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Hemoglobin (Hb) levels have emerged as a useful tool for risk stratification and the prediction of outcome after myocardial infarction. We aimed at evaluating the prognostic impact of this parameter among patients in advanced age, where the larger prevalence of anemia and the higher rate of comorbidities could directly impact on the cardiovascular risk.All the patients in the ELDERLY-2 trial, were included in this analysis and stratified according to the values of hemoglobin at admission. The primary endpoint of this study was cardiovascular mortality within one year. The secondary endpoints were all-cause mortality, MI, Bleeding Academic Research Consortium (BARC) type 2-3 or 5 bleeding, any stroke, re-hospitalization for cardiovascular event or stent thrombosis (probable or definite) within 12 months after index admission.We included in our analysis 1364 patients, divided in quartiles of Hb values (lt;12.2; 12.2-13.39; 13.44-14.49; ≥ 4.5 g/dl). At a mean follow- up of 330.4 ± 99.9 days cardiovascular mortality was increased in patients with lower Hb (HR[95%CI] = 0.76 [0.59-0.97], p = 0.03). Results were no more significant after correction for baseline differences (adjusted HR[95%CI] = 1.22 [0.41-3.6], p = 0.16). Similar results were observed for overall mortality. At subgroup analysis, (according to Hb median values) a significant interaction was observed only with the type of antiplatelet therapy, but not with major high-risk subsets of patients.Among elderly patients with acute coronary syndrome managed invasively, lower hemoglobin at admission is associated with higher cardiovascular and all-cause mortality and major ischemic events, mainly explained by the higher risk profile.

The characteristics and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients with ST-Elevation Myocardial Infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) are still poorly known.The PANDEMIC study was an investigator-initiated, collaborative, individual patient data (IPD) meta-analysis of registry-based studies. MEDLINE, ScienceDirect, Web of Sciences, and SCOPUS were searched to identify all registry-based studies describing the characteristics and outcome of SARS-CoV-2-positive STEMI patients undergoing PPCI. The control group consisted of SARS-CoV-2-negative STEMI patients undergoing PPCI in the same time period from the ISACS-STEMI COVID 19 registry. The primary outcome was in-hospital mortality; the secondary outcome was postprocedural reperfusion assessed by TIMI flow.Of 8 registry-based studies identified, IPD were obtained from 6 studies including 941 SARS-CoV-2-positive patients; the control group included 2005 SARS-CoV-2-negative patients. SARS-CoV-2-positive patients showed a significantly higher in-hospital mortality (p lt; 0.001) and worse postprocedural TIMI flow (lt;3, p lt; 0.001) compared with SARS-CoV-2-negative subjects. The increased risk for SARS-CoV-2-positive patients was significantly higher in males compared to females for both the primary (psubinteraction/sub = 0.001) and secondary outcome (psubinteraction/sub = 0.023). In SARS-CoV-2-positive patients, age ≥ 75 years (OR = 5.72; 95%CI: 1.77-18.5), impaired postprocedural TIMI flow (OR = 11.72; 95%CI: 2.64-52.10), and cardiogenic shock at presentation (OR = 11.02; 95%CI: 2.84-42.80) were independent predictors of mortality.In STEMI patients undergoing PPCI, SARS-CoV-2 positivity is independently associated with impaired reperfusion and with a higher risk of in-hospital mortality, especially among male patients. Age ≥ 75 years, cardiogenic shock, and impaired postprocedural TIMI flow independently predict mortality in this high-risk population.

Drug-coated balloons (DCBs) have emerged for percutaneous coronary interventions (PCI) of in-stent restenosis or particular anatomical subsets. We provide a real-world analysis of the prognostic determinants and long-term outcomes of patients treated with DCB for any lesion in a comprehensive multicenter registry. The primary study endpoint was the occurrence of major cardiovascular events (MACE: composite of all-cause death, myocardial infarction, and target vessel revascularization) at the longest available follow-up. We included 267 patients (196 treated for in-stent restenosis and 71 for de novo lesions), with a median follow-up of 616 [368–1025] days. MACE occurred in 70 (26.2%) of the patients and related with higher rates of in-stent restenosis (P = .04), longer and more type C lesions ( P = .05 and P = .04). At multivariate Cox-regression, type C lesions emerged as the only independent predictor of MACE (adjusted OR [95% CI] = 1.83[1.13–2.97], P = .014), mainly driven by target vessel revascularization (adjusted OR[95% CI] = 1.78[1.05–2.95], P = .03) not conditioning survival. In-stent restenosis emerged as major determinant of TLF (adjusted OR[95% CI] = 2.59[1.17–5.75], P = .02). DCBs represent a treatment option for any lesion; however, type C and restenotic lesions are associated with an increased risk of MACE and target lesion failure, where the optimal strategies for patients’ selection and lesion preparation are still undefined.

ispartof: KARDIOLOGIA POLSKA vol:80 issue:4 pages:485-488 ispartof: location:Poland status: published

Special interest has been raised on vitamin D association with the metabolic profile, potentially interfering with lipid parameters and lipid-lowering therapies. The aim of the present study was to assess the impact of vitamin D on the cholesterol levels among patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI.A consecutive cohort of 450 patients admitted for STEMI treated with pPCI were retrospectively identified and divided according to tertiles values of 25(OH). The levels of 25(OH)D were assessed at admission by chemiluminescence immunoassay kit LIAISON®Vitamin D assay (Diasorin Inc). Lower vitamin D was associated to a higher use of diuretics (p = 0.03), lower prevalence of lesions on bifurcations (p = 0.001) and smaller diameter of the target coronary vessel (p = 0.03), but higher coronary calcifications (p = 0.007). Total and LDL cholesterol levels were significantly increased in patients with lower vitamin D (p = 0.05 and p = 0.005), inversely relating with total cholesterol (r = -0.09, p = 0.06) and LDL-C (r = -013, p = 0.007), and directly with HDL-C (r = 0.16, p = 0.001). Results were not affected by statin therapy, with a significant relationship being confirmed for atherogenic lipids, but not for HDL-C in statin treated patients. In fact, at multivariate analysis, vitamin D in lower tertiles emerged as an independent predictor of LDL-C elevated or above the target (adjusted OR [95%CI] = 2.6 [1.51-4.44], p = 0.001).The present study shows that among patients with STEMI undergoing primary revascularization, lower levels of vitamin D are independently associated with a more atherogenic lipid profile. Similar results were observed in statin treated or naïve patients.

Sex differences in coronary physiology and in the pathogenesis of coronary artery disease (CAD) have been previously described. Contrasting data have been reported, so far, about the impact of sex on the assessment of the functional significance of intermediate coronary stenoses by fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR). The present study aimed at assessing the sex differences in the results of iFR in a cohort of patients undergoing coronary angiography . Methods We included patients undergoing coronary angiography and the functional assessment of intermediate (40 to 70%) coronary lesions in 2 centers. iFR measurement was performed by pressure-recording guidewire and automatically calculated at the core laboratory using the manufacturers' dedicated software. Quantitative parameters of the coronary lesions were calculated by an automatic edge-detection system. Minimal luminal diameter (MLD), reference diameter (RD), percent diameter stenosis, and length of the lesion were measured. Positive iFR was considered for values Results We included 325 patients undergoing coronary angiography and iFR evaluation of 371 intermediate coronary stenoses, including 20.6% of women. Females were older, displayed lower body weight and hemoglobin, lower rate of active smoking (p = 0.04), lower platelet count ( p = 0.001) and creatinine (p = 0.02). Systolic blood pressure and heart rate at admission were more elevated in women ( p = 0.001 and p = 0.05, respectively). At angiography, multivessel coronary artery disease was more uncommon (p = 0.001) and proximal lesions were more frequently assessed by iFR (p = 0.04). Mean values of iFR did not differ with sex and neither the percentage of positive iFR (19.1% vs 18.8%, p = 0.99, adjusted OR[95%CI] = 0.51[0.18–1.48], p = 0.22). Conclusion Among patients undergoing functional assessment of intermediate coronary lesions by instantaneous wave-free ratio, no impact of sex was observed on the absolute values or the rate of positivity of iFR.

Contains fulltext : 291566.pdf (Publisher’s version ) (Open Access) BACKGROUND: The constraints in the management of patients with ST-segment elevation myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the registry ISACS-STEMI COVID-19. METHODS: This retrospective multicenter registry was performed in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI in March-June 2019 and 2020. Patients were divided according to age (< or ≥75 years). The main outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon longer than 30 min), and in-hospital or 30-day mortality. RESULTS: We included 16,683 patients undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825-0.861, p < 0.0001). We found a significant age-related reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore, we observed significantly higher 30-day mortality during the pandemic period, especially among the elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24-1.93], p < 0.001) as compared to younger patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05-1.49], p = 0.013), as a potential consequence of the significantly longer ischemia time observed during the pandemic. CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients, which may have contributed to increase in-hospital and 30-day mortality during the pandemic.

Contains fulltext : 290798.pdf (Publisher’s version ) (Open Access) BACKGROUND: Several reports have demonstrated the impact of the COVID-19 pandemic on the management and outcome of patients with ST-segment elevation myocardial infarction (STEMI). The aim of the current analysis is to investigate the potential gender difference in the effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI patients within the ISACS-STEMI COVID-19 Registry. METHODS: This retrospective multicenter registry was performed in high-volume primary percutaneous coronary intervention (PPCI) centers on four continents and included STEMI patients undergoing PPCIs in March-June 2019 and 2020. Patients were divided according to gender. The main outcomes were the incidence and timing of the PPCI, (ischemia time ≥ 12 h and door-to-balloon ≥ 30 min) and in-hospital or 30-day mortality. RESULTS: We included 16683 STEMI patients undergoing PPCIs in 109 centers. In 2020 during the pandemic, there was a significant reduction in PPCIs compared to 2019 (IRR 0.843 (95% CI: 0.825-0.861, p < 0.0001). We did not find a significant gender difference in the effects of the COVID-19 pandemic on the numbers of STEMI patients, which were similarly reduced from 2019 to 2020 in both groups, or in the mortality rates. Compared to prepandemia, 30-day mortality was significantly higher during the pandemic period among female (12.1% vs. 8.7%; adjusted HR [95% CI] = 1.66 [1.31-2.11], p < 0.001) but not male patients (5.8% vs. 6.7%; adjusted HR [95% CI] = 1.14 [0.96-1.34], p = 0.12). CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures similarly observed in both genders. Furthermore, we observed significantly increased in-hospital and 30-day mortality rates during the pandemic only among females. Trial registration number: NCT 04412655.

Patient presentation. We present the case of an 85-years old woman, hypercholesterolemic, with a previous history of microvascular angina treated with nitrates, ASA and ranolazine. She presented in our emergency department for repeated episodes of seizure and “drop attacks” and she underwent neurological and cardiological evaluation. ECG showed sinus tachycardia, 110/min, left anterior hemiblock. Transthoracic echocardiogram was normal. Head CT-scan and cerebral magnetic resonance documented mild hyperintense areas in the subcortical part of white matter suggestive for chronic cerebrovascular disease. Carotid Doppler was negative for significant stenosis. Thus, suspecting an unexplained syncope, she underwent loop recorder implantation. One month later she was admitted to the emergency room for dysarthria, left hemiparesis and ataxia, that completely regressed after 24-hours, posing the diagnosis of transient ischemic stroke. Physical examination was normal. During in-hospital stay, the patient progressively developed dyspnoea and oxygen desaturation (SpO2 < 90%). Initial work-up. Due to oxygen desaturation non-invasive ventilation with Venturi mask (60%) was started. Blood tests were normal. The arterial blood gas analysis in Venturi mask showed: pH 7.47, pCO2 48 mmHg, pO2 136 mmHg, P/F 226. Despite non-invasive ventilation with Venturi mask, P/F remained low and so continuous positive airway pressure (CPAP) was started. A repeated echocardiogram showed a mild reduction of ejection fraction (45-50%) due to hypokinesia of the septum, secondary to right ventricular overload and compression. Pulmonary embolism was excluded by angio-CT. Medical management with vasodilators and diuretics finally allowed to wean off the non-invasive ventilation, still maintaining oxygen support with nasal cannulas. However, surprisingly, the mobilization of the patient in a sitting position resulted impossible, due to the occurrence of sudden desaturation. Diagnosis and Management. Suspecting a manifestation of platypnea-orthodeoxia syndrome (POS) a transoesophageal echocardiogram was performed. It revealed a wide patent foramen ovale (PFO), maximum diameter 1.5 cm, with a baseline mild right-to-left shunt, confirmed with sonicated contrast, that increased in the sitting position. Therefore, the diagnosis of POS syndrome and paradoxical cerebral embolization was posed. Elective PFO closure with the percutaneous positioning of an atrial septal defect (ASD) Occluder n.15 was successfully performed. Conclusions The platypnea-orthodeoxia syndrome is a rare cause of hypoxemia. The most common structural abnormality associated with this syndrome is the PFO, which can remain asymptomatic for decades. A shift in the relationship between right-and left intra-cardiac pressures, a change in the anatomy of the adjoining structures with age, stretching the atrial septum and favouring the blood inflow into the PFO (as ascending aorta dilatation or Thoracic Kyphosis) can lead to POS. The closure of the atrial defect is generally resolutive. However, the heterogeneous clinical presentations, the rarity of the disease and the confounding role of comorbidities can often result misleading, especially in advanced age.

Background Myocardial infarction with non-obstructed coronary arteries (MINOCA) is an increasingly recognized condition with challenging management. Prognosis of this patients could be of concern, in particular for those who experienced recurrent acute myocardial infarction (re-AMI). Moreover, there are limited data on characteristics of re-AMI among MINOCA patients. Methods In this retrospective multicentre cohort study involving seven Hub Hospitals across Italy we enrolled consecutive patients 18 years and older discharged with diagnosis of MINOCA according to the IV universal definition of myocardial infarction who experienced hospitalization for re-AMI during follow-up. Results A total of 54 patients were included (mean age 66±13). Compared to MINOCA patients without re-AMI (n=695), on first angiography MINOCA patients with re-AMI showed less frequently angiographically normal coronaries (37 versus 53%, p=0,032) and had higher prevalence of atherosclerosis involving 3 vessels or left main stem (17% versus 8%, p=0,049). Twenty four patients (44%) with re-AMI underwent a new coronary angiography and 25% had normal coronary arteries, 12% had mild luminal irregularities ( Among patients undergoing new angiography, only 4% had LDL cholesterol under 55 mg/dL, atherosclerosis progression was observed in 11 (46%), 38% received revascularization and 33% experienced a new cardiovascular event (death, AMI, heart failure, stroke) at subsequent follow-up. Conclusions In the present study near one out of two patients with re-AMI after MINOCA showed angiographic atherosclerosis progression requiring revascularization in the majority of cases. These patients rarely presented with recommended LDL cholesterol levels and are at risk for further cardiovascular events, indicating a possible underestimation of cardiovascular risk in this population.

Background Several reports have described the negative prognostic impact of ageing in patients with ST-Elevation Myocardial Infarction (STEMI) undergoing primary angioplasty. During the COVID-19 pandemic, increased mortality was observed in patients admitted for STEMI. However, there are no data on the impact of ageing on the outcome of this high-risk patients during the pandemic. Objectives The ISACS-STEMI COVID-19 is a large-scale retrospective multicenter registry involving primary PCI centers from Europe, Latin America, South-East Asia and North-Africa, including patients treated from 11920 of March until June 30, 2019 and 2020). Primary study endpoint of this analysis was in-hospital mortality. Secondary endpoints was 30-day mortality. Results Our population is represented by 16083 STEMI patients undergoing mechanical reperfusion, who were divided according to age (< 55 years, n = 4179 (25,98%); 55-65 years, n = 4814 (29,93%); 65-75 years, n = 4016 (24,97%); 75-65 years, n = 2226 (13,84%); >85 years, n = 821 (5,10%). Ageing was linearly and independently associated with in-hospital (figure 1) and 30-day mortality (adjusted p < 0.0001). The COVID pandemic had a significant impact on in-hospital and 30-day mortality (adjusted p < 0.001), that was linearly related to age, particularly for in-hospital mortality (Figure 1). Conclusions Our study showed that among STEMI patients undergoing primary angioplasty, age was linearly associated to mortality in both precovid and covid era. The COVID-19 pandemic had a significant impact on mortality, especially in more advanced age.

Background and Aims The pandemic proportion of vitamin D deficiency has raised particular concerns on its association with mortality and cardiovascular disease (CVD). However, the independent and causative role of hypovitaminosis D in CVD is still debated. Few data have been reported, so far, among STEMI patients undergoing primary percutaneous coronary intervention (pPCI), that was therefore the aim of the present study. Methods A consecutive cohort of patients admitted for STEMI treated with pPCI were included. The levels of 25(OH)D were assessed at admission by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc). Hypovitaminosis D was defined for 25(OH)D < 10 ng/ml. The primary study endpoint was net adverse cardiovascular events (a composite of death, recurrent MI and target vessel revascularization) at the longest available follow-up. Secondary endpoints were overall mortality, major bleedings or the individual components of the primary endpoint. Results We included 136 patients divided according to tertiles values of 25(OH)D (< 12.98 ng/ml, n=44; 12.98-22.1 ng/ml, n=41; ≥ 22.1 ng/ml, n=51). The prevalence of renal failure (p=0.047) and coronary calcifications inversely related with vitamin D. Lower vitamin D levels were associated with “no reflow” (10.3% vs 6.7% vs 0%, p=0.04), with increased use of adenosine. At a mean follow-up of 305± 217 days (mean + SD), the primary endpoint (NACE) was slightly increased in patients with lower vitamin D values (adjusted HR [95% CI] = 3.07 [0.85-11.1], p = 0.09). Similar results were observed for ischemic events (MACE: adjusted HR [95% CI] = 2.78 [0.68-11.48], p = 0.16). However, when considering separately patients with severe hypovitaminosis D ( Conclusion The present study shows that among patients with STEMI undergoing pPCI, extremely low levels of vitamin D are independently associated with impaired outcomes. Future dedicated studies will shed light on the prognostic implications of hypovitaminosis D in these patients and the potential therapeutic perspectives.

SARS-Cov-2 has been suggested to promote thrombotic complications and higher mortality. The aim of the present study was to evaluate the impact of SARS-CoV-2 positivity on in-hospital outcome and 30-day mortality in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) enrolled in the International Survey on Acute Coronary Syndromes ST-segment elevation Myocardial Infarction (ISACS-STEMI COVID-19 registry. The 109 SARS-CoV-2 positive patients were compared with 2005 SARS-CoV-2 negative patients. Positive patients were older ( P = .002), less often active smokers ( P = .002), and hypercholesterolemic ( P = .006), they presented more often later than 12 h ( P = .037), more often to the hub and were more often in cardiogenic shock ( P = .02), or requiring rescue percutaneous coronary intervention after failed thrombolysis (P < .0001). Lower postprocedural Thrombolysis in Myocardial Infarction 3 flow ( P = .029) and more thrombectomy ( P = .046) were observed. SARS-CoV-2 was associated with a significantly higher in-hospital mortality (25.7 vs 7%, adjusted Odds Ratio (OR) [95% Confidence Interval] = 3.2 [1.71-5.99], P < .001) in-hospital definite in-stent thrombosis (6.4 vs 1.1%, adjusted Odds Ratio [95% CI] = 6.26 [2.41-16.25], P < .001) and 30-day mortality (34.4 vs 8.5%, adjusted Hazard Ratio [95% CI] = 2.16 [1.45-3.23], P < .001), confirming that SARS-CoV-2 positivity is associated with impaired reperfusion, with negative prognostic consequences.

No study has so far evaluated the impact of chronic kidney disease (CKD) on high-on treatment platelet reactivity (HRPR) with ticagrelor and their prognostic consequences, that were therefore the aim of the present study.Patients on dual antiplatelet therapy with ASA+ticagrelor (90mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome (MI), target vessel revascularization) at the longest available follow-up.We included 396 patients, that were divided according to CKD (eGFRor≥ 60 m l/min). Mean platelet reactivity was comparable irrespective of renal function Prevalence of high platelet reactivity (HRPR) on Ticagrelor was similar among patients with or without CKD (9.7% vs. 11.8%, P=0.84). At a mean follow-up of 939±581.4 days, 21.2% of the patients experienced the primary composite endpoint, with a similar rate of events in patients CKD or normal renal function (22.2% vs. 21.2% HR [95%CI]= 0.92[0.52-1.61], P=0.77), and no difference in survival, ischemic and bleeding endpoints. After correction for baseline differences CKD did not emerge as an independent predictor of either HRPR (adjusted OR [95%CI]=0.47 [0.18;1.25], P=0.13) or MACE (adjusted HR [95%CI]=0.66 [0.34-1.29] P=0.18).In the present study we demonstrated that among ACS patients on DAPT with ASA and ticagrelor after PCI, renal failure is not associated with a higher rate of HRPR or to an increased risk of mortality or major ischemic and bleeding events.

Our understanding of the pathophysiology of acute coronary syndrome and of the vascular biology of coronary atherosclerosis has made enormous progress with the implementation of intravascular imaging. Intravascular imaging contributes to overcoming the known limitations of coronary angiography and allows for the in vivo discrimination of plaque morphology giving insight into the underlying pathology of the disease process. The possibility of using intracoronary imaging to characterize lesion morphologies and correlate them with clinical presentations may influence the treatment of patients and improve risk stratification, offering the opportunity for tailored management. This review examines the current role of intravascular imaging and describes how intracoronary imaging represents a valuable tool for modern interventional cardiology in order to improve diagnostic accuracy and offer a tailored approach to the treatment of patients with coronary artery disease, especially in the acute setting.

Background and aims Dual antiplatelet therapy (DAPT) and Renin-angiotensin system inhibitors (RASi) represent the cornerstone in the treatment of patients undergoing percutaneous coronary interventions (PCI), mainly after an acute ischemic event. However, high-on treatment residual platelet reactivity (HRPR), is not infrequent despite optimal medical treatment. Homocysteine (Hcy) is a metabolite of methionine catabolism linked to atherothrombosis. Recently, a potential crosstalk between RAS and Hcy has been suggested, potentially favouring platelet aggregation and cardiovascular disease.Therefore, we aimed to investigate the impact of RASi on Hcy levels and platelet aggregation in patients on DAPT after PCI. Methods and results Patients undergoing PCI on DAPT with ASA plus an ADP-antagonist (clopidogrel, ticagrelor or prasugrel), were included. RASi comprised angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). Aggregation tests were performed by Multiple Electrode Aggregometry. We included 1210 patients, of whom 862 (71.2%) were on treatment with RASi. Overall, DAPT composition was ASA+clopidogrel in 566 (46.8%) patients, ASA+ticagrelor in 428 (35.4%) and ASA+prasugrel in 216 (17.9%). Median values of Hcy were higher in RASi patients (p = 0.006), who displayed a higher percentage of Hcy above the median value (52.4% vs. 44.8%, p = 0.019, adjustedOR [95%CI] = 1.40 [1.04–1.88], p = 0.027). No differences in HRPR rate were found according to RASi use for ASPI test (3.6% vs. 3.3%, p = 0.88) and ADP test (25.6% vs. 24.3%,p = 0.62; adjustedOR [95%CI] = 1.23 [0.89–1.70], p = 0.220) and according to ADP-antagonist type. A direct linear relationship was observed between platelet reactivity and Hcy in both patients receiving RASi and untreated ones, with higher values of platelet aggregation being observed in patients with Hcy above the median, independently from RASi administration and DAPT strategy. Conclusion In patients on DAPT after PCI, RASi treatment did not emerge as an independent predictor of HRPR. However, the levels of Hcy were significantly elevated in patients on RASi and related to higher values of platelet reactivity, independently from the DAPT strategy.

Vitamin D deficiency represents a pandemic health problem with a broad spectrum of clinical implications. Several studies have involved lower levels of vitamin D with inflammatory disorders including cardiovascular, autoimmune and infectious disease. Indeed, the pathophysiological mechanisms are still poorly ascertained. We aimed at evaluating the impact of cholecalciferol (25(OH)D) levels on the biomarkers of acute-phase response and inflammation in a large cohort of patients with cardiovascular disease.Consecutive patients undergoing coronary angiography were included. Main clinical features and chemistry parameters were assessed at admission. 25(OH)D levels were measured by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc, Stillwater, US). Hypovitaminosis D was defined for 25(OH)D 10 ng/ml.A total of 3974 patients were included, of whom 29.4% had hypovitaminosis D. 25(OH)D deficiency was associated to age, female gender, diabetes mellitus, renal failure, previous percutaneous coronary intervention and smoke, acute presentation, severe coronary disease, higher glycemia and cholesterol and lower hemoglobin and ejection fraction (p 0.001), higher platelet count (p = 0.004) and BMI (p = 0.05). 25(OH)D significantly directly related with white blood cells count and the different components of leukocytes formula, Neutrophils-to-Lymphocytes Ratio, Monocytes-to-Lymphocytes Ratio and C-reactive protein, but not with lymphocytes levels. In fact, hypovitaminosis D predicted levels above the median for both Neutrophils-to-Lymphocytes Ratio (≥2.56; 57.3% vs. 47.6%; p 0.001; adjusted OR[95%CI] = 1.28[1.07-1.52; p = 0.007) and Monocytes -to-Lymphocytes Ratio (≥0.33; 59.1% vs. 49.8%; p 0.001; adjusted OR[95%CI] = 1.3[1.1-1.54; p = 0.002), results were confirmed in major subgroups of patients.The present study demonstrates that, among patients with cardiovascular disease, 25(OH)D deficiency is associated with a higher metabolic and clinical risk profile and with an elevation of cellular and humoral inflammatory parameters. Future dedicated studies should be, therefore, advocated in order to define whether 25(OH)D supplementation can modulate the mediators of the acute phase response and therefore potentially offer clinical and prognostic advantages on a broad spectrum of inflammatory disease.

Contains fulltext : 233810.pdf (Publisher’s version ) (Closed access) BACKGROUND AND AIMS: The impact of advanced age on the optimal duration of dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary revascularization (PCI) is still greatly debated. Therefore, the aim of the present sub-analysis of the REDUCE trial was to assess the impact of age on the comparison between a short 3 months vs standard 12 months DAPT in ACS patients treated with the COMBO Dual Stent Therapy. METHODS: The REDUCE trial is a prospective, multicenter, investigator-initiated study that randomized ACS patients undergoing PCI with the COMBO drug eluting stent to either 3 or 12 months of DAPT. The study population was divided according to age (

Homocysteine (Hcy) elevation and vitamin D deficiency have emerged as potential markers of coronary artery disease (CAD). However, even tough hypovitaminosis D has been suggested to interfere with Hcy catabolism, no study has so far addressed the interaction of vitamin D and Hcy and their impact on CAD, that was the aim of present study. A cohort of consecutive patients undergoing coronary angiography in a single center were included and analyzed within the year 2019. Significant CAD was defined as at least 1 vessel stenosis > 50%, while severe CAD as left main and/or three-vessel disease. Hcy and vitamin D levels were assesssed at admission. We included 3150 patients undergoing coronary angiography at our centre, who were divided according to the quartiles values of vitamin D. Patients with lower levels of Vitamin D displayed a higher cardiovascular risk profile and a higher prevalence of CAD. We observed an inverse linear relationship between lower levels of vitamin D and higher Hcy (r = − 0.092, p

BACKGROUND: Reduced levels of hemoglobin (Hb) represent an established marker of impaired outcomes and increased cardiovascular risk in patients with coronary artery disease, challenging the management of dual antiplatelet therapy (DAPT). However, while anemia has emerged as an independent predictor of suboptimal platelet inhibition in patients receiving clopidogrel, no study has so far evaluated the impact of Hb levels on high-on treatment platelet reactivity (HRPR) with ticagrelor and their prognostic consequences, that were the aim of the present study. METHODS: Patients on DAPT with ASA + Ticagrelor (90 mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. Aggregation tests were performed by multiple electrode aggregometry. Suboptimal platelet inhibition (HRPR-high residual platelet reactivity was defined if above the lower limit of normality (417 AU*min). The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome [MI], target vessel revascularization) at longest available follow-up. RESULTS: We included 397 patients that were divided according to tertiles values of Hb (< 12.7, 12-7-14.09, ≥14.1 g/dl). Patients with lower Hb were older and displayed a more severe cardiovascular risk profile. Mean levels of platelet reactivity were enhanced in patients with lower Hb after stimulation with TRAP peptide (TRAP test, p = .03) and ADP (p = .02). Elevated platelet reactivity (HRPR) on Ticagrelor was more frequent among patients with reduced Hb (16.4% vs. 12% vs. 5.4%, p = .005, adjusted OR [95%CI] = 1.71[0.996;3.01], p = .056). At a mean follow-up of 820.9 ± 553.4 days, 21.4% of the patients experienced the primary composite endpoint, with a higher rate of events in patients with lower Hb (27.6% vs. 22.6% vs. 13.5%, p = .006, adjusted HR [95%CI] = 1.51[1.12; 2.03], p = .006), mainly driven by a higher rate of recurrent ACS. After correction for baseline differences lower Hb tertiles but not HRPR emerged as independent predictor of MACE (adjusted HR [95%CI] = 0.98[0.50; 1.92], p = .95). CONCLUSIONS: In the present study, we demonstrated that among patients on DAPT with ASA and ticagrelor after PCI for ACS, lower Hb levels are independently associated with a higher rate of HRPR and an increased rate of major ischemic events, and especially for recurrent ACS, although with no impact on survival. Neutral prognostic effect of HRPR was observed across Hb tertiles.

Resumen Introduccion y objetivos La interrupcion muy precoz (entre 1 y 3 meses) del tratamiento antiagregante plaquetario doble (TAPD), ha aparecido recientemente en el intervencionismo percutaneo con la nueva generacion de stents liberadores de farmacos. El objetivo del presente metanalisis fue evaluar el impacto pronostico de los diferentes regimenes de doble terapia antiagregante corta o muy corta, comparada con la clasica durante 12 meses en pacientes tratados con intervencionismo coronario percutaneo con un stent liberador de farmacos (SLF) de nueva generacion. Metodos Se buscaron ensayos clinicos aleatorizados en la literatura y en las principales sesiones cientificas. El objetivo primario de eficacia fue la mortalidad y el objetivo primario de seguridad fueron las hemorragias mayores. Un analisis pre-especificado se realizo de acuerdo con el antiagregante elegido a largo plazo. Resultados Se incluyeron 5 ensayos clinicos aleatorizados con un total de 30.621 pacientes; entre los cuales, un 49,97% fueron aleatorizados a una TAPD muy corta (1-3 meses), seguidos de acido acetilsalicilico o P2Y12I en monoterapia. Una TAPD mas corta redujo significativamente el ratio de hemorragias mayores (2 frente a 3,1%, OR = 0,62; IC95%, 0,46-0,84; p = 0,002; phet = 0,02), aunque no se observo un impacto significativo en la mortalidad (1,3 frente a 2%, OR = 0,97; IC95%, 0,73-1,29; p = 0,84; phet = 0,18). La reduccion de eventos como las hemorragias fue incluso mas significativa en los ensayos aleatorizados en los que los pacientes estaban libres de eventos en el momento de la suspension de la DAT. La aparicion de infarto agudo de miocardio y la trombosis del stent fue similar en ambas estrategias (TAPD muy corta frente a TAPD clasica de 12 meses). Conclusiones Basandonos en el actual metanalisis, un periodo muy breve (1-3 meses) de TAPD se asocia con una reduccion significativa de hemorragia mayor en comparacion con la terapia clasica de 12 meses, sin incremento de eventos isquemicos mayores y con una supervivencia similar.

Current research on cardiovascular prevention predominantly focuses on risk-stratification and management of patients with coronary artery disease (CAD) to optimize their prognosis. Several basic, translational and clinical research efforts aim to determine the etiological mechanisms underlying CAD pathogenesis and to identify lifestyle-dependent metabolic risk factors or genetic and epigenetic parameters responsible for CAD occurrence and/or progression. A log-linear association between the absolute exposure of LDL cholesterol (LDL-C) and the risk of atherosclerotic cardio-vascular disease (ASCVD) was well documented over the year. LDL-C was identified as the principal enemy to fight against, and soluble proprotein convertase subtilisin kexin type 9 (PCSK9) was attributed the role of a powerful regulator of blood LDL-C levels. The two currently available antibodies (alirocumab and evolocumab) against PCSK9 are fully human engineered IgG that bind to soluble PCSK9 and avoid its interaction with the LDLR. As documented by modern and dedicated “game-changer” trials, antibodies against soluble PCSK9 reduce LDL-C levels by at least 60 percent when used alone and up to 85 percent when used in combination with high-intensity statins and/or other hypolipidemic therapies, including ezetimibe. Their clinical indications are well established, but new areas of use are advocated. Several clues suggest that regulation of PCSK9 represents a cornerstone of cardiovascular prevention, partly because of some pleiotropic effects attributed to these newly developed drugs. New mechanisms of PCSK9 regulation are being explored, and further efforts need to be put in place to reach patients with these new therapies. The aim of this manuscript is to perform a narrative review of the literature on soluble PCSK9 inhibitor drugs, with a focus on their indications and clinical impact.

Cardiovascular disease still represents the main cause of mortality worldwide. Despite huge improvements, atherosclerosis persists as the principal pathological condition, both in stable and acute presentation. Specifically, acute coronary syndromes have received substantial research and clinical attention in recent years, contributing to improve overall patients’ outcome. The identification of different evolution patterns of the atherosclerotic plaque and coronary artery disease has suggested the potential need of different treatment approaches, according to the mechanisms and molecular elements involved. In addition to traditional risk factors, the finer portrayal of other metabolic and lipid-related mediators has led to higher and deep knowledge of atherosclerosis, providing potential new targets for clinical management of the patients. Finally, the impressive advances in genetics and non-coding RNAs have opened a wide field of research both on pathophysiology and the therapeutic side that are extensively under investigation.

Recent evidence on ischemia, rather than coronary artery disease (CAD), representing a major determinant of outcomes, has led to a progressive shift in the management of patients with ischemic heart disease. According to most recent guidelines, myocardial revascularization strategies based on anatomical findings should be progressively abandoned in favor of functional criteria for the guidance of PCI. Thus, emerging importance has been assigned to the assessment of coronary physiology in order to determine the ischemic significance of coronary stenoses. However, despite several indexes and tools that have been developed so far, the existence of technical and clinical conditions potentially biasing the functional evaluation of the coronary tree still cause debates regarding the strategy of choice. The present review provides an overview of the available methods and the most recent acquirements for the invasive assessment of ischemia, focusing on the most widely available indexes, fractional flow reserve (FFR) and instant-wave free ratio (iFR), in addition to emerging examples, as new approaches to coronary flow reserve (CFR) and microvascular resistance, aiming at promoting the knowledge and application of those “full physiology” principles, which are generally advocated to allow a tailored treatment and the achievement of the largest prognostic benefits.

The control of cardiovascular risk factors, the promotion of a healthy lifestyle, and antithrombotic therapy are the cornerstones of secondary prevention after acute coronary syndrome (ACS). However, many patients have recurrent ischemic events despite the optimal control of traditional modifiable risk factors and the use of tailored pharmacological therapy, including new-generation antiplatelet and lipid-lowering agents. This evidence emphasizes the importance of identifying novel risk factors and targets to optimize secondary preventive strategies. Lipoprotein(a) (Lp(a)) has emerged as an independent predictor of adverse events after ACS. New molecules such as anti-PCSK9 monoclonal antibodies, small interfering RNAs, and antisense oligonucleotides can reduce plasma Lp(a) levels and are associated with a long-term outcome benefit after the index event. The inflammatory stimulus and the inflammasome, pivotal elements in the development and progression of atherosclerosis, have been widely investigated in patients with coronary artery disease. More recently, randomized clinical trials including post-ACS patients treated with colchicine and monoclonal antibodies targeting cytokines yielded promising results in the reduction in major cardiovascular events after an ACS. Gut dysbiosis has also raised great interest for its potential pathophysiological role in cardiovascular disease. This evidence, albeit preliminary and needing confirmation by larger population-based studies, suggests the possibility of targeting the gut microbiome in particularly high-risk populations. The risk of recurrent ischemic events after ACS is related to the complex interaction between intrinsic predisposing factors and environmental triggers. The identification of novel risk factors and targets is fundamental to customizing patient clinical management with a precision medicine perspective.

Whether Vitamin D deficiency represents an independent predictor of mortality and major cardiovascular events or rather the mirror of a more advanced clinical condition with increased comorbidities is still debated. We aimed at assessing the impact of vitamin D levels on the long-term outcomes among patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention.Consecutive patients from a single centre were included. Vitamin D levels were measured at admission by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc). Severe deficiency was defined for 25(OH)D10 ng/ml. The primary study endpoint was overall mortality. Secondary endpoints were cardiovascular mortality, recurrent acute coronary syndrome or major cardiovascular events (a composite of death, recurrent MI and target vessel revascularization) at the longest available follow-up.We included a total of 705 patients, that were divided according to vitamin D tertiles (12.7; 12.7-21.59; ≥21.6 ng/ml). Lower levels of Vitamin D were associated with renal failure (p=0.03), more severe coronary disease (p=0.001), diabetes mellitus and previous CABG (p0.001), lower ejection fraction (p=0.02), acute presentation (p=0.04), use of statins (p=0.02), diuretics, nitrates and clopidogrel (p0.001) and RASI (p=0.008). An inverse association was documented with BMI, glycemia, total cholesterol (p0.001), creatinine and WBC (p=0.001). At a median follow-up of 996.5 [377-1552] days, 3.8% of the patients died. Vitamin D deficiency was significantly associated with overall mortality (7.6% vs 2.9% vs 0.4%, adjusted HR[95%CI]=3.6[1.43-8.9], p=0.006), MACE (adjusted HR[95%CI]=1.32[1.07-1.63], p=0.01) and the composite of death and MI (adjusted HR[95%CI]=1.3[1.03-1.65], p=0.03). A similarly increased risk was confirmed for all major higher-risk subsets of patients, with no significant interaction according to age, gender, diabetes mellitus or chronic kidney disease.Among patients undergoing percutaneous coronary interventions, lower levels of vitamin D are associated with an over 3-fold increased risk of mortality and major cardiovascular events. Future larger studies are certainly warranted in order to define the prognostic implications of cholecalciferol supplementation among high-risk patients with established coronary artery disease.

Tetralogy of Fallot (TOF) is a heterogeneous congenital heart disease that is occasionally diagnosed during adulthood. However, although they are often asymptomatic, adult patients with uncorrected TOF often have a poor prognosis. Poor outcomes indicate the importance of the identification and management of these patients, especially in the context of intercurrent disease or noncardiac surgery. We describe a case of clinically silent TOF in a 51-year-old woman. TOF was unmasked during a major noncardiac surgery for a polytrauma and successfully treated with the cooperation of a multidisciplinary team. (Level of Difficulty: Advanced.)

Background The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality. Objectives The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of “at-risk” patient cohorts for failure to present or delays to treatment. Methods This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality. Results A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p, Central Illustration

The association between vitamin D and the prevalence and severity of coronary artery disease (CAD), major established cardiovascular risk factors, and acute ischemic events has been consistently demonstrated in large-scale observational studies and meta-analyses, with relevant prognostic implications. The rise in prevalence of hypovitaminosis D in recent years, reaching pandemic pro-portions, has pointed to the importance of the identification and optimization of the indications and strategies for the therapeutic use of vitamin D, with particular relevance for cardiovascular health. However, vitamin D supplementation has provided so far inconsistent results in primary prevention, with even fewer data reported in patients with established CAD. The present review aims to provide an updated overview of the available evidence and potential therapeutic applications of vitaminD in patients with CAD.

The optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) admitted with acute coronary syndrome (ACS) and treated with a drug-eluting stent (DES) remains unclear. This is a prespecified sub-study from the Randomised Evaluation of short-term DUal antiplatelet therapy in patients with acute Coronary syndromE treated with a new generation DES (REDUCE) trial that was designed to determine the efficacy and safety of short-term versus standard 12 months DAPT in diabetic patients with ACS undergoing percutaneous coronary intervention (PCI) using the COMBO stent.In this study we included ACS diabetic patients enroled in the REDUCE trial treated with the COMBO stent and randomly assigned to either 3 or 12 months of DAPT. The primary study endpoint was the composite of all-cause mortality, myocardial infarction (MI), stent thrombosis (ST), stroke, target vessel revascularisation (TVR), and bleeding complications at 12 and 24 months follow-up.A total of 307 diabetic patients were included, of which 162 (52.8%) in the 3 months DAPT group and 145 (47.2%) in the 12 months DAPT group. Patient characteristics, PCI success, and number of stents used were similar in the 3 and 12 months DAPT groups. Occurrence of the primary study endpoint at 12 and 24 months follow-up was comparable between the two groups (3.1 vs. 3.5%, p = 0.865, and 15.8 vs. 14.9%, p = 0.824, respectively). Moreover, the prevalence of the specific clinical outcome parameters (all-cause mortality), MI, ST, stroke, TVR, and bleeding was similar in both study groups.This sub-analysis shows similar clinical outcomes following 3 months DAPT as compared to 12 months DAPT in diabetic patients undergoing PCI for ACS using the COMBO stent. These results suggest that, even in this particular subset of patients, short duration of DAPT might be considered safe. Future larger studies are warranted to provide more precise estimations in terms of safety and efficacy of short term DAPT in these high-risk patients.

Background. Optimization of the techniques and larger accessibility to mechanical reperfusion have significantly improved the outcomes of patients with ST-segment elevation myocardial infarction (STEMI). However, suboptimal results have been observed in certain higher-risk subsets of patients, as in advanced age, where the benefits of primary PCI are more debated. We evaluated the impact of systematic primary percutaneous coronary intervention (PCI) and an optimized STEMI network on the long-term prognosis from a single centre experience. Methods. We included STEMI patients included in the FAST-STEMI network between 2016 and 2019. Ischemia duration was defined as the time from symptoms onset to coronary reopening (pain-to-balloon, PTB). The primary study endpoint (PE) was a composite of mortality and recurrent MI at long-term follow-up. Indywidual outcome endpoints were also assessed. Results. We included 253 patients undergoing primary PCI and discharged alive. Mean age was 67.2 ± 12.5 years, 75.1% males and 19.8% diabetics. At a median follow-up of 581 [307–922] days, the primary endpoint occurred in 24 patients (7.9%), of whom 5.5% died. The occurrence of a cardiovascular event was significantly associated with advanced age (p < 0.001), renal failure (p = 0.03), lower ejection fraction at discharge (p = 0.04) and longer in-hospital stay (p = 0.01). The median PTB was 198 minutes [IQR: 125–340 min], that was significantly longer among patients experiencing the PE (p = 0.01). A linear relationship was observed between age and PTB (r = 0.13, p = 0.009). However, both age ≥ 75 years and PTB above the median emerged as independent predictors of the primary endpoint (age: HR [95%CI] = 5.56 [2.26–13.7], p < 0.001, PTB: HR [95%CI] = 3.59 [1.39–9.3], p = 0.01). Similar results were observed for overall mortality. Conclusion. The present study shows that among STEMI patients undergoing primary PCI in a single centre, the duration of ischemia and advance age are independently associated to long-term mortality and recurrent myocardial infarction. However, longer time to reperfusion was observed among elderly patients.

Background Increased comorbidities and a perceived high-bleeding risk often prevent the use of dual antiplatelet therapy (DAPT) in female patients. However, more aggressive antiplatelet treatment would certainly offer additional outcome benefits in coronary artery disease, especially among diabetic patients. The aim of the present study was to evaluate the gender differences in high-residual on treatment platelet reactivity (HRPR) among diabetic patients treated with DAPT. Methods Our population is represented by a consecutive cohort of diabetic patients treated with DAPT (ASA + clopidogrel, ticagrelor or dose-adjusted prasugrel) for an acute coronary syndrome or elective PCI, undergoing platelet reactivity assessment at 30–90 days post-discharge. Aggregation was assessed by multiple-electrode aggregometry and in diabetic patients naive to antiplatelet therapy, by light transmission aggregometry, surface expression of P-selectin and plasma concentration of Thromboxane B2. Results We included 472 patients, 113 (23.9%) women. Female gender was associated with more advanced age, and increased comorbidities. Mean platelet reactivity did not differ according to gender. The rate of HRPR was similar in women as compared to men (for ASA: adjusted OR[95%CI] = 0.59[0.27–1.33], p = 0.21, for ADP-antagonists: adjusted OR[95%CI] = 1.24[0.25–1.80], p = 0.27), however, the benefits of the new ADP-antagonists on platelet reactivity were lower in women than in men (p interaction = 0.01). No impact of gender on platelet reactivity was confirmed among 50 diabetic patients naive to antiplatelet therapy. Conclusions Among diabetic patients receiving dual antiplatelet therapy gender does not affect platelet reactivity or high-on treatment platelet reactivity. However, the enhanced platelet inhibition provided by the new-ADP antagonists of new-ADP antagonists could be mitigated in women.