Merging virtual and physical experiences: extended realities in cardiovascular medicine.

Technological advancement and the COVID-19 pandemic have brought virtual learning and working into our daily lives. Extended realities (XR), an umbrella term for all the immersive technologies that merge virtual and physical experiences, will undoubtedly be an indispensable part of future clinical practice. The intuitive and three-dimensional nature of XR has great potential to benefit healthcare providers and empower patients and physicians. In the past decade, the implementation of XR into cardiovascular medicine has flourished such that it is now integrated into medical training, patient education, pre-procedural planning, intra-procedural visualization, and post-procedural care. This review article discussed how XR could provide innovative care and complement traditional practice, as well as addressing its limitations and considering its future perspectives.

An Era of Digital Healthcare-A Comprehensive Review of Sensor Technologies and Telehealth Advancements in Chronic Heart Failure Management.

Heart failure (HF) is a multi-faceted, complex clinical syndrome characterized by significant morbidity, high mortality rate, reduced quality of life, and rapidly increasing healthcare costs. A larger proportion of these costs comprise both ambulatory and emergency department visits, as well as hospital admissions. Despite the methods used by telehealth (TH) to improve self-care and quality of life, patient outcomes remain poor. HF management is associated with numerous challenges, such as conflicting evidence from clinical trials, heterogeneity of TH devices, variability in patient inclusion and exclusion criteria, and discrepancies between healthcare systems. A growing body of evidence suggests there is an unmet need for increased individualization of in-hospital management, continuous remote monitoring of patients pre and post-hospital admission, and continuation of treatment post-discharge in order to reduce re-hospitalizations and improve long-term outcomes. This review summarizes the current state-of-the-art for HF and associated novel technologies and advancements in the most frequently used types of TH (implantable sensors), categorizing devices in their preclinical and clinical stage, bench-to-bedside implementation challenges, and future perspectives on remote HF management to improve long-term outcomes of HF patients. The Review also highlights recent advancements in non-invasive remote monitoring technologies demonstrated by a few pilot observational prospective cohort studies.

Ten-Year All-Cause Death According to Completeness of Revascularization in Patients With Three-Vessel Disease or Left Main Coronary Artery Disease: Insights From the SYNTAX Extended Survival Study.

BACKGROUND: Ten-year all-cause death according to incomplete (IR) versus complete revascularization (CR) has not been fully investigated in patients with 3-vessel disease and left main coronary artery disease undergoing percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). METHODS: The SYNTAX Extended Survival study (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]) evaluated vital status up to 10 years in patients who were originally enrolled in the SYNTAX trial. In the present substudy, outcomes of the CABG CR group were compared with the CABG IR, PCI CR, and PCI IR groups. In addition, in the PCI cohort, the residual SYNTAX score (rSS) was used to quantify the extent of IR and to assess its association with fatal late outcome. The rSS of 0 suggests CR, whereas a rSS>0 identifies the degree of IR. RESULTS: IR was more frequently observed in patients with PCI versus CABG (56.6% versus 36.8%) and more common in those with 3-vessel disease than left main coronary artery disease in both the PCI arm (58.5% versus 53.8%) and the CABG arm (42.8% versus 27.5%). Patients undergoing PCI with CR had no significant difference in 10-year all-cause death compared with those undergoing CABG (22.2% for PCI with CR versus 24.3% for CABG with IR versus 23.8% for CABG with CR). In contrast, those with PCI and IR had a significantly higher risk of all-cause death at 10 years compared with CABG and CR (33.5% versus 23.7%; adjusted hazard ratio, 1.48 [95% CI, 1.15-1.91]). When patients with PCI were stratified according to the rSS, those with a rSS≤8 had no significant difference in all-cause death at 10 years as the other terciles (22.2% for rSS=0 versus 23.9% for rSS>0-4 versus 28.9% for rSS>4-8), whereas a rSS>8 had a significantly higher risk of 10-year all-cause death than those undergoing PCI with CR (50.1% versus 22.2%; adjusted hazard ratio, 3.40 [95% CI, 2.13-5.43]). CONCLUSIONS: IR is common after PCI, and the degree of incompleteness was associated with 10-year mortality. If it is unlikely that complete (or nearly complete; rSS<8) revascularization can be achieved with PCI in patients with 3-vessel disease, CABG should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00114972. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03417050.

Angiography-derived physiology guidance vs usual care in an All-comers PCI population treated with the healing-targeted supreme stent and Ticagrelor monotherapy: PIONEER IV trial design.

BACKGROUND: Current ESC guidelines recommend the use of intra-coronary pressure guidewires for functional assessment of intermediate-grade coronary stenoses. Angiography-derived quantitative flow ratio (QFR) is a novel method of assessing these stenoses, and guiding percutaneous coronary intervention (PCI). METHODS/DESIGN: The PIONEER IV trial is a prospective, all-comers, multi-center trial, which will randomize 2,540 patients in a 1:1 ratio to PCI guided by angiography-derived physiology or usual care, with unrestricted use in both arms of the Healing-Targeted Supreme sirolimus-eluting stent (HT Supreme). The stent's fast, biologically healthy, and robust endothelial coverage allows for short dual-antiplatelet therapy (DAPT); hence the antiplatelet regimen of choice is 1-month DAPT, followed by ticagrelor monotherapy. In the angiography-derived physiology guided arm, lesions will be functionally assessed using on-line QFR, with stenting indicated in lesions with a QFR ≤0.80. Post-stenting, QFR will be repeated in the stented vessel(s), with post-dilatation or additional stenting recommended if the QFR<0.91 distal to the stent, or if the delta QFR (across the stent) is >0.05. Usual care PCI is performed according to standard clinical practice. The primary endpoint is a non-inferiority comparison of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, any myocardial infarction, or any clinically, and physiologically driven revascularization with a non-inferiority risk-difference margin of 3.2%, at 1-year post-procedure. Clinical follow-up will be up to 3 years. SUMMARY: The PIONEER IV trial aims to demonstrate non-inferiority of QFR-guided PCI to usual care PCI with respect to POCE at 1-year in patients treated with HT Supreme stents and ticagrelor monotherapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov UNIQUE IDENTIFIER: NCT04923191 CLASSIFICATIONS: Interventional Cardiology.

The Utility of the SYNTAX Score II and SYNTAX Score 2020 for Identifying Patients with Three-Vessel Disease Eligible for Percutaneous Coronary Intervention in the Multivessel TALENT Trial: A Prospective Pilot Experience.

Background: Personalized prognosis plays a vital role in deciding between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel disease (3VD). The aim of this study is to compare the modality of revascularization chosen by the local heart team to that recommended by using individualized predictions of medium, and long-term all-cause mortality amongst patients with 3VD screened in the Multivessel TALENT trial. Methods: The SYNTAX score II (SS-II) and SS-2020 were evaluated in 200 consecutive patients by a core laboratory and compared to the decision of the "on site" heart team. Results: According to the SS-II, CABG was the recommended treatment in 51 patients (25.5%) however 34 (66.6%) of them received PCI. According to SS-2020 the predicted absolute risk differences (ARD) between PCI and CABG were significantly higher in patients receiving CABG compared to those treated by PCI for major adverse cardiovascular and cerebrovascular events, a composite of all-cause mortality, stroke or myocardial infarction at 5-years (8.8 ± 4.6% vs 6.0 ± 4.0%, p < 0.001) and all-cause mortality at 5- (5.2 ± 3.5% vs 3.7 ± 3.0%, p = 0.008) and 10-years (9.3 ± 4.8% vs 6.2 ± 4.2%, p < 0.001). Based on the novel threshold of equipoise (individual absolute risk differences [ARD] < 4.5%), 133 patients were eligible for PCI however 23 of them underwent CABG; conversely, amongst the 67 patients where CABG was recommendation (individual ARD > 4.5%), only 19 received it. Conclusions: Despite the robustness of the risk models proposed for screening, several deviations from the recommended mode of revascularization were observed by the core laboratory among the first 200 patients with 3VD screened in the Multivessel TALENT trial. Clinical Trial Registration: ClinicalTrials.gov reference: NCT04390672.

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.

Design and Haemodynamic Analysis of a Novel Anchoring System for Central Venous Pressure Measurement.

BACKGROUND/OBJECTIVE: In recent years, treatment of heart failure patients has proved to benefit from implantation of pressure sensors in the pulmonary artery (PA). While longitudinal measurement of PA pressure profoundly improves a clinician's ability to manage HF, the full potential of central venous pressure as a clinical tool has yet to be unlocked. Central venous pressure serves as a surrogate for the right atrial pressure, and thus could potentially predict a wider range of heart failure conditions. However, it is unclear if current sensor anchoring methods, designed for the PA, are suitable to hold pressure sensors safely in the inferior vena cava. The purpose of this study was to design an anchoring system for accurate apposition in inferior vena cava and evaluate whether it is a potential site for central venous pressure measurement. MATERIALS AND METHODS: A location inferior to the renal veins was selected as an optimal site based on a CT scan analysis. Three anchor designs, a 10-strut anchor, and 5-struts with and without loops, were tested on a custom-made silicone bench model of Vena Cava targeting the infra-renal vena cava. The model was connected to a pulsatile pump system and a heated water bath that constituted an in-vitro simulation unit. Delivery of the inferior vena cava implant was accomplished using a preloaded introducer and a dilator as a push rod to deploy the device at the target area. The anchors were subjected to manual compression tests to evaluate their stability against dislodgement. Computational Fluid Dynamics (CFD) analysis was completed to characterize blood flow in the anchor's environment using pressure-based transient solver. Any potential recirculation zones or disturbances in the blood flow caused by the struts were identified. RESULTS: We demonstrated successful anchorage and deployment of the 10-strut anchor in the Vena Cava bench model. The 10-strut anchor remained stable during several compression attempts as compared with the other two 5-strut anchor designs. The 10-strut design provided the maximum number of contact points with the vessel in a circular layout and was less susceptible to movement or dislodgement during compression tests. Furthermore, the CFD simulation provided haemodynamic analysis of the optimum 10-strut anchor design. CONCLUSIONS: This study successfully demonstrated the design and deployment of an inferior vena cava anchoring system in a bench test model. The 10-strut anchor is an optimal design as compared with the two other 5-strut designs; however, substantial in-vivo experiments are required to validate the safety and accuracy of such implants. The CFD simulation enabled better understanding of the haemodynamic parameters and any disturbances in the blood flow due to the presence of the anchor. The ability to place a sensor technology in the vena cava could provide a simple and minimally invasive approach for heart failure patients.

Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial.

BACKGROUND: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. METHODS: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. FINDINGS: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months. INTERPRETATION: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. FUNDING: Medtronic.

Usefulness of updated logistic clinical SYNTAX score based on MI-SYNTAX score in patients with ST-elevation myocardial infarction.

OBJECTIVES: To compare the predictive performances of the prewiring, postwiring MI-SYNTAX scores, prewiring, and postwiring Updated Logistic Clinical SYNTAX score (LCSS) for 2-year all-cause mortality post percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients. BACKGROUND: In patients with STEMI and undergoing primary PCI, coronary stenosis(es) distal to the culprit lesion is often observed after the restoration of coronary flow. To address comprehensively the complex coronary anatomy in these patients, prewiring and postwiring MI-SYNTAX scores have been reported in the literature. Furthermore, to enable individualized risk estimation for long-term all-cause mortality, the Updated LCSS has been developed by combining the anatomical SYNTAX score and clinical factors. METHODS: In the randomized GLOBAL LEADERS trial, anatomical SYNTAX score analysis was performed by an independent angiographic corelab for the first 4,000 consecutive patients as a prespecified analysis; of these, 545 presented with STEMI. The efficacy of the mortality predictions of the four scores at 2 years were evaluated based on their discrimination and calibration abilities. RESULTS: Complete data was available in 512 patients (93.9%). When the patients were stratified into two groups based on the median of the scores, the prewiring and postwiring Updated LCSSs demonstrated that the high-score groups were associated with higher rates of 2-year all-cause mortality compared to the low-score groups (6.6 vs. 1.2%; log-rank p = .001 and 6.6 vs. 1.2%; log-rank p = .001, respectively). There were no statistically significant differences for predicting the mortality between the prewiring (area under the curve [AUC] 0.625), postwiring MI-SYNTAX score (AUC 0.614), prewiring (AUC 0.755), and postwiring Updated LCSS (AUC 0.757). In the integrated discrimination improvement (IDI), the prewiring MI-SYNTAX score had a better discrimination for the mortality than the postwiring MI-SYNTAX score (IDI -0.0082; p = .029). The four scores had acceptable calibration abilities for 2-year all-cause mortality. CONCLUSIONS: The prewiring Updated LCSS predicts long-term all-cause mortality with clearly useful discrimination and acceptable calibration. Since the postwiring MI-SYNTAX score does not improve mortality prediction, the prewiring MI-SYNTAX score may be preferred for the 2-year mortality prediction using the Updated LCSS.

Rationale and design of the Aortic Valve replAcemenT versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR trial): A randomized multicenter controlled event-driven trial.

Aortic valve replacement (AVR) therapy is an obvious choice for symptomatic severe aortic stenosis (AS) patients as it improves symptoms, left ventricular function, and survival. The treatment decisions and indication for AVR in asymptomatic patients with severe AS and normal left ventricular ejection fraction are less well established and the subject of ongoing debate. Many efforts have been made to define the best treatment option in asymptomatic AS patients with normal left ventricular ejection fraction. Retrospective and observational data imply that elective AVR for asymptomatic severe AS may lead to improvement in outcomes in comparison to surgery performed after onset of symptoms. The AVATAR trial will aim to assess outcomes among asymptomatic AS patients randomized to either elective early AVR or medical management with vigilant follow-up. In the latter group, AVR would be delayed until either the onset of symptoms or changes in predefined echocardiographic parameters. To the best of the authors' knowledge, it will be the first large prospective, randomized, controlled, multicenter clinical trial that will evaluate the safety and efficacy of elective AVR in this specific group of patients.

Feasibility of intracoronary frequency domain optical coherence tomography derived fractional flow reserve for the assessment of coronary artery stenosis.

Frequency domain optical coherence tomography (FD-OCT) provides cross-sectional images of coronary arteries and deployed stents with micron resolution and measures lumen dimensions with excellent reproducibility. FD-OCT combined with a blood flow resistances model can overcome many limitations of conventional measures of stenosis severity based on quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). The aim of this feasibility study was to investigate the relationship between pressure derived fractional flow reserve (FFR) and FD-OCT derived FFR, a new method for quantitative measure of stenosis severity that estimates the blood flow resistance and microvascular resistance of the vessel segments imaged by FD-OCT. A total of 26 coronary stenoses in 20 patients were studied consecutively with QCA, pressure derived FFR, and FD-OCT. There was a moderate but significant correlation between pressure derived FFR and FD-OCT derived FFR (r = 0.69, P < 0.001). Bland-Altman analysis showed that the mean differences between pressure derived FFR and FD-OCT derived FFR were 0.05 ± 0.14 (limits of agreement: -0.09 to 0.19). The root mean square error (RMSE) between FD-OCT derived FFR and pressure derived FFR was found to be ± 0.087 FFR units. FD-OCT derived FFR has the potential to become a valuable tool for the assessment of coronary artery stenosis.

Features and Limitations of Robotically Assisted Percutaneous Coronary Intervention (R-PCI): A Systematic Review of R-PCI.

Background: Ischaemic heart disease is one of the major drivers of cardiovascular death in Europe. Since the first percutaneous coronary intervention (PCI) in 1977, developments and innovations in cardiology have made PCI the treatment of choice for stenotic coronary artery disease. To address the occupational hazards related to chronic exposure to radiation and wear and tear from heavy lead-based radioprotective aprons, the concept of robotically assisted PCI (R-PCI) was introduced in 2005. Aim: To explore the features and limitations of R-PCI, we first discuss the concept and evolution of R-PCI platforms and then systematically review the available clinical data. Methods: A systematic review has been performed across the Pubmed, Embase and Cochrane databases in order to assess the efficacy and safety of R-PCI. Secondary endpoints, such as operator and patient exposure to radiation, contrast volume used and procedural time, were assessed when available. Results: In selected patients, R-PCI provides high technical and clinical success rates, ranging from 81 to 98.8% and from 93.3 to 100%, respectively. In-hospital and 1-year MACE rates ranged from 0 to 10.4% and 4.8 to 10.5%, respectively. R-PCI is able to significantly reduce the operator's exposure to radiation. Further research analysing the patient's and cath lab staff's exposure to radiation is needed. Therapy escalation with R-PCI seems to be limited to complex lesions. R-PCI procedures add approximately 10 min to the procedural time. Conclusions: The efficacy and safety of R-PCI have been proven, and R-PCI is able to significantly reduce occupational hazards for the first operator. The lack of adoption in the community of interventional cardiologists may be explained by the fact that current generations of R-PCI platforms are limited by their incompatibility with advanced interventional devices and techniques needed for escalation in complex interventions.

Exploring Potential Referral Pathways for Renal Artery Denervation and Developing a Centre of Excellence in Ireland.

Arterial hypertension is one of the most significant and prevalent risk factors for cardiovascular disease. Despite widespread awareness of the condition, as well as a multitude of available antihypertensive drug classes, rates of uncontrolled hypertension remain high on a global scale. Frequently, poor compliance with anti-hypertensive medication plays a big role in patients' inability to attain adequate blood pressure control. In individuals with resistant and/or uncontrolled hypertension, renal denervation is an emerging device-based therapy that has shown to be efficacious and safe in reducing blood pressure in several sham controlled trials. Additionally, it represents a treatment option for patients intolerant to oral pharmacotherapy. University Hospital Galway has been performing renal denervation procedures over the past number of years within multicentre, international sham-controlled trials and registries. Representing a novel and emerging antihypertensive treatment option, sources of referral for renal denervation are diverse and multiple; thus, there is an unmet need for standardised referral structures in Ireland. Herein, we review current and developing referral pathways for renal denervation at our institution, and discuss streamlined patient management and requirements to establish a centre of excellence.

Performance of wearable watch-type home blood pressure measurement devices in a real-world clinical sample.

BACKGROUND: Independent testing of home blood pressure (BP) measurement (HBPM) devices is often lacking, particularly among older and multi-morbid patients. METHODS: We studied the Bpro G2 (using tonometry), Omron HeartGuide (using occlusive oscillometric technology), and Heartisans (using photoplethysmography) wrist watch HBPM devices against a gold standard brachial sphygmomanometer. To test device performance, we used the ISO81060-2 protocol (though this protocol cannot formally validate cuffless devices). We also used linear mixed models to compare adjusted longitudinal BP measurements between devices. Finally, as a surrogate for usability, we recorded instances of device failure where no BP measurement was returned. RESULTS: We enrolled 128 participants (median [Q1-Q3] age 53 [40-65] years, 51% male, 46% on antihypertensive drugs), of whom 100 were suitable for the primary analysis. All three devices had mean BP values within 5 mmHg of sphygmomanometry. However, due to insufficient reliability (e.g., wider than accepted standard deviations of mean BP), none of the three devices passed all criteria required by the ISO81060-2 protocol. In adjusted longitudinal analyses, the Omron device also systematically underestimated systolic and diastolic BP (- 8.46 mmHg; 95% CI 6.07, 10.86; p < 0.001; and - 2.53 mmHg; 95% CI - 4.03, - 1.03; p = 0.001; respectively). Nevertheless, compared to the Omron device, BPro and Heartisans devices had increased odds of failure (BPro: odds ratio [OR] 5.24; p < 0.0001; Heartisans: OR 5.61; p < 0.001). CONCLUSIONS: While we could not formally validate the cuffless devices, our results show that wearable technologies will require improvements to offer reliable BP assessment. This study also highlights the need for validation protocols specifically designed for cuffless BP measurement technologies.

Does renal denervation require cardiovascular outcome-driven data?

Hypertension is a major driver of cardiovascular disease with a prevalence of 32-34% in adults worldwide. This poses a formidable unmet challenge for healthcare systems, highlighting the need for enhanced treatment strategies. Since 2017, eight major sham-controlled randomised controlled trials have examined the effectiveness and safety of renal denervation (RDN) as therapy for BP control. Although most trials demonstrated a reduction in systolic 24-hour/daytime ambulatory BP compared to control groups, open to discussion is whether major adverse cardiovascular events (MACE)-driven RDN trials are necessary or whether the proof of BP reduction as a surrogate for better cardiovascular outcomes is sufficient. We conducted an analysis of the statistical methods used in various trials to assess endpoint definitions and determine the necessity for MACE-driven outcome data. Such comprehensive analysis provides further evidence to confidently conclude that RDN significantly reduces blood pressure compared to sham controls. Importantly, this enables the interpolation of RDN trial endpoints with other studies that report on outcome data, such as pharmacological trials which demonstrate a significant reduction in MACE risk with a decrease in BP. Moreover, limitations associated with directly evaluating outcome data further support the use of BP as a surrogate endpoint. For example, conducting lengthier trials with larger numbers of participants to ensure robust statistical power presents a substantial challenge to evaluating outcome data. Thus, in light of the crucial need to tackle hypertension, there are notable advantages of considering BP as a surrogate for outcome data.

Twelve-month follow-up results from the SIRONA 2 clinical trial.

AIMS: In the SIRONA 2 trial, the safety and efficacy of pulmonary artery (PA) pressure (PAP)-guided heart failure (HF) management using a novel PAP sensor were assessed at 30 and 90 days, respectively, and both endpoints were met. The current study examines the prespecified secondary endpoints of safety and accuracy of the PA sensor along with HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance through 12 months. METHODS AND RESULTS: SIRONA 2 is a prospective, multi-centre, open-label, single-arm trial evaluating the Cordella™ PA Sensor System in 70 patients with New York Heart Association (NYHA) functional class III HF with a prior HF hospitalization and/or increase of N-terminal pro-brain natriuretic peptide within 12 months of enrolment. Sensor accuracy was assessed and compared with measurements obtained by standard right heart catheterization (RHC). Safety was defined as freedom from prespecified adverse events associated with use of the Cordella PA Sensor System and was assessed in all patients who entered the cath lab for PA sensor implant. HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance were also assessed. At 12 months, there was good agreement between the Cordella PA Sensor System and RHC, with the average difference for mean PAP being 2.9 ± 7.3 mmHg. The device safety profile was excellent with 98.4% freedom from device/system-related complications. There were no pressure sensor failures. HF hospitalizations and mortality were low with a rate of 0.33 event per patient year. Symptoms as assessed by NYHA (P < 0.0001) and functional capacity as measured by 6 min walk test (P = 0.02) were significantly improved. Patients' adherence to daily transmissions of PAP and vital signs measurements was 95%. CONCLUSIONS: Long-term follow-up of the SIRONA 2 trial supports the safety and accuracy of the Cordella PA Sensor System in enabling comprehensive HF management in NYHA class III HF patients.

Editorial: Is the axiom of balloon angioplasty, "the more you gain the more you lose", still true in the era of DCB with paclitaxel?

Balloon angioplasty achieves luminal enlargement by fracturing the atherosclerotic intima at its point of least resistance, thereby creating a dissection plane and space with dehiscence of the intima from the media. This barotraumatic dissection triggers an inflammatory and proliferative reaction, resulting in a restenosis process at medium-term. In the era of plain old balloon angioplasty, quantitative angiographic studies at follow-up demonstrated that - the greater the acute luminal gain was after balloon angioplasty, the greater the late luminal loss was at follow-up. The interventional cardiologists coined the following motto "the more you gain, the more you lose". However, in the current era of drug coated balloon (DCB), it appears that this vexing conundrum could have been abrogated. A recently published DCB study in small de novo vessel has demonstrated that there was a slightly negative correlation between the volume of dissection assessed by optical coherence tomography and the angiographic late luminal loss (now gain) after Paclitaxel coated balloon treatment. In other words, the barotraumatic dissection does not necessarily herald a restenosis process in the era of DCB. This article revisits the mechanism of balloon angioplasty and explores how DCB with Paclitaxel may change the paradigm of balloon angioplasty as default treatment in CAD percutaneous treatment.

The association between trimethylamine N-oxide levels and coronary microvascular dysfunction and prognosis in patients with ST-elevation myocardial infarction.

BACKGROUND AND AIMS: Coronary microvascular dysfunction (CMD) is common after ST-elevation myocardial infarction (STEMI), leading to adverse clinical outcomes. However, its diagnosis remains difficult, and mechanisms elusive. This study explores the role of Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, as a potential biomarker for diagnosing CMD in STEMI patients. METHODS: This prospective, observational study enrolled 210 STEMI patients with multivessel coronary artery disease who underwent primary percutaneous coronary intervention (PCI). TMAO levels were measured at baseline, 3 months, and 12 months post-PCI, whilst coronary physiology was assessed at 3 months. The primary endpoint was the incidence of CMD at 3 months, with the secondary endpoint being major adverse cardiovascular and cerebrovascular events (MACCE) at 12 months. An additional 59 consecutive patients were enrolled for validation. RESULTS: TMAO levels varied from baseline to 3 months, then stabilised. The areas under the ROC curve for baseline TMAO and TMAO at 3-month were 0.55 (95 % CI 0.46-0.64; p = 0.426), and 0.80 (95 % CI 0.73-0.87; p < 0.001), respectively. The optimal cut-off for TMAO at 3-month to diagnose CMD was 3.91, with similar sensitivity and specificity in the derivation and validation cohort. The incidence of MACCE was higher in patients with TMAO≥3.91 (41.4 % vs 10.7 %; p < 0.001). The addition of 3-month TMAO improved the diagnostic performance of traditional risk factors. CONCLUSION: TMAO is a robust biomarker for CMD and is significantly associated with the incidence of MACCE. TMAO has the potential in guiding clinical decision-making and suggests an interplay between gut microbiota and CMD.