2-Year Clinical and Echocardiography Follow-Up of Transcatheter Mitral Valve Replacement With the Transapical Intrepid System.

BACKGROUND: Thirty-day outcomes with the investigational Intrepid transapical (TA) transcatheter mitral valve replacement (TMVR) system have previously demonstrated good technical success, but longer-term outcomes in larger cohorts need to be evaluated. OBJECTIVES: The authors sought to evaluate the 2-year safety and performance of the Intrepid TA-TMVR system in patients with symptomatic, ≥moderate-severe mitral regurgitation (MR) and high surgical risk. METHODS: Patient eligibility was determined by local heart teams and approved by a central screening committee. Clinical events were adjudicated by an independent clinical events committee. Echocardiography was evaluated by an independent core laboratory. RESULTS: The cohort included 252 patients that were enrolled at 58 international sites before February 2021 as part of the global Pilot Study (n = 95) or APOLLO trial (primary cohort noneligible + TA roll-ins, n = 157). Mean age was 74.2 years, mean STS-PROM was 6.3%, 60.3% were male, and 80.6% were in NYHA functional class III/IV. Most presented with secondary MR (70.1%), and nearly all had ≥moderate-severe MR (98.4%). All-cause mortality was 13.1% (30-day), 27.3% (1-year), and 36.2% (2-year). The 30-day ≥major bleeding event rate was 22.3%. Heart failure rehospitalization was 9.6% (30-day) and 36.2% (2-year). At 2 years, >50% of patients were alive with improvement in NYHA functional class (82.1%, class I/II), and all patients with available echocardiograms had ≤mild MR. CONCLUSIONS: This analysis represents the largest reported TA-TMVR experience with the longest follow-up in high-risk ≥moderate-severe MR patients. Early mortality and heart failure rehospitalizations were significant, exacerbated by early TA-related bleeding events; however, meaningful improvements in clinical outcomes and marked reductions in MR severity were observed through 2 years.

Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial.

BACKGROUND: The International Liaison Committee on Resuscitation has called for a randomised trial of delivery to a cardiac arrest centre. We aimed to assess whether expedited delivery to a cardiac arrest centre compared with current standard of care following resuscitated cardiac arrest reduces deaths. METHODS: ARREST is a prospective, parallel, multicentre, open-label, randomised superiority trial. Patients (aged ≥18 years) with return of spontaneous circulation following out-of-hospital cardiac arrest without ST elevation were randomly assigned (1:1) at the scene of their cardiac arrest by London Ambulance Service staff using a secure online randomisation system to expedited delivery to the cardiac catheter laboratory at one of seven cardiac arrest centres or standard of care with delivery to the geographically closest emergency department at one of 32 hospitals in London, UK. Masking of the ambulance staff who delivered the interventions and those reporting treatment outcomes in hospital was not possible. The primary outcome was all-cause mortality at 30 days, analysed in the intention-to-treat (ITT) population excluding those with unknown mortality status. Safety outcomes were analysed in the ITT population. The trial was prospectively registered with the International Standard Randomised Controlled Trials Registry, 96585404. FINDINGS: Between Jan 15, 2018, and Dec 1, 2022, 862 patients were enrolled, of whom 431 (50%) were randomly assigned to a cardiac arrest centre and 431 (50%) to standard care. 20 participants withdrew from the cardiac arrest centre group and 19 from the standard care group, due to lack of consent or unknown mortality status, leaving 411 participants in the cardiac arrest centre group and 412 in the standard care group for the primary analysis. Of 822 participants for whom data were available, 560 (68%) were male and 262 (32%) were female. The primary endpoint of 30-day mortality occurred in 258 (63%) of 411 participants in the cardiac arrest centre group and in 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival 1·00, 95% CI 0·90-1·11; p=0·96). Eight (2%) of 414 patients in the cardiac arrest centre group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention. INTERPRETATION: In adult patients without ST elevation, transfer to a cardiac arrest centre following resuscitated cardiac arrest in the community did not reduce deaths. FUNDING: British Heart Foundation.

Management of coronary artery disease in patients with aortic stenosis.

Aortic stenosis (AS) is the most common valvular heart disorder in the elderly population. As a result of the shared pathophysiological processes, AS frequently coexists with coronary artery disease (CAD). These patients have traditionally been managed through surgical aortic valve replacement (SAVR) and coronary artery bypass grafting. However, increasing body of evidence supports transcatheter aortic valve implantation (TAVI) as an alternative treatment for severe AS across the spectrum of operative risk. This has created the potential for treating AS and concurrent CAD completely percutaneously. In this review we consider the evidence guiding the optimal management of patients with severe AS and CAD. While invasive coronary angiography plays a central role in detecting CAD in patients with AS undergoing surgery or TAVI, the benefits of complementary functional assessment of coronary stenosis in the context of AS have not been fully established. Although the indications for revascularisation of significant proximal CAD in SAVR patients have not recently changed, routine revascularisation of all significant CAD before TAVI in patients with minimal angina is not supported by the latest evidence. Several ongoing trials will provide new insights into physiology-guided revascularisation in TAVI recipients. The role of the heart team remains essential in this complex patient group, and if revascularisation is being considered careful evaluation of clinical, anatomical and procedural factors is essential for individualised decision-making.

A 20-year journey in transcatheter aortic valve implantation: Evolution to current eminence.

Since the first groundbreaking procedure in 2002, transcatheter aortic valve implantation (TAVI) has revolutionized the management of aortic stenosis (AS). Through striking developments in pertinent equipment and techniques, TAVI has now become the leading therapeutic strategy for aortic valve replacement in patients with severe symptomatic AS. The procedure streamlining from routine use of conscious sedation to a single arterial access approach, the newly adapted implantation techniques, and the introduction of novel technologies such as intravascular lithotripsy and the refinement of valve-bioprosthesis devices along with the accumulating experience have resulted in a dramatic reduction of complications and have improved associated outcomes that are now considered comparable or even superior to surgical aortic valve replacement (SAVR). These advances have opened the road to the use of TAVI in younger and lower-risk patients and up-to-date data from landmark studies have now established the outstanding efficacy and safety of TAVI in patients with low-surgical risk impelling the most recent ESC guidelines to propose TAVI, as the main therapeutic strategy for patients with AS aged 75 years or older. In this article, we aim to summarize the most recent advances and the current clinical aspects involving the use of TAVI, and we also attempt to highlight impending concerns that need to be further addressed.

Emergent Off-Label TAVR for Native Aortic Valve Endocarditis.

A 76-year-old-male transferred to our center with severe breathlessness (New York Heart Association class III-IV). He was afebrile, hypoxic, and tachycardic with a wide pulse-pressure. Chest auscultation revealed a systolic and early diastolic murmur. Two weeks prior to admission, he reported severe cellulitis treated with intravenous antibiotics. Transthoracic echocardiogram demonstrated severe aortic valve (AoV) stenosis and evidence of AoV disruption with mobile vegetations and severe aortic regurgitation (AR) in keeping with plausible infectious endocarditis (IE). Following 3 sets of blood cultures, we treated the patient with intravenous antibiotics and diuretics. Blood cultures were negative, likely due to previous antibiotics treatment. Due to the acute decompensation, he underwent early heart team discussion with a view to urgent surgical AoV replacement. This case example suggests that TAVR with cerebral protection might be a safe treatment option in inoperable patients with AoV IE.

The Impact of a Dedicated Chronic Total Occlusion PCI Program on Heart Team Decision Making.

BACKGROUND: Guidelines endorse a heart team (HT) approach to standardize the decision-making process for patients with complex coronary artery disease (CAD). With percutaneous treatment options for complex CAD increasing, we hypothesized that practice had changed over the past decade-and that more individuals, previously deemed too high risk for intervention, would now be referred for either surgical or percutaneous revascularization. METHODS: This observational study was conducted at St Thomas' Hospital (London, United Kingdom). All patients discussed at HT meetings were recorded and treatment recommendations audited. A subset of historic cases was selected for blinded, repeat discussion. RESULTS: From April 2018 to 2019, a total of 52 HT meetings discussing 375 cases were held. Patients tended to be male, with a majority demonstrating multivessel CAD in the context of preserved left ventricular function. SYNTAX scores were balanced across the tertiles. Thirty-five percent of patients had at least 1 chronic total occlusion (mean J-CTO, 3 [interquartile range, 2-3]), affecting the right coronary artery in 60%. Fifteen historic patients with isolated CTOs were re-presented an average of 8 years later; only 3 patients received the same outcome, with 80% now receiving a recommendation for revascularization over medical therapy. CONCLUSIONS: A dedicated program supporting complex coronary intervention is associated with a change in treatment recommendations issued by the local HT. In line with international guidelines, this might indicate that any complex or multivessel CAD should be discussed at HT meetings with, ideally, the presence of CTO operators.

Outcomes of Redo Transcatheter Aortic Valve Replacement According to the Initial and Subsequent Valve Type.

BACKGROUND: As transcatheter aortic valve (TAV) replacement is increasingly used in patients with longer life expectancy, a sizable proportion will require redo TAV replacement (TAVR). The unique configuration of balloon-expandable TAV (bTAV) vs a self-expanding TAV (sTAV) potentially affects TAV-in-TAV outcome. OBJECTIVES: The purpose of this study was to better inform prosthesis selection, TAV-in-TAV outcomes were assessed according to the type of initial and subsequent TAV. METHODS: Patients from the Redo-TAVR registry were analyzed using propensity weighting according to their initial valve type (bTAV [n = 115] vs sTAV [n = 106]) and subsequent valve type (bTAV [n = 130] vs sTAV [n = 91]). RESULTS: Patients with failed bTAVs presented later (vs sTAV) (4.9 ± 2.1 years vs 3.7 ± 2.3 years; P < 0.001), with smaller effective orifice area (1.0 ± 0.7 cm2 vs 1.3 ± 0.8 cm2; P = 0.018) and less frequent dominant regurgitation (16.2% vs 47.3%; P < 0.001). Mortality at 30 days was 2.3% (TAV-in-bTAV) vs 0% (TAV-in-sTAV) (P = 0.499) and 1.7% (bTAV-in-TAV) vs 1.0% (sTAV-in-TAV) (P = 0.612); procedural safety was 72.6% (TAV-in-bTAV) vs 71.2% (TAV-in-sTAV) (P = 0.817) and 73.2% (bTAV-in-TAV) vs 76.5% (sTAV-in-TAV) (P = 0.590). Device success was similar according to initial valve type but higher with subsequent sTAV vs bTAV (77.2% vs 64.3%; P = 0.045), primarily because of lower residual gradients (10.3 mm Hg [8.9-11.7 mm Hg] vs 15.2 mm Hg [13.2-17.1 mm Hg]; P < 0.001). Residual regurgitation (moderate or greater) was similar after bTAV-in-TAV and sTAV-in-TAV (5.7%) and nominally higher after TAV-in-bTAV (9.1%) vs TAV-in-sTAV (4.4%) (P = 0.176). CONCLUSIONS: In selected patients, no association was observed between TAV type and redo TAVR safety or mortality, yet subsequent sTAV was associated with higher device success because of lower redo gradients. These findings are preliminary, and more data are needed to guide valve choice for redo TAVR.

Risk of infective endocarditis after surgical and transcatheter aortic valve replacement.

OBJECTIVE: To define the incidence and risk factors for infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). METHODS: All patients who underwent first SAVR or TAVI in England between 2007 and 2016 were identified from the NICOR databases. Hospital admissions with a primary diagnosis of IE were identified by linkage with the NHS Hospital Episode Statistics database. Approval was obtained from the NHS Research Ethics Committee. RESULTS: 2057 of 91 962 patients undergoing SAVR developed IE over a median follow-up of 53.9 months-an overall incidence of 4.81 [95% CI 4.61 to 5.03] per 1000 person-years. Correspondingly, 140 of 14 195 patients undergoing TAVI developed IE over a median follow-up of 24.5 months-an overall incidence of 3.57 [95% CI 3.00 to 4.21] per 1000 person-years. The cumulative incidence of IE at 60 months was higher after SAVR than after TAVI (2.4% [95% CI 2.3 to 2.5] vs 1.5% [95% CI 1.3 to 1.8], HR 1.60, p<0.001). Across the entire cohort, SAVR remained an independent predictor of IE after multivariable adjustment. Risk factors for IE included younger age, male sex, atrial fibrillation, and dialysis. CONCLUSIONS: IE is a rare complication of SAVR and TAVI. In our population, the incidence of IE was higher after SAVR than after TAVI.

Two-year outcomes from the MitrAl ValvE RepaIr Clinical (MAVERIC) trial: a novel percutaneous treatment of functional mitral regurgitation.

AIMS: We report the 2-year outcomes of the MitrAl ValvE RepaIr Clinical (MAVERIC) trial. Functional mitral regurgitation (FMR) is associated with poor outcomes for which there remains an unmet clinical need. ARTO is a transcatheter annular reduction device for the treatment of FMR and an emerging alternative for patients at high surgical risk. The MAVERIC trial was designed to evaluate the safety and performance of the ARTO system in FMR and heart failure (HF). METHODS AND RESULTS: MAVERIC is an international multicentre, prospective, single arm study enrolling patients with FMR grade ≥ 2, New York Heart Association (NYHA) class ≥II symptoms despite maximal medical therapy. Patients were excluded if they had significant structural mitral valve abnormality or life expectancy <1 year. The primary outcome measures were a composite safety outcome and efficacy defined as mitral regurgitation (MR) reduction 30 days post-procedure. Secondary outcome measures included safety, change in MR grade, NYHA class and hospitalization for HF at 2 years. Forty-five patients were enrolled. The composite safety outcome was met (2/45 adverse events at 30 days) and no device-related deaths occurred at 2-year follow-up. A sustained reduction in MR [grade < 2: 21/31 (68%) vs. 31/31(0%); P < 0.0001], left ventricular end-diastolic volume index (90.0 ± 30 vs. 106 ± 26 mL/m2 ; P = 0.004) and anteroposterior diameter (35.5 ± 4.7 vs. 41.4 ± 4.6 mm; P < 0.0001) was seen at 2 years compared to baseline. Progressive symptomatic improvement [NYHA class ≤II: 27/34 (80%) vs. 12/34 (36%); P < 0.0001] and a reduction in HF hospitalizations (19.8% 2 years post vs. 52.3% 2 years prior; P < 0.001) were seen at 2 years compared to baseline. CONCLUSIONS: The ARTO system is a safe and effective treatment for FMR with reductions in left ventricular end-diastolic volumes sustained to 2 years.

Coagulation derangement and risk factors for valve thrombosis following transcatheter aortic valve implantation.

AIMS: Durability of transcatheter aortic valve implantation (TAVI) is key to its expansion. We sought to identify incidence of valve thrombosis and predictors of valve thrombosis in our single centre with associated coagulation testing pre-TAVI and post-TAVI. METHODS AND RESULTS: This single-centre observational study comprised patients undergoing transfemoral TAVI discussed in the Heart Team meeting . Patients were followed up with echocardiography at 120 days to identify incidence of elevated transvalvular gradient and multivariable analysis was performed to identify factors associated with an increased odds of developing valve thrombosis. In addition, 11 patients underwent baseline, day 1 and day 120 post-TAVI coagulation testing. Between August 2017 and August 2019, 437 consecutive patients underwent transfemoral TAVI. Of these patients, 207/437 (47.4%) had 3-month follow-up echo data available and were analysed. Of these patients, 26/207 (12.6%) had elevated transvalvular gradients. These patients tended to be younger (80±14 vs 83±6 years; p=0.047) with a lower ejection fraction (49±13 vs 54%±11%; p=0.021), with a greater proportion of the population experiencing atrial fibrillation (14/21, 54% vs 68/181, 38%; p=0.067). Following multivariable analysis, there remained a trend towards higher eccentricity index associated with elevated gradients. Baseline (pre-TAVI) elevation of thrombin antithrombin levels (56±63; reference range 1.0-4.1 ng/L) and PF 1+2 (791±632; reference range 69-229 ng/mL) normalised at 120 days post-TAVI CONCLUSION: This study demonstrated that in the cohort of patients undergoing transfemoral TAVI in our centre: younger age, poor ejection fraction, atrial fibrillation and increased baseline eccentricity of the aortic valve annulus were present to a greater extent in patients exhibiting elevated transvalvular gradients at 3-month follow-up. Further work is required to delineate the extent of coagulation derangement and confirm predictors of thrombosis.

Impact of coronary artery disease on contractile function and ventricular-arterial coupling during exercise: Simultaneous assessment of left-ventricular pressure-volume and coronary pressure and flow during cardiac catheterization.

Coronary artery disease (CAD) can adversely affect left ventricular (LV) performance during exercise by impairment of contractile function in the presence of increasing afterload. By performing invasive measures of LV pressure-volume and coronary pressure and flow during exercise, we sought to accurately measure this with comparison to the control group. Sixteen patients, with CCS class >II angina and CAD underwent invasive simultaneous measurement of left ventricular pressure-volume and coronary pressure and flow velocity during cardiac catheterization. Measurements performed at rest were compared with peak exercise using bicycle ergometry. The LV contractile function was measured invasively using the end-systolic pressure-volume relationship, a load independent marker of contractile function (Ees). Vascular afterload forces were derived from the ratio of LV end-systolic pressure to stroke volume to generate arterial elastance (Ea). These were combined to assess cardiovascular performance (ventricular-arterial [VA] coupling ratio [Ea/Ees]). Eleven patients demonstrated flow-limiting (FL) CAD (hyperemic Pd/Pa <0.80; ST-segment depression on exercise); five patients without flow-limiting (NFL) CAD served as the control group. Exercise in the presence of FL CAD was associated impairment of Ees, increased Ea, and deterioration of VA coupling. In the control cohort, exercise was associated with increased Ees and improved VA coupling. The backward compression wave energy directly correlated with the magnitude contraction as measured by dP/dTmax (r = 0.88, p = 0.004). This study demonstrates that in the presence of flow-limiting CAD, exercise to maximal effort can lead to impairment of LV contractile function and a deterioration in VA coupling compared to a control cohort.

Incidence, Causes, and Outcomes Associated With Urgent Implantation of a Supplementary Valve During Transcatheter Aortic Valve Replacement.

Importance: Transcatheter aortic valve replacement (TAVR) failure is often managed by an urgent implantation of a supplementary valve during the procedure (2-valve TAVR [2V-TAVR]). Little is known about the factors associated with or sequelae of 2V-TAVR. Objective: To examine the incidence, causes, and outcomes of 2V-TAVR. Design, Setting, and Participants: A retrospective cohort study was performed using data from an international registry of 21 298 TAVR procedures performed from January 1, 2014, through February 28, 2019. Among the 21 298 patients undergoing TAVR, 223 patients (1.0%) undergoing 2V-TAVR were identified. Patient-level data were available for all the patients undergoing 2V-TAVR and for 12 052 patients (56.6%) undergoing 1V-TAVR. After excluding patients with missing 30-day follow-up or data inconsistencies, 213 2V-TAVR and 10 010 1V-TAVR patients were studied. The 2V-TAVR patients were compared against control TAVR patients undergoing a 1-valve TAVR (1V-TAVR) using 1:4 17 propensity score matching. Final analysis included 1065 (213:852) patients. Exposures: Urgent implantation of a supplementary valve during TAVR. Main Outcomes and Measures: Mortality at 30 days and 1 year. Results: The 213 patients undergoing 2V-TAVR had similar age (mean [SD], 81.3 [0.5] years) and sex (110 [51.6%] female) as the 10 010 patients undergoing 1V-TAVR (mean [SD] age, 81.2 [0.5] years; 110 [51.6%] female). The 2V-TAVR incidence decreased from 2.9% in 2014 to 1.0% in 2018 and was similar between repositionable and nonrepositionable valves. Bicuspid aortic valve (odds ratio [OR], 2.20; 95% CI, 1.17-4.15; P = .02), aortic regurgitation of moderate or greater severity (OR, 2.02; 95% CI, 1.49-2.73; P < .001), atrial fibrillation (OR, 1.43; 95% CI, 1.07-1.93; P = .02), alternative access (OR, 2.59; 95% CI, 1.72-3.89; P < .001), early-generation valve (OR, 2.32; 95% CI, 1.69-3.19; P < .001), and self-expandable valve (OR, 1.69; 95% CI, 1.17-2.43; P = .004) were associated with higher 2V-TAVR risk. In 165 patients (80%), the supplementary valve was implanted because of residual aortic regurgitation after primary valve malposition (94 [46.4%] too high and 71 [34.2%] too low). In the matched 2V-TAVR vs 1V-TAVR cohorts, the rate of device success was 147 (70.4%) vs 783 (92.2%) (P < .001), the rate of coronary obstruction was 5 (2.3%) vs 3 (0.4%) (P = .10), stroke rate was 9 (4.6%) vs 13 (1.6%) (P = .09), major bleeding rates were 25 (11.8%) vs 46 (5.5%) (P = .03) and annular rupture rate was 7 (3.3%) vs 3 (0.4%) (P = .03). The hazard ratios for mortality were 2.58 (95% CI, 1.04-6.45; P = .04) at 30 days, 1.45 (95% CI, 0.84-2.51; P = .18) at 1 year, and 1.20 (95% CI, 0.77-1.88; P = .42) at 2 years. Nontransfemoral access and certain periprocedural complications were independently associated with higher risk of death 1 year after 2V-TAVR. Conclusions and Relevance: In this cohort study, valve malposition was the most common indication for 2V-TAVR. Incidence decreased over time and was low overall, although patients with a bicuspid or regurgitant aortic valve, nontransfemoral access, and early-generation or self-expandable valve were at higher risk. These findings suggest that compared with 1V-TAVR, 2V-TAVR is associated with high burden of complications and mortality at 30 days but not at 1 year.

Physiological Impact of Afterload Reduction on Cardiac Mechanics and Coronary Hemodynamics Following Isosorbide Dinitrate Administration in Ischemic Heart Disease.

Understanding the cardiac-coronary interaction is fundamental to developing treatment strategies for ischemic heart disease. We sought to examine the impact of afterload reduction following isosorbide dinitrate (ISDN) administration on LV properties and coronary hemodynamics to further our understanding of the cardiac-coronary interaction. Novel methodology enabled real-time simultaneous acquisition and analysis of coronary and LV hemodynamics in vivo using coronary pressure-flow wires (used to derive coronary wave energies) and LV pressure-volume loop assessment. ISDN administration resulted in afterload reduction, reduced myocardial demand, and increased mechanical efficiency (all P<0.01). Correlations were demonstrated between the forward compression wave (FCW) and arterial elastance (r=0.6) following ISDN. In the presence of minimal microvascular resistance, coronary blood flow velocity exhibited an inverse relationship with LV elastance. In summary this study demonstrated a reduction in myocardial demand with ISDN, an inverse relationship between coronary blood flow velocity and LV contraction-relaxation and a direct correlation between FCW and arterial elastance. The pressure volume-loop and corresponding parameters b The pressure volume loop before (solid line) and after (broken line) Isosorbide dintrate.

Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS): a double-blind randomised placebo-controlled crossover trial.

BACKGROUND: Glucagon-like peptide-1 receptor (GLP-1R) activation may improve myocardial performance in the context of ischaemia, independent of glycaemic control, in individuals with and without type 2 diabetes mellitus. METHODS: The LIONESS trial was a single-centre randomised double-blind placebo-controlled crossover study to determine whether prolonged GLP-1R activation could improve exercise haemodynamics in chronic stable angina patients. Eligibility criteria comprised angiographic evidence of obstructive coronary artery disease (CAD) and an abnormal baseline exercise tolerance test (ETT) demonstrating > 0.1 mV of planar or downsloping ST-segment depression (STD). Those randomised to active agent started with a 1-week run-in phase of 0.6 mg liraglutide daily, an established injectable GLP-1R agonist, followed by 1 week of 1.2 mg liraglutide, after which patients performed a week 2 ETT. Patients then self-administered 1.8 mg liraglutide for a week before completing a week 3 ETT. The placebo arm received visually and temporally matched daily saline injections. Participants then crossed over to a 3-week course of saline injections interspersed with a week 5 ETT and week 6 ETT and vice versa. Co-primary endpoints were rate pressure product (RPP) at 0.1 mV STD and magnitude of STD at peak exercise. RESULTS: Twenty-two patients (21 without diabetes) were randomised. There was no significant difference between saline versus liraglutide in the co-primary endpoints of RPP achieved at 0.1 mV STD (saline vs. liraglutide 1.2 mg p = 0.097; saline vs. liraglutide 1.8 mg p = 0.48) or the degree of STD at peak exercise (saline vs. liraglutide 1.2 mg p = 0.68; saline vs. liraglutide 1.8 mg p = 0.57). Liraglutide did not cause symptomatic hypoglycaemia, renal dysfunction, acute pancreatitis or provoke early withdrawal from the trial. Liraglutide significantly reduced weight (baseline 88.75 ± 16.5 kg vs. after liraglutide 87.78 ± 16.9 kg; p = 0.0008) and improved the lipid profile (mean total cholesterol: at baseline 3.97 ± 0.88 vs. after liraglutide 3.56 ± 0.71 mmol/L; p < 0.0001). CONCLUSION: Liraglutide did not enhance exercise tolerance or haemodynamics compared with saline placebo during serial treadmill testing in patients with established obstructive CAD. It did, however, significantly reduce weight and improve the lipid profile. Trial Registration ClinicalTrials.gov Identifier NCT02315001. Retrospectively registered on 11th December 2014.

Transcatheter Replacement of Transcatheter Versus Surgically Implanted Aortic Valve Bioprostheses.

BACKGROUND: Surgical aortic valve replacement and transcatheter aortic valve replacement (TAVR) are now both used to treat aortic stenosis in patients in whom life expectancy may exceed valve durability. The choice of initial bioprosthesis should therefore consider the relative safety and efficacy of potential subsequent interventions. OBJECTIVES: The aim of this study was to compare TAVR in failed transcatheter aortic valves (TAVs) versus surgical aortic valves (SAVs). METHODS: Data were collected on 434 TAV-in-TAV and 624 TAV-in-SAV consecutive procedures performed at centers participating in the Redo-TAVR international registry. Propensity score matching was applied, and 330 matched (165:165) patients were analyzed. Principal endpoints were procedural success, procedural safety, and mortality at 30 days and 1 year. RESULTS: For TAV-in-TAV versus TAV-in-SAV, procedural success was observed in 120 (72.7%) versus 103 (62.4%) patients (p = 0.045), driven by a numerically lower frequency of residual high valve gradient (p = 0.095), ectopic valve deployment (p = 0.081), coronary obstruction (p = 0.091), and conversion to open heart surgery (p = 0.082). Procedural safety was achieved in 116 (70.3%) versus 119 (72.1%) patients (p = 0.715). Mortality at 30 days was 5 (3%) after TAV-in-TAV and 7 (4.4%) after TAV-in-SAV (p = 0.570). At 1 year, mortality was 12 (11.9%) and 10 (10.2%), respectively (p = 0.633). Aortic valve area was larger (1.55 ± 0.5 cm2 vs. 1.37 ± 0.5 cm2; p = 0.040), and the mean residual gradient was lower (12.6 ± 5.2 mm Hg vs. 14.9 ± 5.2 mm Hg; p = 0.011) after TAV-in-TAV. The rate of moderate or greater residual aortic regurgitation was similar, but mild aortic regurgitation was more frequent after TAV-in-TAV (p = 0.003). CONCLUSIONS: In propensity score-matched cohorts of TAV-in-TAV versus TAV-in-SAV patients, TAV-in-TAV was associated with higher procedural success and similar procedural safety or mortality.

Baseline NT-proBNP Accurately Predicts Symptom Response to Transcatheter Aortic Valve Implantation.

Background Up to 30% of patients undergoing transcatheter aortic valve implantation (TAVI) experience minimal symptomatic benefit or die within 1 year, indicating an urgent need for enhanced patient selection. Previous analyses of baseline NT-proBNP (N-terminal pro-brain natriuretic peptide) and TAVI outcomes have assumed a linear relationship, yielding conflicting results. We reexamined the relationship between baseline NT-proBNP and symptomatic improvement after TAVI. Methods and Results Symptom status, clinical and echocardiographic data, and baseline NT-proBNP were reviewed from 144 consecutive patients undergoing TAVI for severe symptomatic aortic stenosis. The primary end point was change in New York Heart Association functional class at 1 year. There was a nonlinear, inverted-U relationship between log-baseline NT-proBNP and post-TAVI change in NYHA class (R2=0.4559). NT-proBNP thresholds of <800 and >10 000 ng/L accurately predicted no symptomatic improvement at 1 year (sensitivity 88%, specificity 83%, positive predictive value 72%, negative predictive value 93%). In adjusted analyses, baseline NT-proBNP outside this "sweet-spot" range was the only factor independently associated with poor functional outcome (high: NT-proBNP >10 000 ng/L, odds ratio [OR], 65; 95% CI, 6-664; low: NT-proBNP <800 ng/L, OR, 73; 95% CI, 7-738). Conclusions Baseline NT-proBNP is a useful prognostic marker to predict poor symptom relief after TAVI and may indicate when intervention is likely to be futile. Both low (<800 ng/L) and very high (>10 000 ng/L) levels are strongly associated with poor functional outcome, suggesting an alternative cause for symptoms in the former scenario and an irrevocably diseased left ventricle in the latter. Further evaluation of this relationship is warranted.

Incidence and outcomes of infective endocarditis following transcatheter aortic valve implantation.

INTRODUCTION: Prosthetic valve infective endocarditis is a feared and potentially catastrophic complication of valvular intervention. Transcatheter aortic valve implantation has transformed the modern management of aortic stenosis and vastly altered the demographics of those patients undergoing valve replacement. AREAS COVERED: As a relatively nascent development, what TAVI means for the epidemiology of infective endocarditis, how to identify those patients undergoing the procedure at greatest risk, and how best to prevent and manage the condition remains the subject of fervent research activity. In this review, we appraise relevant contemporary data discussing the incidence, microbiological profiles, associated risk factors and clinical outcomes of infective endocarditis after TAVI. EXPERT OPINION: Present outcomes are poor, with exceedingly high in-hospital and long-term mortality. Evidence to support surgical management in this patient group is lacking. Prevention is therefore paramount and a logical focus for future research attention.