RESUMEN

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.

RESUMEN

BACKGROUND: CYP2C19 genotype-guided de-escalation from ticagrelor or prasugrel to clopidogrel may optimize the balance between ischemic and bleeding risk in patients with acute coronary syndrome (ACS). OBJECTIVES: This study sought to compare bleeding and ischemic event rates in genotyped patients vs standard care. METHODS: Since 2015, ACS patients in the multicenter FORCE-ACS (Future Optimal Research and Care Evaluation in Patients with Acute Coronary Syndrome) registry received standard dual antiplatelet therapy (DAPT). Since 2021, genotype-guided P2Y12 inhibitor de-escalation was recommended at a single center, switching noncarriers of the loss-of-function allele CYP2C19∗3 or CYP2C19∗2 from ticagrelor or prasugrel to clopidogrel, whereas loss-of-function carriers remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction, or stroke, and the primary bleeding endpoint, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, were compared between a genotyped cohort and a cohort treated with standard DAPT after 1 year. RESULTS: Among 5,321 enrolled ACS patients, 406 underwent genotyping compared with 4,915 nongenotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n = 265) were noncarriers, 88.7% (n = 235) of whom were switched to clopidogrel. The primary ischemic endpoint occurred in 5.2% (n = 21) of patients in the genotyped cohort compared to 6.9% (n = 337) in the standard care cohort (adjusted HR: 0.82; 95% CI: 0.53-1.28). The primary bleeding rate was significantly lower in the genotyped cohort compared to the standard care cohort (4.7% vs 9.8%; adjusted HR: 0.47; 95% CI: 0.30-0.76). CONCLUSIONS: The implementation of a CYP2C19 genotype-guided P2Y12 inhibitor de-escalation strategy in a real-world ACS population resulted in lower bleeding rates without an increase in ischemic events compared to a standard DAPT regimen.

RESUMEN

BACKGROUND: Angina with Non-Obstructed Coronary Arteries (ANOCA) involves abnormal vasomotor responses. While reduced coronary flow is an established contributor to myocardial hypoxia, myocardial blood volume (MBV) independently regulates myocardial oxygen uptake but its role in ANOCA remains unclear. OBJECTIVES: We hypothesized that reduced MBV contributes to ANOCA, and associates with insulin resistance in ANOCA. METHODS: MBV in ANOCA patients was compared to age- and sex-matched healthy controls. ANOCA patients underwent coronary angiography with invasive coronary function testing (CFT) to identify vasospasm and coronary microvascular dysfunction. In all subjects MBV was quantified at baseline, during hyperinsulinemia and during dobutamine-induced stress using myocardial contrast echocardiography (MCE). The hyperinsulinemic-euglycemic clamp was used to assess insulin resistance. RESULTS: Twenty-eight ANOCA patients (21% men, 56.8 ± 8.6 years) and 28 healthy controls (21% men, 56.5 ± 7.0 years) were included. During CFT 11% of patients showed epicardial vasospasm, 39% microvascular vasospasm, 25% coronary microvascular dysfunction, and 11% of patients had a negative CFT. ANOCA patients had significant lower insulin-sensitivity (p < 0.01). During MCE, ANOCA patients showed a significantly lower MBV at baseline (0.388 vs 0.438 mL/mL, p = 0.04), during hyperinsulinemia (0.395 vs 0.447 mL/mL, p = 0.02), and during dobutamine-induced stress (0.401 vs 0.476 mL/mL, p = 0.030). CONCLUSIONS: In ANOCA patients MBV is diminished at baseline, during hyperinsulinemia and dobutamine-induced stress in the absence of differences in microvascular recruitment. These findings support the presence of capillary rarefaction in ANOCA patients. ANOCA patients showed metabolic insulin resistance, but insulin did not acutely alter myocardial perfusion.

Asunto(s)

RESUMEN

Background: Coronary vasomotor dysfunction, an important underlying cause of angina and non-obstructive 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 non-invasive 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). Methods: Forty-three consecutive ANOCA patients underwent ICFT, with intracoronary acetylcholine, adenosine, and flow measurements, to assess coronary vasomotor dysfunction. Cutaneous microvascular function was assessed using LASCA, combined with vasodilators acetylcholine, sodium-nitroprusside and insulin and using EndoPAT, by measuring the reactive hyperemia index (RHI). Results: Of the 43 included ANOCA patients (79% women, 59±9 years), 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 83.95APU resulted in 86.1% sensitivity and 80.0% specificity for coronary vasomotor dysfunction (area under the ROC curve: 0.883; p=0.006). Conclusions: This study provides evidence of a systemic vascular smooth muscle dysfunction in ANOCA patients with coronary vasomotor dysfunction, and diagnostic value of peripheral microvascular function testing as non-invasive tool for detecting coronary vasomotor dysfunction.

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

Asunto(s)

RESUMEN

OBJECTIVES: We sought to investigate the impact of sex on myocardial perfusion changes following chronic total coronary occlusion (CTO) percutaneous coronary intervention (PCI) as measured by [15O]H2O positron-emission tomography (PET) perfusion imaging. BACKGROUND: CTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization. As such, data on the impact of sex on myocardial perfusion following CTO PCI is scarce. METHODS: A total of 212 patients were prospectively enrolled and underwent CTO PCI combined with [15O]H2O PET perfusion imaging prior to and 3 months after PCI. Hyperemic myocardial blood flow (hMBF, mL·min-1·g-1) and coronary flow reserve (CFR) allocated to the CTO territory were quantitatively assessed. RESULTS: This study comprised 34 (16 %) females and 178 (84 %) males. HMBF at baseline did not differ between sexes. Females showed a higher increase in hMBF than males (Δ1.34 ± 0.67 vs. Δ1.06 ± 0.74, p = 0.044), whereas post-PCI hMBF was comparable (2.59 ± 0.85 in females vs. 2.28 ± 0.84 in males, p = 0.052). Female sex was independently associated with a higher increase in hMBF after correction for clinical covariates. CFR increase after revascularization was similar in females and males (Δ1.47 ± 0.99 vs. Δ1.30 ± 1.14, p = 0.711). CONCLUSIONS: The present study demonstrates a greater recovery of stress perfusion in females compared to males as measured by serial [15O]H2O PET imaging. In addition, a comparable increase in CFR was found in females and males. These results emphasize the benefit of performing CTO PCI in both sexes. CLINICAL PERSPECTIVE: What is new? What are the clinical implications?

RESUMEN

PURPOSE: Hodgkin lymphoma (HL) survivors are at increased risk of cardiovascular disease (CVD) due to former lymphoma treatment. In 2013, cardiovascular screening for 5-year HL survivors according to national guidelines was implemented in Dutch survivorship clinics. We aim to assess the following: (1) adherence to screening guidelines and (2) the yield of (risk factors for) CVD in the screening program. METHODS: The study population consisted of 5-year HL survivors who received survivorship care at three University Medical Centers from 2013 to 2016 through 2021. Patient characteristics, cardiovascular screening procedures, and outcomes were collected from the medical records. RESULTS: In 186 survivors eligible for cardiovascular screening (mean age 47.8 years, 60.8% female), the following diagnostics were performed: complete blood tests (81.0%, median frequency: yearly instead of advised 5-yearly evaluation), electrocardiogram (93.0%), echocardiography (94.6%). Fifty-five percent of survivors had at least one modifiable cardiovascular risk factor (i.e., current smoking, overweight, new/insufficiently controlled hypertension, dyslipidemia, or diabetes). Screening detected ≥ 1 CVD in 31.1% of survivors. Among survivors with available echocardiography report (n = 106), screening detected new aortic and/or mitral valve dysfunction(s) in 51.0% (with grades 3-4 in 4.9%) and impaired left ventricular ejection fraction in 10.3%. CONCLUSIONS: Adherence to the screening guidelines in the Dutch HL survivorship care program was reasonable to good and a substantial number of actionable (risk factors for) CVD were diagnosed. IMPLICATIONS FOR CANCER SURVIVORS: Our findings inform HL survivors at high risk of late cardiotoxicity about cardiovascular screening findings and demonstrate appropriate therapeutic actions after diagnosis of (risk factors for) CVD.

RESUMEN

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.

Asunto(s)

RESUMEN

Coronary endothelial dysfunction (CED) and coronary artery spasm (CAS) are causes of angina with no obstructive coronary arteries in patients. Both can be diagnosed by invasive coronary function testing (ICFT) using acetylcholine (ACh). This study aimed to evaluate the diagnostic yield of a 3-minute ACh infusion as compared with a 1-minute ACh bolus injection protocol in testing CED and CAS. We evaluated 220 consecutive patients with angina and no obstructive coronary arteries who underwent ICFT using continuous Doppler flow measurements. Per protocol, 110 patients were tested using 3-minute infusion, and thereafter 110 patients using 1-minute bolus injections, because of a protocol change. CED was defined as a <50% increase in coronary blood flow or any epicardial vasoconstriction in reaction to low-dose ACh and CAS according to the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria, both with and without T-wave abnormalities, in reaction to high dose ACh. The prevalence of CED was equal in both protocols (78% vs 79%, p = 0.869). Regarding the endotypes of CAS according to COVADIS, the equivocal endotype was diagnosed less often in the 3 vs 1-minute protocol (24% vs 44%, p = 0.004). Including T-wave abnormalities in the COVADIS criteria resulted in a similar diagnostic yield of both protocols. Hemodynamic changes from baseline to the low or high ACh doses were comparable between the protocols for each endotype. In conclusion, ICFT using 3-minute infusion or 1-minute bolus injections of ACh showed a similar diagnostic yield of CED. When using the COVADIS criteria, a difference in the equivocal diagnosis was observed. Including T-wave abnormalities as a diagnostic criterion reclassified equivocal test results into CAS and decreased this difference. For clinical practice, we recommend the inclusion of T-wave abnormalities as a diagnostic criterion for CAS and the 1-minute bolus protocol for practicality.

Asunto(s)

RESUMEN

BACKGROUND: The microvascular resistance reserve (MRR) is an innovative index to assess the vasodilatory capacity of the coronary circulation while accounting for the presence of concomitant epicardial disease. The MRR has shown to be a valuable diagnostic and prognostic tool in the general coronary artery disease (CAD) population. However, considering the fundamental aspects of its assessment and the unique hemodynamic characteristics of women, it is crucial to provide additional considerations for evaluating the MRR specifically in women. AIM: The aim of this study was to assess the diagnostic and prognostic applicability of the MRR in women and assess the potential differences across different sexes. METHODS: From the ILIAS Registry, we enrolled all patients with a stable indication for invasive coronary angiography, ensuring complete physiological and follow-up data. We analyzed the diagnostic value by comparing differences between sexes and evaluated the prognostic value of the MRR specifically in women, comparing it to that in men. RESULTS: A total of 1494 patients were included of which 26% were women. The correlation between MRR and CFR was good and similar between women (r = 0.80, p < 0.005) and men (r = 0.81, p < 0.005). The MRR was an independent and important predictor of MACE in both women (HR 0.67, 0.47-0.96, p = 0.027) and men (HR 0.84, 0.74-0.95, p = 0.007). The optimal cut-off value for MRR in women was 2.8 and 3.2 in men. An abnormal MRR similarly predicted MACE at 5-year follow-up in both women and men. CONCLUSION: The MRR seems to be equally applicable in both women and men with stable coronary artery disease.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

AIM: Diabetes mellitus (diabetes) is common amongst patients with NSTEMI. We describe presentation, care and outcomes of patients admitted with NSTEMI by diabetes status. METHODS: Prospective cohort study including 2928 patients (1104 with prior diabetes, 1824 without) admitted to hospital with NSTEMI from 287 centres in 59 countries. Quality of care was evaluated based on 12 guideline-recommended care interventions. Outcomes included in-hospital acute heart failure, cardiogenic shock, repeat myocardial infarction, stroke/transient ischaemic attack (TIA), BARC Type ≥ 3 bleeding and death, as well as 30-day mortality. RESULTS: Patients with diabetes had higher comorbidity burden and more frequently presented with Killip Class II-IV heart failure (10.2% vs 3.7%, P < 0.001), haemodynamic instability (7.1% vs 3.7%, P < 0.001) and ongoing chest pain (43.1% vs 37.0%, P < 0.001), than those without diabetes. Overall, care quality received was similar by diabetes status (60.0% vs 60.5% received ≥ 80% of eligible care interventions, P = 0.786), but patients with diabetes experienced higher rates of in-hospital acute heart failure (15.3% vs 6.8% P < 0.001), cardiogenic shock (4.5% vs 2.5%, P = 0.002), stroke/TIA (2.0% vs 0.8%, P = 0.006) and death (2.5% vs 1.4%, P = 0.022), and higher 30-day mortality (3.3% vs 2.0%, P = 0.025). Of NSTEMI with diabetes, only 1.9% and 9.0% received prescription for GLP-1 RAs and SGLT2 inhibitors, respectively, on discharge, and only 45.9% were referred for cardiac rehabilitation. CONCLUSION: NSTEMI patients with diabetes, compared to those without, present more clinically unwell and have worse outcomes despite receiving equal quality of care. Prescription of cardiovascular-protective glycaemic agents is an actionable target to reduce risk of further events.

RESUMEN

AIMS: Women have historically been disadvantaged in terms of care and outcomes for non-ST-segment elevation myocardial infarction (NSTEMI). We describe patterns of presentation, care, and outcomes for NSTEMI by sex in a contemporary and geographically diverse cohort. METHODS AND RESULTS: Prospective cohort study including 2947 patients (907 women, 2040 men) with Type I NSTEMI from 287 centres in 59 countries, stratified by sex. Quality of care was evaluated based on 12 guideline-recommended care interventions. The all-or-none scoring composite performance measure was used to define receipt of optimal care. Outcomes included acute heart failure, cardiogenic shock, repeat myocardial infarction, stroke/transient ischaemic attack, BARC Type ≥3 bleeding, or death in-hospital, as well as 30-day mortality. Women admitted with NSTEMI were older, more comorbid, and more frequently categorized as at higher ischaemic (GRACE >140, 54.0% vs. 41.7%, P < 0.001) and bleeding (CRUSADE >40, 51.7% vs. 17.6%, P < 0.001) risk than men. Women less frequently received invasive coronary angiography (ICA; 83.0% vs. 89.5%, P < 0.001), smoking cessation advice (46.4% vs. 69.5%, P < 0.001), and P2Y12 inhibitor prescription at discharge (81.9% vs. 90.0%, P < 0.001). Non-receipt of ICA was more often due to frailty for women than men (16.7% vs. 7.8%, P = 0.010). At ICA, more women than men had non-obstructive coronary artery disease or angiographically normal arteries (15.8% vs. 6.3%, P < 0.001). Rates of in-hospital adverse outcomes and 30-day mortality were low and did not differ by sex. CONCLUSION: In contemporary practice, women presenting with NSTEMI, compared with men, less frequently receive antiplatelet prescription, smoking cessation advice, or are considered eligible for ICA.

Asunto(s)

RESUMEN

Background: Coronary pressure- and flow-derived parameters have prognostic value. Objectives: This study aims to investigate the individual and combined prognostic relevance of pressure and flow parameters reflecting resting and hyperemic conditions. Methods: A total of 1,971 vessels deferred from revascularization after invasive pressure and flow assessment were included from the international multicenter registry. Abnormal resting pressure and flow were defined as distal coronary pressure/aortic pressure ≤0.92 and high resting flow (1/resting mean transit time >2.4 or resting average peak flow >22.7 cm/s), and abnormal hyperemic pressure and flow as fractional flow reserve ≤0.80 and low hyperemic flow (1/hyperemic mean transit time <2.2 or hyperemic average peak flow <25.0 cm/s), respectively. The clinical endpoint was target vessel failure (TVF), myocardial infarction (MI), or cardiac death at 5 years. Results: The mean % diameter stenosis was 46.8% ± 16.5%. Abnormal pressure and flow were independent predictors of TVF and cardiac death/MI (all P < 0.05). The risk of 5-year TVF or MI/cardiac death increased proportionally with neither, either, and both abnormal resting pressure and flow, and abnormal hyperemic pressure and flow (all P for trend < 0.001). Abnormal resting pressure and flow were associated with a higher rate of TVF or MI/cardiac death in vessels with normal fractional flow reserve; this association was similar for abnormal hyperemic pressure and flow in vessels with normal resting distal coronary pressure/aortic pressure (all P < 0.05). Conclusions: Abnormal resting and hyperemic pressure and flow were independent prognostic predictors. The abnormal flow had an additive prognostic value for pressure in both resting and hyperemic conditions with complementary prognostic between resting and hyperemic parameters.

Asunto(s)

RESUMEN

Graphical AbstractClinical outcomes and treatment adherence during 12 months follow-up. *Second bleeding event in same patient. PCI, percutaneous coronary intervention; TVR, target vessel revascularization.

RESUMEN

Background: Treatment of patients diagnosed with angina due to epicardial or microvascular coronary artery spasm (CAS) is challenging because patients often remain symptomatic despite conventional pharmacological therapy. In this prospective, randomized, double-blind, placebo-controlled, sequential cross-over proof-of-concept study, we compared the efficacy and safety of macitentan, a potent inhibitor of the endothelin-1 receptor, to placebo in symptomatic patients with CAS despite background pharmacological treatment. Methods: Patients with CAS diagnosed by invasive spasm provocation testing with >3 anginal attacks per week despite pharmacological treatment were considered for participation. Participants received either 10 mg of macitentan or placebo daily for 28 days as add-on treatment. After a wash-out period patients were crossed over to the alternate treatment arm. The primary endpoint was the difference in anginal burden calculated as [1] the duration (in minutes) * severity (on a Visual Analogue Scale (VAS) pain scale 1-10); and [2] the frequency of angina attacks * severity during medication use compared to the run-in phase. Results: 28 patients of whom 22 females (79%) and a mean age of 55.3 ± 7.6 completed the entire study protocol (epicardial CAS n = 19 (68), microvascular CAS n = 9 (32)). Change in both indices of anginal burden were not different during treatment with add-on macitentan as compared to add-on placebo (duration*severity: -9 [-134 78] vs -45 [-353 11], p = 0.136 and frequency*severity: -1.7 [-5.8 1.2] vs -1.8 [-6.2 0.3], p = 0.767). The occurrence and nature of self-reported adverse events were closely similar between the treatment phase with macitentan and placebo. Conclusion: In patients with angina due to epicardial or microvascular CAS despite background pharmacological treatment, 28 days of add-on treatment with the ET-1 receptor antagonist, macitentan 10 mg daily, did not reduce anginal burden compared to add-on treatment with placebo.Trial Registrationhttps://trialsearch.who.int/, Identifier: EUCTR2018-002623-42-NL. Registration date: 20 February 2019.

RESUMEN

BACKGROUND AND AIMS: The management of chronic coronary syndrome (CCS) is informed by studies predominantly including men. This study investigated the relationship between patients sex and different endotypes of CCS, including sex-specific clinical outcomes. METHODS: In patients with CCS undergoing coronary angiography, invasive Fractional Flow Reserve (FFR) and Coronary Flow Reserve (CFR) were measured. Patients were stratified into groups: 1) obstructive coronary artery disease (oCAD) (FFR≤0.80, no revascularization), 2) undergoing revascularization, 3) non-obstructive coronary artery disease with coronary microvascular dysfunction (CMD) (FFR>0.80, CFR≤2.5), and 4) non-obstructive coronary artery disease without CMD (FFR>0.80 and CFR>2.5). RESULTS: 1836 patients (2335 vessels) were included, comprising 1359 (74.0%) men and 477 (26.0%) women. oCAD was present in 14.1% and was significantly less prevalent in women than in men (10.3% vs 15.5%, respectively p < 0.01). Revascularization was present in 30.9% and was similarly prevalent in women and men (28.2% vs. 31.9%, respectively p = 0.13). CMD was present in 24.2% and was significantly more prevalent in women than men (28.6% vs 22.6%, respectively p < 0.01). Normal invasive measurements were found in 564 patients (33.0% women vs 30.0% men, p = 0.23). Male sex was associated with an increased risk of target vessel failure compared to women (HR.1.89, 95% CI 1.12-3.18, p = 0.018), regardless of CCS-endotype. CONCLUSIONS: Sex differences exist in the prevalence and outcomes of different endotypes of CCS in symptomatic patients undergoing invasive coronary angiography. In particular, oCAD (and subsequent revascularization) were more prevalent in men. Conversely, CMD was more prevalent in women. Overall, men experienced a worse cardiovascular outcome compared to women, independent of any specific CCS endotype.

Asunto(s)