Prospective Evaluation of the Correlation Between Gated Cardiac Computed Tomography Detected Vascular Fibrosis and Ease of Transvenous Lead Extraction.

BACKGROUND: Difficulty of lead extraction does not track well with procedural complications, but several small retrospective studies have lead fibrosis on computed tomography as an important indicator of difficult lead extraction. The purpose of the present study was to apply a standardized gated cardiac computed tomography (CT) protocol to assess fibrosis and study it prospectively to examine the need for powered sheaths and risk outcomes. METHODS: We performed a prospective, blinded, multicenter, international study at high-volume lead extraction centers and included patients referred for transvenous lead extraction with at least one lead with a dwell time >1 year and ability to receive a cardiac CT. The degree of fibrosis (as measured by amount of lead adherence to vessel wall) was graded on a scale of 1 to 4 by dedicated CT readers in 3 zones (vein entry to superior vena cava, superior vena cava, and right atrium to lead tip). The primary outcome of the study was number of extractions requiring powered sheaths at zone 2 for each fibrosis group. RESULTS: A total of 200 patients were enrolled in the trial with 196 completing full gated CT and lead extraction analysis. The primary endpoint of powered sheath (laser and mechanical) sheath use was significantly higher in patients with higher fibrosis seen on CT (scores 3+4; 67.8%) at the zone 2 compared to patients with lower fibrosis (scores 1+2; 38.6%; P<0.001). There were 5 major complications with 3 vascular lacerations all occurring in zone 2 in the study. CONCLUSIONS: Gated, contrasted CT can predict the need for powered sheaths by identification of fibrosis but did not identify an absolute low-risk cohort who would not need powered sheaths. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03772704.

Quality of life after the initial treatment of atrial fibrillation with cryoablation versus drug therapy.

BACKGROUND: The STOP AF First trial recently demonstrated that initial treatment with cryoballoon ablation (CBA) is safe and superior to antiarrhythmic drug (AAD) therapy for preventing atrial arrhythmia recurrence in patients with symptomatic atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to evaluate the change in quality of life (QoL) and symptoms after first-line CBA vs AAD therapy. METHODS: Patients with symptomatic AF not previously receiving rhythm control therapy were randomized to AAD (class I or III) or CBA (Arctic Front Advance, Medtronic, Mounds View, MN). QoL was evaluated at baseline and at 6 and 12 months by using the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and the European Quality of Life-5 Dimensions questionnaires. A review of AF-associated symptoms was conducted at baseline and at 1, 3, 6, and 12 months. RESULTS: In total, 203 subjects received either CBA (n = 104 [51.2%]) or AAD therapy (n = 99 [48.8%]). Improvements in the AFEQT summary and subscale scores were significantly larger with CBA than with AAD therapy at 6 and 12 months (P < .02 for all). Clinically meaningful improvement (>5 points) in the AFEQT summary score from baseline to 12 months was observed in 96.0% (100) of patients in the CBA arm vs 72.2% (71) of patients in the AAD arm (P < .001). No significant between-group differences were observed in the change in the European Quality of Life-5 Dimensions index or visual analog scale scores. Overall, 54.4% (57) of the CBA group vs 29.7% (29) of the AAD group reported no AF-specific symptom recurrence after a 90-day blanking period (P = .0005). CONCLUSION: First-line CBA vs AAD therapy is associated with larger improvements in AF-specific QoL and a higher rate of symptom resolution.

Simultaneous determination of 9 environmental pollutants including bisphenol A in vegetable oil by solid phase extraction-liquid chromatography-tandem mass spectrometry.

In this study, a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method with solid phase extraction was established for the simultaneous determination of bisphenol A, bisphenol F, bisphenol S, 4-nonylphenol, n-nonylphenol, octylphenol, n-octylphenol, perfluorooctane sulfonate acid and perfluorooctanoic acid in vegetable oil. The sample was extracted with ammonia acetonitrile solution (1 : 9, V/V) by ultrasonication. And the obtained extract was purified by using a PRIME HLB solid phase extraction column. The identification and quantification of the compounds was performed by liquid chromatography-tandem mass spectrometry in multiple reaction monitoring (MRM) mode. The internal standard method was used for quantitative analysis. Under optimal experimental conditions, the limits of quantitation of bisphenol A, bisphenol F, bisphenol S, 4-nonylphenol, n-nonylphenol, octylphenol and n-octylphenol in vegetable oil were 1.0 µg kg-1. The limits of quantitation of perfluorooctane sulfonic acid and perfluorooctanoic acid in vegetable oil were 0.1 µg kg-1. The average spiked recoveries of the method were in the range of 89.2-117.1% with the relative standard deviations (RSD) of 2.9-9.8% (n = 6). This method is sensitive, versatile and reproducible, and is suitable for the simultaneous determination of bisphenol A, bisphenol F, bisphenol S, 4-nonylphenol, n-nonylphenol, octylphenol, n-octylphenol, perfluorooctane sulfonate acid and perfluorooctanoic acid in vegetable oil.

Validating and implementing cardiac telemetry for continuous QTc monitoring: A novel approach to increase healthcare personnel safety during the COVID-19 pandemic.

BACKGROUND: Minimizing direct patient contact among healthcare personnel is crucial for mitigating infectious risk during the coronavirus disease 2019 (COVID-19) pandemic. The use of remote cardiac telemetry as an alternative to 12­lead electrocardiography (ECG) for continuous QTc monitoring may facilitate this strategy, but its application has not yet been validated or implemented. METHODS: In the validation component of this two-part prospective cohort study, a total of 65 hospitalized patients with simultaneous ECG and telemetry were identified. QTc obtained via remote telemetry as measured by 3 independent, blinded operators were compared with ECG as assessed by 2 board-certified electrophysiologists as the gold-standard. Pearson correlation coefficients were calculated to measure the strength of linear correlation between the two methods. In a separate cohort comprised of 68 COVID-19 patients treated with combined hydroxychloroquine and azithromycin, telemetry-based QTc values were compared at serial time points after medication administration using Friedman rank-sum test of repeated measures. RESULTS: Telemetry-based QTc measurements highly correlated with QTc values derived from ECG, with correlation coefficients of 0.74, 0.79, 0.85 (individual operators), and 0.84 (mean of all operators). Among the COVID-19 cohort, treatment led to a median QTc increase of 15 milliseconds between baseline and following the 9th dose (p = 0.002), with 8 (12%) patients exhibiting an increase in QTc ≥ 60 milliseconds and 4 (6%) developing QTc ≥ 500 milliseconds. CONCLUSIONS: Cardiac telemetry is a validated clinical tool for QTc monitoring that may serve an expanding role during the COVID-19 pandemic strengthened by its remote and continuous monitoring capability and ubiquitous presence throughout hospitals.

Impact of an electronic medical record-based appointment order on outpatient cardiology follow-up after hospital discharge.

Outpatient follow-up after hospital discharge improves continuity of care and reduces readmissions, but rates of follow-up remain low. It is not known whether electronic medical record (EMR)-based tools improve follow-up. The aim of this study was to determine if an EMR-based order to secure cardiology follow-up appointments at hospital discharge would improve follow-up rates and hospital readmission rates. A pre-post interventional study was conducted and evaluated 39,209 cardiovascular medicine discharges within an academic center between 2012 and 2017. Follow-up rates and readmission rates were compared during 2 years prior to EMR-order implementation (pre-order era 2012-2013, n = 12,852) and 4 years after implementation (EMR-order era 2014-2017, n = 26,357). The primary endpoint was 90-day cardiovascular follow-up rates within our health system. In the overall cohort, the mean age of patients was 69.3 years [SD 14.7] and 60.7% (n = 23,827) were male. In the pre-order era, 90-day follow-up was 56.7 ± 0.4% (7286 of 12,852) and increased to 67.9 ± 0.3% (17,888 of 26,357, P < 0.001) in the EMR-order era. The use of the EMR follow-up order was independently associated with increased outpatient follow-up within 90 days after adjusting for patient demographics and payor status (OR 3.28, 95% CI 3.10-3.47, P < 0.001). The 30-day readmission rate in the pre-order era was 12.8% (1642 of 12,852) compared with 13.7% (3601 of 26,357, P = 0.016) in the EMR-order era. An EMR-based appointment order for follow-up appointment scheduling was associated with increased cardiovascular medicine follow-up, but was not associated with an observed reduction in 30-day readmission rates.

Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation.

BACKGROUND: In patients with symptomatic paroxysmal atrial fibrillation that has not responded to medication, catheter ablation is more effective than antiarrhythmic drug therapy for maintaining sinus rhythm. However, the safety and efficacy of cryoballoon ablation as initial first-line therapy have not been established. METHODS: We performed a multicenter trial in which patients 18 to 80 years of age who had paroxysmal atrial fibrillation for which they had not previously received rhythm-control therapy were randomly assigned (1:1) to receive treatment with antiarrhythmic drugs (class I or III agents) or pulmonary vein isolation with a cryoballoon. Arrhythmia monitoring included 12-lead electrocardiography conducted at baseline and at 1, 3, 6, and 12 months; patient-activated telephone monitoring conducted weekly and when symptoms were present during months 3 through 12; and 24-hour ambulatory monitoring conducted at 6 and 12 months. The primary efficacy end point was treatment success (defined as freedom from initial failure of the procedure or atrial arrhythmia recurrence after a 90-day blanking period to allow recovery from the procedure or drug dose adjustment, evaluated in a Kaplan-Meier analysis). The primary safety end point was assessed in the ablation group only and was a composite of several procedure-related and cryoballoon system-related serious adverse events. RESULTS: Of the 203 participants who underwent randomization and received treatment, 104 underwent ablation, and 99 initially received drug therapy. In the ablation group, initial success of the procedure was achieved in 97% of patients. The Kaplan-Meier estimate of the percentage of patients with treatment success at 12 months was 74.6% (95% confidence interval [CI], 65.0 to 82.0) in the ablation group and 45.0% (95% CI, 34.6 to 54.7) in the drug-therapy group (P<0.001 by log-rank test). Two primary safety end-point events occurred in the ablation group (Kaplan-Meier estimate of the percentage of patients with an event within 12 months, 1.9%; 95% CI, 0.5 to 7.5). CONCLUSIONS: Cryoballoon ablation as initial therapy was superior to drug therapy for the prevention of atrial arrhythmia recurrence in patients with paroxysmal atrial fibrillation. Serious procedure-related adverse events were uncommon. (Supported by Medtronic; STOP AF First ClinicalTrials.gov number, NCT03118518.).

Hydrogen Diffusion Guided Design of Pt-Based Alloys for Inhibition of Butadiene Over-Hydrogenation.

Alloying Pt with other metals is an effective strategy to tune its performance towards selective hydrogenation reactions. Herein, we have demonstrated a process to screen Pt-based alloys for inhibition of butadiene over-hydrogenation with a model comprising isolated single atoms (ISA) embedded into Pt(111). DFT calculations reveal that the diffusion energy barrier of H co-adsorbed with 1-butene is a key parameter for the screening. The output from the ISA model was validated by testing several typical Pt-based alloys towards butadiene hydrogenation. Furthermore, an unexpected higher selectivity to cis-2-butene compared to the trans isomer and 1-butene over the PtZn alloy was explored employing the ISA model.

Association of Initial and Serial C-Reactive Protein Levels With Adverse Cardiovascular Events and Death After Acute Coronary Syndrome: A Secondary Analysis of the VISTA-16 Trial.

Importance: Higher baseline high-sensitivity C-reactive protein (hsCRP) levels after an acute coronary syndrome (ACS) are associated with adverse cardiovascular outcomes. The usefulness of serial hsCRP measurements for risk stratifying patients after ACS is not well characterized. Objective: To assess whether longitudinal increases in hsCRP measurements during the 16 weeks after ACS are independently associated with a greater risk of a major adverse cardiac event (MACE), all-cause death, and cardiovascular death. Design, Setting, and Participants: Secondary analysis of the double-blind, multicenter, randomized clinical Vascular Inflammation Suppression to Treat Acute Coronary Syndromes for 16 Weeks (VISTA-16) trial conducted between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012), which included 5145 patients from 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America assigned to receive varespladib or placebo on a background of atorvastatin treatment beginning within 96 hours of presentation with an ACS. The present study evaluated data from patients with available baseline and longitudinal hsCRP levels measured at weeks 1, 2, 4, 8, and 16 after randomization to treatment or placebo. Statistical analysis was performed from June 15, 2018, through September 15, 2018. Main Outcomes and Measures: Outcomes were MACE (composite of cardiovascular death, myocardial infarction, nonfatal stroke, or unstable angina with documented ischemia requiring hospitalization), cardiovascular death, and all-cause death after adjustment for baseline clinical, treatment, and laboratory characteristics, including baseline hsCRP levels. Results: Among 4257 patients in this study, 3141 (73.8%) were men and the mean age was 60.3 years (interquartile range [IQR], 53.5-67.8 years). The median 16-week low-density lipoprotein cholesterol level was 64.9 mg/dL (IQR, 50.3-82.3 mg/dL), and the median hsCRP level was 2.4 mg/L (IQR, 1.1-5.2 mg/L). On multivariable analysis, higher baseline hsCRP level (hazard ratio [HR], 1.36 [95% CI, 1.13-1.63]; P = .001) and higher longitudinal hsCRP level (HR, 1.15 [95% CI, 1.09-1.21]; P < .001) were independently associated with MACE. Similar significant and independent associations were shown between baseline and longitudinal hsCRP levels and cardiovascular death (baseline: HR, 1.61 per SD [95% CI, 1.07-2.41], P = .02; longitudinal: HR, 1.26 per SD [95% CI, 1.19-1.34], P < .001) and between baseline and longitudinal hsCRP levels and all-cause death (baseline: HR, 1.58 per SD [95% CI, 1.07-2.35], P = .02; longitudinal: HR, 1.25 per SD [95% CI, 1.18-1.32], P < .001). Conclusions and Relevance: Initial and subsequent increases in hsCRP levels during 16 weeks after ACS were associated with a greater risk of the combined MACE end point, cardiovascular death, and all-cause death despite established background therapies. Serial measurements of hsCRP during clinical follow-up after ACS may help to identify patients at higher risk for mortality and morbidity.

ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression: The ELEKT-D study protocol.

Major depressive disorder (MDD) is the most common mental illness and the leading cause of disability worldwide. Electroconvulsive therapy (ECT) is the most effective treatment for MDD and the gold-standard therapy for treatment-resistant depression (TRD), yet it remains underutilized due to factors such as limited availability, stigma, and concerns about cognitive side effects. Ketamine has emerged as the first rapid-acting antidepressant and shows robust short-term efficacy in clinical trials, but there are concerns about its long-term safety and efficacy. While response rates are similar between ECT and ketamine in clinical trials, these treatments have never been compared head-to-head in a sufficiently large, well-powered randomized study. Here we describe the study protocol for ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression (ELEKT-D), a non-inferiority, comparative effectiveness trial. Patients with TRD seeking clinical treatment are randomized (1:1) to receive ECT (thrice weekly) or intravenous ketamine (twice weekly) for 3-5 weeks. The primary outcome is the proportion of responders in each group at the end of study visit, as measured by a patient-reported outcome measure (Quick Inventory of Depressive Symptomatology-Self Report). The study is powered such that the non-inferiority margin allows for ketamine to retain 90% of the ECT treatment effect, with a projected sample size of 400 patients (200 per group). Secondary outcomes include remission rates, depression severity, cognitive functioning, quality of life, adverse events, and tolerability. The results of the ELEKT-D study will have important implications for patient choice, clinical practice, and health insurance policies.

[Simultaneous determination of perfluoric acid, perfluorooctane sulfonic acid, bisphenol A, nonylphenol in infant milk powder by high-performance liquid chromatography-tandem mass spectrometry].

A rapid confirmative method was developed for determining the residues of perfluoric acid (PFOA), perfluorooctane sulfonic acid (PFOS), bisphenol A (BPA), and nonylphenol (NP) in infant milk powder by HPLC-MS/MS. The sample was dissolved in water by ultrasonication, and the protein was removed by dissolving in acetonitrile. The analytes were separated on a Hypersil GOLD C18 column (150 mm×2.0 mm, 5 µm) using 30 mmol/L ammonium acetate solution and methanol as mobile phases, with gradient elution at a flow rate of 0.3 mL/min. Finally, the samples were determined by HPLC-MS/MS. Internal matrix-matched calibration was used for quantification. The limits of quantification (LOQs, S/N=10) of PFOA, PFOS, BPA, and NP were 0.5, 1.0, 10.0, and 5.0 µg/kg, respectively. The recoveries ranged from 86.1% to 106.8%, and the relative standard deviations (RSDs) were in the range from 2.87% to 9.53%. The method was also applied to real samples. The results showed that the method was simple and accurate, and can be used for determining the residues of PFOA, PFOS, BPA, and NP in infant milk powder.

Effect of Aspirin Coadministration on the Safety of Celecoxib, Naproxen, or Ibuprofen.

BACKGROUND: The safety of nonsteroidal anti-inflammatory drug (NSAID) and aspirin coadministration is uncertain. OBJECTIVES: The aim of this study was to compare the safety of combining NSAIDs with low-dose aspirin. METHODS: This analysis of the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen) trial included 23,953 patients with osteoarthritis or rheumatoid arthritis at increased cardiovascular risk randomized to celecoxib, ibuprofen, or naproxen. The on-treatment population was used for this study. Outcomes included composite major adverse cardiovascular events, noncardiovascular death, gastrointestinal or renal events, and components of the composite. Cox proportional hazards models compared outcomes among NSAIDs stratified by aspirin use following propensity score adjustment. Kaplan-Meier analysis was used to compare the cumulative probability of events. RESULTS: When taken without aspirin, naproxen or ibuprofen had greater risk for the primary composite endpoint compared with celecoxib (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.22 to 1.90, p <0.001; and HR: 1.81; 95% CI: 1.46 to 2.26; p <0.001, respectively). Compared with celecoxib, ibuprofen had more major adverse cardiovascular events (p < 0.05), and both ibuprofen and naproxen had more gastrointestinal (p < 0.001) and renal (p < 0.05) events. Taken with aspirin, ibuprofen had greater risk for the primary composite endpoint compared with celecoxib (HR: 1.27; 95% CI: 1.06 to 1.51; p < 0.01); this was not significantly higher with naproxen (HR: 1.18; 95% CI: 0.98 to 1.41; p = 0.08). Among patients on aspirin, major adverse cardiovascular events were similar among NSAIDs, and compared with celecoxib, ibuprofen had more gastrointestinal and renal events (p < 0.05), while naproxen had more gastrointestinal events (p < 0.05), without a difference in renal events. Similar results were seen on adjusted Kaplan-Meier analysis. CONCLUSIONS: Celecoxib has a more favorable overall safety profile than naproxen or ibuprofen when taken without aspirin. Adding aspirin attenuates the safety advantage of celecoxib, although celecoxib is still associated with fewer gastrointestinal events than ibuprofen or naproxen and fewer renal events than ibuprofen. (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen [PRECISION]; NCT00346216).

Warfarin Use Is Associated With Progressive Coronary Arterial Calcification: Insights From Serial Intravascular Ultrasound.

OBJECTIVES: This study compared serial changes in coronary percent atheroma volume (PAV) and calcium index (CaI) in patients with coronary artery disease who were treated with and without warfarin. BACKGROUND: Warfarin blocks the synthesis and activity of matrix Gla protein, a vitamin K-dependent inhibitor of arterial calcification. The longitudinal impact of warfarin on serial coronary artery calcification in vivo in humans is unknown. METHODS: In a post hoc patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound examinations, this study compared changes in PAV and CaI in matched arterial segments in patients with coronary artery disease who were treated with (n = 171) and without (n = 4,129) warfarin during an 18- to 24-month period. RESULTS: Patients (mean age 57.9 ± 9.2 years; male 73%; prior and concomitant 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statin) use, 73% and 97%, respectively) demonstrated overall increases in PAV of 0.41 ± 0.07% (p = 0.001 compared with baseline) and in CaI (median) of 0.04 (interquartile range [IQR]: 0.00 to 0.11; p < 0.001 compared with baseline). Following propensity-weighted adjustment for clinical trial and a range of clinical, ultrasonic, and laboratory parameters, there was no significant difference in the annualized change in PAV in the presence and absence of warfarin treatment (0.33 ± 0.05% vs. 0.25 ± 0.05%; p = 0.17). A significantly greater annualized increase in CaI was observed in warfarin-treated compared with non-warfarin-treated patients (median 0.03; IQR: 0.0 to 0.08 vs. median 0.02; IQR: 0.0 to 0.06; p < 0.001). In a sensitivity analysis evaluating a 1:1 matched cohort (n = 164 per group), significantly greater annualized changes in CaI were also observed in warfarin-treated compared with non-warfarin-treated patients. In a multivariate model, warfarin was independently associated with an increasing CaI (odds ratio: 1.16; 95% confidence interval: 1.05 to 1.28; p = 0.003). CONCLUSIONS: Warfarin therapy is associated with progressive coronary atheroma calcification independent of changes in atheroma volume. The impact of these changes on plaque stability and cardiovascular outcomes requires further investigation.

Unrecognized venous injuries after cardiac implantable electronic device transvenous lead extraction.

BACKGROUND: The major complication rate of transvenous lead extraction (TLE) is estimated to be 1%-2%. Laceration of the central veins can be fatal. OBJECTIVES: To define the incidence and extent of venous injuries on a microscopic level after TLE and compare these data with those of clinically documented events of venous laceration. METHODS: We studied all patients who underwent TLE at our tertiary center within 30 months via a variety of techniques. Extracted leads and tissue around them were fixed in formalin. Pathologic examination was standardized to examine the leads identifying the areas covered by tissue cuffs along the length of the lead. The cuffs were removed and sectioned transversely to their longitudinal axis. Microscopic examination was performed using hematoxylin and eosin stains and Movat stains to identify the presence of vein tissue. RESULTS: In all, 861 leads (585 pacemaker and 272 defibrillator leads) were extracted from 461 patients (median age 63 years, standard deviation 15 years), with an average of 1.9 leads per patient and a median lead age of 2546 days. On microscopic review, 80 leads (9.3%) in 72 of 461 patients (15.6%) showed segments of vein, most of which were transmural (venous tissue including adventitia). Despite this finding, only 5 catastrophic complications (1.1%) occurred that required emergent surgical intervention. Risk factors for venous injury included implantable cardioverter defibrillator lead, age of lead, and the use of laser sheath. CONCLUSIONS: Microscopic venous injuries during lead extraction are common but often not recognized clinically.

Lipoprotein(a) and coronary atheroma progression rates during long-term high-intensity statin therapy: Insights from SATURN.

BACKGROUND & AIMS: Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL)-like particle that associates with major adverse cardiovascular events (MACE). We examined relationships between Lp(a) measurements and changes in coronary atheroma volume following long-term maximally-intensive statin therapy in coronary artery disease patients. METHODS: Study of coronary atheroma by intravascular ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) used serial intravascular ultrasound measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. Baseline and follow-up Lp(a) levels were measured in 915 of the 1039 SATURN participants, and were correlated with changes in percent atheroma volume (ΔPAV). RESULTS: Mean age was 57.7 ± 8.6 years, 74% were men, 96% were Caucasian, with statin use prior to study enrolment occurring in 59.3% of participants. Baseline [median (IQR)] LDL-cholesterol (LDL-C) and measured Lp(a) levels (mg/dL) were 114 (99, 137) and 17.4 (7.6, 52.9) respectively; follow-up measures were 60 (47, 77), and 16.5 (6.7, 57.7) (change from baseline: p < 0.001, p = 0.31 respectively). At baseline, there were 676 patients with Lp(a) levels <50 mg/dL [median Lp(a) of 10.9 mg/dL], and 239 patients with Lp(a) levels ≥ 50 mg/dL [median Lp(a) of 83.2 mg/dL]. Quartiles of baseline and follow-up Lp(a) did not associate with ΔPAV. Irrespective of the achieved LDL-C ( 50 mg/dL. CONCLUSIONS: In coronary artery disease patients prescribed long-term maximally intensive statin therapy with low on-treatment LDL-C levels, measured Lp(a) levels (predominantly below the 50 mg/dL threshold) do not associate with coronary atheroma progression. Alternative biomarkers may thus associate with residual cardiovascular risk in such patients.

Atrial fibrillation, progression of coronary atherosclerosis and myocardial infarction.

Background Despite atrial fibrillation representing an established risk factor for stroke, the association between atrial fibrillation and both progression of coronary atherosclerosis and major adverse cardiovascular events is not well characterized. We assessed the serial measures of coronary atheroma burden and cardiovascular outcomes in patients with and without atrial fibrillation. Methods Data were analyzed from nine clinical trials involving 4966 patients with coronary artery disease undergoing serial intravascular ultrasonography at 18-24 month intervals to assess changes in percent atheroma volume (PAV). Using a propensity weighted analysis, and following adjustment for baseline variables, patients with ( n = 190) or without ( n = 4776) atrial fibrillation were compared with regard to coronary plaque volume and major adverse cardiovascular events (death, myocardial infarction, and stroke). Results Atrial fibrillation patients demonstrated lower baseline PAV (36.0 ± 8.9 vs. 38.1 ± 8.9%, p = 0.002) and less PAV progression (-0.07 ± 0.34 vs. + 0.23 ± 0.34%, p = 0.001) compared with the non-atrial fibrillation group. Multivariable analysis revealed atrial fibrillation to independently predict both myocardial infarction [HR, 2.41 (1.74,3.35), p<0.001] 2.41 (1.74, 3.35), p < 0.00) and major adverse cardiovascular events [HR, 2.2, (1.66, 2.92), p<0.001] 2.20 (1.66, 2.92), p < 0.001]. Kaplan-Meier analysis showed that atrial fibrillation compared with non-atrial fibrillation patients had a significantly higher two-year cumulative incidence of overall major adverse cardiovascular events (4.4 vs. 2.0%, log-rank p = 0.02) and myocardial infarction (3.3 vs. 1.5%, log-rank p = 0.05). Conclusions The presence of atrial fibrillation independently associates with a heightened risk of myocardial infarction despite a lower baseline burden and progression rate of coronary atheroma. Further studies are necessary to define the pathogenesis of myocardial infarction in the setting of atrial fibrillation.

Home monitoring of heart failure patients at risk for hospital readmission using a novel under-the-mattress piezoelectric sensor: A preliminary single centre experience.

Introduction A piezoelectric sensor (PS) converts mechanical deformations into electrical signals. We used a contactless under-the-mattress PS to monitor physiological vibrations resulting from breathing, pumping of the heart, and body movements, among individuals at home following hospitalization for heart failure (HF). Our objectives were to assess acceptability of the device in the home, to assess physiological patterns, and to determine if altered patterns correlate with readmission. Methods We conducted a prospective observational study of 30 patients discharged home following HF hospitalization. PS data included a continuous nightly assessment of heart rate, respiration rate, movement rate, rapid and shallow respiration duration, and a behaviour score. We utilized random forest classification to classify average nightly data by readmission status. Results We collected 640 nights of PS data from 29 patients. There were nine readmissions, of which four were for HF. PS monitoring was tolerated by all but one of the participants. We inspected continuous nightly physiological profiles and noted differences between patients who were and were not readmitted. Patients readmitted for HF had higher average heart and respiration rates, and more respiration variability. Average nightly respiratory rate was most predictive of readmission. Discussion We are the first to study nocturnal physiological patterns of HF patients at home using a contactless under-the-mattress monitoring system. We noted patterns that may be unique to patients at risk for readmission due to HF. Respiratory rate was the most important risk-adjusted associate of readmission for HF. Further studies should investigate the efficacy of home PS monitoring in HF populations.

Coronary atheroma progression rates in men and women following high-intensity statin therapy: A pooled analysis of REVERSAL, ASTEROID and SATURN.

BACKGROUND AND AIMS: High-intensity statin therapy (HIST) reduces cardiovascular events, however, sex-related differences in treatment effects are not well characterized. METHODS: A patient-level post hoc pooled analysis of 3 randomized trials utilizing serial coronary intravascular ultrasound was undertaken, testing the anti-atherosclerotic effects of HIST in coronary disease patients. Sex-related differences in changes (Δ) in coronary percent atheroma volume (PAV) were ascertained following 18-24 months of HIST (atorvastatin 80 mg or rosuvastatin 40 mg daily), and further characterized according to on-treatment lipid and lipoprotein levels. RESULTS: In women (n = 451) compared with men (n = 1190), on-treatment levels of LDL-C (68 ± 24 vs. 67 ± 22 mg/dl, p=0.62) and apoB (77 ± 23 vs. 76 ± 20 mg/dL, p=0.51) were similar; levels of HDL-C (53 ± 12 vs. 47 ± 11 mg/dl, p < 0.001), apoA1 (154 ± 26 vs. 140 ± 24 mg/dl, p < 0.001), triglycerides [122 (95, 158) vs. 114 (89, 154) mg/dl, p=0.012] and CRP [1.7 (0.9, 3.8) vs. 1.1 (0.6, 2.7) mg/l, p < 0.001] were higher; while the total cholesterol/HDL-C (TC/HDL-C) ratio was lower (2.9 ± 0.8 vs. 3.1 ± 0.8, p < 0.001). Compared with men, women harbored significantly lower baseline PAV (34.8 ± 8.7 vs. 38.3 ± 8.8%, p < 0.001), yet demonstrated significantly greater PAV regression (ΔPAV -1.07 ± 0.26 vs. -0.66 ± 0.23%, p=0.02). When achieved on-treatment levels of LDL-C were <64 mg/dl, apoB <73 mg/dl, non-HDL-C <88.8 mg/dl, and TC/HDL-C <2.99, women demonstrated significantly greater PAV regression than men. Multivariable analysis revealed female sex to independently associate with PAV regression (coefficient -0.66, p=0.02). CONCLUSIONS: Women demonstrate greater degrees of coronary plaque regression compared with men following long-term HIST, especially in the setting of lower achieved atherogenic lipoprotein levels.

Non-HDL Cholesterol and Triglycerides: Implications for Coronary Atheroma Progression and Clinical Events.

OBJECTIVES: Non-high-density lipoprotein cholesterol (non-HDLC) levels reflect the full burden of cholesterol transported in atherogenic lipoproteins. Genetic studies suggest a causal association between elevated triglycerides (TGs)-rich lipoproteins and atherosclerosis. We evaluated associations between achieved non-HDLC and TG levels on changes in coronary atheroma volume. APPROACH AND RESULTS: Data were analyzed from 9 clinical trials involving 4957 patients with coronary disease undergoing serial intravascular ultrasonography to assess changes in percent atheroma volume (ΔPAV) and were evaluated against on-treatment non-HDLC and TG levels. The effects of lower (<100 mg/dL) versus higher (≥100 mg/dL) achieved non-HDLC levels and lower (<200 mg/dL) versus higher (≥200 mg/dL) achieved TG levels were evaluated in populations with variable on-treatment low-density lipoprotein cholesterol (LDLC) 0) was associated with achieved TG levels >200 mg/dL, respectively. Lower on-treatment non-HDLC and TG levels associated with significant PAV regression compared with higher non-HDLC and TG levels across all levels of LDLC and C-reactive protein and irrespective of diabetic status (P<0.001 across all comparisons). ΔPAV were more strongly influenced by changes in non-HDLC (ß=0.62; P<0.001) compared with changes in LDLC (ß=0.51; P<0.001). Kaplan-Meier sensitivity analyses demonstrated significantly greater major adverse cardiovascular event rates in those with higher versus lower non-HDLC and TG levels, with an earlier separation of the non-HDLC compared with the LDLC curve. CONCLUSIONS: Achieved non-HDLC levels seem more closely associated with coronary atheroma progression than LDLC. Plaque progression associates with achieved TGs, but only above levels of 200 mg/dL. These observations support a more prominent role for non-HDLC (and possibly TG) lowering in combating residual cardiovascular risk.

Randomized Study of Persistent Atrial Fibrillation Ablation: Ablate in Sinus Rhythm Versus Ablate Complex-Fractionated Atrial Electrograms in Atrial Fibrillation.

BACKGROUND: Achieving long-term successful outcomes with ablation of persistent atrial fibrillation (AF) remains a clinical and procedural challenge. We aimed to assess 2 ablation strategies for persistent AF: pulmonary vein antral isolation (PVAI) in sinus rhythm after direct current cardioversion versus PVAI and ablation targeting complex-fractionated atrial electrograms while in AF. METHODS AND RESULTS: Between June 2009 and July 2013, patients with continuous persistent AF for ≥3 months were prospectively randomized to either direct current cardioversion before PVAI and posterior wall/septum ablation while in sinus rhythm (group 1), versus same ablation in group 1 in addition to complex-fractionated atrial electrogram ablation while in AF (group 2). The procedural profiles and clinical outcomes of the 2 strategies were compared. Ninety patients were randomized to group 1 (n=46) or group 2 (n=44). There were no differences in baseline characteristics between groups. Over 365 days of follow-up after the index procedure, 16 patients (35%) in group 1 and 13 patients (30%) in group 2 remained arrhythmia-free off antiarrhythmic medications. Over long-term follow-up (median, 867 days), arrhythmia-free survival off antiarrhythmic medications was more likely in group 1 than in group 2 in Kaplan-Meier analysis (Log Rank P=0.04). Group 1 ablation was associated with significantly shorter procedural duration and fluoroscopy time (231±72 versus 273±76 min; P=0.008 and 54 [Q1-Q3: 46-67] versus 66 (Q1-Q3: 53-83] min; P=0.018, respectively). CONCLUSIONS: In patients with persistent AF, PVAI in sinus rhythm after direct current cardioversion is associated with higher success and shorter procedural and fluoroscopy times compared with PVAI in AF with additional complex-fractionated atrial electrogram ablation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02429648.

The beneficial effects of raising high-density lipoprotein cholesterol depends upon achieved levels of low-density lipoprotein cholesterol during statin therapy: Implications for coronary atheroma progression and cardiovascular events.

AIMS: Controversy exists regarding benefits of raising HDL-C in statin-treated coronary artery disease (CAD) patients. We assessed the anti-atherosclerotic efficacy of raising HDL-C in statin-treated individuals with CAD across a range of achieved LDL-C, including lower (<70 mg/dL) versus higher (≥70 mg/dL) levels. METHODS AND RESULTS: In seven prospective randomized trials utilizing serial coronary intravascular ultrasound, 3469 statin-treated CAD patients were stratified according to achieved LDL-C (< vs ≥70 mg/dL) and changes in HDL-C (≥ vs < median), as well as across a broader spectrum of changes in HDL-C and achieved LDL-C levels. Changes in coronary percent atheroma volume and MACE (cardiovascular death, non-fatal MI, stroke, coronary revascularization, hospitalization for unstable angina) were evaluated across these groups. RESULTS: Overall, median change in HDL-C was +6.03%, and mean achieved LDL-C in the lower and higher LDL-C groups were 55.1 ± 11 and 97.4 ± 22 mg/dL, respectively. Following multivariable adjustment, in patients with achieved LDL-C < 70 mg/dL, greater HDL-C-raising did not associate with disease progression/regression. In those with achieved LDL-C ≥ 70 mg/dL, greater HDL-C-raising associated with less disease progression (OR 0.80 (95% CI 0.67, 0.97)) and MACE (HR 0.78 (95% CI 0.64, 0.96)). Greater increases in HDL-C (up to 25% from baseline) across the continuous range of on-treatment LDL-C levels associated with less disease progression )OR 0.90 (95% CI 0.83, 0.98)) and lower MACE (HR 0.87 (95% CI 0.77, 0.998)). CONCLUSIONS: Increasing HDL-C via a broad spectrum of mechanisms appears beneficial in statin-treated CAD patients, but is likely of greater benefit in patients with achieved LDL-C levels ≥70 mg/dL.