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Surgery remains the only recommended intervention for patients with native aortic regurgitation. A transcatheter therapy to treat patients at high risk for mortality and complications with surgical aortic valve replacement represents an unmet need. Commercial transcatheter heart valves in pure aortic regurgitation are hampered by unacceptable rates of embolisation and paravalvular regurgitation. The Trilogy transcatheter heart valve (JenaValve Technology, Irvine, CA, USA) provides a treatment option for these patients. We report outcomes with transfemoral transcatheter aortic valve implantation (TAVI) in patients with pure aortic regurgitation using this dedicated transcatheter heart valve.

ABSTRACTBackgroundSymptomatic severe aortic regurgitation (ssAR) is a Class I recommendation for surgical aortic valve replacement (SAVR). We sought to evaluate the practice patterns and drivers of ssAR patients receiving SAVR treatment.MethodsUsing a US dataset of de-identified electronic health records, we identified integrated delivery network patients diagnosed with ssAR between 2008 and 2016 with ≥2 symptom-related notes (heart failure, angina, dyspnea, pre-syncope, or syncope) within six months prior to diagnosis.ResultsFrom a final cohort of 4,608 ssAR patients, 25.7% of ssAR patients underwent SAVR within 1 year of diagnosis; mortality at 1 year was 9% after SAVR, and 24% for those untreated. Using multilevel, multivariable, cause-specific models, women and patients >80 years old were found to be treated significantly less likely [hazard ratios (HR) 0.79 (95% confidence interval [CI]: 0.69–0.90) and 0.28 (0.22–0.37), respectively]. Patients with concomitant moderate/severe aortic stenosis [1.70 (1.43–2.03)], bicuspid aortic valve disease [1.33 (1.13–1.56)], and endocarditis [2.70 (1.04–3.57)] were more likely to be treated. Using multivariable Cox proportional hazard models, ssAR patients managed by cardiologists in the highest SAVR treatment rate tertile had a 23% lower risk of 1-year mortality compared to patients managed by cardiologists in the lowest SAVR treatment rate tertile [0.77 (0.60–0.98)].ConclusionsWe identified significant disparities in the treatment of ssAR patients, specifically women, older patients, and patients managed by cardiologists with a lower SAVR treatment rate. These gaps should be addressed to level the quality of care delivered to all ssAR patients.

ABSTRACTBackgroundOutcomes of transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BAV) might be improved through better transcatheter heart valve (THV) sizing and positioning. Patient-specific computer simulation may be used to identify an optimal THV size and implant depth that minimizes paravalvular regurgitation. We sought to examine whether the usage of optimal THV sizing and positioning would be associated with improved clinical outcomes.MethodsA multi-center retrospective study was performed on patients who had undergone TAVR in BAV. Finite element models of the aortic root were created and then finite element analysis was performed using different THV sizes and implant depths. Computational fluid dynamics was undertaken. Patients were classified as having optimal THV sizing and positioning if the predicted paravalvular regurgitation of the computer simulation corresponding to the implanted THV size and implant depth was within 5 mL/sec of the best possible computer simulation, and non-optimal if not. Clinical outcomes were compared between the two patient groups.ResultsA total of 50 patients were included in the study. Paravalvular regurgitation severity was higher in patients where non-optimal THV sizing and positioning was used (P< 0.001). At 2 years, the Kaplan-Meier estimate of the rate of death from any cause was higher in the group where non-optimal THV sizing and positioning was used (34.5% vs. 9.1%; hazard ratio, 6.23; 95% confidence interval, 1.04 to 37.44; P= 0.02 by log-rank test).ConclusionComputer simulation suggests that the usage of optimal THV sizing and positioning might improve clinical outcomes of TAVR in BAV.Abbreviations:AUC: area under the receiver operating characteristic curve; BAV: bicuspid aortic valve; BAVi: bicuspid aortic valve imaging; CI: confidence interval; CPI: contact pressure index; CT: computed tomography; TAVR: transcatheter aortic valve replacement; THV: transcatheter heart valve

IMPORTANCE: Bioprosthetic mitral valves are implanted with increasing frequency but inevitably degenerate, leading to heart failure. Reoperation is associated with high morbidity and mortality. Transcatheter mitral valve-in-valve (MViV) using balloon-expandable transcatheter valves has emerged as an alternative for high–surgical risk patients. OBJECTIVE: To assess contemporary outcomes of SAPIEN 3 (Edwards Lifesciences) MViV replacement. DESIGN, SETTING, AND PARTICIPANTS: In this registry-based prospective cohort study of SAPIEN 3 MViV, patients entered in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry from June 2015 to July 2019 were analyzed. US Centers for Medicare and Medicaid linkage ensured comprehensive collection of death and stroke data. EXPOSURES: Mitral valve-in-valve for degenerated bioprosthetic mitral valves. MAIN OUTCOMES AND MEASURES: The primary efficacy end point was 1-year mortality. The primary safety end point was procedural technical success as defined by the Mitral Valve Academic Research Consortium criteria. Secondary end points included 30-day mortality, New York Heart Association–defined heart failure, and mitral valve performance. RESULTS: A total of 1529 patients (mean [SD] age, 73.3 [11.84] years; 904 women [59.1%]) underwent transseptal or transapical MViV implant at 295 hospitals between June 2015 and July 2019. The mean (SD) Society of Thoracic Surgeons predicted risk of mortality was 11.1% (8.7%). Procedural technical success was achieved for 1480 of 1529 patients (96.8%). All-cause mortality was 5.4% at 30 days and 16.7% at 1 year. Transseptal access was associated with lower 1-year all-cause mortality than transapical access (15.8% vs 21.7%; P = .03). Transcatheter MViV led to early, sustained, and clinically meaningful improvements in heart failure (class III/IV New York Heart Association heart failure of 87.1% at baseline vs 9.7% at 1 year). The mean (SD) mitral valve gradient at 1 year was 7 (2.89) mm Hg. CONCLUSIONS AND RELEVANCE: Transcatheter MViV using the SAPIEN 3 transcatheter heart valve is associated with high technical success, low 30-day and 1-year mortality, significant improvement of heart failure symptoms, and sustained valve performance. Transseptal MViV should be considered an option for most patients with failed surgical bioprosthetic valves and favorable anatomy.

Despite growing evidence of cardiovascular complications associated with coronavirus disease 2019 (COVID-19), there are few data regarding the performance of transthoracic echocardiography (TTE) and the spectrum of echocardiographic findings in this disease.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

ABSTRACTBackground:Index hospital costs for transcatheter aortic valve replacement (TAVR) remain high. Next-day discharge (NDD) is a safe and feasible strategy in select patients. We sought to explore cost savings associated with NDD TAVR.Methods:We conducted a retrospective observation cohort study of all fee-for-service Medicare beneficiaries who underwent elective, uncomplicated, transfemoral TAVR in 2016. We employed a cross-sectional regression analysis to estimate risk-adjusted hospital costs savings of NDD relative to longer length of stay (LOS), and logistic regression to determine differences in direct home discharge and readmission.Results:Among 14,765 patients (59.2% of all TAVR), 2,169 (14.7%) were identified as NDD. They were younger (81.3 vs. 82.2, p< 0.01), more likely to be male (63% vs. 52%, p< 0.01), and had lower Charlson Comorbidity Index scores (2.73 vs. 2.98, p< 0.01). The adjusted cost for NDD was $7,499 lower compared to non-NDD (p< 0.001), and $5,188 when controlling for hospital fixed effects (p< 0.001); estimated total cost savings ranged from $6,522,183 to $16,265,331. NDD was associated with higher rates of discharged home (83% vs. 59%, p< 0.0001) without home health (16% vs. 28%, p< 0.0001), and lower incidence of readmission at 30 days [OR 0.72 (0.61–0.86), p= 0.0003], 60 days [0.71 (0.61–0.82), p< 0.0001] and 90 days [0.74 (0.65–0.85), p< 0.0001] than non-NDD.Conclusions:There is significant heterogeneity in LOS after TAVR. Cost savings could be achieved with the implementation of clinical pathways and other strategies. Future research is needed to fully capture the multiple effects associated with LOS.

To explore the burden and clinical correlates of valvular heart disease in Hispanics/Latinos in the United States.

In irregular heart rhythms, echocardiographic calculation of aortic effective orifice area (EOA) requires averaging measurements from multiple cardiac cycles. Whether a single cycle length method can be used to calculate aortic EOA in aortic stenosis with nonsinus rhythms is not known.

ABSTRACTBackground:Subjective frailty assessment is widely employed in risk stratification of patients with severe aortic stenosis (AS), but the association with objective frailty parameters is poorly characterized.Methods:Frailty was subjectively assessed (dichotomously as frail or not frail) in high-risk patients with AS referred to a Heart Valve Clinic. An objectively derived composite frailty score was derived by summing quartiles of the following frailty measures: 15-foot walk time, grip strength, independence in activities of daily living (ADL), and serum albumin. The objective measures and composite score were compared between those considered frail and not frail by subjective assessment. The relationship between frailty status and outcomes was analyzed.Results:Of 100 subjects, 31 were frail by subjective assessment. When compared to those considered not frail, there were no differences in age, sex, and BMI. However, frail subjects had higher STS scores and had significantly greater dependence in ADL, slower gait speed, weaker grip strength, and lower albumin than non-frail subjects. The composite frailty score was highly correlated with frailty designation by subjective assessment. Subjective and objective frailty were both highly predictive of treatment assignment to either medical therapy or aortic valve replacement, and of mortality.Conclusion:Among patients with AS evaluated in a Heart Valve Clinic, those considered frail by subjective assessment were slower, weaker, more malnourished, and had greater ADL impairment. Subjective assessment of frailty and objective frailty measures were similarly predictive of treatment assignment and mortality.

ABSTRACTBackground:Patients with severe aortic stenosis (AS) at intermediate surgical risk, treated with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) have similar 2-year survival. Significant obesity (SigOb), defined as body mass index (BMI) ≥ 35 kg/m2, has been associated with increased surgical risk and post-operative complications. There are no data comparing clinical outcomes after SAVR versus TAVR in patients with SigOb.Methods:In the PARTNER 2A trial, 2032 patients with severe AS and intermediate surgical risk were randomized to TAVR with the SAPIEN XT valve or SAVR. After excluding 32 patients who had very low BMI < 18.5 kg/m2, the remaining 2000 patients were categorized based on BMI at baseline to SigOb or not SigOb, and compared in regards to 2-year risk of adverse cardiovascular events.Results:A total of 250 patients (12.5%) were SigOb and were younger, more often female, and more frequently diabetic. The 30-day and 2-year rates of the primary composite endpoint death and disabling stroke as well as the risks of its components, were similar for patients with versus without SigOb. However, the 2-year relative risk of cardiovascular death was lower with TAVR versus SAVR for SigOb patients (5.7% vs 15.4%, p = 0.02; HR 0.36, 95% CI 0.15–0.88) but not for not SigOb patients (10.6% vs 10.7%, p = 0.91; HR 0.98, 95% CI 0.73–1.32; pinteraction = 0.03). These results remained consistent after multivariable adjustment.Conclusions:In the PARTNER 2A Trial, intermediate-risk patients with severe AS and BMI ≥ 35 kg/m2undergoing TAVR experienced significantly lower cardiovascular mortality than similar patients undergoing SAVR.

ABSTRACTBackground:Patients with chronic kidney disease (CKD) and aortic stenosis (AS) have poor prognosis after both transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). The objective of our study was to assess the outcomes of TAVR versus SAVR for severe AS among patients with moderate to severe CKD (stage ≥3).Methods:PubMed, Cochrane Center Register of Controlled Trials and clinical trial registry were searched through April 2017. Seven studies comparing TAVR (n = 878) and SAVR (n = 2531) in patients with CKD stage ≥3 were included. End points were clinical and qualitative outcomes. Odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI) was computed and p < 0.05 was considered significant.Results:There was no difference in all-cause mortality (p = 0.7), cerebrovascular accidents (p = 0.28), myocardial infarction (p = 0.55) or new permanent pacemaker placement (p = 0.06) with TAVR compared with SAVR. Post-procedural worsening renal failure or acute kidney injury (AKI), new dialysis and length of intensive care unit stay were lower with TAVR compared with SAVR (OR:0.47, CI:0.33–0.68, p < 0.0001; OR:0.44, CI:0.25–0.74, p = 0.002 and MD: −68.32 hours, CI: −86.35 to −50.28 hours, p < 0.00001 respectively). Major vascular complications were higher and red blood cell transfusion was lower with TAVR compared with SAVR (OR:8.84, CI:1.6–49, p = 0.01 and OR:0.39, CI:0.18–0.82, p = 0.01 respectively).Conclusion:The results of our meta-analysis comparing TAVR with SAVR in patients with severe AS and moderate to severe CKD suggest that TAVR is comparable to SAVR with the advantage of a decreased incidence of worsening of renal failure or AKI, new dialysis, and intensive care unit stay.

IMPORTANCE: Use of transcatheter aortic valve replacement (TAVR) for severe aortic stenosis is growing rapidly. However, to our knowledge, the durability of these prostheses is incompletely defined. OBJECTIVE: To determine the midterm hemodynamic performance of balloon-expandable transcatheter heart valves. DESIGN, SETTING, AND PARTICIPANTS: In this study, we analyzed core laboratory–generated data from echocardiograms of all patients enrolled in the Placement of Aortic Transcatheter Valves (PARTNER) 1 Trial with successful TAVR or surgical AVR (SAVR) obtained preimplantation and at 7 days, 1 and 6 months, and 1, 2, 3, 4, and 5 years postimplantation. Patients from continued access observational studies were included for comparison. INTERVENTIONS: Successful implantation after randomization to TAVR vs SAVR (PARTNER 1A; TAVR, n = 321; SAVR, n = 313), TAVR vs medical treatment (PARTNER 1B; TAVR, n = 165), and continued access (TAVR, n = 1996). Five-year echocardiogram data were available for 424 patients after TAVR and 49 after SAVR. MAIN OUTCOMES AND MEASURES: Death or reintervention for aortic valve structural indications, measured using aortic valve mean gradient, effective orifice area, Doppler velocity index, and evidence of hemodynamic deterioration by reintervention, adverse hemodynamics, or transvalvular regurgitation. RESULTS: Of 2795 included patients, the mean (SD) age was 84.5 (7.1) years, and 1313 (47.0%) were female. Population hemodynamic trends derived from nonlinear mixed-effects models showed small early favorable changes in the first few months post-TAVR, with a decrease of −2.9 mm Hg in aortic valve mean gradient, an increase of 0.028 in Doppler velocity index, and an increase of 0.09 cm2 in effective orifice area. There was relative stability at a median follow-up of 3.1 (maximum, 5) years. Moderate/severe transvalvular regurgitation was noted in 89 patients (3.7%) after TAVR and increased over time. Patients with SAVR showed no significant changes. In TAVR, death/reintervention was associated with lower ejection fraction, stroke volume index, and aortic valve mean gradient up to 3 years, with no association with Doppler velocity index or valve area. Reintervention occurred in 20 patients (0.8%) after TAVR and in 1 (0.3%) after SAVR and became less frequent over time. Reintervention was caused by structural deterioration of transcatheter heart valves in only 5 patients. Severely abnormal hemodynamics on echocardiograms were also infrequent and not associated with excess death or reintervention for either TAVR or SAVR. CONCLUSIONS AND RELEVANCE: This large, core laboratory–based study of transcatheter heart valves revealed excellent durability of the transcatheter heart valves and SAVR. Abnormal findings in individual patients, suggestive of valve thrombosis or structural deterioration, were rare in this protocol-driven database and require further investigation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00530894

Concomitant coronary artery disease (CAD) is highly prevalent among patients with severe aortic stenosis (AS). Historically, surgical aortic valve replacement with coronary artery bypass grafting was the only treatment option for patients with severe AS and significant CAD. The rapid expansion of transcatheter aortic valve replacement has led to significant paradigm shifts in the treatment of severe AS and has raised new questions regarding the optimal management of CAD in these patients. We review the evidence regarding management of concomitant CAD in severe AS patients, specifically focusing on issues surrounding transcatheter aortic valve replacement. In the absence of robust evidence supporting specific treatment strategies, decisions regarding coronary revascularization in severe AS should be individualized and made within the context of a multidisciplinary heart team.

Three-dimensional (3D) echocardiographic (3DE) imaging is an alternative to multi–detector row computed tomography (MDCT) for aortic annular measurement before transcatheter aortic valve replacement (TAVR). A commonly used direct planimetry from a reconstructed short-axis view has not been compared with semiautomated 3DE methods. Typically accepted optimal cutoffs for percent prosthesis-area oversizing of the balloon-expandable SAPIEN or SAPIEN XT valve to native annular size are approximately 5% to 15%. The aim of this study was to compare semiautomated and direct planimetric 3DE methods for aortic annular sizing with a gold standard of MDCT to determine predictive value for paravalvular regurgitation (PVR) and balloon postdilatation.

In 2022, the Food and Drug Administration approved a second mitral transcatheter edge-to-edge repair device for the treatment of primary mitral regurgitation (PASCAL Precision Transcatheter Valve Repair System, Edwards Lifesciences, Irvine, CA). The PASCAL Precision system consists of a guide sheath, implant system, and accessories. The implant system consists of a steerable catheter, an implant catheter, and the implant (PASCAL or PASCAL Ace). The guide sheath and steerable catheter move and flex independently from each other and are not keyed, allowing for freedom of rotation in three dimensions. This manuscript provides an overview of the PASCAL Precision system and describes the basic and advanced steering maneuvers to facilitate effective and safe mitral transcatheter edge-to-edge repair.

Baseline left ventricular diastolic dysfunction (LVDD) is associated with poor health status in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), but health status improvement after TAVR appears similar across all grades of LVDD. Here, we aim to examine the relationship between changes in LVDD severity and health status outcomes following TAVR.

Cardiac computed tomography angiography was used to identify anatomical characteristics of the aortic root in patients with severe aortic regurgitation (AR) as compared to those with aortic stenosis (AS) to judge feasibility of transcatheter aortic valve replacement (TAVR) with the JenaValve Trilogy system.

Background:There are concerns that transcatheter or surgical aortic valve replacement (TAVR/SAVR) procedures are preferentially available to White patients.Methods:We stratified Medicare beneficiaries hospitalized with principal diagnosis of AS between 2012 and 2019 (n=299,976) by self-reported race/ethnicity (Black, Hispanic, Asian, Native American, and White). We evaluated AVR rates within 6 months of index hospitalization and associated procedural outcomes, including 30-day and 1-year mortality, and discharge disposition. We fitted Cox-proportional hazard models for outcomes, adjusting for demographics and comorbidities using race/ethnicity subgroup-specific-stabilized inverse probability weights.Results:Within 6 months of an index admission for AS, 86.8% (122,457 SAVR; 138,026 TAVR) patients underwent AVR. Overall, compared with White people, Black [HR 0.87 (0.85-0.89)], Hispanic [0.92 (0.88 - 0.96)], and Asian [0.95 (0.91 - 0.99)] people were less likely to receive AVR (Figure). Among patients who were admitted emergently/urgently, White patients (41.1%, 95% CI 40.7-41.4) had a significantly higher AVR rate within 6 months compared with Black (29.6%, 95% CI 28.3-30.9), Hispanic (36.6%, 95% CI 34.0-39.3), and Asian patients (35.4%, 95% CI 32.3-38.9). AVR rates increased annually for all race/ethnicities. There were no significant differences in 30-day or 1-year mortality by race. Black people were significantly more likely to be discharged to a facility compared with others.Conclusion:Within 6 months of AS admission, AVR rates are lower for Black, Hispanic, and Asian people compared with White people. These race-based differences in ultimate treatment of AS likely represent complex issues across the diagnosis and management of AS, warranting a comprehensive reassessment of the entire care spectrum for disadvantaged populations.

Echocardiographic calculation of effective orifice area (EOA) after transcatheter aortic valve replacement is integral to the assessment of transcatheter heart valve (THV) function. The aim of this study was to determine the most accurate method for calculating the EOA of the Edwards SAPIEN and SAPIEN XT THVs.

Transcatheter mitral valve replacement (TMVR) is an emerging new treatment option in patients with advanced mitral valve disease deemed a high or prohibitive risk for surgery. Designing an ideal TMVR device requires a detailed understanding of different mitral valve pathologies and the complex, dynamic anatomy and physiology of the mitral apparatus. This review aims to critically evaluate design implications in TMVR in the context of mitral valve disease, imaging prerequisites, procedural approaches, potential complications, and outcomes assessment.

The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that mortality at 1 year, 2 years, and 3 years is much the same with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) for high-risk patients with aortic stenosis. We report here the 5-year outcomes.

The higher risk of adverse outcomes after transapical (TA) versus transfemoral (TF) transcatheter aortic valve replacement (TAVR) could be attributable to TA-TAVR being an open surgical procedure or to clinical differences between TA- and TF-TAVR patients. We compared outcomes after neutralizing patient differences using propensity score matching.

Supplemental Digital Content is available in the text.

Previous studies have shown cross-sectional 3-dimensional (3D) transesophageal echocardiographic (TEE) measurements to severely underestimate multidetector row computed tomographic (MDCT) measurements for the assessment of aortic annulus before transcatheter aortic valve replacement. This study compares annulus measurements from 3D-TEE using off-label use of commercially available software with MDCT measurements and assesses their ability to predict paravalvular regurgitation.

The success of transcatheter aortic valve implantation (TAVI) is centred around the collaboration between cardiac surgeons and interventional cardiologists. A report from the German Quality Assurance Registry on TAVI now suggests that clinical outcomes in hospitals without cardiac surgery departments are similar to those in centres with onsite cardiac surgery support.

Supplemental Digital Content is available in the text.Right ventricular pressure-volume (PV) analysis characterizes ventricular systolic and diastolic properties independent of loading conditions like volume status and afterload. While long-considered the gold-standard method for quantifying myocardial chamber performance, it was traditionally only performed in highly specialized research settings. With recent advances in catheter technology and more sophisticated approaches to analyze PV data, it is now more commonly used in a variety of clinical and research settings. Herein, we review the basic techniques for PV loop measurement, analysis, and interpretation with the aim of providing readers with a deeper understanding of the strengths and limitations of PV analysis. In the second half of the review, we detail key scenarios in which right ventricular PV analysis has influenced our understanding of clinically relevant topics and where the technique can be applied to resolve additional areas of uncertainty. All told, PV analysis has an important role in advancing our understanding of right ventricular physiology and its contribution to cardiovascular function in health and disease.

Introduction:Advanced tricuspid regurgitation (TR) is associated with adverse cardiovascular outcomes. Herein, we report demographics of patients presenting to a tertiary valve center and characterize measures of TR severity and right ventricular (RV) function.Methods:We conducted a single center retrospective analysis of patients referred to a specialty valve clinic from January 2016 to September 2020 with a primary or secondary diagnosis of tricuspid regurgitation. Baseline clinical, echocardiographic, and hemodynamic variables were evaluated.Results:A total of 348 patients were included. Median age was 79 years (IQR 70, 84), and 54% were female. Torrential TR was present in 41% (n = 146), massive in 11% (n = 40), severe 34% (n = 120), and moderate or less in 9% (n = 31). Increase in TR severity was associated with RV, right atrial, and annular dilatation. There was no difference in RV function between groups assessed by TAPSE or S’. Right atrial pressure v-wave was higher with increase in TR severity. Pulmonary arterial (PA) pressures were significantly different between groups, as was pulmonary vascular resistance (PVR): lower PA pressures and PVR were seen with increase in TR severity. There were no differences in cardiac output across groups, though a numeric trend in decreasing cardiac output was noted with increase in TR severity from severe to torrential. There was increase in S’/PASP and decrease in pulmonary artery pulsatility index seen with increasing TR severity.Conclusion:Patients referred for TR are frequently advanced in age with massive or torrential tricuspid regurgitation and evidence of adverse right ventricular remodeling. Increasing severity of advanced TR was associated with RV hemodynamic decompensation. Preservation of two-dimensional measures of right ventricular function in the setting of progressive TR, as well as markers of right ventricular-vascular coupling, may suggest these are late markers of right ventricular compromise.

N6-Cyclopentyladenosine (CPA), an A1 adenosine receptor agonist, increased EEG slow-wave activity in nonREM sleep when administered either systemically (0.1–3 mg/kg) or intracerebroventricularly (3.5–10 μg) in the rat. The power spectrum of EEG changes (as calculated by Fourier analysis) matched that produced by total sleep deprivation in the rat. The effects of CPA on the nonREM-sleep EEG were dose-dependent. These findings suggest that adenosine is an endogenous mediator of sleep-deprivation induced increases in EEG slow-wave activity, and therefore that increased adenosine release is a concomitant of accumulation of sleep need and may be involved in homeostatic feedback control of sleep expression.

Spontaneous intercellular Ca2+waves were observed in groups of neurons in two different culture preparations: primary mouse cortical neurons and GT1-1 immortalized neurons. Waves of increased intracellular Ca2+concentration propagated at rates of 100–200 μm/s over as many as 200 cells and were abolished by the removal of extracellular calcium, by nimodipine, by tetrodotoxin, and by the gap junction inhibitor octanol. A sister clone of the GT1 line, GT1-7 neurons, showed no intercellular Ca2+waves and were found to have a significantly lower level of connexin26 mRNA than the GT1-1 line. Although we cannot definitively rule out a role for synaptic communication, we propose that intercellular Ca2+waves in cultured neurons are generated by Ca2+influx caused primarily by the propagation of depolarization via gap junctions. Intercellular Ca2+signaling via gap junctions may represent an important mechanism for nonsynaptic neuronal signaling.

The novel coronavirus disease 2019, otherwise known as COVID-19, is a global pandemic with primary respiratory manifestations in those who are symptomatic. It has spread to >187 countries with a rapidly growing number of affected patients. Underlying cardiovascular disease is associated with more severe manifestations of COVID-19 and higher rates of mortality. COVID-19 can have both primary (arrhythmias, myocardial infarction, and myocarditis) and secondary (myocardial injury/biomarker elevation and heart failure) cardiac involvement. In severe cases, profound circulatory failure can result. This review discusses the presentation and management of patients with severe cardiac complications of COVID-19 disease, with an emphasis on a Heart-Lung team approach in patient management. Furthermore, it focuses on the use of and indications for acute mechanical circulatory support in cardiogenic and/or mixed shock.

Background:Currently there is no consensus regarding indications and timing of permanent pacemaker implantation (PPI) following transcatheter aortic valve replacement (TAVR). Despite all patients receiving a balloon-expandable valve platform with the same inclusion criteria and no baseline electrocardiographic exclusion criteria, the rates of new PPI ranged from 0% to 33.3% at 6 low (<100 TAVR/year), 4 medium (100 to 200 TAVR/year), and 3 high-volume (>200 TAVR/year) centers. We sought to understand this variability by comparing peri-procedural ECG characteristics and PPI rates at centres with different procedural volumes.Methods:As per protocol, patients could be discharged home with a new intraventricular conduction delay in the absence of a new high-grade AV block if the length of the QRS was stable or decreasing after 24 hrs. PPI indication and timing was at the discretion of the individual site. Of the total cohort, 61 patients had pre-existing pacemakers and were excluded, resulting in a final cohort of 350 patients.Results:The overall PPI rate was 6.6% (23) in pacemaker-na?ve patients. The rate of new PPI was similar at high (4.6%), medium (9.9%) and low (7.1%) volume centres (p=0.32). The baseline ECG characteristics of the total cohort were: 209 sinus rhythm (59.7%), 61 atrial fibrillation (17.4%), 35 LBBB (10%), and 45 RBBB (12.9%). In patients with no pre-existing BBB, the rate of new LBBB following TAVR was 28.1%, of which 48.7% had resolution of their LBBB prior to discharge. The rate of BBB was similar by site volume at both baseline (High: 25%, Medium: 22.5%, Low: 20.5%, P=0.67) and immediately post TAVR (High: 36.2%, Medium: 45%, Low: 47.2%, P=0.15). Of the total cohort, 16 (4.6%) had PPI during index admission, and 7 (2%) had PPI within 15 days post procedure with no associated harm. In patients that received PPI, the proportion of patients who achieved next day discharge was 39.1% versus 80.1% in the overall cohort (p<0.001).Conclusion:Although there was a heterogenous approach to new conduction disorders, the peri-procedural electrocardiographic characteristics and rates of PPI were similar when assessed by hospital volume. A consistent approach with adherence to the Vancouver 3M Clinical Pathway may further improve outcomes and reduce LOS.

Tricuspid valve imaging is frequently challenging and requires the use of multiple modalities. Knowledge of limitations and methodologic discrepancies among different imaging techniques is crucial for planning transcatheter valve interventions.