGN) in 1993, HCV has been described with other types of glomerular diseases, although less frequently. Focal segmental glomerulosclerosis (FSGS) is one such glomerular disease that has been rarely reported in association with HCV. Antiviral therapy with interferon and ribavirin has been shown to be beneficial in HCV-associated MPGN. The optimal therapy of HCV-associated FSGS is not currently known. To our knowledge, long-term response to pegylated interferon monotherapy in treatment of HCV-associated FSGS has not been reported. We report an adult patient with HCV-associated FSGS who presented with nephrotic syndrome and renal failure. Treatment with pegylated interferon alfa-2a monotherapy resulted in sustained virological response with a clinical remission of nephrotic syndrome and stabilization of renal function. Patient continued to remain in clinical remission of nephrotic syndrome with stable renal function, 5 years after treatment. We also briefly review the literature on HCV-associated glomerular diseases, particularly HCV-associated FSGS.

Complete remission of hepatitis B virus-associated nephrotic syndrome from IgA nephropathy following peginterferon therapy.

Hepatitis B virus (HBV) infection is a major cause of acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV has also been associated with various common and uncommon glomerular diseases, including IgA nephropathy (IgAN). We report a patient with chronic HBV infection who presented with atypical features of IgAN with management and long-term follow-up. Much of the data on the treatment of HBV-associated glomerular diseases come from patients with membranous nephropathy, whereas the information on treatment of other glomerulopathies remains largely anecdotal. To the best of our knowledge, treatment of an adult patient with HBV-associated nephrotic syndrome from IgAN with pegylated interferon has not been previously reported. Treatment with pegylated interferon alfa-2b in our patient resulted in complete clinical remission of the nephrotic syndrome as well as a dramatic decrease in HBV viral load. Patient continued to remain in clinical remission 5 years after treatment.

Validation of a Deep Learning Algorithm for Continuous, Real-Time Detection of Atrial Fibrillation Using a Wrist-Worn Device in an Ambulatory Environment.

BACKGROUND: Wearable devices may be useful for identification, quantification and characterization, and management of atrial fibrillation (AF). To date, consumer wrist-worn devices for AF detection using photoplethysmography-based algorithms perform only periodic checks when the user is stationary and are US Food and Drug Administration cleared for prediagnostic uses without intended use for clinical decision-making. There is an unmet need for medical-grade diagnostic wrist-worn devices that provide long-term, continuous AF monitoring. METHODS AND RESULTS: We evaluated the performance of a wrist-worn device with lead-I ECG and continuous photoplethysmography (Verily Study Watch) and photoplethysmography-based convolutional neural network for AF detection and burden estimation in a prospective multicenter study that enrolled 117 patients with paroxysmal AF. A 14-day continuous ECG monitor (Zio XT) served as the reference device to evaluate algorithm sensitivity and specificity for detection of AF in 15-minute intervals. A total of 91 857 intervals were contributed by 111 subjects with evaluable reference and test data (18.3 h/d median watch wear time). The watch was 96.1% sensitive (95% CI, 92.7%-98.0%) and 98.1% specific (95% CI, 97.2%-99.1%) for interval-level AF detection. Photoplethysmography-derived AF burden estimation was highly correlated with the reference device burden (R2=0.986) with a mean difference of 0.8% (95% limits of agreement, -6.6% to 8.2%). CONCLUSIONS: Continuous monitoring using a photoplethysmography-based convolutional neural network incorporated in a wrist-worn device has clinical-grade performance for AF detection and burden estimation. These findings suggest that monitoring can be performed with wrist-worn wearables for diagnosis and clinical management of AF. REGISTRATION INFORMATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04546763.

Clinical Characteristics of Patients Returning to Emergency Department With Initial False-Negative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)-Based COVID-19 Test.

Background: The coronavirus disease 2019 (COVID-19) outbreak is an international public health emergency. Early identification of COVID-19 patients with false-negative RT-PCR tests is paramount in the ED to prevent both nosocomial and community transmission. This study aimed to compare clinical characteristics of repeat emergency department (ED) visits among coronavirus disease 2019 (COVID-19) patients with initial false-negative reverse transcriptase-polymerase chain reaction (RT-PCR)-based COVID-19 test. Methods: This is a retrospective, multi-center, cohort study conducted at 12 hospitals affiliated with Baylor Scott & White Health system. Patients visiting the EDs of these hospitals between June and August 2020 were screened. Patients tested negative for viral RNA by quantitative RT-PCR in the first ED visit and positive in the second ED visit were included. The primary outcome was the comparison of clinical characteristics between two consecutive ED visits including the clinical symptoms, triage vital signs, laboratory, and chest X-ray (CXR) results. Results: A total of 88 confirmed COVID-19 patients with initial false-negative RT-PCR COVID-19 test in the ED were included in the final analyses. The mean duration of symptoms in the second ED visit was significantly higher (3.6 ± 0.4 vs. 2.6 ± 0.3 days, p = 0.020). In the first ED visit, lymphocytopenia (35.2%), fever (32.6%), nausea (29.5%), and dyspnea (27.9%) are the most common signs of COVID-19 infection during the window period. There were significant increases in the rate of hypoxia (13.6% vs. 4.6%, p = 0.005), abnormal infiltrate on CXR (59.7% vs. 25.9%, p < 0.001), and aspartate aminotransferase (AST) elevation (26.1% vs. 9.1%, p < 0.001) in the second ED visit. Conclusions: Early COVID-19 testing (less than 3 days of symptom duration) could be associated with a false-negative result. In this window period, lymphocytopenia, fever, nausea, and dyspnea are the most common early signs that can potentially be clinical hints for COVID-19 diagnosis.

Maternal immune response and placental antibody transfer after COVID-19 vaccination across trimester and platforms.

The availability of three COVID-19 vaccines in the United States provides an unprecedented opportunity to examine how vaccine platforms and timing of vaccination in pregnancy impact maternal and neonatal immunity. Here, we characterize the antibody profile after Ad26.COV2.S, mRNA-1273 or BNT162b2 vaccination in 158 pregnant individuals and evaluate transplacental antibody transfer by profiling maternal and umbilical cord blood in 175 maternal-neonatal dyads. These analyses reveal lower vaccine-induced functions and Fc receptor-binding after Ad26.COV2.S compared to mRNA vaccination and subtle advantages in titer and function with mRNA-1273 versus BN162b2. mRNA vaccines have higher titers and functions against SARS-CoV-2 variants of concern. First and third trimester vaccination results in enhanced maternal antibody-dependent NK-cell activation, cellular and neutrophil phagocytosis, and complement deposition relative to second trimester. Higher transplacental transfer ratios following first and second trimester vaccination may reflect placental compensation for waning maternal titers. These results provide novel insight into the impact of platform and trimester of vaccination on maternal humoral immune response and transplacental antibody transfer.

A novel mutation in the KCNH2 gene associated with short QT syndrome.

A gain of function mutation N588K in the KCNH2 gene that encodes HERG channels has been shown to underlie the SQT1 form of short QT syndrome (SQTS). We describe a different mutation in the KCNH2 gene in a Chinese family with clinical evidence of SQTS. A Chinese family with a markedly short QT interval (QTc=316 ± 9 ms, n=4) and a strong family history of sudden death was investigated. Analysis of candidate genes contributing to ventricular repolarization identified a C1853T mutation in the KCNH2 gene coding for the HERG channel, resulting in an amino acid change (T618I) that was found to 100% co-segregate with the SQTS phenotype (n=4). Whole cell voltage clamp studies of the T618I mutation in HEK-cells demonstrated a 6-fold increase in maximum steady state current (146.1 ± 16.7 vs 23.8 ± 5.5 pA/pF) that occurred at a 20 mV more positive potential compared to the wild type channels. The voltage dependence of inactivation was significantly shifted in the positive voltage direction (WT -78.6 ± 6.8 vs T618I -29.3 ± 1.7 mV). Kinetic analysis revealed slower inactivation rates of T618I but faster rates of recovery from inactivation. Quinidine (5 µM) and sotalol (500 µM) had similar inhibitory effects on steady currents measured at +20 mV in WT and T618I but were less effective in inhibiting tail currents of mutant channels. The altered function of T618I-HERG channels suggests that this mutation in the KCNH2 gene is responsible for the SQTS phenotype in this family. Both quinidine and sotalol may be therapeutic options for patients with the T618I HERG mutation.

Role of antiarrhythmic drugs: frequent implantable cardioverter-defibrillator shocks, risk of proarrhythmia, and new drug therapy.

The implantable cardioverter-defibrillator (ICD) is the standard of care in patients with ischemic and nonischemic cardiomyopathy who are at high risk for arrhythmic events and sudden cardiac death. Although an ICD saves life, ICD shocks are emotionally and physically debilitating. Most patients receive adjuvant antiarrhythmic drug therapy to circumvent episodes of recurrent ventricular and supraventricular arrhythmias. Antiarrhythmic drugs including b-blockers, sotalol, amiodarone, and azimilide are effective at reducing the shock burden. This article describes data supporting the need for and potential risks and benefits of adjuvant antiarrhythmic drug therapy and examines the benefits and pitfalls of the same in ICD-implanted patients.

Rhabdomyolysis-induced acute kidney injury in a patient with non-compliance to levothyroxine therapy.

SUMMARY: Hypothyroidism is a common medical condition and is often easily managed with excellent outcomes, when treated adequately. Compliance with levothyroxine (LT4) therapy is often compromised because of the need for a daily and lasting schedule. Overt rhabdomyolysis due to under-treatment or non-compliance is a rare occurrence. We report a case of rhabdomyolysis leading to acute kidney injury (AKI) on chronic kidney disease (CKD) requiring hemodialysis (HD) in a 68-year-old Caucasian male due to non-compliance with levothyroxine (LT4) therapy. Our patient 'ran out of levothyroxine' for approximately 4 weeks and developed gradually progressive muscle pain. The diagnosis of severe AKI due to rhabdomyolysis was made based on oliguria, elevated creatinine kinase (CK), and renal failure. Resuming the home dose of LT4 failed to correct CK levels, and there was a progressive decline in renal function. Although increasing doses of LT4 and three cycles of HD improved CK levels, they remained above baseline at the time of discharge. The patient recovered gradually and required HD for 4 weeks. CK levels normalized at 6 weeks. Through this case report, we highlight that non-compliance with LT4 therapy can lead to life-threatening complications such as renal failure and hence the need to educate patients on the significance of compliance with LT4 therapy should be addressed. LEARNING POINTS: Non-compliance to levothyroxine therapy is common and can lead to serious complications, including rhabdomyolysis. Rhabdomyolysis is an uncommon presentation of hypothyroidism and severe rhabdomyolysis can result in renal failure requiring hemodialysis. Rhabdomyolysis associated with hypothyroidism can be further exacerbated by concomitant use of statins.

Malnutrition-Inflammation Complex Syndrome: A Cause of Low Parathyroid Hormone in Patients With Chronic Kidney Disease.

Secondary hyperparathyroidism is commonly seen in patients with chronic kidney disease (CKD) due to hypocalcemia, hyperphosphatemia and low vitamin D levels and is associated with high-turnover bone disease. In contrast, some patients with advanced CKD, including those requiring dialysis (end-stage renal disease [ESRD]), develop adynamic bone disease with features of low-turnover bone disease. Low serum parathyroid hormone (PTH) has been used as a biochemical marker of adynamic bone disease. Low PTH levels may not necessarily be due to adynamic bone disease but could be a manifestation of the malnutrition inflammation complex syndrome (MICS). The optimal management of hypoparathyroidism associated with MICS is not well known. Currently, there is insufficient evidence to suggest if there is any role in improving nutritional and inflammatory status among patients with CKD and MICS. Furthermore, it also remains unclear whether these changes will help address low PTH levels seen in these patients. We report three patients with advanced CKD who had very low PTH levels possibly attributed to MICS. In addition, we briefly discuss other characteristics and pathophysiology of MICS.

Dronedarone.

Amiodarone is the most effective antiarrhythmic drug for maintaining sinus rhythm for patients with atrial fibrillation. Extra-cardiac side effects have been a limiting factor, especially during chronic use, and may offset its benefits. Dronedarone is a noniodinated benzofuran derivative of amiodarone that has been developed for the treatment of atrial fibrillation and atrial flutter. Similar to amiodarone, dronedarone is a potent blocker of multiple ion currents, including the rapidly activating delayed-rectifier potassium current, the slowly activating delayed-rectifier potassium current, the inward rectifier potassium current, the acetylcholine activated potassium current, peak sodium current, and L-type calcium current, and exhibits antiadrenergic effects. It has been studied for maintenance of sinus rhythm and control of ventricular response during episodes of atrial fibrillation. Dronedarone reduces mortality and morbidity in patients with high-risk atrial fibrillation, but may be unsafe in those with severe heart failure. This article will review evidence of safety and effectiveness of dronedarone in patients with atrial fibrillation.

Ventricular transmural repolarization sequence: its relationship with ventricular relaxation and role in ventricular diastolic function.

AIMS: We investigated the role of ventricular repolarization sequence in ventricular diastolic function. METHODS AND RESULTS: Arterially perfused canine left ventricular wedge preparation with simultaneous recording of action potentials and isometric contractile force was used to establish the relationship between ventricular repolarization and relaxation sequences. An isolated rabbit working heart model was used to investigate role of ventricular repolarization sequence in ventricular diastolic function. Under controlled conditions, similar to transmural dispersion of repolarization (TDR), there existed a time difference between initiation of epicardial and endocardial relaxation (TR(Epi-Endo), 47.4 +/- 13.9 ms) with epicardium relaxing earlier. There was a strong correlation between TDR and TR(Epi-Endo) (r(2) = 0.99, n = 5) and the interventions that changed transmural repolarization sequence led to parallel changes in transmural relaxation sequence. In isolated rabbit working hearts, reversal of the transmural repolarization sequence that manifested as negative T wave was associated with a significant increase in isovolumic relaxation time (from 49.2 +/- 19.1 to 76.4 +/- 12.1 ms, n = 5, P = 0.001). CONCLUSION: There is a strong correlation between transmural repolarization and relaxation sequences. A positive T wave that denotes transmural repolarization sequence from epicardium to endocardium is essential for normal diastolic function of ventricle and the reversal of such sequence is associated with ventricular diastolic dysfunction.

Trends and effect of atrial fibrillation on inpatient outcomes after transcatheter aortic valve replacement.

BACKGROUND: Atrial fibrillation (AF) is common in patients undergoing transcatheter aortic valve replacement (TAVR) but there is conflicting evidence on whether AF impacts outcomes after TAVR. METHODS: Hospitalizations of adults ≥50 years old who had undergone elective TAVR from 2012 to 2015 were included. Poisson regression was used to assess changes in in-hospital complications, average length of stay (LOS) after TAVR, and discharge disposition over time. Multivariable logistic, linear, and generalized logistic regression models, adjusting for patient and hospital characteristics, were used to estimate the effect of AF on inpatient outcomes. RESULTS: A total of 7,266 TAVR hospitalizations were included; AF was present in 44% of patients. Between 2012 and 2015, there was a significant decrease in the incidence of acute kidney injury, blood transfusion, average LOS, and inpatient mortality both for AF and non-AF patients. However, the incidences of vascular complications and major bleeding decreased only among non-AF patients. After adjustment, AF was associated with increased incidences of TIA/stroke (OR 1.36, 95% CI: 1.01, 1.85), acute kidney injury (OR 1.54, 95% CI: 1.33, 1.78), blood transfusion (OR 1.14, 95% CI: 1.00, 1.30), transfer to a skilled nursing facility (OR 1.38, 95% CI: 1.23, 1.55), and longer average LOS (CIE 1.30, 95% CI: 1.06, 1.54). AF was not associated with inpatient mortality (OR 1.09, 95% CI: 0.81, 1.48). CONCLUSIONS: AF is prevalent among patients undergoing TAVR, and is associated with higher incidences of inpatient complications, discharge to a skilled nursing facility, and longer average LOS. While the incidence of many complications has declined in the past few years, continued efforts to further reduce complications in patients with AF is urgently required for expansion of TAVR to broader populations.