The Impact of Frailty and Surgical Risk on Health-Related Quality of Life After TAVI.

Symptomatic aortic stenosis and frailty reduce health-related quality of life (HrQoL). Transcatheter aortic valve implantation (TAVI) in patients at high to extreme risk has been proven to have a beneficial effect on HrQoL. Currently, TAVI is also considered in patients at intermediate risk. Our meta-analysis investigates whether benefits to HrQoL after TAVI is more pronounced in frail patients and patients at high to extreme vs. intermediate surgical risk. A systematic search of the literature was performed in November 2021 and updated in November 2023 in PUBMED, EMBASE, and the Cochrane Controlled Trials Register. Statistical analysis was performed according to the inverse variance method and the random effects model. A total of 951 studies were assessed, of which 19 studies were included. Meta-analysis showed a mean increase in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score of 29.6 points (6.0, 33.1) in high to extreme risk patients versus 21.0 (20.9, 21.1) in intermediate risk patients (p < 0.00001) and 24.6 points (21.5, 27.8) in frail patients versus 26.8 (20.2, 33.4) in the general TAVI population (p = 0.55). However, qualitative analyses of non-randomized studies showed the opposite results. In conclusion, TAVI improves HrQoL more in high to extreme than intermediate risk patients. Frailty's impact on HrQoL post-TAVI is inconclusive due to varying outcomes in RCTs vs. non-RCTs.

Cardiac (tele)rehabilitation in routine clinical practice for patients with coronary artery disease: protocol of the REHAB + trial.

Introduction: Cardiac rehabilitation programs face the challenge of suboptimal participation, despite being a level Ia recommendation. Cardiac telerehabilitation, with its potential to engage patients who might otherwise not show interest, necessitates the adaption of existing center-based cardiac rehabilitation programs to facilitate rehabilitation at home. REHAB + is a mobile cardiac telerehabilitation program cocreated with patients and rehabilitation centers, aiming to future-proof cardiac rehabilitation and improve accessibility. The REHAB + application enables users to remotely communicate with their coach, receive on-demand feedback on health goal progression, and reduces the need for frequent in-person meetings at the cardiac rehabilitation center. The REHAB + study seeks to compare patient-related outcomes and characteristics of patients between those offered the option to participate in cardiac telerehabilitation and those attending center-based cardiac rehabilitation over a twelve-month period. Methods: The REHAB + study is a multicenter, prospective, matched controlled, observational study that includes (N)STEMI patients eligible for cardiac rehabilitation. We aim to enroll 300 participants for cardiac telerehabilitation and 600 for center-based cardiac rehabilitation. Participants opting for cardiac telerehabilitation (REHAB+) will be matched with center-based cardiac rehabilitation participants. Additionally, characteristics of patients unwilling to participate in either center-based rehabilitation or telerehabilitation but are willing to share their demographics will be collected. The primary endpoint is quality of life measured with the SF-36 questionnaire at three and twelve months, with patient-related characteristics driving intervention choice as the most important secondary endpoint. Secondary endpoints include physical activity, modifiable risk factors, and digital health experience. The trial is registered at clinicaltrials.gov with registration number NCT05207072. Discussion: The REHAB + trial is unique by offering patients freedom to choose between cardiac telerehabilitation and center-based rehabilitation. The integration of digital components into cardiac rehabilitation has the potential to complement behavioral change strategies for specific patient groups. Offering patients the option of cardiac telerehabilitation next to center-based rehabilitation could enhance overall cardiac rehabilitation participation rates.

The impact of stroke and bleeding on mortality and quality of life during the first year after TAVI: A POPular TAVI subanalysis.

BACKGROUND: Bleeding and stroke are frequent complications after transcatheter aortic valve implantation (TAVI). The mortality risk associated with these events has been reported before, but data regarding their impact on health-related quality of life (QoL) is limited. AIM: To evaluate the impact of bleeding and stroke occurring within 30 days after TAVI, on mortality and QoL during the first year after TAVI. METHODS: POPular TAVI was a randomized clinical trial that evaluated the addition of clopidogrel to aspirin or oral anticoagulation in patients undergoing TAVI. Besides clinical outcomes, QoL was assessed using the Short Form-12 and EuroQoL Five Dimensions questionnaires before, and at 3, 6, and 12 months after TAVI. RESULTS: Major or life-threatening bleeding occurred in 81 patients (8.3%) and was associated with an increased risk of death (hazard ratio [HR] 1.95 [95% confidence interval (CI) 1.00-3.79]); minor bleeding occurred in 104 patients (10.6%) and was not associated with mortality (HR 0.75 [95% CI 0.30-1.89]). Stroke occurred in 35 patients (3.6%) and was associated with an increased risk of death (HR 2.90 [95% CI 1.23-6.83]). Mean mental component summary (MCS-12) scores over time were lower in patients with major or life-threatening bleeding (p = 0.01), and similar in patients with minor bleeding, compared to patients without bleeding; mean physical component summary (PCS-12) scores, EQ-5D index, and visual analog scale (VAS) were similar between those patients. Mean MCS-12 scores were lower in patients with stroke (p = 0.01), mean PCS-12, EQ-5D index, and VAS were similar compared to patients without stroke. CONCLUSION: Major or life-threatening bleeding and stroke were associated with an increased risk of death and decreased mental QoL in the first year after TAVI.

2023 European Society of Cardiology guidelines for the management of acute coronary syndromes : Statement of endorsement by the NVVC.

This review discusses the new recommendations in the 2023 European Society of Cardiology guidelines on the management of acute coronary syndrome and provides a perspective on topics specific to clinical practice in the Netherlands, including pre-treatment, antiplatelet agent strategies, the use of risk scores and logistical considerations with regard to the timing of coronary angiography.

Modeling creatine-kinase MB concentrations following coronary artery bypass grafting.

BACKGROUND: An increase in cardiac biomarkers is a prerequisite for diagnosing periprocedural myocardial infarction (PMI) after coronary artery bypass grafting (CABG). Early-phase risk detection may be aided by modeling time-dependent serum creatine kinase-MB (CK-MB) concentrations. This study aimed to model the kinetics of CK-MB while identifying its influencing factors. METHODS: Patients who underwent elective CABG and had CK-MB measurements within 72 hours postoperatively were included. The primary outcome was the modeled post hoc kinetics of CK-MB in patients without potential PMI. These patients were defined as having no potential PMI based on the absence of ischemic electrocardiographic abnormalities, imaging abnormalities, in-hospital cardiac arrest, mortality, or postoperative unplanned catheterization. A web-based application was created using mixed-effect modeling to provide an interactive and individualized result. RESULTS: A total of 1589 CK-MB measurements from 635 patients who underwent elective isolated CABG were available for analysis. Of these, 609 patients (96%) had no potential PMI and 26 (4%) had potential PMI. Male sex, aortic cross-clamp time, and cardioplegia type significantly impacted CK-MB concentrations. The diagnostic accuracy of the model had an area under the receiver operating characteristic curve of 82.8% (95% confidence interval, 72.6%-90.2%). A threshold of 7 µg/L yielded a sensitivity of 94% and a specificity of 80% (positive predictive value, 17%; negative predictive value, 99%) for excluding potential PMI in our study population. CONCLUSIONS: CK-MB release after CABG depends on the timing of measurement, patient sex, aortic cross-clamp time, and cardioplegia type. The model (available at https://www.cardiomarker.com/ckmb) can be validated, reproduced, refined, and applied to other biomarkers.

Percutaneous coronary intervention with drug-eluting stents versus coronary bypass surgery for coronary artery disease: A Bayesian perspective.

OBJECTIVES: Coronary revascularization is frequently performed for coronary artery disease (CAD). This study aims to assess the totality of randomized evidence comparing percutaneous coronary intervention with drug-eluting stents (DES-PCI) with coronary artery bypass grafting (CABG) for CAD. METHODS: A systematic search was applied to 3 electronic databases, including randomized trials comparing DES-PCI with CABG for CAD with 5-year follow-up. A Bayesian hierarchical meta-analytic model was applied. The primary outcome was all-cause mortality at 5 years; secondary outcomes were stroke, myocardial infarction, and repeat revascularization. End points were reported in median relative risks (RRs) and absolute risk differences, with 95% credible intervals (CrIs). Kaplan-Meier curves were used to reconstruct individual patient data. RESULTS: Six studies comprising 8269 patients (DES-PCI, n = 4134; CABG, n = 4135) were included. All-cause mortality at 5 years was increased with DES-PCI (median RR, 1.23; 95% CrI, 1.01-1.45), with a median absolute risk difference of +2.3% (95% CrI, 0.1%-4.5%). For stroke, myocardial infarction, and repeat revascularization, the median RRs were 0.79 (95% CrI, 0.54-1.25), 1.84 (95% CrI, 1.23-2.75), and 1.80 (95% CrI, 1.51-2.16) for DES-PCI, respectively. In a sample of 1000 patients undergoing DES-PCI instead of CABG for CAD, a median of 23 additional deaths, 46 myocardial infarctions, and 85 repeat revascularizations occurred at 5 years, whereas 10 strokes were prevented. CONCLUSIONS: The current data suggest a clinically relevant benefit of CABG over DES-PCI at 5 years in terms of mortality, myocardial infarction, and repeat revascularization, despite an increased risk of stroke. These findings may guide the heart-team and the shared decision-making process.

Medically Treated Nonischemic Thin-Cap Fibroatheroma Lesions Versus Fractional Flow Reserve-Guided Complete Revascularization in Diabetic Patients.

Background: Fractional flow reserve (FFR) is an established method to guide decisions on revascularization; however, in patients with diabetes mellitus (DM), FFR-negative lesions carrying an optical coherence tomography-detected thin-cap fibroatheroma (TCFA) remain at high risk for adverse cardiac events. Methods: In this prespecified subanalysis of the COMBINE OCT-FFR trial, DM patients with ≥1 FFR-negative, TCFA-positive medically treated target lesions referred to as vulnerable plaque (VP group), were compared to patients with exclusively FFR-positive target lesions who underwent complete revascularization (CR group). The primary endpoint was first and recurrent event analysis for target lesion failure and the secondary endpoint was a composite of cardiac death, target vessel myocardial infarction, target lesion revascularization, or hospitalization due to unstable angina. Results: Among 550 patients enrolled, 98 belonged to the VP group while 93 to the CR group and were followed up to 5 years. The VP group had a higher occurrence of the primary endpoint (20.4% vs 8.6%; HR, 2.22; 95% CI, 0.98-5.04; P = .06). Recurrent event analysis showed that the VP group had significantly higher rates of the primary and secondary endpoints (9.17 vs 3.76 events per 100 PY; RR, 2.44; 95% CI, 1.16-5.60; P = .01 and 13.45 vs 5.63 events per 100 PY; RR, 2.39; 95% CI, 1.30-4.62; P < .01). Conclusions: In a population with DM, medically treated nonischemic, TCFA-carrying target lesions were associated with higher risk of reoccurring adverse cardiac events compared to target lesions that underwent complete revascularization, opening the discussion about whether a focal preventive revascularization strategy could be contemplated for highly vulnerable lesions.

Outcomes of Mitral Valve Regurgitation Management after Expert Multidisciplinary Valve Team Evaluation.

Background/Objectives: Mitral regurgitation (MR) affects millions worldwide, necessitating timely intervention. There are significant clinical challenges in the conservative management of MR, leaving a knowledge gap regarding the impact of multidisciplinary decision-making on treatment outcomes. This study aimed to provide insights into the impact of multidisciplinary decision-making on the survival outcomes of MR patients, focusing on conservative approaches. Methods: This study retrospectively analyzes 1365 patients evaluated by an expert multidisciplinary heart team (MDT) in a single center from 2015 to 2022. Treatments included surgery, catheter-based interventions, and conservative management. Propensity matching was utilized to compare surgery and conservative approaches. Results: Surgical intervention was associated with superior long-term survival outcomes compared to conservative and catheter-based treatments, particularly for degenerative MR (DMR). Survival rates of patients deemed by the MDT to have non-severe DMR were comparable to surgical patients (HR 1.07, 95% CI: 0.37-3.12, p = 0.90). However, non-severe functional MR (FMR) patients trended towards elevated mortality risk (HR 1.77, 95% CI: 0.94-3.31, p = 0.07). Pharmacological treatment for DMR was associated with significantly higher mortality compared to surgery (HR 8.0, 95% CI: 1.78-36.03, p = 0.001). Functional MR patients treated pharmacologically exhibited a non-significantly higher mortality risk compared to surgical intervention (HR 1.93, 95% CI: 0.77-4.77, p = 0.20). Conclusions: Survival analysis revealed significant benefits for surgical intervention, contrasting with elevated mortality risks associated with conservative management. "Watchful waiting" may be appropriate for non-severe DMR, while FMR may require closer monitoring. Further research is needed to assess the impact of regular follow-up or delayed surgery on survival rates, as pharmacological therapy has limited long-term efficacy for DMR.

The prognostic impact of unplanned invasive coronary angiography following coronary artery bypass grafting.

OBJECTIVES: Myocardial ischaemia following coronary artery bypass grafting (CABG) is a potentially devastating complication. Nevertheless, the incidence, aetiology and prognostic relevance of unplanned coronary angiography (uCAG) remain understudied. We aimed to investigate the prevalence and outcome of patients undergoing urgent, uCAG in the postoperative period following CABG. METHODS: We screened all patients undergoing isolated elective CABG in an academic referral centre between 2016 and 2021 and identified patients undergoing uCAG within 30 days of surgery. For uCAG patients, a distinction was made between patients undergoing re-revascularization (REV) and patients receiving conservative management (CON). The primary outcomes were 30-day mortality and unadjusted and adjusted long-term survival. Secondary outcomes were the indication for and prevalence of uCAG and urgent revascularization. RESULTS: Of the 1918 patients undergoing isolated CABG, 78 individuals needed uCAG (4.1%), of whom 45 underwent immediate revascularization (REV group; 2.3% overall, 57% within the uCAG group, median age 69.9 years) and 33 were treated conservatively (CONS group; 1.7% overall, 42% within the uCAG group, median age 69.1 years). Patients undergoing uCAG (n = 78) had a higher 30-day mortality than patients not undergoing uCAG (n = 1840, 30-day mortality: 9.0% vs 0.4%, P < 0.001). Long-term survival was significantly decreased in patients undergoing uCAG in both unadjusted (hazard ratio 2.20, 95% confidence interval 1.30-3.73) and EuroSCORE-, age- and sex-adjusted models (hazard ratio uCAG 2.03, 95% confidence interval 1.16-3.56). CONCLUSIONS: Unplanned postoperative coronary angiography is performed in 4.1% of isolated CABG procedures, and patients in need of such urgent invasive evaluation are subjected to decreased short- and long-term survival.

Continuation versus Interruption of Oral Anticoagulation during TAVI.

BACKGROUND: One third of patients undergoing transcatheter aortic-valve implantation (TAVI) have an indication for oral anticoagulation owing to concomitant diseases. Interruption of oral anticoagulation during TAVI may decrease the risk of bleeding, whereas continuation may decrease the risk of thromboembolism. METHODS: We conducted an international, open-label, randomized, noninferiority trial involving patients who were receiving oral anticoagulants and were planning to undergo TAVI. Patients were randomly assigned in a 1:1 ratio to periprocedural continuation or interruption of oral anticoagulation. The primary outcome was a composite of death from cardiovascular causes, stroke from any cause, myocardial infarction, major vascular complications, or major bleeding within 30 days after TAVI. RESULTS: A total of 858 patients were included in the modified intention-to-treat population: 431 were assigned to continuation and 427 to interruption of oral anticoagulation. A primary-outcome event occurred in 71 patients (16.5%) in the continuation group and in 63 (14.8%) in the interruption group (risk difference, 1.7 percentage points; 95% confidence interval [CI], -3.1 to 6.6; P = 0.18 for noninferiority). Thromboembolic events occurred in 38 patients (8.8%) in the continuation group and in 35 (8.2%) in the interruption group (risk difference, 0.6 percentage points; 95% CI, -3.1 to 4.4). Bleeding occurred in 134 patients (31.1%) in the continuation group and in 91 (21.3%) in the interruption group (risk difference, 9.8 percentage points; 95% CI, 3.9 to 15.6). CONCLUSIONS: In patients undergoing TAVI with a concomitant indication for oral anticoagulation, periprocedural continuation was not noninferior to interruption of oral anticoagulation during TAVI with respect to the incidence of a composite of death from cardiovascular causes, stroke, myocardial infarction, major vascular complications, or major bleeding at 30 days. (Funded by the Netherlands Organization for Health Research and Development and the St. Antonius Research Fund; POPular PAUSE TAVI ClinicalTrials.gov number, NCT04437303.).

Temporary omission of oral anticoagulation in atrial fibrillation patients undergoing percutaneous coronary intervention: rationale and design of the WOEST-3 randomised trial.

The optimal antithrombotic management of atrial fibrillation (AF) patients who require oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) remains unclear. Current guidelines recommend dual antithrombotic therapy (DAT; OAC plus P2Y12 inhibitor - preferably clopidogrel) after a short course of triple antithrombotic therapy (TAT; DAT plus aspirin). Although DAT reduces bleeding risk compared to TAT, this is counterbalanced by an increase in ischaemic events. Aspirin provides early ischaemic benefit, but TAT is associated with an increased haemorrhagic burden; therefore, we propose a 30-day dual antiplatelet therapy (DAPT; aspirin plus P2Y12 inhibitor) strategy post-PCI, temporarily omitting OAC. The study aims to compare bleeding and ischaemic risk between a 30-day DAPT strategy following PCI and a guideline-directed therapy in AF patients requiring OAC. WOEST-3 (ClinicalTrials.gov: NCT04436978) is an investigator-initiated, international, open-label, randomised controlled trial (RCT). AF patients requiring OAC who have undergone successful PCI will be randomised within 72 hours after PCI to guideline-directed therapy (edoxaban plus P2Y12 inhibitor plus limited duration of aspirin) or a 30-day DAPT strategy (P2Y12 inhibitor plus aspirin, immediately discontinuing OAC) followed by DAT (edoxaban plus P2Y12 inhibitor). With a sample size of 2,000 patients, this trial is powered to assess both superiority for major or clinically relevant non-major bleeding and non-inferiority for a composite of all-cause death, myocardial infarction, stroke, systemic embolism or stent thrombosis. In summary, the WOEST-3 trial is the first RCT temporarily omitting OAC in AF patients, comparing a 30-day DAPT strategy with guideline-directed therapy post-PCI to reduce bleeding events without hampering efficacy.

Health-related quality of life in elderly cardiac patients undergoing cardiac rehabilitation and the association with exercise capacity: The EU-CaRE study.

AIMS: The ability to be physically active is pivotal to the quality of life in elderly patients. This study aims to describe the association between exercise capacity and health-related quality of life (HRQoL), anxiety, and depression following an exercise-based cardiac rehabilitation (CR) program in elderly cardiac patients. METHODS: Patients aged ≥65 years with acute and chronic coronary syndrome or heart valve surgery were consecutively included from 8 CR centers in 7 European countries. Exercise capacity (VO2peak(ml/kg/min)) was assessed with a cardiopulmonary exercise test (97%) or a six-minute walk test. Outcome variables included HRQoL (SF-36 physical and mental component scores (PCS and MCS)), anxiety (GAD-7), and depression (PHQ-9). Mixed models were used to address the association between baseline and the development in VO2peak, and outcome variables stratified on sex, and adjusted for baseline values, age, and CR center. RESULTS: A total of 1,633 patients were included (T0), 1,523 (93%) completed end-of-CR assessment (T1), and 1,457 (89%) 1-year follow-up (T2). Women had higher % of predicted VO2peak, but poorer scores in HRQoL, anxiety and depression at all time-points. All scores improved in both sexes at follow-up. We found significant associations between VO2peak at baseline as well as development in VO2peak and all outcome variables at T1 and T2 in men (all p < 0.001). In women, VO2peak was only associated with PCS scores (p < 0.001). CONCLUSIONS: Improvements in exercise capacity was strongly associated with improvements in HRQoL and mental health, however with stronger associations in men. The results highlight the importance of physical fitness for HRQol and mental health. The findings from this study might be useful to better target individual CR programs.

This study explores the association between exercise capacity and the well-being of elderly cardiac patients participating in a cardiac rehabilitation program, focusing on health-related quality of life (HRQoL), anxiety, and depression. Key Findings:Women, despite having higher percentages of predicted exercise capacity, consistently reported poorer HRQoL, anxiety, and depression scores compared to men at all assessed time points.Improvements in exercise capacity were strongly associated with positive changes in HRQoL and mental health, with these associations being more pronounced in men.

Critical Analysis of Thrombocytopenia Associated With Glycoprotein IIb/IIIa Inhibitors and Potential Role of Zalunfiban, a Novel Small Molecule Glycoprotein Inhibitor, in Understanding the Mechanism(s).

Thrombocytopenia is a rare but serious complication of the intravenous glycoprotein IIb/IIIa (GPIIb/IIIa; integrin αIIbß3) receptor inhibitors (GPIs), abciximab, eptifibatide, and tirofiban. The thrombocytopenia ranges from mild (50 000-100 000 platelets/µL), to severe (20 000 to <50 000/µL), to profound (<20 000/µL). Profound thrombocytopenia appears to occur in <1% of patients receiving their first course of therapy. Thrombocytopenia can be either acute (<24 hours) or delayed (up to ~14 days). Both hemorrhagic and thrombotic complications have been reported in association with thrombocytopenia. Diagnosis requires exclusion of pseudothrombocytopenia and heparin-induced thrombocytopenia. Therapy based on the severity of thrombocytopenia and symptoms may include drug withdrawals and treatment with steroids, intravenous IgG, and platelet transfusions. Abciximab-associated thrombocytopenia is most common and due to either preformed antibodies or antibodies induced in response to abciximab (delayed). Readministration of abciximab is associated with increased risk of thrombocytopenia. Evidence also supports an immune basis for thrombocytopenia associated with the 2 small molecule GPIs. The latter bind αIIbß3 like the natural ligands and thus induce the receptor to undergo major conformational changes that potentially create neoepitopes. Thrombocytopenia associated with these drugs is also immune-mediated, with antibodies recognizing the αIIbß3 receptor only in the presence of the drug. It is unclear whether the antibody binding depends on the conformational change and whether the drug contributes directly to the epitope. Zalunfiban, a second-generation subcutaneous small molecule GPI, does not induce the conformational changes; therefore, data from studies of zalunfiban will provide information on the contribution of the conformational changes to the development of GPI-associated thrombocytopenia.

Stroke reduction by cerebral embolic protection devices in transcatheter aortic valve implantation: a systematic review and Bayesian meta-analysis.

OBJECTIVES: The use of cerebral embolic protection (CEP) during transcatheter aortic valve implantation (TAVI) has been studied in several randomised trials. We aimed to perform a systematic review and Bayesian meta-analysis of randomised CEP trials, focusing on a clinically relevant reduction in disabling stroke. METHODS: A systematic search was applied to three electronic databases, including trials that randomised TAVI patients to CEP versus standard treatment. The primary outcome was the risk of disabling stroke. Outcomes were presented as relative risk (RR), absolute risk differences (ARDs), numbers needed to treat (NNTs) and the 95% credible intervals (CrIs). The minimal clinically important difference was determined at 1.1% ARD, per expert consensus (NNT 91). The principal Bayesian meta-analysis was performed under a vague prior, and secondary analyses were performed under two informed literature-based priors. RESULTS: Seven randomised studies were included for meta-analysis (n=3996: CEP n=2126, control n=1870). Under a vague prior, the estimated median RR of CEP use for disabling stroke was 0.56 (95% CrI 0.28 to 1.19, derived ARD 0.56% and NNT 179, I2=0%). Although the estimated posterior probability of any benefit was 94.4%, the probability of a clinically relevant effect was 0-0.1% under the vague and informed literature-based priors. Results were robust across multiple sensitivity analyses. CONCLUSION: There is a high probability of a beneficial CEP treatment effect, but this is unlikely to be clinically relevant. These findings suggest that future trials should focus on identifying TAVI patients with an increased baseline risk of stroke, and on the development of new generation devices. PROSPERO REGISTRATION NUMBER: CRD42023407006.

Conservative versus Invasive Strategy in Elderly Patients with Non-ST-Elevation Myocardial Infarction: Insights from the International POPular Age Registry.

This registry assessed the impact of conservative and invasive strategies on major adverse clinical events (MACE) in elderly patients with non-ST-elevation myocardial infarction (NSTEMI). Patients aged ≥75 years with NSTEMI were prospectively registered from European centers and followed up for one year. Outcomes were compared between conservative and invasive groups in the overall population and a propensity score-matched (PSM) cohort. MACE included cardiovascular death, acute coronary syndrome, and stroke. The study included 1190 patients (median age 80 years, 43% female). CAG was performed in 67% (N = 798), with two-thirds undergoing revascularization. Conservatively treated patients had higher baseline risk. After propensity score matching, 319 patient pairs were successfully matched. MACE occurred more frequently in the conservative group (total population 20% vs. 12%, adjHR 0.53, 95% CI 0.37-0.77, p = 0.001), remaining significant in the PSM cohort (18% vs. 12%, adjHR 0.50, 95% CI 0.31-0.81, p = 0.004). In conclusion, an early invasive strategy was associated with benefits over conservative management in elderly patients with NSTEMI. Risk factors associated with ischemia and bleeding should guide strategy selection rather than solely relying on age.

Platelets and the Atherosclerotic Process: An Overview of New Markers of Platelet Activation and Reactivity, and Their Implications in Primary and Secondary Prevention.

The key role played by platelets in the atherosclerosis physiopathology, especially in the acute setting, is ascertained: they are the main actors during thrombus formation and, thus, one of the major investigated elements related to atherothrombotic process involving coronary arteries. Platelets have been studied from different points of view, according with the technology advances and the improvement in the hemostasis knowledge achieved in the last years. Morphology and reactivity constitute the first aspects investigated related to platelets with a significant body of evidence published linking a number of their values and markers to coronary artery disease and cardiovascular events. Recently, the impact of genetics on platelet activation has been explored with promising findings as additional instrument for patient risk stratification; however, this deserves further confirmations. Moreover, the interplay between immune system and platelets has been partially elucidated in the last years, providing intriguing elements that will be basic components for future research to better understand platelet regulation and improve cardiovascular outcome of patients.

Breathing pattern and pulmonary gas exchange in elderly patients with and without left ventricular dysfunction-modification with exercise-based cardiac rehabilitation and prognostic value.

Background: Inefficient ventilation is an established prognostic marker in patients with heart failure. It is not known whether inefficient ventilation is also linked to poor prognosis in patients with left ventricular dysfunction (LVD) but without overt heart failure. Objectives: To investigate whether inefficient ventilation in elderly patients with LVD is more common than in patients without LVD, whether it improves with exercise-based cardiac rehabilitation (exCR), and whether it is associated with major adverse cardiovascular events (MACE). Methods: In this large multicentre observational longitudinal study, patients aged ≥65 years with acute or chronic coronary syndromes (ACS, CCS) without cardiac surgery who participated in a study on the effectiveness of exCR in seven European countries were included. Cardiopulmonary exercise testing (CPET) was performed before, at the termination of exCR, and at 12 months follow-up. Ventilation (VE), breathing frequency (BF), tidal volume (VT), and end-expiratory carbon dioxide pressure (PETCO2) were measured at rest, at the first ventilatory threshold, and at peak exercise. Ventilatory parameters were compared between patients with and without LVD (based on cardio-echography) and related to MACE at 12 month follow-up. Results: In 818 patients, age was 72.5 ± 5.4 years, 21.9% were women, 79.8% had ACS, and 151 (18%) had LVD. Compared to noLVD, in LVD resting VE was increased by 8%, resting BF by 6%, peak VE, peak VT, and peak PETCO2 reduced by 6%, 8%, and 5%, respectively, and VE/VCO2 slope increased by 11%. From before to after exCR, resting VE decreased and peak PETCO2 increased significantly more in patients with compared to without LVD. In LVD, higher resting BF, higher nadir VE/VCO2, and lower peak PETCO2 at baseline were associated with MACE. Conclusions: Similarly to patients with HF, in elderly patients with ischemic LVD, inefficient resting and exercise ventilation was associated with worse outcomes, and ExCR alleviated abnormal breathing patterns and gas exchange parameters.