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PURPOSE OF REVIEW: Heart failure is a highly prevalent condition caused by many different aetiologies and characterised by cardiac dysfunction and congestion. Once developed, congestion leads to signs (peripheral oedema) and symptoms (breathlessness on exertion), adverse cardiac remodelling, and an increased risk of hospitalisation and premature death. This review summarises strategies that could enable early identification and a more objective management of congestion in patients with heart failure. RECENT FINDINGS: For patients with suspected or diagnosed heart failure, combining an echocardiogram with assessment of great veins, lungs, and kidneys by ultrasound might facilitate recognition and quantification of congestion, the management of which is still difficult and highly subjective. Congestion is a one of the key drivers of morbidity and mortality in patients with heart failure and is often under-recognised. The use of ultrasound allows for a timely, simultaneous identification of cardiac dysfunction and multiorgan congestion; ongoing and future studies will clarify how to tailor diuretic treatments in those with or at risk of heart failure.
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Cardiomiopatias , Insuficiência Cardíaca , Humanos , Diuréticos/uso terapêutico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/diagnóstico , Hospitalização , PulmãoRESUMO
Percutaneous coronary intervention (PCI) is considered a relatively safe procedure associated with low rates of complications, but is inevitably associated with short and mid-to-long term increased bleeding risk. Besides the short term risk associated with the arterial access to perform PCI, enhanced bleeding risk persists for several months, given the need for antithrombotic therapy to prevent procedure-related thrombotic complications as well as ischemic recurrences. Bleeding is a powerful harbinger of adverse outcomes. This awareness has fuelled intense research on bleeding reduction strategies, including new PCI devices and techniques as well as new medications and antithrombotic regimens. We here review the mechanisms and prevalence of bleeding in PCI patients, discuss the available evidence from a practical point of view, and explore future perspectives on how to treat and prevent bleeding complications in these patients.
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BACKGROUND: The efficacy of bypass surgery in patients with ischemic cardiomyopathy is not easily predictable; preoperative clinical conditions may be similar, but the outcome may differ significantly. We hypothesized that the growth reserve of cardiac stem cells (CSCs) and circulating cytokines promoting CSC activation are critical determinants of ventricular remodeling in this patient population. METHODS AND RESULTS: To document the growth kinetics of CSCs, population-doubling time, telomere length, telomerase activity, and insulin-like growth factor-1 receptor expression were measured in CSCs isolated from 38 patients undergoing bypass surgery. Additionally, the blood levels of insulin-like growth factor-1, hepatocyte growth factor, and vascular endothelial growth factor were evaluated. The variables of CSC growth were expressed as a function of the changes in wall thickness, chamber diameter and volume, ventricular mass-to-chamber volume ratio, and ejection fraction, before and 12 months after surgery. A high correlation was found between indices of CSC function and cardiac anatomy. Negative ventricular remodeling was not observed if CSCs retained a significant growth reserve. The high concentration of insulin-like growth factor-1 systemically pointed to the insulin-like growth factor-1-insulin-like growth factor-1 receptor system as a major player in the adaptive response of the myocardium. hepatocyte growth factor, a mediator of CSC migration, was also high in these patients preoperatively, as was vascular endothelial growth factor, possibly reflecting the vascular growth needed before bypass surgery. Conversely, a decline in CSC growth was coupled with wall thinning, chamber dilation, and depressed ejection fraction. CONCLUSIONS: The telomere-telomerase axis, population-doubling time, and insulin-like growth factor-1 receptor expression in CSCs, together with a high circulating level of insulin-like growth factor-1, represent a novel biomarker able to predict the evolution of ischemic cardiomyopathy following revascularization.
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Ponte de Artéria Coronária , Isquemia Miocárdica/patologia , Isquemia Miocárdica/cirurgia , Miocárdio/patologia , Células-Tronco/patologia , Idoso , Biomarcadores/sangue , Proliferação de Células , Células Cultivadas , Citocinas/sangue , Feminino , Seguimentos , Fator de Crescimento de Hepatócito/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Valor Preditivo dos Testes , Receptor IGF Tipo 1/sangue , Células-Tronco/ultraestrutura , Telomerase/fisiologia , Telômero/ultraestrutura , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
BACKGROUND: The aim of this study was to assess the relationship among anthropometric indexes of adiposity (body mass index [BMI], waist circumference [WC]), endothelial progenitor cells (EPC) and carotid intima-media thickness (IMT) in patients with morbid obesity, and the effect of diabetes and weight loss. METHODS AND RESULTS: BMI, WC, IMT and circulating EPC (defined as CD34+/KDR+/CD45- cells) were assessed in 100 patients (37 with diabetes). Fifty patients underwent bariatric surgery, and in 48 of them a complete re-assessment after an average follow-up of 252±108 days was carried out. In 29 of them subcutaneous and visceral adipose tissue samples were obtained at the time of intervention and analyzed for the presence and number of EPC. EPC were directly correlated with weight, BMI, WC and insulin level, and inversely with mean IMT. All correlations were confined to non-diabetic patients. EPC were found in both subcutaneous and visceral adipose tissue specimens. Circulating EPC significantly decreased after weight loss (P=0.002). CONCLUSIONS: EPC are positively related to markers of adiposity in severe obesity, when not complicated by diabetes. Weight loss is associated with decrease in EPC level. EPC are inversely correlated with IMT, confirming their protective role also in severe obesity. Diabetes has a negative modulating action.
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Células Endoteliais , Obesidade Mórbida/metabolismo , Obesidade Mórbida/patologia , Células-Tronco , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Adulto , Cirurgia Bariátrica , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Células-Tronco/metabolismo , Células-Tronco/patologia , Túnica Íntima/metabolismo , Túnica Íntima/patologiaRESUMO
AIMS: A high, Doppler-derived, tricuspid regurgitation velocity (TRV) indicates pulmonary hypertension, which may contribute to right ventricular dysfunction and worsening tricuspid regurgitation leading to systemic venous congestion, reflected by an increase in inferior vena cava (IVC) diameter. We hypothesized that venous congestion rather than pulmonary hypertension would be more strongly associated with prognosis. METHODS AND RESULTS: 895 patients with chronic heart failure (CHF) (median (25th and 75th centile) age 75 (67-81) years, 69% men, LVEF 44 (34-55)% and NT-proBNP 1133 (423-2465) pg/ml) were enrolled. Compared to patients with normal IVC (< 21 mm) and TRV (≤ 2.8 m/s; n = 504, 56%), those with high TRV but normal IVC (n = 85, 9%) were older, more likely to be women and to have LVEF ≥ 50%, whilst those with dilated IVC but normal TRV (n = 142, 16%) had more signs of congestion and higher NT-proBNP. Patients (n = 164, 19%) with both dilated IVC and high TRV had the most signs of congestion and the highest NT-proBNP. During follow-up of 860 (435-1121) days, 239 patients died. Compared to those with both normal IVC and TRV (reference), patients with high TRV but normal IVC did not have a significantly increased mortality (HR: 1.41; CI: 0.87-2.29; P = 0.16). Risk was higher for patients with a dilated IVC but normal TRV (HR: 2.51; CI: 1.80-3.51; P < 0.001) or both a dilated IVC and elevated TRV (HR: 3.27; CI: 2.40-4.46; P < 0.001). CONCLUSION: Amongst ambulatory patients with CHF, a dilated IVC is more closely associated with an adverse prognosis than an elevated TRV.
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Insuficiência Cardíaca , Hiperemia , Hipertensão Pulmonar , Insuficiência da Valva Tricúspide , Masculino , Humanos , Feminino , Idoso , Insuficiência da Valva Tricúspide/diagnóstico , Veia Cava Inferior/diagnóstico por imagem , PrognósticoRESUMO
BACKGROUND AND AIMS: Congestion is a key driver of morbidity and mortality in heart failure. Implanted haemodynamic monitoring devices might allow early identification and management of congestion. Here, we provide a state-of-the-art review of implanted haemodynamic monitoring devices for patients with heart failure, including a meta-analysis of randomised trials. METHODS AND RESULTS: We did a systematic search for pre-print and published trials in Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) on the 22nd of September 2021. We included randomised trials that compared management with or without information from implanted haemodynamic monitoring devices for patients with heart failure. Outcomes selected were hospitalisation for heart failure and all-cause mortality. Changes in treatment associated with haemodynamic monitoring resulted in only a small reduction in mean pulmonary artery pressure (typically < 1 mmHg as a daily average), which generally remained much greater than 20 mmHg. Haemodynamic monitoring reduced hospitalisations for heart failure (HR 0.75; 95% CI 0.58-0.96; p = 0.03) but not mortality (RR 0.92; 95% CI 0.68-1.26; p = 0.48). CONCLUSIONS: Haemodynamic monitoring for patients with heart failure may reduce the risk of hospitalization for heart failure but this has not yet translated into a reduction in mortality, perhaps because the duration of trials was too short or the reduction in pulmonary artery pressure was not sufficiently large. The efficacy and safety of aiming for larger reductions in pulmonary artery pressure should be explored. After selecting key words, a systematic review for implanted haemodynamic telemonitoring devices was performed in different dataset and 4 randomised clinical trials were identified and included in this meta-analysis. Three different devices (Chronicle, Chronicle/ICD and CardioMEMS) were tested. All-cause mortality and total heart failure hospitalisations were selected as outcomes. No reduction in all-cause mortality rate was reported but a potential benefit on total heart failure hospitalisation was identified.
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Insuficiência Cardíaca , Hospitalização , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Hemodinâmica , Monitorização Fisiológica , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Heart failure (HF) represents a major health and economic issue, with increasing morbidity and mortality in spite of novel therapeutic weapons. The disappointing results of HF management may be due to the current therapeutic approach based on the paradigm "one fits all", that cannot apply to a complex and multifaceted syndrome as HF. At this regard, the European Union is developing policies to move from reductionism to precision medicine, in order to identify specific disease biomarkers and develop targeted therapeutic strategies. The institution of biobanks may represent the game changer in HF scenario, providing a collection of human biological materials with the related medical and epidemiological data fueling the development of personalized therapeutic approach and fostering current and/or future research projects.
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Bancos de Espécimes Biológicos , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapiaRESUMO
Water and salt retention, in other words congestion, are fundamental to the pathophysiology of heart failure and are important therapeutic targets. Echocardiography is the key tool with which to assess cardiac structure and function in the initial diagnostic workup of patients with suspected heart failure and is essential for guiding treatment and stratifying risk. Ultrasound can also be used to identify and quantify congestion in the great veins, kidneys and lungs. More advanced imaging methods might further clarify the aetiology of heart failure and its consequences for the heart and periphery, thereby improving the efficiency and quality of care tailored with greater precision to individual patient need.
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AIMS: Coronary artery disease (CAD) is a common cause of heart failure (HF). Whether coronary revascularization improves outcomes in patients with HF receiving guideline-recommended pharmacological therapy (GRPT) remains uncertain; therefore, we conducted a systematic review and meta-analysis of relevant randomized controlled trials (RCTs). METHODS AND RESULTS: We searched in public databases for RCTs published between 1 January 2001 and 22 November 2022, investigating the effects of coronary revascularization on morbidity and mortality in patients with chronic HF due to CAD. All-cause mortality was the primary outcome. We included five RCTs that enrolled, altogether, 2842 patients (most aged <65 years; 85% men; 67% with left ventricular ejection fraction ≤35%). Overall, compared to medical therapy alone, coronary revascularization was associated with a lower risk of all-cause mortality (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.79-0.99; p = 0.0278) and cardiovascular mortality (HR 0.80, 95% CI 0.70-0.93; p = 0.0024) but not the composite of hospitalization for HF or all-cause mortality (HR 0.87, 95% CI 0.74-1.01; p = 0.0728). There were insufficient data to show whether the effects of coronary artery bypass graft surgery or percutaneous coronary intervention were similar or differed. CONCLUSIONS: For patients with chronic HF and CAD enrolled in RCTs, the effect of coronary revascularization on all-cause mortality was statistically significant but neither substantial (HR 0.88) nor robust (upper 95% CI close to 1.0). RCTs were not blinded, which may bias reporting of the cause-specific reasons for hospitalization and mortality. Further trials are required to determine which patients with HF and CAD obtain a substantial benefit from coronary revascularization by either coronary artery bypass graft surgery or percutaneous coronary intervention.
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Doença da Artéria Coronariana , Insuficiência Cardíaca , Intervenção Coronária Percutânea , Masculino , Humanos , Feminino , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Insuficiência Cardíaca/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ponte de Artéria Coronária/efeitos adversos , Volume Sistólico , Intervenção Coronária Percutânea/efeitos adversos , Resultado do TratamentoRESUMO
Background Guidelines recommend using multiple drugs in patients with heart failure (HF) with reduced ejection fraction, but there is a paucity of real-world data on the simultaneous initiation of the 4 pharmacological pillars at discharge after a decompensation event. Methods and Results A retrospective data mart, including patients diagnosed with HF, was implemented. Consecutively admitted patients with HF with reduced ejection fraction were selected through an automated approach and categorized according to the number/type of treatments prescribed at discharge. The prevalence of contraindications and cautions for HF with reduced ejection fraction treatments was systematically assessed. Logistic regression models were fitted to assess predictors of the number of treatments (≥2 versus <2 drugs) prescribed and the risk of rehospitalization. A population of 305 patients with a first episode of HF hospitalization and a diagnosis of HF with reduced ejection fraction (ejection fraction, <40%) was selected. At discharge, 49.2% received 2 current recommended drugs, ß-blockers were prescribed in 93.4%, while a renin-angiotensin system inhibitor or an angiotensin receptor-neprilysin inhibitor was prescribed in 68.2%. A mineralocorticoid receptor antagonist was prescribed in 32.5%, although none of the patients showed contraindications to mineralocorticoid receptor antagonist prescription. A sodium-glucose cotransporter 2 inhibitor could be prescribed in 71.1% of patients. On the basis of current recommendations, 46.2% could receive the 4 foundational drugs at discharge. Renal dysfunction was associated with <2 foundational drugs prescribed. After adjusting for age and renal function, use of ≥2 drugs was associated with lower risk of rehospitalization during the 30 days after discharge. Conclusions A quadruple therapy could be directly implementable at discharge, potentially providing prognostic advantages. Renal dysfunction was the main prevalent condition limiting this approach.
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Insuficiência Cardíaca , Nefropatias , Disfunção Ventricular Esquerda , Humanos , Alta do Paciente , Volume Sistólico/fisiologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Estudos Retrospectivos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêuticoRESUMO
BACKGROUND: The impact of myocardial revascularization on outcomes and prognosis in patients with chronic coronary syndrome (CCS) without left main (LM) disease or reduced left ventricle ejection fraction (LVEF) may be influenced by the revascularization strategy adopted. METHODS: We performed a network meta-analysis including 18 randomized controlled trials comparing different revascularization strategies, including angiography-guided percutaneous coronary intervention (PCI), physiology-guided PCI and coronary artery bypass graft (CABG), in patients with CCS without LM disease or reduced LVEF. RESULTS: Compared with medical therapy, all revascularization strategies were associated with a reduction of the primary endpoint, as defined in each trial, the extent of which was modest with angiography-guided PCI (IRR 0.86, 95% CI 0.75-0.99) and greater with physiology-guided PCI (IRR 0.60, 95% CI 0.47-0.77) and CABG (IRR 0.58, 95% CI 0.48-0.70). Moreover, angiography-guided PCI was associated with an increase of the primary endpoint compared to physiology-guided PCI (IRR 1.43, 95% CI 1.14-1.79) and CABG (IRR 1.49, 95% CI 1.27-1.74). CABG was the only strategy associated with reduced myocardial infarction (IRR 0.68, 95% CI 0.52-0.90), cardiovascular death (IRR 0.76, 95% CI 0.64-0.89), and all-cause death (IRR 0.87, 95% CI 0.77-0.99), but increased stroke (IRR 1.69, 95% CI 1.04-2.76). CONCLUSIONS: In CCS patients without LM disease or reduced LVEF, physiology-guided PCI and CABG are associated with better outcomes than angiography-guided PCI. Compared with medical therapy, CABG is the only revascularization strategy associated with a reduction of myocardial infarction and death rates, at the cost of higher risk of stroke. STUDY REGISTRATION: This study is registered in PROSPERO (CRD42022313612).
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Doença da Artéria Coronariana , Infarto do Miocárdio , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Metanálise em Rede , Resultado do Tratamento , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Infarto do Miocárdio/etiologia , Acidente Vascular Cerebral/etiologiaRESUMO
Background: Despite continuous advancement in the field, heart failure (HF) remains the leading cause of hospitalization among the elderly and the overall first cause of hospital readmission in developed countries. Implantable hemodynamic monitoring is being tested to anticipate the clinical exacerbation onset, potentially preventing an emergent acute decompensation. To date, only pulmonary artery pressure (PAP) sensor received the approval to be implanted in symptomatic heart failure patients with reduced ejection fraction. However, PAP's indirect estimation of left ventricular filling pressure can be inaccurate in some contexts. Methods: The VECTOR-HF study (NCT03775161) is examining the safety, usability and performance of the V-LAP system, a latest-generation device capable of continuously monitoring left atrial pressure (LAP). In our center, five advanced HF patients have been enrolled. After confirmation of the transmitted data reliability, LAP trends and waveforms have guided therapy optimization. The aim of this work is to share clinical insights from our center preliminary experience with V-LAP application. Results: Over a median follow-up time of 18 months, LAP-based therapy optimization managed to reduce intracardiac pressure over time and no hospital readmission occurred. This result was paralleled by an improvement in both functional capacity (6MWT distance 352.5 ± 86.2 meters at baseline to 441.2 ± 125.2 meters at last follow-up) and quality of life indicators (KCCQ overall score 63.82 ± 16.36 vs. 81.92 ± 9.63; clinical score 68.47 ± 19.48 vs. 83.70 ± 15.58). Conclusion: Preliminary evidence from V-LAP application at our institution support a promising efficacy. However, further study is needed to confirm the technical reliability of the device and to exploit the clinical benefit of left-sided hemodynamic remote monitoring.
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We report the case of a 65-year-old man referred to our department because of a complex coronary aneurysmal disease presenting as subacute ST-segment elevation myocardial infarction due to intraluminal thromboembolism. The patient's past medical history (recurrent episodes of lymphadenopathies, parotid swelling, prostatitis, and dacryoadenitis) raised the suspicion of a unifying systemic disorder with coronary involvement. An extensive infectious and autoimmune screening was performed, leading to the final diagnosis of IgG4-related disease. Our case highlights the importance to include this rare and recently described disease in the diagnostic workup of acquired coronary aneurysms.
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Síndrome Coronariana Aguda/etiologia , Aneurisma Coronário/diagnóstico , Vasos Coronários/diagnóstico por imagem , Doença Relacionada a Imunoglobulina G4/complicações , Síndrome Coronariana Aguda/diagnóstico , Idoso , Aneurisma Coronário/complicações , Angiografia Coronária , Diagnóstico Diferencial , Eletrocardiografia , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Masculino , Tomografia Computadorizada Multidetectores , Tomografia por Emissão de PósitronsRESUMO
Anderson-Fabry's disease (AFD) is a rare, X-linked lysosomal storage disorder caused by the complete deficiency or attenuated activity of the enzyme α-galactosidase A, leading to progressive systemic intracellular accumulation of glycosphingolipids and subsequent cellular dysfunction, inflammation and fibrosis. Fever is a frequently misinterpreted symptom in the early stages of the disease, leading to diagnostic delay. We present the case of a 35-year-old man admitted to our Periodic Fever Research Centre for long-lasting recurrent episodes of fever of unknown origin. After extensive assessment, we diagnosed AFD associated with a novel GLA mutation. We started enzyme replacement therapy with clinical benefit and complete remission of fever. LEARNING POINTS: Anderson-Fabry's Disease (AFD) is an inherited lysosomal storage disorder, in which progressive multi-organ glycosphingolipid accumulation leads to multi-systemic dysfunction. Diagnosis requires a high level of suspicion as the clinical presentation can be very heterogeneous.As fever is an early uncommon symptom causing diagnostic delay, it is important to consider AFD in the differential diagnosis of recurrent fevers, particularly when febrile episodes are not associated with an increase in acute phase reactants and when other signs or symptoms suggestive of AFD are present.Prognosis depends on an early diagnosis because promptly initiation of enzyme replacement therapy (ERT) can prevent the progression of organ damage. In our case fever disappeared after ERT initiation, a finding not previously reported to our knowledge. Therefore, fever remission could be an early marker of response to ERT.
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Background- Adaptive immune-response is associated with a worse outcome in acute coronary syndromes. Statins have anti-inflammatory activity beyond lowering lipid levels. We investigated the effects of ex-vivo and in-vivo atorvastatin treatment in acute coronary syndromes on CD4+T-cells, and the underlying molecular mechanisms.Approach and results- Blood samples were collected from 50 statin-naïve acute coronary syndrome patients. We assessed CD4+T-cell activation by flow-cytometry, the expression of 84 T-helper transcription-factors and 84 T-cell related genes by RT-qPCR, and protein expression by Western-blot, before and after 24-hours incubation with increasing doses of atorvastatin: 3-10-26 µg/ml (corresponding to blood levels achieved with doses of 10-40-80 mg, respectively). After incubation, we found a significant decrease in interferon-γ-producing CD4+CD28nullT-cells (P = 0.009) and a significant increase in interleukin-10-producing CD4+CD25highT-cells (P < 0.001). Atorvastatin increased the expression of 2 genes and decreased the expression of 12 genes (in particular, EGR1, FOS,CCR2 and toll like receptor-4; >3-fold changes).The in-vivo effects of atorvastatin were analyzed in 10 statin-free acute coronary syndrome patients at baseline, and after 24h and 48h of atorvastatin therapy (80 mg/daily): EGR1-gene expression decreased at 24h (P = 0.01) and 48h (P = 0.005); EGR1-protein levels decreased at 48h (P = 0.03).Conclusions-In acute coronary syndromes, the effects of atorvastatin on immune system might be partially related to the inhibition of the master regulator gene EGR1. Our finding might offer a causal explanation on why statins improve the early outcome in acute coronary syndromes.
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Síndrome Coronariana Aguda/imunologia , Atorvastatina/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Proteína 1 de Resposta de Crescimento Precoce/biossíntese , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Síndrome Coronariana Aguda/tratamento farmacológico , Western Blotting , Células Cultivadas , Feminino , Citometria de Fluxo , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: Epicardial adipose tissue (EAT) has a close functional and anatomic relationship with epicardial coronary arteries. Accumulating evidence suggests that host microbiome alterations may play a role in several inflammatory/immune disorders, triggering a robust proinflammatory response also involving interleukin-1ß (IL-1ß) and the NALP3 inflammasome. In the current study, we explore the hypothesis that in patients with non-ST elevation acute coronary syndrome (ACS), EAT contains potentially pro-atherosclerotic bacteria that might elicit inflammasome activation. METHODS: EAT samples were obtained during coronary artery bypass grafting from ACS (n=18) and effort stable angina (SA; n=16) patients, and as controls, from patients with angiographically normal coronary arteries undergoing surgery for mitral insufficiency (MVD; n=13). In all patients, NALP3 and proIL-1ß mRNA expressions were evaluated with qRT-PCR. In 3 patients from each group, EAT microbiota composition was determined using next-generation sequencing technologies. RESULTS: In EAT, mRNA expression of both NALP3 and pro-IL1ß was significantly higher in ACS than in SA and MVD (P=0.028 and P=0.005, respectively). A broad range of bacterial species (n=76) was identified in both ACS and SA, with different predominant species. In contrast, microbial DNA was barely observed in MVD. CONCLUSIONS: Our study demonstrated the presence of bacterial DNA directly into EAT, surrounding diseased coronary arteries, of patients with ACS. Furthermore, ACS is associated with NALP3/inflammasome pathway activation in EAT. Our data suggest that the EAT environment is susceptible to microbial colonization that might stimulate a proinflammatory response. These findings add new elements to the pathogenesis of ACS and suggest novel therapeutic targets.