LANDMARK comparison of early outcomes of newer-generation Myval transcatheter heart valve series with contemporary valves (Sapien and Evolut) in real-world individuals with severe symptomatic native aortic stenosis: a randomised non-inferiority trial.

BACKGROUND: Transcatheter aortic valve implantation is an established, guideline-endorsed treatment for severe aortic stenosis. Precise sizing of the balloon-expandable Myval transcatheter heart valve (THV) series with the aortic annulus is facilitated by increasing its diameter in 1·5 mm increments, compared with the usual 3 mm increments in valve size. The LANDMARK trial aimed to show non-inferiority of the Myval THV series compared with the contemporary THVs Sapien Series (Edwards Lifesciences, Irvine, CA, USA) or Evolut Series (Medtronic, Minneapolis, MN, USA). METHODS: In this prospective, multinational, randomised, open-label, non-inferiority trial across 31 hospitals in 16 countries (Germany, France, Sweden, the Netherlands, Italy, Spain, New Zealand, Portugal, Greece, Hungary, Poland, Slovakia, Slovenia, Croatia, Estonia, and Brazil), 768 participants with severe symptomatic native aortic stenosis were randomly assigned (1:1) to the Myval THV or a contemporary THV. Eligibility was primarily decided by the heart team in accordance with 2021 European Society of Cardiology guidelines. As per the criteria of the third Valve Academic Research Consortium, the primary endpoint at 30 days was a composite of all-cause mortality, all stroke, bleeding (types 3 and 4), acute kidney injury (stages 2-4), major vascular complications, moderate or severe prosthetic valve regurgitation, and conduction system disturbances resulting in a permanent pacemaker implantation. Non-inferiority of the study device was tested in the intention-to-treat population using a non-inferiority margin of 10·44% and assuming an event rate of 26·10%. This trial is registered with ClinicalTrials.gov, NCT04275726, and EudraCT, 2020-000137-40, and is closed to new participants. FINDINGS: Between Jan 6, 2021, and Dec 5, 2023, 768 participants with severe symptomatic native aortic stenosis were randomly assigned, 384 to the Myval THV and 384 to a contemporary THV. 369 (48%) participants had their sex recorded as female, and 399 (52%) as male. The mean age of participants was 80·0 years (SD 5·7) for those treated with the Myval THV and 80·4 years (5·4) for those treated with a contemporary THV. Median Society of Thoracic Surgeons scores were the same in both groups (Myval 2·6% [IQR 1·7-4·0] vs contemporary 2·6% [1·7-4·0]). The primary endpoint showed non-inferiority of the Myval (25%) compared with contemporary THV (27%), with a risk difference of -2·3% (one-sided upper 95% CI 3·8, pnon-inferiority<0·0001). No significant difference was seen in individual components of the primary composite endpoint. INTERPRETATION: In individuals with severe symptomatic native aortic stenosis, the Myval THV met its primary endpoint at 30 days. FUNDING: Meril Life Sciences.

Tricuspid valve disease and cardiac implantable electronic devices.

The role of cardiac implantable electronic device (CIED)-related tricuspid regurgitation (TR) is increasingly recognized as an independent clinical entity. Hence, interventional TR treatment options continuously evolve, surgical risk assessment and peri-operative care improve the management of CIED-related TR, and the role of lead extraction is of high interest. Furthermore, novel surgical and interventional tricuspid valve treatment options are increasingly applied to patients suffering from TR associated with or related to CIEDs. This multidisciplinary review article developed with electrophysiologists, interventional cardiologists, imaging specialists, and cardiac surgeons aims to give an overview of the mechanisms of disease, diagnostics, and proposes treatment algorithms of patients suffering from TR associated with CIED lead(s) or leadless pacemakers.

Understanding cardiac events in breast cancer (UCARE): pilot cardio-oncology assessment and surveillance pathway for breast cancer patients.

PURPOSE: In Ireland, over 3000 patients are diagnosed with breast cancer annually, and 1 in 9 Irish women will be diagnosed with breast cancer in their lifetime. There is evidence that female breast cancer survivors are more likely to die of cardiovascular disease than their age-matched counterparts. Specific services for cancer patients suffering from cancer therapy related cardiovascular toxicity have led to a higher incidence of safe anti-cancer treatment completion. Such services are not widely available in our jurisdiction, and the purpose of this trial is to remedy this situation. METHODS: This protocol describes a prospective, single arm, pilot feasibility study implementing a dedicated Cardio-Oncology assessment and surveillance pathway for patients receiving multimodal breast cancer treatment. It incorporates novel biomarker and radiomic surveillance and monitoring approaches for cancer-therapy related cardiac dysfunction into routine care for breast cancer patients undergoing adjuvant systemic chemotherapy. RESULTS: Declaration of results will via peer reviewed academic journals, and communicated directly to key knowledge users both nationally and internationally. This engagement will be critical to enable to healthcare services and policy sector make informed decisions or valuable changes to clinical practice, expenditure and/or systems development to support specialized Cardio-Oncology clinical pathways. All data is to be made available upon request. CONCLUSION: Dedicated cardio-oncology services have been recommended in recent literature to improve patient outcomes. Our protocol describes a feasibility study into the provision of such services for breast cancer.

A systematic review and meta-analysis of the efficacy and safety of Mavacamten therapy in international cohort of 524 patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a first-in-class cardiac myosin inhibitor, targets the main underlying pathology of HCM. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Mavacamten in patients with HCM. PRISMA flow chart was utilized using PubMed, SCOPUS, and Cochrane databases for all up-to-date studies using pre-defined keywords. Pre-specified efficacy outcomes comprised several parameters, including an improvement in peak oxygen consumption (pVO2) and ≥ 1 NYHA class, the need for septal reduction therapy (SRT), change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ), changes in biochemical markers and LVEF, along with peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Safety outcomes included morbidity and serious adverse events. This systematic review included five studies, four RCTs and one non-randomized control trial comprised a total of 524 (Mavacamten [273, 54.3%] vs placebo [230, 45.7%] adult (≥ 18 years) patients with a mean age of 56 years. The study. comprised patients with Caucasian and Chinese ethnicity and patients with obstructive (oHCM) and non-obstructive (nHCM) HCM. Most baseline characteristics were similar between the treatment and placebo groups. Mavacamten showed a statistically significant increase in the frequency of the primary composite endpoint (RR = 1.92, 95% CI [1.28, 2.88]), ≥ 1 NYHA class improvement (RR = 2.10, 95% CI [1.66, 2.67]), a significant decrease in LVEF, peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Mavacamten also showed a significant reduction in SRT rates (RR = 0.29, 95% CI [0.21, 0.40], p < 0.00001), KCCQ clinical summary scores (MD = 8.08, 95% CI [4.80, 11.37], P < 0.00001) troponin levels and N-terminal pro-B-type natriuretic peptide levels. However, there was no statistically significant difference between Mavacamten and placebo regarding the change from baseline peak oxygen consumption. Mavacamten use resulted in a small increase in adverse events but no statistically significant increment in serious adverse events. Our study showed that Mavacamten is a safe and effective treatment option for Caucasian and Chinese patients with HCM on the short-term. Further research is needed to explore the long-term safety and efficacy of Mavacamten with HCM. In addition, adequately powered studies including patients with nHCM is needed to ascertain befits of Mavacamten in those patients.

Intermittent levosimendan infusion in ambulatory patients with end-stage heart failure: a systematic review and meta-analysis of 984 patients.

We sought to synthesize the available evidence regarding safety and efficacy of intermittent levosimendan (LEVO) infusions in ambulatory patients with end-stage heart failure (HF). Safety and efficacy of ambulatory intermittent LEVO infusion in patients with end-stage HF are yet not established. We systematically searched MEDLINE, EMBASE, SCOPUS, Web of Science, and Cochrane databases, from inception to January 30, 2021 for studies reporting outcome of adult ambulatory patients with end-stage HF treated with intermittent LEVO infusion. Fifteen studies (8 randomized and 7 observational) comprised 984 patients (LEVO [N = 727] and controls [N = 257]) met the inclusion criteria. LEVO was associated with improved New York Heart Association (NYHA) functional class (weighted mean difference [WMD] -1.04, 95%CI: -1.70 to -0.38, p < 0.001, 5 studies, I2 = 93%), improved left ventricular (LV) ejection fraction (WMD 4.0%, 95%CI: 2.8% to 5.3%, p < 0.001, 6 studies, I2 = 9%), and reduced BNP levels (WMD -549 pg/mL, 95%CI -866 to -233, p < 0001, 3 studies, I2 = 66%). All-cause death was not different (RR 0.65, 95%CI: 0.38 to 1.093, p = 0.10, 6 studies, I2 = 0), but cardiovascular death was lower on LEVO (RR 0.34, 95%CI: 0.13 to 0.87, p = 0.02, 3 studies, I2 = 0) compared to controls. Furthermore, health-related quality of life (HRQoL) was improved alongside with reduced LV size following LEVO infusions. Major adverse events were not different between LEVO and placebo. In conclusion, intermittent LEVO infusions in ambulatory patients with end-stage HF is associated with less frequent cardiovascular death alongside with improved NYHA class, quality of life, BNP levels, and LV function. However, the current evidence is limited by heterogeneous and relatively small studies.

Genetic and RNA-related molecular markers of trastuzumab-chemotherapy-associated cardiotoxicity in HER2 positive breast cancer: a systematic review.

Cancer-therapy related cardiotoxicity (CTRCT) is a significant and frequent complication of monoclonal antibody directed therapy, especially Trastuzumab, for human epidermal growth factor receptor 2 (HER2) overexpressing breast cancers. Reliable, clinically available molecular predictive markers of CTRCT have not yet been developed. Identifying specific genetic variants and their molecular markers, which make the host susceptible to this complication is key to personalised risk stratification. A systematic review was conducted until April 2021, using the Medline, Embase databases and Google Scholar, to identify studies genetic and RNA-related markers associated with CTRCT in HER2 positive breast cancer patients. So far, researchers have mainly focused on HER2 related polymorphisms, revealing codons 655 and 1170 variants as the most likely SNPs associated with cardiotoxicity, despite some contradictory results. More recently, new potential genetic markers unrelated to the HER2 gene, and linked to known cardiomyopathy genes or to genes regulating cardiomyocytes apoptosis and metabolism, have been detected. Moreover, microRNAs are gaining increasing recognition as additional potential molecular markers in the cardio-oncology field, supported by encouraging preliminary data about their relationship with cardiotoxicity in breast cancers. In this review, we sought to synthesize evidence for genetic variants and RNA-related molecular markers associated with cardiotoxicity in HER2-positive breast cancer.

Right ventricular functional assessment by 2D multi-plane echocardiography prior to left ventricular assist device implantation.

OBJECTIVES: Right ventricular (RV) failure post left ventricular assist device (LVAD) implantation is associated with increased morbidity and mortality. A novel RV multi-plane imaging method using two-dimensional echocardiography and electronic plane rotation (MPE) was used to quantify RV function prior to LVAD implantation and to identify potential added value in this patient population. METHODS: In twenty-five end-stage heart failure patients (age 58.9 ± 6.8 years, 76% male), systolic function of four different RV walls (lateral, anterior, inferior and inferior coronal) were evaluated from one focussed apical view using MPE. RESULTS: Feasibility of tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular peak systolic velocity (RV-S') measurements were high (84-100%), with lower TAPSE values measured in the inferior (14.2 ± 4.6 mm) and inferior coronal (12.3 ± 5.0 mm) walls compared to the lateral (16.3 ± 4.5 mm) and anterior walls (16.0 ± 4.5 mm). RV wall longitudinal strain (RV-LS) measurement was most feasible in the lateral wall (80%; mean: -12.1 ± 4.2%). TAPSE and RV-LS values were significantly reduced in patients compared to matched healthy individuals (p = <0.001). Seven (28%) patients who developed moderate to severe RV failure (RVF) early post-implant (≤30 days) had lower pre-implant values across all multi-plane parameters compared to those without significant post-implant RVF, notably four-wall averaged TAPSE (11.1 ± 3.4 mm vs 15.9 ± 4.0 mm; p = 0.02). CONCLUSION: 2D MPE was highly feasible for RV wall quantification pre-LVAD surgery, detecting differences in regional wall function. This novel method comprehensively quantifies RV wall function and could complement current pre-LVAD screening protocols.

Rationale and design of a randomized clinical trial comparing safety and efficacy of myval transcatheter heart valve versus contemporary transcatheter heart valves in patients with severe symptomatic aortic valve stenosis: The LANDMARK trial.

BACKGROUND: The recent approval of transcatheter aortic valve replacement (TAVR) in patients with low operative risk has paved the way for the introduction of novel and potentially improved technologies. The safety and efficacy of these novel technologies should be investigated in randomized control trials against the contemporary TAVR devices. The objective of the LANDMARK trial is to compare the balloon-expandable Myval transcatheter heart valve (THV) series with contemporary THV (SAPIEN THV and Evolut THV series) series in patients with severe symptomatic native aortic stenosis. METHODS/DESIGN: The LANDMARK trial (ClinicalTrials.govNCT04275726, EudraCT number 2020-000,137-40) is a prospective, randomized, multinational, multicenter, open-label, and noninferiority trial of approximately 768 patients treated with TAVR via the transfemoral approach. Patients will be allocated in a 1:1 randomization to Myval THV series (n = 384) or to contemporary THV (n = 384) (either of SAPIEN THV or Evolut THV series). The primary combined safety and efficacy endpoint is a composite of all-cause mortality, all stroke (disabling and nondisabling), bleeding (life-threatening or disabling), acute kidney injury (stage 2 or 3), major vascular complications, prosthetic valve regurgitation (moderate or severe), and conduction system disturbances (requiring new permanent pacemaker implantation), according to the Valve Academic Research Consortium-2 criteria at 30-day follow-up. All patients will have follow-up to 10 years following TAVR. SUMMARY: The LANDMARK trial is the first randomized head-to-head trial comparing Myval THV series to commercially available THVs in patients indicated for TAVR. We review prior data on head-to-head comparisons of TAVR devices and describe the rationale and design of the LANDMARK trial.

External validation of the GRACE risk score 2.0 in the contemporary all-comers GLOBAL LEADERS trial.

OBJECTIVES: This study aimed to assess the predictive ability of the Global Registry of Acute Coronary Events (GRACE) risk score 2.0 in contemporary acute coronary syndrome (ACS) patients, and its relation to antiplatelet strategies. BACKGROUND: The predictive value of the GRACE risk score in the contemporary ACS cohort and the appropriate antiplatelet regimen according to the risk remain unclear. METHODS: This is a subgroup analysis of the all-comers, randomized GLOBAL LEADERS trial, comparing ticagrelor monotherapy versus conventional dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). The GRACE risk score 2.0 with 1-year mortality prediction was implemented. The randomized antiplatelet effect was assessed in predefined three GRACE risk-groups; low-risk (GRACE <109), moderate-risk (GRACE 109-140), and high-risk (GRACE >140). RESULTS: The GRACE risk score was available in 6,594 out of 7,487 ACS patients among whom 1,743, 2,823, and 2,028 patients were classified as low-risk, moderate-risk, and high-risk, respectively. At 1 year, all-cause mortality occurred in 120 patients (1.8%). The discrimination ability of the GRACE model was moderate (C-statistic = 0.742), whereas 1-year mortality risk was overestimated (mean predicted mortality rate: 3.9%; the Hosmer-Lemeshow chi-square: 21.47; p = 0.006). There were no significant interactions between the GRACE risk strata and effects of the ticagrelor monotherapy on ischemic or bleeding outcomes at 1 year compared to the reference strategy. CONCLUSION: The GRACE risk score 2.0 is valuable in discriminating high risk ACS patients, however, the recalibration of the score is recommended for better risk stratification. There is no significant differences in efficacy and safety of ticagrelor monotherapy across the three GRACE risk strata.

The Effectiveness of Levosimendan on Veno-Arterial Extracorporeal Membrane Oxygenation Management and Outcome: A Systematic Review and Meta-Analysis.

OBJECTIVES: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides a temporary support system for patients with cardiogenic shock refractory to conventional medical therapies. It has been reported that levosimendan may facilitate VA-ECMO weaning and improve survival. The primary objective of this review was to examine the effect of levosimendan use on VA-ECMO weaning and mortality in critically ill patients on VA-ECMO. DESIGN: MEDLINE, EMBASE, and CENTRAL were searched. A pair of reviewers identified eligible clinical trials. Two reviewers extracted data and independently assessed the risk of bias. A random-effect model was used to combine data. The primary outcome was the success of weaning from VA-ECMO. MEASUREMENTS AND MAIN RESULTS: Seven studies of observational design, including a total of 630 patients, were selected in the final analysis. The sample size ranged from ten-to-240 patients, with a mean age between 53 and 65 years, and more than half of them underwent cardiac surgeries. The VA-ECMO durations varied between four and 11.6 days. Overall, levosimendan use was significantly associated with successful weaning compared with control (odds ratio [OR] 2.89, 95% CI, 1.53-5.46; poverall effect = 0.001); I2 = 49%). For survival, six studies (n = 617) were included in the meta-analysis involving 326 patients in the levosimendan group and 291 in the comparator group. Pooled results showed a significantly higher survival rate in the levosimendan group (OR 0.46, 95% CI, 0.30-0.71; poverall effect = 0.0004; I2 = 20%). CONCLUSIONS: Levosimendan therapy was significantly associated with successful weaning and survival benefit in patients with cardiogenic or postcardiotomy shock needing VA-ECMO support for severe cardiocirculatory compromise. To date, there is limited literature and absence of evidence from randomized trials addressing the use of levosimendan in VA-ECMO weaning. This study may be considered a hypothesis-generating research for randomized controlled trials to confirm its findings.

Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study.

AIMS: It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China. Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection. Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs. 1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17-3.82, P = 0.013]. Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs. 3.2%, adjusted HR 2.17, 95% CI 1.03-4.57, P = 0.041). The mortality rates were similar between the renin-angiotensin-aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs. 3.6%, adjusted HR 0.85, 95% CI 0.28-2.58, P = 0.774). However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45-0.94, P = 0.20). CONCLUSION: While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19. However, the results should be considered as exploratory and interpreted cautiously.

Uncertainties and challenges in surgical and transcatheter tricuspid valve therapy: a state-of-the-art expert review.

Tricuspid regurgitation (TR) is a frequent and complex problem, commonly combined with left-sided heart disease, such as mitral regurgitation. Significant TR is associated with increased mortality if left untreated or recurrent after therapy. Tricuspid regurgitation was historically often disregarded and remained undertreated. Surgery is currently the only Class I Guideline recommended therapy for TR, in the form of annuloplasty, leaflet repair, or valve replacement. As growing experience of transcatheter therapy in structural heart disease, many dedicated transcatheter tricuspid repair or replacement devices, which mimic well-established surgical techniques, are currently under development. Nevertheless, many aspects of TR are little understood, including the disease process, surgical or interventional risk stratification, and predictors of successful therapy. The optimal treatment timing and the choice of proper surgical or interventional technique for significant TR remain to be elucidated. In this context, we aim to highlight the current evidence, underline major controversial issues in this field and present a future roadmap for TR therapy.

Safety and efficacy of a sirolimus-eluting coronary stent with ultra-thin strut for treatment of atherosclerotic lesions (TALENT): a prospective multicentre randomised controlled trial.

BACKGROUND: Supraflex is a sirolimus-eluting stent with a biodegradable polymer coating and ultra-thin struts. We aimed to compare Supraflex with the standard of care, Xience, an everolimus-eluting stent with a durable polymer coating, regarding clinical outcomes with a randomised trial in an all-comer population. METHODS: We did a prospective, randomised, single-blind, multicentre study (TALENT) across 23 centres in Europe (the Netherlands, Poland, the UK, Spain, Bulgaria, Hungary, and Italy). Eligible participants were aged 18 years or older, had one or more coronary artery stenosis of 50% or greater in a native coronary artery, saphenous venous graft, or arterial bypass conduit, and had a reference vessel diameter of 2·25-4·50 mm. Patients underwent percutaneous coronary intervention in an all-comer manner. We randomly assigned patients (1:1) to implantation of either a sirolimus-eluting stent with a biodegradable polymer coating and ultra-thin struts (Supraflex) or an everolimus-eluting stent with a durable polymer coating (Xience). Randomisation was done by local investigators by use of a web-based software with random blocks according to centre. The primary endpoint was a non-inferiority comparison of a device-oriented composite endpoint-cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation-between groups at 12 months after the procedure, assessed in an intention-to-treat population. On assumption of 1-year composite endpoint prevalence of 8·3%, a margin of 4·0% was defined for non-inferiority of the Supraflex group compared with the Xience group. This trial is registered with ClinicalTrials.gov, number NCT02870140. FINDINGS: Between Oct 21, 2016, and July 3, 2017, 1435 patients with 1046 lesions were randomly assigned to Supraflex, of whom 720 received the index procedure, and 715 patients with 1030 lesions were assigned to Xience, all receiving the index procedure. At 12 months, the primary endpoint had occurred in 35 patients (4·9 %) in the Supraflex group and in 37 patients (5·3%) in the Xience group (absolute difference -0·3% [one-sided 95% upper confidence bound 1·6%], pnon-inferiority<0·0001). Definite or probable stent thrombosis prevalence, a safety indicator, was low in both groups and did not differ between them. INTERPRETATION: The Supraflex stent was non-inferior to the Xience stent for a device-oriented composite clinical endpoint at 12 months in an all-comer population. Supraflex seems a safe and effective alternative drug-eluting stent to other stents in clinical practice. FUNDING: European Cardiovascular Research Institute.

Impact of Continuous Flow Left Ventricular Assist Device Therapy on Chronic Kidney Disease: A Longitudinal Multicenter Study.

BACKGROUND: Many patients undergoing durable left ventricular assist device (LVAD) implantation suffer from chronic kidney disease (CKD). Therefore, we investigated the effect of LVAD support on CKD. METHODS: A retrospective multicenter cohort study, including all patients undergoing LVAD (HeartMate II (n = 330), HeartMate 3 (n = 22) and HeartWare (n = 48) implantation. In total, 227 (56.8%) patients were implanted as bridge-to-transplantation; 154 (38.5%) as destination therapy; and 19 (4.7%) as bridge-to-decision. Serum creatinine measurements were collected over a 2-year follow-up period. Patients were stratified based on CKD stage. RESULTS: Overall, 400 patients (mean age 53 ± 14 years, 75% male) were included: 186 (46.5%) patients had CKD stage 1 or 2; 93 (23.3%) had CKD stage 3a; 82 (20.5%) had CKD stage 3b; and 39 (9.8%) had CKD stage 4 or 5 prior to LVAD implantation. During a median follow-up of 179 days (IQR 28-627), 32,629 creatinine measurements were available. Improvement of kidney function was noticed in every preoperative CKD-stage group. Following this improvement, estimated glomerular filtration rates regressed to baseline values for all CKD stages. Patients showing early renal function improvement were younger and in worse preoperative condition. Moreover, survival rates were higher in patients showing early improvement (69% vs 56%, log-rank P = 0 .013). CONCLUSIONS: Renal function following LVAD implantation is characterized by improvement, steady state and subsequent deterioration. Patients who showed early renal function improvement were in worse preoperative condition, however, and had higher survival rates at 2 years of follow-up.

Advances in transcatheter mitral and tricuspid therapies.

BACKGROUND: While rheumatic mitral stenosis has been effectively treated percutaneously for more than 20 years, mitral and tricuspid regurgitation treatment appear as a contemporary unmet need. The advent of transcatheter therapies offer new treatment options to often elderly and frail patients at high risk for open surgery. We aimed at providing an updated review of fast-growing domain of transcatheter mitral and tricuspid technology. MAIN BODY: We reviewed the existing literature on mitral and tricuspid transcatheter therapies. Mitraclip is becoming an established therapy for secondary mitral regurgitation in selected patients with disproportionately severe regurgitation associated with moderate left ventricle dysfunction. Evidence is less convincing for primary mitral regurgitation. Transcatheter mitral valve replacement is a promising emerging alternative to transcatheter repair, for secondary as well as primary mitral regurgitation. But further development is needed to improve delivery. Transcatheter tricuspid intervention arrives late after similar technologies have been developed for aortic and mitral valves and is currently at its infancy. This is likely due in part to previously under-recognized impact of tricuspid regurgitation on patient outcomes. Edge-to-edge repair is the most advanced transcatheter solution in development. Data on tricuspid annuloplasty and replacement is limited, and more research is warranted. CONCLUSION: The future appears bright for transcatheter mitral therapies, albeit their place in clinical practice is yet to be clearly defined. Tricuspid transcatheter therapies might address the unmet need of tricuspid regurgitation treatment.

Impact of long-term ticagrelor monotherapy following 1-month dual antiplatelet therapy in patients who underwent complex percutaneous coronary intervention: insights from the Global Leaders trial.

AIMS: To evaluate the impact of an experimental strategy [23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT)] vs. a reference regimen (12-month aspirin monotherapy following 12-month DAPT) after complex percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the present post hoc analysis of the Global Leaders trial, the primary endpoint [composite of all-cause death or new Q-wave myocardial infarction (MI)] at 2 years was assessed in patients with complex PCI, which includes at least one of the following characteristics: multivessel PCI, ≥3 stents implanted, ≥3 lesions treated, bifurcation PCI with ≥2 stents, or total stent length >60 mm. In addition, patient-oriented composite endpoint (POCE) (composite of all-cause death, any stroke, any MI, or any revascularization) and net adverse clinical events (NACE) [composite of POCE or Bleeding Academic Research Consortium (BARC) Type 3 or 5 bleeding] were explored. Among 15 450 patients included in this analysis, 4570 who underwent complex PCI had a higher risk of ischaemic and bleeding events. In patients with complex PCI, the experimental strategy significantly reduced risks of the primary endpoint [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.48-0.85] and POCE (HR: 0.80, 95% CI: 0.69-0.93), but not in those with non-complex PCI (Pinteraction = 0.015 and 0.017, respectively). The risk of BARC Type 3 or 5 bleeding was comparable (HR: 0.97, 95% CI: 0.67-1.40), resulting in a significant risk reduction in NACE (HR: 0.80, 95% CI: 0.69-0.92; Pinteraction = 0.011). CONCLUSION: Ticagrelor monotherapy following 1-month DAPT could provide a net clinical benefit for patients with complex PCI. However, in view of the overall neutral results of the trial, these findings of a post hoc analysis should be considered as hypothesis generating.

Derivation and Validation of a Novel Right-Sided Heart Failure Model After Implantation of Continuous Flow Left Ventricular Assist Devices: The EUROMACS (European Registry for Patients with Mechanical Circulatory Support) Right-Sided Heart Failure Risk Score.

BACKGROUND: The aim of the study was to derive and validate a novel risk score for early right-sided heart failure (RHF) after left ventricular assist device implantation. METHODS: The EUROMACS (European Registry for Patients with Mechanical Circulatory Support) was used to identify adult patients undergoing continuous-flow left ventricular assist device implantation with mainstream devices. Eligible patients (n=2988) were randomly divided into derivation (n=2000) and validation (n=988) cohorts. The primary outcome was early (<30 days) severe postoperative RHF, defined as receiving short- or long-term right-sided circulatory support, continuous inotropic support for ≥14 days, or nitric oxide ventilation for ≥48 hours. The secondary outcome was all-cause mortality and length of stay in the intensive care unit. Covariates found to be associated with RHF (exploratory univariate P<0.10) were entered into a multivariable logistic regression model. A risk score was then generated using the relative magnitude of the exponential regression model coefficients of independent predictors at the last step after checking for collinearity, likelihood ratio test, c index, and clinical weight at each step. RESULTS: A 9.5-point risk score incorporating 5 variables (Interagency Registry for Mechanically Assisted Circulatory Support class, use of multiple inotropes, severe right ventricular dysfunction on echocardiography, ratio of right atrial/pulmonary capillary wedge pressure, hemoglobin) was created. The mean scores in the derivation and validation cohorts were 2.7±1.9 and 2.6±2.0, respectively (P=0.32). RHF in the derivation cohort occurred in 433 patients (21.7%) after left ventricular assist device implantation and was associated with a lower 1-year (53% versus 71%; P<0.001) and 2-year (45% versus 58%; P<0.001) survival compared with patients without RHF. RHF risk ranged from 11% (low risk score 0-2) to 43.1% (high risk score >4; P<0.0001). Median intensive care unit stay was 7 days (interquartile range, 4-15 days) versus 24 days (interquartile range, 14-38 days) in patients without versus with RHF, respectively (P<0.001). The c index of the composite score was 0.70 in the derivation and 0.67 in the validation cohort. The EUROMACS-RHF risk score outperformed (P<0.0001) previously published scores and known individual echocardiographic and hemodynamic markers of RHF. CONCLUSIONS: This novel EUROMACS-RHF risk score outperformed currently known risk scores and clinical predictors of early postoperative RHF. This novel score may be useful for tailored risk-based clinical assessment and management of patients with advanced HF evaluated for ventricular assist device therapy.

Clinical outcomes of the Lotus Valve in patients with bicuspid aortic valve stenosis: An analysis from the RESPOND study.

AIMS: Patients with bicuspid valves represent a challenging anatomical subgroup for transcatheter aortic valve implantation (TAVI). This analysis evaluated the clinical outcomes of the fully repositionable and retrievable Lotus Valve System in patients with bicuspid aortic valves enrolled in the RESPOND post-market registry. METHODS AND RESULTS: The prospective, open-label RESPOND study enrolled 1,014 patients at 41 centers in Europe, New Zealand, and Latin America, 31 (3.1%) of whom had bicuspid aortic valves. The mean age in the bicuspid patient cohort was 76.4 years, 64.5% were male, and the baseline STS score was 6.0 ± 10.2. Procedural success was 100%, with no cases of malpositioning, valve migration, embolization, or valve-in-valve. Repositioning was attempted in 10 cases (32.3%). There was one death (3.2%) and one stroke (3.2%) at 30-day follow-up. Mean AV gradient was reduced from 48.7 ± 17.0 mmHg at baseline to 11.8 ± 5.1 mmHg at hospital discharge (P < 0.001); mean effective orifice area (EOA) was increased from 0.6 ± 0.2 cm2 to 1.7 ± 0.4 cm2 (P < 0.001). There were no cases of moderate or severe paravalvular leak (PVL) adjudicated by the core laboratory; four subjects (13.8%) had mild PVL, 5 (17.2%) had trace PVL. The rate of pacemaker (PM) implantation for PM-naïve patients was 22.2% (6/27). CONCLUSIONS: Data from the RESPOND registry demonstrate good clinical and echocardiographic outcomes up to 1 year postimplantation in patients with bicuspid aortic valves using the repositionable Lotus Valve.

Feasibility study of a synchronized diastolic injection with low contrast volume for proper quantitative assessment of aortic regurgitation in porcine models.

OBJECTIVES: To evaluate the in vivo feasibility of aortography with one accurately timed diastolic low-volume contrast injection for quantitative assessment of aortic regurgitation (AR) post transcatheter aortic valve replacement (TAVR). BACKGROUND: With the rise of a minimalistic approach for TAVR, aortography (re)emerges as a pragmatic tool for AR assessment. In a mock circulation system, we have validated the accuracy of a single diastolic injection triggered by electrocardiogram (ECG) with low-contrast volume. METHODS: Two-phase experiment: first, a series of aortograms were performed in a porcine model, with 8 mL of contrast using the synchronized (SYNC) and the conventional non-synchronized (NS) injections. In a second phase, we developed a model of AR by inserting partially unsheathed Wallstents of 6-10 mm of diameter across the pig's aortic valve, performing SYNC injections with 8 mL of contrast and NS injections with 8 mL and 15 mL (rate: 20 mL/sec). Respective accuracies of SYNC vs. NS were assessed using Passing-Bablock regression. An angiography core laboratory performed quantitative AR assessment with videodensitometry (VD-AR). RESULTS: The SYNC injections produced higher opacification of the aortic root compared with NS injections (P = 0.04 for density). In the second phase, a regression line for predicting VD-AR based on the SYNC injection resulted in a lower intercept and a slope closer to the line of identity (y = 11.9 + 0.79x, P < 0.001, r2 = 0.94) with the NS-8 mL than with the NS-15 mL injection (y = 26.5 + 0.55x, P < 0.001, r2 = 0.81). CONCLUSION: Synchronized diastolic injection with low contrast volume produced denser images in the aortic root and more accurate than the conventional injection; thus, may be an appealing alternative for assessment of AR post TAVR.