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Background: This study aimed to evaluate the effect of treatment with tafamidis on clinical, laboratory, functional, and structural cardiovascular imaging parameters at the 12-month follow-up timepoint in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) and to assess the response to treatment in terms of disease progression. Methods: Patients with ATTRwt-CM undergoing treatment with tafamidis for >12 months were included. The patients underwent a comprehensive evaluation (including echocardiography, cardiac magnetic resonance imaging, six-minute walking test, assessment of quality of life, and laboratory tests) at baseline and the 12-month follow-up timepoint. Disease progression was assessed using a set of tools proposed by an international panel of experts, evaluating three main domains (clinical, biochemical, and structural). Results: The study cohort consisted of 25 patients (mean age of 75.9 ± 6.1 years, with 92% males). At the 12-month follow-up timepoint, an improvement in quality of life calculated with the KCCQ overall score (64 ± 20 vs. 75 ± 20, p = 0.002) and a reduction in pulmonary artery pressure (34 ± 10 mmHg vs. 30 ± 5 mmHg, p-value = 0.008) and in native T1 time were observed (1162 ± 66 ms vs. 1116 ± 52 ms, p-value = 0.001). Clinical, biochemical, and structural disease progression was observed in 6 (24%), 13 (52%), and 7 (28%) patients, respectively. Overall disease progression was observed in two patients (8%). Conclusions: This study described the impact of tafamidis treatment on clinical, laboratory, and functional parameters. Disease progression, assessed using a multiparametric tool recommended by a recent position paper of experts, was observed in a minority of patients.
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Optimizing the anticoagulation therapy is of pivotal importance in patients with a malignant tumor, as venous thromboembolism (VTE) has become the second-leading cause of death in this population. Cancer can highly increase the risk of thrombosis and bleeding. Consequently, the management of cancer-associated VTE is complex. In recent years, translational research has intensified, and several studies have highlighted the role of inflammatory cytokines in cancer growth and progression. Simultaneously, the pleiotropic effects of anticoagulants currently recommended for VTE have emerged. In this review, we describe the anti-inflammatory and anticancer effects of both direct oral anticoagulants (DOACs) and low-molecular-weight heparins (LWMHs).
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BACKGROUND: This study aims to evaluate the prevalence and the clinical significance of the right ventricular pulmonary arterial (RV-PA) uncoupling in patients with cardiac amyloidosis (CA). METHODS: The study population consisted in 92 consecutive patients with CA (age 71.1 ± 12.2 years, 71% males; 47% with immunoglobulin light chain (AL), 53% with transthyretin [ATTR]). A pre-specified tricuspid anulus plane systolic excursion on pulmonary arterial systolic pressure (TAPSE/PASP) value <0.31 mm/mmHg was used to define RV-PA uncoupling and to dichotomize the study population. RESULTS: Thirty-two patients (35%) showed RV-PA uncoupling at baseline evaluation (15/44 [34%] AL and 17/48 [35%] ATTR). Patients with RV-PA uncoupling, in both AL and ATTR, showed worse NYHA functional class, lower systemic blood pressure, and more pronounced left ventricular and RV systolic dysfunction than those with RV-PA coupling. During a median follow-up of 8 months (IQR 4-13), 26 patients (28%) experienced cardiovascular death. Patients with RV-PA uncoupling showed lower survival at 12 months follow-up than those with RV-PA coupling (42.7% [95%CI 21.7-63.7%] vs. 87.3% [95%CI 78.3-96.3%], p-value<0.001). Multivariate analysis identified high-sensitivity troponin I values (HR 1.01 [95%CI 1.00-1.02] per 1 pg/mL increase; p-value 0.013) and TAPSE/PASP (HR 1.07 [95%CI 1.03-1.11] per 0.01 mm/mmHg decrease; p-value 0.002) as independent predictors of cardiovascular death. CONCLUSIONS: RV-PA uncoupling is common among patient with CA, and it is a marker of advanced disease and worse outcome. This study suggest that TAPSE/PASP ratio has the potential to improve risk stratification and guide management strategies in patients with CA of different etiology and advanced disease.
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Amiloidosis , Hipertensión Pulmonar , Disfunción Ventricular Derecha , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Ecocardiografía Doppler , Prevalencia , Relevancia Clínica , Arteria Pulmonar/diagnóstico por imagen , Amiloidosis/diagnóstico por imagen , Amiloidosis/epidemiología , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/epidemiología , Función Ventricular Derecha/fisiologíaRESUMEN
The thrombosis-related diseases are one of the leading causes of illness and death in the general population, and despite significant improvements in long-term survival due to remarkable advances in pharmacologic therapy, they continue to pose a tremendous burden on healthcare systems. The oxidative stress plays a role of pivotal importance in thrombosis pathophysiology. The anticoagulant and antiplatelet drugs commonly used in the management of thrombosis-related diseases show several pleiotropic effects, beyond the antithrombotic effects. The present review aims to describe the current evidence about the antioxidant effects of the oral antithrombotic therapies in patients with atherosclerotic disease and atrial fibrillation.
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Atherosclerosis is a multifactorial inflammatory pathology that involves metabolic processes. Improvements in therapy have drastically reduced the prognosis of cardiovascular disease. Nevertheless, a significant residual risk is still relevant, and is related to unmet therapeutic targets. Endothelial dysfunction and lipid infiltration are the primary causes of atherosclerotic plaque progression. In this contest, mitochondrial dysfunction can affect arterial wall cells, in particular macrophages, smooth muscle cells, lymphocytes, and endothelial cells, causing an increase in reactive oxygen species (ROS), leading to oxidative stress, chronic inflammation, and intracellular lipid deposition. The detection and characterization of mitochondrial DNA (mtDNA) is crucial for assessing mitochondrial defects and should be considered the goal for new future therapeutic interventions. In this review, we will focus on a new idea, based on the analysis of data from many research groups, namely the link between mitochondrial impairment and endothelial dysfunction and, in particular, its effect on atherosclerosis and aging. Therefore, we discuss known and novel mitochondria-targeting therapies in the contest of atherosclerosis.
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Aterosclerosis , Placa Aterosclerótica , Humanos , Células Endoteliales/metabolismo , Aterosclerosis/metabolismo , Placa Aterosclerótica/metabolismo , Mitocondrias/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , LípidosRESUMEN
Percutaneous patent foramen ovale (PFO) closure by traditional, double disc occluder devices was shown to be safe for patients with PFO, and more effective than prolonged medical therapy in preventing recurrent thromboembolic events. The novel suture-mediated "deviceless" PFO closure system overcomes most of the risks and limitations associated with the traditional PFO occluders, appearing to be feasible in most interatrial septum anatomies, even if data about its long-term effectiveness and safety are still lacking. The aim of the present review was to provide to the reader the state of the art about the traditional and newer techniques of PFO closure, focusing both on the procedural aspects and on the pivotal role of transesophageal echocardiography (TEE) in patient's selection, peri-procedural guidance, and post-interventional follow-up.
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Advancements in clinical management, pharmacological therapy and interventional procedures have strongly improved the survival rate for cardiovascular diseases (CVDs). Nevertheless, the patients affected by CVDs are more often elderly and present several comorbidities such as atrial fibrillation, valvular heart disease, heart failure, and chronic coronary syndrome. Standard treatments are frequently not available for "frail patients", in particular due to high surgical risk or drug interaction. In the past decades, novel less-invasive procedures such as transcatheter aortic valve implantation (TAVI), MitraClip or left atrial appendage occlusion have been proposed to treat CVD patients who are not candidates for standard procedures. These procedures have been confirmed to be effective and safe compared to conventional surgery, and symptomatic thromboembolic stroke represents a rare complication. However, while the peri-procedural risk of symptomatic stroke is low, several studies highlight the presence of a high number of silent ischemic brain lesions occurring mainly in areas with a low clinical impact. The silent brain damage could cause neuropsychological deficits or worse, a preexisting dementia, suggesting the need to systematically evaluate the impact of these procedures on neurological function.
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Fibrilación Atrial , Enfermedades de las Válvulas Cardíacas , Intervención Coronaria Percutánea , Accidente Cerebrovascular , Anciano , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Fibrilación Atrial/terapia , Infarto Cerebral , Humanos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiologíaRESUMEN
OBJECTIVES: We aimed to evaluate the use of bare metal stent (BMS) implantation in current percutaneous coronary intervention (PCI) era, focusing on indications for use and clinical outcomes. BACKGROUND: Limited data on BMS usage in current clinical practice are available. METHODS: All patients who underwent PCI with at least one BMS implantation in 18 Italian centers from January 1, 2013 to December 31, 2017, were included in our registry. Rates of BMS use and reasons for BMS implantations were reported for the overall study period and for each year. Primary outcomes were mortality, bleeding (Bleeding Academic Research Consortium-BARC and Thrombolysis in Myocardial Infarction-TIMI non-CABG definitions), and major adverse cardiac events (MACE) defined as the composite of all-cause and cardiac death, any myocardial infarction, target vessel revascularization, or any stent thrombosis. RESULTS: Among 58,879 patients undergoing PCI in the study period, 2,117 (3.6%) patients (mean age 73 years, 69.7% males, 73.3% acute coronary syndrome) were treated with BMS implantation (2,353 treated lesions). The rate of BMS implantation progressively decreased from 10.1% (2013) to 0.3% (2017). Main reasons for BMS implantation were: ST-elevation myocardial infarction (STEMI) (23.1%), advanced age (24.4%), and physician's perception of high-bleeding risk (34.0%). At a mean follow-up of 2.2 ± 1.5 years, all-cause and cardiac mortality were 25.6 and 12.7%, respectively; MACE rate was 35.3%, any bleeding rate was 13.0% (BARC 3-5 bleeding 6.3%, TIMI non-CABG major bleeding 6.1%). CONCLUSION: In a large, contemporary, real-world, multicenter registry, BMS use progressively reduced over the last 5 years. Main reasons for BMS implantation were STEMI, advanced age, and physician's perception of high-bleeding risk. High rates of mortality and MACE were observed in this real-world high-risk population.
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Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Femenino , Humanos , Italia , Masculino , Intervención Coronaria Percutánea/efectos adversos , Sistema de Registros , Stents , Resultado del TratamientoRESUMEN
During transcatheter aortic valve implantation (TAVI) the native valve is not removed but crushed. Thus, a slight prosthesis insufficiency is not uncommon and has been reported up to 25% of patients for both available types of percutaneous valves. However, the definition of "clinically significant" valve regurgitation is not fully established yet. In most cases, aortic insufficiency is mild and clinical acceptable; however, severe insufficiency can occur. Paravalvular insufficiency is usually prevalent, and it may be the consequence of prosthesis-patient mismatch due to an undersizing of the implanted device or an incomplete expansion of the prosthesis stent frame, or also to incorrect site of prosthesis implantation. Thus, accurate assessment of the aortic valve annulus before TAVI is mandatory in order to select the optimal valve size. The presence of large calcium burden or bicuspid valve as well as the correct implantation of the device are other key determinants of final valve insufficiency. When severe regurgitation is present, an integration of hemodynamic, angiographic, transthoracic and transesophageal echocardiography data is necessary to tailor the best clinical decision on a per-patient basis.
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Insuficiencia de la Válvula Aórtica , Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/etiología , Insuficiencia de la Válvula Aórtica/prevención & control , Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Diseño de Prótesis , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del TratamientoRESUMEN
AIM: To investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS). METHODS: Ninety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio RESULTS: The majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62 ± 13 vs. 68 ± 12 years, p = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio (270 ± 104 vs. 117 ± 57 mmHg, p < 0.001). In the non-survivors, PASP was increased (42 ± 12 vs. 30 ± 7 mmHg, p < 0.001), while TAPSE was decreased (19 ± 4 vs. 25 ± 4 mm, p < 0.001). Accordingly, the TAPSE/PASP ratio was lower than in the survivors (0.51 ± 0.22 vs. 0.89 ± 0.29 mm/mmHg, p < 0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR: 0.026; 95%CI 0.01-0.579; p: 0.019) and PaO2/FIO2 (HR: 0.988; 95%CI 0.988-0.998; p: 0.018) ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively. CONCLUSIONS: COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO2/FIO2 in ARDS on COVID-19.
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COVID-19/complicaciones , COVID-19/mortalidad , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/virología , Síndrome de Dificultad Respiratoria/mortalidad , Síndrome de Dificultad Respiratoria/virología , Disfunción Ventricular Derecha/etiología , Disfunción Ventricular Derecha/mortalidad , Anciano , COVID-19/epidemiología , Ecocardiografía , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios Prospectivos , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/fisiopatología , SARS-CoV-2 , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/fisiopatologíaRESUMEN
BACKGROUND: During fractional flow reserve (FFR) measurement, the simple presence of the guiding catheter (GC) within the coronary ostium might create artificial ostial stenosis, affecting the hyperemic flow. We aimed to investigate whether selective GC engagement of the coronary ostium might impede hyperemic flow, and therefore impact FFR measurements and related clinical decision-making. METHODS: In the DISENGAGE (Determination of Fractional Flow Reserve in Intermediate Coronary Stenosis With Guiding Catheter Disengagement) registry, FFR was prospectively measured twice (with GC engaged [FFReng] and disengaged [FFRdis]) in 202 intermediate stenoses of 173 patients. We assessed (1) whether ΔFFReng-FFRdis was significantly different from the intrinsic variability of repeated FFR measurements (test-retest repeatability); (2) whether the extent of ΔFFReng-FFRdis could be clinically significant and therefore able to impact clinical decision-making; and (3) whether ΔFFReng-FFRdis related to the stenosis location, that is, proximal and middle versus distal coronary segments. RESULTS: Overall, FFR significantly changed after GC disengagement: FFReng 0.84±0.08 versus FFRdis 0.80±0.09, P<0.001. Particularly, in 38 stenoses (19%) with FFR values in the 0.81 to 0.85 range, GC disengagement was associated with a shift from above to below the 0.80 clinical cutoff, resulting into a change of the treatment strategy from medical therapy to percutaneous coronary intervention. The impact of GC disengagement was significantly more pronounced with stenoses located in proximal and middle as compared with distal coronary segments (ΔFFReng-FFRdis, proximal and middle 0.04±0.03 versus distal segments 0.03±0.03; P=0.042). CONCLUSIONS: GC disengagement results in a shift of FFR values from above to below the clinical cutoff FFR value of 0.80 in 1 out of 5 measurements. This occurs mostly when the stenosis is located in proximal and middle coronary segments and the FFR value is close to the cutoff value.
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Angina Inestable/diagnóstico , Cateterismo Cardíaco , Enfermedad de la Arteria Coronaria/diagnóstico , Estenosis Coronaria/diagnóstico , Vasos Coronarios/fisiopatología , Reserva del Flujo Fraccional Miocárdico , Infarto del Miocardio sin Elevación del ST/diagnóstico , Anciano , Angina Inestable/fisiopatología , Angina Inestable/terapia , Artefactos , Bélgica , Cateterismo Cardíaco/efectos adversos , Cateterismo Cardíaco/instrumentación , Catéteres Cardíacos , Toma de Decisiones Clínicas , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/terapia , Estenosis Coronaria/fisiopatología , Estenosis Coronaria/terapia , Femenino , Humanos , Hiperemia/fisiopatología , Masculino , Persona de Mediana Edad , Infarto del Miocardio sin Elevación del ST/fisiopatología , Infarto del Miocardio sin Elevación del ST/terapia , Intervención Coronaria Percutánea , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Sistema de Registros , Reproducibilidad de los ResultadosRESUMEN
AIMS: Significant platelet activation after long stented coronary segments has been associated with periprocedural microvascular impairment and myonecrosis. In long lesions treated either with an everolimus-eluting bioresorbable vascular scaffold (BVS) or an everolimus-eluting stent (EES), we aimed to investigate (a) procedure-related microvascular impairment, and (b) the relationship of platelet activation with microvascular function and related myonecrosis. METHODS AND RESULTS: Patients (n=66) undergoing elective percutaneous coronary intervention (PCI) in long lesions were randomised 1:1 to either BVS or EES. The primary endpoint was the difference between groups in changes of pressure-derived corrected index of microvascular resistance (cIMR) after PCI. Periprocedural myonecrosis was assessed by high-sensitivity cardiac troponin T (hs-cTnT), platelet reactivity by high-sensitivity adenosine diphosphate (hs-ADP)-induced platelet reactivity with the Multiplate Analyzer. Post-dilatation was more frequent in the BVS group, with consequent longer procedure time. A significant difference was observed between the two groups in the primary endpoint of ΔcIMR (p=0.04). hs-ADP was not different between the groups at different time points. hs-cTnT significantly increased after PCI, without difference between the groups. CONCLUSIONS: In long lesions, BVS implantation is associated with significant acute reduction in IMR as compared with EES, with no significant interaction with platelet reactivity or periprocedural myonecrosis.
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Implantes Absorbibles , Enfermedad de la Arteria Coronaria/cirugía , Stents Liberadores de Fármacos/efectos adversos , Everolimus/administración & dosificación , Intervención Coronaria Percutánea/métodos , Complicaciones Posoperatorias/diagnóstico por imagen , Andamios del Tejido , Tomografía de Coherencia Óptica/métodos , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Everolimus/uso terapéutico , Humanos , Intervención Coronaria Percutánea/efectos adversos , Complicaciones Posoperatorias/prevención & control , Diseño de Prótesis , Resultado del TratamientoRESUMEN
BACKGROUND: The prognostic impact of coronary microvascular dysfunction after percutaneous coronary intervention (PCI) remains unclear in patients with stable coronary artery disease. This study sought to investigate the prognostic value of microvascular function measured immediately after PCI in patients with stable coronary artery disease. METHODS: We enrolled 572 patients with stable coronary artery disease who underwent PCI and elective measurement of the index of microcirculatory resistance (IMR) immediately after PCI from 8 centers in 4 countries. Impaired microvascular function was defined as IMR≥25 (high IMR). Major adverse cardiac events, including death, myocardial infarction (MI) and target vessel revascularization, were evaluated. RESULTS: During a median follow-up duration of 4.0 years, the cumulative major adverse cardiac events rate was significantly higher in the high IMR group (n=66/148) compared with the low IMR group (n=128/424; hazard ratio [HR], 1.56; 95% CI, 1.16-2.105; P=0.001), primarily due to a higher rate of periprocedural MI (HR, 1.59; 95% CI, 1.11-2.28; P=0.004) but also due to higher rates of mortality (HR, 1.59; 95% CI, 0.76-3.35; P=0.22), spontaneous MI (HR, 2.10; 95% CI, 0.67-6.63; P=0.20) and target vessel revascularization (HR, 1.40; 95% CI, 0.77-2.54; P=0.27). Cumulative risk for death, spontaneous MI, and target vessel revascularization was higher in the high IMR group (HR, 1.55; 95% CI, 0.99-2.43; P=0.056), as was death and spontaneous MI alone (HR, 1.79; 95% CI, 0.96-3.36; P=0.065). On multivariable analysis, high IMR post-PCI was an independent predictor of major adverse cardiac events. CONCLUSIONS: IMR measured immediately after PCI predicts adverse events in patients with stable coronary artery disease.
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Enfermedad de la Arteria Coronaria/terapia , Circulación Coronaria , Microcirculación , Intervención Coronaria Percutánea , Anciano , Australia , Bélgica , Cateterismo Cardíaco , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/fisiopatología , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Valor Predictivo de las Pruebas , Sistema de Registros , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Resistencia VascularRESUMEN
Importance: Whether the improvement in myocardial perfusion provided by percutaneous coronary intervention (PCI) is associated with symptomatic relief or improved outcomes has not been well investigated. Objective: To investigate the prognostic value of the improvement in fractional flow reserve (FFR) after PCI (ΔFFR) on patients' symptoms and 2-year outcomes. Design, Setting, and Participants: This study is a post hoc analysis of data from patients undergoing FFR-guided PCI in the randomized clinical trials Fractional Flow Reserve vs Angiography for Multivessel Evaluation (FAME) 1 (NCT00267774; 2009) and FAME 2 (NCT01132495; 2012), with inclusion of 2 years of follow-up data. The FAME 1 trial included patients with multivessel coronary artery disease from 20 medical centers in Europe and the United States. The FAME 2 trial included patients with stable coronary artery disease involving up to 3 vessels from 28 sites in Europe and North America. Lesions from the group in the FAME 1 trial from whom FFR was measured and the group in the FAME 2 trial who received FFR-guided PCI plus medical therapy were analyzed. Data analysis occurred from May 2017 to May 2018. Interventions: Measure of post-PCI FFR. Main Outcomes and Measures: Vessel-oriented clinical events at 2 years, a composite of cardiac death, target vessel-associated myocardial infarction, and target vessel revascularization. Results: This analysis included 639 patients from whom pre-PCI and post-PCI FFR values were available. Of their 837 lesions, 277 were classified into the lowest tertile (ΔFFR≤0.18), 282 into the middle tertile (0.19≤ΔFFR≤0.31), and 278 into the highest tertile (ΔFFR>0.31). Vessel-oriented clinical events were significantly more frequent in the lowest tertile (n = 25 of 277 [9.1%]) compared with the highest tertile (n = 13 of 278 [4.7%]; hazard ratio, 2.01 [95% CI, 1.03-3.92]; P = .04). In addition, a significant association was observed between ΔFFR and symptomatic relief (odds ratio, 1.33 [95% CI, 1.02-1.74]; P = .02). Conclusions and Relevance: In this analysis of 2 randomized clinical trials, the larger the improvement in FFR, the larger the symptomatic relief and the lower the event rate. This suggests that measuring FFR before and after PCI provides clinically useful information.
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Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Reserva del Flujo Fraccional Miocárdico/fisiología , Infarto del Miocardio/terapia , Intervención Coronaria Percutánea/métodos , Anciano , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/complicaciones , Muerte , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Evaluación de Resultado en la Atención de Salud , Intervención Coronaria Percutánea/tendencias , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The principle of continuous thermodilution can be used to calculate absolute coronary blood flow and microvascular resistance (R). The aim of the study is to explore the safety, feasibility, and reproducibility of coronary blood flow and R measurements as measured by continuous thermodilution in humans. METHODS AND RESULTS: Absolute coronary flow and R can be calculated by thermodilution by infusing saline at room temperature through a dedicated monorail catheter. The temperature of saline as it enters the vessel, the temperature of blood and saline mixed in the distal part of the vessel, and the distal coronary pressure were measured by a pressure/temperature sensor-tipped guidewire. The feasibility and safety of the method were tested in 135 patients who were referred for coronary angiography. No significant adverse events were observed; in 11 (8.1%) patients, bradycardia and concomitant atrioventricular block appeared transiently and were reversed immediately on interruption of the infusion. The reproducibility of measurements was tested in a subgroup of 80 patients (129 arteries). Duplicate measurements had a strong correlation both for coronary blood flow (ρ=0.841, P<0.001; intraclass correlation coefficient=0.89, P<0.001) and R (ρ=0.780, P<0.001; intraclass correlation coefficient=0.89, P<0.001). In Bland-Altman plots, there was no significant bias or asymmetry. CONCLUSIONS: Absolute coronary blood flow (in L/min) and R (in mm Hg/L/min or Wood units) can be safely and reproducibly measured with continuous thermodilution. This approach constitutes a new opportunity for the study of the coronary microcirculation.
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Síndrome Coronario Agudo/diagnóstico , Angina Estable/diagnóstico , Cateterismo Cardíaco/instrumentación , Catéteres Cardíacos , Enfermedad de la Arteria Coronaria/diagnóstico , Circulación Coronaria , Vasos Coronarios/fisiopatología , Microcirculación , Resistencia Vascular , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/fisiopatología , Angina Estable/diagnóstico por imagen , Angina Estable/fisiopatología , Velocidad del Flujo Sanguíneo , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/fisiopatología , Vasos Coronarios/diagnóstico por imagen , Estudios de Factibilidad , Humanos , Valor Predictivo de las Pruebas , Derivación y Consulta , Reproducibilidad de los Resultados , Termodilución/instrumentaciónRESUMEN
BACKGROUND: Fractional flow reserve (FFR)-guided coronary artery bypass graft (CABG) surgery has been associated with lower number of graft anastomoses, lower rate of on-pump surgery, and higher graft patency rate as compared with angiography-guided CABG surgery. However, no clinical benefit has been reported to date. METHODS AND RESULTS: Consecutive patients (n=627) treated by CABG between 2006 and 2010 were retrospectively included. In 198 patients, at least 1 stenosis was grafted according to FFR (FFR-guided group), whereas in 429 patients all stenoses were grafted based on angiography (angiography-guided group). The 2 coprimary end points were overall death or myocardial infarction and major adverse cardiovascular events (composite of overall death, myocardial infarction, and target vessel revascularization) up to 6-year follow-up. In the FFR-guided group, patients were significantly younger (66 [57-73] versus 70 [63-76]; P<0.001), more often male (82% versus 72%; P=0.008), and less often diabetic (21% versus 30%; P=0.023). Clinical follow-up (median, 85 [66-104] months) was analyzed in 396 patients after 1:1 propensity-score matching for these 3 variables. The rate of overall death or myocardial infarction was significantly lower in the FFR-guided (n=31 [16%] versus n=49 [25%]; hazard ratio, 0.59 [95% confidence interval, 0.38-0.93]; P=0.020) as compared with the angiography-guided group. Major adverse cardiovascular events rate was also numerically lower in the FFR-guided than in the angiography-guided group (n=42 [21%] versus n=52 [26%]; hazard ratio, 0.77 [95% confidence interval, 0.51-1.16]; P=0.21). CONCLUSIONS: FFR-guided CABG is associated with a significant reduction in the rate of overall death or myocardial infarction at 6-year follow-up as compared with angiography-guided CABG.
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Cateterismo Cardíaco , Angiografía Coronaria , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/cirugía , Estenosis Coronaria/cirugía , Vasos Coronarios/cirugía , Reserva del Flujo Fraccional Miocárdico , Anciano , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/fisiopatología , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/mortalidad , Estenosis Coronaria/fisiopatología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Femenino , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Infarto del Miocardio/fisiopatología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
AIMS: The aim of this study was to explore the evolution of coronary lesions which had repeated physiologic evaluation by FFR as an endpoint, describe the clinical significance of longitudinal FFR change (ΔFFR=FFRfollow-up-FFRbaseline) and its correlation with angiographic indices, and identify predictors of FFRfollow-up. METHODS AND RESULTS: A retrospective, single-centre analysis of 414 stenoses (331 patients) with consecutive FFR measurements at least six months apart was performed (median time interval: 24 [17, 37] months). The change in percent diameter stenosis was 2% (-5%, 11%). FFR values at baseline and follow-up were 0.86 (0.82, 0.90) and 0.83 (0.79, 0.90), respectively (<0.0001). The median ΔFFR was -0.007 (-0.028, 0.010) per year. Worsening FFR (ΔFFR <-0.05) was observed in 105 (25%) stenoses, stable FFR (-0.05 ≤ΔFFR ≤0.05) in 276 (67%) and improving FFR (ΔFFR >0.05) in 33 (8%) stenoses. The number of haemodynamically significant stenoses (FFR ≤0.80) was higher at follow-up compared to baseline (33% versus 17%, p<0.0001); ΔFFR correlated weakly with delta diameter stenosis (Δ%DS, ρ=-0.111, p=0.024). In mixed effects repeated measures analysis, only lesion location had an independent correlation with FFR values after adjusting for multiple confounders. In ROC analysis, FFRbaseline values predicted future clinically significant values (c-statistic: 0.736 [95% CI: 0.682-0.783]). CONCLUSIONS: FFR values decrease slowly over a two-year follow-up. FFRbaseline, but not angiographic indices, is a predictor of significant functional atherosclerosis progression, predicting which stenoses will require revascularisation.
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Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Angiografía Coronaria , Vasos Coronarios , Hemodinámica , Humanos , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
The role of low-density lipoproteins (LDLs) as a major risk factor for cardiovascular disease has been demonstrated by several epidemiological studies. The molecular basis for LDLs in atherosclerotic plaque formation and progression is not completely unraveled yet. Pharmacological modulation of plasma LDL-C concentrations and randomized clinical trials addressing the impact of lipid-lowering interventions on cardiovascular outcome have clearly shown that reducing plasma LDL-C concentrations results in a significant decrease in major cardiovascular events. For many years, statins have represented the most powerful pharmacological agents available to lower plasma LDL-C concentrations. In clinical trials, it has been shown that the greater the reduction in plasma LDL-C concentrations, the lower the rate of major cardiovascular events, especially in high-risk patients, because of multiple risk factors and recurrent events. However, in a substantial number of patients, the recommended LDL target is difficult to achieve because of different factors: genetic background (familial hypercholesterolemia), side effects (statin intolerance), or high baseline plasma LDL-C concentrations. In the last decade, our understanding of the molecular mechanisms involved in LDL metabolism has progressed significantly and the key role of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged. This protein is an enzyme able to bind the LDL receptors (LDL-R) on hepatocytes, favoring their degradation. Blocking PCSK9 represents an intriguing new therapeutic approach to decrease plasma LDL-C concentrations, which in recent studies has been demonstrated to also result in a significant reduction in major cardiovascular events.
RESUMEN
BACKGROUND: Among patients with documented stable coronary artery disease and in whom no revascularization was performed, we compared the respective values of angiographic diameter stenosis (DS) and fractional flow reserve (FFR) in predicting natural history. METHODS: The present analysis included the 607 patients from the FAME 2 trial (Fractional Flow Reserve Versus Angiography in Multivessel Evaluation 2) in whom no revascularization was performed. FFR varied from 0.20 to 1.00 (average 0.74±0.16), and DS (by quantitative coronary analysis) varied from 8% to 98% (average 53±15). The primary end point, defined as vessel-oriented clinical end point (VOCE) at 2 years, was a composite of prospectively adjudicated cardiac death, vessel-related myocardial infarction, vessel-related urgent, and not urgent revascularization. The stenoses were divided into 4 groups according to FFR and %DS values: positive concordance (FFR≤0.80; DS≥50%), negative concordance (FFR>0.80; DS<50%), positive mismatch (FFR≤0.80; DS<50%), and negative mismatch (FFR>0.80; DS≥50%). RESULTS: The rate of VOCE was highest in the positive concordance group (log rank: X2=80.96; P=0.001) and lowest in the negative concordance group. The rate of VOCE was higher in the positive mismatch group than in the negative mismatch group (hazard ratio, 0.38; 95% confidence interval, 0.21-0.67; P=0.001). There was no significant difference in VOCE between the positive concordance and positive mismatch groups (FFR≤0.80; hazard ratio, 0.77; 95% confidence interval, 0.57-1.09; P=0.149) and no significant difference in rate of VOCE between the negative mismatch and negative concordance groups (FFR>0.80; hazard ratio, 1.89; 95% confidence interval, 0.96-3.74; P=0.067). CONCLUSIONS: In patients with stable coronary disease, physiology (FFR) is a more important determinant of the natural history of coronary stenoses than anatomy (DS). CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01132495.
Asunto(s)
Angiografía Coronaria , Estenosis Coronaria/patología , Reserva del Flujo Fraccional Miocárdico/fisiología , Anciano , Estenosis Coronaria/mortalidad , Femenino , Estudios de Seguimiento , Hemodinámica , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
BACKGROUND: The correlation between angiographic assessment of coronary stenoses and fractional flow reserve (FFR) is weak. Whether and how risk factors impact the diagnostic accuracy of angiography is unknown. We sought to evaluate the diagnostic accuracy of angiography by visual estimate and by quantitative coronary angiography when compared with FFR and evaluate the influence of risk factors (RF) on this accuracy. METHODS AND RESULTS: In 1382 coronary stenoses (1104 patients), percent diameter stenosis by visual estimation (DSVE) and by quantitative coronary angiography (DSQCA) was compared with FFR. Patients were divided into 4 subgroups, according to the presence of RFs, and the relationship between DSVE, DSQCA, and FFR was analyzed. Overall, DSVE was significantly higher than DSQCA (P<0.0001); nonetheless, when examined by strata of DS, DSVE was significantly smaller than DSQCA in mild stenoses, although the reverse held true for severe stenoses. Compared with FFR, a large scatter was observed for both DSVE and DSQCA. When using a dichotomous FFR value of 0.80, C statistic was significantly higher for DSVE than for DSQCA (0.712 versus 0.640, respectively; P<0.001). C statistics for DSVE decreased progressively as RFs accumulated (0.776 for ≤1 RF, 0.750 for 2 RFs, 0.713 for 3 RFs and 0.627 for ≥4 RFs; P=0.0053). In addition, in diabetics, the relationship between FFR and angiographic indices was particularly weak (C statistics: 0.524 for DSVE and 0.511 for DSQCA). CONCLUSIONS: Overall, DSVE has a better diagnostic accuracy than DSQCA to predict the functional significance of coronary stenosis. The predictive accuracy of angiography is moderate in patients with ≤1 RFs, but weakens as RFs accumulate, especially in diabetics.