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Background: Real-world data on the use of lipid-lowering therapy (LLT) in clinical practice show that about 80% of (very) high-cardiovascular (CV)-risk patients disregard the 2019 European Society of Cardiology (ESC) Guidelines' recommendations on dyslipidemias. The availability of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9mAb) should reduce this gap. Our aim was to provide data on PCSK9mAb use in clinical practice, investigating the achievement of the ESC Guidelines' recommendations in the real world. Methods: Between April 2018 and December 2022, patients who started on PCSK9mAb therapy (140 mg of evolocumab or 75 mg or 150 mg of alirocumab, subcutaneous injection every 2 weeks) were included in a prospective registry. Our cohort consisted of 256 patients: 95 (37.1%) were women (mean age: 65.43 ± 11.12 yrs), 53 (20.7%) were at high CV risk, and 203 (79.3%) were at very high CV risk. Results: After one year of PCSK9mAb treatment, nearly 60% of patients demonstrated full adherence to the ESC Guidelines' recommendations, defined as achieving at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C) levels along with reaching LDL-C target levels (≤55 and ≤70 mg/dL for very high and high risk, respectively). Concomitant high-dose statin therapy emerged as the primary predictor of LDL-C target attainment. Heterozygous familial hypercholesterolemia (HeFH), statin intolerance, and female gender were associated with a significant lower probability of achieving LDL-C target levels. Conclusions: Our analysis confirms that PCSK9mAb treatment is safe and effective, enabling 60% of our cohort to fully achieve the LDL-C guideline recommendations. The use of high-intensity statins emerged as a significant predictor of efficacy. Conversely, familial hypercholesterolemia and female gender were identified as predictors of therapeutic failure. Hence, it is crucial to address disparities in cardiovascular disease prevention between genders and to enhance strategies for managing elevated LDL-C in HeFH patients.
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Background: In February 2021, a few cases of unusual, severe thrombotic events associated with thrombocytopenia reported after vaccination with ChAdOx1 nCoV-19 (Vaxzevria) or with Johnson & Johnson's Janssen vaccine raise concern about safety. The vaccine-induced thrombotic thrombocytopenia (VITT) has been related to the presence of platelet-activating antibodies directed against platelet Factor 4. Objectives: We investigated VITT subject genetic background by a high-throughput whole exome sequencing (WES) approach in order to investigate VITT genetic predisposition. Methods: Six consecutive patients (females of Caucasian origin with a mean age of 64 years) were referred to the Atherothrombotic Diseases Center (Department of Experimental and Clinical Medicine, Azienda Ospedaliero-Universitaria Careggi, Florence) with a diagnosis of definite VITT underwent WES analysis. WES analysis was performed on the Illumina NextSeq500 platform. Results:WES analysis revealed a total of 140,563 genetic variants. Due to VITT's rare occurrence, we focused attention on rare variants. The global analysis of all high-quality rare variants did not reveal a significant enrichment of mutated genes in biological/functional pathways common to patients analyzed. Afterwards, we focused on rare variants in genes associated with blood coagulation and fibrinolysis, platelet activation and aggregation, integrin-mediated signaling pathway, and inflammation with particular attention to those involved in vascular damage, as well as autoimmune thrombocytopenia. According to ACMG criteria, 47/194 (24.2%) rare variants were classified as uncertain significance variants (VUS), whereas the remaining were likely benign/benign. Conclusion: WES analysis identifies rare variants possibly favoring the prothrombotic state triggered by the exposure to the vaccine. Functional studies and/or extensions to a larger number of patients might allow a more comprehensive definition of these molecular pathways.
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Secuenciación del Exoma , Humanos , Persona de Mediana Edad , Femenino , Anciano , Trombocitopenia/genética , Trombocitopenia/inducido químicamente , ChAdOx1 nCoV-19/efectos adversos , Trombosis/genética , Predisposición Genética a la Enfermedad , Factor Plaquetario 4/genética , Masculino , Vacunación/efectos adversosRESUMEN
Background: Cardiac surgery is a high-risk setting for heparin-induced thrombocytopenia (HIT). However, large differences in its incidence, rate of thrombotic complications, and mortality have been reported in this context. Few studies address the pharmacologic management of HIT specifically in this setting. Objectives: To describe the incidence, outcomes, and management of patients with HIT in our cohort and to compare them with patients presenting platelet factor 4/heparin antibodies but without platelet-activating capacity. Methods: A retrospective observational study was conducted over a period of 10 years and 6 months on 13,178 cardiac operations in a single high-volume cardiac surgery center. Results: HIT was diagnosed in 0.22% of patients. HIT with associated thromboembolic complications occurred in 0.04% of cases. Two deaths at 30 days were registered, both in patients with associated thrombosis. The 4T score showed a 99.9% negative predictive value. The immunoglobulin G-specific chemiluminescence test positivity rate was highly predictive of HIT. Warfarin was often started early after surgery, and although it was rarely stopped when the diagnosis of HIT was made, no new thromboembolic complications subsequently occurred. Thrombocytopenia appeared to be a poor prognostic sign, whatever the cause. Conclusion: Although rare, HIT is characterized by high mortality in this setting, especially if thrombotic complications occur. Large multicentric studies or an international registry should be created to enhance the scientific evidence on HIT diagnosis and management in this context.
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AIMS: Long-term oral anticoagulation is the primary therapy for preventing ischemic stroke in patients with atrial fibrillation (AF). Different types of oral anticoagulant drugs can have specific effects on the metabolism of patients. Here we characterize, for the first time, the serum metabolomic and lipoproteomic profiles of AF patients treated with anticoagulants: vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). MATERIALS AND METHODS: Serum samples of 167 AF patients (median age 78 years, 62 % males, 70 % on DOACs treatment) were analyzed via high resolution 1H nuclear magnetic resonance (NMR) spectroscopy. Data on 25 metabolites and 112 lipoprotein-related fractions were quantified and analyzed with multivariate and univariate statistical approaches. KEY FINDINGS: Our data provide evidence that patients treated with VKAs and DOACs present significant differences in their profiles: lower levels of alanine and lactate (odds ratio: 1.72 and 1.84), free cholesterol VLDL-4 subfraction (OR: 1.75), triglycerides LDL-1 subfraction (OR: 1.80) and 4 IDL cholesterol fractions (ORs â¼ 1.80), as well as higher levels of HDL cholesterol (OR: 0.48), apolipoprotein A1 (OR: 0.42) and 7 HDL cholesterol fractions/subfractions (ORs: 0.40-0.51) are characteristic of serum profile of patients on DOACs' therapy. SIGNIFICANCE: Our results support the usefulness of NMR-based metabolomics for the description of the effects of oral anticoagulants on AF patient circulating metabolites and lipoproteins. The higher serum levels of HDL cholesterol observed in patients on DOACs could contribute to explaining their reduced cardiovascular risk, suggesting the need of further studies in this direction to fully understand possible clinical implications.
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Anticoagulantes , Fibrilación Atrial , Metabolómica , Vitamina K , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/sangre , Masculino , Femenino , Anciano , Vitamina K/antagonistas & inhibidores , Anticoagulantes/uso terapéutico , Anticoagulantes/farmacología , Anticoagulantes/administración & dosificación , Administración Oral , Anciano de 80 o más Años , Metabolómica/métodos , Metaboloma/efectos de los fármacos , Persona de Mediana Edad , Espectroscopía de Resonancia MagnéticaRESUMEN
This review article focuses on the role of adenosine in coronary artery disease (CAD) diagnosis and treatment. Adenosine, an endogenous purine nucleoside, plays crucial roles in cardiovascular physiology and pathology. Its release and effects, mediated by specific receptors, influence vasomotor function, blood pressure regulation, heart rate, and platelet activity. Adenosine therapeutic effects include treatment of the no-reflow phenomenon and paroxysmal supraventricular tachycardia. The production of adenosine involves complex cellular pathways, with extracellular and intracellular synthesis mechanisms. Adenosine's rapid metabolism underscores its short half-life and physiological turnover. Furthermore, adenosine's involvement in side effects of antiplatelet therapy, particularly ticagrelor and cangrelor, highlights its clinical significance. Moreover, adenosine serves as a valuable tool in CAD diagnosis, aiding stress testing modalities and guiding intracoronary physiological assessments. Its use in assessing epicardial stenosis and microvascular dysfunction is pivotal for treatment decisions. Overall, understanding adenosine's mechanisms and clinical implications is essential for optimizing CAD management strategies, encompassing both therapeutic interventions and diagnostic approaches.
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Adenosina , Enfermedad de la Arteria Coronaria , Humanos , Adenosina/metabolismo , Enfermedad de la Arteria Coronaria/metabolismo , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Animales , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adenosina Monofosfato/metabolismo , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacologíaRESUMEN
BACKGROUND: The accuracy of available prediction tools for clinical outcomes in patients with atrial fibrillation (AF) remains modest. Machine Learning (ML) has been used to predict outcomes in the AF population, but not in a population entirely on anticoagulant therapy. METHODS AND AIMS: Different supervised ML models were applied to predict all-cause death, cardiovascular (CV) death, major bleeding and stroke in anticoagulated patients with AF, processing data from the multicenter START-2 Register. RESULTS: 11078 AF patients (male n = 6029, 54.3%) were enrolled with a median follow-up period of 1.5 years [IQR 1.0-2.6]. Patients on Vitamin K Antagonists (VKA) were 5135 (46.4%) and 5943 (53.6%) were on Direct Oral Anticoagulants (DOAC). Using Multi-Gate Mixture of Experts, a cross-validated AUC of 0.779 ± 0.016 and 0.745 ± 0.022 were obtained, respectively, for the prediction of all-cause death and CV-death in the overall population. The best ML model outperformed CHA2DSVA2SC and HAS-BLED for all-cause death prediction (p < 0.001 for both). When compared to HAS-BLED, Gradient Boosting improved major bleeding prediction in DOACs patients (0.711 vs. 0.586, p < 0.001). A very low number of events during follow-up (52) resulted in a suboptimal ischemic stroke prediction (best AUC of 0.606 ± 0.117 in overall population). Body mass index, age, renal function, platelet count and hemoglobin levels resulted the most important variables for ML prediction. CONCLUSIONS: In AF patients, ML models showed good discriminative ability to predict all-cause death, regardless of the type of anticoagulation strategy, and major bleeding on DOAC therapy, outperforming CHA2DS2VASC and the HAS-BLED scores for risk prediction in these populations.
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Anticoagulantes , Fibrilación Atrial , Aprendizaje Automático , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Masculino , Femenino , Anciano , Anticoagulantes/uso terapéutico , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Anciano de 80 o más Años , Sistema de Registros , Persona de Mediana Edad , Estudios de Seguimiento , Valor Predictivo de las Pruebas , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Resultado del Tratamiento , Medición de Riesgo/métodosRESUMEN
BACKGROUND: The impact of non-vitamin K antagonist oral anticoagulants (NOACs) on platelet function is still unclear. We conducted a comprehensive ex vivo study aimed at assessing the effect of the four currently marketed NOACs on platelet function. METHODS: We incubated blood samples from healthy donors with concentrations of NOACs (50, 150 and 250 ng/mL), in the range of those achieved in the plasma of patients during therapy. We evaluated generation of thrombin; light transmittance platelet aggregation (LTA) in response to adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), human γ-thrombin (THR) and tissue factor (TF); generation of thromboxane (TX)B2; and expression of protease-activated receptor (PAR)-1 and P-selectin on the platelet surface. RESULTS: All NOACs concentration-dependently reduced thrombin generation compared with control. THR-induced LTA was suppressed by the addition of dabigatran at any concentration, while TF-induced LTA was reduced by factor-Xa inhibitors. ADP- and TRAP-induced LTA was not modified by NOACs. TXB2 generation was reduced by all NOACs, particularly at the highest concentrations. We found a concentration-dependent increase in PAR-1 expression after incubation with dabigatran, mainly at the highest concentrations, but not with FXa inhibitors; P-selectin expression was not changed by any drugs. CONCLUSIONS: Treatment with the NOACs is associated with measurable ex vivo changes in platelet function, arguing for antiplatelet effects beyond the well-known anticoagulant activities of these drugs. There are differences, however, among the NOACs, especially between dabigatran and the FXa inhibitors.
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Background: Direct oral anticoagulants (DOACs) are recommended for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. We aimed to describe the prevalence of inappropriate DOACs dose prescription in the START2-AF Registry, the outcomes according to the appropriateness of the dosage, and the factors associated with inappropriate dose prescription. Methods: Patients' demographics and clinical data were prospectively collected as electronic files in an anonymous form on the website of the START2-Registry; DOACs dosage was determined to be appropriate when prescribed according to the European Heart Rhythm Association Guidelines. Results: We included 5943 NVAF patients on DOACs; 2572 (46.3%) were female patients. The standard dose (SD) was prescribed to 56.9% of patients and the low dose (LD) was prescribed to 43.1% of patients; 38.9% of all NVAF patients received an inappropriate LD DOAC and 0.3% received inappropriate SD. Patients treated with LD DOAC had a significantly higher rate of all bleedings (RR 1.5; 95% CI 1.2-2.0), major bleedings (RR 1.8; 95% CI 1.3-1.7), and mortality (RR 2.8; 95% CI 1.9-4.1) with respect to patients treated with SD DOAC. No difference was found among patients treated with appropriate and inappropriate LD regarding bleeding, thrombotic, and mortality rates. Age, body weight <60 kg, and renal failure were significantly associated with inappropriate LD DOAC prescription. Conclusions: Inappropriate LD DOACs in NVAF patients is not associated with a reduction in bleeding risk, nor with an increased thrombotic risk. Instead, it is associated with higher mortality rate, suggesting that, in clinical practice, underdosing is preferred for patients at particularly high risk for adverse events.
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BACKGROUND: Lipoprotein(a) [Lp(a)] level variability, related to atherothrombotic risk increase, is mainly attributed to LPA gene, encoding apolipoprotein(a), with kringle IV type 2 (KIV2) copy number variation (CNV) acting as the primary genetic determinant. Genetic characterization of Lp(a) is in continuous growth; nevertheless, the peculiar structural characteristics of this variant constitute a significant challenge to the development of effective detection methods. The aim of the study was to compare quantitative real-time PCR (qPCR) and digital droplet PCR (ddPCR) in the evaluation of KIV2 repeat polymorphism. METHODS: We analysed 100 subjects tested for cardiovascular risk in which Lp(a) plasma levels were assessed. RESULTS: Correlation analysis between CNV values obtained with the two methods was slightly significant (R = 0.413, p = 0.00002), because of the wider data dispersion in qPCR compared with ddPCR. Internal controls C1, C2 and C3 measurements throughout different experimental sessions revealed the superior stability of ddPCR, which was supported by a reduced intra/inter-assay coefficient of variation determined in this method compared to qPCR. A significant inverse correlation between Lp(a) levels and CNV values was confirmed for both techniques, but it was higher when evaluated by ddPCR than qPCR (R = -0.393, p = 0.000053 vs R = -0.220, p = 0.028, respectively). When dividing subjects into two groups according to 500 mg/L Lp(a) cut-off value, a significantly lower number of KIV2 repeats emerged among subjects with greater Lp(a) levels, with stronger evidence in ddPCR than in qPCR (p = 0.000013 and p = 0.001, respectively). CONCLUSIONS: Data obtained support a better performance of ddPCR in the evaluation of KIV2 repeat polymorphism.
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Variaciones en el Número de Copia de ADN , Kringles , Humanos , Kringles/genética , Variaciones en el Número de Copia de ADN/genética , Lipoproteína(a)/genética , Polimorfismo Genético , Reacción en Cadena en Tiempo Real de la Polimerasa/métodosAsunto(s)
Factor Plaquetario 4 , Púrpura Trombocitopénica Idiopática , Trombosis , Humanos , Trombosis/etiología , Trombosis/inmunología , Trombosis/sangre , Femenino , Púrpura Trombocitopénica Idiopática/inmunología , Púrpura Trombocitopénica Idiopática/sangre , Púrpura Trombocitopénica Idiopática/inducido químicamente , Masculino , Factor Plaquetario 4/inmunología , Persona de Mediana Edad , Adulto , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , AncianoRESUMEN
BACKGROUND AND AIMS: Lowering low-density lipoprotein cholesterol (LDL-C) is the cornerstone of cardiovascular disease prevention. Collection of epidemiological data is crucial for monitoring healthcare appropriateness. This analysis aimed to evaluate the proportion of high-risk patients who achieved guidelines recommended LDL-C goal, and explore the predictors of therapeutic failure, with a focus on the role of gender. METHODS AND RESULTS: Health administrative and laboratory data from seven Local Health Districts in Tuscany were collected for residents aged ≥45 years with a history of major adverse cardiac or cerebrovascular event (MACCE) and/or type 2 diabetes mellitus (T2DM) from January 1, 2019, to January 1, 2021. The study aimed to assess the number of patients with optimal levels of LDL-C (<55 mg/dl for patients with MACCE and <70 mg/dl for patients with T2DM without MACCE). A cohort of 174 200 individuals (55% males) was analyzed and it was found that 11.6% of them achieved the target LDL-C levels. Female gender was identified as an independent predictor of LDL-C target underattainment in patients with MACCE with or without T2DM, after adjusting for age, cardiovascular risk factors, comorbidities, and district area (adjusted-IRR 0.58 ± 0.01; p < 0.001). This result was consistent in subjects without lipid-lowering therapies (adjusted-IRR 0.56 ± 0.01; p < 0.001). CONCLUSION: In an unselected cohort of high-risk individuals, females have a significantly lower probability of reaching LDL-C recommended targets. These results emphasize the need for action to implement education for clinicians and patients and to establish clinical care pathways for high-risk patients, with a special focus on women.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Femenino , Masculino , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , LDL-Colesterol , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Sexismo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Factores de RiesgoRESUMEN
AIMS: Whether pregnancy is a modifier of the long-term course and outcome of women with hypertrophic cardiomyopathy (HCM) is unknown. We assessed the association of pregnancy with long-term outcomes in HCM women. METHODS AND RESULTS: Retrospective evaluation of women with HCM from 1970 to 2021. Only women with pregnancy-related information (pregnancy present or absent) and a follow-up period lasting ≥1 year were included. The peri-partum period was defined as -1 to 6 months after delivery. The primary endpoint was a composite for major adverse cardiovascular events [MACE: cardiovascular death, sudden cardiac death, appropriate defibrillator shock and heart failure (HF) progression]. Overall, 379 (58%) women were included. There were 432 pregnancies in 242 (63%) patients. In 29 (7.6%) cases, pregnancies (n = 39) occurred after HCM diagnosis. Among these, three carrying likely pathogenic sarcomeric variants suffered MACEs in the peri-partum period. At 10 ± 9 years of follow-up, age at diagnosis [hazard ratio (HR) 1.034, 95% confidence interval (CI) 1.018-1.050, P < 0.001] and New York Heart Association (NYHA) class (II vs. I: HR 1.944, 95% CI 0.896-4.218; III vs. I: HR 5.291, 95% CI 2.392-11.705, P < 0.001) were associated with MACE. Conversely, pregnancy was associated with reduced risk (HR 0.605; 95% CI 0.380-0.963, P = 0.034). Among women with pregnancy, multiple occurrences did not modify risk. CONCLUSIONS: Pregnancy is not a modifier of long-term outcome in women with HCM and mostly occurs before a cardiac diagnosis. Most patients tolerate pregnancy well and do not show a survival disadvantage compared to women without. Pregnancy should not be discouraged, except in the presence of severe HF symptoms or high-risk features.
Hypertrophic cardiomyopathy (HCM) is the most common genetic disorder of the myocardium and is characterized by important gender-related differences: women are typically 5 years older than men at diagnosis, over half are diagnosed >50 years of age and consistently show greater propensity than men for heart failure (HF)-related complications and adverse outcome. Whether pregnancy is a modifier of the long-term course and outcome of women with HCM is unknown. In this study, pregnancy was not a modifier of long-term outcome in women with HCM. In particular: At 10 ± 7 years, most patients tolerated pregnancy well and did not show a survival disadvantage compared to women without pregnancies. Only baseline heart failure symptoms and age were associated with adverse outcome.Pregnancy should not be discouraged, except in the presence of severe HF symptoms or high-risk features. Nevertheless, cardio-obstetric counselling and close supervision are key in all instances, particularly in the peri-partum period.
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Cardiomiopatía Hipertrófica , Embarazo , Humanos , Femenino , Masculino , Estudios Retrospectivos , Factores de Riesgo , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/epidemiología , Cardiomiopatía Hipertrófica/terapia , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Modelos de Riesgos ProporcionalesRESUMEN
In anticoagulated atrial fibrillation (AF) patients, the validity of models recommended for the stratification of the risk ratio between benefits and hemorrhage risk is limited. We hypothesize that both circulating and neuroimaging-based markers might improve the prediction of bleeding and thrombotic risk in anticoagulated AF patients. The Strat-AF study is an observational, prospective, single-center study enrolling 170 patients with AF; recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral magnetic resonance imaging and circulating biomarkers assessment. The main outcome is the evaluation of cerebral microangiopathy related to the levels of circulating biomarkers of inflammation and extracellular matrix (ECM) remodeling. At multivariate logistic regression analysis adjusted for age, sex, CHA2DS2-VASc, HAS-BLED and type of anticoagulant, matrix metalloproteinases (MMP)-2 levels were significantly and positively associated with the presence of cerebral microbleeds (CMBs). A significant association between MMP-2, tissue inhibitor of metalloproteinases (TIMP)-1,-2,-4 levels and white matter hyperintensity was also found. Concerning the small vessel disease (SVD) score, MMP-2 and TIMP-1,-2 levels were associated with the presence of two and three or more signs of SVD, whereas TIMP-4 levels were associated with the presence of three signs of SVD with respect to patients with no instrumental signs of SVD. As regarding the presence of enlarged perivascular spaces (EPVS), a significant association was found for high levels of interleukin (IL)-8 and TIMP 1-2-3. These results demonstrate that patients with AF have evidence of impaired ECM degradation, which is an independent risk factor for thrombotic complications of AF patients on oral anticoagulant therapy. The incorporation of these markers in the prognostic schemes might improve their clinical capability in predicting stroke risk and thrombotic complications.
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Ticagrelor is currently considered a first-line choice in dual antiplatelet therapy (DAPT) following revascularization of acute coronary syndrome (ACS). However, its use is correlated with an increased incidence of two side effects, dyspnea and bradyarrhythmias, whose molecular mechanisms have not yet been defined with certainty and, consequently, neither of the therapeutic decisions they imply. We report the case of a patient with acute myocardial infarction treated with ticagrelor and aspirin as oral antithrombotic therapy after primary percutaneous coronary intervention (PCI), manifesting in a significant bradyarrhythmic episode that required a switch of antiplatelet therapy. Starting from this case report, this article aims to gather the currently available evidence regarding the molecular mechanisms underlying these side effects and propose possible decision-making algorithms regarding their management in clinical practice.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Ticagrelor/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Aspirina/uso terapéutico , Infarto del Miocardio/terapia , Resultado del TratamientoRESUMEN
INTRODUCTION: Patients with hypertrophic cardiomyopathy (HCM) are at increased risk of stroke, but the incidence and factors associated with cardioembolic events in HCM patients without atrial fibrillation (AF) remain unresolved. We determined the incidence of stroke in patients in sinus rhythm (SR) monitored with a cardiac implantable electronic device (CIED). METHODS: All consecutive patients diagnosed with HCM and referred to CIED implantation with >16 years at diagnosis and ≥ 1 year follow-up post CIED implantation were retrospectively reviewed. Severe LA dilatation was defined as ≥48 mm. Patients were stratified by rhythm as: Pre-existing AF (AF present prior to CIED); De novo AF (AF present after CIED implantation); SR: no episodes of AF. RESULTS: Of 1651 patients, 185 (11.2%) implanted with a CIED were included (57% men, age: 54 ± 17 years). Baseline, pre-existing AF was present in 73 (39%) patients. Ischemic stroke was reported in 19 (10.3%, 1.78%/year) patients and was similar across the three groups (2.3%/year vs 1.1%/year vs 0.6%/year in patients in SR vs pre-existing AF vs de novo AF, respectively, p = 0.235). In SR patients, a LAD≥48 mm posed the greatest risk of stroke (Hazard Ratio: 10.03,95% Confidence-Interval 2.79-16.01). At Cox multivariable analysis, after adjustment for oral anticoagulation, LA was independently associated with stroke while rhythm was not. CONCLUSIONS: in HCM patients with CIED long-term monitoring and no prior history of AF, stroke rates were similar in those with de novo AF or stable SR. Severe LA dilatation was a powerful risk factor, irrespective of AF.
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Fibrilación Atrial , Cardiomiopatía Hipertrófica , Accidente Cerebrovascular , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Femenino , Estudios Retrospectivos , Incidencia , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/complicaciones , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Factores de RiesgoRESUMEN
Single antiplatelet therapy represents the cornerstone of thrombosis prevention in atherosclerotic cardiovascular disease. Dual antiplatelet therapy (DAPT), consisting of aspirin plus a P2Y 12 inhibitor, is the standard of care for patients with acute coronary syndrome or undergoing both coronary and peripheral percutaneous interventions. Recent data suggest the efficacy of DAPT also after minor stroke. In this setting, a large body of evidence has documented that genetic and acquired patients' characteristics may affect the magnitude of platelet inhibition induced by antiplatelet agents. The implementation of tools allowing the identification and prediction of platelet inhibition has recently been shown to improve outcomes, leading to an optimal balance between antithrombotic efficacy and bleeding risk. We are therefore clearly moving towards tailored antiplatelet therapy. The aim of this paper is to summarize the available evidence on the evaluation of platelet inhibition in patients with coronary, peripheral, or cerebrovascular atherosclerosis. We will here focus on antiplatelet therapy based on both aspirin and P2Y 12 inhibitors. In addition, we provide practical insights into the clinical settings in which it appears reasonable to implement antiplatelet therapy monitoring.
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Aterosclerosis , Intervención Coronaria Percutánea , Accidente Cerebrovascular , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Aspirina/efectos adversos , Anticoagulantes/efectos adversos , Accidente Cerebrovascular/prevención & control , Quimioterapia Combinada , Resultado del TratamientoRESUMEN
Background: The current understanding of the clinical course and long-term outcome of patients with hypertrophic cardiomyopathy (HCM) has been extrapolated from cohorts with relatively short follow-up, usually <10 years. Extended assessments more closely reflecting HCM lifetime burden are not available. Objectives: The purpose of this study was to report the lifetime clinical course of HCM. Methods: We analyzed the clinical course of HCM patients diagnosed at our center from 1970 to 1992 and followed annually to the present. Cumulative incidence functions were used to estimate the incidence of HCM-related mortality (including heart failure [HF]/stroke related, sudden cardiac death [SCD]) and non-HCM related. Results: A total of 202 patients (age 41 ± 17 years; 63% male) were followed 27 ± 6 [range: 3-50] years. Overall, 97 (48%) survived and 105 (52%) died during the particularly long follow-up; 69 deaths were related to HCM, including 53 HF related, 11 fatal embolic strokes, and 16 SCDs. Annual overall HCM-related mortality was 1.3%/y, increasing from 0.7% during the first decade to 1.8% in the second/third decade (P < 0.01), mainly driven by increase in HF-/stroke-related events (from 0.6% to 1.3%). The SCD mortality rate was similar in the 2 periods (0.1% vs 0.44%, P = 0.10). Of the 69 HCM deaths, 29 (42%) occurred before the widespread availability of effective contemporary treatment strategies and are considered potentially preventable. Conclusions: In this unique HCM cohort followed for up to 50 years, often before contemporary therapies became widely implemented for HCM, HF frequently progressed over time, while arrhythmic SCD events were less common and remained constant over time. Despite spanning different management eras over 5 decades, HCM-related mortality remained relatively low (1.3%/y).
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Aims: Ventricular cardiomyocytes from hypertrophic cardiomyopathy (HCM) patient hearts show prolonged action potential duration (APD), impaired intracellular Ca2+ homeostasis and abnormal electrical response to beta -adrenergic stimulation. We sought to determine whether this behaviour is associated with abnormal changes of repolarization during exercise and worsening of diastolic function, ultimately explaining the intolerance to exercise experienced by some patients without obstruction. Methods and results: Non-obstructive HCM patients (178) and control subjects (81) underwent standard exercise testing, including exercise echocardiography. Ventricular myocytes were isolated from myocardial samples of 23 HCM and eight non-failing non-hypertrophic surgical patients. The APD shortening in response to high frequencies was maintained in HCM myocytes, while ß-adrenergic stimulation unexpectedly prolonged APDs, ultimately leading to a lesser shortening of APDs in response to exercise. In HCM vs. control subjects, we observed a lesser shortening of QT interval at peak exercise (QTc: +27 ± 52â ms in HCM, -4 ± 50â ms in controls, P < 0.0001). In patients showing a marked QTc prolongation (>30â ms), the excessive shortening of the electrical diastolic period was linked with a limited increase of heart-rate and deterioration of diastolic function at peak effort. Conclusions: Abnormal balance of Ca2+- and K+-currents in HCM cardiomyocytes determines insufficient APD and Ca2+-transient shortening with exercise. In HCM patients, exercise-induced QTc prolongation was associated with impaired diastolic reserve, contributing to the reduced exercise tolerance. Our results support the idea that severe electrical cardiomyocyte abnormalities underlie exercise intolerance in a subgroup of HCM patients without obstruction.
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BACKGROUND: The implantable cardioverter defibrillator(ICD) has revolutionized the management of patients with hypertrophic cardiomyopathy (HCM) at risk of sudden cardiac death (SCD). However, the identification of ideal candidates remains challenging. We aimed to describe the long-term impact of the ICD for primary prevention in patients with HCM based on stringent (high SCD risk) vs lenient indications (need for pacing/personal choice). METHODS: Data from two Italian HCM Cardiomyopathy Units were retrospectively analyzed. Only patients >1 follow-up visits were divided into two groups according to ICD candidacy:stringent (high SCD risk) and lenient (need for pacing, patients' choice, physician advice despite lack of high SCD risk). Major cardiac events (composite of appropriate shock/intervention and SCD) was the primary endpoint. A safety endpoint was defined as a composite of inappropriate shocks and device-related complications. RESULTS: Of 2009 patients, 252(12.5%) received an ICD, including 27(1.3%) in secondary prevention and 225(11.2%) in primary prevention (age at implantation 49 ± 16 years; men 65.3%). Among those in primary prevention, 167(74.2%) had stringent, while 58(25.8%) had lenient indications. At 5 ± 4 years, only stringent ICD patients experienced major cardiac events (2.84%/year, 5-year cumulative incidence: 8.1%, 95%CI [3.5-14.1%]). ICD-related complications were similar across stringent and lenient subgroups. However, patients implanted >60 years had a significantly higher risk of adverse events. CONCLUSION: One third of ICD recipients with HCM in primary prevention received a lenient implantation and had no appropriate intervention. ICD implantation due to systematic upgrade in patients requiring pacing and increased risk perception may offer little advantage and increase complication rates.