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1.
Heart Fail Rev ; 29(2): 535-548, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38285236

RESUMEN

In the last decades, several classifications and definitions have been proposed for advanced heart failure (ADVHF) patients, including clinical, functional, hemodynamic, imaging, and electrocardiographic features. Despite different inclusion criteria, ADVHF is characterized by some common items, such as drug intolerance, low arterial pressure, multiple organ dysfunction, chronic kidney disease, and diuretic use dependency. Additional features include fatigue, hypotension, hyponatremia, and unintentional weight loss associated with a specific laboratory profile reflecting systemic multiorgan dysfunction. Notably, studies evaluating guideline-directed medical therapy recently endorsed by guidelines in stable HF, including the 4 drug classes all together (i.e., betablocker, mineral corticoid antagonist, renin angiotensin inhibitors/neprilysin inhibitors, and sodium glucose transporter inhibitors), remain scarcely analyzed in ADVHF and New York Heart Association (NYHA) Class IV. Additionally, due to the common conditions associated with advanced stages, the balance between drug tolerance and potential benefits of the contemporary use of all agents is questioned. Therefore, less hard endpoints, such as exercise tolerance, quality of life (QoL) and self-competency, are not clearly demonstrated. Specific analyses evaluating outcome and rehospitalization of each drug provided conflicting results and are often limited to subjects with stable conditions and less advanced NYHA class. Current European Society of Cardiology/American Heart Association (ESC/AHA) Guidelines do not indicate the type of treatment, dosage, and administration modalities, and they do not suggest specific indications for ADVHF patients. Due to these concerns, there is an impelling need to understand what drugs may be used as the first line, what management leads to the better outcome, and what is the best treatment algorithm in this setting. In this paper, we summarize the most common pitfalls and limitations for the use of the traditional agents, and we propose a personalized approach aiming at preserve drug tolerance and maintaining adverse event protection and satisfactory QoL.


Asunto(s)
Insuficiencia Cardíaca , Calidad de Vida , Estados Unidos , Humanos , Pérdida de Peso , Diuréticos/uso terapéutico , Antihipertensivos/uso terapéutico
2.
Eur J Clin Invest ; 54(2): e14110, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37837616

RESUMEN

BACKGROUND: An exuberant and dysregulated inflammatory response contributes to the development and progression of cardiovascular diseases (CVDs). METHODS: This narrative review includes original articles and reviews published over the past 20 years and found through PubMed. The following search terms (or combination of terms) were considered: "acute pericarditis," "recurrent pericarditis," "myocarditis," "cardiac sarcoidosis," "atherosclerosis," "acute myocardial infarction," "inflammation," "NLRP3 inflammasome," "Interleukin-1" and "treatment." RESULTS: Recent evidence supports the role of inflammation across a wide spectrum of CVDs including myocarditis, pericarditis, inflammatory cardiomyopathies (i.e. cardiac sarcoidosis) as well as atherosclerotic CVD and heart failure. Interleukins (ILs) are the signalling mediators of the inflammatory response. The NACHT, leucine-rich repeat and pyrin-domain containing protein 3 (NLRP3) inflammasome play a key role in producing IL-1ß, the prototypical pro-inflammatory cytokine involved in CVDs. Other pro-inflammatory cytokines (e.g. tumour necrosis factor) have been implicated in cardiac sarcoidosis. As a proof of this, IL-1 blockade has been proven efficacious in pericarditis and chronic coronary syndrome. CONCLUSION: Tailored strategies aiming at quenching the inflammatory response have emerged as promising to treat CVDs. In this review article, we summarize recent evidence regarding the role of inflammation across a broad spectrum of CVDs. We also review novel evidence regarding targeted therapeutic strategies.


Asunto(s)
Aterosclerosis , Miocarditis , Pericarditis , Sarcoidosis , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Inflamación/metabolismo , Citocinas/metabolismo , Interleucina-1beta/metabolismo , Aterosclerosis/metabolismo , Pericarditis/tratamiento farmacológico
3.
J Cardiovasc Pharmacol ; 84(2): 210-219, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39115720

RESUMEN

ABSTRACT: Cardiogenic shock (CS) is a life-threatening condition. The aim of this study is to evaluate the clinical characteristics, management, and complication rate of patients with CS admitted to a high-volume hospital in Italy. We retrospectively reviewed the clinical, echocardiographic, and laboratory data, therapeutic management, and outcomes of patients with CS admitted to the Policlinico Gemelli (Rome) between January 1, 2020, and January 1, 2023. We included 96 patients [median age 71 years, interquartile range 60-79; 65 (68%) males], of whom 49 patients (51%) presented CS secondary to acute myocardial infarction and 60 (63%) with a de novo presentation of CS. Dobutamine was the most frequently used inotrope and noradrenaline the most frequently used vasopressor (adopted in 56% and 82% of cases, respectively). Forty-five (47%) patients died during the hospitalization. Nonsurvivors were older and had a higher inflammatory burden at admission, elevated lactate levels, a greater increase in lactate levels, higher left ventricular filling pressures, and worse right ventricular function. C-reactive protein levels [odds ratio (OR) 1.03, 95% confidence interval (CI) (1.00-1.04), P = 0.027], lactate levels at admission (OR 3.49, 95% CI, 1.59-7.63, P = 0.02), and increase in lactate levels (OR 2.8, 95% CI, 1.37-5.75, P = 0.005) were independent predictors of in-hospital all-cause death. Our data contribute to the assessment of the regional variations in the management and outcomes of patients with CS. We observed a high mortality and complication rate. Lactate acidosis and C-reactive protein measured at admission may help in identifying patients at higher risk of adverse in-hospital outcomes.


Asunto(s)
Mortalidad Hospitalaria , Hospitales de Alto Volumen , Choque Cardiogénico , Humanos , Choque Cardiogénico/mortalidad , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/terapia , Choque Cardiogénico/fisiopatología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Italia/epidemiología , Resultado del Tratamiento , Factores de Riesgo , Unidades de Cuidados Coronarios , Factores de Tiempo , Biomarcadores/sangre , Medición de Riesgo , Cardiotónicos/uso terapéutico
4.
J Pharmacol Exp Ther ; 386(2): 156-163, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37037651

RESUMEN

Interleukin-1 (IL-1) blockade with anakinra given within 12 hours from reperfusion has been shown to reduce the inflammatory response as well as prevent heart failure (HF) events in patients with STEMI. We sought to determine whether time-to-treatment influences the efficacy of anakinra on systemic inflammation and incidence of HF events in patients with STEMI. We divided the cohort in two groups base6d on the median time from percutaneous coronary intervention (PCI) to investigational drug, and analyzed the effects of anakinra on the area-under-the-curve for C reactive protein (AUC-CRP) and on incidence of the composite endpoint of death or new onset HF. We analyzed data from 139 patients: 84 (60%) treated with anakinra and 55 (40%) with placebo. The median time from PCI to investigational treatment was 271 (182-391) minutes. The AUC-CRP was significantly higher in patients receiving placebo versus anakinra both in those with time from PCI to treatment <271 minutes (222.6 [103.9-325.2] vs. 78.4 [44.3-131.2], P < 0.001) and those with time from PCI to treatment ≥271 minute (235.2 [131.4-603.4] vs. 75.5 [38.9-171.9], P < 0.001) (P > 0.05 for interaction). Anakinra significantly reduced the combined endpoint of death or new onset HF in patients with time from PCI to treatment <271 minutes (5 [11%] vs. 9n[36%], log-rank χ 2 5.985, P = 0.014) as well as in patients with time from PCI to drug ≥271 minutes (2n[5%] vs. 7 [23%], log-rank χ 2 3.995, P = 0.046) (P > 0.05 for interaction). IL-1 blockade with anakinra blunts the acute systemic inflammatory response and prevents HF events independent of time-to-treatment. SIGNIFICANCE STATEMENT: In patients with ST segment elevation presenting within 12 hours of pain onset and treated within 12 hours of reperfusion, interleukin-1 blockade with anakinra blunts the acute systemic inflammatory response, a surrogate of interleukin-1 activity, and prevents heart failure events independent of time-to-treatment.


Asunto(s)
Insuficiencia Cardíaca , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Inflamación/complicaciones , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Interleucina-1 , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Tiempo de Tratamiento , Resultado del Tratamiento
5.
Rev Cardiovasc Med ; 24(3): 77, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-39077487

RESUMEN

Acute pericarditis is the most frequent pericardial disease characterized by inflammation of the pericardial layers resulting in pain, dyspnea and fatigue. Often limited to an isolated event, up to 30% of patients experience one or more recurrences. There is limited knowledge about the pathophysiology of this disease, possibly due to the limited availability of animal models. More recently, following seminal clinical trials with colchicine and interleukin-1 (IL-1) blockers and a novel murine model of acute pericarditis using zymosan A, it has become clear that the NLRP3 (NACHT, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome/IL-1 ß axis plays a central role in driving acute pericardial inflammation and in sustaining this process during recurrences. Diagnostic management of pericarditis has been implemented with multimodality imaging including echocardiography, cardiac computed tomography, and cardiac magnetic resonance. These imaging modalities provide essential diagnostic and pathogenetic information, and are able to characterize pericardial inflammation, allowing to refine risk stratification and personalize treatment. Recent acquisitions yield relevant implications with regard to the therapeutic management of acute and recurrent pericarditis. Non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are cornerstone therapies either for acute and recurrent pericarditis. However, the benefits of targeted agents, such as anakinra - a recombinant human IL-1 receptor antagonist - and rilonacept - an IL-1 α /IL-1 ß trap, are being increasingly recognized. To this end, phenotyping patients with pericarditis and addressing such therapies to those presenting with auto-inflammatory features (elevated C-reactive protein, sustained pericardial and systemic inflammation, multiple recurrences) is of utmost importance to identify patients who might be more likely to benefit from NLRP3 inflammasome/IL-1 ß pathway blockade.

6.
Artículo en Inglés | MEDLINE | ID: mdl-37815298

RESUMEN

ABSTRACT: Heart failure (HF) is a complex syndrome that remains a leading cause of morbidity and mortality worldwide. Abundant evidence suggests inflammation plays a key role in the development and perpetuation of HF, but there are currently no anti-inflammatory treatments approved for use in HF. Interleukin-1 (IL-1), the prototypical pro-inflammatory cytokine, has been implicated in adverse cardiac remodeling and left ventricular dysfunction. Multiple early phase clinical trials using IL-1 blockade in patients at risk for or diagnosed with HF have suggested favorable safety and efficacy in reducing inflammatory biomarkers, as well as positive signals in surrogate and clinical endpoints. Additional large scale clinical trials are urgently needed to confirm the safety and efficacy of this therapeutic approach specifically in HF. In this narrative review, we discuss current evidence regarding IL-1 blockade in the prevention and treatment of HF.

7.
J Transl Med ; 20(1): 270, 2022 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-35706006

RESUMEN

BACKGROUND: Heart failure (HF) is a global leading cause of mortality despite implementation of guideline directed therapy which warrants a need for novel treatment strategies. Proof-of-concept clinical trials of anakinra, a recombinant human Interleukin-1 (IL-1) receptor antagonist, have shown promising results in patients with HF. METHOD: We designed a single center, randomized, placebo controlled, double-blind phase II randomized clinical trial. One hundred and two adult patients hospitalized within 2 weeks of discharge due to acute decompensated HF with reduced ejection fraction (HFrEF) and systemic inflammation (high sensitivity of C-reactive protein > 2 mg/L) will be randomized in 2:1 ratio to receive anakinra or placebo for 24 weeks. The primary objective is to determine the effect of anakinra on peak oxygen consumption (VO2) measured at cardiopulmonary exercise testing (CPX) after 24 weeks of treatment, with placebo-corrected changes in peak VO2 at CPX after 24 weeks (or longest available follow up). Secondary exploratory endpoints will assess the effects of anakinra on additional CPX parameters, structural and functional echocardiographic data, noninvasive hemodynamic, quality of life questionnaires, biomarkers, and HF outcomes. DISCUSSION: The current trial will assess the effects of IL-1 blockade with anakinra for 24 weeks on cardiorespiratory fitness in patients with recent hospitalization due to acute decompensated HFrEF. TRIAL REGISTRATION: The trial was registered prospectively with ClinicalTrials.gov on Jan 8, 2019, identifier NCT03797001.


Asunto(s)
Insuficiencia Cardíaca , Adulto , Método Doble Ciego , Humanos , Proteína Antagonista del Receptor de Interleucina 1/farmacología , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Interleucina-1 , Calidad de Vida , Volumen Sistólico/fisiología , Resultado del Tratamiento
8.
Cardiovasc Diabetol ; 21(1): 211, 2022 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-36243750

RESUMEN

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are considered as a homogeneous cohort of patients. However, the specific role of diabetic microvascular complications (DMC), in determining the features of coronary plaques is poorly known. We investigated whether the presence of DMC may identify a different phenotype of patients associated to specific clinical, angiographic, optical coherence tomography (OCT) features and different prognosis. METHODS: We prospectively enrolled consecutive T2DM patients with obstructive coronary artery disease (CAD) at their first coronary event. Patients were stratified according to the presence or absence of DMC, including diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. OCT assessment of the culprit vessel was performed in a subgroup of patients. The incidence of major adverse cardiac events (MACEs) was assessed at follow-up. RESULTS: We enrolled 320 T2DM patients (mean age 70.3 ± 8.8 years; 234 [73.1%] men, 40% acute coronary syndrome, 60% chronic coronary syndrome). Patients with DMC (172 [53.75%]) presented a different clinical and biochemical profile and, of importance, a higher prevalence of multivessel CAD (109 [63.4%] vs. 68 [45.9%], p = 0.002). At OCT analysis, DMC was associated to a higher prevalence of large calcifications and healed plaques and to a lower prevalence of lipid plaques. Finally, MACEs rate was significantly higher (25 [14.5%] vs. 12 [8.1%], p = 0.007) in DMC patients, mainly driven by a higher rate of planned revascularizations, and DMC predicted the occurrence of MACEs (mean follow-up 33.4 ± 15.6 months). CONCLUSIONS: The presence of DMC identifies a distinct diabetic population with more severe CAD but with a more stable pattern of coronary atherosclerosis.


Asunto(s)
Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Placa Aterosclerótica , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Vasos Coronarios/diagnóstico por imagen , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Lípidos , Fenotipo , Placa Aterosclerótica/complicaciones , Pronóstico , Factores de Riesgo , Tomografía de Coherencia Óptica/métodos
9.
Curr Opin Cardiol ; 37(6): 481-487, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36094542

RESUMEN

PURPOSE OF REVIEW: Myocardial infarction with nonobstructive coronary arteries (MINOCA) represents about 6-8% of all patients with myocardial infarction (MI), and several pathophysiological mechanisms showed to be involved in this heterogeneous clinical condition. Of note, MINOCA proved to be associated with a significant risk of mortality, angina burden and socioeconomic costs. RECENT FINDINGS: Results from randomized clinical trials evaluating the clinical effectiveness of a comprehensive diagnostic algorithm, along with the acute and long-term management of patients with MINOCA, are pending. SUMMARY: In this review article, we aim at providing an overview of the clinical features, diagnostic work-up and the therapeutic management of patients presenting with MINOCA, highlighting the recent acquisition along with the remaining important knowledge gaps in this field.


Asunto(s)
Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/terapia , Vasos Coronarios/diagnóstico por imagen , Humanos , MINOCA , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Medicina de Precisión , Factores de Riesgo
10.
J Cardiovasc Pharmacol ; 79(6): 774-780, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35170493

RESUMEN

ABSTRACT: Patients with ST elevation myocardial infarction (STEMI) are at risk of future heart failure (HF), particularly those with anterior STEMI. Interleukin-1 (IL-1) is a key mediator of the inflammatory response, and its blockade has emerged as a potential therapeutic strategy to prevent HF events. The aim of this analysis was to explore the effects of anakinra, an IL-1 receptor antagonist, on HF outcomes based on anterior versus nonanterior location STEMI and to explore whether this effect is mediated through the amelioration of left ventricular systolic function and cardiac remodeling. We pooled data from 3 early phase randomized clinical trials. The primary end point was a composite of all-cause death and new-onset HF at 1-year follow-up. The left anterior descending coronary artery as culprit vessel was used to identify anterior STEMI. We included 139 patients, 47 (34%) with anterior STEMI and 92 (66%) with nonanterior STEMI. Anakinra significantly reduced the combined end point of death or new-onset HF in patients with anterior STEMI [4 (13%) vs. 7 (42%), log-rank P value = 0.049] and in patients with nonanterior STEMI [3 (6%) vs. 9 (24%), log-rank P value = 0.014]. We found no significant differences comparing anakinra versus placebo in interval changes in left ventricular ejection fraction and volumes in anterior and nonanterior STEMI. In conclusion, anakinra is associated with a reduction of HF events in patients with STEMI, irrespective of anterior or nonanterior location, or of changes in left ventricular ejection fraction or cardiac remodeling.


Asunto(s)
Insuficiencia Cardíaca , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/etiología , Humanos , Proteína Antagonista del Receptor de Interleucina 1/efectos adversos , Interleucina-1 , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Volumen Sistólico , Función Ventricular Izquierda , Remodelación Ventricular
11.
J Cardiovasc Pharmacol ; 80(5): 672-678, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-35881895

RESUMEN

BACKGROUND: Modulation of the inflammatory response is a promising therapeutic strategy in acute myocardial infarction. The novel approach is based on the anti-inflammatory and cytoprotective properties mediated by the engagement of the low-density lipoprotein‒related protein 1 (LRP1) receptor. SERPIN peptide 16 (SP16) is a synthetic, selective LRP1 agonist. We herein present the results of a study with a single subcutaneous administration of SP16 in 10 patients with STEMI, to appraise its safety and tolerability and explore the effects on the acute inflammatory response, infarct size, and cardiac function. METHODS: Ten patients with ST-segment elevation myocardial infarction (STEMI) were enrolled within 12 hours of symptoms onset and 6 hours of percutaneous coronary intervention in a single-center, single-arm, open-label study of a single subcutaneous administration of SP16 (0.2 mg/kg). Serial clinical biomarkers and echocardiography data were collected up to 12 months. The data are presented separately for the treatment group and compared with historical controls from a placebo-treated arm in a recently completed clinical trial (N = 28) with similar enrollment criteria. RESULTS: All ten patients with STEMI received subcutaneous administration of SP16, 381 [272-478] minutes after percutaneous coronary intervention, without any treatment-related adverse events. The area under the curve for C-reactive protein was 133 [46-528] mg·d/L in the SP16-treated group versus 286 [141-581] mg·d/L in the historical placebo-treated group ( P = 0.161). The area under the curve for creatine kinase-myocardial band was 1432 [675-3089] ng·d/mL in the SP16-treated group versus 2367 [830-4750] ng·d/mL in the historical placebo-treated patients ( P = 0.428). Left ventricular ejection fraction was 46% [39-54] at baseline and 51% [46-58] at 1 year follow-up in SP16-treated patients (interval change 5% [-0.3% to +9%] P = 0.05) and 44% [38%-56%] at baseline and 53% [43%-59%] at 1 year follow-up in historical placebo-treated patients (interval change 3% [-5% to 10%], P = 0.305). CONCLUSION: A single subcutaneous administration of SP16, a synthetic targeted LRP1 agonist, was safe and well-tolerated in patients with STEMI. A trend toward reduction in the inflammatory response and infarct size with SP16 was noted; however, the sample size for this study was not based on formal statistical criteria. More extensive studies are planned to determine the clinical efficacy of SP16 in STEMI.NCT: NCT04225533.


Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Serpinas , Humanos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Volumen Sistólico , Serpinas/farmacología , Función Ventricular Izquierda , Lipoproteínas LDL/farmacología , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/etiología , Inflamación/diagnóstico , Inflamación/tratamiento farmacológico , Inflamación/etiología , Resultado del Tratamiento , Péptidos/efectos adversos
12.
Intern Med J ; 52(6): 921-925, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34935270

RESUMEN

Platypnoea-orthodeoxia syndrome (POS) is an uncommon but challenging clinical condition characterised by positional dyspnoea (platypnoea) and arterial desaturation (orthodeoxia) in the upright position that improve in the supine position. Since its first description, many cases have been reported and many conditions have been associated with this syndrome. Herein, we review the clinical presentation, pathophysiology, diagnostic work-up and management of patients with POS, aiming to increase the awareness of this often misdiagnosed condition.


Asunto(s)
Foramen Oval Permeable , Disnea/complicaciones , Disnea/etiología , Foramen Oval Permeable/diagnóstico , Foramen Oval Permeable/diagnóstico por imagen , Humanos , Hipoxia/complicaciones , Hipoxia/etiología , Postura , Síndrome
13.
Curr Cardiol Rep ; 24(10): 1505-1515, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35972638

RESUMEN

PURPOSE OF REVIEW: Ischemic cardiomyopathy refers to systolic left ventricular dysfunction in the setting of obstructive coronary artery disease and represents the most common cause of heart failure worldwide. It is often the combination of an irreversible loss of viable mass following an acute myocardial infarction (AMI) with a dysfunctional, but still viable, myocardium in the context of a chronically reduced myocardial blood flow and reduced coronary reserve. Medical treatments aiming at modulating neurohumoral response and restoring blood flow to the ischemic cardiomyocytes were shown to dramatically abate the occurrence of ventricular dysfunction and adverse remodeling in ischemic cardiomyopathy. RECENT FINDINGS: Novel therapeutic approaches, such as mechanical unloading and modulation of the inflammatory response, appear to be promising. Furthermore, the understanding of the mechanisms by which, despite optimal treatment, heart failure ensues after AMI, with or without adverse remodeling and systolic dysfunction, is a critical step in the search for novel ways to tackle heart failure risk beyond preservation of left ventricular volumes and systolic function. In this review article, we explore the principal pathophysiological mechanisms and pathways of heart failure in ischemic cardiomyopathy, therapeutic opportunities, and knowledge gaps in this area.


Asunto(s)
Cardiomiopatías , Insuficiencia Cardíaca , Infarto del Miocardio , Isquemia Miocárdica , Disfunción Ventricular Izquierda , Cardiomiopatías/complicaciones , Insuficiencia Cardíaca/complicaciones , Humanos , Isquemia Miocárdica/complicaciones
14.
J Cardiovasc Pharmacol ; 78(4): 501-514, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34269700

RESUMEN

ABSTRACT: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors showed benefit in patients with heart failure. In this updated meta-analysis, we evaluate the therapeutic efficacy and safety of SGLT-2 inhibitors in patients with heart failure. Different electronic databases were searched to find relevant articles. RevMan 5.4 was used for pooling data using a random/fixed-effects model, complemented by several sensitivity and subgroup analyses. A total of 13 randomized clinical trials including 14,618 patients with heart failure were included in analysis among 6797 studies screened. The overall mortality rate was 12.45% in the SGLT-2 group and 14.67% in the placebo group with 18% lower odds of overall mortality [odds ratio (OR), 0.82; confidence interval (CI), 0.75-0.91] in the SGLT-2 group. Odds of cardiovascular mortality was 18% lower (OR, 0.82; CI, 0.74-0.92) in the SGLT-2 group. The odds of hospitalization for heart failure (HHF) was 38% lower during the study period (OR, 0.62; CI, 0.56-0.68) in the SGLT-2 group. In addition, a benefit was seen for composite outcome HHF or mortality and considering subgrouping based on diabetes status, gender, and age groups. Although genital infection was significantly higher in the SGLT-2 group, the occurrence of severe adverse events, hypoglycemia, urinary tract infection, bone fracture, volume depletion, and other renal events did not differ between the 2 groups. Thus, SGLT-2 inhibitors improved cardiovascular outcomes among patients with heart failure with no significant difference in adverse events. Clinical benefit was comparable in diabetic and nondiabetic individuals, males and females, people in younger and older age groups with underlying heart failure, and HF with reduced ejection fraction.


Asunto(s)
Insuficiencia Cardíaca/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Progresión de la Enfermedad , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Hospitalización , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Resultado del Tratamiento
15.
Am J Ther ; 29(2): e199-e204, 2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-35389572

RESUMEN

BACKGROUND: Recent trials demonstrated the clinical efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with heart failure (HF), regardless of the presence or absence of type 2 diabetes. These data may allow the use of this innovative drug class in clinical routine for treating these patients. STUDY QUESTION: We aimed at further clarifying the role of SGLT2i in patients with diagnosis of HF, capitalizing on pooled sample size and heightened power for clinically relevant safety and efficacy outcomes. DATA SOURCES: We conducted a systematic search of PubMed, reference lists of relevant articles, and Medline database from inception until March 1, 2021. STUDY DESIGN: This meta-analysis was completed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched for randomized trials that evaluated the cardiovascular effects of SGLT2i in patients with HF. Three investigators independently assessed study eligibility, extracted the data, and assessed risk of bias. Hazard ratios and 95% confidence intervals (CIs) were pooled and meta-analyzed using a random-effect model. Numbers needed to treat (NNT) with the relative 95% CIs were also calculated. The primary outcome was a composite of HF hospitalization or an urgent visit for worsening HF and cardiovascular death. RESULTS: Three trials were included in the study. Overall, treatment with SGLT2i was associated with a lower risk of the primary composite outcome [hazard ratios 0.73, 95% CI (0.67-0.80), NNT = 11.3]. Similarly, there was a significantly reduced risk of cardiovascular death, all-cause death, HF hospitalization and need for urgent treatment for HF, and HF hospitalization. CONCLUSIONS: Therefore, the available evidence supports the routine use of these drugs as standard-of-care, also given the highly favorable NNTs.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Enfermedades Cardiovasculares/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosa/uso terapéutico , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Morbilidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Sodio , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
16.
Curr Cardiol Rep ; 23(11): 157, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34599390

RESUMEN

PURPOSE OF REVIEW: Pericarditis is a generally benign disease, although complications and/or recurrences may occur in up to 30% of cases. New evidence on the pathophysiology of the disease has accumulated in recent years. RECENT FINDINGS: Recently, it has been shown that the activation of the NLRP3 (NACHT, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome is central in the pathophysiology of pericarditis. These findings derive from clinical data, an experimental animal model of acute pericarditis supporting a role for the NLRP3 inflammasome in pericarditis, and from indirect evidence of inhibitors of NLRP3 inflammasome in clinical trials. Pericarditis is regarded as a stereotypical response to an acute damage of the mesothelial cells of the pericardial layers. NLRP3 inflammasome, a macromolecular structure sensing damage and releasing pro-inflammatory cytokines, is centrally involved as it releases interleukin (IL)-1ß, whose auto-induction feeds an autoinflammatory disease, mostly responsible for recurrences. Colchicine, an inhibitor of NLRP3 inflammasome formation, and IL-1-targeted therapies, such as anakinra and rilonacept, were found to effectively blunt the acute inflammation and reduce the risk for recurrences.


Asunto(s)
Cardiopatías , Inflamasomas , Animales , Citocinas , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR
17.
Curr Atheroscler Rep ; 22(9): 45, 2020 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-32671519

RESUMEN

PURPOSE OF REVIEW: Omega-3 fatty acid (O3FA) supplementation has shown conflicting evidence regarding its benefit in cardiovascular events. We performed a pairwise and network meta-analysis to elucidate the benefit of different doses of O3FA supplementation in cardiovascular prevention. RECENT FINDINGS: Fourteen studies were identified providing data on 125,763 patients. A prespecified cut-off value of < 1 g per day was set for low-dose (LD) O3FA and > 1 g per day for high-dose (HD) O3FA. The efficacy outcomes of interest were total death, cardiac death, sudden cardiac death, myocardial infarction, stroke, coronary revascularization, unstable angina, and major vascular events. Safety outcomes of interest were bleeding, gastrointestinal disturbances, and atrial fibrillation events. HD treatment was associated with a lower risk of cardiac death (IRR 0.79, 95% CI [0.65-0.96], p = 0.03 versus control), myocardial infarction (0.71 [0.62-0.82], p < 0.0001 versus control and 0.79 [0.67-0.92], p = 0.003 versus LD), coronary revascularization (0.74 [0.66-0.83], p < 0.0001 versus control and 0.74 [0.66-0.84], p < 0.0001 versus LD), unstable angina (0.73 [0.62-0.86], p = 0.0001 versus control and 0.74 [0.62-0.89], p = 0.002 versus LD), and major vascular events (0.78 [0.71-0.85], p < 0.0001 versus control and 0.79 [0.72-0.88], p < 0.0001 versus LD). HD treatment was associated with increased risk for bleeding events (1.49 [1.2-1.84], p = 0.0002 versus control and 1.63 [1.16-2.3], p = 0.005 versus LD) and increased atrial fibrillation events compared to control (1.35 [1.1-1.66], p = 0.004). HD O3FA treatment was associated with lower cardiovascular events compared to LD and to control, but increased risk for bleeding and atrial fibrillation events.


Asunto(s)
Fibrilación Atrial/prevención & control , Muerte Súbita Cardíaca/prevención & control , Suplementos Dietéticos , Ácidos Grasos Omega-3/administración & dosificación , Infarto del Miocardio/prevención & control , Metaanálisis en Red , Accidente Cerebrovascular/prevención & control , Anciano , Relación Dosis-Respuesta a Droga , Ácidos Grasos Omega-3/efectos adversos , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Riesgo , Resultado del Tratamiento
18.
Curr Opin Cardiol ; 34(6): 673-686, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31449091

RESUMEN

PURPOSE OF REVIEW: Takotsubo syndrome represents an increasingly recognized clinical entity characterized by a reversible acute myocardial dysfunction, often triggered by an emotional or physical stress, and independent of an underlying epicardial coronary artery disease. The diagnosis is often challenging because of the nonspecific clinical presentation and the inconclusive noninvasive diagnostic imaging. RECENT FINDINGS: The present review provides a brief overview of Takotsubo syndrome clinical presentation and guides the clinician through the diagnostic work-up of Takotsubo syndrome, highlighting clues into differential diagnosis. A review of clinical management is also provided. SUMMARY: Despite increasing awareness and recognition, the diagnosis of Takotsubo syndrome remains challenging and Takotsubo syndrome is often underdiagnosed or misdiagnosed. The prompt recognition of Takotsubo syndrome portends relevant prognostic and therapeutic implications.


Asunto(s)
Cardiomiopatía de Takotsubo/diagnóstico , Diagnóstico Diferencial , Humanos , Selección de Paciente , Pronóstico , Estrés Fisiológico , Cardiomiopatía de Takotsubo/terapia
20.
J Cardiovasc Pharmacol ; 73(4): 215-222, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30747785

RESUMEN

BACKGROUND: Activation of the NLRP3 inflammasome is a primary driver of sterile inflammation in response to myocardial ischemia reperfusion. Pharmacologic inhibitors of the NLRP3 inflammasome are being developed. We proposed that OLT1177 (dapansutrile), a novel NLRP3 inflammasome inhibitor, could preserve myocardial function after ischemia reperfusion injury in the mouse. METHODS: We used an experimental murine model of myocardial ischemia reperfusion injury through transient ligation of the left coronary artery and measured the effects of OLT1177 (6, 60, or 600 mg/kg intraperitoneal dose) on infarct size at pathology and on systolic cardiac function at echocardiography. To simulate a clinical scenario, we investigated the time window of therapeutic intervention with OLT1177 (60 mg/kg) administered 60, 120, or 180 minutes after reperfusion. RESULTS: OLT1177 was rapidly detectable in the plasma following intraperitoneal injection and had no effect on cardiac function in healthy mice. OLT1177 treatment at reperfusion showed significant dose-dependent reduction in infarct size (-36%, -67%, and -62% for 6, 60, and 600 mg/kg, respectively; P < 0.001 for linear trend, P = 0.010 vs. vehicle for 6 mg/kg, and P < 0.001 vs. vehicle for 60 and 600 mg/kg) and preserved cardiac systolic function measured as left ventricular fractional shortening at 24 hours and 7 days after injury (P = 0.015 for 6 mg/kg and P < 0.01 for 60 and 600 mg/kg). OLT1177 reduced infarct size also when given after 60 minutes of reperfusion (-71%, P < 0.001 vs. vehicle). CONCLUSION: OLT1177 (dapansutrile) limits infarct size and prevents left ventricular systolic dysfunction when given within 60 minutes following ischemia reperfusion injury in the mouse.


Asunto(s)
Antiinflamatorios/farmacología , Inflamasomas/antagonistas & inhibidores , Contracción Miocárdica/efectos de los fármacos , Infarto del Miocardio/tratamiento farmacológico , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Miocardio/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Nitrilos/farmacología , Animales , Antiinflamatorios/sangre , Caspasa 1/metabolismo , Modelos Animales de Enfermedad , Inflamasomas/metabolismo , Ratones , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/fisiopatología , Miocardio/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Nitrilos/sangre , Transducción de Señal
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