Relationship between peripheral and intracoronary blood flow in patients with angina and nonobstructive coronary arteries.

Coronary vasomotor dysfunction, an important underlying cause of angina and nonobstructive coronary arteries (ANOCA), encompassing coronary vasospasm, coronary endothelial dysfunction, and/or coronary microvascular dysfunction, is clinically assessed by invasive coronary function testing (ICFT). As ICFT imposes a high burden on patients and carries risks, developing noninvasive alternatives is important. We evaluated whether coronary vasomotor dysfunction is a component of systemic microvascular endothelial and smooth muscle dysfunction and can be detected using laser speckle contrast analysis (LASCA). Forty-three consecutive patients with ANOCA underwent ICFT, with intracoronary acetylcholine, adenosine, and flow measurements, to assess coronary vasomotor dysfunction. Cutaneous microvascular function was assessed using LASCA in the forearm, combined with vasodilators acetylcholine, sodium nitroprusside, and insulin and using EndoPAT, by measuring the reactive hyperemia index (RHI). Of the 43 included patients with ANOCA (79% women, 59 ± 9 yr old), 38 patients had coronary vasomotor dysfunction, including 28 with coronary vasospasm, 26 with coronary endothelial dysfunction, and 18 with coronary microvascular dysfunction, with overlapping endotypes. Patients with and without coronary vasomotor dysfunction had similar peripheral flow responses to acetylcholine, insulin, and RHI. In contrast, coronary vasomotor dysfunction was associated with lower peripheral flow responses to sodium nitroprusside (P < 0.001). An absolute flow response to sodium nitroprusside of 83.95 APU resulted in 86.1% sensitivity and 80.0% specificity for coronary vasomotor dysfunction (area under the ROC curve, 0.883; P = 0.006). In conclusion, this study provides evidence of systemic vascular smooth muscle dysfunction in patients with ANOCA with coronary vasomotor dysfunction and the diagnostic value of peripheral microvascular function testing as a noninvasive tool for detecting coronary vasomotor dysfunction.NEW & NOTEWORTHY This study provides proof of concept that assessment of the peripheral vasculature, particularly vascular smooth muscle cells measured using the LASCA technology holds potential as a noninvasive tool for detecting coronary vasomotor dysfunction. This finding highlights the potential of the LASCA technology in, for example, medication studies for coronary vasomotor dysfunction, especially when investigating whether medication improves vascular function, as repeated peripheral measurements are less invasive than invasive coronary function testing, the current gold standard.

Presentation, care, coronary intervention and outcomes of patients with NSTEMI according to age: insights from the international prospective ACVC-EAPCI EORP NSTEMI registry.

BACKGROUND: Older people less frequently receive invasive coronary angiography (ICA) for NSTEMI than younger patients. We describe care, ICA data, and in-hospital and 30-day outcomes of NSTEMI by age in a contemporary and geographically diverse cohort. METHODS: Prospective cohort study including 2947 patients with NSTEMI from 287 centres in 59 countries, stratified by age (≥75 years, n = 761). Quality of care was evaluated based on 12 guideline-recommended care interventions, and data collected on ICA. Outcomes included in hospital acute heart failure, cardiogenic shock, repeat myocardial infarction, stroke/transient ischaemic attack, BARC Type ≥3 bleeding and death, as well as 30-day mortality. RESULTS: Patients aged ≥75 years, compared with younger patients, at presentation had a higher prevalence of comorbidities and oral anticoagulation prescription (22.4% vs 7.6%, p < 0.001). Older patients less frequently received ICA than younger patients (78.6% vs 90.6%, p < 0.001) with the recorded reason more often being advanced age, comorbidities or frailty. Of those who underwent ICA, older patients more frequently demonstrated 3-vessel, 4-vessel and/or left main stem coronary artery disease compared to younger patients (49.7% vs 34.1%, p < 0.001) but less frequently received revascularisation (63.6% vs 76.9%, p < 0.001). Older patients experienced higher rates of in-hospital acute heart failure (15.0% vs 8.4%, p < 0.001) and bleeding (2.8% vs 1.3%, p = 0.006), as well as in-hospital and 30-day mortality (3.4% vs 1.3%, p < 0.001; 4.8% vs 1.7%, p < 0.001; respectively), than younger patients. CONCLUSIONS: Patients aged ≥75 years with NSTEMI, compared with younger patients, less frequently received ICA and guideline-recommended care, and had worse short-term outcomes.

Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion.

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min-1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.

The Diagnostic Value of ECG Characteristics for Vasospastic and Microvascular Angina: A Systematic Review.

BACKGROUND: Coronary vascular dysfunction comprises VSA and/or MVA and is more common in women than in men with angina without obstructive coronary artery disease (ANOCA). Invasive coronary function testing is considered the reference test for diagnosis, but its burden on patients is large. We aimed to investigate the potential of electrocardiography (ECG) as noninvasive marker for vasospastic angina (VSA) and microvascular angina (MVA) diagnosis. METHODS: We systematically screened Pubmed and EMBASE databases for studies reporting on ECG characteristics in ANOCA patients with (a suspicion of) coronary vascular dysfunction. We assessed study quality using QUADAS-2. We extracted data on diagnostic values of different ECG characteristics and analyzed whether the studies were sex-stratified. RESULTS: Thirty publications met our criteria, 13 reported on VSA and 17 on MVA. The majority addressed repolarization-related ECG parameters. Only 1 of the 13 VSA papers and 4 of the 17 MVA papers showed diagnostic accuracy measures of the ECG characteristics. The presence of early repolarization, T-wave alternans, and inverted U waves showed of predictive value for VSA diagnosis. The QTc interval was predictive for MVA diagnosis in all six studies reporting on QTc interval. Sex-stratified results were reported in only 5 of the 30 studies and 3 of those observed sex-based differences. CONCLUSIONS: ECG features are not widely evaluated in diagnostic studies for VSA and MVA. Those features predictive for VSA and MVA diagnosis mostly point to repolarization abnormalities and may contribute to noninvasive risk stratification.

In-hospital mortality of patients with acute coronary syndrome (ACS) after implementation of national health insurance (NHI) in Indonesia.

BACKGROUND: The National Health Insurance (NHI) was implemented in Indonesia in 2014, and cardiovascular diseases are one of the diseases that have overburdened the healthcare system. However, data concerning the relationship between NHI and cardiovascular healthcare in Indonesia are scarce. We aimed to describe changes in cardiovascular healthcare after the implementation of the NHI while determining whether the implementation of the NHI is related to the in-hospital mortality of patients with acute coronary syndrome (ACS). METHODS: This is a retrospective comparative study of two cohorts in which we compared the data of 364 patients with ACS from 2013 to 2014 (Cohort 1), before and early after NHI implementation, with those of 1142 patients with ACS from 2018 to 2020 (Cohort 2), four years after NHI initiation, at a tertiary cardiac center in Makassar, Indonesia. We analyzed the differences between both cohorts using chi-square test and Mann-Whitney U test. To determine the association between NHI and in-hospital mortality, we conducted multivariable logistic regression analysis. RESULTS: We observed an increase in NHI users (20.1% to 95.6%, p < 0.001) accompanied by a more than threefold increase in patients with ACS admitted to the hospital in Cohort 2 (from 364 to 1142, p < 0.001). More patients with ACS received invasive treatment in Cohort 2, with both thrombolysis and percutaneous coronary intervention (PCI) rates increasing more than twofold (9.2% to 19.2%; p < 0.001). There was a 50.8% decrease in overall in-hospital mortality between Cohort 1 and Cohort 2 (p < 0.001). CONCLUSIONS: This study indicated the potential beneficial effect of universal health coverage (UHC) in improving cardiovascular healthcare by providing more accessible treatment. It can provide evidence to urge the Indonesian government and other low- and middle-income nations dealing with cardiovascular health challenges to adopt and prioritize UHC.

Migraine and cardiovascular disease: what cardiologists should know.

Migraine is a chronic neurovascular disease with a complex, not fully understood pathophysiology with multiple causes. People with migraine suffer from recurrent moderate to severe headache attacks varying from 4 to 72 h. The prevalence of migraine is two to three times higher in women compared with men. Importantly, it is the most disabling disease in women <50 years of age due to a high number of years lived with disability, resulting in a very high global socioeconomic burden. Robust evidence exists on the association between migraine with aura and increased incidence of cardiovascular disease (CVD), in particular ischaemic stroke. People with migraine with aura have an increased risk of atrial fibrillation, myocardial infarction, and cardiovascular death compared with those without migraine. Ongoing studies investigate the relation between migraine and angina with non-obstructive coronary arteries and migraine patients with patent foramen ovale. Medication for the treatment of migraine can be preventative medication, such as beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, antiepileptics, antidepressants, some of the long-acting calcitonin gene-related peptide receptor antagonists, or monoclonal antibodies against calcitonin gene-related peptide or its receptor, or acute medication, such as triptans and calcitonin gene-related peptide receptor antagonists. However, these medications might raise concerns when migraine patients also have CVD due to possible (coronary) side effects. Specifically, knowledge gaps remain for the contraindication to newer treatments for migraine. All cardiologists will encounter patients with CVD and migraine. This state-of-the-art review will outline the basic pathophysiology of migraine and the associations between migraine and CVD, discuss current therapies, and propose future directions for research.

Overcoming professional barriers encountered by women in interventional cardiology: an EAPCI statement.

Despite the increasing proportion of female medical and nursing students, there is still a significant under-representation of women working as healthcare providers in interventional cardiology, with very few of them reaching senior leadership, academic positions, or acting principal investigators, as well as actively involved in company advisory boards. In this position paper, we will describe the current status of women working in interventional cardiology across Europe. We will also provide an overview of the most relevant determinants of the under-representation of women at each stage of the interventional cardiology career path and offer practical suggestions for overcoming these challenges.

Microvascular resistance reserve: diagnostic and prognostic performance in the ILIAS registry.

AIMS: The microvascular resistance reserve (MRR) was introduced as a means to characterize the vasodilator reserve capacity of the coronary microcirculation while accounting for the influence of concomitant epicardial disease and the impact of administration of potent vasodilators on aortic pressure. This study aimed to evaluate the diagnostic and prognostic performance of MRR. METHODS AND RESULTS: A total of 1481 patients with stable symptoms and a clinical indication for coronary angiography were included from the global ILIAS Registry. MRR was derived as a function of the coronary flow reserve (CFR) divided by the fractional flow reserve (FFR) and corrected for driving pressure. The median MRR was 2.97 [Q1-Q3: 2.32-3.86] and the overall relationship between MRR and CFR was good [correlation coefficient (Rs) = 0.88, P < 0.005]. The difference between CFR and MRR increased with decreasing FFR [coefficient of determination (R2) = 0.34; Coef.-2.88, 95% confidence interval (CI): -3.05--2.73; P < 0.005]. MRR was independently associated with major adverse cardiac events (MACE) at 5-year follow-up [hazard ratio (HR) 0.78; 95% CI 0.63-0.95; P = 0.024] and with target vessel failure (TVF) at 5-year follow-up (HR 0.83; 95% CI 0.76-0.97; P = 0.047). The optimal cut-off value of MRR was 3.0. Based on this cut-off value, only abnormal MRR was significantly associated with MACE and TVF at 5-year follow-up in vessels with functionally significant epicardial disease (FFR <0.75). CONCLUSION: MRR seems a robust indicator of the microvascular vasodilator reserve capacity. Moreover, in line with its theoretical background, this study suggests a diagnostic advantage of MRR over other indices of vasodilatory capacity in patients with hemodynamically significant epicardial coronary artery disease.

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.

Less bleeding by omitting aspirin in non-ST-segment elevation acute coronary syndrome patients: Rationale and design of the LEGACY study.

BACKGROUND: Early aspirin withdrawal, also known as P2Y12-inhibitor monotherapy, following percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can reduce bleeding without a trade-off in efficacy. Still the average daily bleeding risk is highest during the first months and it remains unclear if aspirin can be omitted immediately following PCI. METHODS: The LEGACY study is an open-label, multicenter randomized controlled trial evaluating the safety and efficacy of immediate P2Y12-inhibitor monotherapy versus dual antiplatelet therapy (DAPT) for 12 months in 3,090 patients. Patients are randomized immediately following successful PCI for NSTE-ACS to 75-100 mg aspirin once daily versus no aspirin. The primary hypothesis is that immediately omitting aspirin is superior to DAPT with respect to major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, while maintaining noninferiority for the composite of all-cause mortality, myocardial infarction and stroke compared to DAPT. CONCLUSIONS: The LEGACY study is the first randomized study that is specifically designed to evaluate the impact of immediately omitting aspirin, and thus treating patients with P2Y12-inhibitor monotherapy, as compared to DAPT for 12 months on bleeding and ischemic events within 12 months following PCI for NSTE-ACS.

Impact of cardiac history and myocardial scar on increase of myocardial perfusion after revascularization.

PURPOSE: We sought to assess the impact of coronary revascularization on myocardial perfusion and fractional flow reserve (FFR) in patients without a cardiac history, with prior myocardial infarction (MI) or non-MI percutaneous coronary intervention (PCI). Furthermore, we studied the impact of scar tissue. METHODS: Symptomatic patients underwent [15O]H2O positron emission tomography (PET) and FFR before and after revascularization. Patients with prior CAD, defined as prior MI or PCI, underwent scar quantification by magnetic resonance imaging late gadolinium enhancement. RESULTS: Among 137 patients (87% male, age 62.2 ± 9.5 years) 84 (61%) had a prior MI or PCI. The increase in FFR and hyperemic myocardial blood flow (hMBF) was less in patients with prior MI or non-MI PCI compared to those without a cardiac history (FFR: 0.23 ± 0.14 vs. 0.20 ± 0.12 vs. 0.31 ± 0.18, p = 0.02; hMBF: 0.54 ± 0.75 vs. 0.62 ± 0.97 vs. 0.91 ± 0.96 ml/min/g, p = 0.04). Post-revascularization FFR and hMBF were similar across patients without a cardiac history or with prior MI or non-MI PCI. An increase in FFR was strongly associated to hMBF increase in patients without a cardiac history or with prior MI/non-MI PCI (r = 0.60 and r = 0.60, p < 0.01 for both). Similar results were found for coronary flow reserve. In patients with prior MI scar was negatively correlated to hMBF increase and independently predictive of an attenuated CFR increase. CONCLUSIONS: Post revascularization FFR and perfusion were similar among patients without a cardiac history, with prior MI or non-MI PCI. In patients with prior MI scar burden was associated to an attenuated perfusion increase.

Sex differences in antiplatelet therapy: state-of-the art.

Antiplatelet therapy is a cornerstone of secondary prevention of cardiovascular diseases (CVDs). However, current guidelines are based on data derived primarily from men, as women are generally underrepresented in trials. Consequently, there are insufficient and inconsistent data on the effect of antiplatelet drugs in women. Sex differences were reported in platelet reactivity, patient management, and clinical outcomes after treatment with aspirin, P2Y12 inhibitor, or dual antiplatelet therapy. To evaluate whether sex-specific antiplatelet therapy is needed, in this review we discuss (i) how sex affects platelet biology and response to antiplatelet agents, (ii) how sex and gender differences translate into clinical challenges and (iii) how the cardiological care in women might be improved. Finally, we highlight the challenges faced in clinical practice regarding the different needs and characteristics of female and male patients with CVD and address issues requiring further investigation.

Antiplatelet therapy is a crucial part of cardiovascular disease prevention. Guidelines are based on data from men, as too few women participate in trials. We reviewed differences between women and men in antiplatelet therapy. Sex differences occur in platelet reactivity and in the response to the therapy with aspirin and/or P2Y₁₂ inhibitors. In primary prevention with aspirin, sex should be considered. In secondary prevention, aspirin, clopidogrel, ticagrelor, and prasugrel should be used in women as in men, according to individual patient needs. Female and male cardiac patients might present with different symptoms and risk factors. Healthcare professionals often treat women differently than men and do not satisfy women's needs. Education of researchers and healthcare professionals is required to provide highest standard of cardiological care to women. This review summarizes the evidence on sex differences in antiplatelet therapy ­ from diagnosis, through patient management, to treatment outcomes. It describes how molecular aspects translate into clinical practice and how to provide effective antiplatelet therapy to female patients.Abbreviations: ACS: acute coronary syndrome; ADP: adenosine 5'-diphosphate; BARC: Bleeding Academic Research Consortium; CAD: coronary artery disease; cAMP: cyclic adenosine 5'-monophosphate; COX-1: cyclooxygenase-1; CYP: cytochrome P; CVD(s): cardiovascular disease(s); DAPT: dual antiplatelet therapy; DES: drug-eluting stent; DM: Diabetes mellitus; GP: glycoprotein; MI: myocardial infarction; PCI: percutaneous coronary intervention; PGH₂: prostaglandin H₂; PKA: protein kinase A; TR: thromboxane receptor; TXA₂: thromboxane A₂; VASP: vasodilator-stimulated phosphoprotein; VWF: von Willebrand factor.

Sex-Related Bleeding Risk in Acute Coronary Syndrome Patients Receiving Dual Antiplatelet Therapy with Aspirin and a P2Y12 Inhibitor.

OBJECTIVE: The aim of this work was to study sex differences in major bleeding risk in relation to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). METHODS AND RESULTS: The Rijnmond Collective Cardiology Research registry was designed to evaluate the application and outcomes of DAPT after ACS/PCI in the Rijnmond region in the Netherlands. Overall, 1,172 women (median age 67.5 years) and 3,087 men (median age 62.2 years) with ACS/PCI were enrolled between August 2011 and June 2013. Based on a tailored regional DAPT guideline aiming at bleeding risk minimization, 52.6% women and 66.9% men received prasugrel as first-choice P2Y12 inhibitor, in addition to aspirin. Women more frequently had contraindications for the use of prasugrel (and therefore received clopidogrel) than men (47.9 vs. 26.9%, p < 0.001). Femoral access was more common in women than in men (47.6 vs. 38.1%, p < 0.001). Women had higher incidence of major bleeding at 1 year than men (2.6 vs. 1.6%, p = 0.018). After adjustment for established bleeding risk factors, female sex was associated with over two-fold higher risk of major bleeding (adjusted hazard ratio 2.33; 95% confidence interval 1.26-4.32). This difference was apparent at discharge and appeared to be caused by access site bleedings (0.9 vs. 0.1%, p < 0.001). No sex differences were found in non-access site-related major bleeding up to 1 year. CONCLUSION: Women with ACS/PCI receiving DAPT had higher major bleeding risk caused by an excess in access site bleeds, mainly in relation to the femoral approach.

The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030.

Cardiovascular disease is the leading cause of death in women. Decades of grassroots campaigns have helped to raise awareness about the impact of cardiovascular disease in women, and positive changes affecting women and their health have gained momentum. Despite these efforts, there has been stagnation in the overall reduction of cardiovascular disease burden for women in the past decade. Cardiovascular disease in women remains understudied, under-recognised, underdiagnosed, and undertreated. This Commission summarises existing evidence and identifies knowledge gaps in research, prevention, treatment, and access to care for women. Recommendations from an international team of experts and leaders in the field have been generated with a clear focus to reduce the global burden of cardiovascular disease in women by 2030. This Commission represents the first effort of its kind to connect stakeholders, to ignite global awareness of sex-related and gender-related disparities in cardiovascular disease, and to provide a springboard for future research.

Revascularization strategies for patients with established chronic coronary syndrome.

Coronary artery disease is the most common type of cardiovascular disease, leading to high mortality rates worldwide. Although the vast majority can be treated effectively and safely by medical therapy, revascularization strategies remain essential for numerous patients. Outcomes of both percutaneous coronary intervention and coronary artery bypass grafting improve in a rapid pace, resulting from technical innovation and ongoing research. Progress has been achieved by technical improvements in coronary stents, optimal coronary target and graft selection, and the availability of minimally invasive surgical strategies. Besides technical progress, evidence-based patient-tailored decision-making by the Heart Team is the basic precondition for optimal outcome. The combination of fast innovation and long-term clinical evaluations creates a dynamic field. Research outcomes should be carefully interpreted according to the techniques used and the trial's design. Therefore, more and more trial outcomes suggest that revascularization strategies should be tailored towards the specific patient. Although the European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines on myocardial revascularization date from 2018 and a large variety of trial outcomes on revascularization strategies in chronic coronary syndrome have been published since, we aim to provide an updated overview within this review.

Sex Differences in the Relationship between New York Heart Association Functional Classification and Survival in Cardiovascular Disease Patients: A Mediation Analysis of Exercise Capacity with Regular Care Data.

Background: The New York Heart Association (NYHA) functional class has extensively been used for risk stratification in patients suspected of heart failure, although its prognostic value differs between sexes and disease entities. Functional exercise capacity might explain the association between NYHA functional class and survival, and can serve as an objective proxy for the subjective nature of the NYHA classification. Therefore, we assessed whether sex-differences in exercise capacity explain the association between NYHA functional class and survival in patients suspected of cardiovascular disease. Methods: Electronic health record data from 7259 patients with cardiovascular symptoms, a documented NYHA functional class and cardiac stress electrocardiogram (ECG), was analysed. Follow-up for all-cause mortality was obtained through linkage with Statistics Netherlands. A sex-stratified mediation analysis was performed to assess to what extent the proportional heart rate and -workload during ECG stress testing explain the association between NYHA functional class and survival. Results: In men, increments in NYHA functional class were related to higher all-cause mortality in a dose-response manner (NYHA II vs III/IV: hazard ratio [HR] 1.59 vs 3.64, referenced to NYHA I), whilst in women those classified as NYHA functional class II and III/IV had a similar higher mortality risk (HR 1.49 vs 1.41). Sex-stratified mediation analysis showed that the association between NYHA and survival was mostly explained by proportional workload during stress ECG (men vs women: 22.9%, 95% CI: 18.9%-27.3% vs 40.3%, 95% CI: 28.5%-68.6%) and less so by proportional heart rate (men vs women: 2.5%, 95% CI: 1.3%-4.3% vs 8.0%, 95% CI: 4.1%-18.1%). Post-hoc analysis showed that NYHA classification explained a minor proportion of the association between proportional workload and all-cause mortality (men vs women: 15.1%, 95% CI: 12.0%-18.3% vs 4.4%, 95% CI: 1.5%-7.4%). Conclusions: This study showed a significant mediation in both sexes on the association between NYHA functional class and all-cause mortality by proportional workload, but the effect explained by NYHA classification on the association between survival and proportional workload is small. This implies that NYHA classification is not a sole representation of a patient's functional capacity, but might also incude other aspects of the patient's overall health status.

Residual Quantitative Flow Ratio to Estimate Post-Percutaneous Coronary Intervention Fractional Flow Reserve.

OBJECTIVES: Quantitative flow ratio (QFR) computes fractional flow reserve (FFR) based on invasive coronary angiography (ICA). Residual QFR estimates post-percutaneous coronary intervention (PCI) FFR. This study sought to assess the relationship of residual QFR with post-PCI FFR. METHODS: Residual QFR analysis, using pre-PCI ICA, was attempted in 159 vessels with post-PCI FFR. QFR lesion location was matched with the PCI location to simulate the performed intervention and allow computation of residual QFR. A post-PCI FFR < 0.90 was used to define a suboptimal PCI result. RESULTS: Residual QFR computation was successful in 128 (81%) vessels. Median residual QFR was higher than post-PCI FFR (0.96 Q1-Q3: 0.91-0.99 vs. 0.91 Q1-Q3: 0.86-0.96, p < 0.001). A significant correlation and agreement were observed between residual QFR and post-PCI FFR (R = 0.56 and intraclass correlation coefficient = 0.47, p < 0.001 for both). Following PCI, an FFR < 0.90 was observed in 54 (42%) vessels. Specificity, positive predictive value, sensitivity, and negative predictive value of residual QFR for assessment of the PCI result were 96% (95% confidence interval (CI): 87-99%), 89% (95% CI: 72-96%), 44% (95% CI: 31-59%), and 70% (95% CI: 65-75%), respectively. Residual QFR had an accuracy of 74% (95% CI: 66-82%) and an area under the receiver operating characteristic curve of 0.79 (95% CI: 0.71-0.86). CONCLUSIONS: A significant correlation and agreement between residual QFR and post-PCI FFR were observed. Residual QFR ≥ 0.90 did not necessarily commensurate with a satisfactory PCI (post-PCI FFR ≥ 0.90). In contrast, residual QFR exhibited a high specificity for prediction of a suboptimal PCI result.

An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group.

This consensus document, a summary of the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), appraises the importance of ischaemia with non-obstructive coronary arteries (INOCA). Angina pectoris affects approximately 112 million people globally. Up to 70% of patients undergoing invasive angiography do not have obstructive coronary artery disease, more common in women than in men, and a large proportion have INOCA as a cause of their symptoms. INOCA patients present with a wide spectrum of symptoms and signs that are often misdiagnosed as non-cardiac leading to under-diagnosis/investigation and under-treatment. INOCA can result from heterogeneous mechanism including coronary vasospasm and microvascular dysfunction and is not a benign condition. Compared to asymptomatic individuals, INOCA is associated with increased incidence of cardiovascular events, repeated hospital admissions, as well as impaired quality of life and associated increased health care costs. This consensus document provides a definition of INOCA and guidance to the community on the diagnostic approach and management of INOCA based on existing evidence from research and best available clinical practice; noting gaps in knowledge and potential areas for further investigation.

Sex- and gender-sensitive public health research: an analysis of research proposals in a research institute in the Netherlands.

Taking sex and gender into account in public health research is essential to optimize methodological procedures, bridge the gender gap in public health knowledge, and advance gender equality. The aim of this study was to evaluate the current status of sex and gender considerations in public health research proposals in a Dutch research institute. We screened a random sample of 38 proposals submitted for review to the institute's science committee between 2011 and 2016. Using the Canadian Institutes of Health Research' Gender and Health Institute criteria for gender-sensitive research and qualitative content analysis, we assessed if, and how sex and gender were considered throughout the proposals (background, research aim, design, data collection, and analysis). Our results show that in general, both sex and gender were poorly considered. Gender was insufficiently taken into account throughout most proposals. When sex was mentioned in a proposal, its consideration was often inconsistent and fragmented. Finally, we identified common methodological pitfalls. We recommend that public health curricula and funding bodies increase their focus on implementing sex and gender in public health research, for instance through quality criteria, training programs for researchers and reviewers, and capacity building initiatives.

The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome.

OBJECTIVES: Contradictory results have been reported regarding the association between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD). We assessed the cardiometabolic phenotype and prevalence of CVD in middle-aged women with PCOS, compared with age-matched controls from the general population, and estimated 10-year CVD risk and cardiovascular health score. DESIGN: A cross-sectional study. PARTICIPANTS: 200 women aged >45 with PCOS, and 200 age-matched controls. MEASUREMENTS: Anthropometrics, insulin, lipid levels, prevalence of metabolic syndrome and type II diabetes. Ten-year Framingham risk score and the cardiovascular health score were calculated, and carotid intima-media thickness (cIMT) was measured. RESULTS: Mean age was 50.5 years (SD = 5.5) in women with PCOS and 51.0 years (SD = 5.2) in controls. Increased waist circumference, body mass index and hypertension were more often observed in women with PCOS (P < .001). In women with PCOS, the prevalence of type II diabetes and metabolic syndrome was not significantly increased and lipid levels were not different from controls. cIMT was lower in women with PCOS (P < .001). Calculated cardiovascular health and 10-year CVD risk were similar in women with PCOS and controls. CONCLUSIONS: Middle-aged women with PCOS exhibit only a moderately unfavourable cardiometabolic profile compared to age-matched controls, even though they present with an increased BMI and waist circumference. Furthermore, we found no evidence for increased (10-year) CVD risk or more severe atherosclerosis compared with controls from the general population. Long-term follow-up of women with PCOS is necessary to provide a definitive answer concerning long-term risk for CVD.