Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative. We aimed to test the non-inferiority of FFR-guided PCI plus TAVI versus SAVR plus CABG in patients with severe aortic stenosis and complex coronary artery disease.

This international, multicentre, prospective, open-label, non-inferiority, randomised controlled trial was conducted at 18 tertiary medical centres across Europe. Patients (aged ≥70 years) with severe aortic stenosis and complex coronary artery disease, deemed feasible for percutaneous or surgical treatment according to the on-site Heart Team, were randomly assigned (1:1) to FFR-guided PCI plus TAVI or SAVR plus CABG according to a computer-generated sequence with random permuted blocks sizes stratified by site. The primary endpoint was a composite of all-cause mortality, myocardial infarction, disabling stroke, clinically driven target-vessel revascularisation, valve reintervention, and life-threatening or disabling bleeding at 1 year post-treatment. The trial was powered for non-inferiority (with a margin of 15%) and if met, for superiority. The primary and safety analyses were done per an intention-to-treat principle. This trial is registered with ClinicalTrials.gov (NCT03424941) and is closed.

Between May 31, 2018, and June 30, 2023, 172 patients were enrolled, of whom 91 were assigned to the FFR-guided PCI plus TAVI group and 81 to the SAVR plus CABG group. The mean age of patients was 76·5 years (SD 3·9). 118 (69%) of 172 patients were male and 54 (31%) patients were female. FFR-guided PCI plus TAVI resulted in favourable outcomes for the primary endpoint (four [4%] of 91 patients) versus SAVR plus CABG (17 [23%] of 77 patients; risk difference -18·5 [90% CI -27·8 to -9·7]), which was below the 15% prespecified non-inferiority margin (pnon-inferiority<0·001). FFR-guided PCI plus TAVI was superior to SAVR plus CABG (hazard ratio 0·17 [95% CI 0·06-0·51]; psuperiority<0·001), which was driven mainly by all-cause mortality (none [0%] of 91 patients vs seven (10%) of 77 patients; p=0·0025) and life-threatening bleeding (two [2%] vs nine [12%]; p=0·010).

The TCW trial is the first trial to compare percutaneous treatment versus surgical treatment in patients with severe aortic stenosis and complex coronary artery disease, showing favourable primary endpoint and mortality outcomes with percutaneous treatment.

Isala Heart Centre and Medtronic.

Cardiovascular disease remains the leading cause of mortality and healthcare expenditures in the United States. It is also a major contributor to premature mortality, years lived with disability, and rising healthcare costs around the world. Despite the availability of proven therapies and interventions that could vastly decrease the burden of cardiovascular disease and cardiometabolic conditions, their implementation is poor, with generally less than half of patients being treated with the most effective therapies. Implementation science offers promise in bridging this gap and mitigating disparities. However, even though small studies have shown that there are effective methods to improve the implementation of evidence-based therapies, these methods have not been scaled to make an impact at the level of health systems or nationally. A coordinated, multi-stakeholder approach is essential to identify barriers to implementation on a broad scale and, more critically, to develop and deploy practical solutions. The Duke Clinical Research Institute conducted an Implementation Summit entitled "Scalability, Spread, and Sustainability" to explore strategies for advancing the uptake of evidence-based interventions for cardiometabolic diseases in healthcare in the United States. This manuscript presents the participants' multi-stakeholder perspective on the steps necessary to improve the implementation of evidence-based therapies in cardiometabolic disease. Key recommendations include focused efforts on evidence generation around broad implementation strategies, dissemination of the evidence generated, uptake of evidence into usual care settings, and investment in training the current and next generations of leaders in implementation.

The relationship between degree of coronary artery stenosis and its effect on myocardial perfusion is complex and constitutes a clinical challenge. The aim of this study was to assess diagnostic accuracy of visual assessment of invasive coronary angiography (ICA) for detecting reduced myocardial perfusion determined by quantitative first-pass perfusion (qFPP) cardiac magnetic resonance (CMR) in patients with suspected or established chronic coronary syndrome (CCS). Forty-nine patients with suspected or established CCS were included from the elective ICA list in this prospective, observational study and underwent qFPP CMR prior to ICA. Myocardial perfusion at stress and myocardial perfusion reserve (MPR) were assessed for each vessel territory. Myocardial perfusion at stress <2.0 ml/min/g and MPR <2.4 were considered abnormal. Visually assessed coronary artery stenoses from ICA were considered significant if ≥70%. Sensitivity and specificity of visual assessment of ICA for detecting significant reduction of myocardial perfusion ranged between 32%-41% and 70%-76% on a per vessel level depending on myocardial perfusion measure used as reference. Accuracy ranged between 0.48-0.64. In 59%-68% of vessel territories with reduced stress perfusion or MPR, no significant stenosis was found. Thus, visual assessment of ICA has limited diagnostic accuracy for detecting significant reduction of myocardial perfusion assessed by qFPP CMR in patients with suspected or established CCS. Hence, quantitative myocardial perfusion is required when evaluating the cause of angina to distinguish between coronary stenosis, microvascular dysfunction and non-cardiac causes of chest pain.

Patients with concomitant severe aortic stenosis and significant coronary artery disease present a diagnostic and therapeutic challenge in clinical practice. There are no clear-cut guidelines as to the timing of revascularization in these patients who are referred for transcatheter aortic valve replacement (TAVR). This article aims to show that in patients without high-grade proximal coronary artery disease, revascularization after TAVR is safe, feasible, and practical. Additionally, the use of preoperative TAVR computed tomographic angiography might be used in both intermediate and high-risk patients rather than invasive coronary angiography to assess for significant proximal coronary artery disease to help guide the timing of revascularization.

The American Heart Association/American College of Cardiology (AHA/ACC) 2021 Chest Pain Guidelines introduced a new pre-test probability (PTP) model for obstructive coronary artery disease (CAD). The model recommends a 15 % risk cut-off for referral for further testing. Whether addition of a risk score measured from acoustic detection of coronary turbulence obtained by the noninvasive device CADScor®System (CAD-score) improves the AHA/ACC-PTP capability to assign the correct risk category has not been tested.

Patients with symptoms suggestive of CAD referred for coronary CT angiography and undergoing a same-day CAD-score were included. PTP was calculated based on sex, age, and symptoms. All patients with suspected stenosis on CT angiography were referred for invasive angiography. A CAD-score ≤ 20 was used as cut-off for low likelihood of CAD.

The study population consisted of 2874 patients (47 % women, median age [IQR] 58 [52-65] years). PTP categorized 2044 (71 %) of patients as > 15 % amongst whom 387 (18.9 %) were re-classified to low likelihood by a CAD-score ≤ 20. In patients aged < 70 without hypertension, 37 % were re-classified to low probability. Of the 830 patients with low PTP ≤ 15 %, 68.7 % had a CAD-score ≤ 20 indicating a deferred testing strategy.

Adding an acoustic-based CAD-score to the PTP in patients with AHA/ACC defined-PTP > 15 % risk can reduce the number of diagnostic tests by overall 19 %, and 37 % in subgroups, and may support cost-effective clinical decision-making. Moreover, CAD-score may aid risk stratification in patients, particularly with AHA/ACC-PTP ≤ 15 %.

Previous studies on exercise tolerance screening in asymptomatic individuals before starting physical activity were not cost-effective due to low specificity. However, given progress in diagnosing and treating coronary artery disease (CAD), a reevaluation of this approach is justified. We aimed to examine whether stress echocardiography (SE) would be cost-effective.

The study was conducted on asymptomatic individuals with no known coronary disease. The decision tree had two arms: in one arm, the subjects underwent stress echocardiography (SE) as a screening test before starting physical activity, and in the other, they did not. The probabilities and utilities of variables in the decision tree were taken from medical literature, and the costs of treatments were obtained from the Israeli Ministry of Health Tarif (HealthCare in Israel is universal, participation in one of four official health insurance organizations is compulsory, and "supplementary insurance" is optional). A 5-year Markov model and Monte Carlo simulation with 1000 iterations were used to assess cost-effectiveness from the insurer's perspective. The variables that had the most significant impact on cost-effectiveness were the prior risk of coronary disease and the frequency of physical activity in the population under study. When cost-effectiveness assessment of SE was conducted in subjects receiving optimal medical therapy (OMT) and revascularization either transcutaneously or with bypass surgery, both groups had almost identical benefits, with a slight advantage for those who did not undergo SE. However, the cost was higher for subjects who underwent SE, and the Incremental Cost-Effectiveness Ratio (ICER) favored the No-SE group. On the other hand, when subjects only received OMT without therapeutic catheterization or bypass surgery, a cost-effectiveness assessment of SE demonstrated a lower cost and higher benefit in the group that underwent SE. In fact, SE was found to be absolutely dominant, with a negative ICER of $(-)27,644, which means that performing SE not only adds effectiveness but also saves expenses. Finally, a cost-effectiveness evaluation was conducted to compare the benefits of performing exercise tolerance testing (ETT) without stress echocardiography in subjects receiving OMT without therapeutic catheterization or bypass surgery. The results showed that the group that underwent ETT had a slightly higher benefit at a higher cost, with an ICER of $1804. This value is much lower than a WTP (willingness-to-pay) of $50,000 per year.

Performing SE as a screening test before starting physical activity in asymptomatic individuals is not cost-effective when the therapeutic options include revascularization. However, when the therapeutic policy is medical therapy without revascularization - as recommended in current guidelines - performing SE screening tests improves subjects' utility and results in financial savings. Carrying out ETT also results in improved utility that is inferior to SE as a screening test. At the same time, the ICER for ETT is still much smaller than the WTP, so performing ETT is worthwhile in cases where SE is unavailable.

Abdominal visceral adipose tissue (AVAT) is associated with the incidence of cardiovascular events (CVEs). We retrospectively evaluated the association between AVAT and the incidence of CVEs in 602 patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Patients were divided into four groups according to the quartiles of AVAT areas using computed tomography. The incidence of CVEs (cardiovascular death, ACS recurrence and stroke) during the follow-up period (median 49.5 months) was evaluated. Cox analysis adjusting for cardiovascular risk factors revealed that the AVAT quartile classification exhibited a significant association with the incidence of CVEs. The risk in quartile 3 (moderate AVAT areas, ≥ 106.0 to < 142.6 cm2) was significantly lower than in quartiles 1 (low AVAT areas, < 71.0cm2; P < 0.01; hazard ratio [HR], 5.06), 2 (mild AVAT areas, ≥ 71.0 to < 106.0 cm2; P < 0.01; HR, 4.25) and 4 (severe AVAT areas, ≥ 142.6 cm2; P < 0.01; HR, 4.52). Polynomial analyses revealed that quadratic model was the most appropriate to illustrate the relationship between AVAT area and the hazard ratios for CVEs (corrected Akaike's information criterion, 49.2; R2, 0.47). The AVAT area and the incidence of CVEs exhibited a U-shaped relationship in patients with ACS undergoing PCI independent of conventional cardiovascular risk factors. The risk of CVEs was the lowest in patients with moderate AVAT areas. Evaluating AVAT may provide additional information for the assessment of long-term prognosis in patients with ACS.

In the ISCHEMIA Trial, 5179 patients with stable coronary disease were randomized to initial invasive or conservative management.

PCI was recommended with a SYNTAX score 0-22 (low) and CABG with a SYNTAX score ≥33 (high). Either could be recommended for intermediate scores. The composite primary outcome was cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. There were two cohorts in this analysis. The descriptive cohort included patients who underwent CABG or PCI within 180 days of randomization and had no primary outcome before revascularization. The comparative cohort excluded participants with prior CABG, single vessel disease, SYNTAX score ≥ 45, and without core laboratory assessment. We focused on the intermediate (23-32) SYNTAX comparative group for which either CABG or PCI could be recommended.

For 1935 patients in the descriptive cohort (485 CABG, 1450 PCI), the SYNTAX score was 27.3 ± 11.0 in the CABG group and 15.3 ± 8.6 in the PCI group, p<0.0001. Most patients with low SYNTAX scores underwent PCI (87.1%), while most with high SYNTAX scores underwent CABG (72.6%). For the 1203 patients (385 CABG, 818 PCI) in the entire comparative cohort, the adjusted 4-year primary event rate was 14.5% for CABG and 13.2% for PCI (difference 1.3%, 95% CI, -4.9% to 7.7%). For the 346 patients (163 CABG, 183 PCI) in the intermediate SYNTAX group, the adjusted 4-year primary event rate was 10.6% for CABG and 18.3% for PCI (difference -7.6%, 95% CI, -16.1% to 0.9%).

Selection of revascularization method resulted in more PCI in the low SYNTAX group and more CABG in the high SYNTAX group. There was no statistical evidence of a difference between PCI and CABG in the intermediate SYNTAX group but the CIs are broad, reflecting uncertainty.

NCT01471522; https://clinicaltrials.gov/ct2/show/NCT01471522.

Short dual antiplatelet therapy (DAPT) followed by ticagrelor monotherapy may be a valuable therapeutic option for patients with chronic coronary syndrome (CCS) and high ischaemic risk (HIR) undergoing percutaneous coronary intervention (PCI).

We aimed to compare ticagrelor monotherapy with ticagrelor-based DAPT in CCS patients with and without HIR undergoing PCI.

The present analysis included the CCS cohort of the TWILIGHT trial, which randomised PCI patients to ticagrelor alone or in combination with aspirin for 12 months after 3 months of ticagrelor-based DAPT. Patients were stratified into HIR and non-HIR based on the 2019 European Society of Cardiology (ESC) CCS guidelines definition. Outcomes of interest were major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction or stroke, and Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding at 1 year.

Of the 2,503 CCS patients who underwent randomisation, the ESC definition classified 1,264 (50.5%) as HIR and 1,239 (49.5%) as non-HIR. HIR patients displayed a higher risk of MACCE (3.9% vs 2.3%; p=0.015) and similar rates of BARC Type 2-5 bleeding (5.1% vs 5.7%; p=0.455) as compared to non-HIR patients. Ticagrelor monotherapy and ticagrelor-based DAPT were associated with similar risks of MACCE (HIR: 4.0% vs 3.8%, hazard ratio [HR] 1.06, 95% confidence interval [CI]: 0.60-1.85; non-HIR: 2.1% vs 2.6%, HR 0.80, 95% CI: 0.38-1.66, pinteraction=0.553) and bleeding (HIR: 4.7% vs 5.7%, HR 0.82, 95% CI: 0.50-1.33; non-HIR: 4.9% vs 6.7%, HR 0.71, 95% CI: 0.44-1.14; pinteraction=0.684) in both the HIR and non-HIR groups.

In a post hoc analysis of the TWILIGHT trial that included CCS patients undergoing PCI, ticagrelor monotherapy after 3 months of DAPT appeared to be safe and was not associated with increased risks of ischaemic or bleeding events, regardless of baseline HIR status, compared with standard ticagrelor-based DAPT. These findings suggest the potential to expand guideline recommendations for ticagrelor monotherapy in CCS.

Frailty is common among patients with chronic coronary disease and is associated with worse outcomes.

A pooled, post hoc analysis of the ISCHEMIA and ISCHEMIA-CKD trials was conducted. Baseline frailty was assessed using a Frailty Index (FI), and participants were categorized into data-derived tertiles. Multivariable Cox models with multiplicative interaction terms (frailty × treatment arm) were constructed to evaluate whether baseline frailty status modified the treatment effect of the initial invasive (vs conservative) strategy on a composite outcome of cardiovascular death, myocardial infarction, hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest and the secondary outcome of HRQoL (Seattle Angina Questionnaire [SAQ]).

Among 5322 participants (mean 64 years, 24% female), a high frailty burden (tertile 3 vs. tertile 1) was associated with lower baseline SAQ scores and increased risk of adverse clinical outcomes on follow-up. Baseline frailty burden did not significantly modify the effect of the initial invasive strategy on the primary composite outcome (Pinteractionfrailty × intervention arm = 0.30). However, frailty significantly modified the effect of the initial invasive strategy on HRQoL, with higher baseline frailty burden associated with greater improvement in SAQ scores at 1 year with initial invasive (vs. conservative) treatment (Pinteractionfrailty × intervention arm < 0.001). The treatment effect of an initial invasive vs. conservative strategy on 12-month SAQ score change was most pronounced in individuals with lower baseline SAQ scores in both higher and lower frailty burden groups.

Patients with chronic coronary disease with a higher frailty burden are more likely to experience greater improvements in HRQoL with initial invasive management without a higher risk of adverse clinical events. Lower baseline SAQ scores predicted greater improvement in HRQoL with initial invasive management, independent of frailty burden.

ORBITA-2 (The Placebo-Controlled Trial of Percutaneous Coronary Intervention for the Relief of Stable Angina) found that percutaneous coronary intervention (PCI) relieved angina in patients with single-vessel and multivessel stable coronary artery disease (CAD) on little or no antianginal medication. Whereas symptom characteristics and invasive physiological assessments can predict PCI efficacy, the role of noninvasive imaging with dobutamine stress echocardiography (DSE) remains unclear.

This DSE-stratified secondary analysis of ORBITA-2 investigates the relationship between ischemia, assessed by DSE, and the placebo-controlled efficacy of PCI.

Participants with angina, single-vessel or multivessel CAD, and ischemia were enrolled. Following discontinuation of antianginal medications, patients were evaluated prerandomization using the ORBITA-app, questionnaires, DSE, and exercise treadmill testing. Stress echocardiography scores were calculated for each left ventricular segment at peak stress, with normal, hypokinetic, akinetic, dyskinetic, and aneurysmal segments scoring 0 to 4, respectively. Bayesian proportional odds modeling was used.

Prerandomization DSE data were available for 262 patients. The median age was 65.5 years (Q1-Q3: 59-71 years), and 208 (79.4%) were male. At baseline, the median stress echocardiography score was 1.42 in the PCI group (n = 133) and 1.00 in the placebo group (n = 129), with an overall median score of 1.25 (Q1-Q3: 0.33-2.92). Higher stress echocardiography scores were strongly associated with greater placebo-controlled improvements in angina symptom score following PCI (OR: 1.23; 95% credible interval [CrI]: 1.13-1.35; Pr(interaction) > 99.9%). Higher scores also predicted significant reduction in daily angina episodes (OR: 1.36; 95% CrI: 1.24-1.49; Pr(interaction) > 99.9%), as well as improvement in the Seattle Angina Questionnaire angina frequency score (8.22; 95% CrI: 0.96-15.50; Pr(interaction) = 98.7%), and Seattle Angina Questionnaire quality of life score (8.95; 95% CrI: 2.05-16.00; Pr(interaction) = 99.3%). The relationship between stress echocardiography score and reduction in daily angina episodes remained consistent, irrespective of symptom characteristics.

In patients with single- and multivessel stable CAD on little or no antianginal medication, the placebo-controlled efficacy of PCI was predicted by the degree of ischemia detected on DSE. The greater the burden of baseline ischemia, the greater the improvement in symptoms and quality of life with PCI.

Coronary artery disease is the main cause of mortality worldwide mandating early detection, appropriate treatment, and follow-up. Noninvasive cardiac imaging techniques allow detection of obstructive coronary heart disease by direct visualization of the arteries or myocardial blood flow reduction. These techniques have made remarkable progress since their introduction, achieving high diagnostic precision. This review aims at evaluating these noninvasive cardiac imaging techniques, rendering a thorough overview of diagnostic decision-making for detection of ischemia.

We discuss the latest advances in the field such as computed tomography angiography, single-photon emission tomography, positron emission tomography, and cardiac magnetic resonance; their main advantages and disadvantages, their most appropriate use and prospects. For the review, we analyzed the literature from 2009 to 2024 on noninvasive cardiac imaging in the diagnosis of coronary artery disease. The review included the 78 publications considered most relevant, including landmark trials, review articles and guidelines.

The progress in cardiac imaging is anticipated to overcome various limitations such as high costs, radiation exposure, artifacts, and differences in interpretation among observers. It is expected to lead to more automated scanning processes, and with the assistance of artificial intelligence-driven post-processing software, higher accuracy and reproducibility may be attained.

The journey of assisted reproductive technology (ART) for couples facing recurrent implantation failure (RIF) is fraught with emotional and physical challenges. RIF, often characterized by the failure of high-quality embryos to implant after multiple ART cycles, has directed attention towards interventions like laser-assisted hatching (LAH). However, discrepancies in the literature necessitate a comprehensive review of LAH's efficacy and safety.

Following a thorough search of PubMed, Embase, Cochrane, and Web of Science databases up to November 2023, retrospective studies or RCT were considered for inclusion. Summary effect sizes [odds ratio (OR) or risk ratio (RR) with 95% confidence interval (CI)] were calculated for each outcome.

Eight studies comprising 2,634 patients were included. LAH significantly improved implantation rates (OR: 1.26, 95% CI: 1.05-1.51). Clinical pregnancy rates increased in patients who had fresh embryos transferred (OR: 1.29, 95% CI: 1.05-1.58). Notably, LAH was associated with higher miscarriage rates in frozen embryo transfers (OR: 1.45, 95% CI: 1.04-2.02). No significant increase in ectopic or multiple pregnancy rates was observed. For patients with RIF, especially older women, LAH presents a potential avenue to improve implantation. Its impact on clinical pregnancy rates is less substantial. However, its impact on final live birth rates and the increased miscarriage risk in frozen transfers necessitate a cautious and individualized approach. The technique's safety, while generally upheld, requires careful application and consideration of the specific challenges RIF patients face. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024497329, PROSPERO (CRD42024497329).

Myocardial perfusion imaging (MPI) results in downstream changes to medication prescription. While the benefits of medical therapy for coronary artery disease (CAD) are established, how this varies with MPI findings is unknown. Our goal was to evaluate the association of medical therapy with survival among patients undergoing MPI, including differential associations as a function of imaging findings.

Consecutive patients who underwent single-photon emission computed tomography MPI for suspected CAD between January 2015 and December 2021 were identified. Multivariable Cox regression modeling was used to assess the associations between medical therapy and all-cause mortality.

In total, 7802 patients were included with a mean age of 66.1 ± 12.0 years and 3841 (49.2 %) male patients. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACE inhibitors/ARBs) were associated with lower mortality (adjusted hazard ratio [HR] .66, 95 % confidence interval [CI]: .57-.77, P < .001). Beta-blockers were not associated with mortality overall (adjusted HR .95, 95 % CI: .83-1.10, P = .506) but were associated with lower mortality among patients with more ischemia (HR .94 per summed difference score point, 95 % CI: .90-.97, P-value <.001). Statins were associated with greater survival in patients with coronary calcium (adjusted HR .67, 95 % CI .56-.81, P = <0.001) but not in patients without assessment of coronary calcium (adjusted HR: 1.16, 95 % CI: .91-1.49 P = .236).

ACE/ARB prescription was significantly associated with improved survival. Beta-blocker prescription was associated with greater survival in patients with ischemia and statins were in patients with coronary calcification. Findings from MPI may identify patients more likely to benefit from specific therapies, suggesting a role for hybrid MPI in guiding medical therapy for CAD.

Coronary artery bypass grafting, revascularization by percutaneous coronary intervention, and heart valve surgery are crucial therapeutic interventions for patients with various cardiovascular diseases. The objective of this literature review was to present the main evidence and practical aspects of the perioperative management of patients undergoing coronary artery bypass grafting and heart valve surgery.

Despite advancements in surgical and anesthetic techniques, coronary artery bypass grafting and heart valve surgery present significant risks for perioperative complications and death. These complications increase morbidity, mortality, and length of hospital stay. Coronary artery bypass grafting is indicated for patients with significant left main or advanced coronary artery disease. Most patients undergoing coronary artery bypass grafting with a reasonable life expectancy are advised to adopt a multiple-arterial graft strategy using two or three arterial grafts. Revascularization by percutaneous coronary intervention is frequently performed to alleviate symptoms in patients with stable angina and coronary artery stenoses causing moderate or severe ischemia. Intraoperative coagulation management should include tranexamic acid after the induction of anesthesia and protamine immediately after the termination of extracorporeal circulation. The prophylactic use of fresh-frozen plasma, desmopressin, recombinant activated factor VII, or fibrinogen to reduce bleeding is not recommended. Inhaled anesthetics have recognized cardioprotective properties; however, it is unclear whether anesthesia with a volatile agent can reduce mortality in patients undergoing elective surgery. Echocardiography plays an important role in the perioperative management of patients by defining myocardial structure, assessing intracardiac blood flow, aiding preoperative evaluation, facilitating intraoperative monitoring, and providing real-time guidance for intervention. The perioperative management of patients undergoing coronary artery bypass grafting, percutaneous coronary intervention, and heart valve surgery is highly complex and involves numerous specific conditions. Effective management requires dedicated multidisciplinary teams skilled in timely recognition, prevention, and treatment to ensure appropriate care.

Lackluster results from recently completed gene therapy clinical trials of VEGF-A delivered by viral vectors have heightened the need to develop alternative delivery strategies. This study aims to demonstrate the pre-clinical efficacy and safety of extracellular vesicles (EVs) loaded with VEGF-A mRNA for the treatment of ischaemic vascular disease.

After encapsulation of full-length VEGF-A mRNA into fibroblast-derived EVs via cellular nanoporation (CNP), collected VEGF-A EVs were delivered into mouse models of ischaemic injury. Target tissue delivery was verified by in situ analysis of protein and gene expression. Functional rescue was confirmed by in vivo imaging and histology. The safety of single and serial delivery was demonstrated using immune-based assays.

VEGF-A EVs were generated with high mRNA content using a CNP methodology. VEGF-A EV administration demonstrated expression of exogenous VEGF-A mRNA by in situ RNA hybridization and elevated protein expression by western blot, microscopy, and enzyme-linked immunosorbent assay. Mice treated with human VEGF-A EVs after femoral or coronary artery ligation exhibited heightened neovascularization in ischaemic tissues with increased arterial perfusion and improvement in left ventricular function, respectively. Serial delivery of VEGF-EVs in injured skin showed improved wound healing with repeat administration. Importantly, as compared with adeno-associated viral and lipid nanoparticle VEGF-A gene therapy modalities, murine VEGF-A EV delivery did not trigger innate or adaptive immune responses at the injection site or systemically.

This study demonstrated that VEGF-A EV therapy offers efficient, dose-dependent VEGF-A protein formation with low immunogenicity, resulting in new vessel formation in murine models of ischaemic vascular disease.

Complications of acute myocardial infarction (AMI) can result in significant morbidity and mortality. This document reports the findings and recommendations of a multidisciplinary group of experts on the management of patients with complications of AMI, with particular focus on the use of mechanical circulatory support in this context.

Through the American Association of Thoracic Surgery Clinical Practice Standards Committee, a committee of multidisciplinary experts, including both cardiologists and cardiothoracic surgeons, was established. A list of topics was developed. Committee members were divided into subgroups that developed relevant questions. A systematic literature review was then performed, and the results were synthesized into clinical recommendations. Expert consensus was then established using the Delphi process.

Based on the results of the systematic literature review, as well as the clinical expertise of the committee, clinical recommendations were developed. Each of these recommendations, the strength of each recommendation, and the level or quality of evidence on which the recommendation was based are presented here. Topics addressed include general considerations, revascularization strategies, cardiogenic shock, papillary muscle rupture, postinfarction ventricular septal defect, free wall rupture, arrhythmias, and the use of durable therapies in this context.

AMI may result in cardiogenic shock, malignant arrhythmias, or mechanical complications, each of which is associated with high mortality. Prompt management of these complications, including consideration for mechanical circulatory support, is warranted.

Background Evaluating myocardial viability is critical for developing optimal strategies for ischemic cardiomyopathy. While semiconductor single-photon emission computed tomography (D-SPECT) demonstrated higher image quality than conventional Anger cameras for assessing myocardial viability, its accuracy compared to cardiac magnetic resonance (CMR) in the same patient cohort is still unknown. Methods We conducted a retrospective study on patients with known or suspected coronary artery disease who underwent D-SPECT and CMR within 100 days. Rest deficit score on D-SPECT and depth of contrast enhancement on late gadolinium enhancement (LGE) in CMR were classified and compared using a 16-segment analysis. Follow-up echocardiography was performed about a year after the initial examinations, detecting whether the optimal medical therapy (OMT) was followed by invasive therapy (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI]). The five-year survival rates were also compared. Results The study comprised 336 segments from 21 consecutive patients collected between January 2015 and December 2017. Using LGE as a viability criterion, a D-SPECT score of three had the highest diagnostic accuracy (area under the curve: 0.97). Follow-up echocardiography showed significant improvements in left ventricular ejection fraction in patients receiving OMT + PCI/CABG compared to OMT alone (OMT vs. OMT + PCI/CABG; 1.5% ± 3.4% vs. 7.1% ± 5.0%, p = 0.008); five-year survival rate did not significantly differ between the groups. Conclusions Deficits observed at rest on D-SPECT and LGE extent on CMR showed a strong correlation in evaluating myocardial viability, implying that D-SPECT is a viable alternative to CMR for this purpose.

CCS management, based on the 2024 ESC Guidelines, a cornerstone of contemporary cardiology, aims to prevent cardiovascular events, alleviate symptoms, and enhance quality of life through conservative and invasive strategies. Non-invasive approaches, encompassing patient education, lifestyle interventions, and optimized pharmacological treatments, have demonstrated significant benefits in prognosis and quality of life. The guidelines advocate for a patient-centered approach, tailoring therapies to pathophysiological mechanisms, comorbidities, and individual needs. Pharmacological strategies integrate antithrombotic, lipid-lowering, RAAS-blocking, anti-inflammatory, and antidiabetic agents for event prevention, alongside antianginal medications for symptom relief. Invasive interventions remain essential for high-risk patients with obstructive coronary artery disease (e.g., left main disease, three-vessel disease, or proximal LAD involvement) or refractory angina despite optimal medical therapy. However, the growing efficacy of medical management increasingly challenges the incremental benefits of early revascularization. The guidelines also highlight underdiagnosed conditions such as ANOCA (Angina with Non-Obstructive Coronary Arteries) and INOCA (Ischemia with Non-Obstructive Coronary Arteries). Recognizing diverse endotypes, including microvascular dysfunction and vasospastic angina, enables precise and individualized therapeutic approaches. Conservative therapy remains the foundation of CCS management, demanding a holistic, multidisciplinary, and patient-centered approach to optimize outcomes and improve quality of life.

In patients with established chronic coronary syndrome (CCS), the significance of persistent angina is controversial. We aimed to evaluate the prognostic role of persistent angina in symptomatic CCS patients with abnormal stress cardiovascular magnetic resonance (CMR) and altered angiographic findings undergoing percutaneous revascularization.

We analyzed 334 CCS patients with Canadian Cardiovascular Society angina class ≥2, perfusion deficits on stress CMR and severe lesions in angiography who underwent medical therapy optimization plus CMR-guided percutaneous revascularization. We investigated the association of persistent angina at 6 months postintervention with subsequent cardiac death, myocardial infarction, and hospital admission.

All patients had angina class ≥2 (mean: 2.8±0.7), abnormal stress CMR (mean ischemic burden: 5.8±2.7 segments), and severe angiographic lesions. The angina resolution rates were 81% at 6 months, and 81%, 81%, and 77% at 1, 2, and 5 years, respectively. During a median follow-up of 8.9 years, persistent angina was independently associated with higher rates of subsequent cardiac death (13% vs 4%; HR, 3.7; 95%CI, 1.5-9.2; P=.005), myocardial infarction (24% vs 6%; HR, 4.9; 95%CI, 2.4-9.9; P<.001), and hospital admission for heart failure (27% vs 13%; HR, 2.7; 95%CI, 1.5-5.2; P=.001).

In CCS patients with robust diagnostic evidence from symptoms, stress CMR, and angiography, persistent angina after percutaneous revascularization is a strong predictor of subsequent cardiac death, myocardial infarction, and hospital admission for heart failure.

The significance of evaluating myocardial viability in making decisions regarding coronary artery bypass grafting (CABG) for patients with ischemic left ventricular dysfunction (ILVD) remains controversial. This study aimed to examine the impact of integrated assessment of hibernating myocardium and scars on the survival benefit associated with CABG in patients with ILVD.

Consecutive patients with ILVD who underwent fluorine-18 fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance imaging with late gadolinium enhancement viability testing from January 2015 and April 2018 were retrospectively enrolled. The primary end point was all-cause death. The secondary end point was a composite of cardiovascular death, cardiovascular hospitalization, heart transplantation, revascularization, insertion of an implantable cardioverter-defibrillator, or nonfatal stroke. Cox models calculated hazard ratios (HRs) and CIs for CABG vs medical therapy alone for subgroups with different levels of hibernation and scars.

During a median follow-up of 71.5 months in 507 patients, 98 patients reached the primary end point and 194 reached the secondary end point. After adjustment, CABG was associated with lower risks of all-cause mortality (HR, 0.249; 95% CI, 0.154-0.428; P<.001) and lower incidences of secondary outcomes (HR, 0.457; 95% CI, 0.318-0.658; P<.001) compared with medical treatment alone in the population. Across all 4 subgroups classified by the optimal cutoff value (10% hibernation and 26% scar), CABG was associated with favorable outcomes regardless of the hibernation and scar level.

The extent and severity of hibernating myocardium and scars appear not to influence the effects of CABG in patients with ILVD.

The chronic coronary syndrome can be attributed to different pathophysiological epicardial or microvascular mechanisms. In the current ESC guideline from 2024, a diagnostic algorithm was developed based on a risk-factor-weighted individual pre-test probability. The baseline diagnostic includes anamnesis, electrocardiogram, and a laboratory chemical analysis, especially to exclude an acute coronary syndrome. The early and direct assessments for risk-factor-weighted individual pre-test probability are calculated by taking into account clinical symptoms, individual cardiovascular risk factors, age, and gender. Resting ECG, echocardiography and the evaluation of the peripheral arteries and data on possible known vascular calcifications in previous imaging examinations can further adjust and modify the pre-test probability. Non-invasive imaging methods (computed tomography angiography, magnetic resonance imaging, stress echocardiography, SPECT, PET) or invasive coronary angiography can be used to confirm or exclude the diagnosis of chronic coronary syndrome.

Comparisons of international practice patterns and their impact on percutaneous coronary intervention (PCI) outcomes are lacking. We compared temporal PCI trends between Sweden and a large university hospital system in the US.

Data within the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and the University of California San Diego Health internal National Cardiovascular Data Registry (NCDR) CathPCI Registry were used to identify patients who underwent PCI from 2007 to 2021. Baseline characteristics and practice patterns were assessed using all patients (275 021 Swedish cohort, 9883 US cohort). Mortality was analysed using a random-effects Cox model, restricted to patients treated at university hospitals and excluding those with cardiac arrest or cardiogenic shock (108 136 Swedish cohort, 9592 US cohort). The Swedish cohort was older, had a greater proportion of men, and was more likely to smoke (all P < 0.001). The US cohort had a higher body mass index and was more likely to have diabetes, hyperlipidaemia, prior PCI, congestive heart failure, and peripheral arterial disease (all P < 0.001). Sweden had lower rates of PCI for stable angina and lower use of mechanical circulatory support (all P < 0.001). More STEMI patients were treated with only heparin as anticoagulation in Sweden, even in the contemporary era. There was earlier adoption and increased utilization of ticagrelor and radial access in Sweden, while there was earlier use of drug-eluting stents in the US. Fractional flow reserve was used more frequently in Sweden. There was no difference in adjusted all-cause mortality 1 year post-PCI for any indication between university hospitals in Sweden and the US (hazard ratio [HR] 1.09; 95% CI 0.86-1.37; P = 0.48), and this finding was consistent across subgroups.

Despite significant differences in patient populations and practice variations, we found no difference in post-PCI mortality between university hospitals in Sweden and the US.

Guidelines and international appropriate use criteria increasingly endorse non-invasive stress testing to evaluate patients with suspected chronic coronary disease (CCD). We sought to review the real-world utilisation of non-invasive stress testing and investigate whether their use prior to PCI associates with outcomes in patients with CCD.

Consecutive patients from a multicentre registry who underwent PCI for CCD between 2006 and 2018 were included. Clinical characteristics and outcomes were stratified according to whether stress testing was performed prior to PCI (stress vs no-stress groups). The primary outcome was 3-year all-cause mortality.

Among the 8251 patients included, 4970 (60.2 %) underwent pre-PCI stress testing and this proportion increased over time (p-for-trend<0.001). The stress group had a lower prevalence of prior revascularization, myocardial infarction, or heart failure, and a lower incidence of triple vessel disease, in stent re-stenosis, and ACC/AHA class B2/C lesions (all p < 0.001). When comparing post-procedural outcomes, the stress group had lower rates of arrhythmia (1.5 % vs 2.6 %, p = 0.001), new heart failure (0.2 % vs 0.8 %, p = 0.001), renal impairment, and a shorter length of stay (1.6 vs 2.1 days, p < 0.001). Mortality at 3-years was lower in those undergoing PCI following stress testing (5.8 % vs 8.8 %, p < 0.001). After adjusting for key clinical variables, stress guided revascularization was associated with a significantly lower risk of 3-year mortality (adjusted Hazard Ratio 0.77, 95 % CI 0.64-0.92).

In patients with CCD, PCI guided by non-invasive stress testing is increasingly utilized and associated with improved survival. Further studies are necessary to investigate whether this results from differences in patient characteristics, optimized patient selection, or refined choice of target vessel.

The aim of this study is to compare the clinical benefits associated with different percutaneous coronary intervention (PCI) timing strategies in patients undergoing transcatheter aortic valve implantation (TAVI) who have coexisting coronary artery disease (CAD). A systematic review and meta-analysis were conducted. PubMed, EMBASE, Cochrane Library and Web of Science databases were searched for relevant articles up to April 10th, 2024. Studies that reported comparisons of clinical outcomes between PCI before/concomitant with TAVI (PCI-TAVI) vs. TAVI alone, or comparisons between PCI before/concomitant with TAVI vs. PCI after TAVI (TAVI-PCI) were selected. Primary outcomes were all-cause mortality in the short-term, mid-term and long-term follow-up. A total of 23 studies pooling 15812 patients were included. Compared to TAVI alone, PCI-TAVI showed no significant difference in all-cause mortality at short- and mid-term (RRshort-term = 1.10 95%CI 0.88-1.38; RRmid-term = 1.12 95%CI 0.97-1.30), but an increase during long-term follow-up (RRlong-term = 1.20 95%CI 1.06-1.36). Compared with PCI-TAVI, TAVI-PCI is associated with lower rate of all-cause mortality at both short- and long-term follow-ups. PCI before or concomitant with TAVI may not offer clinical benefits and could potentially lead to worse outcomes in the long term. Conversely, PCI after TAVI is associated with improved clinical outcomes in both the short and long term.

Chronic coronary disease (CCD) is the leading cause of death in the United States. There is an ongoing imperative to disseminate evidence-based and patient-centered care recommendations that further align the management of patients with CCD to updated evidence-based guidelines. The writing committee developed a comprehensive CCD measure set comprising 10 performance measures and 3 quality measures, the focus of which is to include practical steps to specifically advance care in the CCD population. The measure set begins with an assessment of tobacco use and evidence-based cessation interventions. Also included are topics such as antiplatelet therapy, lipid assessment and low-density lipoprotein cholesterol goals, and guideline-directed management and therapy for hypertension and reduced left ventricular dysfunction in patients with CCD. The measure set concludes with an emphasis on the importance of cardiac rehabilitation referral and patient education, including symptom management and lifestyle modification.

Models predicting the likelihood of obstructive coronary artery disease (CAD) on invasive coronary angiography exist. However, as stable patients with new-onset chest pain frequently have lower clinical likelihood and preferably undergo index testing by non-invasive tests such as coronary computed tomography angiography (CCTA), clinical likelihood models calibrated against observed obstructive CAD at CCTA are warranted. The aim was to develop CCTA-calibrated risk-factor- and coronary artery calcium score-weighted clinical likelihood models (i.e. RF-CLCCTA and CACS-CLCCTA models, respectively).

Based on age, sex, symptoms, and cardiovascular risk factors, an advanced machine learning algorithm utilized a training cohort (n = 38 269) of symptomatic outpatients with suspected obstructive CAD to develop both a RF-CLCCTA model and a CACS-CLCCTA model to predict observed obstructive CAD on CCTA. The models were validated in several cohorts (n = 28 340) and compared with a currently endorsed basic pre-test probability (Basic PTP) model. For both the training and pooled validation cohorts, observed obstructive CAD at CCTA was defined as >50% diameter stenosis. Observed obstructive CAD at CCTA was present in 6443 (22.7%) patients in the pooled validation cohort. While the Basic PTP underestimated the prevalence of observed obstructive CAD at CCTA, the RF-CLCCTA and CACS-CLCCTA models showed superior calibration. Compared with the Basic PTP model, the RF-CLCCTA and CACS-CLCCTA models showed superior discrimination (area under the receiver operating curves 0.71 [95% confidence interval (CI) 0.70-0.72] vs. 0.74 (95% CI 0.73-0.75) and 0.87 (95% CI 0.86-0.87), P < 0.001 for both comparisons).

CCTA-calibrated clinical likelihood models improve calibration and discrimination of observed obstructive CAD at CCTA.

This article highlights the rationale for a more accurate and inclusive classification that does not focus solely on epicardial coronary lesions as the causa sine qua non for angina and myocardial ischaemia in all patients but rather represents a more comprehensive classification encompassing both obstructive and non-obstructive causes. Ischaemia may be 'silent' clinically or electrocardiographically and is observed in both acute and non-acute settings, as seen in patients with diabetes and other conditions associated with microvascular dysfunction. By pivoting away from the more restrictive and overly simplistic 'vessel-based' classification that disproportionately focuses on obstructed epicardial arteries to a 'substrate-based' nomenclature inclusive of both obstructive and non-obstructive causes, 'myocardial ischaemic syndromes' will better align and unify a patient-centric approach by harmonising the full spectrum of pathophysiologic causes.

The Drug Coated Balloon Academic Research Consortium project originated from the lack of standardization and comparability between studies using drug-coated balloons in the treatment of obstructive coronary artery disease. This document is a collaborative effort between academic research organizations and percutaneous coronary intervention societies in Europe, the USA, and Asia. This consensus sought to standardize study designs and endpoints for clinical trials involving drug-coated balloons, including defining angiographic, intravascular, and non-invasive imaging methods for lesion assessment, alongside considerations for post-revascularization pharmaco-therapy. The concept of 'blended therapy', which advocates for combining device strategies, is also discussed. This paper delineates study types, endpoint definitions, follow-up protocols, and analytical approaches, aiming to provide consistency and guidance for interventional cardiologists and trialists.

Non-invasive imaging is widely used both for initial diagnosis and to guide management of ischemic heart disease (IHD). Older adults and women with IHD may have different responses to imaging as well as to treatments and outcomes that follow compared with younger adults and men. We aimed to study the representation of older adults and women in randomized controlled trials (RCT) of non-invasive imaging among patients with acute and stable chest pain.

We conducted a systematic search to identify RCTs evaluating non-invasive, imaging-guided diagnosis and management for IHD that were published before September 1, 2023. Participation-to-Prevalence Ratio (PPR) was estimated for women and age subgroups of <65, 65-74, ≥75 years. PPR of <0.8, 0.8-1.2, and >1.2 indicated underrepresentation, appropriate representation, and overrepresentation, respectively.

Among 53 RCTs, sex and age breakdown were available in 53 (n=55,893) and 21 trials (n=35,503), respectively. The median age across all trials was 57.4 years [IQR: 55.0- 60.2]. Participants aged <65 years were overrepresented with a median PPR 2.13 [IQR: 1.73- 2.43], while those aged 65-74 years and ≥75 years were underrepresented with median PPRs of 0.74 [IQR: 0.56-0.83] and 0.21 [IQR: 0.11-0.33], respectively. Women were adequately represented with a median PPR of 1.2 [1.06-1.32].

While women were appropriately represented, adults 65 years or older, especially those ≥75 years, were under-represented in these trials. Future RCTs on non-invasive imaging should target enrollment of older adults to ensure generalizability of results to this growing population.

In a systematic review of 53 randomized controlled trials of non-invasive imaging for chest pain published before September 1, 2023 (n=55,893 participants), adults aged 65 years and older, especially those aged 75 years and above, were significantly underrepresented, whereas women had representation proportional to prevalence estimates. These findings highlight an urgent need to increase enrollment of older adults in future imaging trials to ensure broader applicability and relevance of study results.