New atrial arrhythmia occurrence in single chamber implantable cardioverter defibrillator patients: A real-world investigation.

INTRODUCTION: A current limitation of single chamber implantable cardioverter defibrillators (ICDs) is the lack of an atrial lead to reliably detect atrial fibrillation (AF) episodes. A novel ventricular based atrial fibrillation (VBAF) detection algorithm was created for single chamber ICDs to assess R-R variability for detection of AF. METHODS: Patients implanted with Visia AF™ ICDs were prospectively enrolled in the Medtronic Product Surveillance Registry from December 15, 2015 to January 23, 2019 and followed with at least 30 days of monitoring with the algorithm. Time to device-detected daily burden of AF ≥ 6 min, ≥6 h, and ≥23 h were reported. Clinical actions after device-detected AF were recorded. RESULTS: A total of 291 patients were enrolled with a mean follow-up of 22.5 ± 7.9 months. Of these, 212 (73%) had no prior history of AF at device implant. However, 38% of these individuals had AF detected with the VBAF algorithm with daily burden of ≥6 min within two years of implant. In these 80 patients with newly detected AF by their ICD, 23 (29%) had a confirmed clinical diagnosis of AF by their provider. Of patients with a clinical diagnosis of AF, nine (39%) were newly placed on anticoagulation, including five of five (100%) patients having a burden >23 h. CONCLUSIONS: Continuous AF monitoring with the new VBAF algorithm permits early identification and actionable treatment for patients with undiagnosed AF that may improve patient outcomes.

Attenuated heart rate recovery is associated with higher arrhythmia recurrence and mortality following atrial fibrillation ablation.

AIMS: Heart rate recovery (HRR), the decrease in heart rate occurring immediately after exercise, is caused by the increase in vagal activity and sympathetic withdrawal occurring after exercise and is a powerful predictor of cardiovascular events and mortality. The extent to which it impacts outcomes of atrial fibrillation (AF) ablation has not previously been studied. The aim of this study is to investigate the association between attenuated HRR and outcomes following AF ablation. METHODS AND RESULTS: We studied 475 patients who underwent EST within 12 months of AF ablation. Patients were categorized into normal (>12 b.p.m.) and attenuated (≤12 b.p.m.) HRR groups. Our main outcomes of interest included arrhythmia recurrence and all-cause mortality. During a mean follow-up of 33 months, 43% of our study population experienced arrhythmia recurrence, 74% of those with an attenuated HRR, and 30% of those with a normal HRR (P < 0.0001). Death occurred in 9% of patients in the attenuated HRR group compared to 4% in the normal HRR cohort (P = 0.001). On multivariable models adjusting for cardiorespiratory fitness (CRF), medication use, left atrial size, ejection fraction, and renal function, attenuated HRR was predictive of increased arrhythmia recurrence (hazard ratio 2.54, 95% confidence interval 1.86-3.47, P < 0.0001). CONCLUSION: Heart rate recovery provides additional valuable prognostic information beyond CRF. An impaired HRR is associated with significantly higher rates of arrhythmia recurrence and death following AF ablation.

Synthesis and in vitro study of antiproliferative benzyloxy dihydropyrimidinones.

In this study, we report on antiproliferative benzyloxy dihydropyrimidinones (DHPMs) produced by the Biginelli reaction of benzyloxy benzaldehyde, urea, and diverse 1,3-diones. The reaction was catalyzed by lanthanum triflate and completed within 1-1.5 h, with 74-97% yield. The antiproliferative assay was carried out for all synthesized dihydropyrimidinones against six human solid tumor cell lines. Six compounds showed good antiproliferative activity with GI50 values below 5 µM. Among all the synthesized compounds, the most potent derivative showed good antiproliferative activity against all cell lines with GI50 values in the range of 1.1-3.1 µM. These DHPMs comply with druglikeness. Furthermore, ADMET prediction and the effect of P-glycoprotein on the antiproliferative activity were also studied. Overall, our method allows eco-friendly access to benzyloxy DHPMs as potential anticancer drugs.

Impact of risk-factor modification on arrhythmia recurrence among morbidly obese patients undergoing atrial fibrillation ablation.

BACKGROUND: Morbid obesity is associated with prohibitively high arrhythmia recurrence rates following atrial fibrillation (AF) ablation. DESIGN: This was a single-center study comprising 239 patients with morbid obesity and symptomatic paroxysmal or persistent AF undergoing AF ablation compared to 239 patients with a body mass index less than 30 kg/m2 matched based on age, sex, ejection fraction, AF type, presence and type of heart failure, and left atrial volume index. METHODS: Our primary outcome of interest was arrhythmia recurrence. RESULTS: During a mean follow-up of 29 months, arrhythmia recurrence was observed in 65% of the morbidly obese cohort compared to 27% of the control group (P < .0001). Among those with morbid obesity, sleep apnea screening, and treatment (91% vs 40%; P < .0001), blood pressure control (62% vs 53%; P = .001), glycemic control (85% vs 56%; P = .004), and weight loss more than equal to 5% (33% vs 57% in those who lost less than 5% and 83% in those who gained weight, P < .0001) were associated with lower arrhythmia recurrence. Recurrent arrhythmia was observed in one (4%) patient who accomplished all four goals, compared to 36% who achieved 3 of 4, 85% who modified 2 of 4%, and 97% of those who modified zero or one risk-factor. Risk-factor modification (RFM) was also associated with substantial reductions in the need for repeat ablation or direct-current cardioversion and arrhythmia-related hospitalization (P < .0001). CONCLUSION: RFM through pragmatic noninvasive means such as blood pressure and glycemic control, sleep apnea screening and treatment, and weight loss is associated with substantially lower rates of recurrent arrhythmia among morbidly obese patients undergoing AF ablation.

Predictors of long-term outcomes greater than 10 years after cardiac resynchronization therapy implantation.

BACKGROUND: Cardiac resynchronization therapy (CRT) is indicated in patients with medically refractory heart failure and wide QRS duration. While much is known about predictors of left ventricular (LV) remodeling after CRT implantation and short-term mortality, limited data exist on long-term outcomes after CRT placement. METHODS: We retrospectively reviewed all patients undergoing CRT implantation at our center between 2003 and 2008 and examined mortality using institutional electronic records, social security death index, and online obituary search. We included only patients with preimplant echoes with LV ejection fraction (LVEF) 35% or below. Variable selection was performed using stepwise regression and models were compared using goodness-of-fit criteria. A final model was validated with the bootstrap regression method. RESULTS: Out of the 877 CRT patients undergoing implantation during this time, 287 (32.7%) survived longer than 10 years. Significant (P < .05) predictors of survival in our multivariate model were age, left ventricular diastolic diameter, sex, presence of nonischemic vs ischemic cardiomyopathy, QRS duration, atrial fibrillation, BNP levels, and creatinine levels at the time of CRT implantation. A model using the odds ratios from these variables had a receiver operating curve with an area under the curve score of 0.816 (standard error, 0.019) at predicting survival or freedom from LVAD or heart transplant for longer than 10 years after CRT implantation. The specificity for factors 3 or above and 5 or above was 68% and 77%, respectively. CONCLUSION: A large proportion of patients are still alive 10 years after CRT implantation. Variables at the time of CRT implant can help provide prognostic information to patients and electrophysiologists to determine the long-term benefit and survival of patients after CRT implantation.

Baseline Right Ventricular Dysfunction Predicts Worse Outcomes in Patients Undergoing Cardiac Resynchronization Therapy Implantation.

INTRODUCTION: Cardiac resynchronization therapy (CRT) has been shown to improve survival in patients with systolic heart failure, wide QRS duration, and left-bundle-branch-block. However, CRT outcomes stratified by right ventricular (RV) function at implant have not been well studied. METHODS: We retrospectively reviewed patients at Cleveland Clinic who underwent CRT implantation (n = 777) from 2003 to 2011 with a diagnosis of heart failure, echocardiography with both pre-CRT left ventricular ejection fraction (LVEF) ≤35% and available post-CRT echocardiography at 6 months post-implant. CRT response was defined as LVEF improvement ≥5%. Patients were separated into 2 groups: normal or mild RV dysfunction (n = 570) labeled Normal RV; moderate to severe dysfunction (n = 207) labeled RV DYSFXN based on qualitative echocardiography assessment. Survival was calculated as time from CRT implant to death, left ventricular assist device implant, or heart transplant. RESULTS: CRT response was significantly higher in patients with Normal RV (67%) compared with patients with RV DYSFXN (56%; P = .006). Kaplan-Meier analysis showed that CRT patients with Normal RV had significantly greater survival compared with patients with RV DYSFXN (P < .001). In multivariable Cox regression accounting for a priori covariates, RV DYSFXN was associated with worse survival (HR 1.41 [95% CI: 1.14-1.75], P = .002) and lower CRT response (HR 0.66 [95% CI: 0.44-0.97], P = .03). CONCLUSION: Baseline RV dysfunction at CRT implant is an important predictor of worsened left ventricular remodeling and survival in CRT patients.

Atrial fibrillation ablation in patients with transthyretin cardiac amyloidosis.

AIMS: Atrial fibrillation (AF) occurs in as many as 70% of patients with transthyretin cardiac amyloidosis (ATTR CA). The aim of our study was to investigate the impact of AF ablation on freedom from recurrent arrhythmia, hospitalization for AF or heart failure (HF), and mortality. METHODS AND RESULTS: This was a retrospective observational cohort study of 72 patients with ATTR CA and AF, of whom 24 underwent AF ablation and were matched in a 2:1 manner based on age, gender, ATTR CA stage, New York Heart Association functional class, ejection fraction, and date of AF diagnosis with 48 patients with ATTR CA and AF undergoing medical management. During a mean follow-up of 39 ± 26 months, 10 (42%) patients remained free of recurrent arrhythmia following ablation. Ablation was significantly more effective in those with Stage I or II ATTR CA, with 9/14 (64%) patients with Stage I or II ATTR CA remaining free of recurrent arrhythmia compared to only 1/10 (10%) patients with Stage III disease (P = 0.005). Death occurred in 7 (29%) patients in the ablation group compared to 36 (75%) in the non-ablation arm (P = 0.01). Rates of ischaemic stroke were similar in both groups. Ablation was associated with a significant reduction in the frequency of hospitalization for HF/arrhythmia (1.7 ± 2.4 hospitalizations vs. 4 ± 3.5, P = 0.005). On Cox proportional hazards analyses, ablation was associated with improved survival (hazard ratio 0.38, 95% confidence intervals 0.17-0.86; P = 0.02). CONCLUSION: Atrial fibrillation ablation is associated with reduced mortality in ATTR CA and is most effective when performed earlier during the disease process.

The gap between what patients know and desire to learn about their cardiac implantable electronic devices.

BACKGROUND: Advancement of digital technology now allows patients to have access to data from their cardiac implantable electronic devices (CIEDs). However, patients' understanding regarding CIED data and perceived personal usability remain unclear. The present study is a prospective survey to examine patients' understanding of their CIEDs and their perception of what is important. METHODS: We screened 400 patients between July and December 2018 who presented to our outpatient clinic for a CIED interrogation. Patients received a one-page questionnaire asking baseline demographics, their perception about their own knowledge about their device, and multiple-choice questions in seven basic categories: type of CIED, original indication, functionality, manufacturer, number of active leads, estimated battery life, and number of shocks received. We compared these answers to their interrogation reports to assess accuracy. We also asked participants what they would like to be aware of regarding their CIED. RESULTS: From this cohort, 344 of 400 (86%) (62.9 ± 12.8 years and 64 % males) agreed to take the survey and were included in the analysis. At baseline, 63.2% agreed or strongly agreed that they were knowledgeable about their devices. The overwhelming majority of patients demonstrated CIED knowledge deficits in at least one content area (n = 294, 86%), or more than two content areas (n = 176, 51%). Patients agreed or strongly agreed that they had a desire to have information regarding each of the following: battery life (84%), activity level (79%), heart rate trend (75%), and ventricular arrhythmias (74%). CONCLUSION: There is a large discrepancy in patients' level of knowledge regarding their CIEDs and their wish to know more details. Future technologies should satisfy providers' goals to educate their patients with basic information and fulfill patients' desire to obtain more data from their CIEDs.

Long term outcomes in patients with chronic right ventricular pacing upgraded to cardiac resynchronization therapy.

INTRODUCTION: In patients with chronic systolic heart failure and frequent right ventricular pacing (RVP), upgrade to cardiac resynchronization therapy (CRT) has become common practice despite a lack of randomized clinical trials. We aimed to evaluate long term outcomes in patients upgraded to CRT from chronic RVP compared with de novo CRT implants. METHODS AND RESULTS: We reviewed medical charts on consecutive patients with a left ventricular ejection fraction (LVEF) ≤ 35% and a QRSd ≥ 120 ms undergoing CRT. Survival free of left ventricular assist device (LVAD) and a heart transplant was compared amongst patients on the basis of pre-CRT QRS morphology. Improvement in LVEF was also compared across groups. A total of 1260 patients met inclusion criteria of whom 233 were upgraded from chronic RVP. Over a mean follow up 6.5 ± 4.0 years there were 821 endpoints (27 LVAD, 30 heart transplants, and 764 deaths). In a multivariate Cox regression model, upgraded patients had worse outcomes (HR 1.3(1.1-1.7) P = .007) compared with those with native LBBB and similar outcomes to patients with non-LBBB(HR 0.96(0.76-1.21) P = .7). The survival curve for chronic RVP parallels native LBBB for approximately 2.5 years before dropping sharply. Patients with chronic RVP derive similar improvements in LVEF compared with those with LBBB and superior improvements compared with those with non-LBBB. CONCLUSIONS: Despite achieving similar levels of LVEF improvement, patients with systolic heart failure with chronic RVP undergoing upgrade to CRT have inferior long term outcomes compared with patients with native LBBB. Long term outcomes with CRT in patients with chronic RVP, RBBB, and IVCD are similar.

Cardiac devices in patients with transthyretin amyloidosis: Impact on functional class, left ventricular function, mitral regurgitation, and mortality.

BACKGROUND: The aim of our study was to investigate outcomes of patients with ATTR (amyloidosis and transthyretin) CA (cardiac amyloidosis) and implantable devices with respect to left ventricular ejection fraction (LVEF), mitral regurgitation (MR), New York Heart Association (NYHA) functional class, and mortality. METHODS: This was a retrospective observational cohort study of 78 patients with ATTR CA and implantable devices. During a mean follow-up of 42 months we investigated the impact of right ventricular (RV) pacing burden and biventricular (BiV) pacing on LVEF, MR severity, NYHA functional class, and mortality. RESULTS: Worsening MR occurred in 11% of patients with a RV pacing % <40% compared to 62% of those with a RV pacing burden >40% (P = .002). Similarly, worsening LVEF occurred in 26% of patients who were RV paced <40% and 89% of those who were RV paced >40% of the time (P < .0001) and worsening in NYHA functional class occurred in 22% and 89%, respectively (P < .0001). Improvement in LVEF, NYHA functional class, and MR severity occurred in 78%, 67%, and 67%, respectively, in those with BiV devices. Death occurred in 67% of patients in the cardiac resynchronization therapy group compared to 68% of those with a RV pacing burden <40% and 92% of those with a RV pacing burden >40%. CONCLUSION: A higher RV pacing burden is associated with deleterious remodeling and congestive heart failure in patients with ATTR CA, whereas BiV pacing is associated with improvements in LVEF, NYHA class, and degree of MR. BiV pacing should be considered in patients with ATTR CA and an indication for pacing. However, further larger prospective studies will need to be performed.

Management and outcomes in mitral valve prolapse with ventricular arrhythmias undergoing ablation and/or implantation of ICDs.

BACKGROUND: While there is an association between isolated mitral valve prolapse (MVP) and sudden cardiac arrest (SCA), the baseline characteristics and outcomes of patients with isolated MVP who experience ventricular arrhythmias (VAs) and then subsequently undergo catheter ablation and/or implantable cardioverter defibrillator (ICD) implantation are unknown. METHODS: We performed a retrospective review of all patients at the Cleveland Clinic with isolated MVP between 1997 and 2016 who underwent VA catheter ablation or secondary prevention ICD implantation. RESULTS: Of 617 screened patients, we identified 43 patients with isolated MVP and significant VA who underwent ICD placement (n = 13, 30%) or catheter ablation (n = 30, 70%). Both leaflets were most commonly involved (n = 22, 52%) with posterior MVP being next most common (n = 15, 36%). The most common foci of VA origin was the left ventricular papillary muscle (n = 9, 27%). Ablation was successful in the majority of cases (n = 20, 65%). At a mean follow-up of 2.5 years, 11 patients (26%) had recurrent VT. CONCLUSIONS: Patients with isolated MVP and VA were more likely to have bileaflet prolapse and at least moderate mitral regurgitation. VA originated more commonly from left-sided foci. While ablation was acutely successful in the majority of cases, there was still a moderate rate of VA recurrence. There is still more study needed on factors that will predict malignant VAs and management of these VAs in the MVP population.

Hydroxyl alkyl ammonium ionic liquid assisted green and one-pot regioselective access to functionalized pyrazolodihydropyridine core and their pharmacological evaluation.

Herein our team explored a promising synthetic trail to Functionalized pyrazolodihydropyridine core using hydroxyl alkyl ammonium ionic liquid via one-pot fusion of 3-methyl-1-phenyl-1H-pyrazole-5-amine, different heterocyclic aldehydes and 1, 3-Cyclic diones. The aimed compounds were obtained by Domino-Knoevenagel condensation and Michael addition followed by cyclization. The reaction transformation involves the formation of two CC and one CN bond formation. The perspective of the present work is selectively approached to Functionalized pyrazolodihydropyridine core excluding other potential parallel reactions under environmentally benign reaction condition. The present protocol show features such as the low E-factor, ambiphilic behavior of ionic liquid during reaction transformation, scale-up to a multigram scale, reusability of the ionic liquid, mild reaction condition, and produce water as a byproduct. All newly derived compounds were evaluated for their in vitro biological activities. In preliminary biological studies compound, 4c showed better potency than the standard drug ampicillin against Gram-negative bacteria (E. coli); the compound 4i exhibited outstanding activity against S. aeruginosa which is far better than ampicillin, chloramphenicol, and ciprofloxacin. The compound 4m was found more potent against C. albicans, than that of griseofulvin and show equipotency to nystatin whereas, in preliminary antitubercular screening, compound 4o was exhibited more potency than rifampicin. Noteworthy compounds 4f and 4i were found most active in antiproliferative screening.

The relationship between baseline and follow-up left ventricular ejection fraction with adverse events among primary prevention ICD patients.

BACKGROUND: Left ventricular ejection fraction (LVEF) is used to select patients for primary prevention implantable cardioverter defibrillators (ICDs). The relationship between baseline and long-term follow-up LVEF and clinical outcomes among primary prevention ICD patients remains unclear. METHODS: We studied 195 patients with a baseline LVEF ≤35% ≤6 months prior to ICD implantation and follow-up LVEF 1-3 years after ICD implantation without intervening left ventricular assist device (LVAD) or transplant. The co-primary study endpoints were: (1) a composite of time to death, LVAD, or transplant and (2) appropriate ICD therapy. We examined multivariable Cox proportional hazard models with a 3-year post-implant landmark view; the LVEF closest to the 3-year mark was considered the follow-up LVEF for analyses. Follow-up LVEF was examined using 2 definitions: (1) ≥10% improvement compared to baseline or (2) actual value of ≥40%. RESULTS: Fifty patients (26%) had a LVEF improvement of ≥10% and 44 (23%) had a follow-up LVEF ≥40%. Neither baseline nor follow-up LVEF was significantly associated with the composite endpoint. In contrast, both baseline and follow-up LVEF were associated with risk for long-term ICD therapies, whether follow-up LVEF was modeled as a ≥10% absolute improvement (baseline LVEF HR 0.87, CI 0.91-0.93, P < .001; follow-up LVEF HR 0.18, CI 0.06-0.53, P = .002) or a ≥40% follow-up value (baseline LVEF HR 0.89, CI 0.83-0.96, P = .001, follow-up LVEF HR 0.26, CI 0.08-0.87, P = .03). CONCLUSIONS: Among primary prevention ICD recipients, both baseline and follow-up LVEF were independently associated with long-term risk for appropriate ICD therapy, but they were not associated with time to the composite of LVAD, transplant, or death.

Increased Nonalternans Repolarization Variability Precedes Ventricular Tachycardia Onset in Patients with Implantable Defibrillators.

BACKROUND: T-wave alternans (TWA) is associated with ventricular tachycardia (VT). Nonalternans repolarization variability (NARV) precedes VT in certain experimental models, but its link to clinical arrhythmia is unproven. This study was conducted to determine if NARV increases prior to VT in patients with implantable cardioverter defibrillators (ICDs). METHODS: TWA and NARV were calculated from shock-channel electrograms preceding onset of VT or non-VT events in patients with an ICD. In each patient, presence of both a VT and a non-VT event with the same QRS morphology before the event was required. Mixed linear model was used for data analysis, using heart rate (HR) and the number of analyzed beats as covariates. RESULTS: Five hundred and sixty-eight events from 64 patients (males/females 51/13, 67 ± 13 years) were analyzed. HR preceding non-VT events was higher than before VT events (RR interval 595 ± 159 vs 706 ± 111 ms; P < 0.0001). Both TWA and NARV increased with increasing HR (P < 0.001). TWA decreased with increasing number of analyzed beats. When controlled for number of analyzed beats and HR, both TWA and NARV were higher before VT than before non-VT events (P < 0.002 and P < 0.0005, respectively). CONCLUSIONS: NARV is elevated prior to spontaneous VT onset. Both NARV and TWA increase with HR. The decrease of TWA with increasing number of analyzed beats may indicate contamination with NARV or noise when only a small number of beats is available for analysis. NARV might be useful for VT prediction in the future.

Relaxin suppresses atrial fibrillation by reversing fibrosis and myocyte hypertrophy and increasing conduction velocity and sodium current in spontaneously hypertensive rat hearts.

RATIONALE: Atrial fibrillation (AF) contributes significantly to morbidity and mortality in elderly and hypertensive patients and has been correlated to enhanced atrial fibrosis. Despite a lack of direct evidence that fibrosis causes AF, reversal of fibrosis is considered a plausible therapy. OBJECTIVE: To evaluate the efficacy of the antifibrotic hormone relaxin (RLX) in suppressing AF in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: Normotensive Wistar-Kyoto (WKY) and SHR were treated for 2 weeks with vehicle (WKY+V and SHR+V) or RLX (0.4 mg/kg per day, SHR+RLX) using implantable mini-pumps. Hearts were perfused, mapped optically to analyze action potential durations, intracellular Ca²âº transients, and restitution kinetics, and tested for AF vulnerability. SHR hearts had slower conduction velocity (CV; P<0.01 versus WKY), steeper CV restitution kinetics, greater collagen deposition, higher levels of transcripts for transforming growth factor-ß, metalloproteinase-2, metalloproteinase-9, collagen I/III, and reduced connexin 43 phosphorylation (P<0.05 versus WKY). Programmed stimulation triggered sustained AF in SHR (n=5/5) and SHR+V (n=4/4), but not in WKY (n=0/5) and SHR+RLX (n=1/8; P<0.01). RLX treatment reversed the transcripts for fibrosis, flattened CV restitution kinetics, reduced action potential duration at 90% recovery to baseline, increased CV (P<0.01), and reversed atrial hypertrophy (P<0.05). Independent of antifibrotic actions, RLX (0.1 µmol/L) increased Na⁺ current density, INa (≈2-fold in 48 hours) in human cardiomyocytes derived from inducible pluripotent stem cells (n=18/18; P<0.01). CONCLUSIONS: RLX treatment suppressed AF in SHR hearts by increasing CV from a combination of reversal of fibrosis and hypertrophy and by increasing INa. The study provides compelling evidence that RLX may provide a novel therapy to manage AF in humans by reversing fibrosis and hypertrophy and by modulating cardiac ionic currents.

Risk of Stroke and Death in Atrial Fibrillation by Type of Anticoagulation: A Propensity-Matched Analysis.

BACKGROUND: We examined the effect of novel oral anticoagulants (NOACs) compared to warfarin on the risk of death or stroke in atrial fibrillation (AF) patients in every day clinical practice. METHODS: We examined a cohort of 2,836 AF patients, of whom 2,253 were prescribed warfarin and 583 were prescribed an NOAC. Patients with glomerular filtration rate < 30 mg/mL or history of significant valvular heart disease were excluded. Patients were followed to primary end points of death or stroke. Propensity matching was used to adjust for differences in baseline characteristics between the groups. RESULTS: Compared to patients in the NOAC group, patients on warfarin had more comorbidities and higher CHADS2 and CHA2 DS2 -VASc scores (1.7 vs 1.3 for CHADS2 , 2.8 vs 2.2 for CHA2 DS2 -VASc, P < 0.0001 for both). After adjusting for differences in baseline characteristics, NOAC use was associated with significant reduction in all-cause mortality compared to warfarin (hazard ratio [HR] = 0.47, 95% confidence interval [CI; 0.3-0.8], P = 0.006) but not stroke, over a median follow-up of 42.5 months. The difference in mortality persisted after propensity score matching (HR = 0.51, 95% CI [0.28-0.93], P = 0.03). CONCLUSIONS: Compared to warfarin, NOAC use is associated with decreased all-cause mortality but not stroke risk. These data from real-life clinical practice add to existing evidence for decreased mortality among patients prescribed NOACs compared to warfarin.

QT interval prolongation in end-stage liver disease cannot be explained by nonhepatic factors.

INTRODUCTION: QT interval prolongation in patients with end-stage liver disease (ESLD) is common. However, electrolyte abnormalities, renal insufficiency, treatment with QT-prolonging drugs, and other factors known to prolong QT interval independently of liver disease occur frequently in ESLD. Moreover, elevated heart rate may be present in ESLD and result in spurious QTc prolongation if the Bazett formula is used for rate correction. It thus remains unclear whether QT prolongation in ESLD is directly caused by liver failure, or indirectly by these confounding factors. METHODS: Medical records of all patients (n = 437) who received orthotopic liver transplantation (OLTx) at our institution between 2008 and 2011 were reviewed. Data from 51 patients with available pre-OLTx dobutamine stress echo (DSE), post-OLTx ECG and without nonhepatic factors affecting QT interval duration were analyzed. For each patient, QT versus RR regression line was calculated from ECG tracings obtained during DSE. The QT interval on post-OLTx ECG was compared with the pre-OLTx QT predicted by the regression line for the same RR interval. RESULTS: QT interval shortened significantly post-OLTx (from 394 ± 47 to 364 ± 45 ms at RR interval 750 ± 144 ms; P < 0.002) when compared using the regression method. Corrected QT intervals calculated by Bazett and Fridericia formulas also shortened. Patients with prolonged QT pre-OLTx had significantly higher INR and lower serum albumin. CONCLUSION: ESLD impairs ventricular repolarization even in the absence of other known factors affecting repolarization. QT prolongation in ESLD is associated with impaired synthetic liver function.

Recent trends for chemoselectivity modulation in one-pot organic transformations.

In organic reactions, chemoselectivity refers to the selective reactivity of one functional group in the presence of another. This can be more successful if the reagent and reaction parameters are appropriately chosen. One-pot reactions have been shown to be an effective structural variety technique for the development of novel heterocyclic or carbocyclic compounds. This review article focuses on recent efforts by researchers from around the world to synthesise novel organic molecules utilising these methodologies (2013-2024), as well as their mechanism insights. The substrate, catalyst, solvent, and temperature conditions all have a significant impact on chemoselectivity in the organic reactions described here. The manipulation of chemoselectivity in organic processes creates new potential for the production of novel heterocycles and carbocycles.

Failure-free survival of the Durata defibrillator lead.

AIMS: Given design similarities and a common manufacturer, there have been suspicions regarding the Durata™ defibrillator (ICD) lead, in the aftermath of the Riata™ class I recall. We therefore examined the failure-free survival rates of the Durata™ compared with the Riata™ and Sprint Quattro™ ICD leads. METHODS AND RESULTS: All patients (n = 2475) implanted with a Durata (n = 828), Riata [n = 627; 8 Fr. (n = 472) and 7 Fr. (n = 155)], or Sprint Quattro (n = 1020) leads at our institution were included and Kaplan-Meier failure-free survival curves were constructed for all leads. Lead failure was defined as electrical malfunction resulting in lead replacement, excluding dislodgements or perforations. Annual electrical failure rates were 0.3%, 1.7, and 0.3% for the Durata, Riata, and Sprint Quattro leads, respectively (P < 0.0001 for the comparison of Durata to Riata and P = 0.1.0 for the comparison of Durata to Sprint Quattro). The failure-free survival of the Durata lead was significantly better than that of the Riata lead (P < 0.0001) and similar to that of the Sprint Quattro (P = 0.94). The 7 Fr. Riata ST lead had better survival compared with the 8 Fr. Riata lead (P = 0.050) and comparable survival with the Durata lead (P = 0.12). CONCLUSION: The Durata lead failure-free survival is significantly better than the 8 Fr. Riata, albeit at a shorter follow-up time. Riata and comparable with that of the 7 Fr. Riata ST and the Sprint Quattro ICD leads. These data provide an insight into the mechanism of electrical failure of Riata leads and have implications for patient management.